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TWiV 176

Richard writes:

Hi Vincent,

Just listened to this weeks twiv, and the q dot dyes you mentioned are also used in electronics. There they are used as a ultra precise phosphor. In that application blue light from LEDs can be re-emitted as red, and green. This gives an ultra precise RGB light source, allowing highly accurate colour rendition on LED backlit TVs.

It’s surprising how often these crossover applications crop up. Another good reason to listen to twiv. This should happen more and more, as the technology singularity approaches.

Thanks as always for the interesting podcast.

P.s. no replies regarding magnetotactic bacteria. Though there’s time yet. If not then I might have to experiment. I’m guessing replication of near anaerobic conditions, and elevated CO2, with the correct nutrients (nitrates, nitrides?)

P.p.s Best coffee maker? Airobe airopress, simple but highly effective.

Andrew writes:

Hi TWiV!

I’ve been listening to the show for a long time and I love it. It is great while I am working in the lab doing my plaque assays. Keep up the great work.

I just wanted to say I second Matt’s suggestion from episode 175 to Tessa about the program Papers for organizing references and PDFs. In the new version you can also use it to cite while you right (kind of like EndNote). I know Tessa wanted an online version, but personally I love papers. It makes managing references really easy and it lets you highlight and take notes on articles you’ve read. If you are student you can get a pretty good discount, and they have great customer service.

Sincerely,

Andrew

Neil writes:

Dear Vince, Rich, Alan, and Dick (or V-RAD),

I just listened to TWiV 171. I believe it was Dick who said something along the lines of “wouldn’t it be cool if you could label single virions and watch them in real time” (my paraphrasing, hope I got it right). I wonder what the other people at the gym thought when I blurted “it’s been done!” (or did I just think it?!) Anyway I’m pretty sure this has been done for HIV by Tom Hope (Northwestern University) and more viruses by others. Here are some links to related information:

-images and movies from the Zhuang lab at Harvard: http://zhuang.harvard.edu/virus.html

-review article by Dr. Hope: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209483/pdf/nihms175435.pdf

Anyway I think the technology is definitely out there!

Keep the great podcasts coming, I learn so much from them!

Neil

David Esteban writes:

Dear TWiV folks

This week, one of the founding editors of the Journal of Virology, Lloyd Kozloff, passed away. His daughter, a professor of Film here at Vassar College, notified me of his death. Although his name may not be familiar to many, he began his career at a very exciting time as a member of a group of phage biologists associated with Cold Spring Harbor, that included many more familiar names like James Watson and Max Delbruk. I can only imagine how thrilling it must have been for a young biologist to work at such an important time in the history of virology and molecular biology.

I wrote a brief blog post, with links to some of his early papers. Since you have discussed some historical papers on TWiV recently, I thought some listeners might be interested in seeing these as well. JVI will be publishing a more extensive obituary.

http://blogs.vassar.edu/viva/?p=639

Cheers

Brenna writes:

Dearest TWiV Doctors;

How would you approach current, and future, problems of being “research snubbed”?

About two years ago I was asked to help on a project with another lab. I was struggling to get my own research off the ground, so I had some time. I showed the post-doc how to do plaque assays, but it was obvious he was more inclined to let me do them. So we completed three experiments before my own research had to take priority over helping him. When things had calmed down I contacted to post doc about resuming the studies, but he never contacted me again. At the last experiment I got the impression that they had a new hypothesis about the experiment, and were eager to test it.

A few months ago I see that they have published a paper on that work. Now, no ethics were breeched. They never mention my work (although, to be fair my work likely gave rise to the studies actually shown in the paper), so there is no ethical issue. Just a matter of pride, time, and supplies that were used during their initial studies.

I was talking to a peer and she said that being “research snubbed” was the reason she required everything in writing prior to working with another lab group.

Is that what science has come to? There must be a contractual agreement to protect work and/or ideas? It worries me, because I love talking and sharing ideas. However, I have already come across one professor “borrowing” (stealing) my ideas for a grant, being research snubbed, and hearing stories of a researcher stealing ideas from a grant (and obviously scoring the grant low so it wouldn’t get funded) and later publishing the research. And I don’t even have a PhD yet!

What is a young scientist to do?

Long time listener, first time writer;

~Brenna

Tina writes:

I wonder if you are aware of the most recent study of MS and EBV. Whereas EBV has been a trigger suspect for MS since the 1980s, this new study shows that even if the virus is not actively replicating in the brain cells of MS patients, it is releasing chemicals that cause an immune system response.

I have a cousin with MS. I remember years ago finding out that MS is more common in subtropics compared to other areas. Some studies show it is important where you lived in your childhood and teenage years, as to whether you are at risk, no matter where you lived your adult years.

This and other studies prompted the theory that MS is caused by or triggered by a virus. A study in 2006 showed MS patients have an immune system overreaction to EBV. A 2009 study showed, after accessing 7 million blood samples, that those who had no infection of EBV did not get MS.

I find this very interesting as I am an ME/CFS patient. And MS has many similarities to ME/CFS. They both have post-exertional malaise or fatigue, much more pronounced in ME/CFS though. They both occur more in women. They both have a relapsing / remitting course for most patients. And they both have occurred in outbreaks. Lesions on the brain can also occur in ME/CFS patients, which – along with the similarity of symptoms – causes some with ME/CFS to be misdiagnosed with MS. (The lesions of ME/CFS are pinpoint, small white spots, but MS lesions are oblong.)

Ironically, ME/CFS has also been linked with EBV, even originally called “chronic Epstein-Barr virus syndrome.” Some have noticed increased EBV and other herpes virus titers in ME/CFS patients.

It is well established that many, not all, ME/CFS patients develop the disease after a case of mono, such that a study is onging, following people with mononucleosis to see who develops ME/CFS and possibly why.

EBV hides in B cells, which is why the drug Rituximab is sometimes used off-label in MS treatments. And, in October, a phase II double blind study in Norway found Rituximab, which kills B cells, brings moderate improvement to 2/3rds of ME/CFS patients. A few have seemingly been cured. Those physicians theorize that ME/CFS is autoimmune in the brain. Some others have theorized that killing B cells may reduce ME/CFS symptoms because EBV hides there and could possibly be causing a malfunction in the B cells, causing it to make autoantibodies. Kill the B cells and you kill EBV.

Could EBV behavior inside the cells be the cause of two autoimmune diseases, depending on what part of the central nervous system is being attacked by autoantibodies?

I would love to hear your thoughts on all of this. Ronald Glaser, PhD, has done studies on CFS, and the effect stress has on EBV. Might this be the thing that brings together those who see ME/CFS is triggered by stress and those who think it is triggered or caused by a virus?

Greg writes:

Hi guys,

Great podcast! I’m a PhD student at McGill and I work on HIV, but in more of a biochemical context than a virological one. Your podcast is great at rounding out my knowledge of the virus I work on, and of course many other viruses as well. I’m sure this paper is on your radar, as it comes out of David Baltimore’s lab, but I think gene therapy is an amazing technology and this seems like the perfect application in order to “cure” a difficult virus, HIV. (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10660.html)

Nature. 2011 Nov 30. doi: 10.1038/nature10660. [Epub ahead of print]

Antibody-based protection against HIV infection by vectored immunoprophylaxis.

Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D.

Thanks!

John writes:

Dear TWIVvers,

I loved your Concerto in B episode (TWIV 161). Your discussion left me with a bunch of questions regarding B cells and antibodies.

As I was listening to the discussion of affinity maturation, I kept trying to think of how this process interacts with existing memory B cells, and in particular, how it interacts with original antigenic sin.

What happens when you already have a good population of memory B cells to an antigen. Do you get new germinal centers forming and the affinity maturation process going on again? And if so, does it start with the B cells that have already been through that process, or does it start with new, immature B cells that responded to the soluble antigen? Does that depend on how much new antigen is available (if you have an effective antibody response, does that keep this process from restarting?)

Do some mutations in the affinity maturation process close off the possibility of mutating back in some way that would be helpful later, or is all the raw material still around in a functional B cell after affinity maturation, so that you can get from a good antibody to the 2005 flu strain to a good antibody for the one you get in 2007? It seems like there must be some impact of the existing stock of memory B cells on future affinity maturation, or you wouldn’t observe original antigenic sin. (And it seems like it should work the same way when there’s antibody dependent entry of cells, as with dengue–is this right?)

Is this process the reason why some vaccines require three shots to get protection? (I recall getting the Hep B vaccine many years ago in three doses–the second shot a month after the first, the third six months later.). Or is this more a matter of getting enough antibodies, rather than getting higher affinity antibodies?

Finally, listening to the description of the germinal centers, it seems like they should run out of antigen, since they’re using it up each time a B cell tries to take up and present antigen to the T cells. Is there some mechanism to recycle the antigen? Is the supply of antigen the limiting factor in this process, or is there plenty–maybe my intuitions at this scale are just all wrong?

Anyway, thanks for your wonderful podcasts, and for answering my amateur immunology questions.

Gabriel Victora answers:

Hi Vince,

Please congratulate you listener, these are all excellent questions. Unfortunately, I don’t think we know nearly as much about these things as we should. Vaccine development has historically been mostly empirical, and regimes are usually based on what works best rather than on immunological considerations (most vaccines were actually developed by microbiologists). Part of the difficulty in addressing these issues is technical – it would be very difficult and costly to serially determine the affinities and specificities of B cells responding to antigen during consecutive immunizations of the same individual (or animal).

I’ve written some ideas about what might be going on below each question.

Hope this helps,

Gabriel

>> The original antigenic sin phenomenon is most likely related to the rapid elimination of antigen by existing antibody or by antibody produced soon after the second challenge by existing memory cells. The novel (ignored) determinant would not be capable of priming naive B cells because it would be bound by circulating antibody and complement and eliminated before it ever had a chance to do so. As to new GCs, emerging data suggests that some memory cells (those that haven’t switched their antibody isotype) can make it back into GCs upon second exposure. I would expect that a secondary GC would therefore contain a mixture of B cells derived from naive and memory precursors. Many factors could influence the composition of this putative mixture, including competition between B cell clones for limiting amounts of antigen or T cell help.

>> I think this is mostly a matter of the extent to which the existing memory cells recognize the newcomer variant. If it is enough to trigger an “original antigenic sin”-type phenomenon you would probably not generate new germinal centers, in which case you would get no further affinity maturation. However, naive B cells are constantly being turned over (dying and being re-generated in the bone marrow). Therefore, the likelihood of a “hole” in the repertoire in 2007 arising due to all flu-specific B cells having gone the 2005 way is negligible. But theoretically it is possible that an unswitched 2005 memory cell could re-enter a GC in response to 2007 viruses, and in this case, it is conceivable that some cells could be impaired by 2005-specific mutations, but these would be unlikely to last in the highly competitive environment of the GC.

>> The three shots of vaccine have probably more to do with attaining high titers of circulating antibody in blood than with improving affinity. Serum antibody affinity already increases quite dramatically (up to 10,000 fold) within the first immunization, although serum antibody titers (a composite measure of affinity and amount of antibody) only really really go sky high after one or two booster shots. The idea is that whereas the first contact with antigen generates germinal centers and affinity-matured memory cells, the booster doses “reap the profits” of this germinal center reaction by triggering the ensuing memory cells to proliferate vigorously and differentiate into large numbers of antibody secreting cells within a few days. What the role in vaccination is of GCs emerging during booster doses is not clear (at least as far as I know), but could conceivably involve the recycling of unswitched memory B cells back into GCs for further affinity maturation.

>> This is a good question. Antigen appears not to be limiting, since it can be detected on FDCs many months after the GC reaction has faded, though how available this antigen is at this point is not clear. Many hypothesis exist for why the GC response ends; these include competition between B cells and circulating antibody (which would sequester the antigen available on FDCs) and exhaustion of GC T cells (perhaps through their regulation by GC-resident regulatory T cell populations). I tend to favor the latter, but this is still a topic of fervent investigation.

John writes:

Hello,

Attached are my two questions. I found your podcast even before the death of my sister during the 2009 H1N1 pandemic of ‘09. She died 14 Oct 09 from bilateral pneumonia as a result from a confirmed case of H1N1.

I received both the seasonal and H1N1 vaccines, as I’m not stupid, and not influenced by celebrities or former playboy bunnies (Ref. jenny mccarthy – Name intentionally lower case out of disrespect). I prefer my medical advice from a doctor, imagine that!

I’m sure I’ll have more questions as I make it through the episodes.

Very respectfully yours,

John

Raihan writes:

Hello …insert cool way of addressing you guys….,

In one of your previous twivs you guys mentioned about how after the H1N1 pandemic, the prevalence of Flu infections dropped, suggesting a ‘boost’ in herd immunity.

If you don’t mind I would like to chirp in to this discussion.

I am a grad student studying influenza here in Singapore. In my confirmation presentation (which was at the end of the H1N1 scare),I presented the following chart taken from the Ministry of Health (Singapore)’s website.

flu Singapore

The pink bar (pandemic H1N1) shows a decrease in size over time, corresponding to the end of the pandemic.

But what is interesting is that while pandemic H1N1 dwindles down, the incidences of seasonal flu A strains and flu B increases.

I am curious as to whether or not the same trend is observed in the US. You guys seem to suggest that after the pandemic the incidences of seasonal flu and flu B were not as prevalent, this is obvioulsy not the case here in Singapore.

http://www.cdc.gov/flu/weekly/weeklyarchives2009-2010/09-10summary.htm

On a separate yet related topic, I have to express my dismay in your podcast for not highlighting other types of Influenza. When you guys talk about flu, you exclusively talk abt flu A. This frustrates me as I am studying influenza B. I have only noticed influenza B Being mentioned only aBout 2-3 times in the course of your podcast, and it was always in passing. The only discussion aBt flu B was By Peter Palese where he suggested that flu B could be potentially eradicated due to its lack of an animal reservoir.

Pls dont get me wrong, guys are doing a Brilliant joB with the podcast, But flu B is my BaBy, would love to hear your insights aBt flu B as well.

My take aBout the ‘Are viruses alive or not?’ deBate;

I’ve Been thinking aBt this for quite some time and I totally agree that this is not exactly a biological proBlem as much as it is a philosophical one. As early as I can rememBer amongst the first few things taught in Biology is that the cell is the Basic unit of life. I think this is quite an agreed upon definition and no one would disagree with it, most of us would see this in Biology textBooks in all levels. Therefore since viruses are not classified as cells, it would Be impossiBle to define them as alive as much as organelles are not alive.

Hope my email did not Bore or Bother you guys. Just take my earlier complaint aBout Flu B as the rantings of a PhD student trying to come in terms with his lack of publishaBle data.

Marcie writes:

Dear TWIVers,

I am listening to episode 164 “Six Steps Forward, Four Back” and as you were mentioning the fact that you wished you could reach everyone it occurred to me that the podcast title, This Week in Virology is a little intimidating to people who may only have a high school knowledge of science. I am not suggesting that you change the name of the main show, but maybe you could do an occasional single-topic, explain–it-to-the-layman show when there are hot topics like the HPV vaccine, the H1N1 spread, or the H5N1 publication controversy. These could be the short ~15 minute shows that target a broader audience than your regular shows. The name would need to be something general, so as to cast a wide net (all of microbiology/immunology–you certainly have sufficient connections that you can recruit experts to do bacterial or fungal topics) if not broader ;-). It would also need to be non-threatening to the average person (think “Idiot’s guide to…”) so it would need to avoid words like Virology and Microbiology. Maybe something like “Hot Topics in Health and Disease.”

Marcie

Pittsburgh, PA

Where it is currently 50 degress F, and overcast.

Sven-Urban writes:

Ave, magi virorum!

(That ought to put me pretty high on the list of creative/obscure greetings!)

I have just enjoyed episode 169, where You all discussed the question from Sophie on how to read scientific papers. I fully enjoyed and appreciated Your learned views, all of them very valid for You as scientists. However, not all readers of scientific papers need be or become scientists, so perhaps You might let me add one layman’s perspective.

Just to give You the general picture, I am a Software Quality professional with a 30 year old M.Sc. in computer science. Out of general curiosity and for personal entertainment I occasionally read science papers from other disciplines, mainly from the section Evolutionary Biology in PlosONE. Many of the intricate details in those papers, whether they be on primatology, paleontology, ecology or (particularly) biochemistry, are usually beyond my grasp and knowledge. That’s fair, scientific papers aren’t written for laymen, and Alan’s way of describing a paper as a highly compressed packet of information for transmission over distance was very instructive. What I look for, and hope to find, is something reasonably digestible at the “beginning” and “end”. As Dickson pointed out the pictures and graphs are very important, as they may aid, or sometimes hinder if badly designed, the intuitive understanding of the data, and here too good handiwork might aid my understanding. With well worked out introductions, discussions and illustrations I, the layman, should be able to grasp the general problem/question/hypothesis, as well as the general result/conclusion/implications. And that’s my main point, on some level a scientific paper ought to be accessible also to the non-initiated – if it’s not, the paper and science is in some sense poorly or obscurely presented. (On the other hand, if science papers were always graspable by the populace Alan would be out of business pretty soon…) Of course, as a layman not understanding the details I have no way of assessing the validity of the results presented, but that is of less concern as I am not using the information gleaned for anything else than maintaining my image as an “incurable intellectual” around the coffee pot at work!

Searching my bookshelves for a listener pick-of-the-week I found something that at least distantly tags in with the main theme of the episode. I suggest two highly accessible books on how we tend to overly rely on noisy, possibly meaningless, data, how we tend to extrapolate trends ad infinitum and how we can not disprove the odd/unknown/unobserved phenomenon: ”Fooled by Randomness” and “The Black Swan”, both by Nassim Nicholas Taleb.

Thanks for Your continuing effort!

Sven-Urban

P.S. The greeting supposedly means “Hail Ye, mages of viruses”; kudos to Internet if I’m right, shame on me if I’m wrong…

Colm writes:

Sirs:

I have been listening for a while and finally have enough disjointed comments to merit hitting send, I hope.

First, you frequently make references to temperature conversion. Born and raised in the United States, I have a poor understanding of Celsius as it relates to real life. I know my incubators are at 37, and that’s toasty, and the lab is in the low 20s and that’s “Room Temperature.” I wonder if yo know of a weather application for iOS or Android that displays C and F side by side, for building those associations. I think it would be an amazing feature.

Secondly, I am not a Redditor, but I was recently made aware of their ‘Ask Me Anything’ threads where experts/insiders field questions from the community in long-running dedicated threads. For example, George Pelecanos, a writer and producer for The Wire and Treme recently answered dozens of questions in such a thread. It would undeniably be a massive time sink, but may be a useful way to disseminate Virology to the public.

Third, and finally, you mentioned in this week’s epidemiology TWiV that BSL-4 facilities seem to be predominantly government run affairs. That is generally true, but I am aware of at least one privately operated US BSL-4 in San Antonio at the Texas Biomedical Research Institute. The More You Know.

Best.

Diane writes:

Because I have CFS, I learned about you and your various podcasts during all the XMRV hoopla. After many years of struggling, I have been able to teach part time for several years now. I teach biology at a junior college, both a majors and a non-majors course, and I thought you would appreciate something that happened early on this semester.

I always start my classes with what I call “bioliteracy topics.” I will briefly introduce something in the news that is both interesting (I hope) and usually controversial. So of course I chose as one topic the H5N1 controversy. At the time, my understanding was that the mortality rate was near 60%.

Meanwhile, I had decided to listen to all the current TWIVS, TWIPS, and TWIMS, and to slowly go back and listen to all of the old episodes. So of course you know that I had to correct myself with my students the very next class! It actually helped me to make a point that I love to make – that science is not merely a collection of facts to memorize, it is a process. Those who undertake science must maneuver through this process, and the public needs to understand that, at any given time, the information they have may not be the final word, and in fact, what they are hearing in the media may be misleading or simply incorrect.

I allow my students to earn some bonus points by responding to the bioliteracy topics on exam days and several chose to write about the H5N1 controversy. I’m pleased I was able to provide them with information beyond the headlines – thank you for that!!

TWiV 175

Jane writes:

Dear Vincent,

Just a quick email to say how wonderful it was to meet you yesterday in Amsterdam! I have been an avid TWiV listener since my first “TWiV experience” in 2009 and look forward to many more podcasts.

If you recall, I mentioned to you a book I thought you and your readers might enjoy: Smoking Ears and Screaming Teeth, by Trevor Norton.

Prof Norton is Professor Emeritus at Liverpool University (UK), having retired in 2005 from the chair of Marine Biology. The book is described as “a hilarious celebration of the great eccentrics who have performed dangerous experiments on themselves for the benefit of humankind”. I regard it as a witty and informative romp through the history of scientific discovery, and the self-experimentation practised by the bravest!

I hope you enjoy your upcoming visit to Dublin and congratulations on (yet another) award!

With warmest regards,

Jane, MD MPH

Mark writes:

re poultry staggerers:

Marek’s disease would be worthy of consideration, but there are a number of other possible aetiologies (rye grass staggers, dietary deficiences).

https://en.wikipedia.org/wiki/Marek%27s_disease

Chris writes:

Hi Vince, Rich, Alan, and Dickson,

This is a long overdue e-mail to express my gratitude to you all. I am an Assistant Professor in Virology at UT Austin and have been hooked on your show since I became a new dad ~18 months ago (I’ll get back to that later). I would like to briefly highlight some of the ways TWiV has helped me:

First, as an educator- I teach an upper level undergraduate course on Animal Virology. There is no doubt that I am a better teacher because of TWiV. My breadth of knowledge of virology is greatly expanded as a result of my weekly TWiV fix. As a result of this, the students think I am smarter than I actually am! Your show has inspired an ongoing experiment in my class where as a teaching tool, we incorporate a student-selected current event relevant to virology. Topics typically come from the lay press and are scientifically dissected at the beginning of every class. This appears to be a big hit with the students, especially those who came into the course as a forced requirement as part their degree plan. Rightfully so, nothing peaks a student’s interest more than the relevance and timeliness of the topic. In addition, my students are offered as extra credit the option of summarizing an episode of TWiV. Typically, 60 of my ~90 students opt to participate in this exercise and their response has been very positive– several like it so much that they end up listening to many episodes.

Second, your show has helped me to be a better scientist. In addition to increasing my knowledge of tangential fields and new techniques, there have been several times where a new line of experimentation for my lab has emerged from TWiV. One example that comes to mind came from something Rich said (I believe) regarding consideration of temperature in experiments (I believe this was with regards to temperature sensitive mutants). This dialogue on your show made us consider the simple idea that temperature could account for the lack of an infectious tissue culture model for an upper respiratory virus that we are studying. We don’t yet know if this is the answer to our problems as we are still waiting for the new cooler temperature incubator to arrive. Nonetheless, this is a reasonable hypothesis to test, and this entire line of experimentation was inspired by TWiV.

Also in regards to how your show helps scientists, I must mention the “TWiV bump”. I believe that at least Alan is a Colbert Report fan based on his reference to “truthiness” on TWiV. As you may know, Stephen Colbert claims that artists who have their work mentioned on his show benefit in terms of recognition, sales, prestige, etc.– he refers to this as the “Colbert Bump”. I think it is obvious that this is also true for scientists whose work is mentioned on TWiV. In TWiV 174 you profiled a paper from my lab. Mere hours after that episode was released I was contacted by two different colleagues offering me their congratulations (and envy). You should know that it is a career goal of many of us younger virologists to get the “TWiV Bump”!

Finally, it is also true that you make parenthood easier! When I was a brand new dad and got to spend hours and hours with my son Sam, TWiV served a valuable role. Sam and I would go on long walks and TWiV made the time fly by while appealing to my sense of productivity. So not only is your show helping research professors and high school students alike, arguably it serves a positive role for some infants too!

In summary, I am grateful to you all. Knowing first hand the demands on a faculty member’s time (and imagining it’s similar being a free lance writer/reporter), I don’t know how you find the time to do this. It is a wonderful service to science and science education. As an NSF-funded researcher, I hope the NSF sees the value in what you are doing, and ends up supporting TWiV. I hope you keep up the TWiVing for a very long time!

Many thanks,

Chris

PS- We are trying to come up with a creative way to invite at least two of you to meet some of the faculty and do a show from here at UT Austin. As you know, there are several fans of TWiV here and Austin is a great city. I hope it all works out and that you will decide to come visit us.

—

Christopher S. Sullivan, Ph.D.

Assistant Professor

Dept. Molecular Genetics and Microbiology

The University of Texas at Austin

April writes:

Hi Vincent et al.,

Great show this week! On the note of coffee makers, this one beats them all for taste IMHO. Plus it’s made in the Berkshires! Check out: http://www.chemexcoffeemaker.com/

Keep up the great work!! I really enjoy the podcast on my commute from the Berkshire to Albany.

Best,

April, Ph.D.

The David Axelrod Institute

Wadsworth Center for Laboratories and Research

Ayesha writes:

Dear TWIVlanders,

http://scienceblogs.com/webeasties/2012/02/the_future_of_science_pub.php

http://cyber.law.harvard.edu/hoap/Notes_on_the_Research_Works_Act

http://www.opencongress.org/bill/112-h3699/actions

In trying to form an opinion on the subject, I’d love to hear what you have to say on the matter and why Elsevier are lobbying for this Bill. What will it mean? I’m a bit unclear.

Cheers!

Tessa writes:

Hello TWiV!

I’m rounding up my 4th year in my thesis lab and currently, the stacks of half-read/highlighted/triply-printed-papers are starting to take over all usable space on my desk. Help! I think the only way I can keep sane in graduate school is by keeping myself organized and regular doses of therapeutic humor from PhD Comics (www.phdcomics.com). Technology is getting so sophisticated. Do you know of an online service where a person can electronically accumulate and organize all of these pdfs, be able to search for key words, highlight, add notes, etc. and be accessible from any computer (lab or home)?

I’m super excited to attend a live recording of TWiV this summer at the ASV annual meeting hosted by the University of Wisconsin-Madison. Thanks to you guys I’ve proudly embraced my virology geekiness! Sharing the same sentiments as all your listeners, keep up the good work!

~Tessa, Ph.D. Candidate, Thomas Jefferson University, Philadelphia, PA

Kathryn writes:

Dear regular Twivsters and guests.

I listened to your last episode (#168) while chilling out in the hospital. What better place to learn about viruses.

I enjoyed the pick of Dr. Racaniello. I agree with the point of view of the teacher (as an ESL teacher myself). I can stand on my head and do back flips. The ones who want to be learning English do their homework and participate in class. The ones forced there do just the opposite or worse. They disrupt class or demand (not ask politely) to play games. Part of my teaching philosophy is to get the kids to learn without them knowing they were learning. I remember fondly watching Mr. Wizard’s World growing up. I didn’t realize how much I learned through that show and how it helped me through elementary school science.

Interestingly if you google the name of the blog post, you get an article about a South Korean (where I’m located) pilot project using robots to teach English. The picture shown is not a typical elementary class where there are 30-40 students. And the conclusions made at the end are a direct shot at the foreign teachers.

I should explain the educational philosophy of S. Korea. Kids go to public school in the morning (and then longer as they reach middle and high school) where they study basic subjects. English education starts in the 3rd grade. Many then go to private academies for lessons in specific subjects. Those third graders who have been studying English since approximately the age of 4 are light years ahead of their peers who didn’t go to English preschools (there is no mandatory kindergarten). While a foreign teacher has some kids learning basic phonics she has others not paying attention because they’re learning more grammar than I know. In fact the government is planning on phasing out native speaking teachers by 2015. They say the students are more comfortable learning from an English speaking Korean teacher. The fact is, they can get away with speaking Korean in that model, but not with a native English teacher.

I teach at one of the private schools where I have student from 6 to 14. At least they’re roughly grouped by ability. I do not allow students to use their cell phone dictionaries or portable dictionaries in my class room. I find the students use it as a crutch and don’t learn to use context clues to find meaning. I have my phone and if we, as a class, can’t figure it out, then I’ll look it up and read the Korean word.

Now for my virus question. I’m working back through the archives and just listened to the one on virus structure. Please correct my interpretation if if I get it wrong. We start out with the simplest form such as TMV where the virome (sp?) is simply wrapped in protein. This only works primarily in plants. When we get to non plant hosts you can have a similar structure inclosed in a lipid protein. Am I understanding that this comes from the host cell as the virus replicates and breaks out of the cell. Did I miss a specific word for getting out of the cell? On another level of complexity up is the envelope. And here there are two layers of lipids with protein in the middle. What is the advantage of that? Does it make the virus more resistant to the hosts’ immune defenses? The most complex is the protein shell. Describing it as such makes me assume that it is more rigid. Why is icosohedreal (sp?) the only type of symmetry? Wouldn’t a cube be as simple? 6 squares vs 20 triangles. Does what exists in nature give the most bang from the virus’s buck, so to say? it’s the most rigid with the least parts? Or is there some underlying factor in the tertiary or quantinary form of the proteins themselves?

I again want to thank you for addressing my opinions and well, basic questions. If TWIV had existed 20 years ago, I might be a virologist. I do hope some of my students go on to be scientists as they have said when we talk about jobs and what we want to be when we grow up. I wish I had an answer for that last question for myself.

Joel writes:
Hi TWIV,

The CDC’s EIS program has been mentioned on several recent TWIV episodes. I would like to nominate Tyler Sharp (http://blogs.cdc.gov/publichealthmatters/authors/tyler-sharp/) as a potential guest. I worked with Tyler in Michele Hardy’s lab in the summer of 2003. I had never met someone so passionate about virology as Tyler. One of my most vivid memories of him is how he carried your Principles of Virology textbook around with him all summer. He went on to earn a Ph.D. in Mary Estes’ lab and is now a lieutenant in the EIS.

Tyler recently worked in the Marshall Islands in an effort to control a dengue outbreak. He wrote about this experience in the CDC’s Public Health Matters Blog (http://blogs.cdc.gov/publichealthmatters/2011/12/real-life-contagion/ and http://blogs.cdc.gov/publichealthmatters/2011/12/real-life-contagion-part-2/). Even if it doesn’t work out to have Tyler as a guest, perhaps his two-part blog post could be a listener’s pick of the week.

TWiV 174

Mark writes:

Hi TWIVers,

I love your podcast! I am a postdoc in Joe DeRisi’s lab at UCSF and I know that right now I am supposed to be aiming for a faculty job. But my real goal is to discover something cool enough to end up on TWIV.

Anyway, the main reason I’m writing is to suggest this pick of the week: a fascinating Fresh Air interview with Craig Timberg, the author of Tinderbox, a history of the HIV/AIDS pandemic.

http://www.npr.org/2012/02/27/147491878/tinderbox-how-the-west-fueled-the-aids-epidemic

MP3: http://pd.npr.org/anon.npr-mp3/npr/fa/2012/02/20120227_fa_01.mp3

Thanks for TWIV – it is really a very good thing.

Cheers,

Mark

Postdoc, DeRisi lab, UCSF

Henry writes:

Twiv Team (T^2),

This one is primarily for Rich since he suggested Battlestar Galactica. I lost a week of productivity with that one. Thanks a lot 🙂

http://www.hulu.com/regenesis

I watched the first season while I was in Iraq as a medic. It is pretty good biomedical sci-fi, though the language and content make it for adults over a general audience.

I do not have any questions at this time. I have listened consistently ever since I joined a virology/biochemistry lab for my PhD work. Thanks again for the great show.

Cheers,

Henry

Ian writes:

Re: Alan’s query of rectal swabbing in the ‘A distinct lineage of influenza A virus from bats’ paper…

Wouldn’t the rectal swabs have had more to do with looking for the possibility of transmission of a virus via the guano, with human exposure to the guano (…being collected for use as a crop fertilizer…) being the theoretical infection route?

Jason writes:

Hey TWiV crew,

I took the opportunity to donate blood today and noticed that in addition to the normal information about HIV, Hepatitis, NAT, etc. testing, there was a page an a half of information about XMRV and CFS. I pointed out that the information they provide has effectively been debunked to the first screener, who effectively dismissed my comments. I think they were volunteers and not really medical professionals, so that response seems normal. When I was then screened by an RN, I mentioned the problem again. She seemed taken aback that I would claim their pamphlet was incorrect, and then effectively dismissed my claim.

In looking over the pamphlet now, I notice that it’s the 2008 revision, so I suppose the data on there is accurate for about that timeframe, but I find it somewhat irresponsible to continue spreading incorrect information so many years later.

I do find one of these questions somewhat amusing. They ask whether a person diagnosed with CFS should be donating blood. The answer they provide is that while the person donating should be in good health, it’s up to the medical directors at the blood collection centers to decide whether or not people diagnosed with a history of CFS should donate or not. With all of the precautions prohibiting donations from people who have been in contact with others who are diagnosed with illnesses like hepatitis or HIV, I find it hard to believe that they leave it up to the medical director to make the call on CFS.

At any rate, keep up the interesting podcast. Despite not being in the field, I find it stimulating and I’m learning a lot. Or, at least, learning enough to cause trouble… 😉

Jason ‘XenoPhage’

Roger Dodd, VP for R&D, American Red Cross replies:

Thanks for asking. This is an interesting commentary. My first comment would be that, while most aspects of blood collection are highly standardized, different organizations may have differing approaches to certain issues that are not defined by regulation or voluntary standards. Certainly, management of CFS and XMRV would fall into this particular category. AABB, the professional organization for transfusion medicine did issue some guidance to its members in 2010, recommending that blood collectors “educate” donors and ask them to refrain from donation if they had a medical diagnosis of CFS and providing website information for CFIDS. Interestingly (and to my mind appropriately) XMRV was not explicitly mentioned. For some blood collectors (the Red Cross is one), this procedure is still in place: Red Cross materials, however, do not mention XMRV. However, the task force that originally made the recommendation has advised AABB that its members should revert to whatever practice was in place prior to the recommendation. It is possible that the educational document was handed out along with other materials dated 2008: I doubt that any blood organization in the US had any explicit materials about CFS in 2008 and they would definitely not have cited XMRV then.

Blood collection staff are supposed to be knowledgeable about the materials that they distribute, but they are engrained in a highly disciplined and strongly regulated environment. If they have not been retrained, it is quite possible that they would adhere to prior requirements. Unfortunately, it is also possible that that they would not be particularly knowledgeable about the medical and scientific issues at hand.

Finally, in areas of medical uncertainly, it does fall to the medical director to make final decisions about donor eligibility. The overriding criterion is that the donor should be healthy and feeling well at the time of donation.

Your correspondent has asked astute questions – I hope you can make sense of my responses.

Please do not hesitate to get back t me if more is needed. If you would prefer the one-word answer, it is “inertia”!

Best,

Roger

Keith writes:

Dear Twividae,

My name is Keith and I am with the HIV Reference Laboratory here in the Bahamas and would like to know if you have heard are any online PhD programs where the thesis can be completed at ones own lab. If any of you are ever in the Bahamas send me an email, I can show you around.

Thanks, Keith

Benjamin writes:

Howdy “Hosts”

I’m one of those three highschool geeks who listens to TWiV TWiP and TWiM. I’m sixteen, and while some of the subjects (Like the molecular bio of zinc finger) are above me, your science is down-to-earth and understandable.

I’ve been latently infected since late 2010 since TWiP and TWiM had fewer episodes to get a catchup hold on. A couple of weeks ago, however, it became a full blown clinical infection and got the world’s biggest TWiV fix. What a powerhouse, you guys. Now, thanks to TWiV, I’ve fallen behind in my other podcasts.

I’ve had an unofficial game going with Alan since TWiV 20 to see if I can come up with any bad virus puns that he missed. So far, I’ve only gotten one. In TWiV 58 – Nipah virus in ferrets, the scientists doing the experiments were ferreting out the mode of infection. It’s no secret that I have a droll sense of humor, so maybe other listeners can go through the TWiV backlog to find more.

I would like to offer my take on the aliveness of viruses. Every time you argue the point of viruses, you bring up the prions and transposons. Transposons are not alive since they are genes already in the genome rearranging themselves spontaneously and stochastically as far as I can tell. Thus, they are mutations, not organisms. Prions are misfolded proteins. CJD (Creutzfeldt-Jakob disease) and kuru are basically the protein affecting the tissue and misfolding more proteins. The damage could probably be replicated by injecting pepsin, tripsin, and demyelination factors, which are also proteins, and thus, prions are also not alive. Then, we come to viruses. Viruses are beautifully designed to do what they do best. The characteristics of life list (Bio 221, Earl Beyer–iTunes U–Talaro’s 7th edition of foundations of microbiology) are many, but several include: reproduction (check) a genome (check) and a “cell” barrier (check) by this reasoning, viruses are alive despite a marked lack of things like irritability, (that means response to the environment) metabolism, cellular design et al.

I think I tipped my politico-religious hand in the previous paragraph, but that needs tending to as well. I can’t imagine that me and one of my friends that I hooked on TWiV are the only Christians (shall I say, non-evolutionists?) getting our TWiV fix every Monday morning, so in the future could you please think twice before shamelessly trashing religion?

In TWiV 150, Rich talked about Buda, TX. I happen to have lived close to there (by Texas’ standards…it’s about a hundred miles) for all my sixteen years and have never heard it called anything but BOO-duh.

I’ve written you on TWiP before about a syndrome that I called “Stumbling Poultry Disease” maybe with all the resources of TWiV we can get an answer. DESCRIPTION: It only happens in the summer when the local temperatures soar as high as 115º F in the shade, (I’ll take up Rich on the challenge that no one but a Floridan could survive the Florida climate) superheating the waterers to well above the required 90º F for E polyphaga despite our best efforts. Add that to the fact that chickens and turkeys are sloppy drinkers, (meaning that water runs into their noses) and wallah! We have poultry displaying weird behavior followed by disorientation, stumbling, vertigo-like symptoms and eventually death. Perhaps Alan with his insta-google or Rich with firsthand experience with the southern climate can add some ideas to the pool.

That’s about it for now, love the podcast, hoping for TWiB and TWiF. Live long and podcast,

Greetings from south-central Texas, the summer residence of the golden-cheeked warbler. (cue impromptu ecology lecture by Dick)

Jon writes:

Dear Vincent, Dick, Rich, Alan and the TWIV gang,

I found the recent experimental use of viruses which can only reproduce in cancer cells (reported in TWIV 156 and 131) as anticancer agents to be exciting news. I wonder if it is possible to use natural selection to produce viruses (or for that matter immune-system evading parasites) with improved cancer-killing properties, alleviating the need for rational drug design.

Sincerely,

Jon

Rick writes:

Hi Vincent, Rich, Alan and Dickson.

I’m a software engineer at Google with a bit of education in genetics and computational biology. I’ve been listening to TWiV and really enjoying it for a couple years now, but it makes me really curious to better understand the patterns of infection in my own home. It drives me nuts that we can understand so much about viruses in general, but when I get a cold I don’t know what virus and strain it is or where I likely contracted it from. I can imagine a future where it’s routine and virtually free to sequence someone’s virome whenever they are sick – imagine what we could do with all that data!

So I want to try to learn more about the patterns of infection in my home (eg. what viruses do we get, do my kids tend to get viruses from me or vice versa, etc.). I’ve been reading a number of papers and searching for services/tools I could use but it’s tricky to get a good picture about what techniques would really be practical (and safe) to do myself from home. Perhaps the ideal approach would be to find a lab that would do multiplexed RT-PCR on nasopharyngeal samples I send them, giving me the viral load for the most common URT viruses. Maybe I could also do a little home DNA purification and send it out for sequencing when I wanted to know more about the precise strain. The simplest approach looks like it would be to order some ELISA kits, but it would be nice to have the sensitivity and quantified result of PCR so I can track viral load over the course of an infection. I’m willing to invest a bit in lab equipment and services, but would ultimately like to find something scalable and cost effective. Is there anything you can suggest?

Along these lines, here’s a potential pick-of-the-week for you: BioPunk: DIY Scientists Hack the Software of Life. I like how this book relates the current state of biology to the early years of computing, and suggests what might be possible if biology gets the equivalent of the open source movement and personal computers.

Thanks, keep up all the great work on TWi*!

Liam writes:

Hello twivers,

Have you seen this?

http://www.lukejerram.com/glass/

TWiV 173

Judi writes:

A listener pick – since I know you all really enjoy the visualization of science!

http://www.nsf.gov/news/special_reports/scivis/winners.jsp

Judi (high school teacher, lover of TWIV, TWIM, andTWIP)

Glenn Rall writes:

My very favorite title was the “Super CalTech…” from a couple of weeks back. It takes either a very creative or very sick mind to come up with something that amusing.

Barny writes:

Dear TWIVists

My primary reason for writing is just to thank you all for the countless hours of entertaining education. If you feel that it would be interesting for TWIV it would be great if you could address my personal story, and it may stop others making the same mistake.

I have never been immunized with MMR, and have had all three of the illnesses; due to a bad case of mumps I have permanently lost the hearing in one ear, thankfully not more. When talking to my parents they said that the MMR autism scare was not the primary reason for not immunizing.

They seem to believe that having measles would have given my immune system a “work out”, in my case this has not worked to well. However i would like to know if there is any truth in this “what does not kill you will make you stronger” theory. My ex-family, and their current, doctor supported and encouraged their choice.

I am pro-vaccination in general but do not blindly support all vaccines. I hope this is not a too immunology based query to be addressed on TWIV.

Thank you and keep up the weather based introductions, bad jokes, general informal chat and educating the planet.

Barny

TWIVite

Cardiff. Wales. UK.

Alice writes:

Twivvers —

Just listened to your really in depth review of “Contagion” on TWIV. I thought I would let you know about a short conversation I had with one of the co-stars, Bryan Cranston, who played a military character named Lyle Haggerty (I haven’t seen the movie yet, I got this from IMDB.)

In November, Cranston came to the State Department (where I work) to film some scenes from an upcoming movie called “Argo.” After he finished his scenes, he hung out with us for a little while (very nice guy). I mentioned that my son had seen “Contagion,” and that he had liked the movie.

When I said this, the effect was pretty dramatic — Cranston got real serious, practically did a full-body shiver, and said that after he did “Contagion,” he became very wary of touching door handles or anything else; it really had an effect on him. He said, “It really makes you wonder about what’s on surfaces that might be dangerous.” I didn’t know what to say; all I could do was agree with him because what he said was true — even though a person shouldn’t worry about it to excess.

He probably should listen to TWIV — maybe he’ll feel better.

Anyway, great review and love TWIV, TWIP and TWIM. Keep up the good work.

Cheers,

Alice

Freddie writes:

Hello there Twivers !

My name is Freddie, and I run a software company in London. I came across your wonderful pod-cast on Stitcher by accident back in November, and have been hooked ever since.

Listening to your witty discussions of contemporary science has opened up a whole new world of knowledge and discovery, that I’d previously assumed I’d shut myself off from by not studying science at university. I work long hours at my company, but whatever free time I have is invariably spent watching Vincent’s Introductory Virology lectures. Vincent – thanks so much for putting these online! I finished the 3 lecture introductory series over Christmas, and am now tackling the 26 lecture undergrad series. When I’m done, I intend to work my way through the graduate series, and in time I plan to make the switch from working with computers to working in bio-technology. This is such a fascinating area! With computers, our knowledge all proceeds from first principals. But with biology it’s like we’re reverse-engineering an advanced alien technology, which is really exciting. I hope to one day program living organic systems, much as I now program software systems.

I just finished listening to your last pod-cast, which ended with an email from a listener who complained about the tone of your discussion about the NSABB and their treatment of the H5N1 issue.

I just wanted to say that I had completely the opposite reaction to that listener. I felt that your discussion was completely fair and reasonable, and there there was nothing remotely hubristic about it.

Its true that I’ve never heard you guys get stressed about an issue before on Twiv. But, scientists and lovers of truth and reason as you are, that is completely reasonable. If you’re going to get indignant about anything in life, then scaremongering and group-think are good things to take a stand against, and I applaud you for being outspoken about your very reasonable views.

Science and reason may have a foothold in the western world, but the notion of scientific impartiality has been under a sustained attack of late, and it’s become acceptable to criticise a politician for being ‘too intellectual’. It will be a very dark time for all when science and truth are subordinated to fear and prejudice. Scientific openness is an important issue, and you’re absolutely right to feel the way you do, and speak your minds about this.

You were big to apologise, and see things from that other listener’s perspective. If only self-criticism and open-mindedness to other views were more common in the world today. But I personally don’t think you had anything to apologise for. Compared to all the phoney sensationalism that often dominates popular culture and political decision-making, I found it profoundly refreshing to hear you guys getting passionate about something that really matters, with the facts on your side.

It may be true that in an open debate reason will, eventually, win over fear and prejudice. But not if lovers of reason fall silent because they don’t want to offend the scaredey-cats. So don’t ever feel you need to be ‘polite’, and silent in the face of nonsense. Listening to that episode made me fell passionate about this issue as well, and I spoke with several friends about it. That’s how good ideas are spread, and the tide of fear is held at bay. I suspect that the vast majority of your listeners would agree.

All the best, and thanks again for a wonderful pod-cast 😀 !

Freddie

Josh writes:

Dear TWiV Doctors,

Regarding the situation with the NSABB: I heartily defend the derision that you heaped on the Michael Osterholm and the NSABB, and disagree entirely with the letter from “joe”, the lawyer.

I am not a scientist, but from what I know, it’s not the motives of the persons involved that matter. It’s the science. They either follow the science or they don’t. If they do, then they are fine, and if they don’t then they deserve the same treatment that is reserved for homeopathic “doctors”. Just because Mr. Osterholm is sincere, doesn’t make him somehow above criticism.

Saying ” we know but we can’t tell you” to serious researchers, is an outrage and they deserve whatever they get. If they don’t like it, well, how does that phrase go about the kitchen and the heat?

P.s. Look forward to the show every week.

Sincerely,

Joshua

Paul writes:

Hi TWiVers,

I’ve been listening to TWiV since last October and love it. While listening to the discussion about the single virus genomics paper on TWiV 171, and having read the paper several months ago, it struck me that I would get even more out of TWiV if I knew the papers that you’d be discussing for the upcoming TWiV. I would bet that there is a subset of listeners who would download and read the papers before listening to TWiV or leaf through the papers as you are discussing them. What do you think?

Thank you for all the great podcasts,

Paul

University of Pittsburgh

TWiV 172

Greg writes:

Dear TWiV,

The epidemiology episode with Michael Walsh was great. I loved the philosophical detour into counterfactual statements, time travel, and the meaning of causation. TWiV may indeed be viral, but from listening to it I feel inoculated against the micro-specialization that is endemic to so much of science.

Dr. Walsh’s rigorous stance against making statements of causation based on epidemiological studies reminded me of the following xkcd webcomic:

http://xkcd.com/552/

Allow me to thank you all for putting on TWiV, TWiM, and TWiP. I’m a physicist who has inexplicably become a postdoc in biomedical engineering. I find each of your podcasts to be a revelatory journey into biology. Often I return with something I feel like talking about to complete strangers.

All the best,

-Greg

Øystein writes:

Dear Vincent:

I’m writing you to thank you for a truly inspiring present! I’m a Norwegian veterinarian doing a Phd in virology at the Norwegian School of Veterinary Science. I’m a big fan of your podcast and a little while ago my girlfriend apparently contacted you, regarding our three year anniversary and my birthday in December. I don’t known if you remember this, but she asked if you could write a little letter to me for this occasion. To my surprise, included in her gift was an envelope marked Columbia University, New York. No technological gadget or other materialistic gift could have beaten this present. Inspiration can’t be bought, and I really appreciated that you took the time to write me. You and your crew on TWIV are truly a source of knowledge and motivation. Your podcast has really educated me both in virology and the scientific way of thinking.

In my PhD I’m working on a novel reovirus called Piscine reovirus (PRV). PRV is associated with Heart and Skeletal Muscle Inflammation (HSMI) that is an emerging disease in farmed Atlantic salmon. The virus was actually discovered in 2009/2010 in collaboration between the lab of my supervisor Dr. Espen Rimstad at the Norwegian School of Veterinary Science and Dr. Ian Lipkin’s lab at Colombia University New York, using high throughput sequencing. Thanks to their work a PhD position later opened up to study this new virus, and that’s how I got into virology. I really enjoy the field, and TWIV has made it even more interesting. Thank you, Alan, Rich and Dickson for your superior podcast. Keep up the good work, I hope you are motivated to continue for a long time.

By the way, the temperature in Oslo is -5°C.

Sincerely,

Øystein

Norway

Thomas writes:

Dear sirs,

Firstly, happy new year to the entire gang. I look forward to another wonderful year for all 3 podcasts. I hope you reached your 1000 mark for your listener survey and I am excited to see where TWIV goes from here.

My main reason for writing today is in response to some comments made during the year in review TWIV (#164). I believe it was Rich that made the observation that most of the articles that were chosen were somehow implicated in human disease and pathogenesis. He then went on to mention that many of the issues with some of the more controversial stories dealt with the public’s knowledge of science and how projects, such as the H5N1 influenza project, are portrayed in the media. (P.S. Thank you Vincent for the articles on the TWIV Facebook page! It helps me to keep on top of the issue without having to search through various sources).

I’m not sure what your experiences in college were. but mine involved that of a small Catholic liberal-arts college in rural NY state. Here we were required to complete the compulsory courses to obtain our B.As, B.Ss, etc. along with the compulsory courses as part of the the liberal arts curriculum. Topics in this curriculum included micro-economics, sociology, sacred texts of various religions, and an intro to science and the scientific process, to name a few. I felt I left the school with a general understanding of many topics to an extent where I am less intimidated by balancing a checkbook, confident in being able to converse and interact with peoples of various religious backgrounds, and obviously an extensive knowledge of science given my studies in biochemistry.

My question to you gentlemen is this: Do you feel that a liberal arts education would help the situation discussed during TWIV where it appears that the general public is just not “competent” in the scientific process and how science actually works? I feel that my introduction to foreign subjects such as micro-economics and religious texts was sufficient for me to feel less ignorant of the material and confident enough to make prudent decisions should I be faced with one concerning such topics. Thus, I would hope that my classmates who were not science majors and were introduced to very basic level scientific concepts and the scientific process would similarly feel more confident in not being lead down the wrong path by media or other sources.

I apologize for the length of the e-mail but I sincerely believe that the liberal-arts education I received was excellent for the reasons I alluded to above and I wonder what your opinions are on the matter. Keep up the great work and all the best in 2012 and many years thereafter.

Mike writes:

Hello TWIVites!

I just recently listed to episode # 164, and was delighted to hear your response to my question. Thank you so much for taking the time to contact your colleague and relay my question to her. I very much appreciated her taking the time to respond, and the depth of her answer. However, the answer left me with yet still more questions. The colleague you mentioned in your response seems to be pursuing a type of therapy that involves using various cellular signaling factors to activate transcription of the viral genome in an otherwise latent cell. Once the viral genes are transcribed and the virus begins to actively replicate, antiretroviral therapy is used to prevent the spread of the virus to uninfected cells while attempting to kill the viral infected cell with another form of anti-viral therapy. Your colleague (Kathleen Collins M.D./Ph.D.) said that the trick to all this is finding a balance between efficacy and toxicity – in other words…kill the bad cells, but leave the good ones alone. I found her answer to be very complete and satisfying to the question that I asked, but now I have a few more…

1.) Is it true that HIV can only infect cells that are positive for the CD4 receptor?

2.) If question #1 is true, does a CD4+ cell infected with HIV express any cellular surface markers that uniquely identify it while not alerting the immune system when it is still in a latent state?

3.) If the answer to question #2 is “yes”, would it be possible to engineer a monoclonal antibody that can tag that unique surface receptor?

4.) If the answer to question #3 is “yes”, would it then be possible to tag that antibody with yet another antibody that is ferromagnetic? (Or maybe just make the first antibody ferromagnetic)

I recently saw a program on the Discovery channel that showed a recent experiment involving rats and longevity. In this experiment, the researchers used this kind of antibody tagging system to remove senescent cells from the bodies of aging rats. The whole process used a piece of equipment that looked somewhat similar to a dialysis machine. The machine used a magnetic field to pull senescent cells out of the blood as the blood was filtered through by pulling on a ferromagnetic antibody attached to those cells. The blood was then pumped back into the rat. The rat behaved like a much younger rat after that and did not show many of the aging related diseases that other rats who had not undergone this procedure did. I suppose my ultimate question is this…

Could this same process be adapted for HIV, or for any viral infection for that matter where a unique surface protein/glycoprotein (or any other kind of marker) is expressed on the cellular surface?

Thank you for taking the time to read this, and I will understand if you do not respond due to the length of this email. Also, I would like to thank all of you for what you do. I listen to your podcasts (TWIM, TWIV, and TWIP) on my way to work and it makes the drive go much faster! Please forgive me if this is an ignorant line of question as I am somewhat of a layman – I only have a couple of Bachelor’s degrees in science. Once again…thank you!

P.S. Please tell Dickson that I live in the Chicagoland area and will be touring his vertical farm project in the next few weeks!

Eric writes:

Dear Professors,

I am a twiv listener and I enjoy your podcast and trust your judgement.

I recently came across this story. I would appreciate your thoughts. Is there any truth here at all? The story is fairly short. Knowing what the government did to Soldiers in the 1950’s I can’t reject this out of hand. If this is all just BS, then it needs to be exposed.

Regards,

Eric

Here’s a link to the story which I also pasted below.

http://lewrockwell.com/orig6/larosa6.1.1.html

The linked story also links to a few books; one which has high reviews,

http://www.amazon.com/gp/product/0465021824?ie=UTF8&tag=lewrockwell&linkCode=xm2&camp=1789&creativeASIN=0465021824

Margot writes:

i’ve just started listening to you guys [no gals?] and am enjoying it.

here’s my question [and i’ve only listened to a two so far, maybe you’ve addressed this already]: do viruses have any positive effect on humans? we’ve discovered so many important roles bacteria play but the only good thing i’ve heard about viruses is that they have influenced our evolution.

thanks,

thebloggingnana.wordpress.com

“True compassion is more than flinging a coin to a beggar; it is not haphazard and superficial. It comes to see that an edifice which produces beggars needs restructuring.” MLK

TWiV 171

Daniel writes:

Dear TWIVers,

Great podcasts. I’ve listened to them all (TWIV/TWIP/TWIM).

(insert required adulation)

I enjoyed this and figured you might as well. Takes a bit to load, but it is worth it.

http://htwins.net/scale2/

Thank you all for donating so much of your time for all of our entertainment and education.

Tom writes:

Subject: Nonscientific hypothesis to explain H5N1 claims.

Hi Twivarians,

Old trick to find enemy activity in an area of scientific research:

– Claim a useful result that ‘just works’ but really doesn’t.

– Trace the enemy signals when they test it.

Imagine it’s possible to monitor ferrets or some other signal:

– Track ferrets going to the bad guys.

– The voluntary moratorium and higher BSL requirements cut down the noise.

Big downsides for scientists in this scheme:

– Can’t promote a good idea, or the enemy might make it work.

– Need a way to drop the idea, or risk becoming a Duesberg.

Thanks for the enthusiasm, conversation, knowledge, ideas and great audio!

My health span will end someday, but with your help it won’t be from a microbe.

-tom

PS:

With trepidation I took the survey. I thought it was going to include virology questions (what’s your favorite sequencing service?) or make me feel silly for listening without a formal education in biology (where did you get your PhD?). But the questions were about if I buy stuff that I hear about on podcasts. Easy! Short answer: yes. Long answer: hell yes!

Laurieann writes:

Dear TWIVers,

They say that any press is good press and while the hype concerning Fouchier’s virus is overblown and unfounded, it is heartening to know that the general public has an interest in knowing what virology researchers do and how it might impact them. It’s exciting to hear students chatting about the supervirulent virus and engaging in virology in ways that I can only hope to achieve in the classroom. Thought you might be interested in the attached editorial written by science writer, Laurie Garrett about government regulations on synthetic biology using Fouchier’s experiment as an example.

http://www.jsonline.com/news/opinion/balancing-research-with-safety-is3o3u3-137330538.html

keep up the great work- I started listening to TWIV as a postdoc back when the episode numbers were in the “teens” and haven’t missed an episode since!

Laurieann

Clinical Assistant Professor

Marquette University

Joe writes:

I started listening to TWIV around no. 40. I enjoyed it so much that I listened to all previous episodes and haven’t missed a new one since. You managed to intrigue me so much about virology that I also listened to your entire course at Columbia (twice), read several virology textbooks and engaged in similar self-study in immunology as background to appreciate the field better. Obviously, I am not a microbiologist. In fact, I am just a lawyer (gasp) although my undergraduate degree was in organic chemistry. But thanks in large part to you, I have developed what I believe is well informed side-interest in the viral world.

All of this is to say that I feel I owe you a debt of gratitude. And it is for that reason, and also so that you might take my feedback more seriously, that I am writing you a private email as opposed to simply posting my concerns as a comment on the TWIV site.

For the first time in hundreds of hours of listening to TWIV, during TWIV 169, I actually felt like shutting down my browser right in the middle. In particular, I was completely turned off by the group’s discussion of the NYAS H5N1 dual use forum. It is not that I even disagree with you on the merits of whether or not the details of the Fouchier research should be released. But the disdain and contempt the TWIVers showed for those who disagreed with them, especially Michael Osterholm, was unbecoming.

I have followed the recent dual use research debate and watched the 2-hour NYAS forum. Michael Osterholm might be wrong, but he struck me as sincere and entirely motivated by a genuine desire to discharge his mandate to the best of his ability. Yet the TWIVers were uncharacteristically hostile to him in particular and the other side more generally to the point of even impugning their good faith. There seemed to be no recognition that the NSABB is charged with a horrible responsibility, one which you have the luxury not to bear but just peck at. Instead there was just scoffing at their consideration of unquantifiable risks as fear mongering. And I don’t think you in particular, Vince, were fair in your selective quotations and summary of the event. Your point about the case-fatality rate was obviously right but the show beat that straw horse to death, and you didn’t offer much more than a caricature of the other side’s arguments. You were all over Osterholm but were strangely silent about Arturo Casadevall who was in substantial agreement with him, but also carries the sort of credentials you seem to respect more.

What the TWIVers displayed in this show was an irony one sometimes sees in highly specialized science experts. They are so meticulous and careful in describing their own fields, the precise extent of their knowledge and the limited conclusions that can be drawn from their research. They are hyper-vigilant of outsiders misunderstanding the implications of their work or making exaggerated claims about it. Yet if their interest is piqued in an area outside their chosen fields, especially in policy or political issues that might affect them or their work, they will generalize and make sweeping conclusions and pronouncements with the best of them, assuming knowledge and judgment about outside matters (like national security) that would cause them to breathe fire if an outsider did the same in their field. [I have also been reading a lot of cognitive psychology lately, which has inspired me to call this phenomenon the “hubris heuristic”.]

In fact, that whole part of TWIV 169 had a polemical flavor I’m quite used to as a lawyer but which I dabble in science to escape. How disappointing. One of my favorite things you did on your show back in the early days was ban the occasional political witticism (usually from Dickson and usually aimed at Bush). Maybe you can renew that wise impulse at this time.

Regards,

Joe

PS. I was also really looking forward to the focus on viral epidemiology, hoping that the show would shed some light on some areas I still scratch my head about — like how herd immunity is estimated for different pathogenic viruses. Maybe next time.

Stefan writes:

I also watched the New York Academy of Sciences hosts a panel of leading scientists, publishers, and ethicists who discuss issues surrounding controversial H5N1 research, which you were a part of (http://www.nyas.org/MemberCenter/AcademyNews.aspx?cid=8c61a204-36f6-4df8-8bd2-059882c5e287).

Dr Fouchier’s research pinpointed a threat that mankind was not aware off and thanks to their findings we have been given the chance to act on it ahead of time. I think that Dr. Fouchiers findings should be made accessible to the public and the recombinant virus be shared with select research groups. With the extensive global effort to study influenza, there may already be other labs that also introduced similar mutations into influenza without checking them in ferrets, these people need to know.

The discussion, whether ferrets are a good model is futile, they are only a model, they may lie, they may exaggerate, they may even be precise, we cannot possible know – only guess. The only thing we know is, If ferrets are a good model this is very bad news. The question now is not IF but WHEN a human-transmissible H5N1 appears in the wild. May it be by nature, may it be by hand of a terrorist with a foreign or not so foreign name, or may it be by escaping from a research-lab. Dr. Osterholm mentioned we cannot be wrong on the risk we take studying this virus, but what about the risk NOT studying this virus ? Nature is the fiercest bioterrorist imaginable. Which risk is bigger the chance of this virus escape man-made or the virus appear nature-made ? I cannot predict the risk of the virus being released man-made but the epidemiologists at the CDC surely can predict the risk the virus appear being nature-made using mathematical modeling provided they have all the necessary information. Of course there is a risk of studying this virus, but I sleep better knowing researches do something about it rather than procrastinating the problem until it hits us.

No one can predict the implications of research only history will tell. This current situation is a precedent, so how do we need to learn from it. The role of governments is to protect people i.e. promoting research to develop vaccines and to provide and enforce guidelines to conduct research in a safe way. The role of the scientist is to conduct research in a responsible way, which relies on the freedom and duty to discuss findings publicly and being peer-reviewed. The role of publishers is to provide this platform. This system works if governments act on their responsibility to promote and fund vaccination research. This system works when scientists are well educated, are peer-reviewed, and discuss their findings publicly, this system works if publishers provide editorial guidance to provide a good quality publication suited for the public. However, this system does not work if politicians publicly scrutinize vaccination and governments inadequately fund research. This system also does not work if scientists proclaim sensational research before being reviewed. And this system does not work if the press publicly discusses, whether something should be published or not.

Sorry I had to get this of my chest 😉 and of course feel free to read/post this on TWIV.

Stefan

PS I am still doing some research for a poliovirus lecture and stumbled across this wonderful video about Thomas Francis and Jonas Salk. I think this clip reminds us of the forgotten perils of pre-vaccination times and puts things in perspective. Maybe you want to share this on TWIV should there be suitable context. If you find a public relations contact for Delta airlines they may want to replace some of their more recent videos on vaccination:

http://www.sph.umich.edu/about/polio_video.html

Hail to the polio pioneers,

Stefan

P.P.S.

I googled for a copy of the uncensored Fouchier paper before the press frenzy and there were links that claimed to contain a a draft of the original manuscript. I have not verified or read any of them but it is only a matter of time before this information gets in the wrong hands. The good thing now is that it will be almost impossible to find this among all the comments and tweets about this subject. Mission accomplished 😉

+——————————————————–+

Stefan Taube, PhD

University of Michigan Medical School

Department of Microbiology and Immunology

TWiV 170

Jim writes:

Honored Profs:

May I suggest a pick-of-the-week podcast that captures the difficult aspects of creativity and research that may help students of your craft understand the 90% perspiration part of your work. A download link of, http://www.econtalk.org/archives/2011/05/byers_on_the_bl.html , also describes the hour-long podcast as follows:

“William Byers of Canada’s Concordia University and author of The Blind Spot talks with EconTalk host Russ Roberts about the nature of knowledge, science and mathematics. Byers argues that there is an inherent uncertainty about science and our knowledge that is frequently ignored. Byers contrasts a science of wonder with a science of certainty. He suggests that our knowledge of the physical world will always be incomplete because of the imperfection of models and human modes of thought relative to the complexity of the physical world. The conversation also looks at the implications of these ideas for teaching science and social science.”

Regards,

Jim

Smithfield, VA

John writes:

Good day to the TWIV Nation:

I’m giving a shout out to Dr. Welkin Johnson from TWIV 168. He got us listening for a “Viruses, Genes, and Evolution” course at Boston College. The lectures on Virology 101 have been extremely helpful and refreshing. I got excited to hear he was a guest this past week. Be sure to keep him coming back so his students can eventually make him his own auto-tuned remix of his comments on TWIV and get it going “viral” on YouTube.

I was thinking about the vector immunoprophylaxis results by Baltimore’s lab at CalTech and see them as very exciting (see reference below). Yet, provided these results may yield a future vaccine, it seems likely to me that the final product would only be administered to people in close contact with HIV-infected individuals and not everyone–perhaps those that are traveling or working with patients of HIV such as nurses or paramedics?

Furthermore, with HIV as the target, many new vaccines would be in development for other target surface proteins year after year. The difficulty surely lies in developing various vaccines that elicit specific immune responses effective against the many mutating strains particular to areas of the world. Is this feasible or is it worth investigating yet another mode of inhibition? Whatever the case, it’s a stride all the more.

I do have a technical question about VIP. With the addition of the gene to a cell’s nucleus via the adeno-associated virus, does the gene randomly insert itself in the host genome or is it only a functional gene for that particular cell? My thinking is that with cell division, that gene would be lost or could randomly insert in the genome and trigger complications? All the help and wisdom any of you could impart would be greatly appreciated.

Thank you!

John

Undergraduate at Boston College

Class of 2012

Reference:

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10660.html

Mark writes:

I had a few comments as I listened to this episode. You discussed Zinc Finger Nuclease (ZFN) technology [TWiV 144, probably], and I thought TWIV listeners would love this study:

http://www.ncbi.nlm.nih.gov/pubmed/17965707

Luigi Naldini’s lab used an integrase defective lentiviral vector to express a ZFN and to provide the template DNA used for gene correction. So, they used a virus to provide both the scissors and the patch. This gives highly efficient gene transfer while the integrase deficiency allows transient episomal delivery from a lentivirus, at least in principle.

As a stem cell guy, I listened with interest to the portion of the show that discussed pluripotent stem cells. Alan rightfully pointed out that some people dispute whether pluripotent stem cells can make every cell type. For human cells, this is impossible to ethically prove since we cannot make chimeric humans. But for mouse, it has been shown that entire mice can be made from embryonic stem cells (or induced pluripotent stem cells) using a technique called tetraploid complementation.

The way this works is that a two-celled embryo is zapped with electricity to fuse both cells together. So your two diploid cells are now one tetraploid cell. This tetraploid cell continues to divide after the fusion and is competent to develop to the blastocyst stage, creating functional extraembryonic tissue. When combined with embryonic stem or induced pluripotent stem cells, the tetraploid cells provide the extraembryonic tissue but will rarely contribute to the embryo itself. Using this assay, it has been shown by many groups that mouse embryonic stem cells and mouse induced pluripotent stem cells can give rise to a mouse that is composed almost entirely from these stem cells.

It should be noted that it is almost impossible to prove that 100% of the cells are from the stem cells. And there is data to suggest that not every single cell is derived from the stem cells. But I’d say that, at least where we can do the experiment, there is pretty strong evidence that embryonic stem cells and induced pluripotent stem cells are capable of making nearly every cell in the body.

Our being able to recreate all of those cell types in a dish is another issue entirely. But this experiment, I believe, demonstrates that the potential exists. Our current challenge is to understand the developmental biology required to get to each cell type. We attempt to translate how different pathways are activated and silenced over the course of time from model organisms to a human developmental timeframe. One such success just happened next door to my lab: Lorenz Studer’s group has recently demonstrated the derivation of transplantable midbrain dopamine neurons from human pluripotent stem cells:

http://www.ncbi.nlm.nih.gov/pubmed/2205698

Mark Tomishima, Ph.D.

Head, SKI Stem Cell Research Facility

Kent writes:

Dear Jed-Vri masters,

First I wanted to thank you for the yeoman’s effort all of you put into making a great podcast. I subscribe to over a dozen podcasts, and over the past year or so TWIV has become one of my favorite. As a self described “science geek” I can say that the show you produce is truly one of the best science podcasts that can be found. I am a computer consultant by trade, but I have a decent background in biology and a soft spot in my heart for microbes and virii of all kind (which would probably sound strange to most people, but I think you all feel the same way). I have learned quite a bit listening to you on a weekly basis for the past year, so my thanks to each of you.

You may have covered this recent development in the XMRV world already, (I must confess I am a few weeks behind on my podcasts), but if not I thought this might be a good opportunity for you to address what seems like the nail in the coffin (for now) of the the XMRV to CFS Link.

I’m sure you have seen this: http://news.sciencemag.org/scienceinsider/2011/12/authors-pull-the-plug-on-second.html

It appears that the much disputed evidence for the link between XMRV and CFS may have all but disappeared at this point. As a somewhat educated layperson on this subject thanks to your outstanding podcast discussions on this topic, I am left with a few questions at this point:

1) What, if anything, went wrong in the vetting process for the papers that were published in support of the XMRV/CFS link? Obviously the reviewers can’t be expected to reproduce every experiment, but were there warning flags that should have kept these papers from being published in the first place or is this just the sometimes messy process of scientific inquiry sorting itself out pretty much according to plan, or a bit of both?

2) Did any of the individuals involved act inappropriately during this process, either scientifically or ethically? For example, did Harvey Alter just misspeak at the Croatia conference in 2010 or should he have been much more circumspect with his declarations given the evidence he had at the time? (of course hindsight is 20/20, which is why I caveat it with the “at the time”)

3) My sense is that much of the furor over this XMRV to CFS link may have been due to scientists who were well intentioned but over eager to publish results that in hindsight (and perhaps even in forward-sight) should not have been published or at a minimum that they should have been much more cautious with their public declarations. Additionally, this combined with a small but (understandably) fervid group of CFS sufferers who latched onto what seemed like a promising explanation and pushed for a premature acceptance of this causal link in the public sphere.

I’d be very interested in hearing everyone’s take on this subject. Thanks again for the great work, I know I’m not alone when I say how much I appreciate your efforts.

Sincerely,

Nicholas writes:

Dear Vince, Alan, and Rich,

I absolutely love your podcast and hope you never stop producing it. I count on the three of you to keep me up to speed on some of the most interesting virus research being published and look forward to downloading the podcast every Sunday evening. I also really appreciate the fact that you continued producing TWiV through the holiday break. I wanted to bring a paper to your attention that you might consider covering on TWiV. It just came out in the journal PLoS Pathogens and I thought it was really creative. Basically the group engineers a Dengue virus to be targeted by microRNAs that exist only in macrophages and dendritic cells. While the virus replicates normally in other cells, it is completely blocked wherever this specific microRNA is present. They then use that virus to infect mice and demonstrate that, without the availability of replication in macrophages and dendritic cells, the virus cannot spread in the animal. I found this strategy a really unique way to study the function of particular cell types in response to infection.

Keep up the good work,

Nicolas

If you’re interested in the paper, it can be found here:

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002465

TWiV 169

Sophie writes:

Dear twiv/twip/twim hosts (not really sure where this mail belongs).

I recently started reading a lot more papers than what I’m used to (school related) and I actually find it quite difficult to use them.

Of course it doesn’t help that English is my second language, but I can’t help thinking that it’s more than that, so:

How do you make a paper accessible to yourself? I mean, everybody can read a paper, but actually extracting the relevant information seems more like an art than anything else.

How do you avoid getting lost in the details or missing them completely? When I read the methods for example, everything kind of runs together, especially when they repeat the same experiments just with different doses or a slightly different composition of drugs (vet school student).

In short, I guess I’m asking: How do you decode a paper, to get out the relevant information without getting lost?

Thanks again for the great podcasts:)

Sincerely Sophie

P.S. (Dickson): I just started my parasitology course and I must admit, I never really appreciated the intricacies of protozoa, I mean, they’re amazing (I’m going all “squee” when reading about them)! I can’t comprehend how a single cell can have a “mouth” and everything, I think I might just found out what I want to do my bachelor project on (final project you do at the end of your undergrad).

Joanna writes:

Greetings! I have a question regarding the Influenza Type A H5N1 virus.

Why is its genome purely avian? (Why isn’t it like some other flu virus genomes which are partly human in nature and partly avian…?)

The answer will really be helpful to me. Thank you very much.

Joanna

Simon writes:

Hi Vincent and friends,

I recently finished reading this fascinating book on the black death caused by the parasite Y. pestis which was carried by the oriental rat flea throughout Europe during the 14th Century (1340-1350s) and I thought it would be great to recommend the book to those interested in infectious diseases.

The Great Mortality written by John Kelly is a, fascinating tale concerning the “rise and fall” of plague throughout Europe. John Kelly takes the reader through each country of Europe describing in great detail the horrors of the arrival of a new disease to a continent where little immunity ment 2/3 of the European population perished. The book begins with the arrival of the disease through the ports of Italy with particular attention given to Genoa it then details the advancement of the pestilence giving an idea of the epidermatological considerations for a new pandemic. A discussion of recent scholarship on both the origin and the nature of the plague is also included.

TWiV 168

Mike writes:

Hello Men (and sometimes women) of TWiV!

I have read before that the human genome contains the genetic code of several thousand retroviruses. These retroviruses are in an inactive state, and are believed to be the product of infections that have been passed down through the germ line through many generations of humanity. These viral genomes have in effect become incorporated into the human genome and are now a part of us. I am wondering if it would somehow be possible to use some form of restriction enzyme therapy to remove these viral genomes in order to see what effect (if any) it would have on human health – do you think it could be done? If so, what would you predict the effects would be? Are the viruses in any way, shape, or form driving evolution? Or could they be causing damage just by being there?

Once again, I appreciate you taking the time to read this email. I greatly enjoy listening to your podcast, and I apologize if this is an ignorant line of questioning. I started listening to your podcast regularly in November of this year, and have enjoyed it so much I am now trying to catch up. I am currently still in early 2009, but should be completely up to date within the next two months or so. Once again – thank you for all that you do.

P.S. Please tell Alan that I have already taken the listener survey, so if he could please remove the subliminal message from my brain it would be greatly appreciated. I would very much like to stop waking up in the middle of the night with the sudden inexplicable urge to take a survey over the interweb.

Raihan writes:

Hello TWIV hosts

In TWIV 167 Dr Despommier said that the virus in Contagion is similar to Nipah virus as the virus in the movie is erroneously compared to a bat-pig hybrid. Dr Despommier said abt Nipah as ‘ ….pigs and bats gathered together in the mangrove’

Nipah viruses arose in Malaysia where pigs in a farm were feeding off bat droppings. The bats in turn, were habitating in nearby fruit orchards. No one would place a pig farm or fruit orchard in a mangrove.

http://en.m.wikipedia.org/wiki/Henipavirus

I guess I’m being as nitpicking as Dr Racaniello was on TWIV 167

Stephanie writes:

Dear Twivers,

I was reading a paper on exploring vector immunoprophalysis for HIV and was surprised to hear that the transmission of HIV has been found to be less than 1 infection per 100 heterosexual coital act. When I looked up the reference paper, I found a control in the methods section so amusing that I had to share it with you guys. So, basically, the transmission statistic was based on couples in Uganda with only one spouse positive for HIV (80.4% of the couples reported never using condoms). The point of the study was to follow these couples, monitoring HIV status to evaluate the transmission rate of the virus. After the study was over, they compared the strain of HIV from newly infected spouses with the strain collected from the spouse. Apparently, the authors had to exclude 4 people from the study because their strain of HIV could not have come from their partner. I wonder how each of the 72 couples that underwent seroconversion during the study responded when they saw that in the paper!

Stephanie

Paper: Rates of HIV-1 Transmission per Coital Act, by Stage of HIV-1 Infection, in Rakai, Uganda

Charlotte writes:

Contagion – what a dog!

May I recommend to my fellow twiv addicts a movie about a real virus: Roger Spottiswoode’s film “And the Band Played On” based on the book by Randy Shilts.

And for my fellow twim addicts: Akiru Kurosawa 1952 classic “Ikiru” about Helicobacter pylori (although not explicitly stated in the film). Perhaps a Listener Pick when you bring Marty Blaser up from NYU. http://www.med.nyu.edu/medicine/labs/blaserlab/v1-sld_H-pylori.html

Looking forward to seeing you at ASM in June. Perhaps we can do a live show at Berkeley.

Best regards,

Charlotte

TWiV 167

Joe writes:

Twivers

I did the homework Professor Vince assigned and went to see the movie Contagion. I really liked the movie and was very pleased with the way the science was portrayed.

I am an Environmental Health and Safety Manager for a Bio-Tech company and started listening to TWIV about 2 1/2 years ago when I was researching Avian flu and pandemic response planning about 6 months before it hit the headlines. As someone who had to consider all the social impacts and mitigation measures so I could write a response plan, I thought the movie hit just the right tone with the various stages of panic, denial, fear mongering, and good public health science going on in the background. They touched on the emotional impacts of losing loved ones, quarantine zones, panic buying, looting, and becoming self reliant very well. I liked that the science was done by a number of people within their own specialties and not by a single hero protagonist. I appreciated that they created a slimy huckster fear mongering the uninformed to fill the bill of a Wakefield charlatan (who gets his in the end, yea!).

I can’t speak to accuracy of the details of virus isolation and vaccine development. The only part that seemed weak to me scientifically was at the end when they showed the case zero details. It seemed to me that the woman got exposed to a cook with virus on his hands. Then somehow she contaminated all these other people by touch even though she was not yet producing virus herself. This seems like a fairly small nit to pick when it was just an issue of time compression. If they had shown her 2 days after getting it from the chef when she was just about to have symptoms then it would be more credible.

Very good movie, I may use this a training tool once I can get it on DVD.

Thanks for everything that Y’all do!

Joe

EH&S Manager

Alex writes:

Finally, I’m glad to see that the movie Contagion didn’t fall under TWIV’s radar, as it was selected as a weekly pick in TWIV#148. Thought I might help simulate some conversion on things that I picked up on during the course of the movie. The following contains spoilers so I suggest you view the movie before reading further…

About half way through the movie, we become aware that Matt Damon’s character was probably exposed to the virus but did not exhibit symptoms- by most accounts immune to the virus. They hold him in a containment cell for several days- but eventually he is released. If this was a real world epidemic would they hold him for longer? Really with a novel virus like that-the health officials have no idea how long he could have sequestered the virus within him. Do you have any idea what the CDC protocol is for a situation like this?

In regards the epidemic shelter set up after the virus was in full swing- it seemed like a terrible way to manage an air borne virus. Placing patients in close approximation to one another with little to no barrier between them. If you look at real life pictures of stadium shelters set up in the past, like those of the Astrodome during Hurricane Katrina, it would take a matter of hours for a virus with an airborne virus with R0 factor (Basic Reproduction Rate – vr: not a rate) of 2 or greater to completely overwhelm the entire stadium. I attempted to brainstorm ideas for managing containment of a virus when there is suddenly an influx of 100,000 people infected but came up empty. It does seem like stadiums are a poor choice however. It’s clear that it’s best to catch these types of outbreaks early.

As the investigation of where the virus started progressed, a WHO official reviews the videos from the casino and determines that Gwyneth Paltrow’s character is the originating case. She is viewed blowing on the other executive’s casino chip for good luck- which the WHO official views as transmission. If you take a look at Paltrow’s dress at this time it’s red and sparkling. We know from the camera pictures which Matt Damon views that Paltrow received the virus from the chef via a handshake (who was actively preparing a pig moments before) on the same night (because she is wearing the same dress). How could she could transmitted the virus through her breath? Seems to me that the virus would first have to become established within her respiratory tract before she could transmitted to the other executive. I find the other two examples of transmission- handling a phone and a used glass much more likely.

At the very end of the movie we get a glance of how the actual virus mutation occurred. A bulldozer plows through a forested area disturbing a bat, who then goes to bite a pig. The virus then progresses into humans. Do you think global deforestation and habitat encroachment is leading to an increase in these unfavorable interactions? And thus is putting us at an increased risk for an epidemic of a mutated strain? On a smaller scale, I think there is evidence to support this theory. Take for example the Ebola Outbreak in Mayibout Gabon in 1996 where two men butchered a dead monkey they had found, leading to the spread of the virus.

Cheers,

Alex

Bachelor of Science

Lance writes:

I saw contagion recently and was disappointed. They figure out the incubation period within a week, too fast I think. They seemed to have a crystal structure (which was a protein not a virus) before the virus was grown in cell culture (impossible). It’s odd to have a genome that varies between 14 and 19 kilo bases – variation of over 20% in size! if I could calculate R0 from sequence alone I would be rich.

Thomas writes:

Hey gang,

So I have yet to see Contagion but with my birthday coming up I figured I would dig deep into my graduate school empty pockets and scratch for the cash to treat myself this weekend. However, with its release, I was very interested in how reliable and how true this movie remained to science. Well I did what any student would do to find such information and I “Googl-ed it” and came across this website http://www.scriptphd.com/ (Script PhD).

I was interested in what your thoughts are on this site and I especially hope you will consider a Contagion review podcast because, by the sounds of the reviews, this movie is a great representation of a possible threat. Also, the editor of this website, Jovana J. Grbić, PhD, seems to be well-trained and I love the timing of this websites beginning (very shortly after your TWIV podcasts began). Any friendly or collegial connection there?

Nonetheless, thank you and all your guests and co-hosts for your excellent work in bringing the best of virology (and microbiology and parasitology) to your faithful listeners. I look forward to your comments and future podcasts.

Regards,

Thomas

MD Candidate, Class of 2014

The George Washington University

Nina writes:

First off, love the show! It makes a great alternative to listening to the radio at my desk 🙂

Do you think you could combine my two favorite topics, microbiology and the movies, by discussing the movie Contagion? That’s if you haven’t already…

Keep up the great work!!

Thanks,

Nina

Roberto Cattaneo writes:

Thanks for enthusiastically discussing the measles virus host exit receptor in the “breaking and entering” TWiV 166.

When SSPE was considered, the impression was that measles virus is gone when symptoms occur. However, there is a lot of virus in brain autopsies: 1000-4000 copies of nucleocapsid per average cell were documented by quantitative Northern blots (the paper is from 1987):

http://www.sciencedirect.com/science/article/pii/0042682287900316

By the way, biased hypermutation of viral genomes (up to 50% of the U residues in one gene mutated to C) was discovered (in 1988) in autopsy material of SSPE patients:

http://www.sciencedirect.com/science/article/pii/0092867488900487

On a personal note, after graduating in 1984 I joined to laboratory of Martin Billeter in Zurich, Switzerland. Martin was a bacteriophage Qbeta virologist who just started working on an eukaryotic RNA virus – measles.

The project was of great interest to me because of SSPE – the ultimate example of long-term persistence of a RNA virus. Martin had access to SSPE autopsy material though the group of Volker ter Meulen in Wurzburg, Germany. I was hoping to be able to clone and analyze measles virus genomes that had replicated for 5-10 years in the same person.

In retrospect, ignorance was my luck. More insightful colleagues were scared by the perspective of working with minimal amounts of viral materials (if any!). However, there was a lot of viral mRNA in these autopsy material – piece-of-cake project.

Thanks again for discussing my favorite virus!

Best

Roberto

Kartik writes:

I very much enjoyed listening to the latest TWiV podcast that includes a discussion of our paper about Ebola virus entry and NPC1. I just wanted to clarify that the proteins Ebola and HCV need — NPC1 and NPC1-like1, respectively, are in fact different (but related) proteins. They are paralogs that are ~50% similar. They are both cholesterol transporters, but are expressed in different cells and are regulated differently (NPC1 is present in all cells; NPC1-like1 is present only in gut epithelial cells and liver hepatocytes). We know that Ebola doesn’t need NPC1-like1 at all. Also, Zetia (ezetimibe) blocks NPC1-like1 but has no effect on NPC1, which is why we didn’t use it in our experiments.

Thanks and best,

Kartik

Kartik Chandran, PhD

Assistant Professor of Microbiology and Immunology

Albert Einstein College of Medicine

http://www.chandranlab.org

Judi writes:

Hello professor TWIVers:

First, let me say thanks for all the work you do and the great discussions. I am a high school science teacher and you are my professional development since (for the most part) K12 education is spending their money on kids not teachers – probably a good thing for the short run.

Second, I want to say thanks for the heads up on Emperor of All Maladies – I am almost finished with this book and want more – Vincent, please write one about polio (in your spare time, but you’re not allowed to stop the TWIVs)

Third, I have a question about TWIV 166 and the making of haploid cells. Someone, and I don’t remember who, said you could make haploid cells by disrupting the spindle formation. I was wondering is this is true since DNA is replicated during the S phase of interphase, it seems you’d end up with single chromosomes, yes, but they’d have multiple strands of DNA and therefore multiple copies of genes. I tried to look this up and found that there are polytene chromosomes in Drosophilia salivary glands with 1024 copies of DNA. Am I misunderstanding the life cycle of cells? or do different cells replicate differently? Sorry to ask such a basic biology question, but I don’t want to be giving my students inaccurate information.

Lastly, a reading suggestion from project Guttenberg: a short children’s book; Makers of Many Things by Eva March Tappan, who lived from 1854 to 1930 [ad:she lived backward in time?]http://en.wikipedia.org/wiki/Eva_March_Tappan. She wrote a book that explains how things are made – The little friction match — About india rubber — “Kid” gloves — How rags and trees become paper — How books are made — From goose quill to fountain pens and lead pencils — The dishes on our tables — How the wheels of a watch go around — The making of shoes — In the cotton mill — Silkworms and their work. A fascinating old-style kids book –http://www.gutenberg.org/ebooks/28569

Thanks again for all you do…

Judi

Lori writes:

Part of my graduate work addresses the sweating sickness. Less what it actually might have been, but rather whether people thought it was contagious or not (comparing medical writings with chroncles, letters, and other such materials).

That said, there has been several articles written about the potential identity of the disease, most of which come to different conclusions. Until the latter part of twentieth century, medical historians largely believed that the sweating sickness was a form of typhus, a virulent relapsing or miliary fever, or influenza. Since the 1990s, historians have examined contemporary accounts of the disease’s symptoms in minute detail. Analysing those symptoms in correlation with virulence, spatial and temporal distribution patterns, potential transmission models, concurrent environmental conditions, and the clinical features of modern diseases, they have variously speculated that the disease was a viral hemorrhagic fever, an arbovirus, a hantavirus pulmonary syndrome, an enterovirus, inhalational anthrax, or dengue fever.

Here is a list of some of the better articles written about the disease:

Bridson, Eric. “The English ‘Sweate’ (Sudor Anglicus) and Hantavirus Pulmonary Syndrome.” British Journal of Biomedical Science 58, no. 1 (2001): 1-6

Carlson, J.R. and P.W. Hammond. “The English Sweating Sickness (1485-c.1551): A New Perspective on Disease Etiology.” Journal of the History of Medicine and Allied Sciences 54 (January 1999): 23-54.

Dyer, A. “The English Sweating Sickness of 1551: An Epidemic Anatomized.” Medical History 41, no. 3 (July 1997): 362–384.

Flood, John L. “‘Safer on the Battlefield than in the City’: England, the ‘Sweating Sickness’, and the Continent.” Renaissance Studies 17, no. 2 (June 2003): 147-176.

Hunter, Paul R. “The English Sweating Sickness, with Particular Reference to the 1551 Outbreak in Chester.” Reviews of Infectious Diseases 13, no. 2 (March – April 1991): 303-306.

McSweegan, Edward. “Anthrax and the Etiology of the English Sweating Sickness.” Medical Hypotheses 62, no. 1 (2004): 155–157.

Taviner, Mark, Guy Thwaites, and Vanya Gant. “The English Sweating Sickness, 1485-1551: A Viral Pulmonary Disease?” Medical History 42 (1998): 96-98.

Thwaites, Guy, Mark Taviner, and Vanya Gant. “The English Sweating Sickness, 1485 to 1551.” New England Journal of Medicine 336, no. 8 (February 1997): 580-582.

Wylie, John A. H. and Leslie H. Collier. “The English Sweating Sickness (Sudor Anglicus): A Reappraisal.” Journal of the History of Medicine and Allied Sciences 36, no. 4 (October 1981): 425-445.

Hope this helps.

best wishes

Lori

University of Ottawa

Jon writes:

I must confess, first of all, that I am very critical about retrospective diagnosis as a properly historical exercise as well as rather sceptical about the alleged results provide by new methods from molecular biology and genetics to identify past diseases.

Some years ago I used the case of the mysterious English sweating sickness to rise a historiographical question, namely to what extent the exercise of retrospective diagnosis of epidemic diseases may depend upon the variable, fashionable medical concerns of each time about this group of diseases.

If you were interested on this work, here you have its bibliographical reference: J. Arrizabalaga (2002), “Problematizing retrospective diagnosis in the history of disease”, Asclepio, 54(1): 51-70, pp. 62-67 (specifically on the ESS). It is downloadable from http://asclepio.revistas.csic.es/index.php/asclepio/article/view/135/132

This article is a sort of companion of another more general one I published three years before, namely, J. Arrizabalaga (1999), “Medical causes of death in pre-industrial Europe: some historiographical considerations”, Journal of the History of Medicine and Allied Sciences, 54(2), 241-260. It is downloadable from http://digital.csic.es/bitstream/10261/33163/1/Arrizabalaga%201999%20%28Medical%20causes%20of%20death%29.pdf

Hope that this stuff could be of any help to you. Best wishes,

Jon

CSIC-IMF

Barcelona, Spain

TWiV 166

Eric writes:

Hello Professors,

Thanks again for all the effort and care you invest into your podcasts. I’m writing today to suggest a pick of the week: The Nature of Things with David Suzuki. Suzuki, one of Canada’s scientist/rock-stars, hosts this weekly science program on our public broadcaster. The Nature of Things takes complex and topical ideas in science and presents them in an accessible, informative and entertaining way; much like yourselves.

In particular I would like to recommend an episode from December 8th, 2011 on the potential role of the gut microbiome in autism. The hypothesises discussed in this show are still largely at the bench but they are interesting and touch on some of the themes you’ve discussed on TWIM.

I hope this link will work for your American audience. Episodes are also available in iTunes.

Thanks from Guelph- [partly cloudy, and an unseasonable 4 degrees Celsius (proper fridge temperature)]

Eric

http://www.cbc.ca/natureofthings/episode/autism-enigma.html

Lance writes:

Wired online recently published a great article on why science (specifically focused on biomedical and pharmaceutical) has been failing and the philosophy behind causality and how we as scientists are led astray by our own assumptions.

http://www.wired.com/magazine/2011/12/ff_causation/

Some really interesting work dealing with the philosophy of science.

Thanks, and keep up the great work,

Lance

Nam writes:

Hello,

I would go with “That Week In Virology” for the title of your 30 second segment. You can keep the same acronym we all know and love, though I suppose this might cause confusion.

Stephanie writes:

Dear Twivers,

On last week’s TWIV, you mentioned the concept of the meme. While the common usage of the word meme may be synonymous with the concept of an idea “gone viral”, I am too big of a Dawkin’s fan to not write you guys to flesh out this definition. Richard Dawkins, a prolific writer on the subject of evolutionary biology, first coined the word “meme” in a book, “The Selfish Gene,” discussing evolution. He observed that, like genes, ideas and concepts can be passed on through the generations through a form of natural selection. “Ideas and behaviors that proved most adaptive for our species survived and flourished, replicating themselves in as many minds as possible.” (Susan Blackmore) For people who wish to learn more about memes, I would recommend Susan Blackmore’s “The Meme Machine”

Thanks,

Stephanie

Andrew writes:

Hello from Raleigh North Carolina. First, I’d like to thank TWiV, TWiP, and TWiM for sharing such great information on the micro. I marvel that this world is really a thick soup of life (and viruses) which in neither a bad thing nor a good thing, but just how life has evolved on this wet rock. I’ve always been interested in biology but also by history, so when I watched the Showtime series The Tudors a few episodes peaked my attention. These episodes portrayed the English Sweating sickness epidemic of 1528 and the absolute terror it caused. It show people both suffering from the disease and people (including the King) worrying themselves to sickness. While this series is a dramatic recreation the epidemic did exist, but I could only find limited information on this time period. What is this sickness, how can modern virologist/microbiologist learn about this plague, and the 64,000$ question is it important to examine history for past afflictions? Once again thanks for podcasting and I can’t wait for you guys to tackle this one.

Eager Learner

Ewout writes:

Dear Professor Racaniello and other members of the TWIV-team:

Recently a new Orthobunyavirus (named Schmallenbergvirus, after the German town where it is first detected last November among livestock) is/was circulating in the Netherlands and Germany, causing diarrhea among cattle and congenital malformations in lambs. Here is the URL to a recent human risk assessment made by Dutch (Netherlands) colleagues: http://www.promedmail.org/direct.php?id=20111221.3645. The impact for humans seems so far to be very small (only theoretical), but for the veterinarians it’s very relevant. It’s unknown where the virus came from, and if it’s here to stay.

No hard feelings if your podcast is already too overbooked with other interesting viral issues, but maybe it’s educating and interesting to mention this newly discovered virus.

best regards, thanks for all the interesting podcasts!

Ewout

MD communicable disease control, the Netherlands

Marie writes:

Greetings TWiV crew,

Thanks for your informative and entertaining podcast!

On a natural medicine website, I came across this paper used to support avoiding vaccines: http://www.ncbi.nlm.nih.gov/pubmed/21880755

My understanding of this study from a brief skimming is that children with CF who received the annual flu vaccine had a lower CD8 T cell count (those broadly-reactive against influenza A) than non-CF children who did not regularly receive the vaccine.

What are your thoughts on this study? Is is valid to compare a non-CF group with a CF group? Have there been any studies done examining actual risk of influenza infection in those who have regularly received the vaccine in past years versus those who never received a vaccine (in a year when neither group receives the annual vaccine)?

Thanks,

Marie

TWiV 165

Justin writes:

Are you, Alan Dove and Prof. Racaniello, saying you think Mikovits and/or others on the Lombardi paper lied about the results or blinding? I think circumspection is a natural human reaction to the allegations of theft that have been made against Dr. Mikovits (my impression is that she was at least out of line, maybe worse, but I think we need to wait for all the evidence in those cases to come out before we make final conclusions).

And this rigorous study by Lipkin won’t be believed by you, you say, if the results confirm the Lombardi paper- the burden is on them, not the other less rigorous studies.

You guys do make some good points. There are multiple lines of evidence against XMRV infecting humans in vivo. However, your assumptions and conclusions about the “pro-HGRV” scientists seem to me to be biased once again as compare to your conclusions about the “anti-HGRV” scientists and your silence on the outright fraudulent ‘scientists’ involved in XMRV and in ME science in general- eg CDC, Wessely school including McClure.

There is some circumstantial evidence of potential ‘sketchiness’ re Mikovits and you have no problem assuming the worst (which is a normal human reaction), but why the double standard when it comes to the “other side” – the proven frauds who wage war on ME science? I have asked this numerous times and don’t get an answer.

I appreciate that you published David Tuller’s piece on CDC, but that’s all you’ve done. In this podcast you mentioned that he wrote the piece but you didn’t mention that it’s another documentation of the fake science done on ME by CDC. I can’t think of another way to explain it but bias.

Yours,

Justin, esq.

Suzanne writes:

I believe the main problem some conservatives have with gardasil (sp?) is that the abstinence only sex education programs in a lot of areas focus on “sex will kill you” type messages. HPV is one of the pillars of their argument. You can’t say “Don’t have sex at all or you’re likely to catch this very prevalent virus that can cause cancer.” if your students have been vaccinated against the main cancer causing strains.

Michael writes:

Great men of TWIV,

I’m a new virology/immunology postdoc, and I am very glad your podcast exists to remind me of all the virus out there I don’t personally work on. Before I started listening I had forgotten all the details of everything except herpesviruses and poxviruses. You have a great camaraderie — no matter how interesting the subject matter, I wouldn’t be able to listen if you sounded boring. For some reason I was surprised to see that Rich Condit does not have a beard.

I’d like to know what you think of this paper: http://dx.doi.org/10.1016/j.chom.2011.07.010 (Manley et al [2011], Human Cytomegalovirus Escapes a Naturally Occurring Neutralizing Antibody by Incorporating It into Assembling Virions. Cell Host and Microbe 10:197)

One of the senior authors, Teresa Compton, gave a talk in our department recently and she made reference to some interesting finding that she wasn’t allowed to talk about. This seems like it is probably that finding.

The idea of a virus incorporating an antibody into infectious particles is weird. Although the authors say it “illustrates a general mechanism of viral antibody escape”, they don’t mention this happening with any other antibodies, against CMV glycoprotein H or any other CMV protein. Do you think this is a freak occurrence? Since antibody clones are unique to each person, I’d be surprised if a virus can evolve resistance against a single antibody clone. Especially a herpesvirus which does not exactly have a high mutation rate.

Best wishes,

—

Michael

Penn State M.S. Hershey College of Medicine

Chen writes:

For viruses like CMV(cytomegalovirus), HBV or HIV, those which is characterized of latent infection, what factor controls its re-activation, what priority its genome-encode proteins are expressed and what the virus can be detected as early as you can.

Take CMV for example, most people are naturally infected with it. However, for immunocompromised people, etc, CMV can re-activate from latent state and cause great impair to host. As those people is defiecient in immune system, thus their [health relies on a drug …] healty completely lie in the exterior drug combating the CMV when it reactivates. In such cases, detection of CMV as early as we can is the critical issue in ensuring the life safety of the people.

Sincerely looking forward to your reply and any advice.

best regards

chen

Ph.D. Candidate

Laboratory of Structural Biology

Tsinghua University

Beijing 100084

China

Saul Silverstein writes:

No one knows what controls the switch from latency to virulence. More likely than not it is a manifestation of the host and site of infection. Changes in expression of host genes or activation of heatshock proteins may be the most likely explanation for release from latency.

Jason writes:

Hey guys,

I thought of a cool idea. I think it was Scientific American that used to do a historical look back at what was going on in science 50, 100 and 150 years ago. I reckon it would be great to pick a random virology/viral diseases article each week or month from 50 and 100 years ago and give a quick 30 second outline on what was going on, just to give us a bit of perspective on how far we have come.

Keep up the good work guys, you keep me company on the long drives to and from the lab each day. Actually I have all three podcasts TWIV, TWIP and TWIM on repeat in my car so I must have listened to each episode half a dozen times each. I am usually paying most of my attention to the traffic so I only absorb about 10% of what you are saying, which means I must be just over half way to hearing everything in the podcasts by now??

Anyway G’day from down under, the temperature is about 27DegC (? 81deg Fahrenheit ?) 25% humidity and a light breeze. Definitely a day for the beach 🙂

P.S I found the attached article yesterday I thought you might find it interesting.

You need a whale of a supercomputer to run a simulation like that, makes my little poliovirus virion simulations seem like minnows.

Cheers,

Jay

Senior Medical Scientist

National Enterovirus Reference Laboratory

WHO Poliomyelitis Regional Reference Laboratory

Victorian Infectious Diseases Reference Laboratory

North Melbourne,

Australia, 3051

He sent http://www.twiv.tv./11yt2114.pdf

Peter writes:

Dear Vincent, Rich, Alan and Dickson

As a fairly recent listener to TWiV I have just been trying to catch up with the many past episodes.

In TWiV #5 Vince and guest Saul Silverstein discussed Herpes viruses.

I am in my early 50’s and had chicken pox before I was ten, would it in your opinion be worth me seeking vaccination against varicella zoster to reduce my chances of suffering from shingles in the future?

You also spoke about postherpetic neuralgia as a symptom of zoster.

This brought to mind another podcast I listen to – Dr Ginger Cambel’s Brain Science Podcast.

In BSP Episode 69 Ginger was talking to R. Douglas Fields about his book The Other Brain about the influence of the glial cells on the activity of neurons, including their link to chronic pain.

http://www.brainsciencepodcast.com/bsp/tag/the-other-brain

Is it known if as well as infecting neurons the virus infects the Schwann cells and causes them to release neurotransmitters that make the neurones hypersensitive?

I have heard that vitamin D can have an anti-inflammatory effect and that many people are deficient in vitamin D, would this mean that postherpetic neuralgia could possibly be relieved by either vitamin D supplements or creams or by photo-therapy with UV light to induce vitamin D synthesis directly in the skin?

If chronic neuralgia is due to glial sensitization what other treatments may be of benefit?

Sorry for my rambling questions.

Peter

[I am a photographer from the UK now living in Turkey]

Saul Silverstein writes:

There is no question that the vaccine is efficacious for those over 55 who wish to be protected from zoster, it’s not 100% but it clearly works.

VZV is found predominantly in neurons but there is evidence that it also may be in the supporting satellite cells as well.

Atila writes:

Dear Twivers,

I have heard many times the Myxoma virus and the rabbits in Australia cited as an example of a parasite evolving and causing less harm to its host, and got very intrigued with the question of who was adapted to what. Specially after TWiM 19, when I heard that the Y. pestis from 14th century has been sequenced and harbors very few genetic differences in relation to the strains that circulate today, so that the pathogenicity of the bubonic plague should be in the 14th century Europeans health, not in the bacteria.

As I understand, Myxoma viruses from South American rabbits were introduced in Australia to kill the plague of European rabbits, that never had had contact with this virus. At first, the virus killed something like 99% of the rabbits, but in the latter years it caused less and less deaths, and nowadays it does not kill more. And this is always cited as an example of a parasite that evolved to preserve the host. But who has changed? Is it a change in virus pathogenicity, host resistance, or both?

This made me think if someone has done the following experiments: if the virus was selected to be less pathogenic, the recent Myxoma virus from Australia should not kill the rabbits in Europe. If the rabbit has been selected to be more resistant, as may have been the case of pest survivors in past, Australian rabbits grown with no contact with Myxoma vírus, with no previous immunity, should be resistant to the American original viral lineage. Do you know if someone has tested this?

Thank you again for the great podcast,

Atila

Grant McFadden answers:

Your TWIV listener asks a really great question that gets to the very heart of how virus-host co-evolution actually works out there in biology-land. Remember, the experiment of releasing pathogenic myxoma virus into feral populations of European rabbits in Australia has been cooking for only about 60 years now, which is pretty long from our perspective but only a blink of the eye in evolutionary terms. But at least we can say that, so far, selective genetic adaptations are occurring in both the viruses currently replicating in the wild, as well as the host rabbits that are now hopping about in the Australian outback. The original myxoma virus strain released into Australia around 1950, which originated from Brazil and is called SLS (Standard Laboratory Strain), has now evolved into a collection of virus isolates that cause reduced mortality in the current wild Australian rabbits, down from an original mortality rate of over 99% to current levels of anywhere from 10-60% mortality. Note that the virus continues to transmit efficiently between rabbits via biting insects, especially mosquitoes, and so has established an endemic relationship (called enzootic) with these wild rabbits. These populations continue to co-evolve and so we only can report on a snap shot of what we see so far.

We know that both the rabbits and viruses have changed genetically by mutual evolutionary pressures. If you take the current field rabbits that have not yet been exposed to myxoma virus and challenge them in the lab with the original SLS strain of virus, they are indeed more resistant to the killing effects and thus tend to live longer with less overall mortality. But, interestingly, if you take current virus isolates from the field and put them into the original fully-sensitive European rabbit strains, the death rate varies from much reduced from the original 99% to even more virulent (ie that kills rabbits even faster than the original SLS strain!). What this shows is that evolutionary co-selection pressure has generated not only more resistant rabbits but also a family of virus lineages with very varied virulence characteristics, and these are all competing with each other right now in the wild. We actually don’t know which virus-rabbit pairings will “win out” in the long run, but at least we can say that the disease severity we now see in the Australian wild is uniformly dropping from an original near-universal mortality to one that is now much less lethal but still allows for efficient virus dissemination from rabbit-to-rabbit.

Unfortunately, we don’t really understand what the genetic changes in either the virus or the rabbits are really doing at the molecular level. Attempts have begun to fully sequence representative wild virus isolate strains to compare them to the original SLS strain. Lots of sequence variations in these viruses will be documented, but establishing which ones are functional for disease and which ones are “silent” will take quite some time. On the rabbit side, we know even less: although the full sequence of the original European rabbit (Orytolagus cuniculis) has been reported, nobody I know is currently sequencing the feral virus-resistant rabbits that are now living in the Australian outback. With DNA sequencing costs dropping so dramatically, perhaps somebody out there will one day pursue this scientific question in detail. Maybe even one of your TWIV listeners?

Anyway, I hope these points help clarify the question.

Cheers,

Grant

Thomas writes:

Hello TWiV crew!

Quick question for Dr. Racaniello et al:

In TWiM_21, you mention (roughly around 30 minutes in) that viruses that have a long infection time have an incentive to inhibit apoptosis, which you had brought up because of its connection to lesser known mitochondrial functions (Ca2+ regulation, etc as opposed to only respiration).

In a recent lecture I attended, a review titled “Hallmarks of Cancer” (see attached) mentioned evasion of apoptosis to be one vital pathway in the sustained development of cancer cells into metastatic forms.

Is there any way to trace the development of oncogene associated viruses to inhibition of apoptosis, or do these two mechanisms function independently?

I haven’t been able to study the full details of cancer-correlated viral infections, but I’d imagine tracing phylogenetic heritage is generally much more difficult in viruses, due to smaller genome size and huge mutation rates (compared to the host genome). [Does horizontal gene transfer occur among viral quasi-species?]

**Q2: lately, I’ve been trying to find an effective algorithm to determine the usefulness of various life sciences textbooks online, or at least a quick way to sort out hand-waving quacks and legitimate ground breakers. The problem with this is that the review process is often based on a pitifully small sample size (n is often less than 10), and contain concerns over a) the truthfulness/thoroughness of the review and b) the ability of the reviewer to accurately evaluate what the book has to offer. Given that the avg. cost of a textbook at or above the undergraduate level is nothing to shrug off, it’s a bit of a problem.

One such book is “Evolutionary Dynamics” by Martin A. Nowak. From what I can discern, the book contains a treatment of theoretical biology from a highly mathematical (by a standard biology perspective) approach, but in being a relatively newer and interdisciplinary set of topics it presumably has the advantage of being both ignored by spare-time-deprived academics and potentially very useful.

While I realize a vast portion of his thesis may be invalid once the mathematical obfuscation is removed (default treatment of unknown author is skepticism; his work could easily be legitimate), I write to you about this primarily due to a supposed prediction made about the field of HIV research by Nowak.

If Google Scholar and citation number are worth anything, I believe the relevant publications can be found here.

If you could shed some light on this topic, it would be greatly appreciated. Thank you for your time.

As usual, the shows are fantastic! Keep up the excellent work.

he sent /twiv/wp-content/uploads/sites/2/hanahan.pdf

Tim writes:

Dr. Raceniello & Esteemed Cohorts:

I am hoping that you would take the time to watch this video of Dr. Eric Schadt. You may know the basics — and may want to fast forward through the beginning. This is the current location of the video:

(http://mecfscenter.com/)

Please comment on a couple items within the video. The items I like to hear your comments and discussion about:

· this extraordinary “gadget” he uses to analyze “real-time” and what it is doing and what he is doing at the molecular level and then at these systems level via computer modeling/simulation.

· And near the end of the video there is a very interesting virology/microbiology slide that he shows that he says is based upon unpublished data — that he should publish pretty soon… so you may want to comment on this after it is published….

thank you for all the time that you all put into this podcast — science education is so important!!

Tim

Lance writes:

Dear Doctors,

I just finished TWiV 160 with Dr. Moore. Great interview. I knew Dr. Moore and his wife Dr. Chang while I was doing my MS at the University of Pittsburgh. Great people, but I am really disappointed I never knew that Dr. Moore had an EIS background. I have had an interest in the EIS for many years now and hope to apply soon (when I finish my PhD, but who really knows how and when that happens). I know you have touched on the EIS program a few times, but it would be great if you could bring on some of the virologists that really made it famous e.g. Joseph McCormick, MD, CJ Peters, MD, or Peter Jahrling PhD.

A couple of messages to relay.

First to Dr. Despommier, the vertical farm project is alive and well in Chicago. I am sure he would be proud.

Second to Dr. Condit, tell him goodluck with his Personal Genome Project spit collection. I sent mine in about a month ago. Very interesting.

Thanks again for the great work all of you are doing,

Peter writes:

Dear TWiVsters,

Have you seen this picture of a T4 phage tattoo:

http://blogs.discovermagazine.com/loom/2011/10/14/an-infective-arm-scienceink/

In 2007, science writer Carl Zimmer, having seen someone with a DNA tattoo wondered how common science inspired tattoos were. He asked readers of his blog and their response was massive.

Getting back to the are viruses alive question, I was having this discussion the other day and someone came up with one of the best answers I have heard to the question: “it’s a bit like asking whether an photon is a wave or a particle”

Alison writes:

Hi TWiV gang!

Love love love the podcast. I am a graduate student at the University of Washington and I have found your podcast both fun and informative as a student of virology.

I was wondering about a technique that was mentioned in episode 158 at the University of Michigan. Rich mentioned “mouse blots” when speaking with Kathy Spindler. I tried looking up this technique on pubmed and found a technique used by Louis Villarreal called “fluorography of whole mouse”. I can’t seem to find the publication in which Dr. Spindler describes this technique. Could you or Rich help me find it?

Thanks so much for this awesome service for the public!

Kathy Spindler replies:

The paper in which we used whole mouse blots is Ball et al. (1991) Virology 180:257-265 (PMID 1845825). We used 32P probes, which don’t give as high resolution as some other isotopes (e.g., 3H used by Villarreal in the paper that Alison cites, but which uses a different approach – in situ autoradiography and whole mouse fluorography). I think some “modern” isotopes (33P- or 35S-labeled probes) might give better resolution than 32P with whole mouse blots? We haven’t used the technique since the early 90s…

And I think you are right that Luis did invent the technology – the earliest paper I can find is Dubensky et al. 1984, JVI PMC255737 = PMID 6328007. Fig. 1 shows why we call it “slice mice.”

Ian Lipkin, LPV, and Mike Oldstone are co-authors on a methods paper that I would have to walk to the library to get (horrors! it’s 5 minutes away, inside the building!), but I’ve ordered it as a pdf online from the library and that should come in a day or so. I wonder if it will have a historic perspective on the technique. PMID 2670459 is that paper (1989). I can send that to you and/or Alison once it comes. I can also send her my “bench protocol” if she wants.

Those papers might have more detail than ours, where we merely cite Dubensky et al. and Rochford et al. (PNAS 1987, PMC304225). However, I note that we did mention that we had the microtome sitting in a Sears chest freezer!!! Kind of a useless detail…

Cheers,

Kathy

Danielle writes:

Hello Twiv!

First, I would like to say, I love the show, you guys make repetitive (but still awesome) lab work go much faster!

Before I get to my silliness, I’d like to ask a serious question or two, if I buy the microbe world app you guys get a good cut of the profits right?

Also, were any clustering analysis done on the H1N1 strain that were sequenced, if so did it prove that the strain jumped from swine to humans in mexico? (Sorry if the answer is common knowledge I’m only up to 2009 in your podcasts besides the few recent one’s I’ve listened to).

Anyway, I’m not sure if you guys are aware of Reddit, but they just discovered that the sputnik virus can infect mammavirus. so in a redditors fashion I made this meme and thought I’d share! (here’s the reddit thread http://www.reddit.com/r/todayilearned/comments/n13kg/til_that_some_viruses_are_so_large_other_viruses/)

my virology-related meme: http://www.quickmeme.com/meme/35f6dm/

I hope I didn’t waste too much of your time on this silliness!

Richard writes:

Hi Vincent, Dick and other hosts

I have a question that may be a little outside twivs remit, but at least partially applies.

Recently I have heard in podcasts (via stitcher radio), about the possibility of genetic engineering, of humans, and resurrecting the wooly mammoth. Some of the methods mentioned include cloning, and things outside of virology. However I was wondering if viruses, particularly retrovirus, would allow genes to be edited, removed, or inserted? If so would this be practical, or do better methods exist? Would it even be possible to engineer a retrovirus, so as to insert a gene, or other DNA, reliably into a host? Would this be a temporary change, or inherited by any offspring? My guess is that inserted genes would be inherited, as long as they where present in ‘germ cells’. Much as the remains of retrovirus infections remain in many genomes. Also could a retrovirus be used to edit the genome of an elephant embryo, so as to make it match, say a wooly mammoth? My guess is that retroviruses aren’t that big, and tend to insert things somewhat randomly. I’m thinking that would be a showstopper?

Some random speculation…. I wonder if it would be possible to engineer something, like a ribosome, that would edit DNA, given a template (either RNA, or DNA). So it would run along DNA, and compare the sequence to the template, on finding a match, it could then edit the bases, to match the rest of the template.

Thanks for the podcast, I listen to every episode, and like the way you simplify things enough for the non virologist, such as myself (I’m a water and waste water engineer).

Looking forward to more virology

Regards

Richard

Richard writes:

Hi Vincent, dick and cohosts

I’ve just listened to the science show podcast from he 3rd December. They mention exosomes, a membrained container that is secreted by cells. These contain genetic material (RNA) as well as a number of proteins. I had no idea that the human body contained such a horizontal transport mechanism.

I can’t help but compare these to a virus. Though there are clearly differences, do you think they are related? Maybe cells learned this trick from viruses, or the other way round?

Again thanks for your podcasts.

Regards

Richard

Juanjo writes:

Dear Vincent (and Dick, Alan and Rich),

while waiting for the launching of a variant/sequel of TWiV to be broadcasted in spanish, as proposed by Estanis Nistal with the enthusiastic support of several other spanish-speaking listeners of TWiV, I have submitted a short notice for the journal “Virología”, the bulletin of the Spanish Society for Virology (SEV, Sociedad Española de Virología) to divulgate your netcast.

The note was published in the volume 14, number 3, page 13. A free copy of the journal can be downloaded from:

http://www.cbm.uam.es/sev/revista.html

The note intends to inform the virology community in Spain of the existence of TWiV, including links to Virology Blog and TWiV webpages.

I hope this information will contribute to spread the word about TWiV among spanish virologists, students and the general public.

With warm regards,

Juanjo

Peter writes:

Dear Doctors

I am sure others will send you these links

http://www.scientificamerican.com/podcast/episode.cfm?id=cruise-ship-bug-takes-to-the-skies-11-12-21

http://www.ncbi.nlm.nih.gov/pubmed/21836128

About a series of Norovirus infections on an Air New Zealand plane, there was inadequate cleaning and disinfection between flights.

I have several times come down with fairly severe chest infections (one requiring hospital treatment) after flights it is of course difficult to know exactly where I acquired the infection but at the airport or on the aircraft seem most likely places to be exposed.

I am a regular listener to TWiV, TWiP and TWiM keep up the good work these are all fascinating and informative shows.

Essa writes:

Dear TWiV team,

Happy holiday and happy new year.

Thanks a lot for the great virology blog.

I would like to know if there is any possibility to any virus to be fused with another one, to be infected by other virus?

As we know the infection concept is just a conscious term or scientific term to us, since it causes us to be sick [unwanted health condition] due to our reaction with micro-organisms such as viruses. If viruses are independent [not related to us] organisms, how would they get their compatible receptors to ours on our cells?

In Naica mine, a mine is best known for its extraordinary selenite crystals in the Mexican state of Chihuahua, virologists have discovered millions of viruses in many samples from underground water and crystals. The temperature in such a mine is nearly 50 degrees and the humidity is nearly 100%, after sucking out the emerging water in the cave, roughly for million years ago.

Maybe such these conditions are suitable to form the basic molecules for any living cells such as amino acids which are the basic building blocks of viruses. What if more than aboriginal or primitive viruses or separated molecules fused to form a single genetic material to generate new generation(s) or advanced virus(s)? Consequently, forming more advanced cells to form the aboriginal creatures such as bacteria, abiogenesis ?

Sincerely,

Essa

Joe writes:

All my family members work in a hospitals. There many excellent MD podcasts already. The thing I like about TWIM, TWIV and TWIP is precisely that they are different from those. Having a panelist who is a doc working in emerging diseases is interesting. Local doc stuff, not what i listen for. I listen to every episode of all 3 shows btw. Thanks for what you do.

Tom writes:

Dear TWIVians:

I’ve been listening to TWIV podcasts at lunch for over a year. My anthropology degree from 40 years ago did not prepare me for TWIV, nor did my 30+ year computer software career. However, I’ve been reading Scientific American since the early ’60s, and I subscribe to Science News, so I’m not completely lost.

All that being said, I heartily commend you for your excellent presentation of this subject matter in a way that helps us lay folk follow the story, while stimulating enthusiastic participation by your visiting specialists. Bravo!

================

Oddly enough, my grounding in anthropology is what prompts this comment. I hear lots of interviews on all kinds of subjects on radio, TV and podcasts. I can tell when a researcher is being interviewed, because almost every time they begin to answer a question they start with the word, “So.” Sometimes it’s part of an opening phrase, but more often it appears to be a sentence all by itsef.

And you TWIVians tend to follow the pattern when beginning your follow-up questions. (Replay a segment of one of your podcasts and count how many times you hear “paragraphs” start with “So.”

Since anthropologists are not forbidden to ask the Why questions, I have a hypothesis as to why this happens.

A researcher’s frame of mind is one of gathering evidence for chains of causality. “This and these get together, SO this happens.” This pattern of thought may be carrying over into their patterns of speech. “Researchers think a certain way SO they speak a certain way.”

So, 😉 keep up the good work, and try not to be too self-conscious about starting your comments with “So.”

=================

I found TWIV from a link on an ME/CFS web site when I was researching my wife’s illness.

The variability of the symptoms, not just between patients but from day to day for one patient, has inspired my wife to refer to her illness as WBD (Wierd-Butt Disease). She can never predict how she will feel in a day or even in an hour. Occasionally when asked by acquaintances what illness she has, she says she’s come down with WTF.

Recently Vincent theorized that the illness may have some kind of environmental trigger that, in vulnerable individuals, initiates a cascade of changes over a period of time that finally presents as something we characterize as CFIDS or ME/CFS or any of the other “spectrum” illnesses. At that point, there’s no hope of identifying the long-gone trigger.

Although I find this theory very disheartening, my wife’s medical history would not rule it out. She dates the major onset of her illness to the spring of 2005, but looking back she sees that many of her symptoms began to appear up to fifteen years earlier.

Vincent, I fear that you may be right.

Tom

Austin, Texas

Jim writes:

Hi Vince et al

Heard a Ted talk which I enjoyed a lot. It gives a new way of looking at information to see if life might be present.

This has shifted my vote to thinking viruses are alive.

The video is : http://www.ted.com/talks/christophe_adami_finding_life_we_can_t_imagine.html

73 ( Best Wishes)

Tim writes:

PS> here is my pick of the week (patient zero):

http://www.radiolab.org/2011/nov/14/

pretty darn good storytelling……

Mary writes:

Hi all,

over the past few Twiv episodes, there has been increasing talk about what happens on a day-to-day basis in the life of a scientist (grad student, post-doc, PI, etc) and what life in the lab is like. A book I would recommend to those curious about this is Natural Obsessions by Natalie Angier. I was given this book by my boss when I was working as a technician in a lab after college and trying to decide if grad school was in the cards for me.

This book is based on the true story about the labs that were instrumental in isolating the first oncogenes in the early 1980s. It is a great science story for those who have never heard it, and also gives a very good idea of what life in the lab is like at all levels. It also emphasizes what was said recently in Twiv 161, that life in the lab is very much about social interpersonal interactions, for better and sometimes for worse.

I don’t know if this book has ever been picked before, but if not, I would highly recommend to all as a good read.

thanks! mary

Jimmy writes:

Hey Guys,

I discovered your podcasts a few weeks ago and have really been enjoying them. I toyed with biology as an undergraduate and I love it. But I ended up in business.

I just learned of the Science Exchange today and thought you might be interested given your interests in uses of the internet in the interests of science:

http://scienceexchange.com/

TWiV 164

Garren writes:

Hello Vincent

I wanted to wish you a happy holidays. I also was hoping to submit another science pick of the week for your show.

http://www.physorg.com/news/2011-12-trillion-frame-per-second-video.html

Lets just say that I’m still looking for my jaw under my desk as I type this. This is perhaps the coolest science article that I have read this entire year.

Cheers…

Judi writes:

Hi TWIV, TWIM, AND TWIP Persons of Note!

HHMI has a new video magazine

http://www.ibiomagazine.org/

Short (<15 min) talks that highlight the human side of research. iBioMagazine goes “behind-the-scenes” of scientific discoveries, provides advice for young scientists, and explores how research is practiced in the life sciences. New topics will be covered in each quarterly issue. Subscribe to be notified when a new iBioMagazine is released.

right up your alley – you’ll enjoy these – and they are short enough to use in the classroom or a meeting!

Judi

(High school teacher and FOT (follower of TWIvmp)

Mike writes:

Hello,

I have read/heard before that HIV can sequester itself in various cells in the human body and hide there in an inactive state for years. The information I have seen and heard seems to suggest that the virus is activated by anything that stimulates the immune response (and hence causes an otherwise inactive cell to become active). What I am wondering is this – has anyone ever attempted to intentionally draw out the inactive virus by stimulating the immune system and then bombarded the active replicating virus with anti-viral therapy?

Kathy Collins replies:

The so-called “flushing out” strategy your listener is referring to is a popular idea amongst HIV researchers. It makes a lot of sense based on our understanding of HIV latency. The idea is to activate HIV gene transcription, and induce the production of HIV proteins that are toxic (either directly or via the immune response). Meanwhile, antiretrovirals are maintained to prevent any newly made viral particles from spreading to uninfected cells. (The antiretrovirals themselves do not harm the infected cells, they just inactivate the virus and prevent spread.)

Limited attempts have been made to accomplish this goal using cytokines that activate T cells or histone deacetylase inhibitors that stimulate transcription. To my knowledge, these attempts have not been encouraging so far. However, there is a lot of ongoing work in this area and there is a lot of hope that this strategy will work if we can maximze the efficiency of the approach and minimize the toxicity.

So, your listener is right that this is a good idea and hopefully one day it will work to help eradicate HIV and cure disease.

Best,

Kathy

Marie writes:

Hello TWiV crew,

First off, I want to thank you for the podcasts, TWiV, TWiP, and TWiM. They make the commute and the gym almost pleasant!

It is, however, humbling and a little painful to listen to at times, because I’m a 3rd year graduate student in immunology (I study the immune response to Toxoplasma gondii reactivation in the brain) and yet half the things you say go way over my head, with the laypeople who write in making more insightful comments than this will be. I often wonder how I made it into grad school in the first place! So forgive me if the following is a silly question.

So, we incubate all cells at 37 C. All of them. From fibroblasts to microglia. But winter has made it fairly clear that at least my fibroblasts are not all at 37 C, and microglia probably aren’t, and many other cells probably aren’t. Besides, I’d heard that the 98.6 F temperature was obtained using a faulty thermometer. I know that temperature can alter protein expression, and fevers are at least speculated to inhibit viral replication (is that right?). So has anyone looked at whether small temperature deviations (for example growing microglia or neurons at 37 C vs whatever their normal temperature is) has any effect on cell function, or on say viral replication? Are there parts of our bodies more susceptible to viral infections because of a temperature difference?

A quick Google Scholar search turned up nothing for me, so maybe it’s not a valid question, but I’d like to hear it from folks wiser than I.

Thanks!

Todd writes:

In TWiV #144, you and Dick bantered, saying that the NCIS actors sounded like they didn’t understand what they were saying when using technical terms. You will be delighted to learn then that Pauley Perrette, the actress who plays the forensic scientist Abby, was an undergrad honor student in sociology, psychology and criminal science and had started her masters in Criminal Science at Georgia State. At some point she decided she wanted to act instead, so she left the program, went to New York, did the requisite starving actress bartending for a while, and finally won the role of Abby which was ironically doing the very things she was studying.

A good rule of thumb in our house: Never doubt Abby! 🙂

Sarah writes:

Hi Rich,

Greetings from Virginia. I enjoy twiv very much. It was great to see a Miller spread in episode 162, but I am sorry to say that the electron micrograph is not of bacterial transcription. Those are eukaryotic 35S rRNA genes. I am not sure of the source organism. I have worked predominantly with bacteria and yeast. I will ask Ann and Yvonne who are the experts in spreads from higher eukaryotes. Old papers from Ann’s and Oscar’s labs have pictures of adeno and SV40 transcription if you are interested.

I look forward to each new twiv episode and enjoy revisiting older ones. Thank you for the entertainment and enlightenment.

Sarah

P.S. My non-scientist husband wants you to know that he also really enjoys twiv.

Justin writes:

re: http://www.virology.ws/2011/12/26/authors-retract-paper-on-detection-of-murine-leukemia-virus-releated-sequences-in-cfs-patients/

The full text of this retraction hasn’t been published, but from the excerpts posted on retraction watch, it looks like they probably only retracted their conclusion, not the rest of the paper.

Prof. Racaniello, you were quoted in retraction watch as saying “With the retraction of the Lombardi et al and Lo-Alter papers, this brings to an end any hope that there might be a retrovirus associated with CFS.” You were also quoted in the Washington Post as saying “There’s no evidence at the moment that any virus is associated with chronic fatigue syndrome.”

I hope these were misquotes or taken out of context since you do say it is theoretically possible that ME has a retroviral cause, but it seems to me that they probably were not. Putting aside the evidence for retroviral association with ME, I thought you were aware that it is completely accepted by science that ME is strongly associated with a number of opportunistic viruses such as all or almost all herpes viruses, mycoplasma fermentans, echovirus, enteroviruses, parvovirus and virally-associated blood and lymph cancers.

TWiV 163

Ronnie writes:

Hello Professor Vincent,

First of all, thank you for your wonderful podcasts! I’m a CFS sufferer and also a student Applied Science so I’m interested in many of the topics discussed for those two reasons and always learning new things.

I think I just found a great Listener Pick of the Week. If not, you can always use it as a christmas card. 😉

This is how fungi celebrate christmas: http://geneticist.tumblr.com/post/14473433122/merry-christmas-nerds-heres-some-christmas

Also, I’ve been following your blog posts about the H5N1 news the last few days and it was just on the Dutch news that a debate will be held about the research in Dutch parliament after the holidays. It was quite a long topic on the news. They also interviewed Professor Fouchier. If you want a full translation of it, let me know and I’ll be happy to give you one.

Greetings and happy holidays!

Ronnie

Michael writes:

Dear Twivome,

I greatly enjoyed your discussion this week regarding B cell immunology. Fascinating stuff. I was also pleased with your responses to one of the listener letters you read at the end of the episode. In particular, you guys did a fantastic job dissecting the misrepresented data that a blogger used to promote the fallacious claim that H1N1 vaccine and the HPV vaccines are associated with increases in miscarriages. I went to read that blog post after listening and I was horrified at this bunk, as I am with all the bunk that is being propagated, because it is just so dangerous when people believe this nonsense. I am an epidemiologist and I have to say, Rich, you hit the nail right on the head by pointing out the lack of a denominator in the estimates on which these so called “associations” are based. Unfortunately, you find people doing this kind of thing all over the place. Mainly, I just wanted to write to say thank you for giving a clear description of how this kind of presentation of data is wrong and to tell you that your episode inspired me to record an episode for my own podcast, the Germlines, as a basic introduction to vaccines…what they are, how they work, and what the research process is that they must all undergo to prove safety and efficacy. It is sort of a basic Vaccines 101. I recorded it this week and I’ll be posting it sometime in the next two weeks. So thanks for the inspiration!

Junio writes:

Hello, TWiV crew.

It is fascinating to learn how virus makes the cell machinery to do things that the machinery is designed to do for virus’s benefit, but I am wondering how much of the mechanism explained in this episode is specific to synthesizing virus RNA from virus DNA, as opposed to a normal cell machinery being (ab)used to work on non-host DNA. For example, splicing was mentioned early in the episode, but does it also happen when synthesizing RNA from host DNA?

I assume that the next step, after virus DNA is transcribed to RNA, is for the RNA to be translated to protein. I might be getting ahead of myself, but will we see “Virology 101: Translation” episode later, and if so, I wonder how much of what happens the at ribosome to produce viral protein specific to virus replication cycle, as opposed to being a normal cell machinery that happens to be working on viral stuff. In other words, does “Translation” episode in “Virology 101” class make sense, or is it just “Biology 101”?

Thanks.

Josh writes:

Dear TWiV Doctors,

Regarding the CIDRAP release about the “influenza virus that will kill us all”, and the letter from Thomas on TWiV 162, I have something else relevant to the discussion. It is a book by Nobel Prize winning Professor of physics Robert Laughlin entitled “The Crime of Reason”, where he discusses scientific knowledge that is being hidden, privatized and classified. He discusses how nuclear weapons information was and is hidden(ironically, he can’t tell us what it is, because he has a “Q” security clearance), and how that model is being extended to the life sciences in the name of bioterrorism.

It’s not a great book. It’s short and he is not the best writer, but the topics he raises are interesting and his insider perspective is unique. A better writer than him, with a background in the life sciences, needs to take up the subject and explore it in more depth (Alan Dove, I’m looking at you.).

His radio interviews have been interesting. Here’s some links:

IEEE radio http://itc.conversationsnetwork.org/shows/detail3963.html

To the Best of Our Knowledge http://wpr.org/book/100214b.cfm

WICN http://www.wicn.org/podcasts/audio/inquiry-robert-laughlin-crime-reason-and-closing-scientific-mind

The book on Amazon http://www.amazon.com/Crime-Reason-Closing-Scientific-Mind/dp/0465005071

Thanks,

Joshua

Johan writes:

Hi,

Just found your podcast searching for twit (http://twit.tv/). I’m a biochemist and really fell in love with your podcast.

One pet peeve though, please make more video episodes! http://www.twiv.tv/viral-video/ is so empty 🙁 Just makes it more pleasing to see the person that talks (although I really enjoyed the video of the last episode, about transcription, even though there is no face 🙂

Thanks

Johan

Sweden

James writes:

http://www.cnn.com/2011/12/08/politics/siga-technologies-hhs-contract/index.html?hpt=hp_t1

I am most interested in this statement, “One smallpox expert, Dr. D.A. Henderson of the University of Pittsburgh’s Bio Security Center, said STS-246 has not been proven to work.”

do y’all have any opinions on either the STS-246 is effective against smallpox and/or the alleged allegations?

Grant McFadden responds:

The drug in question is called ST-246, and it was developed by SIGA to target the viral F13 protein (which is highly conserved in all orthopoxviruses) and block the release of extracellular virus at the end of the replication cycle. ST-246 is highly effective against every orthopoxvirus disease model tested to date, including monkeypoxvirus in nonhuman primates. It is also very safe in human clinical trials that measure safety or the ability to be used in conjunction with vaccinia vaccination (it doesn’t hurt the vaccine). It has also been safely used on an emergency basis (all patients the patients recovered from their disease and survived) in three clinical cases of runaway vaccinia infections in humans.

The only real still-unproven aspect about this drug is how well it will work against variola virus in people: ST-246 works very well against variola virus in cultured cells but unfortunately there is no good animal model to test for the ability of this drug to treat the disease caused by this virus in humans. The closest available animal model is to inject high doses of variola virus intravenously into nonhuman primates, which avoids the early phase prodromal phase of the natural disease and proceeds quickly to the end stage high viremic phase, when it kills the monkeys very quickly in a disease that doesn’t mimic smallpox very well at all. Since the drug is designed to stop the amplification and spread of the virus (it blocks the egress of the extracellular form of orthopoxviruses), it is predicted to be less effective if given only at the time of end stage disease, but even so, ST-246 still reduces the skin lesion count in variola-infected nonhuman primates. This is exactly what the FDA is struggling with right now, in terms of whether to licence the drug as a therapeutic measure to treat smallpox: the current status of animal models using variola virus are not good enough to unambiguously answer the question!

But the overwhelming evidence is that ST-246 (as well as a competing drug called CMX001) is safe and efficacious against all orthopoxvirus diseases, but the evidence relating to how well it will work against variola virus in humans is still indirect because of the inherent limitations of the available animal models.

The FDA is meeting next week (Dec 14-15) near Washington to consider this exact issue.

TWiV 162

Sarah writes:

Hello to the TWiV crew,

Here are a couple of picks I thought would be good for provoking thought and generating discussion…

While working on a project, I came across some papers attempting to define what “critical thinking” means. I appreciated the following quote and it reminded me of the many instances in TWiV where you hosts have discussed the scientific method and thinking critically about research findings. It came from a consensus statement on defining and promoting critical thinking, published in 1990 by a university Dean.

“The ideal critical thinker is habitually inquisitive, well-informed, trustful of reason, open-minded, flexible, fairminded in evaluation, honest in facing personal biases, prudent in making judgments, willing to reconsider, clear about issues, orderly in complex matters, diligent in seeking relevant information, reasonable in the selection of criteria, focused in inquiry, and persistent in seeking results which are as precise as the subject and the circumstances of inquiry permit.”

(Quote is from Table 1)

Facione, P. (1990). Critical Thinking: A Statement of Expert Consensus for Purposes of Educational Assessment and Instruction. Retrieved from http://assessment.aas.duke.edu/documents/Delphi_Report.pdf

Next, perhaps less of a pick and more to stimulate episode topic ideas for those of us who are “into” the medical side of virology, here is a paper about diagnosing viral acute respiratory infections using peripheral blood gene expression signatures. If this seems interesting to y’all, Dr. Zaas and/or Dr. Woods would be great guests on the podcast; they’re both infectious disease physician-researchers.

Zaas, A. K. et al. (2009). Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infection in Humans.Cell Host & Microbe 17, 207-217. doi:10.1016/j.chom.2009.07.006

Last, Dr. Woods would be an interesting guest for another reason – his interest and teaching activities in a movement called One Health, which looks at human health from a human, animal, and environmental perspective. I’m still wrapping my head around exactly what One Health is, but apparently it’s even caught on at the CDC.

http://www.onehealthinitiative.com/

http://www.cdc.gov/onehealth/

Keep up the great work – and keep having fun!

From justanotherkinase on twitter:

Dear TWiVatrons: FYI “mock” is a UK term for a practice exam. Loving the virology on TWiV 161. Please keep it up.

Gary writes:

Dear Wonderful TWiV People,

I just finished listening to your 161’st episode, well named “Concerto in B.” Really well done! I’ve felt guilty that as a 30+ year practicing pediatrician, receiving my undergraduate and medical school education when most of this was necessarily only vaguely guessed at, I’ve not had the time and energy to explore the literature and bring myself up to date. This last podcast along with your previous work has provided a truckload of information that has made what would have been a K2 climb into an easy and fun one. Please consider dedicating a few of your future programs to more exploration of immune function basic science. In any case, I love listening to you guys!

All the best,

Gary, MD

Sebastopol, California

Thomas writes:

Dear TWIVers,

Firstly, my sincere gratitude for all the work you put in to making TWIV an absolute gem of a Podcast and a medium through which I can still feel involved in basic science and virology even though my studies currently have me memorizing the various proteins and associations of the coagulation cascade in medical school.

With that run-on sentence out of the way, I would like to comment on last week’s TWIV regarding the CIDRAP release by saying I think you all handled it very well. Perhaps I make this conclusion due to my opinion being that which is shared by you all. Nonetheless, to suggest that science has a role in the progression of bioterrorism is probably not an incorrect statement, however, to suggest that scientists should refrain from certain works as a result of fear that knowledge and advancements may fall into the wrongs scientists’ hands is ludicrous and I am glad you addressed this release.

This brings me to the reason I write you all today. I recently came across a video that shows a 1-on-1 discussion between an out-of-character Stephen Colbert and the always-fascinating Neil deGrasse Tyson. Briefly, the two discuss various issues regarding science, society, the universe, and knowledge. The entire discussion is well worth the 1 hour and 24 minutes, however there is a short section which I hope for you and all TWIV fans to watch which I think best portrays what my feelings (and I’m sure many others’ feelings) regarding the issue that you discussed about scientific discovery in fields that are implicated in potential bio-threats. The section runs from about 16:00 to 17:40 and ends with Dr. Tyson stating that, “Everyone blames the scientists and we are collectively part of a society that is using or not using, to its benefit or its detriment, the discoveries made by science. And at the end of the day, it’s not the discovery itself that is immoral, it’s the application of it.”

They go on to discuss many other issues I think are important regarding the scientific community and what role we take in society now, but I particularly like this one quote since it reminds us of an ever-developing collective scientific knowledge but does not blame the immoral application of this knowledge on science itself.

Either way, I hope you all enjoy the video, keep up the great work, and again thank you all for the weekly edu-tainment!

Sincerely,

Thomas

http://www.youtube.com/watch?feature=player_embedded&v=YXh9RQCvxmg

Kathy writes:

Hi Vincent, Rich, Alan, and Dick,

In TWiV 145, the inVinceable TWiV, a listener (David) wrote in to get suggestions of viruses that alter host behavior, resulting in increased transmission of the disease. He cited some parasitology examples and the classic rabies story, where rabies induces aggression that causes the infected animal to bite and transmit the virus. In TWiV 150, you read a suggestion from another listener (Kimberley), who described how baculovirus-infected caterpillars climb as high as possible, and then when the caterpillar melts from the infection, all the virus goo can fall down onto lower leaves. I have another suggestion, and that is viruses that cause pocks (P-O-C-K-S), including both varicella zoster virus, a virus in the herpesvirus family that causes chicken pox, and Rich’s own vaccinia virus. In both of these cases, the pocks or pustules that form are full of virus. The host response to infection causes these to itch, and scratching of the pocks then can release and spread the virus. I haven’t been able to find a good explanation of why mast cells or basophils might release histamine in the vicinity of pocks — maybe there’s another explanation for the itchiness.

Another case might be any of the respiratory viruses that result in coughing or sneezing (think of the famous sneezing images, such as the top hits in a Google image search for “sneeze”)…

Cheers,

Kathy

Ayesha writes:

A few questions on on HPV.

Maybe you would be so kind as to pose a few questions to the next HPV expert you have as a guest. There are menstral tampon alternatives that women can reuse called the Keeper TM and the Mooncup (http://www.keeper.com/index.html). I was just wondering whether women using these products who are infected with the high risk HPVs could or would shed virus and if the virus could persist in these reusable cups (and act as a place where the virus can persist and reinfect cells on the cervix, leading to more risk for transformation). I can’t find studies addressing this question in pubmed. I wonder what kills HPV: boiling, detergents, vineagar? How well does it persist in water? Maybe a cleaner could be devised to make these eco products safer if in fact HPV does persist in them. Maybe I should just send off an email to the HPV researcher you had on recently.

I work on HIV-1, epithelium and Candida albicans. I was really tantilized by the idea that retroviruses use the immune tolerace caused by gut flora as an opportunity to evade the immnue system. David Moyes a postdoc in the same group has described a mechanism by which oral epithelium tolorates resident yeast but sets off a defensive signalling cascade when hyphae become invasive.

Many thanks for your awesome podcast. It inspires me every time I listen and recommend it to anyone who will listen!

Michelle Ozbun replies:

Really good question. HPVs as non-enveloped viruses are much more resistant to desiccation and environmental assaults compared to enveloped viruses like (e.g.) HIV or flu or herpes. My friend and colleague Richard Roden showed some time ago that HPVs are sensitive to 70% EtOH. This is what we use to disinfect in my lab when working with papillomaviruses. Richard’s work also suggested that boiling for 1 hr would reduce infectivity to near baseline. My lab reported that the particles are sensitive to acid and probably will fall apart in undiluted apple cider vinegar (pH typically between pH 4.25 – 5.00).

I recommend that the products be soaked in ethanol or 70% isopropanol for 1 hour or boiled for 1 hr (depending upon the nature of the product) before thorough rinsing in water.

Roden RBS, Lowy DR, Schiller JT (1997) Papillomavirus is resistant to desiccation. J Infect Dis 176: 1076-1079.

Smith JL, Campos SK, Wandinger-Ness A, Ozbun MA (2008) Caveolin-1 dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for pH-dependent uncoating. J Virol 82: 9505-9512.

I’m sure that both women and men shed virus as a route of transmission. However, I don’t think anyone has investigated the reinfection issues posed, and little is understood about re-infection or infection of adjacent tissues in an infected individual… though I suspect this occurs.

TWiV 161

Ayesha writes:

Honourable TWIVnesses!

I heard this series and thought you might dig it for listener pick of the week: http://www.bbc.co.uk/programmes/b015sqc7

The series is in progress but interviews 1-4 are available on the BBC iplayer or for download as a podcast. Prof Al-Khalili is a physicist but you have science podcasting and science outreach in common with him.

http://www.jimal-khalili.com/

The interview with Paul Nurse is a really interesting window on his work, mind, even personal life!

@neilfws via Twitter:

http://www.abc.net.au/news/2011-11-25/immunise-or-lose-benefits-parents-told/3694236

what do we think about this?

Raphael writes:

Hi, Dr. Racaniello.

Just would like to give you a heads up on an article i recently read with the link: http://medalerts.org/analysis/archives/263

Gardasil (HPV-4) and the H1N1 vaccines giving a high risk of miscarriages. Will you be able to comment on this?

Thank you very much.

Matt writes:

My name is Matt Clarke, I’m 16 and I live in the UK. For the last two months, I have been subscribed to TWiV and enjoy listening to whats going on in the world of Virology when I’m not revising for my mocks.

I’m at a point where I’m deciding what my future career will be. Virology has proved very interesting and is a very vast career option with plenty of discoveries to be found. Even Dr Nathan Wolfe said in a TED talk said ” If an intelligent extra-terrestrial was taxed with writing the encyclopedia of life on our planet, 27 out of 30 of these volumes would be devoted to bacteria and virus, with just a few of the volumes left for plants, fungus and animals, humans being a footnote”.

Coming back to my question. As someone who is involved in Virology, could you give me any information about the field? For example, what is the salary like?, What would a working day consist of? and how would you go through it? This information will help me make a choice for my future.

Please get back to me as soon as possible as I’m very interested. I’ll still be listening to the podcast every week to hear the latest news.

Yours Faithfully,

Ann writes:

Dear TWIV community,

I wanted to make a contribution regarding Episode #145. You read an e-mail from Wendy at University of Iowa regarding the history of cloning technologies. She referenced the 1970s work at the NIH and scientists self-imposed (or externally imposed) moratorium on the work until the risks could be investigated. As you mentioned there was also a moratorium on cloning work in Cambridge, MA. A few weeks ago I stumbled upon this treasure – a (black and white) video recording of the Cambridge City Council hearing on the risks of recombinant DNA work, including city council members, scientists from MIT and Harvard, and a representative from the NIH, and Cambridge citizens. The MIT Library has an edited copy of this video (30min total), including some narration, available on their website as part of one of their 150th anniversary projects. Please post this link for others who may be interested. It is fascinating to me that one scientists tries to defend the ongoing research as very unlikely to be hazardous, while another scientist points out that this new and powerful technology has a huge potential – to help but also to harm, still poorly understood. I think it is important for scientists to be able to talk, with each other and with the public, about the implications of their work – scientific and moral.

I am glad to hear you discuss not only the hot new papers, but also the fascinating investigations from the past that got us where we are today. I think this is wonderfully enriching, for scientists to understand our heritage, so to speak.

Thanks for all your great work!

Ann

Virology Graduate student, Harvard University

P.S. It was a pleasure to meet you, Vincent, when you visited our department retreat in September!

http://mit150.mit.edu/multimedia/hypothetical-risk-cambridge-city-councils-hearings-recombinant-dna-research-1976

” The film Hypothetical Risk, The Cambridge City Council’s hearings on DNA Experimentation in Cambridge was recorded in June 1976 at City Hall, Cambridge, Massachusetts. Mayor Alfred Vellucci and city councillors Saundra Graham and David Clem are among those to question a panel of scientists including Mark Ptashne (Harvard professor of biochemistry and molecular biology), Daniel Branton (chairman, Harvard Safety Committee), Maxine Singer (National Institute of Health biochemist), Ruth Hubbard (Harvard professor of biology) and Jonathan King (MIT associate professor of biology). Produced by the MIT Oral History Program for the Recombinant DNA History Project in 1978.”

TWiV 160

Neva writes:

Hi fellas,

Great programs as always. I look forward to each one: TWIV, TWIM & TWIP. …..Lots of TWIT too. 😉

Here is a list of top science apps forwarded by William Gunn on G+.

Mendeley and PLoS staff both voted on which apps could have the greatest impact on science.

http://www.mendeley.com/blog/highlighting-research/the-top-101-apps-in-the-mendeley-plos-binary-battle/

Very techie and above my pay grade, thought you fellas would find this interesting.

Thanks for your fabulous podcasts.

Godfried writes:

Dear Gentlemen,

Your discussion on the experiments from the Fouchier lab (creating the “most dangerous virus in the world”) reminded me what a joy it is to listen to a good, thorough conversation. While typing this Dr. Fouchier walks around some floors above me (i’m in the same institute but a different lab). I was thinking that it would be really nice if he could join TWIV for one episode and hear his arguments for his approach. Maybe after publication of his story (if at all). Let us see where the differences of opinions occur and try to understand each others point of view.

Who would decline such an invitation from Dr. Racaniello (the man who possess a refined art, that to hurt cruelly whoever does him evil)?

Many thanx for all you’ve offered in the past and for all that will come,

Godfried

ps i did the listeners survey

pps just discovered that Dr. Condit does not have a beard (according to the drawing on the website). For some reason i always pictured him with a Hemingwayesque-beard.

Volker writes:

I am a german science journalist who did listen to your nice blog on the Fouchier Story. I have to say that I liked you discussion a lot although I do not agree on every angel of it.

I did reporting on the story, unfortunatly in German only (http://m.faz.net/aktuell/wissen/medizin/mutmassliche-killerkeime-ein-virus-lernt-fliegen-11542644.html).

I was worried why this was published in Science without publishing or discussing the data, and I could not find many experts willing to discuss the marginal information we have. But I think the public must know about this because in my view, this virus is different from others viruses if it´s true that is probably as deadly and as highly transmissable. Do you know another one on this list?

Although I did appreciate your discussion and the critic of the comments by Enserink and Fouchier, I am wondering whether you send you critical comments to both of them to learn why they did say what they said or wrote. Just looking at the press sensationalizing this story misses the point, namely that the researchers and science reported it first. So the scientific community should deal with the way it communicates and not just blame the press to do it if communication channels fail. That´s one point.

I am also puzzled why you argue that this research should be published if and only if “containment for the scientific community” is guaranteed.

Are you saying that even if the mutation are in the public domain nobody could make such a virus and use it as a biological weapon?

Or are you saying that you don´t believe that this virus will be dangerous in real life?

Or are you saying that the model they did use, ferret, is not predictive what will happen in humans?

So actually I quite don´t understand what you main argument is on why publishing this recipe to build a deadly and transmissible bird flu virus is of no other concern that biosafety?

I not a fan of the bioweapon community, but in this case, I would like to see scientific discussion about what the model is and what it is not.

In trying to get in contact to many scientist I could find only one who had seen the data in Malta. He was in favor of publishing the work because of preventive measure against H5N1 but he was against publishing the five mutations due to Dual-Use. So he was concerned and he was an eminent flu virologist!

So I am really interested why you come to a totally different conclusion without having seen the data?

Hope you can send me some clues..

I wanted to make shure that you understand that for a science journalist this is not about creating panic, but reporting a real concern and discuss the deep questions whether or not some experiment should be done – in the public domain – or not.

This experiment was not stupid, but the knowledge gained may be used by scientist with not so good intentions. So I would argue, there is room and need for honest debate, where society has a say too, it not just internal to the scientific endeavour, therefore journalism kicked in.

The big question is, why did science publish this report without reporting about the science behind it. What is the real agenda here? What are the motive of Fouchier and Osterhaus and Kawaoka?

Thank you for listening to my thoughts. I am member of the German association of Science journalist and we are taking quality issues serious.

So I would love to hear your second thoughts.

Volker Stollorz

Wissenschaftsjournalist

Köln

TWiV 159

Jenny writes:

Hi Vince and the rest of the TWIV-cast!

You might have come across this news already, but it would be interesting to hear the TWIV gang’s take on this study done by Fouchier’s group from the Netherlands.

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/nov1711board.html

Thanks and have a Happy Thanksgiving!

Jeremy Luban writes:

Hey Vincent,

Thought you might want to know about Uta von Schwedler (?TWiV). She was a posdoc with Didier Trono in San Diego, then with Wes Sundquist in Salt Lake. The she worked with ex-Columbian Ila Singh. She has some very important papers in our field, that you might call “classics”. I refer to them again and again. Papers defining the Vif phenotype and HIV-1 CA structure/function/ESCRT.

I knew Uta well from Cold Spring Harbor. She attended frequently. She once took my daughter Maria swimming at CSH. Showed the picture to my Maria, who remembered her. Maria pointed out something ridiculous that I am embarrassed to say I never noticed: UTA lived in UTAh!!!!

Jerm

Wes Sundquist writes:

Jeremy – thank you very much for compiling that information and her papers and passing it along. It was a very thoughtful thing to do. As you say, Uta had a major impact on our field, and touched many people in addition to her scientific contributions.

Vince – if you are interested in any additional information on Uta please let us know. A facebook page has been set up in her honor and it contains a lot of information and memories, from virologist and also from her many friends outside of science. The URL is: http://www.facebook.com/pages/Uta-von-Schwedlers-Memorial-Page/219993061394704?sk=wall. This past summer one of Uta’s papers was selected as one of the thirty most influential papers in the thirty years of HIV research. I was asked to write a commentary on it, which is now out and now includes a dedication to Uta (http://www.hivvaccineenterprise.org/hive/feature/591 – 2003 paper). The selection occurred this past summer, and I’m pleased that Uta knew about the selection and saw the commentary before she passed away.

I’m also cc’ing this message to Almut and Nils because I’ve been telling Uta’s family how many virologists have contacted me to express their shock, condolences and memories of Uta, and I thought they might want to see a particularly good example of this. Feel free to pass this along to other family members that you think would be interested.

You’re right Jeremy – UTA did live in UTAh. She would also sometimes take the light rail or bus systems, which are run here by the Utah Transit Authority (UTA – see http://en.wikipedia.org/wiki/Utah_Transit_Authority). It used to amuse us that over the years we’d sometimes see her sitting at a bus stop bench labeled “UTA” or see billboards that said things like “Go UTA”!

Best,

Wes

Matt Evans writes:

What do you think of this:

http://well.blogs.nytimes.com/2011/11/16/pox-parties-in-the-age-of-facebook/?ref=todayspaper

Matt

anonymous writes:

I writing to tell you how thankful I am, for the work you are doing with your brilliant podcasts.

I’m a bachelor in biochemistry, soon to start in the molecular micro biology masters program. I would like to share with you the last 4 years of my life. In late august 2007 I was travelling in S.E. Asia during my summer vacation from university. I had an amazing time in places like Indonesia (Sumatra) and Malaysia (Penang). Unfortunately i caught a tropical virus along the road, namely Chikungunya. I´m sure you are familiar with this virus.

In rare cases the virus gives you chronically joint pains. I´m one of these rare cases. Over the years, I have consulted numerous different doctors. Recently I consulted an anesthesiologist who provided me with just the right painkiller. (From what I´m told, treatment is basically a “hit-or-miss” approach) My life was changed again. Now I’m able to use my body to all the things I love. First thing I did, was to walk. Just walk. Over the past 4 weeks I have walked more than 200 miles. It´s hard to describe how joyful I am, just being able to walk without feeling intense pain.

For every minute I walked, I was listening to your podcasts. They really helped me getting my fascination for microbiology back. In four years, you forget a lot. Your passion, your drive. It takes a serious blow. You have helped me find this long lost companion. And for this, I am very grateful! So I´m sending you my deepest thanks!

I hope you will keep up the good work! For my part, I´m looking forward to the next many miles in your company.

PS. Did you ever do a part about Chikungunya?

Danielle writes:

Hello!

I am Danielle from the University of California Santa Cruz (an undergrad majoring in Molecular, Cellular, and Developmental Biology/ Bioinformatics) and I was going through your archives and listened to an episode where it was mentioned that an app of some sort of your podcast/blog would be useful. I just wanted to let you guys know that I actually found out about you guys by looking for a microbiology type app and found one that featured content from your blog as well as a few others. Unfortunately a review of this app said it was completely useless/broken and it costs $4.99 (so you guys should totally make you own someday). However, I love to listen to podcasts as I do lab work, so I subscribed to your podcast with my google reader and now I can listen to your podcast on my android phone with ear buds while I’m running around doing whatever. This also works with the iPad and I would imagine it would work with an android tablet and iPhone as well! So until you convince some computer science grad or undergrad to make an app for you guys you could suggest followers subscribe with google reader as a substitute app.

On another note, I want to thank you guys for doing this podcast! As an undergrad I’m not really sure what I want to do post-graduation and I’ve always been interested in virology. My college has Phil Berman (he worked on one of the HIV vaccines) teaching vaccine related classes we don’t really have a virology department and I wasn’t that sure what a virology lab would really do or look like. However, because of your podcast I’m pretty sold on doing something virus related in the future.

Thanks,

Danielle

Chris C responds:

The app does work fine on all iDevices and Android phones as I have it installed on the Samsung Galaxy S, iPod Touch, iPhone 3Gs, iPhone 4, iPad and iPad 2, the only catch is that you have to be connected to 3G or the internet for it to stream or download the latest episodes. Once episodes are downloaded it can be used offline to play the episodes.

I suspect this user downloaded the app and then tried to use it when he/she wasn’t connected to the internet. I have tried to respond to this person using the comment review fields in the iTunes store but my responses have never been published, I believe because I am the content creator.

Unfortunately, no third party has written a new review in iTunes since April to counter the latest comment.

We have sold over 2,000 MicrobeWorld apps so far and this has been the only negative review to date. We did have one bug uncovered when we launched the Android version in December but we responded quickly with a fix and the reviewer updated his comment for us in the Android Market Place.

If you do decide on purchasing the iPhone/iPad version, please let me know how your experience is and I encourage you to write a review.

Simon writes:

Hi Prof Racaniello

I’m delighted to hear that someone of your calibre has jointed the CFIDS Scientific Advisory Board; CFS research needs more high-grade input. I’m also glad you met some patients and discovered that most of us are reasonable people trying to cope with a very difficult disease (and usually our illnesses kicked off after an infectious episode).

I’ve enjoyed your podcasts on XMRV and am sorry about the amount of flak that appeared on your site. A tiny but vocal and vitriolic minority of patients give the rest of us a bad name. Yes, we try to argue with them on forums but you can only be torched so many times before you realise it’s not only deeply unpleasant but also pointless.

Anyway, thank you for your commitment to trying to solve CFS – it is appreciated

Simon

Trudy writes:

[first part read on TWiP]

Now about TWIV…can you cover Herpes B? Actually knew a patient who sustained a bite from an infected monkey quite a few years ago. The patient was a Vet and was treated with a series of IV Acyclovir infusions. She was still living as of a couple years ago when the doc who treated her lost track of her, but it was probable that she is still OK. The treatment was experimental then.

Also got a huge kick out of your comments about DA Henderson’s remark about polio vaccine. I had the pleasure of meeting him a when he came to the College of Public Health at the University of South Florida to speak about WMDs. We spoke about vaccine preventable diseases and the growing disconnect with those who are anti vac “whackaloons”….Since I was involved with outbreaks of assorted diseases, including measles, we had quite a discussion. So many docs today have no idea of what the rash illnesses look like, and there is pressure for the newest grads to adopt CAM. It is of great concern. My mother in law had polio when she was a young mother. She suffers from post polio syndrome now.

I absolutely love your podcasts. Thank you for all your hard work…Between your podcasts and ID doc, Mark Crislip’s (Quackcast, Puscast and Persiflager’s Compendium of Infectious Diseases) http://moremark.squarespace.com/ I am in “hog heaven”…tapeworm free. Holy cow! I eat breathe and dream about tiny animalcules….

No need to respond to this long winded tome…just had to write. Miss working in Public Health.

TWiV 158

Ricardo writes:

http://www.forbes.com/sites/matthewherper/2011/11/07/pediatricians-group-slams-delta-airlines-for-running-video-made-by-vaccine-skeptics/

http://getbetterhealth.com/dont-fly-delta-airline-runs-anti-vaccine-videos-against-medical-advice/2011.11.13

Ken writes:

One of your emails included the request, “For us non academics, I’d love to hear a “day in the life” episode of a graduate student, a post doc, a PI and so on.”

It reminded me that, in 1999, journalist Jon Franklin wrote a long piece for the Raleigh New & Observer, To Make a Mouse, that did a great job conveying the daily life of a senior graduate student, especially the degree to which progress involves failed experiment after failed experiment.

Unfortunately, this was back when newspapers didn’t leave stories on the web for long, so it seems the piece is only available as a document file from the author.

(And I’ll be damned if I know how to make a link to it, but it comes up on top of searches of “To Make a Mouse Jon Franklin”)

http://www.google.com/url?sa=t&rct=j&q=to%20make%20a%20mouse%20jon%20franklin&source=web&cd=1&ved=0CBsQFjAA&url=http%3A%2F%2Fwww.jonfranklin.com%2FStories%2FDocuments%2FTo%2520Make%2520a%2520Mouse.doc&ei=CtK7Tr75Jqfg0QHG0vXeCQ&usg=AFQjCNEr8P0qfrsVs0-B4_5kapi21JZ6Pw&sig2=4k_imJjPKIlhpSi9Y5ExPQ

(links to a Word document)

Jen writes:

hey vince and friends! guess i should start off by saying how much i love your podcasts… i discovered twiv shortly after falling in love with viruses in my first microbiology class and have been addicted to them ever since. i was surprised to discover that such an academic subject would have its own podcast. and pleased!

anyways, i am currently a community college student and plan to transfer to a 4 year university next fall. i had been planning on majoring in biochemistry after transfer, but that was before i discovered how fascinating virology is. my question: assuming i want to get a graduate degree in a virology-related field, should i keep my current biochemistry major or should i major in microbiology/molecular biology? i’m sorry to bug you with such a trivial question but i don’t know anyone else who would have any insight into this subject, and i really want to maximize my chances of getting to study something i love (viruses!). any reply would be much appreciated… and also keep the awesome podcasts coming.

thanks!

jen

Don writes:

Vincent, Dickson, Allen, and Rich,

(I hope you will allow me to address you by your first names. After all the hours I have spent with you I feel that I know you.)

I am a long time listener and believe that your podcast has made my life richer in ways that would be difficult to describe.

There is one thing that bothers me however and I hope you will indulge me for a moment.

It seems that you have a bias toward accepting research at face value without an appreciation that some research is skewed by scientist and drug companies for monetary or other considerations. Please don’t take this as an aspersion or insult to the character or anyone on the podcast. In a word I guess that skepticism is what I see as sometimes missing.

Anyway, I don’t think this email needs to be read online but I would like to recommend a “pick of the week” that expresses my skepticism more eloquently than I am capable of doing. It is a Ted Talk by Ben Goldacre, titled Battling bad science.

http://www.ted.com/talks/ben_goldacre_battling_bad_science.html

Thank you for the great podcast,

Don

James writes:

Dear Vincent, Alan and Rich, Thank you for filling my bicycling and running time with virology discussions which are excellently informative as well as enjoyable. A combination not always to be expected from podcasts. I know that you are working on a grant proposal to generate, what I imagine is, much needed funding. I have a suggestion which might generate a small amount of discretionary funds, as well as provide some verifiable data for consideration by your advertisers. I subscribe (actually pay) for several podcasts, which the provide ‘additional’ material to be downloaded automatically in iTunes. I find it difficult to believe that you would not have 15 minutes of additional discussion already recorded for each podcast, that could be supplied as ‘extra’ listening for subscribers. The ‘extra’ sessions could be: 1) an additional paper that you could not fit in when in ‘journal club mode’; 2) a short interview with an outside expert who did not have time to participate in the entire TWIV recording; 3) an informal discussion of points you did not think or have time to bring up during the regular TWIV discussions; 4) a breaking news item that went to press after recording the podcast, but was of sufficient interest to not wait for the next week; or, 5) shorter versions of your ‘virology 101’ discussions which might be easier to produce than a full hour. I would think that $2 per month for an annual total of $25, which seems reasonable to me, would also be acceptable to others. Thank you for all you instruction, laughs, insight into other topics (e.g., vertical farms) and just plain fun you bring to my week. You are even managing to teach some virology to one who never had time while in school. Best, JP

James, Ph.D.

Tim writes:

One of my friends and colleagues here in Cincinnati, Dick Ward, is now mostly retired but recently penned an autobiography about creating the rotavirus vaccine. The book is called “Deadends to Somewhere” and can be found at this link: http://christophermatthewspub.com/authors-2/richard-ward. It might be of interest to you and your listeners. While the majority of the book is about his personal struggles, and only near the end does he discuss Rotarix, in telling his story he conveys the trials and tribulations of young scientists trying to find their way and establish a niche and a purpose. It is also a lesson in serendipity in science, as his experience in viruses such as reovirus, which at the time seemed to be for naught, ultimately served him well when he found himself working with rotavirus. I had lunch with him last week and told him about TWiV, so I might have found you another listener.

Tim

>>>>>>>>>>>>>>>>>>>>>>

Timothy P. Cripe, M.D., Ph.D.

Professor of Pediatrics

Division of Oncology

Cincinnati Children’s Hospital Medical Center

TWiV 157

Robert writes:

The reason you can’t do an ethical placebo test for vaccines is that it is considered unethical to withhold the current standard of care. {see the Helsinki Declaration} “Alternative medicine” promoters complain fairly frequently that testing of their favorite remedy for <insert anything here> failed its testing because it was tested in conjunction with the current standard of care vs just the current standard of care. Direct testing of anything against placebo when there is a standard of care and any risk to the patient/subject almost never gets past an legally constructed IRB. It happens infrequently, but one thing that is a red flag that an IRB is ineffective (or fraudulent) is repeat approval of placebo controlled trials contrary to an established standard of care.

I’m sure that there is a member of an easy to contact IRB at your university that could explain things much better where I probably just caused confusion.

Thanks for producing something that lets me put my insomnia to productive use, though writing this in the morning might have made it clearer.

Nick writes:

I must say I was pretty excited to see some of my work on TWIV this week (I never thought that would happen). I was one of the authors of the Lancet ID paper on flu vaccine effectiveness. I really enjoyed the discussion and the jokes about meta-analysis. I wish we could have done a tighter meta-analysis by age, vaccine, risk factors, etc but there was not enough data to do that.

I wanted to follow up regarding some of the points for LAIV. It was noted that the LAIV seems to be a much better vaccine. I would agree for children it would be preferred, as you guys noted. However for adults, it’s a much more complicated story. We did find three studies for adults, but they were not significant . LAIV was licensed on non-specific outcomes for adults, which is why that study was not included in our analysis. It could make for a very interesting discussion on TWIV about why LAIV works so well in kids but poorly in adults. Dr. Arnold Monto and his group at Michigan have done a lot of work on this and have some great ideas on why this is the case. Those ideas are encapsulated in this press release (http://ns.umich.edu/new/releases/7322)

With warm regards,

Nick Kelley, PhD

CIDRAP

Ricardo writes:

Hello TWIV members.

This time I have a question. It is related to the flu vaccine efficacy.

What is the reason for the lack of efficacy?

The fact that the vaccine misses the antigens of the virus that is affecting the person (wrong antibodies), which would involve vaccine production tuning (faster), broader antigen coverage, better antigen targets…

(If this is the case then the all family would be at risk in case of a low efficacy vaccine)

or differences in triggering the immune response in different people, which would require better routes of delivery, more reactive target choices and probably more adjuvant research…

In this case family members would have different levels of protection.

Once again thank you for the show, it really brights my day and my enthusiasm for microbiology (all of it).

R i c a r d o M a g a l h ã e s

P r o f e s s o r A s s o c i a d o

U n i v e r s i d a d e F e r n a n d o P e s s o a

Peter writes:

Headline reads –

Horse euthanased with Hendra virus

So they inject a horse with Hendra because it had a broken leg or something?????

Man, I was taught not to write like that when I was like 8. No wonder the netizens hold the old press in such contempt.

Article…

http://news.smh.com.au/breaking-news-national/horse-euthanased-with-hendra-virus-20111011-1li7d.html

TWiV 156

Kevin writes:

Dear Professor Racaniello,

I have just seen some of the ridiculous comments regarding the picture which was posted on your TWiV website.

I have had CFS for over 16 years. I am a very firm believer in scientific method and have found it very frustrating at the lack of top quality scientists who have taken an interest in well-defined patients. It has therefore been a great pleasure to see people like Harvey Alter, John Coffin and others conducting research into XMRV. The data is the data. I hope resources and attention are now swiftly moved to other areas.

I want to personally thank you for giving XMRV a good run. As a CFS patient in the UK, I am used to seeing most apparently novel findings shot down rather quickly or simply not followed up. It has been heartening to see the XMRV issue tackled professionally and thoroughly. A true victory for science, regardless of the unfortunate events now taking place ( the “slide” issue ).

I am sorry you have been on the receiving end of attention from some of the less balanced members of what might loosely be termed the “CFS” community. I think anyone with any objectivity and belief in scientific method would frankly lose the will to live after just five minutes of reading some of the material on mecfsforums. I don’t know if you’re aware of the background, but this forum was set up after a group of very rude and rabidly pro-Mikovits posters left the Phoenix Rising Forums after continual warnings about their conduct. It’s actually possible to spot their contributions on Deckoff-Jones blog and many other places on the internet. They are an extremely vocal minority who misrepresent the vast majority of CFS patients. I’m sorry if you’ve been subjected to this kind of nonsense. Apart from anything else, most CFS patients simply don’t have the energy to sustain the relentless garbage which they produce.

My reading of some scientific literature over the last few years ( my degree is non-science so it’s layman’s opinion ) suggests to me that immune dysfunction rather than a persistent infection results in the immunological manifestations of CFS. However, it would be great for TWiV if Prof Lipkin finds something in his pathogen project. It’s just fantastic that someone of his calibre is doing the work, whatever the data.

Once again, many thanks for your patience and understanding.

Kind regards,

Kevin.

Janet writes:

Hi TWiV gang,

I just wanted to let you guys know that I love listening to your podcast. I only recently discovered it, so I’m still trying to frantically catch up with all the episodes. I remember you guys asking for a transcriber back in Episode 30-something, but judging from the Transcripts section of the website, I guess there weren’t that many takers. I don’t now if you’re still taking transcripts, but I thought I’d try my hand at it, so I’ve attached the transcript of the latest episode. I couldn’t figure out the formatting for the header, so I’ve also sent the .docx file to play around with.

I guess I can see why there aren’t so many people jumping to volunteer for this, as it took a lot longer than I thought it would! Nonetheless, if it’s alright with you guys, I will try to transcribe a few more episodes, especially the Virology 101 episodes, because I feel those would be the most beneficial to both the audience and myself.

I’m starting my PhD in two weeks at the University of Heidelberg in Germany. It’s a charming town and I will be working on foamy virus vectors, in the same building as Prof. Harald zur Hausen, so I’m very excited. It would be great to see an episode on foamy viruses one day; you mentioned them once very briefly in the reverse transcription episode and I find their apathogenicity and therapeutic potential fascinating. I’m coming from a biochemistry background, so I hope I’m not getting in over my head and any advice you could offer on the PhD life, virology, or science in general would be fantastic and greatly appreciated!

Keep up all the good work!

Grüße aus Deutschland,

Janet

Zachary writes:

Dr Racaniello and company,

I am a nursing student at the University of Washington and love listening to TWIV on my commute! In my pathophysiology class my teacher recently told us that the problem with polio is that immunity is not lasting as long as we previously thought. She stated that we are now seeing increasing cases of polio amongst the elderly due to the decrease in memory T & B-cells. I’ve listened to several of the podcasts on polio and do not remember hearing this information. Can you please enlighten me on this topic? Thank you and keep up the amazing podcasts!

-Zach

Kathryn writes:

Dear Twivers

I’m an ESL teacher in South Korea. I discovered your podcast through iTunes about a month ago. Though I now teach I have a background in science (college) and a masters in psychology. I enjoy your podcast greatly as it appeals to my math/science dominant side.

I enjoyed your recent episodes on XMRV and how well it demonstrates how the scientific process and peer review work. I was additionally interested because I was recently diagnosed with fibromyalgia, which seems to be related to CFS at least at a symptom level. Do you know of any work being done on possible viral causes of FM?

I also have a quick story to share. At an ESL training yesterday, we played essentially “Taboo” as an example of an “academic activity” (we can’t call them games here or the parents go nuts). One of the 10 words my team wrote down was phage. The team that got our paper passed on it. The leader asked if anyone knew and then asked whose word it was. I meekly raised my hand admitting it was mine. And she says. Well what the heck is it; we all want to know. After saying it was a virus that infected bacteria someone replied “You weren’t an English major, were you.” That’s where I admitted no, I wasn’t.

Thanks for your show and keep up the good work.

~Kathryn

TWiV 155

Kim writes:

To the TWiVerati Intelligencia,

Each week you begin your show with the tagline, “This Week in Virology: The podcast about viruses, the kind that make you sick.”

I recognize that viruses have been responsible for some of the biggest epidemics and plagues of man, beast and plantlife. But as a long-time TWiV listener, it seems like you also cover viruses have that “positive” effects/impacts on our planet — viruses that are used for varied things as batteries and to fight other pathogens or pathogenic responses. All the work being done on the microbiome suggests that keeping the correct balance of our symbiotic critters (including viruses) may be even more important than which ones are living inside us or on us. So even though it’s catchy, maybe you should reconsider the tagline in an effort to cultivate respect for viruses instead of fear?

Thanks for the great 90 minutes of informative science and thoughtful discussion each week, no matter how you pitch it!

Kim

P.S. It’s cloudy and 22 degrees Celsius.

Luiza writes:

Hi, Professor Racaniello,

I’m a Doctorate student from Federal University of Rio de Janeiro and I’m going to attend the Brasilian Virology Meeting next week. I’m also attending a discipline on my university about Scientific Divulgation, and the students should produce a podcast every week to post on the discipline website. I would like to know if you would accept to give me a short interview during the Meeting next week. It would be an honor if we could have an interview with someone so concerned with Scientific Divulgation (in Brazil, people are still starting to give attention and importance to this matter). Hope You can accept it!

Best wishes,

Luiza

Laboratório de Genética e Imunologia das Infecções Virais – IMPPG

Universidade Federal do Rio de Janeiro

Rio de Janeiro, RJ – Brasil

Vinayaka writes:

The entire saga of the possible (now absent) link between XMRV and CFS that has nearlyconcluded, as discussed in TWIV 150, reminded me of the need for scientists to have the right level of tenacity in their scientific belief. A fabulous guidance on how to do this is provided in an article by R. A. Lyttleton called ‘The Nature of Knowledge’ in a book I read very, very long ago – “The Encyclopedia of Ignorance” (edited by Ron Duncan and Miranda Weston-Smith – 1977).

Lyttleton graphically represents one’s scientific belief, in any concept or hypothesis, as a bead on a straight line. The two extremes of this line are 0 (complete disbelief) and 1 (complete certainty). He argues that one should allow his/her bead to move in either direction based on the accumulation of evidence in favor or against. For example, if you believe greatly in favor of a concept, you allow your bead to approach 1. When evidence disproving that concept is presented, you should be able to move towards the opposite direction. However, he cautions that at the very ends of this straight line, there are deep emotional pits. If one letstheir belief to go too far to either end, they will fall into the deep pit and when the evidence does accumulate against that concept/hypothesis, they will be unable to move towards the other end. We know some people who are already in the pit – Peter Duesberg is one. There are obviously others. I do hope that everyone involved in the XMRV saga, including Dr. Mikavits, will recalibrate and move away to a new position on the line before falling in the emotional pit.

Keep up the fantastic work with TWIV – I will be listening in for years to come….

– Prasad

——————————————————————————————–

Vinayaka R. Prasad, Ph. D.

Professor, Department of Microbiology and Immunology

Director, AIDS International Training and Research Program

Albert Einstein College of Medicine

David writes:

Dear TWiV: enjoy your podcasts, but not being a virologist can have some disadvantages when it comes to trying to understand virology. Two questions for you that have been gnawing at me lately:

1) I cannot understand how any truly novel virus can be discovered using tools that require knowing what to look for: PCR primers have to be made against a known sequence in order to specifically amplifiy it; antibodies have to be made that bind to specific antigens, which means you have to have the antigen you’re looking for in hand before making antibodies necessary to detect it (did that make sense?). It’s very much like generals fighting the last war–how can anyone claim to have found anything totally new and different if the tools and reagents are specific for what is already known? It’s a which-came-first-the-chicken-vs.-egg issue: how can anybody find anything truly novel using reagents and tools that depend on having some pre-knowledge/bias of what to look for? I can understand how these tools would be useful for finding simliar viruses, but how can anyone claim that these specifically limited tools and reagents can find dis-similar/novel stuff that has never been encountered before?

2) I just figured out how Western blots are supposed to work. But if they are prepared by running proteins down a denaturing SDS/PAGE gel, then transferred to a blot, and finally probed with a detecting antibody, doesn’t the antibody have to be specific for the denatured protein of interest? Isn’t it sort of like looking for an egg (the native protein) by detecting scrambled eggs (the protein after being denatured and transferred to a membrane for detection)? So again, unless you previously know what an intact egg already looks like, how are you supposed to deduce anything about an egg (in native, original form) if the methods require you to scramble it up (denature them) in order to detect them? Hope this question makes sense.

Thanks for the podcasts, learning much,

Not A Virologist

Antonio writes:

Hello there, acTWiVists!

Thank you so much for these podcasts. I’m a Filipino programmer / tech geek who’s been following the three of you since the Nile River virus episode. I’ve been absolutely captivated by this window you give the world into biology and the life sciences.

Your other student listeners might find the Nature Video covering the 2011 Nobel Laureates’ Meeting in Lindau fascinating. There’re five short films there featuring one-on-one dialogue between a student and a Nobel laureate who’re both working in the same field – shedding insight on the passing of the torch between generations in science.

All the best,

Antonio

TWiV 154

Gabriel writes:

I just finished listening to TWiV 152, in which you spent quite some time discussing the death of Steve Jobs the past week. Though this mention is certainly well-deserved, I thought it was an oversight not to make any mention of the outstanding immunologist and fellow New Yorker Ralph Steinman, who also passed away due to the same disease that same week, only days before being awarded the Nobel Prize for the discovery of dendritic cells. I know you guys are not the greatest fans of immunology, but I think that it deserved at least a mention, especially given the huge importance of DCs to the way our immune system senses and responds to viral pathogens.

Gabriel

Faleye writes:

Hi TWiV crew,

I’m Faleye Temitope from Nigeria. I’ve finished a masters degree in virology in Nigeria and will be convocating in November 2011.Though I’ve been offered a PhD position in Nigeria, I’l love to experience education in another part of the world. I have been searching for what to do for PhD and in this light i went for IUMS 2011 ICV meeting in Sapporo, Japan and it was mind blowing. It was my first time in an International meeting and a Virology meeting at that. I learnt a lot and just assumed the TWiV crew would be there. I was however not very happy to not see you guys there.

At the meeting I learnt about Saffold virus for the first time. Saffold virus is a Human Cardiovirus that was first identified in 2007 by Morris Jones and his group in California. The virus was isolated in 1981 from an 8 month old female child with Fever of Unknown Origin. On returning to Nigeria, I downloaded everything on Saffold virus listed in pubmed and am churning through it all. I’m surprised to see the likes of Nick knowles, Eric Delwart, Howard Lipton, Don Ganem, Joseph Derisi and Nathan Wolfe already neck deep in the field. What was more surprising was the fact that I have no memory of Saffold virus being discussed on TWiV.

The way you guys covered XMRV has built in me a level of trust in your judgement as a team and i will so appreciate you guys discussing Saffold virus on TWiV. Should I venture out to work on, for PhD, Saffold virus in Nigeria? Please, i will appreciate it if you can, in additon to your opinions, also add the opinions of David Baltimore, Karla Kirkgard, Ian Lipkin and any other individual you feel is well positioned to inform my choice.

You guys have constantly been a source of strength and support to me. I’m glad to inform you that I finished top of my M.Sc class and I have to confess that TWiV and Prof Racaniello’s virology lectures played a big role in my education. You guys thought me a sizable chunk of all I know today about Virology. Thanks guys for all the effort you put into educating me and everybody out there who in one way or the other has benefited from TWiV.

I look forward to hearing from you.

Faleye

(photos at VirusTalk)

Dan writes:

Hello,

I’m a second year medical student and was turned on to your podcast by my medical microbiology professor. I love listening to your shows because they integrate the often dry, tedious, concepts and “bugs” that I’m learning about into relevant, amusing, and easy-to-follow stories. You make learning entertaining.

A few episodes back, you mentioned that you were looking for a Virology for Dummies-style text book for amateur enthusiasts. While, not specifically virology oriented, I’ve found the book ”

Clinical Microbiology Made Ridiculously Simple by Mark Gladwin and William Trattle to be a great resource.

http://www.amazon.com/Clinical-Microbiology-Made-Ridiculously-Simple/dp/1935660039/ref=sr_1_1?ie=UTF8&qid=1317758776&sr=8-1

It takes a humorous and lighthearted approach to a fairly complicated and, as I said before, often tedious subject. Through humor, cartoons, mnemonics, and other imaginative “study tricks,” its a great way to understand the basic concepts of medical microbiology. Since I’ve been completely immersed in all things medicine/science for the past few years, its hard to judge just how “ridiculously simple” the book may appear to a complete lay person. However, for someone with basic science knowledge (e.g. knowing the difference between RNA and DNA), and trying to get more insight into the world of microbiology, I highly recommend it.

The best part about this book is its knack for juggling basic concepts with just the right amount of detail, without overwhelming the reader with technical jargon or complicated, seemingly random, facts. It is able to integrate and link concepts without coming off as a “bug parade” as most micro courses/books often do.

Besides a few chapters on viruses (classification, life cycles, structures, specific viruses, etc), it spans concepts of microbiology from differentiation of gram stained organisms, to specific organisms (Staph vs Strep, food born, etc) to parasites, fungi, prions, and even mentions some pharmacology. Definitely worth the $25 price tag.

Please keep up the good work.

Thank you,

Dan

Ricardo writes:

Hello Vincent and the rest of the twiv gang.

Congratulations for the three years. I haven’t write much but you can be sure I’m there listening every monday on my driving to the University. Talking back to you as if I was there. One of your listeners said it seems like you are our friends. Well, it sure fells like it. I can see a Tertulia about Virus with all of you siting at a café table.

I’m giving a little bit back with this video, once again. You might use it on a public Twiv event while you wait to star the show, so people can see a little bit of the Twiv history.

My best regards to all of you.

http://www.twiv.tv/3DTWIV.m4v

Ricardo Magalhaes, Ph.D.

Associate Professor of Microbiology

Faculty of Health Sciences of Fernando Pessoa University

Portugal

Geoffrey writes:

Doctors and Alan (I don’t remember mention of a PhD for you):

I don’t follow these matters closely but I have a point that I feel probably confuses a lot of people and probably contributes heavily to rumors of continuing US offensive biological weapons programs.

As pointed out in episode 151, there are now quite a few defensive programs in place in the US. As part of their research, some of these programs actually do weaponize biological agents. This is not because they are, necessarily, looking for the next best weapon nor because they think defenses against these will be of direct use in the future. It is, rather, because weaponizing (indeed any genetic manipulation) has unpredictable (at our level of technology) system-wide effects and they are creating these agents to gain insights into how weaponizing might make biological agents more or less susceptible to established defenses. Sure they keep these creations around for future study and that is, I believe, what causes many rumors of weapons development.

However, the difference between defensive and offensive development is mainly in quantity. A few vials of a weaponized strain, while dangerous, is not a weapon. A few tons of micronized smallpox or anthrax ready to be distributed to warheads is a weapon (as was the case before the disbanding of the Soviet Union). To the best of my (the public’s) knowledge, the US is not stockpiling biological weapons and is not, therefore, engaged in any offensive programs. This does not mean that the US does not have some gems in a freezer somewhere that they are prepared to produce in quantity should the need arise but that is not an offensive program.

Geoffrey

Timothy writes:

Dear TWiVers:

I’m responding to your discussion about M.D.-Ph.D. training in your e-mail-only episode #151. You got it mostly right, but there are some nuances that were missed. While M.D.s can do basic research, and Ph.D.s can partner with M.D.s to bring clinical translation to their work, we clearly need people at the interface who do both for a more seamless transition. The two pathways for a person to reach the point where they take care of patients and conduct bench science are, as you said, (1) the combined program or (2) an M.D. to trains extensively in the laboratory. Many of my colleagues that have taken the latter route received their laboratory training during their subspecialty fellowship years and stayed under their mentor’s wing until they were able to procure their own K- then R-level grants. They learned to do science by apprenticeship, however, without the rigorous oversight of a thesis committee or completing the academic requirements of a Ph.D. training program. I believe that the Ph.D. training equips the individual with a more robust toolset for conducting research, and ultimately they are better poised for success. There is a downside, of course, in that the training is long during years of being a student and going further into debt. I myself essentially was in school for 17 years after high-school before my first real job. Of course, talented individuals will be successful no matter which route they take. I do want to emphasize how important it is for there to be people that do both, because they can get things done or see insights that two people from the different spectrums can’t appreciate.

Tim

>>>>>>>>>>>>>>>>>>>>>>

Timothy P. Cripe, M.D., Ph.D.

Professor of Pediatrics

Division of Oncology

Research Director, Musculoskeletal Tumor Program

Medical Co-Director, Office for Clinical and Translational Research

Director of Pilot and Collaborative Clinical and Translational Studies Core,

University of Cincinnati Center for Clinical and Translational Science and Training

Cincinnati Children’s Hospital Medical Center

Georganne writes:

Has Ila Singe made a statement about whether XMRV is still a player in prostate cancer. I’m surprised I haven”t seen a statement from her regarding this issue. Have I missed it. I would think she would go with the latest studies that show XMRV is a contaminant in prostate cancer.

Thanks.

TWiV 153

Jim Pipas writes:

1. Geographic Breakdown. The data can be broken down by location if you download Table S2. It is in the last column. We didn’t discuss the data by location because for this paper we took a single sample from each site. Thus, this is a snapshot of viral diversity at the moment the sample was taken. As we indicate in Equation 1, the probability of detecting a given virus is dictated by a number of time-dependent variables. For example, climate or time of the season might be expected to impact the number of a specific type of virus present. We felt that to make conclusions about location we would need to collect many more samples under a number of different conditions. We are doing this now.

2. I am not sure why we didn’t see any negative strand RNA viruses or poliovirus. There are three possibilities that we are testing. One is that the method of virion enrichment, in this case flocculation, did not capture these particular viruses. The second is that they are present below our limits of detection. That is, we need to sequence deeper. We know that there are viruses present in the samples (detected by PCR) that we do not detect by sequencing. The final formal possibility is that these viruses are not present in our samples. I will let you know what we find.

3. How many species of hosts? The number 1.8 million does include bacteria but clearly this is a serious underestimate. I too have seen that this number is likely to be revised to 8 million but I have not seen this estimate published in a scientific journal yet. We decided to go with the published number. I agree with you that there are many many more bacterial species that await discovery, and that means many many many more viruses.

Michael writes:

In TWiV 151 at about 54:40 Alan says that “the general lifestyle of macrophages, which do kinda make a living this way, they go around eating stuff thats not supposed to be in the blood stream”. I couldn’t help but to catch this error.

Alan, it was my understanding (from my basic Immunology course) that Macrophages are monocytes while in circulation, and it is not until they have left the bloodstream into tissue that they mature into macrophages.

~Michael

P.S. Alan I greatly enjoy your input as a writer!

Jamie writes:

Hello Gentlemen (and Alan),

I wanted to bring to your attention the NUMEROUS dangers of “pitches” or fields, especially ones that aren’t as well kept as the professionals’…

My fiance plays rugby. The field is not only home to rugby games but it serves as a temporary home to plenty of wildlife. By wildlife, I mean Canada geese. The field sees many flocks of geese who are not “potty trained”. The public also allows their canine companions to run and excrete on the field. One home game last fall after extensive rain, the field was very soft. Unfortunately, the field has a hidden slab of concrete about 4 inches below the surface. My fiance launched himself to tackle his opponent and his knee sank more than 4 inches right at the corner of that concrete slab… Sparing the gory details (and the video, I just included a gory still), he was taken by ambulance to hospital where the emergency department decided the wound was too deep to be cleaned while he was conscious.

The Dr. that performed his initial surgery cultured the wound and gave him IV antibiotics overnight. The laceration was stapled completely shut (no drain was placed) and the bandage was instructed to be removed in 5 days, no sooner.

When the bandages were removed the area was swollen, tender, and red coloration extended up his thigh almost to his groin. By the next day my fiance had a high fever and went to the doctor’s office where the original doctor’s partner sent him immediately back to the hospital.

The original cultures were never finished. Secondary cultures showed gram positive and gram negative bacteria and the majority of what was cultured came from “fecal material”. The IV antibiotics were not enough to knock out the infection. He was subjected to 4 more surgeries, lost part of his patella, and stayed another 10 days in the hospital. He will never be without pain in that knee again…. Not because of the accident on the field, but because of the secondary infection.

I know this would be more appropriate for TWIM but I wanted to let the TWIV team know what dangers are on our fields.

Thanks! Hope I don’t gross you out with the pictures. Let me know if you want the video of them cleaning it out with just sub-q analgesics!

Jamie

Tim writes:

Dear Vince, Rich and virology podcasters, thanks for the great podcasts! I am a beginner in the world of science, biology, and dare I say virology. I returned to school two years ago as a 38 year old truck driver, and am seeking a bachelors in science. I would like to enter the medical field in some way, and find your podcasts to be highly stimulating. I have been listening to your virology podcast in addition to your virology class lectures from Columbia for about a year now and find it increasingly interesting. I find it takes me about 4 times per lecture to actually grasp a lot of the info, but I am not giving up. One of the first things I learned was that for a virus to be successful it needs three important parts, entry into a host cell, replication, and it needs release out of the cell. Recently I read information on how the influenza virus can be affected by drugs which can indirectly inhibit the release of new virus particles and I have a couple questions, I am interested to know more about the effects of the antiviral medications amantadine and rimantadine on reducing the severity of the influenza virus. Do these drugs actually stabilize the bodies PH? and if so, how far does the PH have to shift before the virion will release its contents into the cytosol of a host cell? There are also the drugs oseltamivir and zanamavir which effect both A and B types of influenza by blocking the glycoprotein neuraminidase so the new virus particles can not be released. How well do these drugs work? And if they do, why are they not more well known?

Thanks, virology want-to-be

Tim

Tony writes:

Hi TWIVers,

You’re probably bored with hearing this by now, but you guys are great! Congratulations on the great job of making virology accessible to the masses. We are not as dumb as television and the newspapers would lead you to believe.

I’ve been listening since just after you started podcasting, and I’ve been meaning to email you for about two years. I’ve got a lot of question saved up – feel free to stop reading at any point…

1) A few episodes ago, a listener asked for suggestions for virology software. My suggestions is a pc game style virtual virology lab, where you could grow virtual viruses in a virtual culture medium containing virtual cells. The cells may or may not have the correct receptors on their surface to allow the virus to enter, and even then, they may not be able to replicate. You could find this out by doing virtual plaque assays – all this with no undergraduates spilling anything, or catching anything. The virtual virus would mutate at each replication cycle – maybe enhancing its virulence or transmissibility.

2) Last year some time, you reviewed a paper regarding replication of viruses which had been tagged with different coloured fluorescent protein. When they infected cells at quite high moi, there were few progeny expressing mixtures of colours – most expressed single colours. I didn’t really understand the significance of this at the time. Is it just saying a cell is not just a bag of chemicals, but has a very structured interior? Is is saying more than that?

3) For us non academics, I’d love to hear a “day in the life” episode of a graduate student, a post doc, a PI … and so on.

4) Being an Australian, I’m always interested in your discussions of myxomatosis, calcicvirus, henrda and dengue. Alan’s prescription “don’t raise horses in the rainforest” is a little hard to follow – there are large flying fox colonies in the botanical gardens of both Melbourne and Sydney – luckily there are no inner city horses! Here’s a link http://www.csiro.au/science/Myxomatosis-History.html to a myxomatosis story – read the paragraph headed “Hype lead to panic” – there are some famous names in it. My mother told me she had dengue several times as a child, growing up in Queensland, and was really ill.

I’m working my way through Vince’s online virology course – it has really helped me understand the podcasts. (Like Dixon, I now know there are seven fundamental types of viruses).

Regards,

Tony

PS. Here a a couple more things I almost forgot. I’d really like to hear more about the fossil viruses in the human genome. You had a great episode on that quite a while ago, and it left me wanting more. Also, I’d like to hear about the process of getting a vaccine out of the lab and ready for release. You’ve touched on if briefly several times. I had no idea it was such a large undertaking – more details, please…

TWiV 152

Atila writes:

Dear TWiVers,

I have heard recently that some types of herpes virus may protect us from bacterial infections. This made me remember of myxomavirus, viral oncotherapy and how tumor cells have a compromised immune response. Do you think it is possible that one of those long term herpes infections that cause no harm to the host could protect us from some kind of skin cancer?

Keep up the good work, and thanks Dr. Racaniello for the right pronunciation of my name at ASV

Atila

[herpesvirus latency confers protection against listeria: http://www.ncbi.nlm.nih.gov/pubmed/17507983]

David Knipe replies:

Skip Virgin had a Nature paper where they showed that murine herpes virus 68 could induce cross presentation against bacterial infections. There is an old literature on herpes viruses inducing Th1 helper and polyclonal B cell expansion (our paper was Nguyen, L.H., D.M. Knipe and R.W. Finberg. 1994. Mechanisms of virus-induced Ig subclass shifts. Journal of Immunology 152:478-484.). That is probably also a major component of the oncolytic virus effects, induction of innate responses and Th1 helper cell responses and inflammation. There could be some protective effect of latent and reactivating infections against other infections and cancer. So far, it has been too much of a long shot for any clinicians or epidemiologists to do any studies. I think that that is why we have not eliminated herpesviruses.

Bob writes:

Manchester United lost the services of Darren Fletcher with an unspecified “stomach virus” for 4 months.

As far as we know no Soccer Club sweeps their Training and Match Pitches for Faecal and other contamination ? These surfaces are regularly mown but it would seem reasonable that this would only break up contaminations and spread them wider ? Given that some of their players are earning £250,000 a week and may cost up to £50 Million to transfer in would you agree that screening was a worthwhile exercise and if so how often should it be done ?

Date: Tue 27 Sep 2011

Source: CIDRAP News [edited]

<http://www.cidrap.umn.edu/cidrap/content/fs/food-disease/news/sep2711newsscan.html>

Zoonotic rotavirus transmission may have occurred in Denmark

————————————————————

In Denmark, 2 adults were infected in 2006 with a rare rotavirus strain closely related to animal strains, suggesting zoonotic transmission, according to a report today in Epidemiology and Infection. The strain, G8P[14], was found in 2 patients who lived in the same area, and nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of isolates from the 2 people were identical. In addition, phylogenetic analyses showed both viruses closely clustered with rotaviruses of cow and goat origin. The authors conclude, “The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8P[14] strains were acquired through direct zoonotic transmission events,” which are uncommon.

Jane writes:

XMRV has come to mean the V62 clone that was created in Silverman’s lab, as expressed by 22rv1 cell line, which has never been in the WPI labs.

Lombardi et al found gag and env sequences 99% similar to the prostate tumor-associated strains of XMRV (VP62, VP35 and VP42) yet Silverman’s retraction was only for VP62, which incidentally is the clone used as a positive sample in just about all papers that failed to find any wild HGRV’s at all. I wonder if all the conflicting results have something to do with the semantics surrounding the way the labels are applied?

When you bring in the years of research on what MLV’s do in animal models, when you bring in the several earlier discoveries of retroviruses in patients with ME [called CFS since 1988], when you know people who have at the least improved their illness experience using anti-retrovirals (early days yet), you might not be so quick to dismiss the hypothesis.

To get to the BWG 3 results, the following criticisms of the methodology has been made by scientists, patients and advocates:

*The samples used were from patients who were continuing with their medication regimes, to include Ampligen and anti-virals.

*No preservative was used to preserve PBMC’s in samples

*Negative controls were not proven to be negative

*Spiked positives were spiked with VP62

*Sample size was too small to draw meaningful results.

I’d love to hear what Vince thinks about these points

Conrad writes:

Dear Dr Racaniello,

As a person with ME/CFS, I want to thank you for volunteering to work on the Science Advisory Board. I was touched, though not surprised, by your comments on this week’s TWIV about meeting ME/CFS patients. You had kind of a baptism of fire in your encounters with ME/CFS patients reacting to your TWIVs about XMRV. Some people would have turned their backs on both the disease and the patients after that, or decided that we are all, indeed, just a bunch of crazies. The fact that you haven’t speaks to your humanity and empathy. Somehow you were able to understand how someone who is desperately ill could lose their objectivity, and you never seemed to assume that the ones who are angry and unkind speak for all of us. You also haven’t gloated or seemed happy to learn that XMRV wasn’t proved to be the cause. We need virologists of your caliber working to solve the puzzle of this disease, but even more, we need people with your compassion. So thank you.

[from virology.ws comments]

Thank you for your continued coverage of CFS and taking time to help the CFIDS association, I cannot thank you enough for this. As a patient with CFS I would love to see an episode dedicated to CFS as you mentioned. Logical scientific discussion with patients and treating physicians would really bring it home to people that this is real and serious.

The outlandish comments seen in news and blog articles have really overpowered a lot of rational dialogue on CFS and I worry it is doing a great deal of damage to the disease’s reputation. This has only amplified with the recent mess of XMRV. I am hoping an episode on CFS could help clarify to the people we need the most, the scientific community, that the rambling comments they see online are a gross misrepresentation of the patient population.

—

Thanks Dr. Racaniello for sticking with CFS and being part of the CFIDS Associations Science Advisory panel. The MECFS community has, I believe, benefitted greatly, from your objective inputs on XMRV and good luck with your work with the CAA.

Brian writes:

At the beginning of the podcast [episode 151] you say most of the CFS patients you talked to could remember the day their problems started with an infection.

There are many other syndromes that also begin with an infection. For one example, Guillain Barre Syndrome http://www.ninds.nih.gov/disorders/gbs/gbs.htm which can result in paralysis.

I think your answer is correct, that CFS or ME/CFS can be the result of an unusual immune reaction to any pathogen. It is much more likely to be an uncommon response to a common pathogen, than the typical response to an uncommon pathogen. It is also quite unlikely that there is a common precursor pathogen, like XMRV that then requires a “trigger” to set off the CFS.

I am a PhD virologist, not an MD or immunologist, but it is my understanding that Guillain-Barre Syndrome is detectable not only by the symptoms but also by being able to measure the human antibodies that attack myelin in each patient.

There are dozens of other illnesses/syndromes that are also caused by somewhat unusual or uncontrolled immune reactions to common things. Allergies are one. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is another. In many of these, there is no “line in the sand” between a severe case of CIDP and a mild case of Guillain-Barre for example. They are all related and sometimes perhaps even identical in every detail except the level of the reaction/problem.

It is very likely that some cases of CFS are undiagnosed or misdiagnosed Guillain-Barre or CIDP. Other cases may be lingering or permanent effects of a EBV infection.

Some percentage of the cases are sure to be not immune-based but depression or other causes. Just as there are hundreds of ways to end up with paralysis symptoms somewhat like Guillain-Barre Syndrome symptoms. Many other causes of chronic fatigue, such as heart and lung disfunction, get accurately diagnosed so the patients do not end up with an ME/CFS label on their problem(s).

It seems to me, that many of the problems with CFS have to do with lack of insurance coverage, fraudulent doctors/treatments, poor patient understanding of the “fuzzy lines” between one syndrome and another, etc…

The XMRV story was quite a fiasco, and it is not over yet. I hope the Science journal, and USA medical science, can learn something from this.

Brian

HIV Databases

TWiV 151

Stephen writes:

Wildebeest (Gnu) are ruminants as they belong to the family bovidae like the domestic cow etc. Whereas Zebra belong to the family equidae and are monogastrics.

Again a great show.

Stephen

Christos writes:

I have two comments about your latest episode:

1. You read a letter by a neurologist about virus reactivation during immune-modulator therapies and he asked you for examples. You mentioned herpes reactivation during natalizumab therapy. His comment is correct and I guess we will see many more of these cases in the coming years when more biologics immuno-modulators are used. Currently, the most common example of virus reactivation is Hepatitis B during all kinds of anti-TNF treatments (including several antibodies). There are several reports out there and in some countries there is active monitoring of HepB levels during treatment.

2. In a lighter note, you mentioned Bachmann’s comments on the HPV vaccine. This is a video in the Colbert report making fun of the whole issue: http://www.colbertnation.com/the-colbert-report-videos/396674/september-14-2011/rick-perry-s-hpv-vaccine-mandate

Best,

Christos

Judi writes:

Finally- I can help you guys

PBS has a great evolution series (and an associated website http://www.pbs.org/wgbh/evolution/

The videos are good… may need additional info to update.

and then there is the understanding evolution website from UC Berkeley school of paleontology

http://evolution.berkeley.edu/

So glad I get to give back!

Judi

(High school and community college college person)

PS yes – please to the virology 101 podcasts! and keep up the bad jokes and puns

David writes:

Virii guys,

In episode 139, in response to a letter from Eric, Vincent (at about the 1:00:00 mark) made reference to a paper detailing evidence of viruses contained in genomes extending back about 150 million years. Vincent stated he would put a link in the show notes, but I didn’t find it there. Would you please put in that link? I would be interested in reading this paper.

[see http://www.virology.ws/2010/12/10/unexpected-endogenous-viruses/ ]

In episode 141, in part of the discussion about Alan’s pick of the week, there are a few things that to add or correct. The Permian was from 300 to 251 million years ago, not 100 million years ago as Alan stated. Rich asked about what kinds of animals were around, and Alan mentioned Dimetrodons (the sail-back animal that looks like a dinosaur). A Dimetrodon fun fact: We (as a representative of mammals) are more closely related to Dimetrodons than dinosaurs. Dimetrodons are part of the class Synapsids, referred to as ‘proto-mammals’, from which mammals evolved. There were also Gorgons, which had big canines sort of like sabre-tooth cats. Some of the first marine reptiles existed then. All of the landmass was part of a single supercontinent name Pangaea. The Permian ended with the largest mass extinction event (the “mother of all mass extinctions”), when an estimated 90-95% of all marine species and 70% terrestrial species went extinct. By comparison, the last big mass extinction, the one that got the dinosaurs, only rated a puny 75% species extinction 🙂

— David

Jim writes:

Hi Vince et al,

I heard a Ted talk by Angela Belcher on using nature to construct batteries, fuel cells, etc. Viruses are used to move genetic material to bacteria to make materials like abalone and diatomes make.

I vaguely recall a pick of the week for viruses being used in batteries??? If the Angela Belcher talk is different from this it may be of interest.

I am a devoted fan of TWIV, TWIP, and TWIM. It is a privilege to be able to hear you and your colleagues talk.

73,

Jim

Richard writes:

Dear Virologists,

May I try again on Heisenberg? One of the first things a student in physics learns is that we probably know less than 5% of everything there is to know about the universe. And further they learn that we probably never will know all there is to know or even a significant portion of what there is to know. (Indeed there is even one point of view that the human brain, at its current level of development, may not be capable of understanding certain things, but that is another topic.) This leads to a certain level of modesty on the part of physicists about their power to understand any topic. Did I detect a certain sense on your part that virologists are gradually learning all there is to know about viruses and eventually there will be no uncertainties? Yes, Heisenberg’s use of uncertainty is different than the uncertainty of undiscovered phenomena but in the larger philosophical context the point is that no matter how much we study something, it is very, very likely that we will ever understand it in every detail. And I wonder if the more you study and understand viruses, you uncover more questions than you do answers. What do you think?

I forgot to mention that my training is in relativistic quantum mechanics but have become an amateur virologist.

By the way, the virology I work on is of dengue. Your TWIV 147 on dengue and Wolbachia was superb. What do you think are the chances that dengue will become a more virulent virus as it tries to evade Wolbachi in mosquitoes. Are there any precedents?

All the best,

Rich

Richard Mahoney, PhD

Coordinator, Policy & Access

Dengue Vaccine Initiative

International Vaccine Institute

Seoul, Korea

Derek writes:

Hello TWIV,

I love your podcasts. I’m a PhD student in Victoria, BC and drove to San Francisco and back this summer and spent the whole drive catching up on past TWIV episodes. I think I’m saturated!

In podcast 146, you had a pick of the week from the DIY Bio space which happens to be what I was in SF for. There is a new community lab called biocurious that some of your listeners may be interested in, it provides a space to explore wetlab biology in a more casual setting than pursuing an academic degree. http://biocurious.org

Also, Eri Gentry and I have just launched a podcast of our own that may interest your listeners. Garagebio is a podcast devoted to exploring what happens when you put the hottest new biology discoveries in the hands of amateurs and small-scale startups. http://garagebio.org

You’re an inspiration – keep up the great podcasts!

Best regards,

–Derek

Lili writes:

To All Who Make TWiV Happen:

Thanks so much for all the great information on your netcast. I’m a non-scientist, newly introduced to your program, and I’m tuning in every week now. It’s an absolute treat to listen to scientists talk in an absolutely fascinating manner about such a vast array of topics having to do with virology. TWiV 149, where you chat with Trine Tsouderos, was a real eye-opener for me, in particular, and I’ve taken the opportunity to read several of Trine’s informative articles that you’ve linked to the program.

Cheers,

Lili

Peter writes:

Dear TWIVsters,

I am a UK listener and, having recently discovered your excellent podcast, have been doing my best to catch up.

I’m not quite up to date yet so apologies if you have already discussed this but I would be really interested to hear what you guys think about the potential for phage therapy to support or even eventually replace antibiotics. I found this topic fascinating and looked to pursue it both as an undergraduate in biology and a during my MPH. Almost as fascinating is that none of my professors ever seem excited by its potential!

It would be great to hear your views on the topic,

keep up the good work,

Peter

Arnold writes:

Dear Rich,

in one of the last TWiV-shows you said, that HIV is the only RNA virus, which integrates in the host genome. This is not true. You might have missed the papers about Bornavirus or Ebolavirus which showed, that these viruses can or at least did partly integrate in thel genome of its host.

So did you miss these papers or do you have a different opinion on that?

I did not want to say, that it was not an accident. And it is also not obligate for these viruses, I know. But it has happened and maintained – and still might happen. And it also seems not to have a disadvantage neither to the host nor to the virus. One can even turn this and think about if this might have had a beneficial effect for one or both, even though it is no obligate feature.

As always, when people start to dig in things, it turns out to be that there is not only black and white, but also grey – maybe this is the only thing I wanted to say 😉

Best

Arnold

—

Department of Virology – University of Freiburg

Germany

Jason ‘XenoPhage’ writes:

in a previous TWiV, 126 to be precise, you talk about the HPV vaccine. Again, if I understand correctly, you mention that if someone is infected with HPV, they don’t generate antibodies, but that injection of the HPV vaccine does cause generation of antibodies. I believe the question of why was asked, but there was no known answer. Is it possible that with a full-on infection, the virus is able to somehow evade the immune system, effectively preventing the creation of antibodies, but the vaccine is an attenuated form of HPV, allowing the immune system full access to the virus? Just some random speculation from a non-virologist.

Thanks

Jason

—————————

“Something mysterious is formed, born in the silent void. Waiting alone and unmoving, it is at once still and yet in constant motion. It is the source of all programs. I do not know its name, so I will call it the Tao of Programming.”

Michelle Ozbun replies:

This is a good issue requiring clarification. Only a fraction of those with detectable HPV DNA will show an antibody titer, suggesting that a small dose might be able to infect but not generate a measurable immune response. Yes, we know that during infection the virus evades the host immune response quite well. Exposure to the virus does not normally result in inflammation (which is important for an immune response). The skin is an immunologically privileged site and the virus is not lytic and escapes via shedding of dead skin cells. Therefore, antibody titer is not a good measure of whether someone has been infected previously. Viral DNA or sometimes viral transcript detection is the measure of current infection.

Conversely, the HPV vaccine is a pretty high dose of a “subunit” type “virus-like particle” (VLP) preparation with adjuvant (alum) that is injected intramuscularly. The VLP cannot replicate but because of the high dose, route of inoculation, the adjuvant (which causes inflammation), and the fact that the major capsid protein L1 is present in repetitive capsomeric structures (360 copies of L1 arranged in 72 pentamers), the vaccine elicits a strong protective antibody response. The antibody response shows efficacy in protection to well over 5 years of follow-up.

Hope this helps to clear up the difference in exposure and immune response.

Levi writes:

Hi Vince,

It was great to see you at ASV. I just wanted to note that I’m currently watching Ian Lipkin on Charlie Rose. He’s there speaking about the film Contagion, which is about a deadly viral pandemic. Like you, I’m often disappointed with the portrayal of science in film and television. I know exactly what you were talking about when you mentioned NCIS on your TWiV about zinc-finger nucleases. Because of this, I don’t usually watch such shows or films because I know they’ll get it wrong and I wont be able to suspend disbelief and enjoy the work.

However, since reading a couple of good reviews, and now seeing a respected scientist involved with the project, I’m tempted to see the film. I’d be interested to know if you or the rest of the TWiV team have seen it. If so, what are your impressions? I, for one, would love to a see a film that accurately depicts the work of those involved with infectious disease and public health. As virologists, we know many true stories that are more “thrilling” than any Hollywood script (hantavirus at Four Corners comes to mind).

But maybe, as virologists, we are biased. Maybe people who are so fascinated by reality find fiction a bit disappointing or unnecessary.

Thanks for all the great TWiVs so far, and keep up the great work!

—

Levi

Alex writes:

Hello Doctor Racaniello and fellow TWIVzors!

I apologize in advance with the wide spectrum of this email, been meaning to write for a while now.

I extremely enjoyed TWIP#29:Neglected Tropical Diseases with Peter Hotez. It was very inciteful to hear about the neglected tropical diseases and how mortality rate is not always the clearest way to measure the impact of a particular disease. I was wondering if you might be able to inquire him on why he selected the MD/Ph D program in his education. I’ve only recently become aware of this route offered by many medical schools and wondering if he might talk a little on the advantages and disadvantages. While seven years seems like a rather large commitment of time- it appears as though it blends both treatment and novel research well. Additionally, I am also curious in how it is best to approach a faculty member when looking for a mentor for a research project. Reading their current fields of research online is a good start, but I’m not exactly sure where to go from there. Most of the medical schools that I have been investigating require you to have a clear idea of what you intend to research and with who- at the time you apply.

Regarding TWIV#147, I was slightly saddened that the quintessential theoretical endosymbyote was not mentioned. You guessed it, the mighty mitochondria! I know several studies have suggested this organelle was once an independent bacteria that may have fused with a eukaryote cell at some point in it’s lineage. Perhaps one of the oldest examples of mutualism- where the host eukaryote cell gains ATP energy while the bacteria gains protection from the outside environment. How would one explain the presence of unique RNA within the mitochondria otherwise?

Also, is there such a thing as an exosymbiote? Benign bacteria of the gut such falling in the genus of Bacteroides, Clostridium and Fusobacterium seem like they could be labeled as this. The host is protected from more virulent species while the bacteria gets a free source of nutrition.

Thank you for all the diligent work on TWIV! Episode #150 will soon be here, quite a milestone to say the least.

Cheers,

Alex

Bachelor of Science

Charles writes:

Hello TWIVers

In a recent episode there was a passing mention of the fact that, for a cell, a defeated virus is also a source of nucleotides. I was wondering if there are any organisms that deliberately encourage virus penetration, confident that they can neutralise the viruses and then use them as a food supply. Or is this too dangerous a strategy to have evolved?

It seems to me (from my dubious position as a Software Engineer whose knowledge of biology is largely due to your podcasts and Wikipedia searches) that a possible candidate might be a bacteria living inside another organism, luring in viruses that infect its host. As the viruses would have evolved to infect the host rather than the bacteria, inviting them inside might not be immediately suicidal.

Thank you all very much for the work you put into making TWIV. I never miss an episode. May you long continue.

Kindest regards,

Charles

York, UK

Jeffrey writes:

Dear Dr. Racaniello – recently you edited a PLOS Pathogens paper “The Fecal Viral Flora of Wild Rodents” (http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002218) and I had a question that doesn’t need an immediate answer, but perhaps could be addressed in a future TWIV. The authors isolated these viruses through filtration, treating the filtrate with DNAse and RNAse to nix any unprotected nucleic acids. I found it interesting that ~40% of their reads were bacterial and ~2% were eukaryotic. Are these what you would expect from schmootz sticking to the filter? Do you think its possible that these represent phage that are caught mid-transduction (in the case of the bacterial sequences) and maybe eukaryotic viruses doing the same? Just dreaming like a 2nd year graduate student.

That is the question, now the plea: are there any plans to do a program on the various papers that have come out on viruses in the feces of different animals. Ever since graduate school working on adenovirus at Emory Univ, I had wanted to look in day care poopy diapers to address questions of adenovrius excretion and sequence evolution. Now I am a full time teacher at a community college near Atlanta, but I find myself working with others in my department trying to get a shoestring program together to have our non-majors students collecting coyote poop so that we can extract DNA for sequencing to have students look at real world, local applications of what they are learning in class. So far all I have is several coyote scats stored in the freezer and am looking at what exactly we should be amplifying for sequencing. It’s a tougher problem than I had initially thought it would be. Forgive me if you have already done a program like this (I will get to it), but you guys really serve as a weekly (sometimes bi-weekly) lab meeting/journal club for me and help keep me not only current, but excited to bring “hot off the press” science to my students who would otherwise not likely think about these things.

The pepper mottle virus-in-human-feces story would be a GREAT way to get Senor Despommier into the studio as it brings up issues that he specializes on (relationships between different species and the poop-agriculture-pathogen/parasite triad). I would love to hear his opinion of whether he would consider humans to be a vector for this virus.

I consider the communication of science and how it works to my non-science major students to be one of the most important things I do and you really inspire me. We may try to do a simpler version of what you do, but with the focus on the amazing diversity of plants and insects we have around our rural campus.

Thank you for a very entertaining and patently useful program.

Jeff

Eric Delwart replies:

Great question which I’ll rephrase as why don’t we get 100% viral sequences since we “purify” for capsid protected nucleic acids ? A lots of the bacterial and eukaryotic hits are to ribosomal sequences which we reckon are partly protected from nuclease digestion due to their being in a tight complex with proteins. Ribosomes are also about the diameter of a small virus and can easily go through our 400nm filters. Our definition of viral is also quite stringent at E score< 0.00001 so we might actualy have more (divergent) viruses than we report. A lots of the sequences had hits to phages so the proportion of viral sequences (both prokaryotic and eukaryotic) is actually ~13%. I reckon a lot of that background is due to bacterial/protozoa/host DNA and RNA being in some form of small Schmutzy complex with proteins/lipids/glycos and surviving the nuclease treatment. We did notice that these rodents had a very low ratio of eukaryotic virus hits to total sequences relative we saw with other mammals like bats, sea lions, pigs. I think this reflects a generally lower enteric viral load. This may be due to a relatively more isolated life styles for rodents and possibly older age of the feces donors (a lot of the sea lions and pigs were < 1YO).

Peter writes:

as a long time listener of twiv, twip and twim, you and Vincent almost seem like old friends to me, thus it feels somehow special to find your name and your vertical farm project mentioned in the large German periodical “der SPIEGEL”.

Let me take this opportunity to thank you for the work you’re doing. The way you’re shedding light on microscopic life and not-so-life is the best educational entertainment and the most entertaining education I know. My amazement about the interwovenness of all life has grown beyond my wildest beliefs and I’m sure I’ve only just scratched the surface.

http://m.spiegel.de/wissenschaft/mensch/a-773724.html#spRedirectedFrom=www

Jason writes:

Hello TWiV. I am a physicist pretending lately to be a biologist (BS in Math and Physics and now attempting a MS in biology). I was looking for new podcasts recently to listen to for a road trip and came across TWiV starting at around #132. I must say it was a very educational road trip indeed and have been enjoying trying to catch up from TWiV#1. It’s been a few months now, but I remember a conversation about HPV and some of the talkers were from UF down here in sunny Florida. Just wanted to see if they caught the HPV article UNF’s student newspaper published around that same time. Caught some very interesting publicity off their choice of cover picture for the article. I thought it was interesting grab to educate the students at UNF that HPV might not be only a female type problem and the dangers in oral sex, and found it funny that I heard a comment on TWiV just after that about throat cancer risks with HPV. Take care and hopefully sometime this year I’ll catch up before taking my first virology class. My project will have something to do with oral inoculation of arbovirus in mosquitoes and find the little pests very interesting, both of them!

-Jason

UNF

Here is a link to the cover photo for the UNF paper

http://www.outsidethebeltway.com/unf-oral-sex-photo-controversy/

Steve writes:

Hi Alan and Rich,

Superb job co-hosting TWIV #145. You didn’t miss a beat.

Just a small bookkeeping note. The hyperlink to the listener pick of the week is currently incorrectly to the “Small Pox and its eradication” pdf article and not to the “Science Photo Library” webpage. Thanks for fixing this hyperlink.

Keep up the great work, I so enjoy your show and look forward to the Sunday download which I listen to on Sunday evening.

Warm regards,

Steve, MD

Dave writes:

Dear TWiVers,

It was great to have seen the live podcast at ASV! I am looking forward to seeing another one next year in Madison…

I was curious to hear what kind of reactions you had to the July 27 PLoS One paper (Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, et al. (2011) Broad-Spectrum Antiviral Therapeutics. PLoS ONE 6(7): e22572. doi:10.1371/journal.pone.0022572). The news headlines that I saw were akin to “drug that could cure any viral infection.” While trying (specifically) to target cells possessing viral double stranded RNAs seems like a reasonable approach, do you think this DRACO approach actually has the potential to be a broad-spectrum antiviral (ignoring, for now, any possible issues with drug delivery…)?

Thanks in advance for any thoughts…

Keep up the great work…

Cheers,

Dave

P.S. I wanted to share that this Spring, I had my undergraduate virology students use TWiV to learn about potential pieces of literature that they could then download and read as the basis for their in-class oral presentations. Overall, the students liked hearing a little context about the paper from TWiV before going through it themselves in detail to prep for their talks about the experiments/data. An added bonus of the exercise was that a number of them now are regular TWiV listeners!

—————————————

David B. Kushner, Ph.D.

Associate Professor of Biology

Dickinson College

Robin M.D. writes:

Vincent and Dickson

Listen, I love you guys and don’t want to get anyone in trouble, but someone should address our government’s preoccupation this last decade with the development of offensive bioweapons.

Because both of you are retired and no longer dependent on government grants you can speak freely, where most others cannot.

Please find included a excerpt of a recent essay on the subject:

By H. Patricia Hynes

Excerpted from: truth-out.org

“. . . From 1942 until the late ’60s, a highly secretive, offensive, biological weapons research program, [originated] at the US Army’s research facility at Fort Detrick in Frederick, Maryland, gained momentum. World War II German and Japanese scientists, whose war crimes were overlooked were employed there. . .

In 2001, the US Department of Homeland Security began aggressively promoting ‘research’ on biological warfare. The new agency used the anthrax attack that same year, in which anthrax was sent through the US mail to liberal Congressional politicians and journalists, to gain public support for biological weapon ‘research’.

Some have suggested that the domestic terrorism was a deliberate act perpetrated by Homeland Security. Regardless, as a result, the act of terrorism set off a massive flow of federal funding for research on live, virulent bioweapons. . .

Today, in dozens of newly sprung laboratories, research on the most lethal bacteria and viruses with no known cure is being conducted in an atmosphere of secrecy, with hand-picked internal review boards, with no public oversight or accountability. . .

Fort Detrick, Maryland, a military base and major government research facility, is the site of the largest biodefense lab. Here, biowarfare pathogens are created, including new genetically engineered viruses and bacteria. Novel methods of delivery in biowarfare are also being tested. . .

[Despite denials by this and the previous administration], Fort Detrick’s research agenda – – modifying and dispersing lethal and genetically modified organisms – – is clearly and unmistakably an offensive weapons program. . .

By 2009, 400 facilities and 15,000 people were handling biological weapons in sites throughout the country, in many cases unbeknownst to the local community. The $60 billion spent since 2002 on biological weapons research has raised serious concerns for concerned scientists and for informed critics. . .

A Washington Post story revealed that an inventory of deadly pathogens at the government’s premier bioweapons research laboratory at Fort Detrick, Maryland, uncovered that more than 9,000 vials were missing.

In testimony to a House Committee hearing on the proliferation of bioweapons laboratories, Nancy Kingsbury of the GAO revealed that expansion of bioweapons laboratories has been ‘so uncoordinated that no federal agency knows how many exist’; nor is there any sense among federal agencies of their operational safety or the risks they pose to the public.

Keith Rhodes, the GAO’s chief technologist, testified in the same 2007 Congressional hearing: ‘We are at greater risk today’ of an infectious disease epidemic because of the great increase in biolaboratories and the absence of oversight they receive.’ . . .”

Joerg writes:

Hi Twivers,

I’d like to make a correction/comment to a statement made on TWiV 146 at 59:30 – 1:00:00 (not sure how to properly cite podcasts?):

“No one has ever purified MHC molecules and has done sequence analysis to see which sequences of HIV epitopes are in MHC molecules.”

Whilst it appears that no one has eluted peptides from HIV-infected cells – epitopes were eluted from MHC class I molecules from cells infected with HIV-recombinant vaccinia virus– see abstract below and cells transfected with HIV DNA (see attached paper by Tsomides et al.)

This field of research combined with work on synthetic peptides have confirmed the nature of the epitopes and the T cells that recognise them.

The use of transfectants and vaccinia recombinants rather than HIV-infected CD4 T cells may have had practical reasons since large quantities of infected cells are or at least were required to elute and indentify the peptide epitopes.

As somebody who spend a good part of his PhD growing large quantities of melanoma cells in order to elute and identify peptide epitopes recognised by cytotoxic T cells I kind of felt strongly about this point.

Anyway suffice to say that I really enjoy your podcasts as I continuously learn a lot.

Keep up the great work you’re doing.

Regards

Joerg, Munich, Germany

Eur J Immunol. 2000 Sep;30(9):2521-30.

A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules.

Tomiyama H, Yamada N, Komatsu H, Hirayama K, Takiguchi M.

Also J Ex Med vol 180: 1283, 1994

TWiV 150

Mary writes:

Listening to the most recent Republican, I mean Tea Party, presidential debate, I was quite upset (for many reasons), but one of which was to listen to how Michelle Bachmann characterized the HPV vaccine as a “dangerous government injection”, with the implication that it is killing young innocent girls. I am worried already about how the movie Contagion will be received by the public as another government-created virus gone amuck, and now someone else is on the national stage implying that vaccines are dangerous and unsafe. And to hear Rick Santorum’s reply about why vaccines are given was also quite scary. What to do about these kind of uninformed and politically motivated public statements?

mary

Trine Tsouderos writes:

So I was at a birthday party for a friend’s daughter yesterday and she said to me, oh, I saw your facebook update and clicked on This Week in Virology and I had the podcast on while I cleaned the house. And you know, it was REALLY interesting!

She’s a mom of two, works with kids with special needs, no prior interest in virology at all. And she cleaned the house to TWiV!

Person by person, you are spreading the love of science!

Nicola writes:

I am a big fan of TWiV and have been listening in for the past year or so. I thoroughly enjoyed TWiV Number 141, and listening to Matt Evans talking about the new mouse model that supports HCV entry was very exciting and an important step forward for our field. However, I wanted to make a comment on his statement that only liver hepatocytes support HCV entry to high levels, and that liver hepatocytes are the only cell type within the body that express the full complement of HCV entry factors. Not quite true! Currently there is a shift in the thinking that HCV is strictly a liver-tropic virus taking place within the field.

I’m a postdoc working at the University of Birmingham, UK, who started working on HCV just over a year ago. I have been looking at the neurological symptoms associated with HCV in many infected individuals, and the focus of my work is to see whether these symptoms are due to direct viral infection of cells of the brain.

Recently, several groups, including us (details below), reported that brain derived neuroepithelioma cells possess all of the HCV receptors at similar levels to the hepatoma cell lines commonly used to grow HCV. Furthermore, these cells supported HCV entry at levels comparable to hepatoma cells (and even in some cases, higher).

Matt suggested that extrahepatic replication of HCV is controversial; however, this finding is not and has been validated by at least two HCV labs. So – maybe HCV entry is not totally restricted to hepatocytes. Indeed, it suggests that there may not be a ‘liver factor’ that defines HCV infection.

Work on HCV is really in its infancy, it has only been possible to grow the virus in culture since 2005. Every day we find out new and exciting things about this important virus, and partially thanks to Matt’s work, the view that HCV is restricted to hepatocytes is being superseded.

Finally, I’d like to thank you, Rich, Dick and Alan for making virology so accessible to so many people through TWiV. The podcast also makes it really easy for people like me to keep up to date with what is going on in the whole field of virology. I do not want this e-mail to sound like a criticism of your podcast- we here at Birmingham are avid fans!

Best wishes,

Nicola Fletcher

References

1) Fletcher et al, 2010-Hepatitis C virus infection of neuroepithelioma cell lines. Gastroenterology 2010 Oct;139:1365-74.

2) Lindenbach BD, 2010-New cell culture models of hepatitis C virus entry, replication, and virus production. Gastroenterology. 2010 Oct;139(4):1090-3.

3) Bürgel et al., 2010-Hepatitis C virus enters human peripheral neuroblastoma cells – evidence for extra-hepatic cells sustaining hepatitis C virus penetration. J Viral Hepat. 2010 Jun 23. [Epub ahead of print]

Dr. Nicola Fletcher

HCV Research Group,

Institute of Biomedical Research,

School of Immunity and Infection,

College of Medical and Dental Sciences,

University of Birmingham, Birmingham B15 2TT UK

Garren writes:

Hi Twivers

I love your shows, I listen to TWIV, TWIM, TWIP, and FIB among other science shows. Thank you for the entertainment and a special thanks for that show over at Omega Tau.

I am a farmer at the moment and I would really like a couple of shows about plant viruses and fungi.

Ok, my next request is a call for help. My wife teaches biology for a community college and we have been searching for an acceptable video on evolution suitable for college level students. The problem is that they all stink. They all suffer from one or more of the following problems… 1>political slant 2>religious slant 3>no science 4>bad science 5>boring 6>just a pretty animal show and tell, etc. The list of problems goes on. Can somebody please help my wife by recommending something competent. Please help we’re desperate!!!

Thank you…

Jenny writes:

You could have a discussion on how simple is simple when it comes to explaining science/virology to a public audience. I just finished listening to TWIV#146, where a listener was asking about a “virology for dummies” resource, and I thought it must be a bit hard for scientists/researchers themselves to “dumb-down” their topics that’s why we don’t usually have a lot of virology or immunology or science 101 type of books that are more accessible to the public. I appreciate the Virology 101 episodes that you guys did previously, but I think those episodes are still a bit technical for the layperson. It’s a tough task to accomplish, but I think there must be some golden mean to getting the science right without being too engrossed in the technical details that would usually turn off the non-science person. Just my two cents.

Stan writes:

Hello. Forgive me but I just recently started listening to your podcasts and haven’t had the opportunity to listen to all your previous episodes. I am a clinical neurologist and I find that we are moving more and more into the realm of immune modulation for the treatment of more and more chronic diseases that are autoimmune related. The latest crew of drugs that have come out are the “mab” drugs which are humanized monoclonal antibodies. The opportunistic infection progressive multifocal leukoencephalopathy (PML) which, as you know comes from a type of polyomavirus called the JC virus (or John Cunningham virus), is a potential problem with natalizumab treatment. I haven’t seen a lot of other opportunistic infections with using the current immunomodulators, but I was wondering if you could tell me if you know of other potential infections that we may be setting ourselves up for with the greater use of these types of drugs? It would be great if you could add a podcast about the viruses (and parasites) that specifically pertain to neurologic disease. The presentations in neurologic systems are particularly interesting because of many different ways that people can be affected (syphilis and neurosyphilis are excellent examples).

I love the format of your show and you and your guests are excellent examples of what we need more of in today’s media, people who actually know what they are talking about. I would also suggest adding more guest appearances with practicing clinical doctors as throwing in a few case presentations here and there are usually appreciated by all (I wouldn’t want it to get in the way of the basic science information that your show is excellent at providing, however).

Thanks again for your excellent show.

Stan, M.D.

Tallahassee, FL

Jody writes:

Hi all,

I’m catching up with old episodes of TWiV and was listening with interest to “TWiV 103: Shots with LJ Tan”.

During the episode I noted several times that there are no reported side effects from the pandemic influenza vaccinations. I was wondering if you had seen this news that came out since that episode was recorded?

http://www.who.int/vaccine_safety/topics/influenza/pandemic/h1n1_safety_assessing/narcolepsy_statement/en/index.html

Statement on narcolepsy and vaccination

21 April 2011

Since August 2010, following widespread use of vaccines against influenza (H1N1) 2009, cases of narcolepsy, especially in children and adolescents, have been reported. Narcolepsy is a rare sleep disorder that causes a person to fall asleep suddenly and unexpectedly. The rates reported from Sweden, Finland and Iceland have been notably higher than those from other countries. Swedish and Finnish authorities have presented preliminary statements on their investigations in the first quarter of 2011.

This has been quite big news in Finland since the first occurrences were reported last year and almost immediately it was linked to the pandemic vaccination. As it turns out the link seems to be real, although the final Finnish NIH report is not due until end of August this year. Preliminary results seem to connect the vaccination to a genetic predisposition to narcolepsy in sections of the Scandinavian population.

There is more information available from that link above including the preliminary report. The CDC also has some information available. http://www.cdc.gov/vaccinesafety/Concerns/h1n1_narcolepsy_pandemrix.html

Vaccination rates in Finland as a rule are quite high, but any risk from vaccination, real, or not, has an impact on public health. This struck me as being particularly relevant given the discussion in Ep 103 about the vaccine safety and public perceptions. Although not on the scale of the problems from the US vaccinations in the 70’s it does dent quite badly public opinion of vaccine safety.

This went through several very public rounds of confirmation and denial. I guess you caught one of the denial phases. Also the basic description of narcolepsy sounds relatively innocuous, but as it was shown in a TV documentary here several weeks ago it turned out many children suffered behavioural changes, some quite severe. In a few cases so bad they were literally removed from the home.

In closing I just want to say thanks for TWiV. I am a software engineer with no medical training, but I have a strong interest in science in general, so it is always a pleasure to listen even if some things go right over my head. Just when I think it can’t get any better the next episode proves me wrong!

Regards,

Jody

Anttoni writes:

Hi!

A little update on the story..

-“European Medicines Agency recommends restricting use of Pandemrix” http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2011/07/news_detail_001312.jsp&murl=menus/news_and_events/news_and_events.jsp&mid=WC0b01ac058004d5c1&jsenabled=true

sorry about the long link..

It looks like the link between pandemrix and narcolepsy has been confirmed. Apparently the condition needs a genetic disorder that the adjuvant “activates”.

I also recall that this issue was on the table on twiv 110.

What is your take on this whole thing? And how could the medical industry take into account genetic mutations when designing new drugs? Is the time of “one drug fits all” coming to a end? Is there someone looking into the effects of mutations on how drugs behave? And more importantly, will this change the way some drugs are accepted in the US without local testing if the drug has been used in another country for a long period (i recall you talking about this policy in one of your twiv:s unfortunately i can’t remember which one it was..)

Thanks for all the work you do for the program! im loving every episode!

Anttoni

Jon writes:

First, many thanks for the trilogy of podcasts, it’s a wonderful service to humanity but in one sense I think you sell yourselves short. While you may entice a variety of students into the various fields covered in the podcasts, you might have a more dramatic effect. The slowly evolving impact of the Internet on science allows for participation by an army of interested people. It’s easy to point to SETI (http://www.seti.org/), Folding@home (http://folding.stanford.edu/) or the many other similar ways (http://en.wikipedia.org/wiki/List_of_distributed_computing_projects) to contribute unused computer processing time to science but they are not necessarily focused on your areas. I think if you mention areas that need work, you might be surprised how many people have the interest and ingenuity to help solve problems. I am specifically thinking of Cyber-Infrastructure, what used to be called supercomputing, where users can do computer related projects. But there are no doubt many other tasks that can be tackled by part-time home scientists. You might therefore note these areas and specific tasks needing to be done in the show notes. I realize that no one has extra time, except for Vincent because he apparently purchases the unused time of others. But it’s only those with the in-depth knowledge like yourselves who can identify areas that need further research so I suggest you consider this possibility. Perhaps someday you might be considered the Fathers of the Home Micro-Science Movement.

I also applaud the comments of Alan regarding Food Safety and Agriculture and the declining support. When the Chinese prefer U.S. made food and drugs because they are dependable, it would be ironic if not devastating to this country’s industry if one of our products harmed one of their citizens. Keep up the great work.

Less important for the podcast is the following. I am a Food Science PhD. known to some as Doctor Chocolate, but I now work in IT, hence some of the comments above. I work for Clemson University where in the span of five years we went from not in the game to top 100 in the world in Cluster technology (high performance computing). This is the sort of change that allows you to think of possibilities and not limitations. Also recognize that the rest of the world’s computing power is likewise continuing grow at a tremendous rate, we were just catching up to where we should be.

Thanks again.

Jon

Peter writes:

Hi Guys –

I can’t tell you how much I enjoy your show. I recommend it to all the students in my Virology class and several have commented on how much they enjoy it.

I am always behind and was listening to show #141 this morning on my daily walk. Towards the end someone inquired about the idea of interfering with the geometry of icosahedral capsids as a therapeutic strategy. The New Statesman article they referenced refers to the work of Reidun Twarock, a mathematician from York. Reidun and her colleague from Leeds, Peter Stockley have actually organized a meeting called “Mathematical Virology” which brings together virologists, mathematicians, and physicists to talk about mathematical principles in virus assembly. I’ve attended a few of them and it is a very thought provoking meeting.

On the topic of inhibition of assembly I wanted to point out the work of Adam Zlotnick on HBV and Mike Summers on HIV as well as the prescient comments of Don Caspar. Towards this end I’ve attached a couple of reprints that I’ve authored that touch on these topics. The JMB paper cites the Zlotnick, Summers, and Caspar papers, and the 1998 TibTek paper lays out some of the concepts behind this approach. Perhaps you could like the references.

http://www.ncbi.nlm.nih.gov/pubmed/21762804

http://www.ncbi.nlm.nih.gov/pubmed/9487732

Keep up the good work!

Peter

Peter E. Prevelige Jr.

Professor

Dept. of Microbiology

Univ. of Alabama @ Birmingham

Birmingham AL.

Stephen writes:

Hello Vincent, Dickson, Alan and Rich.

I received this email regarding a new open access journal in microbiology you may be interested to know more about (the forward is at the bottom).

I love the show and have been an avid listener since around TWiV 70 and as many before me have done I went back and started from the beginning of the podcasts. I also thouroughly enjoy TWiP and TWiM especially since I can follow both from podcast 1. It is simply a wonderful service the team are providing. Keep up the good work.

I am from the north of Ireland/UK and I am currently a veterinary medicine undergraduate. I have a particular interest in immunology, microbiology and parasites.

In TWiP, 6 I think it was, Dickson said that horses and cows both have a rumen. This was a slip of the tongue more than anything and isn’t in any way microbiology related but given my field of study it made me cringe and I felt I should say. Horses are monogastric animals, and have a very small stomach for their size. Due to the fact they are continuous grazers. This is also why they lack a gall bladder as bile is continuously secreted instead of being stored. Whereas cows are ruminants. As are goats, sheep, giraffes and deer. It is okay for horses to graze with cows. Though it isn’t advised to place horses with sheep. This isn’t due to a possible parasite burden but because the horse may develop a hobby for chasing the sheep.

Thanks again for the wonderful network you provide.

Stephen

http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-8827

John writes:

Dear TWIVers,

I was listening to TWIV144, and felt like I learned a lot from it, particularly the zinc finger DNA paper. I had to rewind and listen a couple times, and probably still missed a lot, since the paper and discussion dealt with some pretty in-depth molecular biology. This led me to a few questions.

a. Since they can make this zinc finger thing that will basically clobber one particular gene, and even encode it in a virus’ genetic material, I wonder whether they have looked at using this to remove or inactivate the HIV provirus from infected cells. Couldn’t you use this trick to make a virus that would infect T cells and inactivate the HIV lurking in their DNA? If I understand correctly that HIV is usually latent in T cells till they’re activated to fight an infection, this might be useful for massively decreasing the number of T cells silently carrying the virus. It seems like this could be done to stem cells before transplantation (didn’t one of your earlier guests talk about doing this to treat some kinds of blood cancers, using an oncolytic virus?), but maybe it could also be done as part of antiretroviral therapy, to decrease the number of places the virus might be hiding out and make it less likely that the virus will eventually mutate to become resistant to the drugs?

b. This led me to wonder what happens to the original T cell population of AIDS patients who go onto antiretroviral therapy after their T cell levels go down to dangerous levels. After the antivirals get the viral level down, what happens to the T cells that are carrying the provirus? When they get activated and then start producing virus, it seems like the medicine will prevent the virus reproducing, but will leave those cells around. Do the infected cells eventually get killed off by cytotoxic T cells? Do AIDS patients who start taking antiretrovirals after their T cell levels go down lose their previous immune memory, and have to get re-vaccinated for things they were previously vaccinated against or exposed to?

c. Finally, the whole discussion made me wonder where the T cells are replenished from. I’ve read some papers that say that that as you get older, more and more of your naive T cells come from existing naive T cells in circulation reproducing, rather than going through the thymus. But for transplant and AIDS patients, where the circulating naive T cell population is mostly gone, their bodies must somehow be changing that, so that hematopoietic stem cells make immature T cells that go through the thymus, because otherwise they wouldnt get working T cells. But I could easily be missing something, since this is far from my own field.

I’m sending along a link to a paper on how T cells are produced at different ages, and how this affects T cell receptor diversity. I’d love to hear it discussed sometime. The discussion on how aging affects the diversity of your T cell receptors seemed really interesting, in terms of effects on stuff like effectiveness of vaccines in older people, and I bet there are a lot of implications of this stuff I don’t know enough to even suspect.

Thanks again for your wonderful podcasts, and for answering this computer scientist’s amateur biology questions.

Paper on TCR diversity as you age: http://www.jimmunol.org/content/174/11/7446.long

–John

Kimberly writes:

Hi TWIV and Dr. Esteban,

I did my graduate studies on Baculovirus-induced apoptosis and consequently came across studies that you might be interested in for your course that was described in TWIV 145. Baculoviruses cause caterpillars to climb as high as possible. At late times in infection, the caterpillar “melts” and all of the virus-rich goo falls onto lower leaves. These leaves are then eaten by new caterpillars and they become infected. Sorry I can’t remember what lab did the studies, but I believe it’s described in an abstract from the ASV meeting that was at UC-Davis in 2003(?) and I know that it’s referenced in the baculovirus section of Field’s. Not a sexually-trasmitted virus, but I thought you might find it interesting none the less.

Kim, PhD

Post-doctoral Fellow

The Laboratory of Diane Griffin, MD PhD

Johns Hopkins Bloomberg School of Public Health

Gopal writes:

Dear TWiV folks,

I presume that someone would already have drawn your attention to this report that appeared recently in the British newspaper, the Guardian. This is just in case no one has done so.

http://www.guardian.co.uk/society/2011/aug/21/chronic-fatigue-syndrome-myalgic-encephalomyelitis

I can understand CFS sufferers being upset that the link with XMRV did not pan out. But it seems to me that death threats against researchers would make scientists more likely to avoid working on this problem, thereby retarding the search for the cause of this mysterious ailment and an effective way to treat it.

Regards,

— Gopal

Science Correspondent, The Hindu newspaper

Al writes:

Aloha Vince and the Gang,

I notice you are going to talk about research funding in an upcoming episode.

I think Science research is too important to leave to the flaky Congress.

Wikipedia is now a massive repository of human knowledge and it is self funding.

I wonder if those who care could fund both targeted and untargeted basic science research thru an independent Science Foundation, where members donate say $500 a year and a body of respected but somewhat out of the box folks make the funding decisions?

I think it could work and this time of waning funding is the perfect time to start it. Love to hear your opinions.

Best regards for the find job you guys are doing on TWIV.

Al (Hawaii)

Neva writes:

Hello Vince et al,

Your podcasts, including TWIP and TWIM, are extraordinary. Thanks so much for giving them to all of us.

The article about academic publishing illuminates a source of frequent frustration for me as I am blocked from viewing articles of interest. I know you are quite familiar with this issue, but this is a good summary I think.

Thanks again for your wonderful teaching,

Neva

Buda, Texas

So when does academic publishing get disrupted?

TWiV 149

John writes:

Re the letter you got about a Spanish version of TWIV: ASM already has a nice Spanish microbiology podcast, called Mundos de los Microbios. Your TWIM co-host Elio has been on that podcast at least once that I’ve heard. Perhaps you could put the would-be Spanish TWIV guy in touch with that podcast’s host, Gary Toranzos, or with Elio. I’d love a virology podcast in Spanish, even though I won’t be able to listen at 2X like I do to the English language podcasts.

–John

Geoffrey writes:

TWIVers:

Just to let you know that my own literary research suggests that the several forms of historical (real life) “zombiism” are probably due to chemical rather than viral factors. If I ever finish it, it will be covered as a chapter in a book that I am writing on shamanism and shamanic drugs.

Although much of the caribbean zombie effect has been assigned to tetradotoxin, I believe that the effects of some of the other components have been underestimated. While caribbean zombies have become well-known (if not accurately portrayed) through the movies, it is less well-known that Europe had its own “zombie hordes”. Greek literature speaks of lycanthropes which were far more like zombies than werewolves and the Norse legends speak of living ghosts (draugr, I believe) of great warriors as well as housewives. Most of the european zombie stories speak of pathetic weak creatures. A few legends (especially norse ones) speak of killing machines eventually dispatched by living warriors. All of the legends describe these zombies as mentally deranged. Interestingly, I believe that a few recovered their mental facilities and “returned to life”. Skipping over a lot of the background, it seems likely that these “living dead” of Europe and the Americas were the result of accidental and deliberate overdoses of Jeckylltropes, tropane-containing herbal concoctions derived from members of the Solanum family (especially daturas). These Jeckylltropes seem to have included the zombie poison of Haiti and the witch’s flying ointment of Europe the effects of which can cause long-term derangement and suggestability.

Thus (real life) zombiism is of chemical etiology. A viral etiology is possible but has not, to the best of my knowledge, been observed.

Geoffrey

Robert writes:

Love twip twim and twip. Found these through FiB. Great explanations and not dumbed down for those of us with at least two brain cells. Find every one able to communicate this field very well. Learning lots. Thanks lots.

Despommier is outstanding. Keep them coming. Can you speak upon the surface layers of viruses and how antibodies bind to this surface.

Natalie writes:

Dear TWIV crew,

I am a newcomer to your podcast and just want to start by saying how much I have been enjoying them. I learn a lot from each podcast and look forward to listening to them each week. A special thanks to Matt Evans for urging me to listen to you guys!

One of the best things about the podcast is the way you can explain things to the general audience. For example, I loved Vince’s definition of microfluidics on TWIV #142: “really tiny tubes, small amounts of fluid.” I wanted to draw your attention to another remarkable microfluidics paper, recently published in Nature Medicine entitled, “Microfluidics-based diagnostics of infectious diseases in the developing world.” The authors are able to detect HIV and syphilis with just 1ul of blood with their “mChip” assay. It is really exciting to think that this low-cost, rapid assay could be used, particularly in the developing world.

All the best, and keep up the good work!

Natalie

P.S. I am currently an MD/PhD student in Peter Palese’s Lab. Vince, I just learned you did your PhD with Peter – I hope you have some good stories you could one day share (on or off the air!)

Thomas writes:

First off, I can’t tell you how awesome it is to have the TWix series! In addition to the witty banter, the shows do a great job of breaking down the normally jargon laden content in a lively and accessible way. While i’m literate in basic biology, ease of information uptake through simplicity works wonders.

Since I’m relatively late on the bandwagon of awesome, I’ve been steadily working through the archives of TWiV…no complaints so far.

This is the kind of content that works so well for shifting education paradigms. Free access, unassuming style, and “further reading” standards (links) seem (to me at least) to make a well-designed tool for the classroom. To what extent have you considered integrating the series with your classroom experience, and vice versa?

also, would you be open to the idea of building an episode or two from the ground up, a sort of “science on the streets” interactive style? It might be really neat to have a question session with a local middle school/high school classroom, to talk about some common misconceptions and otherwise intriguing experiments.

Tried to keep this short, but there’s one more thing:

Have you guys already covered (in unreleased) the latest update in the Haitian cholera paper? If not, it’s absolutely worth checking out:

http://mbioblog.asm.org/mbiosphere/2011/08/did-un-peacekeepers-bring-cholera-to-haiti-new-sequence-data-say-yes.html

Thank you for your time, and keep up the amazing work!

Thomas

*ps, is it possible to balance out the audio slightly? there seems to be a mildly jarring change from speaker-to-speaker.

TWiV 148

Ed writes:

Gentlemen, I think you’ll find that Dylan Thomas was Welsh, not Irish. Though you are of course correct on his penchant for writing and

drinking!

Josh writes:

Dear TWiV Doctors,

I have one question and one comment about your section on the DRACO broad spectrum antiviral:

This might be a stupid question, but: Would not this antiviral interfere with the normal body microbe population by destroying unknown virus activity that we might need to live?

My comment:

Given your comment about the Lincoln Lab at MIT being involved with the Defense Department, wouldn’t this be the antiviral compound you would come up with if you wanted to treat the victims of a bioterrorism attack? I mean, the problem of treatment timing doesn’t fit a normal clinical situation (because when they came in they’d probably be on the downside of it), but it does fit a situation where you know that large numbers of people are exposed at the same time. If you suspected that you had been attacked that way, this antiviral would fit the bill. Of course, this assumes you would know that you have been/are being attacked this way, but that’s a different subject.

What do you think? Am I off in space on this one?

Great show as always,

Josh

Alberto writes:

Hi Twivers,

Here’s a story from 2 years ago covering the release of mosquitoes in Queensland following on from your recent episode regarding control of Dengue Fever. It contains some great images of the release trial and the mosquito breeding cages.

Enjoy!

http://www.abc.net.au/catalyst/stories/2675796.htm

Alberto

Lance writes:

You’ve probably seen this already and I’ve missed yesterday’s TWiV, but the second item (influenza reassortant) is really interesting and it would be good to hear what you think about it.

I’ve not heard about this happening much or even at all like this – my question is why isn’t this more common?

Thanks for all the great work,

Lance

Wellcome Trust Clinical Fellow

INFLUENZA (40): H3N2/H1N1 REASSORTANT ex PATIENT

************************************************

A ProMED-mail post

<http://www.promedmail.org>

Date: Wed 8 Jun 2011

From: Jonathan Gubbay <Jonathan.Gubbay@oahpp.ca> [edited]

Reassortment following coinfection with seasonal H3N2 and pandemic

(H1N1) 2009 viruses in Ontario, Canada

– ———————————————————————-

A 16-month-old infant was admitted to a Greater Toronto Area Hospital on 24 Jan 2011 with respiratory and gastrointestinal symptoms. After 15 hours, he was discharged home and subsequently recovered uneventfully. 2 nasopharyngeal swabs were collected on the day of admission and sent to the Ontario Agency for Health Protection (OAHPP) Public Health Laboratories (PHL) for influenza testing by real-time reverse transcriptase PCR (rRT-PCR). Influenza A [virus] was detected in both specimens by rRT-PCR, and when subtyped were positive for hemagglutinin (H3) gene in a moderately high copy number (cycle thresholds 29 and 31). They were also noted to be positive for the pandemic (H1N1) 2009 (pH1N1) neuraminidase (NA) gene at a very low level (CT values 38 and 39), which was detected using an in-house rRT-PCR (1). Suspecting contamination, primary samples were reextracted and retested; identical results were obtained.

Further sequencing confirmed presence of the following genes in the primary samples:

A. Pandemic H1N1 2009 genes: Matrix, NS, H1, N1 (H1 sequencing was conducted on one primary sample only)

B. Seasonal H3N2 genes: N2 (H3 sequencing was not conducted on either primary sample)

The 1st specimen underwent conventional viral culture in rhesus monkey kidney cells. Whole genome sequence analysis of cultured material showed that the isolate possessed H3 and N2 of seasonal H3N2 in combination with PB2, PB1, PA, NS, NP, and M of pandemic H1N1. Gene sequences obtained in culture and primary specimen were identical. A BLAST [basic local alignment search] was conducted against sequences available in GenBank. The H3 and N2 gene sequences most closely matched the currently circulating A/Perth/16/2009 strain.

The matrix and NS genes amplified from the primary sample were identical to currently circulating pH1N1, most closely matching the A/California/07/2009 strain.

Canada’s National Microbiology Laboratory performed plaque forming assays on the primary sample and culture material using Madin-Darby canine kidney cell lines. Sequencing of individual plaque material in both primary sample reconfirmed a reassortant virus as described above, with no evidence of the HA and NA genes of pH1N1. In addition, gene sequences obtained in both plaque assays matched each other, and were also identical to those obtained at OAHPP. The isolate strain type was A/Perth/16/09 (H3N2) by hemagglutination inhibition assay.

Summary and implications

————————

This case represents coinfection with H3N2 and pH1N1, followed by reassortment in the patient (in vivo reassortment). The low level of pandemic H1N1 2009 NA gene in the primary sample indicates that the reassortment occurred in the child and the lab detected a remnant of NA left behind. If it were just coinfection but not reassortment, we would have expected to find evidence of H3N2 viral genes other than H3 and N2 in the primary sample. The subsequent reassortant virus consisted of HA and NA of H3N2 together with the remaining 6 genes (PB2, PB1, PA, NS, NP and M) of pH1N1.

To the best of our knowledge, this is the 1st case of reassortment involving pH1N1 and seasonal H3N2. We could not document any transmission of this reassortant, which arose during a confection involving both subtypes. In a recent study reverse genetics was used to generate a laboratory reassortant of this type — infection of ferrets with this reassortant resulted in higher levels of virus and more severe respiratory damage when compared to wild-type pH1N1 (2).

This case and the 5 reports of human infection with swine triple reassortant H3N2 in the United States since September 2010 highlight the need for ongoing molecular and phenotypic surveillance for novel influenza strains (3).

– —

[ProMED-mail is indebted to Dr Gubbay and colleagues for drawing the attention of readers to the outcome of an investigation which has established that the coinfection of a child with pandemic H1N1 and seasonal H3N2 influenza viruses in the Toronto area was accompanied by genome reassortment in the patient ( _in vivo_ reassortment). A recombinant (reassortant) virus was recovered from the patient possessing the external protein genes of the H3N2 influenza virus and the internal protein genes of the pandemic H1N1 influenza virus.

During the 2010/2011 influenza epidemic season in North America both the seasonal H3N2 and the pandemic H1N1 viruses have been prevalent and the occurrence of coinfection is not surprising, but this appears to be the 1st demonstration of _in vivo_ reassortment. Fortunately the infected child has recovered and the recombinant (reassortant) virus was not transmitted. It remains to be seen whether this or similar reassortants will appear in subsequent epidemics. – Mod.CP]

Ruth writes:

Dear Vincent & twiv virologists,

I very much enjoy listening to Twiv and find your outlook on topical virology issues both refreshing and extremely interesting. Thank you so much for this!

I am a University teacher in Virology at The University of Glasgow, Scotland. We have recently received MRC funding for a new Virology institute that is currently being built on our Garscube campus and there is a wealth of exciting Virology research going on in Glasgow. I am involved in Virology undergraduate teaching here and my students listen to your podcasts. I am always on the lookout for novel teaching aids for virology and wonder if you can recommend any?

We have your textbooks already, they are excellent!

I appreciate that you are very busy, however I hope that you can recommend something new/fresh to me. Our students receive lectures & tutorials and they read the literature and present virology topics in a number of formats ( projects, dissertations and posters ).

I am looking for some new ideas and have a small budget for this (£600) and am considering developing some good quality teaching software myself, pitched for senior undergraduates .

Please let me know if you can recommend any good teaching resources for virology.

Thanks in advance for your time.

Your sincerely,

Ruth

Kristina writes:

Hi There,

RNA viruses are the cause of so much human suffering. Most often we are presented with estimations of morbidity and mortality for individual viruses, but I’ve never seen a figure for RNA viruses (or DNA viruses) as a whole. Do you have an estimate?

-Kristina

Jenny writes:

Hi TWIV-casters!

I’ve been a listener to TWIV for a while, and I can’t tell you how enough how much I enjoy listening to your podcast. I’m a graduate student working on immune responses to influenza and it is a wonderful addition to my education. I usually listen to TWIV while working in the hood or doing my runs or doing chores at home, allowing me to use my time wisely. Anyways, I came upon this review of a book by Carl Zimmer, maybe you could feature it on your picks of the week. I haven’t read it yet, but it looks to be an interesting read. Here is the link to the book review in PLoS Biology: http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001139.

Thanks so much for all the work you do! I enjoy the witty banter and the geeky punchlines too. Who knew listening to a virology podcast can make you laugh out loud? More power!

Jenny

TWiV 147

Liam writes:

Dear TWiV hosts,

I recently came across a website that I think would be perfect for a pick of the week. It is called Scitable and is produced by the nature publishing group. It is a free to access science library currently focusing on cell biology and genetics. It includes a free online textbook designed to introduce readers to the basic concepts of cell biology. I’m sure this would be appreciated by many TWiV listeners who may not have a science/biology background.

I have finally caught up on your past TWiP, TWiV and TWiM episodes. Keep up the great work.

Liam

Cathy writes:

Hi TWiV folks,

I just finished listening to the latest podcast and heard you ask about “Virology for dummies” type of books. One book that I often recommend for those just starting out in my lab is “How Pathogenic Viruses Work” by Lauren Sompayrac. It is a great introduction to viruses for the layman with each chapter presented as a “lecture” in a fairly entertaining way.

Just thought I would share this with you in case you wanted to share it with your listeners!

Best wishes,

Cathy

Iowa State University

Gopal writes:

Dear TWiV-ers,

I found Rich’s exposition of F.W. Twort’s 1915 paper in The Lancet, “An investigation on the nature of ultra-microscopic viruses,” in TWiV-145 fascinating. I hope that in future TWiV episodes you will similarly look at other landmark papers in virology. It is fascinating to learn about the evolution of ideas in a field, the amazing leaps of intuition, experiments that suddenly shed new light and, sometimes, what ultimately turns out to be the pursuit of false leads.

Keep going!

— Gopal

Science Correspondent, The Hindu newspaper.

The Hindu Online http://www.thehindu.com/

Rich writes:

Twivers,

I enjoyed your discussion about teaching virology to undergraduates – the executive summary of the excutive summary. Why not start the course with a short explanation of Heisenberg’s uncertainty principle? The closer you examine something the less you know about some of its characteristics. Just tell the students that virology is very similar. The closer you look at viruses, the more uncertain you become about how they really work.

All the best,

Rich

Estanis writes:

my name is Estanislao Nistal, I am a former PhD student in Dr. Garcia-Sastre’s lab at Mount Sinai. I met there Juliet Morrison, a former PhD student in your lab which told me your passion about Twiv and putting a voice to the news in the virus field. Currently I work as postdoc in Pamplona, back in my country, Spain, where I started my postdoc working with woodchuck hepatitis virus as a model for chronic hepatitis B infections.

I am a big fan of Twiv that I have the chance to enjoy every other week on my car trips to Leon where my parents live. I find Twiv a very valuable tool to get updates on papers and facts that otherwise would take me much more time to find. It is also a very refreshing way to keep my attention occupied while crossing along the north of Castile and Leon.

The reason I am writing to you is to propose an idea that I have been thinking for some time. As I find Twiv very useful and interesting, I have tried to play the show in the lab and make publicity of it to people in my institute that are passionate about viruses, or about science in general. The English level of some people is not good enough or the ability of some to understand the message in not sufficient. I know that a Scientist should speak, write and understand English correctly, but unfortunately that is not the case for many in my country, particularly in the listening-comprehending part. That yet is not preventing them to keep interest on science and on viruses or the cool interesting things that you talk about in your podcast. So given the situation I think that a Twiv in Spanish would be an excellent tool to transmit and educate Spaniards and other Iberoamericans, or Spanish speaking countries in general about viruses as well as a way to influence people to go one step further to explore the virus world.

I would love to get an opinion from you about this issue and see if it would be possible to organize such podcast in Spanish, sharing the Twiv format. I understand the risks and difficulty of getting something as good as the job that you do, but I will try my best to set it up well before starting, having your approval. Some things for now should be different, like for example the fact that it will be difficult at the begging to have a weekly program.

I am actually in NY until next Monday. We can contact also by mail or Skype.

Thanks for your interest and looking forward to hear from you.

Best!

Estanis

TWiV 146

Jonathan writes:

First and foremost, this and the podcast of the virology course lectures available on iTunes is a gift to the public. I am applying to medical school and I appreciate the material on a topic I did not have time to take but have had a long standing interest. So- thank you! To the question: after listening to the first lecture I found a PLoS ONE article that states that a research team has drafted a double-stranded RNA (dsRNA) that, to the best of my understanding, binds to a viral RNA particle prior to being incorporated into the host’s genetic material, and then exploits a apoptosis pathway in that infected cells, quenching the propagation of future virons in that instance. The article is entitled “Broad-Spectrum Antiviral Therapeutics” by Rider, et al. PLoS ONE 6(7): e22572. doi:10.1371/ Are there any comments about “survival of the fittest” with respect to virus in light of this?

Thank you,

Jonathan

University of South Florida

Dave writes:

Dear TWiVers,

It was great to have seen the live podcast at ASV! I am looking forward to seeing another one next year in Madison…

Thanks in advance for any thoughts…

Keep up the great work…

Cheers,

Dave

David B. Kushner, Ph.D.

Associate Professor of Biology

Dickinson College

Carlisle, PA 17013

Jason writes:

Thanks for your show.

I’d love to hear a discussion about this remarkable paper in PLoS ONE:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572

Broad-Spectrum Antiviral Therapeutics

Thanks,

Jason

Executive Director, PersonalGenomes.org

http://bit.ly/jasonbobe

Michael writes:

Here’s the paper,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144912/

In the media:

Time article – http://healthland.time.com/2011/08/11/mit-scientists-develop-a-drug-to-fight-any-viral-infection/ – “Scientists at MIT are developing a new drug that may fight viruses as effectively as antibiotics like penicillin dispatch bacteria.”

Times of India article – http://timesofindia.indiatimes.com/life-style/health-fitness/health/Soon-a-revolutionary-pill-to-cure-HIV-flu/articleshow/9563867.cms – “Scientists are developing a new drug, which is showing great potential to revolutionize the world of medicine with its ability to cure everything from colds to HIV.”

Alfred writes:

I was hoping the TWIV crew could weigh in on this PLoS paper describing a broad spectrum antiviral:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572

Thank you.

Alex writes:

Good afternoon Dr. Racaniello and fellow TWIV’ers;

Thanks for a great podcast series. I’m an electrical engineer will little background in the biological sciences. I really enjoy listening and learning. You provide a new world that I had no familiarity with, before.

I came across an interesting article about a possible broad spectrum anti-viral. You probably have received other emails about this.

Can you comment about this in a future podcast?

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022572

Thanks and keep up the great podcasts.

Best regards,

Alex

Reynard writes:

I’m sure you are getting requests for this already so I’ll keep it short. I would love to hear a twiv panel comment on the recent success of DRACO. These are exciting times!

Thank you for your continued efforts,

Reynard

Shelby writes:

I’d love to hear your thoughts about chicken pox and if it is really beneficial in the long run to get the vaccine.

Shelby

Camby, IN

Juanjo writes:

Dear Professor Racaniello,

as a plant virologist working in a research institute in Spain, I have been waiting for a good occasion to communicate with you and the rest of co-host of TWiV. I started last February to listen to the shows during my daily commute trips (20 minutes train plus 15 walk thru the campus of the Autonomous University of Barcelona). I got hooked (“memetically” infected?) almost instantly, and since then I wait anxiously for every new chapter while hearing backwards in your archive. At a pace of 4-5 chapters a week, I am afraid I’ll be soon running short of new materials. Please receive my deepest gratitude for this truly entertaining and educational initiative.

The motivation for this letter comes after your nice conversation with Professor Raul Andino (TWiV 138). Dr Andino was extremely didactic when explaining his recent work on RNAi suppression in insect viruses. He was also able to provide a comprehensive revision of the current knowledge on RNAi mechanisms, and how viruses deal with this. When commenting on the mode of action of plant virus suppressors of RNA silencing, he was right to say that most plant viruses have adopted a small-RNA sequestering strategy (Lakatos et al., 2006, EMBO J 25, 2768-80). Interestingly, a few exceptions are also known, and some plant viruses target the RISC complex as the Cricket paralysis virus does. In addition to polerovirus P0 and cucumovirus 2b proteins, shortly after the Nayak et al paper appeared and demonstrated the activity of CrPV-1A on Drosophila Argonaute 2 (Nayak et al. 2010, Nature Structural & Molecular Biology 17, 547-554), two independent studies with Turnip crinckle virus (Azevedo et al., 2010, Genes Dev 24, 904-15) and Sweet potato mild mottle virus (Giner et al., 2010, PLoS Pathogens 6, e1000996) showed an additional mode of action, based on antagonyzing host Argonaute. These two unrelated plant viruses have got RNAi suppression activity by mimicking cellular Argonaute-interacting proteins which contains WG/GW (Tryptophane-Glycine or Glycine-Tryptophane) conserved motifs. Indeed this new strategy adds up an example of the broad variety of modes of action of viral RNAi suppressors.

The final comments of Professor Andino and yourself about the importance, usefulness and basic interest of keeping up the good work with model organisms like Drosophila, Caenorhabditis (and I should add Arabidopsis in the case of plants) were also quite opportune.

Thanks again for TWiV.

Your faithful listener,

Juanjo Lopez-Moya

Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB

Campus UAB Bellaterra (Cerdanyola del Valles) 08193-Barcelona (Spain)

Valorie writes:

Virology fascinates me but alot of it goes right over my head. Can you recommend a basics or beginners book for people outside the medical field so I can start from the ground up? (Something that dumbs the complex ideas down for me like a “..for dummies” or “A Complete Idiots Guide To…” book would be ideal!)

Thanks alot!!

John writes:

Dear TWIVers:

I have a couple of questions related to TWIV138, where you discussed short-term adaptive immunity in insects based on RNA interference. As I understood it, double-stranded RNA injected into insects causes a kind of systemic immunity, based on getting cells all over the insect to produce siRNA that will mark the viral RNA for destruction inside the cell. (Is this more-or-less right?) If I understood right, your guest said that the immunity to the viruses from the siRNA lasted for a week or two, which I guess is a substantial part of a fly’s lifespan.

The first question this raises in my mind: is it a common consequence of viral infections to have viral genetic material (DNA or RNA, depending) end up floating around outside cells? It seems like this would happen when cells burst open with newly-made virus particles, and could also happen just from random luck, with viral RNA or DNA slipping out of the cell when something else exits. And any kind of immune response that kills infected cells could also leave some leaking DNA or RNA. This seems like it would be true both in insects and in mammals. I also wonder whether, under normal circumstances, there’s a lot of host DNA or RNA floating around between cells.

This made me wonder how the insect cells could distinguish self genetic material from nonself genetic material. The mechanism your guest described, if I got it straight, involved ds-RNA. Healthy animal cells shouldn’t be producing ds-RNA, so maybe the answer is that insects only respond to ds-RNA. But this made me wonder if he or other researchers have tried single-stranded RNA viruses or any kind of DNA viruses, to see if similar immune mechanisms there. If they do, then I guess there must be some kind of mechanism to keep from having all the insect’s cells make siRNA against some protein they need to survive.

Finally, I was curious how this ties into DNA vaccines in mammals. The fact that DNA vaccines work at all suggests that having viral genetic material floating around must be a useful signal that there’s a viral infection that needs to be fought off. But I don’t really feel like I understand the mechanisms there–it seems like some antigen presenting cell must be taking up random DNAs it finds by the side of the road and expressing its genes. (Is that right?) Would the same sort of thing work with viral RNA? I’d love a show where you talked about DNA vaccines.

Anyway, thanks again for your wonderful podcasts, which have really opened up a new world for me, and thanks for answering my amateur questions.

–John

Cliff writes:

Hey guys!

My name is Cliff and I am new to the whole podcast scene. I started out with a Nursing podcast, and found my way to yours via i-tunes. Now, I would like to begin by saying I am not a scientist, (like most everyone else that emails you), but I am enjoying learning about viruses. The first time I listened to you all, I actually laughed at my first scientific joke, and then I knew I could make it in the healthcare field. You are educators, and you have become good friends of mine while I work to maintain a woman’s building in Ann Arbor. As you thanked Al in TWIV 132 for spending the afternoon with you, I would like to thank you for spending days with me this summer. You guys are like friends of an athlete that never leave his side until he loses his flair, except for me it’s more like you won’t leave my side until my mp3 player dies. I feel like I can be chatty with you. I can even be sarcastic with you.

Athlete talk is bringing me to my point. I wanted to email ya’ll after listening to episode 133 where, I think it was Rich, asked Kathy if she spoke with Majic Johnson recently since he played ball where she works now (UofM) with HIV. Now, over at MSU where I participate in the Decathlon and am working on getting into the Nursing program, I noticed a big statue of Majic outside the Breslin. I guess MSU loves him even though he went to UofM. (There’s the sarcasm). But not a big deal, I am starting to like all you guys even with the mistake.

Also thought I would share a virus reference I like with you. In the first Matrix movie, Mr. Smith speaks of how, “Humans aren’t actually mammals. But there is another organism on the planet that are like Humans. VIRUSES. You multiply nonstop, use up the resources in an area, and then move to another. You are a virus of this planet” (Matrix, 1998-ish). I’m not a pessimist, I just thought you would enjoy that bit if you haven’t seen it.

Now to make this worth your while I will ask a question… This may not be a good one, but I will ask anyhow. Since sickle cell anemia is a malformation of a blood cell, ( I learned from ya’ll that it was in response to malaria and becoming resistant to it), I would guess there may be different receptors on it as well. Now for some people, sickle cell can be a big problem for them even if half of their blood cells are normal, so I am wondering if it would be possible to create a cure using a virus that would specifically attack sickle cells in the blood stream. But then again, Sickle cells would probably continue to be produced be the host since I am guessing it’s in their DNA to produce them. I could probably google it to find the answer, but I would rather hear your thoughts on it. After all… you are my friends while at work.

I will come back again with some better questions as I start my Nursing courses and they arise. Until then,

Cheers,

Cliff

TWiV 145

David writes:

Hi Twiv folks

I am developing a class on how infections can alter the behaviour of their hosts. There are some fantastic examples of this in parasitology where the parasite alters the behaviour of the host to increase its chances of transmission. The reason I decided to develop this class is that I find it fascinating that rabies induces aggression, causing the infected animal to bite and transmit the disease, but I dont know anything about how it actually does it. I’m developing the class with a physiological psychologist who does animal behaviour research and we are already having too much fun learning about zombie ants and other strange infections.

My question is, other than rabies are there other viruses that alter host behaviour, especially with the effect of increasing transmission?

It seems like there must be a sexually transmitted disease that increases sexual desire or promiscuity, but havent found one. Do you know of any?

Also, do you have any thoughts on the origins of the mythology of zombies and vampires as possibly based on behaviour mediating infections? Certainly many zombie movies portray zombieism as an infectious disease, could these ideas have started with historical cases of altered behavior due to infections?

Cheers

David Esteban

Biology Department

Vassar College

http://faculty.vassar.edu/daesteban

http://blogs.vassar.edu/viva/

Wendy writes:

I was recently listening to your 100th podcast where you featured David Baltimore. One aspect of virological history that was discussed, but is frequently overlooked, is the work by several investigators at NIH in the late 1970s to determine if indeed cloning was safe. These investigators took time from their own studies to identify dangers of cloning and whether such studies could safely be performed. The studies were very important in the history of molecular biology as well as virology and I believe that the details of these studies would be of interest to the community at large. Those individuals who did this work are getting older and that history will be lost once they are gone since there seems to be few details of this work published (as far as I can tell). How about getting some of those scientists on your program to talk about the events?

Wendy

University of Iowa

Joe writes:

Dear TWIVcats.

I would like to wade in to the viruses are they/aren’t they alive debate with a thought experiment.

Like every person on the planet, I am related to every other terrestrial organism via a common ancestor, for a Chimpanzee our shared relative lived relatively recently (geologically speaking), whereas for an E.coli it was probably billions years ago. However, we share grandparents and are all very distant cousins. So, with this in mind, am I also related to Poliovirus, is Ebola my tear-away cousin 10 to the power 30 times removed? And if we are related to viruses, does this have implications for their alive/not-alive/undead status.

Just a thought.

Love the show.

Thanks,

Joe (London, UK)

Joe writes (re Agave viruses, Kevin’s letter on TWiV 137):

As a long time listener to TWIV I was dismayed that the crew was not familiar with the groundbreaking work of Prof. Jose Cuervo regarding the agave life cycle. He identified the T-Kwillia virus as its primary infective agent and showed how it was transmitted by the common Bar Fly. It is one of few agents that also causes diseases in humans, the dreaded Morning After Sickness with the classic symptoms of headache, dry mouth, blurry vision and tremors.

Love the shows

Joe

PS. Allan can probably come up with a better virus name, feel free to edit.

Joe

EH&S Manager

Jeffrey writes:

Hello – In TWIV 139, after describing the loss of the fiber genes from the mimvirus genome upon passage, one of you asked if other viruses lose their fibers as well and someone mentioned adenoviruses. I am now a community college assistant professor, but in my former life I was a researcher and did my dissertation on the persistence of adenoviruses in human lymphocytes. Bringing up adenovirus was interesting for a couple of reasons.

First, if you compare the genomes of the animal adenvoiruses, the conserved genes are in the middle of the genome and its the ends that are the most different (see http://vir.sgmjournals.org/content/84/11/2895.long).

Second, its the fiber genes that are in the middle (not at the ends) and appear to be pretty well conserved.

Anyhow – love the show; thanks for keeping me current on research now that I have to spend my time grading.

Jeff

Assistant Professor of Biology

Georgia Perimeter College

Geoffrey writes:

Doctors:

I feel that I must rebut a point made by Alan Dove in episode 130:

“We’re not looking at a world where we have a choice between these genetically-modified pest-resistant plant and some beautiful organically-grown, no-pesticide, no-evil chemical, no-nothing types of food. In fact, with more than six billion people on the planet, what we have is a choice between these pest[icide – delete?]-resistant, genetically-modified plants or plants that are grown with petrochemical pesticides.”

First, ask Dr. DesPommier to describe permaculture to you. It is proving to be an increasingly more viable method of growing food while improving the environment. Farmers like Mark Shepard in Wisconsin (Here is a little information on Shepard and his farm: http://www.forestag.com/bio.html. Here is an article by him:http://www.nfs.unl.edu/documents/specialtyforest/shepard.pdf) are showing that permaculture can be a financially viableand product ton/acre efficient way to produce food without pesticides. Second, there is at least one other alternative to grow enough food to feed our planet – grow your crops within a semi-customized eco-system (rather than in isolation) and direct natural biological controls towards keeping your crops happy as your first line of defense. Use pesticides as a highly selective and time-limited second line.

This is not to protest against genetic engineering. I strongly believe that it has a valuable place in the future of our culture but it should be used in a manner that promotes rather than degrades the health of the planet.

Yes, this type of agriculture requires a complete re-structuring of our current agricultural system but, then, what do we think will happen to the system when gasoline (and related petrochemicals) reach $5… $10 a gallon?

Thanks for the excellent show,

Geoffrey Tolle

TWiV 144

Mary writes:

What’s the deal with the embargos anyway? I know it’s called the NEJM rule, and I suspect it has to do with perhaps the press or big business somehow taking off with an idea before it’s time, but I haven’t seen that ended by this practice.

In my fields (history and economics) (Ph.D. JHU 1984), we freely discuss research in progress – in fact, that’s when the most good work happens, when you have to answer questions, or deal with stuff you hadn’t yet thought of, or somebody has a new idea or new evidence or knows about a pertinent study you missed.

It’s very common to cite “published manuscript” or “work in progress,” or if I get a good idea and some leads from someone else’s work and they haven’t published yet, we would make up a name of a working paper I could cite in case someone wanted to know more about that person’s work – and since I’ve been very sick for two decades now, a lot of my work circulates in that form, with my permission.

Why is medical science so different from other fields?

I guess I’ve seen some of what can happen – a chance comment by Dr. Alter at a conference somewhere in central Europe ends up in a story in a Dutch newspaper and suddenly all hell’s breaking loose in the United States. But I guess I’m not sure that it should have led to all hell breaking loose.

Maybe it’s nothing more than that the press, and the insurance industry and Big Pharma, and policymakers, all care about your work and really don’t give two hoots about economic history. So you have to be more careful.

But I still don’t understand it.

Thank you.

Mary

Peter writes:

hendra – all the dummies come out of the woodwork

kill all the bats

cut down all the trees

http://www.abc.net.au/pm/content/2011/s3279408.htm

Matt writes:

I have been following the latest outbreaks of hendra virus in Australia, it has killed several horses without any positive results in humans so far . It appears that the virus may be able to infect dogs, or at least can cause an immune response in this species. Not sure if this is a case of “if we look hard enough we will find it” or the detection of hendra moving into a new species for the first time.

http://www.abc.net.au/news/2011-07-26/hendra-virus-infects-dog/2811204

Enjoy the show,

Regards

Matt

Ai-Lin writes:

It’s fascinating that a virophage would so benefit algae populations in Antarctica, as discussed in TWIV 128. I wonder to what extent these virophages can be used in conjunction with current environmental science studies to mitigate global carbon dioxide levels. As you may know, carbon dioxide concentrations are fast approaching 400 ppm in our global atmosphere, as measured in labs in Mauna Loa, Hawaii. One of the mitigation options environmentalists have proposed to use involves the cultivation of algae blooms in suitable bodies of water to not only fix CO2 from the atmosphere, but also perhaps use the biomass as a form of fuel. Of course, the dilemma lies in algae proliferation in the absence of excess phosphate and nitrogen. What are the possibilities that a strain of this virophage can be created so that it can be used in temperate zones to help this CO2 mitigation option?

—

Ai-Lin

Environmental Biology

Barnard College 2011

Ann-Marie writes:

My question to you is related to the many posts you have had about poor coverage of scientific issues in journalism. Although David Tuller is beginning a new dual program at UC Berkley, do you think undergraduate courses could also give the needed scientific background instead of a masters in public health? Clearly every journalist writing about health related topics will not have a major in biology, but do you think that perhaps requiring science classes in a school’s core as an undergraduate could also help minimize this problem? And if so, what specific science classes would be most useful (either as an undergrad or while pursuing a MPH)? I suppose my overall question is do you think that this dual program is really the best option, or is there a better way for journalists to acquire a scientific background?

[Here is Dave Tuller’s reply]:

Vincent, that’s interesting, thanks for sharing. my answer would be, any educational work in these areas would be helpful–adding on the MPH is just one way to do it. Certainly if a student was a public health major as an undergraduate or had a lot of biology/microbiology coursework, that would be a good basis for covering public health, infectious diseases, etc. as a journalist. The MPH I think does add a professional component–you start to think the way someone working in public health would, and that’s a very helpful ability to have as a journalist.

Neva writes:

Yes! More tracking initiatives. I notice they do not mention tracking dengue in Central America though.

Blog: Official Google Blog

Post: Using search patterns to track dengue fever

Link: http://googleblog.blogspot.com/2011/05/using-search-patterns-to-track-dengue.html

http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001206

TWiV 143

Judi writes:

Hello People of TWIV!

Thanks for all the information you give and how you make me think. I really liked your discussions on TWIV 136 – exit XMRV, not as much for the science ( which was cool) but for the discussion of the process of science – how it is not as linear as we often teach our students. I wish all my students could have heard this discussion, but I think many would get lost in the vocabulary of XMRV.

I am a high school science teacher, previously a lab rat in biotech labs (I started in 1975, so I learned to do things without kits, and I remember when getting a milligram of plasmid from a liter of LB was a glorious thing – now they get that from a miniprep!)

The hardest thing for kids to understand is how science works. There is a great website

Understanding Science http://undsci.berkeley.edu/

which greatly helps. Judy Scotchmore and other people in the Museum of Paleontology at Berkeley continue to work on the this site, adding real world examples of science, both good and bad, student misconceptions, and lesson plans for teachers through college. They have also reordered the classic “scientific method” 6 step list into a more realistic (and interactive) circular form check out “how science works – The flowchart” . They also have a ‘science checklist’ to help kids understand what science is – and what it’s not.I do have a request for you and for all the scientists who listen to TWIV – part of the website ( under resources tab) is a section called “the call of science” where scientists talk about how they became scientists. You guys need to put your stories there and share you love of communication of science – after all – you are the cutting edge of how science information can be shared with the general public.

Thanks for all you do – and all the work you put in. I learn much from TWIV, TWIM and TWIP….. and I may be in a minority here, but please don’t add more episodes – if you do I’ll have to quit my job to keep up! (Actually, more TWIPs would be fun – monster stories on a small scale!)

Thanks for being MY teacher!

Judi

San Diego, CA

(70s and Sunny.. that’s about 22 degrees C!)

Atila writes:

Dear hosts,

At TWiV 139 you discussed how after several passages in amoebal cultures the Mimivirus gets bald and loses a big chunk of DNA. This reminded me of a Annual Review about this virus that I read some time ago (reference here), where Claverie and Albergel mention that the Mimivirus fibers serve to mimic the bacteria that are preyed by the acanthamoeba and to be phagocyted. These fibers are even glycosilated to better copy the bacteria and can retain Gram staining, which is the source of confusion behind the discovery of this virus. So, it is not a big surprise that the disappearance of the fibers is followed by the lost of the sugar related genes, it could be that this amoeba used to culture the virus does not need the coating in order to be infected.

The hole story behind the discovery of Mimivirus is due to its resemblance to bacteria. I don’t remember if you have talked about it already, so here goes a brief description. Mimivirus was mistook as a gram-negative intracellular bacterium, during the analysis of a water sample from a cooling tower in search for Legionella. It could be stained and observed inside amoebas, but it could not be cultured, and ribosomal 16s primers didn’t work for them. According to the discoverers “Among all the intra-amoebal “bacteria” that constituted our original collection, one provided us with the most headaches but, ultimately, the most exciting findings.” When they looked at these bacteria under a electronic microscope, they saw the unmistakable icosahedral form of a virus, but a giant one. The name also came from a curious source “We have proposed the name Mimivirus [17], partially as a reflection of its mimicry of microbes and partially as a tribute to one of our forefathers (D.R.), who was a doctor who taught tropical medicine and studied nutrition. When teaching his 10-year-old son about evolution, he referred to the last eukaryotic common ancestor as ‘Mimi the amoeba.'”

As for the complexity in biology that always comes up in discussions, there’s a nice passage from “The Great Influenza”, a book that you recommended in TWiV 15: “Leo Szilard, a prominent physicist, made this point when he complained that after switching from physics to biology he never had a peaceful bath again. As a physicist he would soak in the warmth of a bathtub and contemplate a problem, turn it in his mind, reason his way through it. But once he became a biologist, he constantly had to climb out of the bathtub to look up a fact.”

Sorry about the long mail, full of quotes about things you already have discussed, but I love when you talk about other viruses besides those that make you sick. I like the ones about disease causing viruses too, but discussions of viruses outside the realm of human disease are rare, and being able to hear them from you and your guests is a great opportunity.

I would also ask you to forgive my bad english again but, as Alan says, you don’t speak portuguese very well too. So thanks again for the rich and informative podcast(s), from one of your many Brazilian listeners.

Best regards

Atila

Tim writes:

My dear TWiVists!

We have three brilliant shows. We have TWiV. We have TWiP. And now we have TWiM. How long before TWiF makes an appearance? Let’s not leave our fine fungal friends in the dark!

Keep up the fantastic work. You guys are a valuable resource for a kid who did humanities in high school and is trying to add to his scientific understanding during uni, before eventually applying for med school!

Much love and respect,

Tim G

Victoria, Australia

Adam writes:

Hi Guys!

I’m a long time listener, first time email-er. I really love the show!

I was really intrigued by this weeks show on XMRV (TWIV #136). I wonder how frequently recombination resuscitates endogenous retroviruses in nature, away from the contrivances of the laboratory (ie. propagating human prostate cancer cells in mice). Do you think that Human Endogenous Retroviruses (HERVs) are frequently revived in children whose parents both carry inactive retroviruses? If each parent carried a similar retroviruses that are inactive due to loss of genetic information in different portions of the retrovirus, there might a potential for the retroviruses to recombine and become active again once they are united within a new individual genome (that of the child).

Thanks for the enlightening, inspiring, and entertaining podcasts!

Cheers,

Adam

TWiV 142

Marshall writes:

Dear TWiV hosts,

I’m sure you’ve already heard about this, but I was curious what your take on this study is.

http://www.voanews.com/english/news/health/SIV-Vaccine-Holds-Promise-for-AIDS-121790724.html

I understand that studies showing results in monkeys don’t necessarily translate well to humans, but I thought it was interesting that they might have been able to completely wipe out the virus in some monkeys (if I understood the article correctly. I’m a linguist, science is just a hobby of mine…for now).

So, I was curious what you all thought about this possibly leading to an effective vaccine/cure for AIDS. Best and worst case scenarios?

Thanks for all the free lessons! I enjoy all three podcasts tremendously, and as I said, I’m not a scientist yet, but thanks in large part to your podcast, I am seriously considering it for when I retire from the military in a few years.

Keep up the good work.

-Marshall

[I believe this is the article: http://www.ncbi.nlm.nih.gov/pubmed/21562493]

Kay writes:

Dear TWIVers,

I have been following your podcast from day one but never got around to mailing you. Like everybody else, I love your show and plan to ask you some (more or less) intelligent virus-related question later on.

One of the things that keeps amazing me is the broad range of occupations held by your listeners. In a recent episode, your read an e-mail from somebody working with Rockwell Automation. While mentioning this, you said something along the lines of ‘I wonder what they are producing’. Well, apparently a lot of things, among them the famous Retro-Encabulator (http://www.youtube.com/watch?v=RXJKdh1KZ0w) which is a greatly improved version of the original Turbo-Encabulator (http://www.youtube.com/watch?v=rLDgQg6bq7o). You should really watch the short (~2 minute) videos, they are hilarious.

Best Wishes,

Kay

Debbie writes:

Dear Education Pioneers on TWIV,

I’m a pediatrician in Taiwan. I’ll be finishing my last year of fellowship in pediatric infectious disease this summer. One year ago, I noticed TWIV on iTune. The interesting topics and your witty conversations soon fascinated me. I became a regular listener every since. My favorite show was episode 103, with Dr. LJ Tan. As a specialist of pediatric infectious disease, I was very happy to hear such an organized talk, clearly pointing out the major issues in immunization and providing simple but crucial information.

During the pandemic H1N1 influenza in 2009, we had a large proportion of parents refused H1N1 influenza vaccinations for their children in Taiwan. People learned about H1N1 vaccine mostly from the mass media, especially news or talk shows. It took a great deal of time and efforts in our clinics to clarify the rumors about the vaccines and to emphasize the importance of influenza immunization. During the interviews in the vaccine clinics, I learned that there was a gap between facts and misunderstanding toward vaccination in public. The gap could only be filled by constant education. From time to time, Vincent and Alan would raise this issue and address public awareness about vaccination in different episodes. It was such a motivation for we clinicians, trying to continue the efforts in public health.

On the other hand, there is also a huge gap between lab findings and medical care. Physicians sometimes have a hard time to understand the scientific findings. However, virology becomes far more interesting through your introduction, debates and analysis. I love to learn a variety of topics in virology and microbiology. (Also, thanks to Vincent and ASM to create TWIM.) You inspire me to pursue another adventure in research. I am about to start my PHD program this autumn. You help me to realize the happiness in learning and self-improvement. Thank you all for making science as a vivid and interesting subject. It is always a great pleasure to hear stories of scientific discovery from Rich and Dick. I truly admire your enthusiasm as public educators. Keep up the great work.

ps. A good educational website of evolution from Berkely

http://evolution.berkeley.edu/evolibrary/home.php

(They provide simple and detailed explanations about evolutions, such as phylogeny, through kindergarten to undergraduate.)

Best wishes

Yours,

Debbie:)

Clinical fellow

Infectious disease, Pediatrics

National Taiwan University Hospital

Chad writes:

I don’t know if I heard correctly, but did you say that CFS and Fibromyalgia were related or one and the same?

I’m asking because I don’t want to put words in your mouths.

I was diagnosed with Fibromyalgia about a year and a half ago, and I do notice that unless I get a minimum of 8-10 hours of sleep, I have a hard time functioning.

It would be interesting to be tested to see if I have XMRV.

Thank you,

Chad

Jason writes:

G’day from down under,

You have probably already seen these stories, but I thought I should send them through anyway.

Hendra virus vaccine announcement…

http://www.theaustralian.com.au/news/nation/vaccine-against-hendra-virus-found-17-years-after-trainers-death/story-e6frg6nf-1226057053158

[the paper: http://www.ncbi.nlm.nih.gov/pubmed/21689706]

And a summary of the Nigerian type 2 VDPV outbreak…

http://www.ncbi.nlm.nih.gov/pubmed/21402542?dopt=Abstract

Keep up the good work guys, it is much appreciated.

Cheers,

Jay

Senior Medical Scientist

WHO Poliovirus Reference Laboratory

North Melbourne,

Australia

Jonathan writes:

First off, I am starting from the beginnings of your show and I am currently at episode 31. I am enjoying it very much. Being a person who could never afford to go to college. I am also learning alot about a topic I’ve never really paid much attention to.

This contains spoilers for people who haven’t seen the following show.

I have been watching The Event on NBC. Over the last couple of weeks virology has been fairly important to the episodes.The “aliens” who are 1% different genetically from humans. They can interbreed with humans. The “aliens'” world is dying and they are trying to take over the Earth. In the episodes they dug up a corpse of a Russian soldier. He had died of a particuarly virulant strain of the 1918 flu. The virus would kill humans in a few hours from aerosoled contact. The “aliens” are immune to the virus. They released it on a subway car packed with video cameras to see the spread of the virus. In the show they had the people dying with lesions around the mouth and profuse bleeding from their nose and mouths. To stretch out the infectious period, so more people would be infected they needed to have the virus mutate into a strain that would have a longer infectious period. To do this, they infected one of the hybrid children. They did this via an infected pustule swab into a nostrel. And thus got their super human eliminating virus.

Here is my problems with this.

A) Depending on the 1% genetic difference is crossbreeding possible?I mostly ignore this thanks to many years of Star Trek.

B) Using the Spanish Flu (Russian Variant) because of it’s nastiness.I have heard that if the 1918 flu came out today, that it wouldn’t necessarily be as bad as it was then. Mainly due to better health care and sanitation.

C) It kills people in hours from aerosoled contact?

That would mean they inhailed a virus particle, it incubated, obtained critical mass, became infectious and killed in hours. (again not really a strong point from past education) That’d make this the nastiest airborn virus in the world and why are we even still alive?

D) They are immune?

Must be that 1% part again. If a person can catch a simian virus, swine, or avian virus. I don’t have the numbers exactly but I am certain in all of those cases the genetic difference is greater than 1%.

e)Blood and lesions?

Must be Hollywood-ing it up here. I do not know anyone who has had facial lesions from the flu. I can buy the blood, tearing in the lungs from excessive hard coughing.

f)The Mutation.

So after infecting one person, who apparently fell on the wrong side of the whole 1% line, the “aliens” have obtained the necessary viral mutation. for some reason the likelihood of this happening has sent my BS meter back for refurbishment due to a broken dial. Additionally wouldn’t this have also made the virus possibly infectious to themselves?

I look forward to (eventually) hearing your thoughts on this.

Violated Gorilla

Jonathan

Peter writes:

Dear TWiV hosts,

Many thanks for still keeping up the high quality after 133 episodes. I am looking forward to listening to #134 tonight.

Also many thanks for TWiP and TWiM.

I wanted to bring an article to your attention as a follow-up to TWiV #39 back in July 2009. Yes, it has been a while.

It’s about the Virus contamination at Genzyme’s manufacturing plant in Allston, Ma.

The article is open-access (even the URL address seems to indicate otherwise) and can be found at: http://www.biotechnoblog.net/bioprocessingjournal.com/articles-for-purchase/J92-Plavsic.pdf

You might find it interesting; not much industrial matters, but pure virology background information.

Alan might want to comment on the ‘volunteers’ mentioned in the ‘Physicochemical Properties’ section: “Noroviruses (NV), members of Caliciviridae, retain infectivity in the majority of volunteers following…”

Makes me wonder whether this volunteering is compensated with a cruise ship ride…;-)

And entirely unrelated, could you elaborate on the hypothesis that the stop of smallpox vaccination made way for the HIV epidemic.

This has been in the news recently again in the context of the current discussion over the destruction of the remianing smallpox virus stocks.

If you have discussed this already, could you point me back to the relevant episode?

Kind Regards from Incheon / Korea,

Peter

http://www.sciencedaily.com/releases/2010/05/100517204405.htm

http://www.ncbi.nlm.nih.gov/pubmed/20482754

Michael writes:

Magic Johnson was a Spartan not a Wolverine! MSU not UM!

Ken writes:

Twiv Crew,

Just a quick e-mail. The new perspective you had for Twiv 132 (virology 911) was great. It was very interesting to see the clinical aspects of these viruses, and I would love to see you adopt a clinician as a regular contributer. Thanks always for the wonderful podcast.

Ken

Anthony writes:

The paper discussed in Episode 115, “Color me Infected,” focuses on infection by one type of virus. If multiple different families of viruses were to infect a susceptible cell at the same time, would you expect that certain types would be preferentially replicated over other types? Do you think that the type of viral genome (i.e. RNA vs. DNA), in addition to other factors, would affect which viruses are more competitive for replication in the host cell, given that there is a limit on how many the cell can express at one time?

Thanks,

Anthony

[Check this out: http://www.ncbi.nlm.nih.gov/pubmed/6316646]

Angus writes:

Dear Vince and the TWiV gang,

Maybe this is old news but I thought that you all would enjoy the “Science Weekly with Alok Jha” podcast from the UK’s Guardian Newspaper.

http://www.guardian.co.uk/science/blog/audio/2011/jan/24/science-weekly-podcast-blogging-special

The 24th January 2011 episode offers a fascinating discussion of science-orientated blogging and how this can potentially enhance the dissemination of scientific discoveries and thinking, something dear to the hearts of all involved in TWiV.

I think it is fair to say that many people are growing weary of the kneejerk opinions that dominate the news cycle on TV and radio, and which fuel poorly informed discussion of important matters ranging from vaccines or climate change to birth certificates. With luck we will see a return to more measured and reflective thinking, and folks like you will be at the vanguard of this return to sanity.

One of the bloggers interviewed on this podcast raised the interesting idea of not reporting on a major scientific paper until a few months have elapsed. This would give science journalists and bloggers time to gather measured opinions from independent experts in the area and perhaps include follow up studies that support or refute the original splash. It is pointed out that for most people, it really doesn’t matter if science news is delayed a little and that this does not hold up the science itself. Providing thoughtful and tempered coverage of a complex issue is something you’ve done extraordinarily well with the ups and downs of the XMRV saga. Thinking back to your first discussions of this topic, would TWiV cover this story any differently today if you’d never mentioned it before?

Cheers and keep on ‘casting!

Angus

Angus Wilson, Ph.D.

Associate Professor of Microbiology & NYU Cancer Institute

New York University School of Medicine

TWiV 141

Lance writes:

Many thanks to all of you for such an excellent podcast. I think you all do a really fantastic job. As an ID physician and postdoctoral researcher working on flavivirus immunology in my case you are “preaching to the converted” as I am already an enthusiast for all things virological, but I hope as this podcast grows in profile you can reach an increasing number of people as you are so easy to understand and so good at explaining things and I am telling as may people as I can about it! I am really learning alot.

I have just been listening to TWiV 129 and Rich I think was talking about reverse genetics of viruses – I think one group of viruses for which this has been particularly difficult is the Flaviviruses and Japanese encephalitis virus in particular, which still doesn’t have a working cDNA infectious clone despite many attempts and several reports in the literature. The clones seem to be either very unstable or toxic to the cells used to grow them. That said, there is an interesting report in last months J Virol where the authors show this is because of E coli promoter sequences in the JEV and dengue-2 genomes which result in viral protein expression and toxicity during the cloning process.

Successful Propagation of Flavivirus Infectious cDNAs by a Novel Method To Reduce the Cryptic Bacterial Promoter Activity of Virus Genomes. S.Y Pu, R.H Wu, C.C Yang, T.M Jao, M.H Tsai, J.C Wang, H.M Lin, Y.S Chao, A Yueh. Journal of Virology 2011 vol. 85 (6) pp. 2927.

Also relating to japanese encephalitis virus, some time ago on either TWiV or TWiP Dixon made a interesting comment about Japanese encephalitis virus transmission via worms of some kind; I think they might have Trichuris or Ascaris, I can’t remember. Could you elaborate a bit on this please? Transmission between which species? Pig to human? What’s the evidence for this, and do you have a reference? I’d be intrigued.

I’d like to recommend something to you all on the subject of vaccination – a book by a British family doctor called Mike Fitzpatrick – “MMR & Autism, what parents need to know.” It’s a great and easy to read review of the evidence (or lack of it) that MMR causes autism. What is particularly interesting is that Mike himself has a severely autistic son. He’s a great guy – I met him because my wife did her family medicine training in the same practice.

Your podcasts are keeping me going as I grapple with setting up a Flavivirus immunology study in South India which can be challenging at times! Anyway please keep it up I am throughly hooked and I really look forward to it each week – TWiM and TWiP also. I am slowly catching up with past episodes.

Best wishes,

Lance

Wellcome Trust Clinical Postdoctoral Fellow

Ian writes:

Hi Guys,

I was listening to TWIV 112 and heard Brent’s letter asking about an old film he remembered watching in school that had animated white blood cells attacking viruses. I remember watching that same old film and was able to find it pretty quickly, YouTube never fails, and if it hasn’t already been found, here’s a link:

http://www.youtube.com/watch?v=Zj6G986lpag&feature=related

I particularly like how the viruses all meet up around a campfire at the beginning and conspiratorially develop their plan of attack, complete with evil cackling. They’re a pretty nasty bunch! Luckily the white corpuscles have laser guns.

My question is more focused on the future of Virology. I’ve always been interested in how scientific knowledge ‘grows’, it’s always exciting to look at the history and see how it is rarely a linear accumulation of knowledge, but rather it is often a battle of competing theories and ideas with different schools of thought vying for followers and influence, until eventually over time and with enough evidence, an accepted theory arises. And then sometimes there’s a radical breakthrough that reshapes everything. Do you think that in the next 50-years there will be such a radical breakthrough regarding virology/immunology? Some sort of new technology or discovery that will challenge what we currently hold to be true and reshape the field? Thanks, as always.

Ian

Mitchell writes:

Check this out:

http://www.rdmag.com/News/2011/04/Energy-Solar-Energy-Solar-Power-Goes-Viral/

-Mitchell

Amit writes:

I am a pursuing research in immunology, working on immunological aspect of virus infection. I am lucky to discover your podcasts recently. I have listened some epidoses and found it really interesting. You guys are amazing and make science real fun. I can only imagine the effort you guys must be putting to make these episodes as I also came to know that there are TWIM and TWIP as well. I heard all of your TWIM episodes.Thanks for all the efforts from you guys. I though want to add here that it will be icing on the cake for me and people working in immunology if you pick some papers with immunological aspects. You can add one infection immunologist to your group to discuss immunological aspects of microbial infections as well. It is just a suggestion and not to say that I don’t enjoy your podcasts in present form. Once again, thanks for your efforts.

Best regards,

Amit

Leo writes:

Although I am an Electrical Engineer and my work is to develop Cellular Phones, I have been always interested in Biochemistry, Toxicology and Virology. Actually, I have listened all your episodes, and you both make me think that in my next life, I would study to become a virologist. J

One of my favorite hobbies is to run simulations on the computer about protein folding, I recommend you to take a look to the project Folding@Home if, you have not reviewed this project recently.

I am writing you because I was looking for information about our tiny friend The Tasmanian Devil, after I watched a TV show about Australia/Tasmania, and they commented about this kind of transmissible cancer which is

Killing the whole population of TasDevils. Some reports consider that if not controlled, all the Devils will be finished by 2030 or so.

I would like to know if you may have some time to cover this disease in one of your future episodes. Do we know if its originator is a virus ?

Thank you very much in advance, thanks for your achievements on divulgation of sciences !!!

http://www.tassiedevil.com.au

Leo

Dave writes:

I came across this article on the possible future role of mathematics in virology: http://www.newstatesman.com/ideas/2011/04/viruses-essay-pattern I have heard you and your panel members mention in past episodes that many viruses are icosahedral. However, I don’t recall any discussion of the possibility of attacking viruses by modifying their geometry. Is the stuff on viruses mentioned in this article for real or is this just wild speculation? I’d be interested in your thoughts coming from the perspective of a virologist.

Dave

Stephanie writes:

In TWIV #124, Dr. McFadden says that pox viruses have the ability to steal genes from the host. In fact, this is precisely how they acquired the genes similar to those for MHC class 1 and different cytokine receptors that were discussed in the first part of the podcast. However, if pox virus doesn’t need to go into the nucleus to replicate because it carries/makes all of its own replication machinery, how and when does this pick-up of cellular genes occur?

Stephanie

see: http://www.izs.it/vet_italiana/2011/47_2/147.pdf

TWiV 140

from @Lafrenchfille on Twitter:

French listen to your very cool podcast. So I can confirm, “Mimi” is french !

Peter writes:

Regarding the podcasting advice from the fellow in Israel.

Explain stuff in the beginning of the episode?

That’s what the pause button and google are for.

Edit or don’t edit the episodes?

Don’t! It’s more time wasted and the collegial feel will disappear. At the moment the twiv experience is like were are sitting at the table in Vincent’s office.

In fact, I was in hospital recovering from acute pancreatitis when I listened to CSI Virology (episode 110) on speaker on my iPhone. Whilst listening, every now and then I would laugh or make audible comment. The nurses in the station outside my room door were wondering ‘Who is this patient who is having conversations with these American doctors / Scientists about viruses and arsenic eating bacteria? They even contrived to send a senior nurse into my room to try and figure out what was going on.

Thus, the podcast is so conversational it fooled them into thinking I was in on some sort of conference call, and THAT is what makes your podcasts stand well out from the crowd (..as well as the content of course).

I did not enlighten them as to what was going on, but vicariously enjoyed being a ‘man of mystery’ as they speculated on who I could be.<grin>

peter

sydney australia

Casey writes:

Professors,

I am glad that TWiV evolved into TWiP, which evolved into TWiM. I love listening to all three when I am walking, since I cannot run due to a knee injury during a half-marathon. No worries about safety, I walk on a no-vehicle crossing trail at a park.

I just listened to the TWIM episode regarding the Smallpox Vaccine and military members. As a member of the Army Medical Service Corps and also having received the Smallpox vaccine, I can tell you a lot a Soldiers do not fully understand the Vaccine. When I received my vaccine, we were herded into a room. A nurse stood in the front and briefed us on the numerous vaccines we were to receive along with the whole process for medical clearance station at the Soldiers’ Readiness Program (SRP). The SRP is a program to ensure Soldiers are medically ready to deploy to various combat zones, in my case Iraq (e-Rock, not i-Rack). This occurs usually in a day with many other training events. The focus of the Soldiers can be very low during this process. Although they briefed us on the hazards of the smallpox vaccine, it is easy to understand that all of the information was glossed over by many of the Soldiers. Nearly all Soldiers do not have the microbiology understanding as you and I do. Therefore, they do not understand that touching the site once and lightly can spread the virus.

The vaccine site takes about 40 days to fully heal, with the infectious scab falling off at around Day 30. Mine fell off at Day 35. Throughout this time, Soldiers can forgot the information they have received and can forget that the scab is infectious. This is especially true as most people understand that a scab in general is part of the healing process and is not infectious. Furthermore, the site can be very itchy for some. I remember just wanting to scratch it because it was so bad at times. The information provided to us with the vaccine is to change the band-aid daily. When taking a shower, do not dry the site with a towel, rather let it air dry and then cover it with a new band-aid. Any contact such as wrestling, hand-to-hand combat, or other forms of physical contact are prohibited until the scab falls off.

I must admit that I am 100% a nerd. Figuring that I would receive the vaccine once in my life, I decided to document the site every day. I recorded 42 days of the vaccine process with photos each day. I attached photos of my arm (no HIPAA violation, of course) at Day 4, 11, 14 (with the sunken center), 20, 35 (when the scab fell off), and 36. I do apologize for the clarity of the images. I wish I would have had an object to judge the size of the infection, but I was taking these photos myself.

Thank you and keep up the good work,

Casey

[I posted Casey’s photos at Virus talk – vrr]

Lance writes:

Dear Vincent Alan and Rich,

I would like to mildly disagree with you on hepatitis B vaccine as discussed on TWiV 130. The risk of an infant aquiring hepatitis B IF they are in a low risk population is extremely low, and therefore their chance of passing it on also very low indeed. In fact the chance is so low that in some countries (such as the UK where I come from) the relevant authorities don’t recommend routine hepatitis B vaccination. See below for two links to the UK department of health recommendations on routine vaccination, which don’t include hepatitis B. The public health benefit of hepatitis B vaccine in low risk populations is very different from vaccines such as measles, polio and influenza which are much more likely to occur and to be transmitted (e.g. 14 500 cases of measles in France in the last three years according to today’s ProMED mail). I felt that you didn’t do full justice to the difference between hepatitis B and some of the more infectious childhood illnesses. All that only applies to low risk populations, and in the UK people from areas or communities of high prevalence or for some other reason at high risk are vaccinated against and screened for hepatitis B. Indeed in my own practice (infectious diseases) we do alot of blood borne virus work and vaccinate alot in groups such as HIV+, HCV+, etc.

Having said that, my own view would actually be that if the public health authorities have taken a decision that universal hepatitis B vaccine should be used, then physicians and the public should abide by that decision. Certainly if I had children I would jump at the chance to have them vaccinated against hepatitis B if the opportunity was there. I just wanted to make the point that someone in a low risk group refusing hepatitis B vaccine is not in the same league as, for example, refusing MMR, even if the reason is unfounded.

UK dept of health links:

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_108820.pdf

http://www.nhs.uk/Planners/vaccinations/Pages/Vaccinationchecklist.aspx

Keep up the great work, I really enjoying all your podcasts and I continue to learn alot.

Thanks,

Lance

Wellcome Trust Clinical Postdoctoral Fellow

www.liv.ac.uk/braininfections

[rationale for vaccinating for hep B at birth: http://pediatrics.about.com/od/weeklyquestion/a/0408_hepb_vac.htm]

Komal writes:

I had a question regarding TWiV episode 131, “A REOstat for cancer”. Can reovirus therapy also be effective against hematologic cancers, like leukemias, or would it only work for solid tumors?

Komal
Columbia University, Class of 2012

Shreela writes:

I am curious to know if scientific reporting also brings into picture a vast majority of ?public engagement? wherein a variety of stakeholders can participate in a discourse in a way that the plurality of views notifies research priorities and scientific policies. Also does the lack of proper scientific reporting advocate the mushrooming of cafes scientifiques, where no scientists are really involved, but it is the lay persons who have a deep desire to know more about the science, discuss amongst themselves. Is the aim achieved in the end? That of getting erudite knowledge of science and technology into people!

Haejung writes:

When a new virus emerges, when do governments decide to intervene (e.g. developing a vaccine against it)? Is there a specified mortality rate or number of infected people that is used as criterion?

Adriana writes:

While it is clear that phylogenetic analyses of HIV can be extremely useful in solving criminal cases of sexual crimes (TWiV110), is it fair to consider someone with the disease a ?deadly weapon?? Criminalization of HIV potentially places those who test positive at risk for further discrimination and social prejudice. By classifying a subset of the population as inherently dangerous, what kinds of societal impacts would this have on disease control? Would HIV positive individuals decrease or increase?

TWiV 139

Norma writes:

Some time ago I emailed you about transcribing an episode of TWiV and have finally finished episode 60. Let me join the chorus of appreciative listeners in praise for your podcast! I’ve learned a lot from it I was inspired by your generosity to give something back so please find attached a word document with a transcript of one of the TWiV 101’s. I do work in science but not specifically in science writing so I hope it doesn’t have too many mistakes.

Thanks again to you and your fellow TWiVists.

Best regards,

Norma

[TWiV transcripts are at www.twiv.tv/transcripts]

Peter writes:

After listening to Alen’s pick of The Artful Amoeba, I went to the site and noticed something that you guys may have missed. The diagram showing amoeba structures has an organelle labelled “Plans for world domination”.

What a cracker!

great pick!

keep up the good work etc etc.

peter

Sydney

PS.

I am also going to steal Dick’s di-hydroxy-chickenwire line that he quipped on one of the twips.

John writes:

Dear Doctors,

Thanks for reading my question. I’m glad you guys seemed at least somewhat interested in covering the near future of virology. I think one reason it would be a particularly interesting discussion is that while young at heart the hosts are generally experienced scientists and in one case has moved to emeritus status. This gives a unique perspective as to what the next generation of the field may be looking towards. Unfortunately in the popular media most discussion of the future of science is either at the extreme speculative level of 50 years in the future or silly commercial applications of basic science.

While that’s good for fiction it’s not as interesting as looking at what scientists think are important issues or research opportunities that will or should be explored in the near to mid term future.

Thanks again for a wonderful series of podcasts.

John

PS Yes I am part of the Alan Dove Fan Club.

Eric writes:

I discovered twiv not long ago, and have suffered a “virulent” (excuse the pun) case of virology-mania ever since. From what I have heard so far on twiv, I am not alone in this. That being the case, I can only hope my questions are not victims of severe repetition by other submissions to twiv. Being merely an ill-informed yet viciously curious teenager, I can’t help but ask the obvious questions. Anyways, in my limited (so far) research, it has come to my attention that the exact origin of our tiny infectious friends are as of yet, unknown. According to my findings, the primary speculations are as follows:

1. Viruses arose from non living matter, distinct yet parallel to other forms of life.

2. They are the result of more complex life forms, having become a sort of parasite to host cells, and losing much of their functions as a result.

3. Arose as parts of cell genomes and aquired the ability to separate from the host and infect others.

Why is this so? How is that after several hundred years of scientific breakthroughs within microbiology, that we still cannot pinpoint the orgin of viruses? Is this one of the irrelevant questions, best left to Abiogenisis? If you could touch on these 3 speculations a little, and perhaps introduce your own, it would be much appreciated.

As I said before, my scientific knowledge is limited, however my newfound appreciation and excitement for this field is not. I find it astounding that such an amazing world is hiding right under our noses, and the average person only goes as far as where and when the next flu shot can be obtained. I am starting my first college classes in the fall, and I have a feeling that I will not regret my choice in choosing Biology as my major, thanks in part to twiv. Keep up the great work, Dr.

-Eric

Benjamin writes:

Dear Professors and Allan,

I’m a recent Communications graduate from the University of Washington. In my last quarter of school I discovered TWiV and I realized that I had gone and earned the wrong degree. I enjoyed creating photos and writing marketing copy but I have found, thanks in part to Vincent’s triad of podcasts, that microbiology is what I really should have gone to school for. Unfortunately, I’m now sitting here with a degree in a field that is saturated, and even the odd internship at the local public relations or marketing firm is next to impossible to snag thanks to the down economy and an extremely competitive market.

What are my options as a non-science degree holder to at least associate myself with a research or laboratory environment? I’m 24 years old with zero debt and a decent GPA so reentering school isn’t out of the question, but my old adviser and several trusted sources have been trying to dissuade me from attempting to earn a postbac. Are there options for someone trained in communications to work with companies involved in microbiology that don’t involve being a pharmaceutical sales representative? Should attempt pursuing a microbiology postbac in spite of my people’s advise against doing so? Are there other options or avenues that I just have not considered?

I know I’m asking a lot and I would appreciate any feedback. Even if you pass over my email I want to let you guys know that I appreciate what you have done to make advanced science accessible to the odd photographer. I’ve even managed to hook a few of my friends. This democratization of information that you are spearheading is really a wonderful and exciting thing.

Thanks Again,

Benjamin

MisoStudios.Com

Ben writes:

I noticed that after being badgered by another listener over your use of Fahrenheit temperatures, you’ve been having fun describing your inability to convert between the two. Now, obviously, you know the formula x°C = 5/9 × (y – 32)°F, but I agree that this isn’t really easy to handle in your head. A quick and dirty way to approximate the conversion is to use guideposts at increments of 10°C. Obviously, 32°F = 0°C, but since a Fahrenheit degree is 5/9 of a Celsius degree, every ∆T of 10°C is equal to 18°F. So here’s a list of guideposts to memorize:

-20°C = -4°F

-10°C = 14°F

0°C = 32°F

10°C = 50°F

20°C = 68°F

30°C = 86°F

40°C = 104°F

I bolded 10°C because 50°F is a nice round number that can serve as a starting point in case you forget the rest (remembering 50 + 18 = 68 is pretty easy if you don’t remember 20°C = 68°F).

After setting forth those guideposts, the next step is an approximation. The 9:5 Fahrenheit to Celsius ratio is about a 2:1 ratio, so if you double the deviation from the Celsius guidepost or halve the deviation from the Fahrenheit guidepost, you won’t produce a huge error. For instance, taking 15°C (59°F) and figuring that 10°C equals 50°F and adding 10°F for the extra 5°C, you get 60°F, which is only 1°F off.

Now obviously it’s a bit trickier going the opposite direction, since the guideposts in Fahrenheit aren’t multiples of 10, but for instance 90°F is closest to 86°F, meaning that you start with 30°C and add 2°C for the extra 4°F to get to 90°F, leaving you with 32°C (exact conversion is 32.22222…°C).

After that initial guidepost memorization, I’ve found it much easier to give a rough ballpark conversion of temperature on the fly. Knowing it has also made the Celsius temperature system more intuitive to this American who was raised entirely on Fahrenheit until I had to use Celsius in science classes. I find there’s generally a bit of a value-added to knowing what Celsius means intuitively rather than merely as another number to plug into your experimental equations.

Hope this is helpful,

Ben

TWiV 137

Alex writes:

Although I’m sure there’s a good reason to disqualify this possibility, why can’t HCV be a human specific pathogen that transferred over to dogs? You don’t specifically mention this possibility, so I’m genuinely curious.

Chris writes:

Dear Professors,

I love the TWiV, TWiP and TWiM podcasts because they are entertaining and I learn so much (even though I’ve only taken one biology course in my life). I enjoy listening to all of them as I garden.

It is spring time and the tulips in my yard are starting to get their color. Here in the Maritime Northwest I do not dig up the bulbs each year, but let them stay in the ground. I have some that have lasted for twelve years, and others I have replaced over the years. One reason why some tulips die out also makes them very interesting looking their last season or so:

http://en.wikipedia.org/wiki/Tulip_breaking_virus

This virus is apparently responsible for the insanity surrounding tulips in Holland during the 17th century. Though now there are varieties that are bred to be like that, http://hyg.ipm.illinois.edu/pastpest/200811b.html . Which is why in my first year of growing tulips in my present garden I did not know if the yellow and red tulip in the attached photo was already infected, or just a bulb mix-up in my order of over a hundred bulbs.

If you have time this spring, or next year, it would be an interesting spring time TWiV subject.

Have you seen the tweets from the Pathogen Posse, http://pathogenposse.tumblr.com/ ? I don’t tweet, but they seemed to have picked up a hint from the Bronx Zoo Python, and I read about them here:

http://shotofprevention.com/2011/04/05/a-new-host-for-a-persistent-virus/

Thank you,

Chris

Seattle, WA

[Chris sent this photo of tulips]

Tim writes:

Vincent, et al.:

I enjoyed listening to your latest podcast, twiv 128, with the exception of Alan’s horrendous comment about eating endangered mountain gorillas. I also especially enjoyed your combination of cohosts (co-commentators?). One thing that I like about twiv is that you take the time sometimes to research the show subjects and the subjects posed by your readers in the letters section. I guess I still like to see people do their homework! Since I just dissed Alan, I want to note that it’s obvious that Alan does his homework every week, and the show benefits.

A question has been bugging me for some time, and having recently viewed the NIH conference on the ” State of Knowledge Workshop: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Research, and after watching the antagonistic exchange between Dr. John Coffin and Dr. Judy Mikovits, I was hoping you might discuss this subject. Here it is:

http://www.youtube.com/watch?v=Dktu4RR5QEU&feature=player_embedded#at=223

(the critical point in the video is about 8 minutes in)

Does the federal government or the institutions that employ virologists (and other highly specialized scientists dependent on outside funding ever get training in interpersonal communication/conflict resolution skills? If not, why not?

The apparent lack of prior communication between two of the most important scientists involved in XMRV research baffles me, especially since at least one of them is spending taxpayer dollars. However I want to stay out of the XMRV realm here; it just serves as a good example of this type of lack of communication/conflict (and it just happened to be very public). The history of science is dotted with egotistical conflicts among noted scientists, many times to the detriment of the process. I suspect it’s partially due to the fact that everybody is often scrambling for funding from the same pot of money, and ???. I have worked for many large organizations (but none so large as the federal or a state government), and most of them have always provided training on communication skills – which helps – even the reluctant pupils.

As an added note — I have a background as a scientist.

Thanks for putting in the time you do on this program.

Tim

Fort Collins, Colorado

Kevin writes:

Have you guys seen these gorgeous microscopic photos of various drinks before?

http://www.letscolourproject.com/blog/2011/03/cocktails-through-the-microscope/

http://micro.magnet.fsu.edu/cocktails/index.html

I think I’m going to buy some tequila:

http://micro.magnet.fsu.edu/cocktails/pages/tequila.html

To keep this on topic for TWiV or TWiP, what kind of microorganisms threaten our beloved agave population?

Are there any interesting immune system tricks that flowering plants use to encourage pollination but restrict parasitism?

Kevin

Santa Barbara, CA

TWiV 136

Valerie writes:

What are the implications of the new gag sequences the WPI has been publishing for the debate about XMRV? As of May 21:

http://www.ncbi.nlm.nih.gov/nuccore/JF907633.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907634.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907641.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907643.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907644.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907645.1

http://www.ncbi.nlm.nih.gov/nuccore/JF907646.1

Explicable as lab contaminants? Explicable as lab recombinants?

I’d really, really appreciate your insights about how these sequences might affect the debate.

Thanks

Joshua writes:

I think that anyone interested in XMRV should be familiar with previous episodes of scientific controversy, and a great introduction is Nobel Prize winner Irving Langmuir’s great talk entitled “Pathological Science”:

http://www.cs.princeton.edu/~ken/Langmuir/langmuir.htm

The lessons he learned in 1954 are still completely valid today, and far less emotional to learn from.

I also think anyone who wants to report on XMRV should read Puliter Prize winner Gary Taubes’s wonderful book “Bad Science” (which covers the cold fusion fiasco of 1989). As above, Virologists can learn from the mistakes and successes of Physicists from 20 years ago.

http://www.amazon.com/Bad-Science-Short-Weird-Fusion/dp/0394584562

Love your podcast.

Joshua

Lance writes:

I have just read your blog post on the recombination of XMRV, which is fascinating in itself as well as having implications for the continued study of XMRV as a human pathogen.

I have two questions for you on this subject.

1). How did this recombination event arise? As I understand it these two viruses exist only as integrated provirus and pre-XMRV-1 is replication deficient. Does that mean the “new” virus (XMRV) was generated by the action of the pre-XMRV-2 pol gene on pre-XMRV-1 genome, for example? I don’t know enough about XMRV replication, but a discussion of this on TWiV would be great to hear.

2). What implications does this have for xeno-transplantation? Could you speculate on the potential for the introduction of a new retrovirus through a xeno-transplant to cause a replication deficient hERV for example to become replication competent? Or for a novel virus to be generated?

Many thanks again for all the great work and the growing collection of excellent podcasts. What will be next?!

Lance

Tate writes:

I have a question about XMRV contamination, with this argument also getting a lot of traction in the CFS patient forums. The question involves exactly what constitutes a distinct virus? Some patients and apparently the WPI are claiming that the sequences found by Alter/Lo are simply ‘variants’ of XMRV instead of being distinct from XMRV. Lots of discussion involves mentioning the sequence similarity of XMRV to Alter/Lo’s PMLV being around 96% or so whereas variants of other viruses that are considered to be the same virus can be 80% (random number) or less. I think I might have figured it out (vaguely) and it has to do with how the sequences cluster on a phylogenetic tree but if you would be willing to discuss this it would probably help a lot of people understand the issue a little clearer.

Thank you very much for all the time you have spent following and explaining the issue, it has helped very much to have a reasoned viewpoint on the matter.

Thanks again,

Tate

Marcia writes:

1. If the (XMRV positive) results are due to tests picking up widespread contamination, why aren’t results always 100% positive?

2. If contamination is so widespread, how do you account for study results where no XMRV was found?

3. If WPI says they did not use the contaminated line, in a new laboratory, and have been testing weekly to guard against contamination, what else could they reasonably have done to prevent the alleged problem?

4. Regarding the subsequent study that didn’t show positive for the explicit variety of XMRV referred to in the Oct 2009 study, but did turn up more than one closely-related virus, shouldn’t subsequent studies be looking for those related viruses in the same way HIV testing looks for multiple HIV variants?

5. If the virus is difficult to find in blood, but easier to find in tissue biopsies, why aren’t researchers looking more at tissue biopsies? I don’t think it would be difficult to find volunteers.

6. Maybe this is too obvious an idea, but given all the controversy, shouldn’t there be at least *one* follow-on study that tries to duplicate WPI’s methods exactly, to see what happens? I got through on the phone once to Dr Mikovits, surely it wouldn’t be that difficult for a researcher to call up and ask to meet with her and/or some of the other researchers there to understand their methods better.

7. What do you make of the handful of ME/CFS patients whose condition has improved on anti-retrovirals?

Nicola writes:

Dear TWiV guys,

As perhaps you know Judy Mikovits claimed for some time that she had sequence diversity showing that the viruses isolated from CFS patients were consistent with an infectious virus. Now that she has published a number of sequences in GenBank, she appears to have dropped this claim, as it does not feature in her reply to Science. Now she is saying in this reply that she has shown that patients have antibody diversity which proves that they are mounting an immune response to a diverse group of viruses with MLV ancestry.

From Dr. Mikovits’ letter:

This can also not in any way explain the Env antibodies demonstrated in patient plasma in Lombardi et al. The reactivity demonstrated to Spleen Focus Forming Virus (SFFV) Env was competed by the rat monoclonal antibody which detects all known xenotropic, polytropic and ecotropic MLVs. This again suggests that we have, in fact, detected more than one strain of human gamma retroviruses in these patient samples. Clearly data presented in Lombardi et al. where samples were PCR negative but Western blot positive, using the 7C10 antibody, further support the notion of a family of gammaretroviruses.

I have two questions. Does this constitute evidence of a diverse group of viruses? Could these be cross-reactive antibodies or antibodies being made by an overactive immune system to a nonexistent threat?

Also from her letter:

Moreover, data presented in Lombardi et al. suggested additional strains of gammaretroviruses and viral Gag proteins could be directly immunoprecipitated from the blood of patients supporting a finding that additional strains of HGRV were isolated.

Does the presence of these viral gag proteins constitute evidence of infection, or could they just be present due to contamination? (I think there was more discussion of viral proteins in the original Science paper.)

Personally, I think XMRV is dead as an infectious human virus. However, I think these are still interesting questions. I read Dr. Mikovits’ letter carefully, and these were the two pieces of evidence that remain as questions in my mind.

I am very grateful for all the work that especially you Vincent have done to explain XMRV research. You guys are great fun, and I wish I had more energy to devote to TWiV. I have listened to quite a few non-XMRV podcasts and have learned a lot this way from all four of you, and from your guests. Rich, if I ever get better, it is possible that you will find me knocking on your door asking to wash dishes. I’m not kidding.

Thanks again guys,

Nicola

(CFS patient for 28 years)

Dr. Mikovits’reply to science:

http://www.wpinstitute.org/news/docs/FinalreplytoScienceWPI.pdf

Raihan writes:

Hello strange voices I hear while riding to work,

I would love to propose the following link as a listener Pick of the Week; http://www.youtube.com/watch?v=19KkFCQz8WQ.
Understanding the backlog of emails you guys have, I would anticipate that this would have been already picked, but I’m trying my luck anyway.
The video link is a TED talk about the eradication of Polio virus by Bruce Aylward titled: How we’ll stop polio for good. The video is absolutely riveting.
The pictures that Bruce shows in this talk are like scenes re-lived from another one of your previous picks of the week, Smallpox- the Death of a Disease: The Inside Story of Eradicating a Worldwide Killer.

After watching this video, I can sense that the eradication of this disease is very near; let’s hope that that day comes real soon and Prof Racaniello will be out of a job and will be able to dedicate all his time for TWiV, TWiP and TWiM.

Keep up the amazing work guys,

Your humble parasite
Raihan from Singapore

TWiV 135

Michael writes:

I had previously wondered why the technology discussed on episode “Barking Up the Right Tre” (in which an engineered recombinase has been shown to remove HIV from the genome) couldn’t be similarly used in HPV. I know that a Cre has been used to integrate HPV into cells. However, when I asked Prof. Silverstein about this technology, he indicated that HPV doesn’t integrate predictably and that there is limited clonal expansion. Can you please explain how this virus infects cells so reliably in the transition zone between the endocervix and ectocervix and yet a recombinase cannot be targeted to these (assuming you could get the Cre into the cell, which I realize is maybe the hardest part for both Tre and Cre)???

Additionally, is it fair to think that HPV in cervical cancer is analogous to APC in colon cancer, in that they both set off the steps necessary for tumor growth? Is there any commonality with the other steps (myc? B-raf? K-ras) seen in cervical cancer and/or any order in these changes? Obviously it’s a tough question – how would one even go about trying to understand the order of events if he wanted to know?

Finally, are there any interventions to block E6 and E7 after infection and before tumorigenesis?

Thomas writes:

Hello,

I am a pediatrician in Stoughton, WI and love your show and share your passion for educating “the masses” in whatever corner of the world you are in. Thanks for what you do. I am also passionate about immunizations and would like to clarify some of the points in your recent podcast on HPV (which I thoroughly enjoyed).

1. Pap smears are not routinely recommended at initiation of sexual activity primarily because most adolescent HPV is cleared spontaneously (though we don’t know why). Due to this fact, it has recently been stated by several medical governing bodies that Pap smears do not need to start until females are 21 yrs old.

2. HPV typing is not recommended routinely along with Pap smears for most practices. It is quite a bit more costly than a Pap smear, so what some practices do is if the Pap smear is abnormal, they reflex that specimen to HPV typing. Even HPV typing is not specific because it is a panel of HPV types that includes (I think 13 of ) the most common cancer causing types of HPV (it does include 16 and 18). So, if the reflex HPV testing is positive, that person may get more frequent follow up, if reflex HPV testing is negative they may space out the repeat Pap smear testing.

Hope this helps.

Keep up the good work and the bad jokes.

Thomas Murwin, MD, FAAP

Pediatrics and Adolescent Medicine

Dean Clinic Stoughton

Stoughton, WI

Mark writes:

Hello Vincent and other hosts,

Recurring themes on TWiV are public suspicion against vaccination, decline of infant vaccination, and broader societal effects. I recently heard TWiV #132 wherein you (i.e. third person, plural) speculated that lack of direct or familial awareness of common, preventable diseases is a factor leading to decline in vaccination.

As a listener pick of the week, I nominate the site shotbyshot.org — it has video case studies from people talking about how lack of vaccination hurt family members, friends, or patients who contracted preventable diseases. Take a look. The videos are well done. Be forewarned, many of them are heart breaking.

How did I discover this site? I recently received my decennial booster shot for tetatnus. The administering nurse said that California has an epidemic of pertussis, aka whooping cough. I was given Tdap, a cocktail against tetatus, diptheria, and pertussis. Question about terminology: is it correct to call a vaccination like this, or MMR, trivalent? Or does the term trivalent instead refer to a medicine with three different vaccines in it against a single disease?

I had long thought whooping cough is one of those diseases that scared your parents, and which you never encounter because everyone got vaccinated for it in childhood. I was surprised that it was epidemic here in California — reported cases have increased 100x in the past few years. This is not a California-only issue, there are epidemics in Michigian, Ohio, Florida among other states. Interested listeners can check the CDC’s MMWR report. Here is a link to the PDF for the period ending 5/1/11:http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6017md.htm?s_cid=mm6017md_w — open it and search for pertussis in Table II. You will find regional and state level reporting.

Via Google I found that California’s State Legislature added “personal belief” as a reason for exemption from mandatory vaccination. Opinion and myth trump science. The only comment I will make on California’s elected officials and their policy is that they mandate a higher level of care my cocker spaniels, via mandatory vaccinations against rabies and other disease, than is required for school age children. Maybe this is why some call California the “epicenter of the anti-vaccine movement.”

Keep up the good work with all three of your podcasts. Please, before launching another podcast, invent the 25 hour day to help listeners find time for all your great content.

Mark

TWiV 134

Kristopher writes:

Dear TWIV,

As a developmental biologist and post-doc, I greatly enjoy your show which gives me both information and distraction from pipetting small volumes from one tube to another in the lab. Recently, my lab enjoyment was cut short by a week by a long bout of viral gastroenteritis with a trip to the hospital – an annual to bi-annual experience that I thought I would miss this year (D’oh). I think Vincent mentioned that there was going to an episode on the norovirus – I hope it is still on the to do list. I would like to learn more about “name of my pain,” the description stomach flu doesn’t do it justice… Seriously though, I always dread this disease and sure others do – although it is not responsible for large numbers of deaths, it causes a lot of suffering and a large percentage of the population always comes down with it.

Keep up the great work,

Kristopher

University of Michigan

Alexander writes:

Dear Hosts,

I have been listening to your show and truly treasure every episode; thank you. I’ve learned more from your show, and the resulting wikipedia safaris that it has inspired, than I have in college science classes.

Forgive the following sycophantic sentence, but it seems to me that people in your field are doing some of the best work to help our fellow man. With that in mind, a goal of mine is to assist in whatever small way I can while at the same time carving out a modest career; you see, I am 29 years old and have never completed college (I pay my own way, but this means I have been paying for a long time). My question is thus: is it too late to realistically pursue this path and be an asset to the field, or are my energies better directed elsewhere? College must be completed either way if I am ever to climb the ladder, so why not direct my efforts and funds towards something that has the possibility of contributing towards real good in this world?

Because of the recovering economy (hopefully this will continue!), I have found myself in a financial position whereupon I can finally seriously finish college within less than 2 years. I do have an interest in microbiology (obviously, since I listen to Twiv, twip, and twim), but I fear that this is a field one must get into right out of high school, not at 29; what are your thoughts on this? I gave up on Med School long ago due to financial obligation to my family, my ever-increasing age, and my own lack of funds, but if I could be an asset to ongoing research even at my age that might be even better. I respect your opinions, and would like to hear them if you would be so kind as give me your time.

As I’m sure time for letters on your podcast is precious and there are other, more worthy, questions to be showcased (as evidenced by the caliber of previous letters read), if you could at least give me a reply via email with your council, I would greatly appreciate it. I have been told that I am better off doing something else, but this would be the first time I consulted with someone in the actual field.

As an aside, when is Twip going to go weekly? It doesn’t seem like there is much of a danger of running out of parasites to enlighten us about; is it mostly an issue of time? That would be completely understandable, but alas.

I greatly appreciate you all for providing these podcasts for us; it helps get a laborer though his day.

Thank you for your time,

-Alexander

Phoenix, AZ

Geoffrey writes:

Gentlemen:

In regards to your question of whether or not bacteriophages infect humans in episode 112. I may be a little late but here is my view: it depends on your definition of human as an organism.

As a person learning about permaculture and trying to start a permaculture-based farm, I have to constantly think about the features of my land from geology to microbes to plants to insects to livestock to how to construct and power my buildings and tools. I may not be very good at it yet but I try to think both on the organismal and meta-organismal level knowing that many of my organisms will not function well (or at all) if they don’t have the support of the meta-organism. Examples of this are nitrogen-fixing plants, parasite loads in livestock (an humans), multiple fish species in ponds to make proper use of food resources, trees and shrubs to shade other plants that don’t like much direct sun, etc.

Thus, my answer is that bacteriophage probably don’t infect the human organism but they do infect the human meta-organism (which comprises the human and a plethora of dynamic micro-organisms). Here, however, is where it gets tricky. If the human meta-organism picks up a strain of bacteriophage that affects one of the semi-symbiotic bacteria inhabiting the human (such as lacto-bacilli in the human gut), then a support symbiote could be wiped out temporarily. This could, in turn, produce a down-turn in human biological functioning which I would interpret as “being sick”. Thus a bacteriophage infection could make a human sick without actually infecting the host human organism. I know that I suffer from periodic changes in gastro-intestinal functioning that do not seem to correlate well with my food intake. Could these be due to changes in GI-tract bacteriomes? I certainly feel sick when it happens. As studies of the human bacteriome and virome proceed, it will be interesting to see how our understanding of these interactions develop.

I would also add that viruses, being the tricky little things that they are, have a lot of resources of which we are still unaware. I would not be at all surprised to find out that, in the vast operations of the human meta-organism, there aren’t some bacteriophages that either reside in or are stored by human and bacterial cells as another layer of bacterial defense. Certainly, we have seen that some hymenoptera (especially parasitic wasps) have incorporated viruses into their gene structure which they then replicate and incorporate into their egg coverings. These viruses, then, “hide” the eggs from the host caterpillar’s immune system. There are other instances where bacteria and algae are accumulated (sometimes even maternally transmitted) and utilized by host organisms in a symbiotic relationship. I see no reason to assume that such a situation hasn’t arisen where some cells and micro-organisms “host”specific viruses and control their replication and dispersion. As such, what is the term for such a residence and even possible replication? Infection isn’t necessarily the right word or is it? How would such a situation be differentiated from, for instance, quiescent HIV infection?

Come to think of it, viral symbiosis, its implications, and biological applications would make a great episode or three for TWIV.

Keep up the good work.

Thanks,

Geoffrey

Chris writes:

Hi TWiV Team:

I’m a medical and graduate student interest in virology and love the podcast.

The Editor-in-Chief of Virology Journal has just retracted an article and apologized effusively on the journal’s home page. I wondered what sort of paper would warrant that sort of mea culpa. Then, I read it. Here’s the link to the .PDF

http://www.virologyj.com/content/pdf/1743-422X-7-169.pdf

…and the apology: http://www.virologyj.com/content/7/1/169/comments#424680

Best line in the article: “One final consideration that one might have is whether the illness was inflicted by a demon or devil.”

Thanks,

Chris

TWiV 133

Welkin Johnson answered John’s question from TWiV 132 about TRIM5a selection:

I get this question a lot, but never as well thought out as this. The listener clearly understands population dynamics better than the average virologist! However, I don’t think ERV can possibly be a major selective force working on Trim5alpha. First, any ERV sequence present in the genome must have gotten past Trim5alpha in the first place, so would have been preselected for resistance to the major allele(s) present in it’s host. Second, most ERV probably go through a powerful selective filter for nonpathogenesis or nonfunctionality at the time of acquisition – if not, the first individual(s) to carry the ERV would suffer decreased fitness and be less likely to pass the ERV on as a genetic element to the next generation. Random mutations and silencing by methylation are more likely to “deal” with the ERV in a short evolutionary time period, and more probable than a chance match between ERV target and Trim5 alleles.

The scenario posed by the listener in which different ERV select for maintenance of different Trim5 variants could work, but I suspect the impact of exogenous retroviral spread would outweigh by orders of magnitude the effects of rare activation of ERV, especially given these two points. To put it another way, a retroviral epidemic sweeping through a population of related individuals should have a much stronger effect than a rarely activated ERV appearing generations apart. However, the scenario might apply in the specific case where expression of the ERV had taken on a cellular function, with Trim5 playing the role of a regulatory protein – but that would be an unlikely exception.

Welkin Johnson

Microbiology and Mol. Genetics

Harvard Medical School

Jesse writes:

Hello,

Thank you so much for your podcast! I am currently practicing as a small animal veterinarian while also studying toward a masters of public health in the veterinary concentration at the University of Tennessee, Knoxville.

My question is regarding the Wolbachia studies which were discussed in episode #115 (release of W infected mosquitoes). Recent protocols for the treatment of canine heartworm disease suggest pretreatment with doxycycline to kill off the Wolbachia which many of the Dirofilaria immitis larvae harbor. It is thought that Wolbachia may contribute significantly to the inflammatory response post-traditional treatment with Melarsomine. So I wonder, how might the infection of an Aedes mosquito with Wolbachia affect the transmission of this nematode which itself is infected with Wolbachia. Perhaps as was suggested this is an unnatural infection for these mosquitoes so any released populations may die off? Thanks,

Jesse DVM

shammah writes:

http://www.npr.org/2011/04/05/135121451/how-the-pox-epidemic-changed-vaccination-rules?sc=fb&cc=fp

i saw this article on early vaccination attempts. i’m going to bed i’ll read it in the morning. still love your podcast.

Tom writes:

Dear TWiV,

Thanks for the great (as always) episode this on HPV. I am a big fan of the show in general. It’s been wonderfully helpful as a grad student working on a virology (HIV) project, and I recommend it to all my peers. And, I have really enjoyed consuming your weekly picks as well, particularly the book recommendations.

I feel that one important point was omitted during the discussion of the rational of vaccinating men against HPV. In addition to serving as a vector for cervical cancer in women, men are susceptible to anal cancer linked to HPV. Rates of anal cancer are particularly high in at-risk populations like men who have sex with men (JAMA. 1982;247(14):1988.) I don’t know if the cost-benefit analysis has been performed for vaccinating to prevent anal cancer, as it was with cervical cancer. But it is an important point that parents and individual patients should consider when thinking about getting vaccinated against HPV.

Great episode though. The HPV vaccine is such an important accomplishment in modern medicine, and I appreciate you highlighting it. Thanks also to Michelle Ozbun for sharing her insights.

Best,

Tom

MD/PhD student, Mount Sinai School of Medicine

TWiV 132

Maki writes:

To the hosts of TWiV (I find the fact that you’re called “hosts” of a virology-centered show endlessly amusing.):

Having been the weird kid reading Virus Hunters on the playground in elementary school, I’ve had an intense love for virology and epidemiology for as long as I can remember. Fast forward a decade and I find myself as a post-bac research tech with my mind drifting toward the possibility of grad school. I’ve been trying to study on my own in order to focus my brain toward a future of classroom education, but after a demanding day of trying to keep up with advanced-degree level work, it’s hard to crack open a textbook and read about singledoublestrandDNARNAblahblah without my eyes glazing over. Let’s not even get into what happens while reading journals.

I just discovered your podcast last week and since, it’s been a constant source of entertainment (oh yes, I consider it the height of entertainment) during transit and the rote tasks of my day. I want to sincerely thank you for the work you do. I’m eager to listen to the rest of TWiV/ TWiM/ TWiP and I know that you’re going to be great for the advancement of my education. (Heck, you already have been with the first ten podcasts!)

Every day that I arrive at work after listening to you, I feel inspired by the possibilities of research, which can be so demoralizing some days, and ready to throw myself into my own current research, despite it not being in my field of choice. Again, thank you so much. Your insight and knowledge are very, very much appreciated, as is your patience with my verbosity if you’ve made it this far down.

Sincerely,

Maki

The Scripps Research Institute

San Diego, CA

John writes:

Dear TWIVers,

I was just listening to TWIV 122, and this made me think of two somewhat related questions.

First, you discussed a gene involved in innate immunity inside the cell (TRIM-5 alpha), which provides a natural defense against retroviruses, and which has some alleles that have been preserved, more-or-less, across species that diverged millions of years ago. You talked about a bunch of possible explanations, but one you didn’t discuss involved endogenous retroviruses. I am curious if that could explain the preservation of some of these alleles in primates. (I should point out I’m not a biologist, but a computer scientist. So I may be misunderstanding things here.)

The way I imagine this working is that there’s a population of ERVs hiding out in the genes of different species of primates, Some ERVs reawaken pretty regularly, so that in the average individual, it’s not surprising to have the ERV showing up. In those species, the allele of TRIM-5 alpha that protects against them will be really common, because it provides a big fitness advantage. But it seems like there should also be some ERVs that reawaken only much more rarely–perhaps they need a helpful mutation, or some really unlikely sequence of events inside the cell, before they can come back out. And those would support balancing selection between alleles–if you have some ERV that only comes out once per generation, the value of an allele that resists it is based on how common that allele is in the population. If almost everyone else has it, you hardly need it–most likely, the retrovirus will never spread to you, and you’re not at all likely to be the one individual per generation in which the ERV reawakens. The more rare that allele becomes in the population, the higher its fitness value to an individual, and so the more it is selected for–once-per-generation epidemics of some nasty retrovirus should keep some level of the resistance allele in the population. The more rare the events that allow the ERV to come back to life and start spreading again, the more rare you’d expect the allele that provides resistance to it to become, but it seems like that should still keep some level of the allele around. Imagine a once-per-twenty-generations epidemic of something as nasty as HIV sweeping though your population. When that epidemic comes out, the fraction of the population carrying the allele that gives resistance to it will very quickly jump from a small fraction to nearly everyone.

My question is, could this account for some of the preservation of these TRIM-5 alpha alleles across long-separated species? As long as you have the same (or similar) ERV reawakening from time to time in two distant lineages of monkeys, it makes sense you’d have the same (or similar) alleles to provide resistance to that ERV. But this assumes that the ERVs can stick around that long in forms that can replicate under the right circumstances. (It seems like the ERVs could stick around by managing to re-insert themselves into the germline when they manage to come out and trigger another epidemic, after most of the population had lost its resistance.)

Is this at all plausible? The more time I spend writing this out, the more assumptions I find I’m making that I don’t know enough to confirm. That’s the problem with speculating far outside your area of expertise, I guess.

My second question involves a book I want to recommend as a pick of the week, if you haven’t already chosen it. It’s a book published in 1949 called _Earth Abides_, by George R Stewart, in which a sudden epidemic of some unknown thing nearly wipes out the human race, with perhaps one person in a thousand surviving. Reading this around the same time I listened to your discussion in TWIV 122 made me wonder how likely it is that some epidemic could arise that kills that large a fraction of humanity. I know the original population of American Indians was nearly wiped out by disease, though I think it was multiple diseases–Measles, mumps, chicken pox, influenza, smallpox, the whole package all at once. How common is it that a single disease kills 99% of the people who get it, and also spreads easily?

This made me think of HIV, because it’s always seemed to me that if HIV had been spread by casual contact, it would have killed off most of humanity. (The several-year incubation period before it becomes lethal would have kept us from noticing it–who noticed one more flu bug going through the gay communitiy in San Francisco, till people started dying from it years later?) I know there’s some fraction of people that don’t get it (they have a variant coreceptor that keeps the virus from entering, right?) and others that catch the virus but seem to control it indefinitely (from having the right set of MHC molecules to be able to recognize all the HIV mutations that arise in their bodies, I think). Is there a good figure for what fraction of people, total, don’t die of HIV? How common is it historically to see one disease nearly wipe out a whole population?

Thanks for your wonderful podcasts, and for answering my amateur questions.

–John

James writes:

Hey Doctors,

After reading this article I immediately thought of TWIV. Now It looks like there is hope to combine my field of cytogenetics with your field of virology.

http://www.nytimes.com/2011/03/08/science/08obscope.html?_r=1&scp=1&sq=a%20tool%20gives%20a%20new%20view&st=cse

Keep up the great work. I look forward every Monday for a new episode.

-James

Northwestern Memorial Hospital

Human Genetics Laboratory

Cytogenetic Technologist

Shammah writes:

I found your podcast while browsing thru iTunes and i have to say i’m hooked. I have the most boring job but i get to listen to my MP3 player. I have nothing to do with the medical field so some of the stuff is way over my head but it’s fun to learn about viruses, especially the freaky ones. I was wondering if there have been any studies looking at HIV, generic drugs, and resistance; specifically if generic drugs lead to resistance faster. While the FDA and drug manufactures say generic and name brand are bio-equivalent, I have my doubts. I take Zyrtec for allergies and have tried every store brand i could but within 3 days I’m feeling horrible and have to switch back to the expensive, name brand. Since they generic seem not to work for me, I was wondering if the same could be true for generic HIV drugs. While there are only a few generics in the US, third world countries count on them to keep costs low. Thanks and thank you for a wonderful podcast.

shammah

Sarah writes:

I would totally buy a TWiV T-shirt, mug, or tote bag that said “Does a virus shift in the woods?”

🙂

–Sarah

TWiV 131

Ivan writes:

Hello TWIV team,

I am an avid listener to this show, TWIP and now TWIM and this will be the second time I wrote with a question.

We all know about the use of lytic viruses in the treatment of cancers, which can be very promising. I was thinking if there could be another way to use viruses in cancer treatment. If the tumor cells are infected with a modified virus that will promote overexpression of MHC class I proteins then hypothetically the immune system will be stimulated to get rid of the infected cells by CD8 cytotoxicity, NK cells (overexpressed MHC class I) and by the natural proliferation of the virus. I was just wondering if such a treatment is possible? I haven’t seen any research papers describing such a methodology and my knowledge is still not sufficient enough in order to answer this question myself.

Keep up the good work and I’m looking forward for many more future episodes of TWIV.

Regards

Ivan the part time Biomedical student and Electrician (and hopefully future Virologist) from London, UK.

John writes:

Liked the picture with the TWIV 124 with the rabbits. This picture brought back lots of memories. It featured in the Web of Life – A Biology text book in Australia in the 70s. It was proported to be taken on Wardang Island near where i first taught. A small island just off the coast, rabbits had been released onto it, with none of the control measures. Water was extremely limiting especially in the summer. Hence the concentration of rabbits.

It also featured later in the rabbit control story in Australia. In the late 80s trials were run there with another potential disease control measure – calici virus. It was evidentally working well however and before an official release it escaped and did considerable damage to rabbit numbers. I remember hearing that the suspected culprit for aiding and abetting the escape were the local blowflies.

Thanks for the podcasts – gives me both understanding and a few stories with which to embellish my secondary school teaching.

Eric writes:

Hello disembodied voices that come from my iPod while I am passaging my cells.

Recently TWIV has discussed online resources for researchers. The conversation made me think of a very interesting group of sites called the Stack Exchange, which collectively can be found at http://stackexchange.com/

The basic design of these sites is to provide a free place for questions on a variety of subjects to be answered by people in the know. It all started with code monkeys who wanted to build a site where programmers could ask questions and get useful, well thought out answers from other programmers. So you know the site was designed well. The idea was so successful that they’ve adapted their site to be used by many other disciplines. The brilliant kick is that its not a forum. The community votes on the answers given to questions, those answers with the highest scores appear first and foremost underneath the question itself. Also, community members gain reputation based upon their activity on the site and how well their answers are received. So in a way, answers to questions are peer reviewed!

There is a Biology site that is currently in the proposal stage, meaning its ultimate scope has not been fully fleshed out. It needs people to follow the site and mold the final product by suggesting on and off topic questions and rating those that are already there. From what I’ve seen from reading the example questions this site would focus on technical questions pertaining to research. Stack exchange wants specific questions with specific answers. Interesting note, one of the proposed questions was “Is a virus a living being or not?” Strangely, the question hasn’t been shot down yet despite not having a concrete answer. I would encourage people who want to see this site reach the beta phase to register and follow it.

Guess I should end by applauding TWIV. I am a graduate student in microbiology and I found TWIV and virology blog to be an incredible resource for my development as a scientist. I am also broadening my horizons by listening to TWIP and TWIM. You are all inspirations. Plus I got a Drobo out of it so that’s cool.

-Erik-

This is an update to my recent E-mail regarding the stack exchange biology site. The site has moved from the planning phase to the commitment phase. They are looking for people to agree to participate in the beta phase before the site goes live. Unless the site generates enough activity and traffic, at the end of the beta phase it will just die. Anyone who’s interested can check out this long URL below:

http://area51.stackexchange.com/proposals/12502/biology?referrer=dShGsINHqOaJcDcQkP0RAg2

Jose writes:

Hi TWIV crew,

i’m Jose and i’m still a PhD student in Mexico working with innate immunity against dengue virus. This is my second letter to the show, and i’m very thankful for the comments to my doubts in my first letter (TWIV 82).

i’m still a big fan of TWIV since the early episodes.

My letter it’s about some thoughts about all this miRNA stuff, you guys give a wonderful analysis Herpesvirus saimiri paper where i hear that Dr. Racaniello mention a short comment about the HCV virus history.

i forgot all about that until now, i’m in at the NIH making some collaboration experiments at Dr. Steve Whitehead’s lab, were a post doc in the lab next door apparently want to use this miRNA mechanism in a vaccine against WNV, directing the viral RNA to degradation and maybe changing the neurotropism, awesome right!, i just read the Science paper that shows miR-122 as a cellular factor needed for the HCV replication, it ‘s a very interesting paper and make sense with the cell type restriction of HCV, they found 2 possible complementary sequences one in the 5′ and other in the 3′ and apparently the one in the 3′ its less important for the accumulation of HCV RNA (replication, apparently doesn’t affects translation) , i just remember that RIG I ligand in Huh7.5 suppose to be in the 3′ UTR close to this complementary sequence to mR-122 and it’s sequence specific. do you thin k that the recognition of HCV genome by RIG I might be the complex between mR-122 and this sequence?

Maybe thats why the recognition of RNA by RIG I in a sequence specific manner only been clearly described in HCV infection of hepatic cells, in the paper where the PUUC sequence it’s suggested as the ligand of RIG-I, HuH 7.5 cells was used, the structure formed by miR-122 and HCV 5’ UTR may be better ligand for RIG I??

in the paper suggest that the inactivation of miR 122 did’t affect the total protein synthesis by 35S incorporation, suggesting that there is no effect on cell response however, i would like to see the protein synthesis when the complex between viral genome/mR-122 is in the cytoplasm.

i found another related paper that shown that the interferon and rivavirin doesn’t increases the miRNA concentration, but they didn’t really measure the recognition of the genome we don’t really know if the recognition of viral RNA by RIG I might be increased in complex with mR-122.

thank you, keep the wonderful job, and sorry my english still crappy

Matt Evan’s response:

Since Peter Sarnow’s lab first showed that miR-122 directly interacts with the HCV genome to stimulate replicate, a very important question has been how this effect is actually mediated. In their original paper in Science, they showed that translation was not greatly stimulated by miR-122 binding, and after some controversies this has seemed to pan out. Instead miR-122 seems to influence either HCV RNA replication or stability. In fact, a recent paper from the Sarnow lab (Machlin et al, PNAS 2011) has provided some of the keenest insights into this subject. MiR-122 doesn’t only bind with its short ‘seed’ sequence to the two targets near the 5′ end of the positive strand of the HCV genome, but also makes additional contacts at the very 5′ (uncapped) end. They speculated that this may shield this end from nucleases or prevent its detection by RIG-I. Thus I think the actual effect may be the opposite of that suggested by this TWiV listener – miR-122 binding to the 5′-end of the HCV genome may actually shield the 5′ triphosphate from RIG-I surveillance. Sure the poly-UC track in the 3′-end of the HCV genome can strongly stimulate the RIG-I response but the 5′ end may also contribute to this effect. This is probably being furiously investigated in many labs right now.

Christina writes:

Hi,

i’m a neuro grad student and i love twiv. i only wish there were a neuroscience equivalent. maybe someday you will make twin 🙂

i’m writing because i was just thinking about how much i loved mathcamp in high school, and how many other people i know went to some kind of math centric summer school. neuroscience seems to also run lots of summer schools at woods hole or csh or elsewhere. is there a virology equivalent?

Timothy writes:

Vincent et al.:

I’m an avid listener to TWiV, the one who listens at 2X speed! I just wanted to let you know that you inspired me to create my own podcast. I hope you forgive the name similarity to your series, but its so good I couldn’t resist. We are calling it TWiPO for “This Week in Pediatric Oncology.” I pay hommage to you in my opening monologue of the first episode (at timemark ~5:20). We just went live on iTunes today; here is the link:

http://itunes.apple.com/us/podcast/this-week-in-pediatric-oncology/id431855109

Thanks again for all your work with TWiV, TWiM, and TWiP!

Tim

>>>>>>>>>>>>>>>>>>>>>>

Timothy P. Cripe, M.D., Ph.D.

Professor of Pediatrics

Division of Oncology

University of Cincinnati

Cincinnati Children’s Hospital Medical Center

TWiV 130

Suzanne writes:

I know it has nothing to do with viruses and would be a better question for FiB (if he did questions 🙂 But I figure you guys would at least have some idea and know who to ask if you needed to. I’ve been curious for a while about the techniques used in the creation of genetically engineered crops. Is it the same as bio engineers in medicine use? I know these days scientists can do some amazingly precise manipulation of DNA. I also remember hearing that the companies on the agricultural side of it were using older, more random ways of getting new genes into seeds and then growing them to see what works. If so would this make a difference in the outcome? Would it make it more likely that the plants would create proteins that people are allergic to, for instance?

I’m not a conspiracy theorist 🙂 or even anti-GMO. I think it has its place. I’m amazed by some of the stuff that’s going on in medicine. It’s wonderful! But I do remember a decade or so ago when there was a recall on several foods that turned out to contain GE feed corn that people were having fairly severe allergic reactions to. Star something or other. I just have to wonder about anything that we’re going to eat and I haven’t seen any really in-depth discussion of how these things work other than to hear proponents say “Oh, all the dna is digested, it can’t hurt you.” That’s not going to fix any problems we might have dealing with new proteins, is it? And that’s without even getting into the containment problems which is another issue entirely. I won’t bother you with that discussion 🙂

Ooh. I do have a comment on vaccination, though. I do happen to be one of those people who’ve taken advantage of the philosophical exemption for my kids. But *not* for the big childhood diseases, don’t worry. They were caught up on everything required when they started pre-school except for HepB. The HepB vaccine is routinely given to newborns even if their mother tests negative. Even our pediatrician suggested we wait. I don’t feel like I’m putting my kids or anyone else’s kids at very much risk by not vaccinating them for a sexually transmitted disease during their infancy and I’ve been told there are risks associated with vaccinating newborns with undiagnosed heart problems. I just wanted to let you guys know that there are other reasons besides fears of autism for skipping some vaccines. Maybe my judgment of probabilities was off. If so, I guess I’m just lucky things have worked out. But that’s the way it goes a lot of the time. A lot of us are out here doing our best going over things as rationally as we can and we still make mistakes. The CDC is judging probabilities that something will happen to a huge group of people. We sometimes then have to figure out where we’re going to fit individually among the statistics. Maybe it’s not mathematically correct to decide my kids are unlikely to be exposed to something in their first few years of life but there you go.

Love the show. You guys teach me a lot!

—

Suzanne http://hardielander.blogspot.com

“the Dalai Lama and Charlie Brown make me want to stick around”

Erin writes:

I’m sure you guys are receiving a constant slew of complementative emails on a daily basis. I would like to add to them.

I recently finished my first degree at Belmont University here in Nashville, TN. During my time there, I found a passion for science through basic general education courses. Immediately I decided I should take science courses as all my electives in order to see if I enjoyed the tougher ones, but was not able to fit many in. As a student of the humanities, I had little idea of where to start scientifically or what options are available. Since my interests became clear, I began asking everyone about their experiences.

I don’t say all that to tell my story, but rather to let you guys know that you have been one of these very valuable resources. I have had always had a fascination with your areas of expertise, but never really thought about them as a whole. Furthermore, I have struggled with finding a way to really benefit and help other people benefit from both my love of language/culture and science. It actually caused me to feel quite depressed. I felt limited to either medicine or a more global path without scientific involvement. Then comes TWiV.

Your program and topics are the perfect example of how important every area of education, research, and medicine is. The discussion motivates me to continue on this path and gives me assurance that my ultimate goal of helping promote global awareness of such topics is doable and worth working for. I hope I can use my experiences from traveling and language studies (German, Spanish, and Portuguese) to help promote this sort of knowledge globally and to also help be an ambassador between the always adjoined clinical and research related fields.

As for the content of your program, it is the perfect balance of facts, personal experiences, and opinions. If a German student with little scientific background can follow and comprehend such topics through you guys, anyone can! I cannot get enough of the podcast. I have had actually had to set an alarm while listening in order to remind myself that I need to stop and study!

Thanks for taking the time to read this. I am overjoyed to get insight into a completely foreign world as far as science and academics go.

Erin (from Nashville)

Mitchell writes

Hi TWiV people,

I’ve heard many discussions on your show regarding the cold chain for vaccines. I found this article today about a company that has a fridge-free flu vaccine that is currently stable for one year. There are promising preclinical results and they are hoping to enter real clinical trials in a year or so.

It’s preliminary, but exciting:

http://www.fiercevaccines.com/story/vbi-has-its-eye-refrigration-free-vaccines/2011-03-24?utm_medium=nl&utm_source=internal

—

Mitchell

[link is dead; we talked about this on twiv 70 /twiv/twiv-70-hacking-aphid-behavior/]

Alex writes:

Hello Professor Racaniello and others!

I was sitting in on a lecture on the modes of infection. The lecture began with many relationships between humans and organisms described below.

Symbiosis: Benefits only the human; no harm to the organism.

Mutualism:Benefits the human and the organism.

Commensalism: Benefits only the organism; no harm to the human.

Pathogenicity: Benefits the organism; harms the human.

My mind briefly escaped the lecture to wonder whether whole structure viruses ever actually benefit the human in a Symbiotic or Mutualistic fashion. I’ve heard of opportunistic bacteria which compete for nutrients and space on the human body- preventing the establishment of more pathogenic species. After class I went to explore TWIV to find the latest pocast- “Viruses that make you better #124”. The discussion of tanapox virus was remarkable, but you suggested that the virus only creates the TNF antagonist to evade the immune response. To your knowledge is that any virus which provide long-term purposeful benefit to the host? I know you have explained thoroughly that the “best” virus is not necessarily the most fatal.

Finally, I would like to sincerely thank you of the foundation of TWIV. I am a student currently finishing up my undergraduate degree in Biomedical Sciences at Grand Valley University in western Michigan. Next year I will be starting a Master’s degree with an emphasis in Microbiology in London. I am finding the content…particularly the Virology 101 extremely helpful for preparation. I know,as evidenced by your mailbag- that hundreds others have discovered the same. Again, this is a remarkable service to the public, you guys are truly inspiring the next generation of Microbiologists.

Thanks!

Alex

Anna writes:

Hello all,

I was just listening to episode TWiV 125, in which one of the discussion points was the co-option of Cafeteria infection centers by the smaller, Mavirus. I was struck by the commonalities between Mavirus and defective interfering particles, since DI particles too can interfere with production of particles with full length genomes. This has then prompted a few questions or thoughts that I would love to hear your thoughts on.

To start, if a DI is like a parasite of a virus, could they be a viable treatment for an infection. Alone DI particles are not infectious and they can specifically interfere with production of their progenitor virus if they get into the same cell. Do you know of any studies where this has been tried?

This parallel has also made me start re-thinking the lifecycle of a DI. I had always thought of DIs as being gained and lost continuously during infection, but I wonder if there are particularly successful DIs that are continuously maintained, more like an independent parasitic virus.

Would it even maybe be possible for a DI particle to change the virus that it’s dependent on? I.e. could it jump to infect another, similar virus? You could then end up having distinct genetic content between a DI and the viral population it infects. I recently went to a lecture by Marco Vignuzzi of the Pasteur Institute in Paris, where he said in passing that DIs could theoretically recombine with full length viruses, acting as a source of new mutations. If DIs could jump from virus to virus and there were recombination, then just as how viral infections has lead to lateral transfer of genetic information, as in bacteria, DIs or “viruses of viruses” might have similarly helped pass along viral genes.

Thanks so much for the inspiration, this is exactly why I’m a regular listener of the podcast,

Anna

MSc candidate, University of Ottawa

TWiV 129

Bryce writes:

I enjoyed your discussion of the Molecular Therapy paper in this week’s TWiV. My lab (and others) have worked on using virus particles as scaffolds to increase the immunogenicity of various targets for quite some time. One thing that wanted to point out (and to correct one of the comments of Rich, I believe), is that this strategy actually IS effective at targeting self-antigens—we can efficiently overcome the mechanisms of B cell tolerance by displaying self-antigens on virus particles. My lab has done a number of studies in animal models, and a Swiss company, Cytos, has actually run clinical trials of virus-particle-based vaccines targeting self-molecules involved in various diseases (Alzheimer’s and hypertension).

Thanks again for the enjoyable podcast.

-Bryce

Associate Professor

Dept. of Molecular Genetics and Microbiology

University of New Mexico

http://hsc.unm.edu/som/micro/bryce.shtml

Jim writes:

Brandeis study shows economic impact of dengue virus in Americas

Dengue illness, the most common mosquito-borne viral disease in the world, has expanded from its Southeast Asian origins and is resurgent in countries such as Argentina, Chile and the continental United States.

Daniel writes:

I am a graduate student in biophysics who discovered your podcast in December after finding your blog, all while working on a term paper about EBOV vaccines for my mammalian viruses biochemistry course… Despite my physics background, i have been interested in viruses since reading “The Hot Zone” in junior high.

I just listened to twiv 119, and after looking at some of the comments posted below 119, i have wondered what consideration has been taken to produce a vaccine based on a killed virus via formalin or oxidizing radiation, or attenuation. But i must be jumping ahead, since i have not done any journal search about whether or not the virus has been cultured (e.g. HeLa, monkey kidney cells).

I have been working backwards through the TWIV archive, and have yet to get to the double digits, but so far i do not recall if yourself and the other hosts have mentioned that topic about XMRV. If XMRV has crossed the species barrier into humans, then it seems likely that most of the population would have antibodies against it, much like the Epstein Barr V, given that mice follow humans everywhere (there are no rats in alberta).

Good show overall. Keep up the good work, eh.

-Daniel

Peter writes:

Congratulations on your great netcast.

I will shortly commence my Virology course for 2011, and I have 165 students, up from 74 last year. I’m thrilled and delighted to have discovered TWIV, which covers so much of the exciting, stimulating stuff that I talk about to my students.

I will be telling them to go straight to your site, so please keep it up.

By the way, if either of you are ever in Adelaide, Australia, let me know. You will be in grave danger of being dragged in to talk to my students, to tell them just how fascinating viruses are,

with best regards

Peter Speck, PhD

Lecturer,

School of Biological Sciences,

Flinders University

South Australia.

John Terry MD writes:

With regard to Nebraska, my individual 30 year radiology experience (many chest X-rays) is Cavitary TB 5 cases, lung cancer 300 cases. Your personal experience based of knowing many more lung cancer victims then TB victims is verified.

Vince writes:

Hello,

This week in science, there was an article way at the bottom concerning a phenomenal display of virus/host evolution.

http://www.sciencemag.org/content/331/6018/775.abstract

This study found that metastasizing Leishmania parasites actually harbor a virus that stimulates the immune system creating an inflated inflammatory response in the human host, which was seen to lead to a higher reproductive success for the parasite. WOW! From a wider lens in virology, this may not seem to be surprising, as in bacteria this is more common. Phage can transfer many beneficial genes to help bacteria to adapt to many diverse environments, including humans. Although in this particular case were talking about a different type of assistance, dsRNA mediated inflammatory enhancement. Furthermore, in a article on a science news website(http://www.physorg.com/news/2011-02-virus-parasite-combine-humans.html), the authors said “This is the first reported case of a viral infection in a pathogen of this type leading to increased rather than reduced pathogenicity,”. This raises many questions concerning other protozoan parasites and whether their virus partners (exogenous…or endogenous?) assist their parasitic lifestyle. Certain virologists have long assumed that viruses assist symbiotic interactions between distant species (such as Luis Villarreal at UCI), where for example, they extend gene addiction to a possible mechanism of mutualism generation.

How widespread do you think this phenomenon is? Could viruses be used as defense, phage from our normal microbiome that possibly infect invading bacteria? Or, persistent viruses like TT viruses, which possibly infect cellular pathogens? No evidence for that however….

Thanks

Vince

Benjamin writes:

I noticed a set of strange coincidences related to your most recent podcast (TWiV #120) related to Egypt. Here they are:

1) Your podcast was recorded on February 11 (the day Mubarak stepped down)

2) You recorded the podcast in Alexandria, Virginia, which shares its name with the second largest city in Egypt

3) Your guest was named Ed Niles (I know, corny)

Ben

Julie writes:

Thanks so much for your podcasts. I always learn a lot from you. I just finished listening to your interview with David Tuller, which I enjoyed.

You made a number of confident statements about the certainty that science will figure out what’s really going on with XMRV. I’d love to hear more about your perspective on Elaine Defreitas’s work on an HLTV2-like retrovirus from a long time ago, because one of the discouraging things about what I’ve heard about that story is that it seemed like science didn’t figure out what was really going on. I’d love to hear if you agree with that perspective or if there’s more to the story than what I understand.

Thanks so much for your work.

Best,

Julie

Freelance Math and Science Writer

Math Columnist for Science News: http://bit.ly/mathtrek

and Wired: http://bit.ly/wired_equation

Amit writes:

Dear TWiV hosts,

I enjoy your program for several weeks. I enjoy it very much (including TWiP). I find it very interesting, even for people which are not from the discipline. I wish to give something back, so I have several suggestion which, I think, will make it even better.

The podcast is usually very long, and un-edited. It will be nicer if every episode will be specific for limited number of topics which can be discussed during up to one hour.

The topic of discussion should be cleared at the beginning. New terms and method should be explained at the first mention. Vincent does it in TWiP, and maybe forget it in TWiV, because he is so familiar with the subject, he forget that not every body are.

No need for reading all e-mails in the podcast 🙂

Hopefully, I will start my own science podcast (the first Hebrew one), inspired by you, and other podcast on the sciencepodcasters.org

and one last thing before wishing best regards and closing this letter, use Celsius degrees (or Kelvin), out of the US no one can understand if it cold or warm there 🙂

Best regards and have a nice week

Amit

Technion – Israel Institute of Technology

Haifa

Israel

Martin writes:

Hi Vincent,

Here is a study showing transmission of yellow fever, the same yellow fever strain used in the vaccine is found to be infecting babies from mothers milk.

Do you still think it is a good idea to vaccinate pregnant women

Best as always,

Martin

http://www.cmaj.ca/cgi/content/abstract/cmaj.100619v1?ijkey=f2ac013091fb86333a58f6bdc8db63f379200b13&keytype2=tf_ipsecsha

David writes:

Hi Twiv

Im listening to twiv #118, one of the emails asked about virus like particles used in vaccines and you discussed that capsid proteins are capable of self assembly. I believe it was Allan that said it was like a bag of magnets coming together to form the structure. Here is a link to a video of magnetic “capsid proteins”, which when shaken in a container eventually form an icosahedral shell. I use it in my virology class to demonstrate what I mean by self assembly.

http://www.youtube.com/watch?v=X-8MP7g8XOE

Cheers

David Esteban

Biology Department

Vassar College

http://faculty.vassar.edu/daesteban

http://blogs.vassar.edu/viva/

Mike writes:

I have an MS in biology & chemistry but it is from the late 1960’s and I’ve been a self-employed programmer for the last 30+ years after 10 years in a hospital lab. Many things have changed in the last 40 years! I don’t know if Kudo’s is still used in protozology, but it was my favorite text.

I began listening to TWiV to learn the current state of understanding of XMRV because my wife has had Fibromyalgia/Chronic Fatigue for about 2 1/2 years. This was diagnosed at the Mayo Clinic in February 2010. I found your podcasts dealing with XMRV interesting and educational and have become hooked on TWiV and TWiP (have my TWiV coffee mug ordered) and am in the process of listing to all the back episodes.

I also wanted to let you know about the website bookfinder.com. In episode #9 you mentioned a book named Fever by John G Fuller. It is not currently in print, but you can get used copies through bookfinder. I collect first edition speculative fiction (science fiction) and use this site daily. If it has been published you can probably find it here.

Love TWiV – keep up the great wool,

Mike

Ilya writes:

Hello,

A few weeks ago I defended my PhD thesis and this is the photo of the last slide with gratitudes.

Last line says: “To prof. V.R. Racaniello for inspiration” and that couple of times, when I thought my project was going to fail, you and all the wonderful people on TWIV indeed inspired me to carry on.

Ilya

Chumakov’s Inst. of Poliomyelitis and Viral Encephalitis, Russian Academy of Medical Sciences

Marc writes:

Welkin,

That was a great episode. I love it when there are guests on TWIV that get into the ‘oral history’ of different viral subjects. I debating whether I should assign you intro about TRIM to my virology class this week. I wonder if anyone would object to having a podcast as an assignment? I’m already having them update virology entries on wikipedia for extra credit.

Vincent,

If you ever have Alan Rein on again should ask him to tell you about how the word ‘pseudotyping’ was coined. It’s another really interesting science history story that I don’t believe has been written down anywhere.

Marc Johnson

Assistant Professor, Molecular Microbiology and Immunology

University of Missouri

Columbia, MO

Penny writes:

It’s being reported on Facebook that neither Frank and Sandra Ruscetti nor Judy Mikovits has been invited to the upcoming CROI conference. The committee also rejected at least one of their abstracts on XMRV and immune dysfunction.

While there will be discussion of XMRV at the conference the emphasis will be on contamination and negative studies. The absence of Mikovits and the Ruscetti means that they will not be able to offer even a critique of these arguments, let alone defend their own work.

I’ve appreciated your programs on XMRV and the last one with David Tuller, even if sometimes I’ve been critical of things you’ve said. But how much faith can a lay person like me have in the “scientific process” if important views are marginalized. Where does the debate take place if not at a meeting like this?

Thanks,

Penny

Michael writes:

Dear TWiV Team,

My name is Michael Walsh and I am on the faculty at SUNY, Downstate in the the School of Public Health in the Department of Epidemiology and Biostatistics. I have enjoyed listening to your podcasts for quite sometime. I find TWiV, TWiP, and now TWiM, very engaging. I really appreciate the personalities of each of you four, Vincent, Dickson, Rich, and Alan, and the casual, yet unflinching approach taken with each topic.

As an epidemiologist, one of my primary areas of research is the interface between infectious disease, climate, and geography. I use the application of GIS methods frequently in my work and was quite interested by a recent paper in the American Journal of Tropical Medicine and Hygiene reporting on land use and West Nile virus, a focus of some of my own work here in New York State. I found the results interesting, though as a skeptic and a bias-wary epidemiologist, I think it is difficult to draw inference from county level data of WNV cases. And as we all know, correlation does not equal causation. When I was reading this paper, I immediately thought of Dickson. I have listened to the many discussions you’ve had on TWiV regarding WNV and I’ve always quite appreciated Dickson’s point of view with respect to the complex ecology of this infection. For example, I think the hypothesis that increased incidence of human WNV infection can result from drier weather that provokes greater bird dispersal leaving humans as a more available mosquito host is well-founded. I would like to see (or undertake) some better studies that combine population-based epidemiology and multi-species ecology to get at a better understanding of this process. As regards the paper, I’d like to hear Dickson’s opinion on the juxtaposition of an “Eastern” and “Western” WNV in the United States, based on the former being an urban disease and the latter being a rural disease as described by the authors. The authors posit that regional differences in the distribution of human WNV incidence between the eastern US and western US can be delineated by distinctions in land cover across these two regions (developed/urban land versus rural land). Moreover, they suggest that these land cover differences correspond to similar differences in the distributions of Culex pipiens and C. tarsalis between the two regions. The authors attribute differences in WNV incidence to the exploitation of different local environments by the two culicine mosquitoes. I am interested to hear your thoughts, particularly with respect to how such regional distinctions, if true, may fit with the overall dissemination of the virus from east to west across the United States from 1999 to 2006. I am wary of the aggregate data which were used to measure incidence, and we also do not get a clear picture of the finer resolution of the mosquito and bird ecologies that must also be at play. Nevertheless, I do think it is an interesting hypothesis-paper.

Keep up the excellent quality of your podcasts. All four of you provide a true gem to anyone interested in virology, infectious disease, or science in general. You do a great public service and I, for one, very much appreciate your efforts.

Also, I have a blog on infectious disease called Infection Landscapes, at http://infectionlandscapes.blogspot.com/

The idea behind this blog is to discuss the epidemiology and ecology, and the physical and social landscapes of infectious disease. Have a look and see what you think. I do weekly postings.

Cheers,

Mike

Michael Walsh, PhD, MPH

Assistant Professor, Epidemiology and Biostatistics

School of Public Health

State University of New York, Downstate

Brooklyn, NY 11203

http://infectionlandscapes.blogspot.com/

Garren writes:

Greeting Semi-divine TWiV hosts

I have a quick podcast recommendation for everybody. We all want more science, so what I would like to recommend is basically what TWiE should be (This Week in Engineering). The podcast is called Omega tau and can be found athttp://omegataupodcast.net/category/podcast-en/ The host is German but is kind enough to do a fair number of really interesting English podcasts. The show is a bit like Futures in Biotech in style (ie interviews vs panel). Topics range from quantum computing to flying the space shuttle to electron microscopes. Check it out.

Cheers…

Garren

Manuel writes:

Dear TWiV,

Could it be that viruses are implied in a wider range of diseases than we currently think? Sciencedaily published an article today where they state that ALS could be caused by a human retrovirus. I know that we are in a discussion right now, where XMRV could turn out not be the cause of CFS or some other disease but this does not have to be true for other diseases and retroviruses. Please keep up the great work and I’d love to hear you guys talk about it.

Best Wishes

Manuel

The Sciencedaily article: http://www.sciencedaily.com/releases/2011/03/110302121911.htm

The full study: http://onlinelibrary.wiley.com/doi/10.1002/ana.22149/pdf

Kari writes:

Hello Vincent, Dick, Alan, and Rich,

My name is Kari. I am currently a graduate student in the Baric lab at UNC Chapel Hill in the Department of Microbiology and Immunology. I love listening to your podcast, being turned onto it by Eric Donaldson whom you have had on to talk about the bat virome. Eric’s work on bats is great, but equally great is his work with noroviruses. I may be a little bit biased, working on noroviruses and all, but I think it’s high time you do an episode on this virus since it affects pretty much everyone at one point or another (I like to call it the puking/pooping virus). In the United States alone, over 23 million people get norovirus each year! I could go on and on about my virus, but I would rather have you guys do that on an upcoming episode 🙂 Thanks again for doing TWIV! I love it!

Best Regards,

Kari

UNC-Chapel Hill

Didier writes:

here is a new english music group ” The Vaccines” …http://www.myspace.com/thevaccines

can’t be ignored by twiv !!!!!maybe a “pick of the week”

|///

(o o)

————————–oOOo~(_)~oOOo—————

Didier

Virologie Moléculaire et Structurale

Gif sur Yvette France

Marcia writes:

Several weeks ago I had occasion to speak with Dr Judy Mikovits. I mentioned your podcast show to her, and she said that she and Frank (I assume she meant Dr Frank Ruscetti) would be willing to be guests on TWIV. I think it would be fascinating to have both of them on the same show, and hear your usual free-ranging chat between you regulars and the two of them. From what I understand from our conversation, WPI has finally been able to raise enough funds to buy their own sequencer, and they have a lot of ideas about what they’d like to investigate in regards to XMRV, polymorphic forms, etc.

I am including the contact information for the Whittemore Peterson Institute below, in case it would be useful to you. In my experience trying to speak to Dr Mikovits, the “guardians at the gate” are diligent in screening her calls. If you don’t have any luck arranging something through the media contact below, you might succeed by speaking to Dr Mikovits directly, since she did clearly say in our conversation that she’d be interested in talking with you. (I eventually got through to her by doing some name dropping, “Dr Klimas suggested i…” etc. I’m not proud–whatever works!)

Disclaimer: Although I listen to all episodes of TWIV and find them fascinating, I have a particular interest in XMRV because I tested positive for XMRV via serology (antibodies). This was through WPI and participation in one of their studies. I’ve been ill for many years with CFS, and I follow as much as I can of the science relating to CFS. I don’t know whether XMRV will turn out to be the answer, but it certainly is interesting. The work with spinal fluid proteins associated with CFS and fibromyalgia is also very promising. I was raised with a scientific background, and I hope very much that CFS will become understood and effective treatments available some day.

Again, thank you for a very interesting show.

Sincerely,

Marcia

Sophie writes: (with respect to ‘The decline effect and the scientific method’)

I think this article is quite disturbing. Even if the author is right I have a serious problem with sentences like: “If replication is what separates the rigor of science from the squishiness of pseudoscience, where do we put all these rigorously validated findings that can no longer be proved? Which results should we believe?” It seems to me that it is a problem at the moment, for the general public to distinguish between real science and more alternative things (like homeopathy) and I think this article might give, as Mr. Marc Crislip puts it: “The alternative wackaloos” even more ammunition, even though it is unwarranted. I also think it is a big problem that, as Alan points out, the beginning is sensational, because if somebody doesn’t read the article through, they might draw the wrong conclusions.

Besides that I find it really interesting, and would like you guys to talk more about it. At least in Denmark, it isn’t a problem most science-students know about and it isn’t discussed in class and I think it should, to avoid bachelor students ending up finding out about this in their first really important paper/assignment.

In general I think there should be more focus on the problems with science, so we are prepared to handle these things before we get out in the “real world”.

We just had a case of a cheating brain-scientist, who now has been convicted of using research money for clothes and stuff, trying to blame this on one of her students and faking mouse-experiments results. It was quite clear that the system isn’t really geared towards handling these cases. Both this and the MRI-autism study might have been caught way earlier, if scientist were more aware of potential problems.

Please discuss and sorry for the rant:)

Sincerely Sophie

Ina writes:

Hi Vincent, Dick, Alan, et al.

In TWIV 70 you talked about host manipulation by ‘outside invaders’, i.e., viruses, parasites, etc. An article giving many examples of this type of manipulation can be found in the Scientific American of March 2003. The author of this article is Robert Sapolsky & is entitled ‘Bugs In The Brain’.

I enjoy TWIV immensely & was introduced to TWIV by a friend whose daughter took a virology course at Columbia University. Listening to TWIV was part of her assignments. I, myself, am an alumna of Barnard & have worked extensively in various areas of cardiovascular physiology. Keep up the great programs of TWIV & TWIP.

Respectfully submitted,

Ina P., PhD

Michael writes:

Hi Vincent and gang,

First I would like to say thank you for a great podcast. I am a parasitologist who recently started a job in Virology and I found twiv after watching your lecture series at http://microbiology.columbia.edu/w3310.html (thanks for that too!). I drive for 2 to 3 hours a day, depending on traffic, and twiv and twip have been keeping me sane as well as brushing up my science.

By the way, I am now up to date with twip – 1 month is too long to wait for the next one! So my question relates to a statement you made about growing influenza in cell culture. You said that in order to get a high titre of virus from a cell monolayer you had to start with a low MOI. This is general question but I work with avian influenza and I can’t understand why this would be the case. This is why: There are a limited number of cells in the monolayer Influenza causes lysis of the cell and presumably there is a limit to the number of virus particles produced by each cell Therefore the MOI will only affect how fast the final virus titre is reached. The variability in final virus titre may therefore be due to when the flasks are harvested. If I have got this wrong I would gladly be corrected.

I have not finished listening to all twiv episodes (thank goodness as it really does help with the driving), so you may have answered this question.

Thanks and keep up the good work,

Mike

John writes:

Dear TWiVtastic Four,

I must disclose that I thoroughly enjoyed this most recent episode (#124).

I think it had a nice mix of detailed science, some insight into how science in the modern age works, a nice nuanced discussion of what to do about smallpox and plenty of puns. If people think in anyway similar to me they think of some nebulous ‘smallpox’ vials kept in cold storage somewhere like the DNA was in Jurassic Park, where security is as weak as having just one Wayne Knight as the IT guy. Obviously that’s a bit of a caricature but I think you get the idea. When the listener e-mail about funding came up in my head I was already rambling similar to what Alan said so I was quite pleased to hear him articulate my reactionary thoughts better than I was rambling internally. Speaking of Alan, I knew this would be a good episode due to a critical measure in TWiV quality. That is the time-to-pun measure. When Alan is in top form it’s nice and low. And there was Dick right at the end for the walk-off victory with the vertical farming quip.

So in summary, great guest, great topics, great to have everyone back and to know that Dick has no escape from the podcasting. Someone send him a fishing video game so he won’t have to travel.

Sincerely,

John

Sven-Urban writes:

Gentlemen,

In the latest epi… Oh, by the way, why am I able to address you like that? Why not “Ladies and Gentlemen”?… Sorry, that was a glitch, let’s reboot:

Gentlemen,

In the latest episode as of this writing, #124, you were once again talking about the possibly pending call for destruction of all known smallpox virus stocks. You also mentioned that nowadays, as the genetic code is known (for some of the lines, at least), it would be possible to reconstruct the virus from scratch, although it would be with som difficulties. Not that I’m about to try it at home (my wife might object – and she’s both a better chemist and a better cook than I am anyway), but how would you go about it, and what would the largest hurdles be? Would it be done in test tubes and reactors, or would you enlist the aid of some poor, doomed cell to do it for you? And would you, really, get a “proper”, healthy virus, alive and kicking, as a result? A somewhat thorough step-by-step overview would be much appreciated!

As an aside, I would once again like to suggest a “listener POTW”, this time the three “The Science of Discworld” books by Terry Pratchett, Ian Stewart and Jack Cohen:

The Science of Discworld

The Science of Discworld II, The Globe

The Science of Discworld III, Darwins Watch

In these books (all available in paper back) the authors explore science – particularly physics, cosmology and evolution – as seen through the eyes and sharp but weird minds of the denizens and wizards of Discworld. These books are GOOD, and anyone who is at least reasonably familiar with science and happens to like Discworld will love these hilarious, but also very serious, books!

Best Regards from a thawing Sweden!

/Sven-Urban

David writes:

Hi Guys:

Love the show. Absolutely one of the best overall podcasts. Great dynamic of science, humor, humanism and camaraderie.

One the last episode, you played some examples of DNA music that I would like to acquire. Would you please send me the link (couldn’t find it the site) or the name of the composer.

Thank you again.

Dave

TWiV 128

John writes:

Dear Doctors,

It seems the Russians are going to penetrate the oldest subglacial lake on Antarctica soon.

http://www.newscientist.com/article/dn19918-mysteries-of-lake-vostok-on-brink-of-discovery.html

I really don’t care if they find oil or natural gas there. But I would be very interested to know what they find if they get a nice microbial soup they can sequence. I’d be especially interested in adding to a timeline of viral dna that’s inhabited other species’ genomes. So the question is, from a microbial perspective, what would we expect to find there and will we get any cool stories about it in the next few years?

One final note. I am an economist by training and in the Fall of last year the NSF sent out a call for white papers to get the opinions of the field on where research is or should be headed in the next decade in all subfields of economics. I haven’t had time to sift through them all but I thought it would be an interesting thing to touch on for TWiV e.g. long term on going studies, novel ways of using viruses as a tool either natural or engineered, etc.

Thanks again for the entertaining education and a belated happy new year to the crew.

Sincerely,

John

PS “Another TWiP is spiral” is clearly a masterpiece tagline and should be reconsidered.

Daniel writes:

Dear Vince et al, 29 July 2010

I have been listening to TWIP for the last few months and then started crossing over to TWIV and find both podcasts refreshingly spontaneous. I download these and other science-related podcasts and play them on my IPOD when I take my morning walks along the Clearwater River Canyon in No. Id.

I am a lipid biochemist currently working on neuro-psychiatric disorders. Specifically I’m examining the methylation patterns of certain neurochemical and peptide/receptor and neuroimmune ligand/receptor pairs in rodent brain from animals reared in differing social and stress-inducing environments.

I also teach a medical oral micro course in the Dental School.

I am looking into the molecular genetics of inherited and somatic-environmentally-

acquired CpG methyaltion and the potential mechanisms underlying these covalent and reversible modifications. After listening to your podcasts in both TWIP and TWIV, I am obtaining more discrete information about the tremendous impact eukaryotic parasites and certain viruses have on both the architecture of mammalian genome and the activity of the immune response. I believe these are co-adaptive phenomena.

My question is directed to you and either and both TWIP and TWIV cohosts:

What do you know and could you speculate about the impact of parasitic challenge and/or viral infection on the early development of the human immune system as these relate to the accumulation of copy number variations in the host genome?

Sorry for this long-winded email but I think some background was necessary to frame my question coherently.

Thank you,

Dan Guerra PhD

Washington State University and Eastern Washington State University/University of Washington School of Dentistry.

PS. On an unrelated topic, what does Dick about the similarities between “nurse cells” and the Rhizobium spp root nodule involved in symbiotic nitrogen fixation in leguminous plants?

Nissin writes:

http://www.sodis.ch/methode/index_EN

Guys,

Do you think that if the water is contaminated with Noravirus or Rotavirus the viruses will be killed with this method? They claimed that polio titer is reduced by several logs.

Best

Nissin

Research Associate Professor

Department of Molecular Genetics and Microbiology

University of Florida

Gainesville FL

Viktor writes:

First I want to thank you for the excellent podcast! I started from episode 1 and I am up to 80+ now enjoying every single episode along the way.

I love the science, the stories, the personal touch, even the sound quality! But above all I love learning about the whole new world of virology.

I am a software developer and I find it very refreshing to discover thought provoking knowledge outside of software and computing that broadens my understanding of the world around us.

I came across today a podcast episode that might interest you. It is an interview with the investigative journalist Brian Deer about his seven years of reporting and legal issues surrounding the 1998 article in The Lancet claiming that the MMR vaccine causes autism and bowel problems. It is fascinating to hear the minute details around the history, the documentation trail, the litigation, that led to the “erasure” of Dr Wakefield from the medical register. I knew most of the facts, however this interview paints a very disturbing picture of corruption, dishonesty and lack of moral judgement.

You can find this episode from the EconTalk podcast here: http://www.econtalk.org/archives/2011/01/deer_on_autism.html

Best wishes to you and the team and keep the good work. It is much appreciated!

Viktor

London, UK

Kelly writes:

Excellent conversation with David Tuller. Many journalists do not understand science or only receive training in public health with no emphasis in the biomedical sciences.

Vincent you wondered aloud how many XMRV grant applications the virology SEP will receive for review. Apparently it depends on the disease being studied. All CFS studies regarding XMRV are being automatically referred to the CFS and Fibromyalgia SEP where Myra McClure has been appointed to review those CFS/XMRV applications. Good virologist – specific point of view.

Given that that the CFS/Fibromyalgia NIH SEP is funded at the same level of funds as hayfever ($4 million per year) – with only approximately 6 percent of those funds actually going to CFS research in 06,07, and 09 according to NIH figures – it isn’t very realistic to expect enough funding to have sufficiently powered XMRV studies coming from this area.

Do they automatically send XMRV applications involving prostate cancer to a cancer SEP?

Regards,

Kelly

TWiV 127

David writes:

Dear Twiv Folks

I teach an intro biology course on viruses at Vassar College. We do our introductory biology a little bit differently; each class has a theme through which we explore the fundamental principles of biology. Mine is on viruses and their hosts, its a great way to explore everything in biology (cells, genetics, evolution etc) and get students hooked on virology in their freshman year.

We had a recent discussion in class on the evolutionary benefits of lysogeny, specifically relating to the temperate phage CTX-phi, which expresses the cholera toxin responsible for the severe diarrhea seen in cholera. The students wondered why not just stick with the lytic cycle, when you can potentially infect so many more cells? What is the benefit of being able to make that switch?

We had also discussed the balance of virulence and transmission, that viruses will evolve towards an appropriate level of virulence based on their mode of transmission (among other factors). So here is an explanation I came up with:

You can think of the lytic cycle as highly virulent (100% mortality, since infected cells will lyse and die) or lysogenic as non-virulent (no negative effect on the host while the phage is present as a prophage). So when would high virulence be favored for transmission and when would low virulence be favored? A highly virulent pathogen runs the risk of wiping out its host population. If the cells are growing actively in an environment like the gut, and the virus is replicating to high levels, it could spread to the entire host population eventually killing every cell. (Viral replication is much faster than cell division and when cells divide, only two cells are made but when viruses replicate, 10s of virions are made.) The virus would then depend on either more V. cholera entering the gut, or getting out of the gut and spreading to a new human host infected with cholera. Alternatively, cholera can also grow in the environment, so the phage could infect a cell in the environment. However there is some obvious risk there, that of finding the next host cholera cell either in a gut or the environment. Its a big world out there for a tiny phage and a tiny bacterial cell to meet each other. A less risky approach might be to limit virulence and allow prophage infected cells to survive. The cholera cells will be returned to the environment, where they can replicate or to a new human host where it can also replicate. Either way, the phage is guaranteed to find a host, because its already in it.

Now if the prophage finds itself in cells that are no longer growing, there may be an advantage to getting out and finding “happy” hosts. Cells that are not growing could be at greater risk of cell damage and death, perhaps they are not acquiring the nutrients and energy necessary to grow or repair cellular damage. If the cell dies, the phage will not be able to replicate. So the phage would enter the lytic cycle and release progeny. The risk of not finding a new host would presumably be lower than the risk of staying within a dying host. High virulence therefore is advantageous for transmission in this situation.

What are your thoughts on this explanation? Im sure there are other ideas and Id be interested in hearing them.

Great show!

Cheers

David

Biology Department

Vassar College

http://faculty.vassar.edu/daesteban

http://blogs.vassar.edu/viva/

Rao writes:

http://edition.cnn.com/2011/US/01/04/arkansas.bird.mystery/

Is this due to a virus? Bird flu?

Rao

Jacob writes:

Hi Vincent,

I thought that your readers and listerners would be interested in this.

The following is a link to an article (free access) in the British Medical Journal (published 5/1/11) detailing the story behind how the MMR vaccine-autism paper was forged.

I recommend that you read it and forward it on to as many people as you can, because many people still believe that the conclusions from this paper are true (i.e. vaccines cause autism) even though the original paper has been retracted and the PI (Mr Andrew Wakefield) has been sued for fraud and had his medical licence revoked by the British Medical Association.

I would post a link to the original Wakefield article but it is behind a paywall.

http://www.bmj.com/content/342/bmj.c5347.full

How the case against the MMR vaccine was fixed

Brian Deer, journalist

In the first part of a special BMJ series, Brian Deer exposes the bogus data behind claims that launched a worldwide scare over the measles, mumps, and rubella vaccine, and reveals how the appearance of a link with autism was manufactured at a London medical school.

Thanks,

Jacob

Kathy writes:

Hi guys,

I saw this and immediately had to take a picture. Another way of thinking about the cold chain!

Thanks for the recent mention when Rich used my suggestion for Weekly science pick – the story about the grade school children’s research about bee behavior! I’ve now had my 15 seconds of fame 😉

Cheers,

Kathy

Jim writes:

Two references; the first from Slashdot ( http://www.google.com/reader/view/?hl=en&tab=wy#stream/feed%2Fhttp%3A%2F%2Fslashdot.org%2Findex.rss )

has this intro:

“The Logical Leap: Induction In Physics

from Slashdot by samzenpus

FrederickSeiler writes “When David Harriman, this book’s author, was studying physics at Berkeley, he noticed an interesting contrast: ‘In my physics lab course, I learned how to determine the atomic structure of crystals by means of x-ray diffraction and how to identify subatomic particles by analyzing bubble-chamber photographs. In my philosophy of science course, on the other hand, I was taught by a world-renowned professor (Paul Feyerabend) that there is no such thing as scientific method and that physicists have no better claim to knowledge than voodoo priests. I knew little about epistemology [the philosophy of knowledge] at the time, but I could not help noticing that it was the physicists, not the voodoo priests, who had made possible the life-promoting technology we enjoy today.’ Harriman noticed the enormous gulf between science as it is successfully practiced and science as is it described by post-Kantian philosophers such as Feyerabend, who are totally unable to explain the spectacular achievements of modern science.”

And all that makes me think we’d be better off telling students they need to research anything they wish, but they have to apply certain rules as they do it. Isn’t that what’s done for graduate work in England that doesn’t require all the American testing, but uses mentor evaluations and a final oral exam?

Then, although I initially thought about traditional courses and what kind of word problems, I then ran across this:http://esciencenews.com/articles/2011/01/10/secondary.students.should.be.required.receive.cpr.training that says”

“All secondary school students should be required to be trained in cardiopulmonary resuscitation (CPR) and receive an overview of automated external defibrillators (AEDs), according to an American Heart Association science advisory.”

And that reminded me that while we have loads of word problems, I don’t know if we yet are including examples that deal with daily situations (CPR-like) concerned with balancing check books, student loan size versus projected salary size, income tax preparation, or buying that car Vince mentioned at different purchases rates.

No solutions; just meandering thoughts…

Jim

Smithfield, VA

Kathy writes:

Hi guys,

I think it was on #115 where Vincent made a comment about defensins and viruses. There has been some work on that, at least in adenoviruses. A new assistant professor, Jason Smith, at UW in Seattle is continuing work he began as a postdoc with Glen Nemerow. Here’s a screenshot of a PubMed search I did. (I half expected Alan to do the search during the show…). (There are a lot more hits if you don’t limit it to “smith”.)

I enjoyed the discussion about the paper on colored pseudorabies virus from Lynn Enquist’s lab. Now I’ll have to read it (the first time), then listen again with paper in hand, and maybe read it several more times (from what Rich says)!

I listened to your influences in science while shoveling my driveway (jealous, Rich?!). One of my influences in science (beyond my parents [chemists] and teachers/advisors/mentors) was reading at a young age my father’s copy of a translation of the biography of Marie Curie written by her daughter Eve in 1937.

Cheers,

Kathy

Sara writes:

Hi gentlemen,

I discovered the podcast relatively recently and really enjoy your work. I did my undergrad in microbiology and some grad school in public health, and after working for several years as a technician/analyst doing molecular biology and other techniques in academic labs and a vaccine biotech, I just started nursing school.

My goal is to not leave the mentality or love of basic science research behind, and to that end I recently attended a seminar on campus by Paul Goepfert of U Alabama Birmingham with the title: Cryptic Epitopes: Implications for HIV Vaccine Design. The closest-related paper I could find of his with a brief search was published on 18Jan10 in Journal of Experimental Medicine (Pubmed abstract).

I’m not an HIV expert by any means but am fascinated by the challenges this virus poses in practice, namely vaccine development and mutations that lead to multiple drug resistance. (Never mind all the ways human behavior can affect the trajectory of HIV infection, e.g. adherence to ART!)

In this talk, Goepfort honed in on a realization that some HIV vaccines being tested in the field attempt to raise an immune response to epitopes whose sequences have been codon optimized for optimal expression in humans. This is in contrast to other clinical studies using non-codon optimized sequences derived from known field isolates of HIV. The problem with this codon optimization strategy is that the population of immunogenic epitopes from all the other reading frames (2 forward and 3 reverse) is completely different than what the “wildtype” epitope population would look like. If I understand the consequences right, this would mean that even if the vaccine material is expressed well in the patient, the immune response would be largely irrelevant and unprotective (at best).

Is it just me or does the use of codon optimization of a HIV antigen sequence for vaccine use seem like a big “DUH” bad idea in hindsight, because of this issue of the alternative reading frame antigens?

I am aware of vaccine development programs for other viruses, e.g. HSV, that also use codon optimization in the antigen sequence. Would this issue of raising an immune response to antigens expressed from codon optimized sequences cause a similar problem with other vaccine programs? Do all viruses or just retroviruses produce these black box proteins from alternative reading frames? Could the changes resulting from codon optimization also be affecting the effective immunogenicity of vaccines being tested for viruses other than HIV? What are the implications of these unconventional alternative reading frame epitopes in vaccine development? Is this phenomenon studied very often in terms of trying to understand what the ARF proteins made by viruses do in the first place?

This may not be a TWiV appropriate discussion, but I thought it was a riveting real world issue at the junction of the wily behavior of a virus, what that means for individual patients’ disease processes, and the expenditures of vast amounts of resources on clinical trials.

Thanks very much for such an accessible, enjoyable, and educational podcast!

Sarah

BSN/RN student, Duke University

BS Microbiology ’03 NCSU

Name witheld writes:

I am interested in understanding the means by which XMRV or MLV is ‘transmitted’. Is it transmitted by way of vaccination development and becomes operative when a person’s immune system is suppressed for whatever reason? As yet I’ve not seen any article which addresses this issue.

Please note I am an interested private individual. I am not associated with any particular organization etc.

Charles writes:

Hi TWiV Team,

I thought you might find this video entertaining if you have not already seen it. I’m sure some of your followers might enjoy it also. It is a Lady Gaga parody about a bad lab project.

http://www.youtube.com/watch?v=Fl4L4M8m4d0

-Charles

Neil writes:

Hi guys,

I think in the past I’ve heard you read emails with “picks of the week”. If so, please consider the following book: Denialism by Michael Specter. Have you read it? there is also a short TED talk which touches on the main themes but is too short to convey everything in the book, of course.

http://www.ted.com/talks/michael_specter_the_danger_of_science_denial.html

Anyway he touches on a lot of the recurring issues that you do in the podcast including the need for more scientific literacy in the general public, the vaccine/autism debacle, poor flu vaccine uptake rates, etc.

Two of my favorite recent quotes have come from Mr. Specter; one from the TED talk (“we leap into the arms of big placebo”, and from the last chapter of the book, “Experts chosen to represent a specific point of view are cheerleaders, not scientists. And people who rely on them are denialists.”

I highly recommend it.

Neil

John writes:

Dear Doctors,

First some context. My status as a science fan (layperson) goes hand-in-hand with my passion for skepticism. In that regard Carl Sagan would be my intellectual hero in both fields.

So I thought about writing in to give some general comments on the episode partway through. I wanted to express my general disappointment in science communication these days and simultaneously praise efforts like yours to communicate science. When you were talking about what can we (scientists) do to better inform people (decisions based on science vs emotion) I was thinking “well you’re already doing it”. As a skeptic we encounter this problem on a regular basis. The situation that your guest Mr. Mnookin was describing is a regular occurrence in all areas of woo and pseudoscience. This often arises from the use of a ‘token skeptic’. A perfect example of how the media gets it wrong is the recent astrology news. I watched CNN report that the zodiac was changing and therefore your horoscopes might be wrong then juxtaposed it with some random astrologers saying don’t worry we know about it already. They all missed the real story which is “why does such a large proportion of the population of an industrialized country believe in magic?”. So I would like to add on my toned down reaction which is we need scientists both great and small to become public intellectuals in their spare time. The more they discuss the merits of recent research in their fields the better laypeople are able to understand and be critically skeptical of new stories. Sadly I do not have the patience of wiser men and women and so when I hear about things like jenny mccarthy vs 100,000 doctors it makes me quite angry. Which leads to my next general comment.

I can’t believe one of your listeners could be that dense, so willfully ignorant, as to be deifying the likes of andrew wakefield. I understand your show is an educational show about science and rightly eschews emotional reactions and political commentary. Your comment that the fellow’s emails “did not reflect that” was perhaps the most diplomatic thing I’ve heard in a long time. I wish that we as a nation could critically look at the evidence, conclude that this person was a repugnant, morally bankrupt fraud willing to put the lives of children in danger to make a quick buck, exile him to the arctic circle and move on with our collective lives. Once again my background as a skeptic makes me intimately familiar with the arguments used by the anti-vaccine crowd. Whether via cum hoc ergo propter hoc fallacies or their ability to move goalposts faster than the Army Corps of Engineers they spread ignorance and paranoia like the plague. Sadly their ‘follow the money’ arguments do not trigger any ironic neurons in their brains and prompt them to check on the monetary incentives that wakefield had.

Ranting aside, this all goes to the overarching theme of the episode, in my eyes, which is ‘the failure of the scientific community to effectively communicate to the public’. I am perhaps framing the problem unfairly and should add ‘and the failure of -insert here- to produce a nation of critical thinkers’. One of the reasons that I like your show and similar groups of scientists discussing science is that I get to hear respectful critical thinking in action. I know it’s not virology but part of the show is the communication of science and its role in the public (you aren’t keeping Alan Dove around just for his jokes are you?) so given the wakefield debacle perhaps it would be useful to discuss science in the public discourse, what young scientists can do, what science fans can do, kindly urge us to be patient or spur us to action.

So thanks for being my psychiatrists today in addition to my virologists (and parasitologist) while I rant.

Best regards, fan of the show, keep up the good work, lame joke about Alan, shake fist at Rich while it’s -2 degrees out, and looking forward to more.

Sincerely,

John

TWiV 126

Aaron writes:

Hi folks,

I’m a chemical engineer by background and I’ve done downstream process development in biopharma for years. Just lately, I’ve started working on a part-time bio Masters I’ve been taking all the standard cell/molecular bio classes I never had before. I’m about to start a course on “Biology of HIV/AIDS” and I’ve been using your back episodes to fortify my meager background in general virology. Thanks so much!

Okay, here’s my question, and stop if you’ve heard this one before:

One of the primary phenomena I work on is chemistry and physics in the freeze-concentrated state of frozen protein solutions. When you freeze the ice crystals out of an aqueous solution, the remaining excipients concentrate in interstitial space (like a slurpee). This gives you the opposing kinetics of high concentration at low temperature, which can lead to different chemistry than in the liquid state.

All this RNA talk raises a question I’ve thought about for awhile: I’m sure you guys are familiar with the Miller-Urey abiogenesis reflux experiments and some of the follow-up work showing that amino acids can be synthesized from H2O, CO2, NH3, CH4 and H2. Some follow-on experiments seem to show that the original frozen samples from this experiment formed even more amino acids when stored frozen for decades, possibly due to decomposition of some precursors formed in the original experiment. Additional work has shown that all 4 nucleotides can be synthesized from long term freezing of aqueous cyanide compounds (1).

I found some other articles that say that freeze-concentration is favorable for extra-cellular RNA polymerization (2), and for the spontaneous assembly of polynucleotides from precursors (3).

All of this points to the idea that the primordial cell-like environment in which life first evolved was the interstitial spaces of freeze concentrate in “dirty” ice. It makes sense to me because freeze-concentration is one of the few natural phenomena that dramatically reduce local entropy in a concentrated liquid. I’ve never heard of this idea before in my bio courses. Is “cryo-abiogenesis” a common part of the RNA-world hypothesis? Are there other major problems with this theory I am unaware of? Looking at these papers, it seems like primordial freeze concentration is the best explanation out there for the initial formation of organized bio-macromolecules. But, if this is so, I’m surprised I’ve never heard of it before. Any thoughts?

Thanks again for the wonderful podcast,

Aaron

1: The prebiotic synthesis of pyrimidines in frozen solution, Cleaves, Nelson, Miller

2: Ice as a protocellular medium for RNA replication, Attwater, et al, Nature Communications, September 2010 http://www.nature.com/ncomms/journal/v1/n6/full/ncomms1076.html

3: Eutectic Phase Polymerization of Activated Ribonucleotide Mixtures Yields Quasi-Equimolar Incorporation of Purine and Pyrimidine Nucleobases, J.A.C.S., Monnard, et al., 2003

Lillian writes:

re: episode #125 and XMRV contamination

My question about contamination is: if it is so common via cell lines, reagents, etc., why are there so many XMRV studies that found no evidence of XMRV either in controls or cases? It would seem that if contamination were a recurrent/ common issue, many studies would find some positives, even if a low number, equally in cases and controls. Of course, this might get down to the nitty-gritty of the exact cell lines, reagents, PCR primers, what experiments the lab had performed in the past, and even what experiments the authors had done in the past (and thus what they were exposed to), etc. but these issues should be explored rather than just hand-waving explanations that with positive studies, the cases’ blood samples were “handled” more than the controls or that these labs have been contaminated.

Thanks.

Bob Krug writes:

Hi Vince,

I enjoyed your podcast at the University of Washington. Several people here brought it to my attention. I just wanted to tell you one thing. I was NOT the second (nasty) reviewer of your paper.

I think that you would enjoy holding a podcast here at UT-Austin. People here would enjoy it. In particular, I think that you would enjoy meeting with two young virologists here, Sara Sawyer and Chris Sullivan.

Best regards, Bob

Robert M. Krug, Ph.D.

Professor and Chair

Molecular Genetics and Microbiology

University of Texas at Austin

Brian writes:

Dear Vince, Dick, Alan, Rich, et. al.

On a number of TWIV podcasts you’ve mentioned the quasi-species concept. In one podcast, Alan or Rich said something about having to look into that concept more closely. I assume this involves more than the elementary definition.

“Steps Toward Life” Manfred Eigen, Ruthild Winkler-Oswatitsch, Paul Woolley, provides among other things a rather concise “vignette” of the quasi-species concept for those of us who need the elementary approach. http://www.amazon.com/Steps-towards-Life-Perspective-Evolution/dp/0198547528

In addition, the authors provide scenarios for the beginnings of life from inorganic matter. (Less than perfect replication and compartments) And if that’s not enough, there is a fascinating treatment of viral evolution positing that viruses replicate their genetic material with enough error and enough accuracy that they sit at the edge of thermodynamic dissolution while having the maximum flexibility for adaptation.

I have no formal background in microbiology other than a reading of the 3rd edition of “The Molecular Biology of the Cell” (Alberts et al.) Now it’s time to buy the 5th edition to catch up with the last 20 years. That said, I have little trouble following the discussion.

I do have a question. I’m in my early 60’s, have time and enough money so I don’t have to work much. Is there any place in virology or parasitology for amateur participation?

Thank you so much for the podcasts, and for TWIP as well.

Best

Brian (The guy who sent Dick the Swiss vertical farm pics)

David writes:

Hi Vincent,

Was listening to your latest podcast (interesting and informative as always), and thought you might find a few additional items of interest.

First, you discussed in Ode to a Plaque the wonderful mechanisms that viruses use to move from cell to cell, and wondered if there were other examples. Here’s a paper you might want to discus: http://www.ncbi.nlm.nih.gov/pubmed/20023636; “Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses.” by Pais-Correia AM, Sachse M, Guadagnini S, Robbiati V, Lasserre R, Gessain A, Gout O, Alcover A, Thoulouze MI at the Pasteur Institute.

Another item: you discussed the PacBio sequencing system, a very clever nanotechnology method for ultra-high throughput sequencing. There’s another technology that just came on the market that also uses very clever nano chemistry: the Ion Torrent system, now sold by Life Technology (www.iontorrent.com). It uses semiconductor technology to build tiny pH-sensitive chambers, each one containing a single synthesizing DNA molecule, and then detects the addition of each nucleotide by the change in pH caused by the release of a proton when the nucleotide triphosphate is hydrolyzed during incorporation. In that way, it doesn’t require any special reagents, such as fluorescent-labeled nucleotides or fancy cameras, but just uses normal nucleotides and polymerase, which should result in reduced costs. Like the PacBio system, they are still trying to optimize read-length and accuracy, but it’s a pretty clever idea.

Finally, you discussed the difficulties of conducting vaccine trials in humans. You may want to check out the work of John Treanor at Univ. of Rochester, who conducts influenza virus trials in volunteers, who are quarantined for 10 days following exposure to attenuated viruses, and provide daily nasal swabs to watch the replication and ultimate clearance of the viruses. See: http://www.urmc.rochester.edu/news/story/index.cfm?id=2899

“The investigational vaccine to be tested in this first isolation trial is similar to FluMist, the licensed nasal spray vaccine for seasonal flu, except that it contains two genes that help it mimic the H7N3 strain.

To participate, study volunteers must be between 18 and 49 years old and must not be pregnant, have an allergy to eggs, or have another medical condition that compromises their immune system and thereby would make live-virus vaccinations unsafe. If selected, study volunteers must stay a minimum of 12 days (two days before receiving vaccine, or “day -2” and “day -1;” the day of the vaccine, or “day 0;” and at least nine days following the vaccine, “day 1” through “day 9”). While on the unit, they will undergo daily physical examinations (e.g., vital signs) and nasal washes (to see how long the weakened virus remains in the nasal cavity, where vaccine is initially sprayed), and provide several blood samples. To be discharged, volunteers must go two consecutive days (after day 7) with no febrile or flu-like symptoms, including a negative nasal culture. Three separate outpatient follow-up visits, each requiring a nasal wash and blood sample, will be scheduled for one, two and six months after initially receiving vaccine.”

It’s popular amongst college students, who can make a couple of thousand dollars by participating.

Keep up the good work.

David
(the write is Professor of Pathology and Microbiology, New York University School of Medicine)

Jim writes:

Dick,

Your interest in information organization and display prompts me to send this link which is useful with the current public interest in the topic of radiation exposure: http://xkcd.com/radiation/

It’s interesting to me as a retired nuclear power plant worker, too. We were just converting from rem to sieverts as I retired and this link helps in that regard. Five rem is the current federal standard maximum allowed exposure for a nuclear worker. You can see what that equates to in sieverts at this site.

Regards,

Jim

Smithfield, VA

TWiV 125

Todd writes:

Hey Docs!

I’m a computer programmer who listens to podcasts on my long commute. The highest science education that I’ve had was college Chemistry. As an Electrical Engineer the science classes we took tended to not be biology oriented, so while some of it is over my head, to say that I find biotech and molecular biology fascinating is an understatement.

Virus related question: I also have a picture of me with the mumps at around 4 years old (1974). When did the MMR come out? Was I one of the last in my generation to have it? I’ve never met anybody my age who’s had the mumps, only older than me.

P.S. Lately I’ve been listening to the FiB, TWiV, and TWiP podcasts to the point where I’m neglecting my techie podcasts. You guys are causing me to lose some of my geek creds 🙂

Regards… Todd

Peter writes:

I really enjoy twiv and especially twip. The Socratic method to teaching parasitism works for me.

I am an Aerospace engineer but I now work in IT. I am an engineer at heart, but I find parasitology fascinating, and viruses are like little machines, so also fascinating to an engineer.

In your recent TWIP discussion of giardia, you noted that your UV pen is ineffective against cysts because of their low metabolic rate. Or more specifically, I think it was because their DNA was inactive? I didn’t know that was a requirement for UV to work. So I wonder, is UV light effective in killing viruses in water?

I seem to recall that radiation is an effective treatment for cancer because cancer cells divide so rapidly. Is that the same effect?

Thanks.

peter

Aaron writes:

Dear TWIV,

I know my last set of questions about ERVs was long, but I’m still holding out hope that you can answer some of them in an upcoming TWIV. I’ve sent similar questions to several virologists and haven’t received any answers.

In the meantime, I have a couple more basic questions where I need some clarification.

I’ve heard you guys talk about viruses evolving to become less virulent. Could you explain this to me? Are we really saying that the immune systems of their hosts have evolved to resist the viruses rather than the viruses changing something to become less virulent?

My understanding of viruses is that they harm the host merely by reproducing and using up the cell’s systems. I understand that very few produce proteins that are actually toxic to the cell. Since viruses consist of only a handful of genes that are dedicated to the production of new viruses, what genes can be mutated to decrease the virulence of a virus? It seems that if one of the viral genes are seriously mutated, the virus will be unable to produce new viable viruses. While that mean the virus is less virulent, it also means the virus will cease to exist.

On the other hand, a virus host is a complex organisms with many genes. A host can experience a mutation in an immunity gene that allows it to resist a viral infection without changing anything else in the host. A virus doesn’t have this luxury – any mutation will either cripple it or allow it to sustain its infection – as is the case with HIV. The only “neutral” mutation I can think of in a virus is one that causes it to infect a different cell type. Is this what you mean by a virus evolving to become less virulent? That it now infects a new type of cell that isn’t as critical to the host organism?

The way I understand it, a virus is either replicating and causing damage to the host – or it is not replicating and it is latent or eliminate. I’m not sure what the middle ground is where a virus is happily replicating yet is not virulent.

I hope you understand the gist of what I’m trying to say.

Thanks a bunch,

Aaron

TWiV 124

Norm writes:

First, I love your podcasts.

You guys are constantly grousing about the lack of research funding.

I was curious.

NIH, funding has risen every year since 2000, from $17B to the current $31B (supports 325,000 researchers)

NSF funding has risen every year since 2000, from $2.5B to $5.5B

I assume money is also available from Corporations, Charities, Foundations, State Governments, Foreign governments, Department of Defense, CDC, FDA, Universities, etc.

Looks to me like we are spending lots of money on research.

I wonder…

Is it possible that we are not spending money on the “right” things because politics and bureaucracy push the money to the “wrong” things?

My local government spends lots of money, but strangely never seems to be able to fix potholes. Some people say we need to give the government more money so they can fix the potholes, but when get more money, the potholes stay unfixed. Strange that.

I am suspicious that you could double the funding of NIH and research you advocate would still not get funded and you would still be complaining about too little money for research.

As a last thought, it seems to me that the cost of research should be going down, after all much of modern research equipment and services are computer based and these should get cheaper and more powerful every year.

Am I missing something?

Norm

Lynn Enquist writes:

I enjoyed hearing you discuss our recent paper on some basic virology using colorful herpesviruses. I have some answers to questions you raised about the phenomenon of limited viral genome expression and replication.

First, the FACs sorting experiment says that the viral genomes that are being expressed in the cell are the same ones that are replicated and packaged. Expression, replication, packaging are all linked! You don’t have a pool of genomes all expressing things and a subset get replicated. Or a random pool of genomes replicating and expressing with a subset being packaged. Rather, a few genomes are chosen early to be transcribed, replicated, and packaged in to virions (that go on to infect the next cell).

Second, Oren has shown that the effect is not due to the promoter used. He did a beautiful set of experiments where the PRV VP26 capsid protein was fused to each of three different fluorescent proteins and these hybrid genes replaced the normal VP26 gene. These hybrid genes are transcribed from the VP26 promoter – which is a PRV promoter expressed only after DNA begins to replicate. Cells infected with mixtures of these viruses reproduce the same phenomenon as we reported in the paper. They also provide more data since these fusion proteins assemble into capsids in the nucleus. The dots of colors in each nucleus are all the same color verifying again that only a few genomes are chosen to be expressed and replicated. Amazing, I think (and very colorful too, for Rich’s benefit).

Oren has infected primary neurons, primary fibroblasts, and other cell lines with the colorful herpesviruses we have on hand. All cells show the same restriction of color as we reported.

Lynn Enquist
Professor, Princeton University

TWiV 123

Sven writes:

Dear TWiV Captain and Officers,

I am a Swedish listener in my fifties, with a neolithic MSc in computer science and nowadays active within software quality (and yes, that’s an oxymoron…). I found TWiV in September 2010 and I have now soon listened to them all. I am, as you understand, deeply hooked by TWiV and TWiP, and look forward to TWiM! Like so many others I listen during my commute, possibly to the detriment of my driving ability (no comments, please…). While sometimes much of the biochemical details are beyond my comprehension, the general structures and phenomena within the field are very interesting and stimulating. I also agree wholeheartedly with the majority in praising your style and tone!

Now and then you touch upon the subject of evolution of this or that mechanism in cells, and several times you have used the approximate phrase “evolution makes use of whatever it can get hold of”. There are, of course, many examples of that in nature as you have mentioned, but also (at least) one artificial that I find very instructive. In a paper by Adrian Thompson (“Exploring Beyond the Scope of Human Design: Automatic generation of FPGA configurations through artificial evolution.”, 1999 I think, unfortunately I can only find an “extended abstract”) he describes how “evolution” was used to produce an integrated circuit capable of discriminating between tones of two frequencies. Even though the circuit was, to an engineer, too small, and also digital rather than analog, the evolutionary process used managed to achieve the goal. At first glance this may not seem so surprising. One of the more intriguing aspects, however, was the fact that although some parts of the chip appeared not at all to be connected to the “core” of the developed function, they could nevertheless not be eliminated. The author assumes that these parts still contributed through other means such as “[…] electromagnetic coupling, or interaction through the power-supply or substrate.” The author continues “Evolution was able to exploit this physical behaviour, even though it would be difficult to analyse.” So, the evolutionary process actually found, and exploited, phenomena an engineer would consider parasitic and unwelcome – to wit, phenomena an engineer would not look for and certainly would (should…) not dare use. But as evolution is blind to what we term “purpose” it had no such qualms! I find this very intriguing, as I see clear parallels in the microscopic world of cells as well as in the macroscopic world of ecology – there are so many intricate dependencies and mechanisms that, because they have evolved rather than been designed, are not fully analysable and are completely devoid of intentional “purpose”.

Let me finally suggest as a POTW a book, unrelated to the previous subject: “The Ghost Map: A Street, an Epidemic and the Hidden Power of Urban Networks” by Steven Johnson. A fascinating tale about the cholera in London in 1854 and how John Snow traced the source of the outbreak – a combination of detective story and science mind, if ever there was one!

Thanks for a great show and service to the public.

Live Long and Prosper!

/Sven-Urban

Sweden

Ed writes:

Dear TWiV,

Your tongue-in-cheek discussion after Alan’s pick of the Avian Vocalization Center on TWiV 112 that suggested recoding the sounds of viruses reminded me of an email I received from a friend of mine that pointed to that fact that this is already being done. I also heard mention on a Nature Medicine podcast that a grad student in Georgia, Alexandra Pajak, composed a symphony using the HIV sequence.

Here are the links: http://www.hhmi.org/bulletin/nov2010/centrifuge/scientific_artwork.html

http://www.scientificamerican.com/blog/post.cfm?id=what-does-hiv-sound-like-2010-10-27

I think it would be really interesting to find out what each viral symphony would sound like, and the result of viral evolution on each score. I understand that Ms Pajak also converted the amino acids and not just nucleotide sequence into music. Thus, silent mutations in the nucleotide sequence would obviously result in no change to the amino acid score. Do you think this could be utilized as a way to analyze sequences in the future by immediately converting it into notes that correspond to each nucleotide and comparing the music by listening? It would obviously have to be free of artistic interpretation in that case as both artists I linked to here adjusted rhythm and tempo to make the pieces more pleasing to listen to.

Thanks again for your fantastic podcast.

Multiple Sclerosis Research Center of New York

Dan writes:

Hi TWIV,

Thank you for your podcast. Please don’t feel the need to read this email on the show; I don’t want to turn TWIV into TWICFS.

Listening to TWIV and reading virologists discuss a potential XMRV/CFS link, I’m impressed by the thoroughness and caution which virologists take about drawing conclusions.

This makes a striking contrast with earlier CFS research. Take this paper* asserting a link between early childhood abuse and CFS. The link between the paper’s findings and conclusions involved a complex chain of causal links, none of which were investigated. Many of the limitations of the study aren’t discussed, including similar limitations which are frequently discussed in XMRV research (difficulty identifying patients, contradicting results of other groups, lack of blindedness). This study appears to me to be much weaker than virtually any virology study. Yet, at the time that it was done, the study was uncritically hailed in much of the news media. There has been no gauntlet of studies attempting to poke holes in the hypothesis, as there are in virology. And this is just one example of many.

It seems to me that the bar of evidence required in different areas of science is quite different. I believe this creates a systemic bias, where the least cautious areas of science will have their results most broadly accepted until another area contradicts it. I don’t really know what could be done about this, but I’m curious about your thoughts. It has a real and large impact on people with CFS, as bad research often leads to bad policies.

Thank you again,

Dan

Austin, TX

*http://archpsyc.ama-assn.org/cgi/content/full/66/1/72

Heather writes:

Hello, TWiV guys,

In response to Ken’s podcast idea on TWiV #111, I say go for it! I’m a medical student at Columbia University P&S, and I disagree with Alan about how much time you’ll have while you’re in school. Here at P&S, activities outside of our regular curriculum are actively encouraged, especially in the first two years (that’s actually when you’ll have the most free time). Students play sports, do art, put on concerts and plays, volunteer at free clinics, and still have time to study and learn medicine. When you start school, ask around and you’ll likely find several people who would be interested in helping you start a podcast, especially if you also talk to students in other programs or years at your school. You’ll probably even find that working on the podcast will help you learn the information you need for classes better!

Heather

P.S. Alan, you’d be surprised at how much effort goes into the plays and musicals we do here at P&S. The students involved put in hours and hours on many rehearsals, set design, sound and lighting, even during exam periods (and yes, we do still manage to pass all of our exams) and we invite everyone on campus to the multiple performances we do. Not to brag, but the students and faculty are almost as proud of our extracurricular achievements as we are of our medical knowledge.

Jeff writes:

Hi TWIV guys,

I was just listening to your show with Alan Rein on XMRV. Both you and Dr. Rein seemed to think that identifying junctions in samples between XMRV and human genome from tissue and mouse genome IAP controls would be good evidence for legitimate XMRV infection in patients.

Both of these seem like they would address contamination with mouse genomic DNA, but my reading of the Hue et al. Retrovirology paper was that they were asserting that false positives could be from contamination with human cell lines such as 22Rv1. Do you think such contamination could be responsible for some false positives for XMRV in patient samples? If so, is there a way to control for such contamination?

I’d be interested in your thoughts.

Jeff

TWiV 122

Luke writes:

Hello TWiV hosts,

I’m currently working as a technician in the biochemistry and molecular biophysics department at Columbia, having just received my BA from here in the Spring. First of all, I’d like to join the chorus of praises for your dedication to doing this podcast. I first heard about it this past Spring when I took the virology class as an undergrad and have always found it to be a very entertaining and informative discussion of a topic which I find very interesting. If I may, I’d like to ask if you could touch on two subjects that I’ve recently read about. The first is one that I think you’ve talked a little about before, and that is the subject of CRISPRs. Specifically, I would love to hear a bit more about the mechanisms by which they help defend bacteria against phage and how they could have gotten into the genome (perhaps these things are not very well understood yet, but even some speculation would be interesting).

The second is an article in the July issue of PLoS Pathogens entitled, Unexpected Inheritance: Multiple Integrations of Ancient Bornavirus and Ebolavirus/Marburgvirus Sequences in Vertebrate Genomes. The authors find several sequences in vertebrates including humans that seem to have been integrated from viruses in the two virus families mentioned in the title. Not only are there long ssRNA viral sequences integrated into a dsDNA genome, but they seem to be conserved and even expressed in some cases. One big question that I have is regarding the mechanism by which a single stranded RNA virus’s genome could be integrated into the genome of its host (they go into a possible mechanism involving LINE elements in the paper, but I’m not sure if I fully understood the details). I believe Bornaviruses go into the nucleus, which is unusual for an RNA virus, but does the same go for the other two? Are these integrations a result of an error in a pathway, and if so, is it a viral or a host pathway? I happened to read this article shortly after listening to your ASV episode where one of your guests mentioned that there is a potential for using viral proteins as drugs which could interfere with the formation of viable virus particles when a virus infects a cell. Could this be a case of nature already having used this idea?

Thanks again for the wonderful podcasts.

Best,

Luke

PS: Although from my understanding it’s not really relevant to humans disease, could Dick talk about the liver fluke worm, dicrocoelium dendriticum on TWiP? I recently heard about it, and it’s life cycle seems absolutely fascinating.

Aron writes:

I recently developed a science obsession that led me to learning about viruses and ERVs. I found your show in the search, and although most of the terminology is unfamiliar to me, my progression through your virology 101 podcasts, as well as some serious web searching is helping to bring me up to speed. I listened to your podcast on ERVs – and I’ve read numerous articles and scientific papers.

In all of that, I’ve never heard a comprehensive description of how an ERV enters the germline.

In those regards, I have some specific questions:

1.) How does a retrovirus bypass the blood-testes barrier to reach the germ cells? I understand that HIV does so by “hiding” in white blood cells. Are any other retroviruses capable of doing this (i.e.: they must be able to bind to CD4 receptors)?

2.) Of the 5 types of ERVs: Alpharetroviruses, Betaretroviruses, Gammaretroviruses, Lentiviruses, and Spumaviruses, is it known that any of them have the correct surface proteins to bind to germ cell specific binding sites? I read that the common sperm cell binding sites are heparan sulfate and mannose receptors. I’m not sure if those are the same for spermatagonia.

3.) Once inside a germ cell, how does a retrovirus successfully integrate its DNA into the host DNA? I read some HIV studies where the sperm of deceased HIV patients were examined – as well as studies where HIV was introduced to sperm in vitro. In no case was the viral DNA inserted into the host’s chromosomes – even though the virus was found within the germ cells. One study suggested that a low hydrolytic activity in the cytosol of sperm prohibited viral uncoating. Could the tightly wound structure of sperm chromatin also hinder viral DNA insertion?

4.) My guess is that a retrovirus would have more success inserting its DNA in a spermatagonia stem cell than in a developed sperm. How would the spermatagonia be able to survive such an infection? Wouldn’t the viral infection and subsequent release of new viruses eventually destroy the stem cell? It if survived, would the host produce sperm cells with the retrovirus insert for the rest of host’s life? Or would the host have to reproduce while actively infected with the retrovirus before the immune system wipes it out?

5.) Lastly, if the retrovirus was able to jump through the previously mentioned hoops and a provirus infected sperm fertilized an egg, how would the forming baby be able to survive having a provirus in every cell of its body? It’s my understanding that the majority of modern day exogenous retroviruses cause cancers, lymphomas, and leukemia. How does any child survive long enough to reproduce when these pathogenic forces are at work in every cell of its body?

I appreciate any help you can lend. I’m also wondering if I will have to listen to a podcast to hear my answers read to me, or if you will respond via email?

Aaron

Tim writes:

A fan of your show….. I would like to hear your comments upon reading this relatively recent publication in the Journal of Virology:

Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets ….J Virol. 2010 April; 84(7): 3690–3694. Published online 2010 January 27. doi:10.1128/JVI.02715-09.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838105/?tool=pubmed

thanks,

tim

TWiV 121

Gopal writes:

Hello, TWiV-ers,

I am a science journalist based in India and have, over time, become addicted to TWiV. I enjoy the jokes and puns that come along, making TWiV a nice way to to broaden my knowledge and keep up to date. (Oh – and I also faithfully listen to TWiP.)

I just read an article in The Scientist about Charlie Rice’s work with the Hepatitis C virus (http://www.the-scientist.com/2010/12/1/24/1/ ). The article says:

“Vertex’s protease inhibitor, VX-950 (now known as telaprevir), has emerged as a leading agent for the treatment of HCV patients with the genotype-1 strain of the disease. A second compound, boceprevir, developed by Schering-Plough, proved equally effective in those patients.”

I have two questions:

As both drugs in question treat just one genotype, is it the case that there is no conserved region in the protease that can be targeted so that all or most strains of Hepatitis C can be treated? I presume that treatment will be a lot cheaper if a single drug can be used against multiple strains than when different drugs are needed for various strains. The latter might also mean no drugs being developed for strains common in developing countries.

If not, are there any other viral proteins that are being or could be looked at for the same purpose?

Maybe you could consider taking up Hepatitis C as a topic in TWiV and perhaps have Dr. Rice join the discussion.

Regards,

— Gopal

Jacob writes:

Hi all,

I am a molecular biologist working in Biometrology. I want to say that as someone who can understand much of the technical details, you guys do a very good job of relaying information to audiences from many different educational backgrounds. Also, as an Australian, it is nice to hear us getting a mention quite often, mostly in regards to our rabbits.

I was just listening to TWIV 112 and wanted to add something to Rich’s pick of the week (The Scientists top 10 innovations 2010; #1 was third gen seq, eg Pac Bio). The 3rd generation sequencing technology is certainly amazing, but you guys missed one of the most amazing things about it. Someone mentioned about the background of the other nucleotides floating around but the thing with this technology is that the reaction vessel is smaller than the wavelength of light. This prevents the background fluorescence from reaching the detector. It works in a similar way to your microwave oven, in that the microwaves cannot pass through the holes in the door, but visible light can, as its wavelength is smaller. The polymerase is attached to a transparent layer at the bottom of the reaction vessel, so the light from the fluorescently tagged diphosphate is able to pass through this transparent layer and reach the detector. This means that there is essentially no background so a single dNTP incorporation can be detected.

On an entirely separate note, Vincent and Dickson have spoken on several occasions about a podcast about physics similar to TWIV. I only listen to four podcasts regularly including TWIV, TWIP and Futures in Biotech, but the fourth is one that I really think that you will enjoy. It is called Astronomy Cast (http://www.astronomycast.com/) and features two people, one an educated amateur (Frazier Cain) and the other an astronomy researcher (Dr Pamela Gay) discussing topics relating to astronomy, astrophysics, planetary geology, scientific history and cosmology, and even had a recent episode on exobiology in response to the arsenic incorporating bacteria story. As I write this, they are up to episode 210, each dealing with a particular topic, similar to your virology 101 episodes. The hosts also have their own blogs, as you do, and post many fascinating stories from the astronomy field (http://www.universetoday.com/ and http://www.starstryder.com/). I hope that you enjoy it.

Keep up the good work,

Jacob

Vince writes:

Hello

Although phage do not alter our health directly, they do provide novel genetic functions to their unicellular hosts, giving them access to new environments including the confines of our own bodies. My question is, can phage that are produced within our bodies transform otherwise harmless bacteria into pathogens? Or conversely, can phage produced by our endogenous microbiota infect other related invaders?

Thanks

Vince

Patricia writes:

Hello TWIV hosts!

I am a PhD student in Virology (Hepatitis C virus) at the University of Saskatchewan (Sus-KAT-choo-W’N, nobody says it right the first time), and I have been saving up comments for over a year now. Unfortunately, I have always neglected to send them in, because I am so frequently behind in my listening that I figure someone else will have said it before me! Plus, it’s rather difficult to take notes or write emails when you’re in the biosafety hood, which is where I listen to most of your ‘casts – thus, most of my comments are kept in my head, a notoriously disorganzed place where it is easy to lose things.

That being said, I was actually reading Letters on the TWIV site, and realized that I can help respond to one of them (assuming you haven’t already) while actually at my computer. Annamaria (in TWIV 114) asks about a site for people to post examples of things they have tried that have absolutely not worked. I have two links for you:

1) The Journal of Negative Results in BioMedicine: http://www.jnrbm.com/info/about/

This one is, of course, not for “I did a Western blot with this antibody and there was a lot of background,” but moreso for “No matter what I tried, I could not demonstrate any interaction between this cellular protein and this viral protein.” Still very useful for eliminating roads of investigation because others have tried them already.

2) Scientist Solutions: http://www.scientistsolutions.com/

This site is more immediately useful, as most protocols that people post are then treated as a blog, where they write back and forth, and folks can ask for clarification. It’s a great way to get hints and help from very experienced people to very inexperienced people, and I fnd that I keep going back to it to look for more protocols.

And I’ve one other “immediate” comment to make:

With regards to recent comments from the TWIV – 10 of 2010 episode, I just wanted to point out a hazard of using microRNAs when we don’t yet know “everything” – or at least, “enough” – about them. While the idea of using microRNAs to down-regulate or inhibit replication of an adenovirus vector in tissues outside the CNS is in principle quite clever, it could so very easily backfire. Hepatitis C Virus relies heavily on the liver-specific and liver-abundant miR-122 to enhance or permit its replication (which term to use is a matter of debate). What if a microRNA enhances the vector in a tissue rather than inhibiting it? We still don’t know how microRNAs define whether to inhibit or enhance translation of mRNAs (they do both, although the enhancement findings are less common) – the suspicion is that it depends on where the microRNA-complementary site is on the mRNA, but that hasn’t been fully defined yet.

(See: Ørom, U.A., F.C. Nielsen, and A.H. Lund. (2008). MicroRNA-10a Binds the 5’UTR of Ribosomal Protein mRNAs and Enhances Their Translation. Molecular Cell 30(4): 460-471.)

In the case of Hepatitis C virus, there are multiple miR-122 binding sites throughout the genome – two for sure at the 5′ end, one whose binding has not been proven at the 3’ end, and several proposed sites within the genome which have been presented at meetings but not yet published. Clearly, in this case, the enhancement (not of translation, but of replication) supercedes any inhibitory effect the microRNA might have.

Taking a different approach (I don’t recall if this ever came up in TWIV), researchers have published a paper using an antagomiR (LNA that is complementary to miR-122 and should therefore mop it up) to inhibit this miR-122-mediated enhancement of HCV. The work was done in chimpanzees and they do show reduced viral titers while the LNA is still in the chimp’s system.

Lanford, R.E., E.S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, M.E. Munk, S. Kauppinen, and H. Ørum. (2010). Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection. Science 327(5962): 198-201.

Thanks so much to all of you – VIncent, Alan, Rich, Dick – for your commitment to this podcast. You have made me smile and laugh to myself while in the hood (which makes me look like a crazy person, but oh well!), or shake my head and frown until someone catches a mistake, or re-explains something for me. You’ve made me – like many others – feel like we have a better grasp on the world of virology, outside of our own little niches. Above that, I get to share super-cool stories with my friends; sadly, they are less amused by some of the things that I find fascinating, but I keep trying! I hope you never, ever stop sharing with us.

Best regards,

Patricia

Kirsten writes:

I was wondering if a connection is being considered between the information presented by the Canadian group (TWIV 77) that correlates enhanced disease following flu vaccination in a percentage of cases and the data presented by Monsalvo et. al. (TWIV 112) that attributes enhanced disease to the presence of non-neutralizing antibodies and immune complexes. Could the non-neutralizing antibodies be present due to previous influenza vaccination?

Consider the RSV vaccine that was found to contribute to the presence of a low avidity, pathogenic antibody (TWIV 13), could there be a similar situation occurring?

Thanks,

Kirsten

Peter writes:

phage usage as an antibacterial cleaning solution

http://en.wikipedia.org/wiki/Intralytix

peter

Sydney

TWiV 120

Ashley writes:

Vincent, I am a huge fan of TWIV and thank you and the others for taking time out of your busy schedule to do the program. I have my B.S> in Biology and Chemistry and would love to go back to school. I read textbooks, listen to podcasts from itunesU and so forth because the information about the world around us is free! I am about to begin producing my own podcast and wondered if you would answer a few questions regarding how you go about producing yours. Mine is going to be a library of general science podcasts specifically for Christian Homeschool Students. The point is to provide extra material that can be coupled with their daily lessons, making learning fun. Hope to hear from you soon.

1. What audio editing software do you use?

2. Is there a video editing software you use?

3. How do you do about having multiple guests via Skype?

4. Would you be willing to be a guest on my show once it’s up and running?

David writes:

Sir,

Would you have any recommendations on a good primer into microbiology that I can read or listen to on as an audiobook? I am interested in extremophilic organisms. I’m looking into reading up during the holidays. Thank you.

Respectfully,

David

Microbiologist in training

NC State

Jim writes:

I tried playing the game for about an hour and ran thru the tutorial 3 times. I made one successful match at the lowest level during that time and don’t feel I can learn the rules. Just wonder if TWIV participants have tried the game and how they do/did.

http://phylo.cs.mcgill.ca/eng/index.html

Jim,

Smithfield, VA

David writes:

Dear Twiv folks

I am an assistant professor at Vassar College, just up the Hudson River from you guys. I love twiv and try my best to keep up with the episodes. I teach courses in virology and microbiology and an introductory biology course in which we explore the fundamental principles of biology from the perspective of viruses. Rather than doing broad survey courses for intro biology, each section taught by a different professor is taught from the perspective of their field of interest. Mine is on viruses and their hosts; its great to be able to introduce freshmen to virology right off the bat, and it is actually quite easy to talk about everything important in biology (evolution, genetics, cells etc) while discussing viruses.

I have a blog (which was actually inspired by twiv) and I use it to keep my students thinking about virology outside of the classroom and introduce them to interesting new work going on in virology. Ive also had my students write posts, and Im quite impressed – keep in mind these are freshmen! I want to increase activity on it from people outside the college – it would be great and beneficial for students to know that Im not the only one reading their work, and I bet the quality of their work would increase knowing there is a broader audience.

So Im hoping that you will read this on twiv and send all those millions (or is it billions?) of twiv fans my way.

The blog is called Viva: Virology at Vassar

http://blogs.vassar.edu/viva/

Cheers

David

Biology Department

Vassar College

Damien writes:

Dear Vincent, Dick, Alan, Rich,

I recently saw this article about a former colleague’s group that I thought may be of interest. The article is in Swedish (which I can neither read nor speak). I usedtranslate.google.com. I would be interested in your thoughts as to this being another way of targeting influenza. The website is http://lundagard.se/2010/12/08/lundaforskare-kan-losa-influensavirusens-gata/

I really enjoy the TWIV and TWIP, they are great for a Scientist who specialized in Chemistry with a limited amount of Biochemistry who studied Photosynthesis (Oxygen Evolving Centre structure and mechanism) as a graduate student in the Chemistry School.

Keep up the good work.

Best Wishes for Christmas and the New Year,

Damien

Melbourne Australia

André writes:

G’day TWIV team,

I love your show!

I have a question on Dengue infection and the severe haemorrhagic fever (DHF) and shock syndrome (DSS) that often occurs upon subsequent infection by another serotype.

I got aware of Sanofi-Pasteur Australia looking for participants for a phase III trial of a “live” dengue vaccine (see attached brochure and link http://clinicaltrials.gov/ct2/show/NCT01134263). I totally see the need for such a vaccine, however when I read “attenuated live vaccine” I remembered my Strauss and Strauss textbook and your show ep. 82 (Zellweger et al, 2010), stating the fact of enhanced severity of disease upon subsequent dengue infection by another serotype.

It confuses me, especially after the HRSV vaccine debakel, that they pursue what seems to be an avenue that could put vaccinated people in a worse position than unvaccinated. There are also only limited animal models to mimic the severe disease development upon second infection that could help with vaccine development (Zellweger et al., 2010).

I have great faith in the scientific advisory board who regulates clinical trials and also in Sanofi-Pasteur to be aware of this fact, so I must have overlooked something that would eliminate my suspicion.

Q1) The vaccine is tetravalent, covering all known four serotypes. But do you think one can be sure that it will generate a good enough antibody response against all serotypes in all individuals? Do we know all serotype and does our grouping into serotypes make sense with regard to predict DHF/DSS?

Q2) Do you think the vaccine could have been / was tested reliably in an animal model in order to investigate what effect a subsequent natural infection post vaccination would have in terms of the severe disease? Zellweger et al. also couldn’t use a wild type mouse model.

Q3) The participants in that phase III study will not be challenged with virus after vaccination, of course, so only blood work will be available to tell their immunity status. By doing so do you think the status of protection against Dengue (DHF/DSS) can be assessed?

Please help me understand this.

Many thanks!

Kind regards and keep on doing TWIV.

André

Zellweger et al., 2010 (Discussion)

“Our results confirm in vivo that even neutralizing antibodies have the potential to induce ADE (Mehlhop et al., 2007; Pierson et al., 2007), provided that the occupancy threshold required for neutralization is not reached (Burton, 2002). To be neutralizing, and therefore optimally protective, an antibody must be of high enough affinity for neutralizing epitopes on the surface of the virus, and it must be present in sufficient concentration (Pierson and Diamond, 2008). Failure to fulfill either of these requirements will prevent neutralization. This idea can be applied to sequential DENV infections to explain why antibodies induced by one DENV serotype, although protective against that serotype (Whitehead et al., 2007), may increase the risk of severe disease upon infection with a heterologous serotype due to enhanced infection of cells bearing FcgRs by subneutralized viral particles (Halstead, 2003).”

Dr. André Paul | Postdoctoral Research Officer | Children’s Cancer Research Unit

TWiV 118

Jenny writes:

Hi TWiVers,

I’m currently listening to episode 84-Gators go viral and I’m so excited to hear you talk about my virus, EHV1, even if it was only briefly and I decided it was finally time to write you guys a letter.

I am a PhD student in Melbourne, Australia. I found TWiV when I attended ASV in Bozeman (in a strange coincidence I am actually wearing the T-shirt from the meeting) and have been busily trying to catch up on past episode. I actually meet Vincent and was fortunate enough to sit with him and Karla Kirkegaard at dinner following the live TWiV session. I love the addition of Rich to the group because he always asks or make the comments I would ask if I was part of the conversation, sometimes I even talk to the radio when I’m listening in the car. I’ve recently been collecting samples about 2 hours out of Melbourne almost everyday and that has really helped me catch up.

So I have a question and a suggestion:

The question is about Vaccinia. From what I understand (which may be wrong) Vaccinia is the virus that causes cowpox or is very closely related to it. Is it still around in the environment and does it still cause disease in cows? If so can people become naturally infected with Vaccina?

My suggestion is for you to get someone in to talk about EHV1 because it’s a really interesting virus and a very important veterinary pathogen (I might be biased). It can cause, apart from the respiratory disease and abortions you mentioned on episode 84, a serious melyoencephalitis that was classified as a potentially emerging disease by the USDA in 2007. One of the main focuses of my research is why we see much lower levels of this form of the disease in Australiaas well as trying to understand the pathogenesis. A paper that has had a big impact on reseach into the virus is Nugent el at JOURNAL OF VIROLOGY, Apr. 2006, p. 4047–4060 and would be a good place to start if you were interested.

I love the podcast and am dreding catching up because then I will have to wait a week between episodes. I recommend it to anyone who will listen but I don’t think I’ve converted that many people yet. Most people think I’m a bit strange for thinking viruses are fascinating.

Sorry if any of this doesn’t make sense I’ve been in the lab since 5AM.

Keep up the great work and I’ll keep listening and telling people,

Jenny

Conor writes:

Hi Twivers (or Twivists),

As everyone says, love the show. It gives me a great view of virology outside of my own work in HIV. I just wanted to send on 2 papers from the HIV field which may help in answering the question posited by Pretesh in TWiV 107 about the distribution of glycoproteins on the surface of virions. It has been shown in the interaction between HIV and CCR5 that multiple chemokine receptors are required for successful viral entry (Kuhmann et al 2000). Also as multiple glycoprotein trimers are involved in the receptor interactions, the majority of the virion surface trimers are present at the site of interaction with the host cell (Sougrat et al 2007). These results indicate that the distribution of glycoproteins is not only heterogeneous across the virion surface but plays a major role in the binding of host receptors during cell entry.

I hope those papers shed some light on this topic. Thanks again for all the great weekly info.

Regards,

Conor

(In transit between NUI Galway, Ireland and Dalhousie University, Halifax, Canada)

Paper links:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC112217/?tool=pubmed

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1864992/?tool=pubmed

Noel writes:

Dear Vincent Racaniello and Dick Despommier,

I am an undergraduate and just signed up for a biology of viruses. I am starting a little undergrad research with Candida albicans. I asked the professor in charge of my research if there were any viruses that infect C. albicans. We went on talking about how it’s hard for a virus to break through the membrane to infect it and there is little research about it. We figured out that we could do a little experiment using histone deacetylase inhibitors to manipulate the expressed genes, and we could possibly see viral DNA if it exists in the different strains of C. albicans we have. I am brand new to virology and brand new to research. I would personally be grateful if you two did a TWiV about viruses in fungi and maybe the modern techniques of research within this growing field.

Very Respectfully,

Noel

Cheryl writes:

Hello! I first want to say, you guys make two excellent podcasts-keep up the fantastic work!

I have a few questions:

Can someone taking immune suppressants be at an increased risk of developing cancer? If yes, how so? My guess is yes.

Can you guys make an episode about the Tanapox virus? I worked in a virology lab at Western Michigan University and the model there is Tanapox. I learned more basic lab techniques and watched the graduate students using tanapox, but sometimes they were too busy and couldn’t explain everything that they were doing, which I totally understand. So then I would then try to read the articles but a lot of the time it became rather difficult as I had not taken any virology or immunology courses. I don’t know, I just think it would be really neat to hear you guys discussing about it. It seems to me that viruses can open to the doors to help fight cancer or help detect other non-viral diseases.

I obviously want to learn more about virology and immunology and at the point where I’ve just graduated and I’m trying to find what exactly where I want to focus my energy, where do I want to do an internship… where to find a job… perhaps continue my education… I need to read a lot more… Although, your podcasts are a tremendous help.

I think this article is also cool: “Differential Susceptibility of Human Cancer Cell Lines to Wild-Type Tanapoxvirus Infection” Hui Lin Lee and Karim Essani

[http://www.ncbi.nlm.nih.gov/pubmed?term=essani%20tanapoxvirus]

I love also the virology 101 podcasts. 🙂

Also, I really would like it if the TWiP podcast was more than just once a month!

Sorry for the quick changing subjects of this email! I hope some of it made sense…

cheers from Northern Germany

Cheryl

Mary writes:

Hi gang,

Just listened to episode 101 and thought of a good YouTube link (http://www.youtube.com/watch?v=dBnniua6-oM) that you may or may not be aware of. It is called Sugar, the Bitter Truth, which is a seminar given by Dr. Robert Lustig of UCSF. This seminar is a great combination of science (good & bad), politics, sociology, and epidemiology, making a solid case for sugar being a major culprit in today’s obesity epidemic. As a scientist (virologist by training), I found this seminar a very compelling and I recommend this as viewing to anyone interested in this topic. I don’t remember seeing this as anyone’s pick on TWIV, so I thought I would pass this along. Watch it, and I would like to know what all of you think of it.

Keep up the good podcasts! mary

Sam writes:

Thank you for your comments on this topic.

I love your programme having been a fan of Twit, but not so enwrapped now, i find your podcast somehow as nourishing as chicken soup. 🙂

This topic is not going to go away so maybe at some time you might do a programme on the original viral break through and how that paradigm shift has played out since then.

I was surprised that DNA can be so precisely manufactured and ordered off the shelf even. This is the infrastructure that you guys are now laying which will support future research and development.

I must say that the mechanisms and organisms involved lead me to think of cyborg as a really useful descriptor of current methodology. Some may hope to be completely synthetic by a certain date , but as you say we really do not understand how to go down that route. some are trying though and maybe you could comment on that in this programme.

Some links for your programme on artificial virus: http://www.microbeworld.org/index.php?option=com_jlibrary&view=article&id=3890

Jason writes:

Hi there,

I’m not a virologist, nor any other medical professional, but I am a TWiV listener. It’s fun to expand my horizons every once in a while.

I have a question about the Influenza vaccine. Should a person with a family history of autoimmune disease, specifically Rheumatoid Arthritis, avoid getting the flu shot? If not, do they run a higher risk of an autoimmune reaction?

Thanks!

Jason ‘XenoPhage’

Bunny writes:

Dear Professors, et al,

Can’t help but think of HeLa cells during each episode I listen to now after having read about Henrietta Lacks’ immortal life. What a delight to find my favorite podster referred to in the book. Makes me curious if there is anything any of you could add to the story. I’m curious about the continued use of these cells, ethical issues re: the use of cells obtained in this manner, or anything else you might want to comment on to fill in the next chapter, so to speak, of this science story.

Keep up the chatter. Enjoy the show a great deal. And..who couldn’t love a podcast hosted by guys with names making them sound like rivals straight out of a romance novel!

Bunny

Portland Oregon

Mudaliar writes:

Respected sir,

I am a PhD scholar working in virology. I would like to know what MOI should i use to infect cells so that

1) all cells are infected

2) High amplification of virus is achieved when, strictly one replication cycle of virus is permitted

3) Least no of defective interfering particles are achieved.

Eagerly waiting for your kind response.

Yours truly

Mudaliar

PhD Scholar,

INDIA

Doug writes:

I have a question regarding your discussion of the rapid rate of spread of the obesity epidemic. You commented that the change in diet could not account for the rapid rate, however there was no discussion of the introduction of genetically modified foods which has somewhat paralleled the obesity epidemic. Do you think there is any possibility that genetically modified foods may be contributing to the rising rates of obesity? Hamish mentioned that there was no high-fructose corn syrup in Europe, but what he didn’t mention is that there is also no genetically modified food in Europe.

Thanks,

Doug

Charles writes:

Dear TWIV Team

Could I start by saying how much I enjoy your podcasts. I am a 51 year-old software engineer in York, England, who gave up Chemistry at age 16 and Biology even earlier when I was only 11, and yet listening to TWIV I am developing a deep interest in Virology. I love your camaraderie, and the way you bring complicated topics down to a level which even I can start to understand.

Listening to one of your recent podcasts you mentioned double-stranded circular DNA. The question I would like to ask is, if a strand of DNA had complementary ends, say a GTAG at one end and a CATC at the other, whether it is possible for to join its ends together using base-base pairings, so that it ends up somewhere in between being single or double-stranded? I suppose the end case for this would be a strand of DNA in the form of a mobius loop.

Please keep your podcasts coming.

Kindest regards,

Charles

Sheldon writes:

Hi:

Although they aren’t viruses, could you please explain how virus like particles are created and used in vaccines like Gardasil and Cervarix? And that are being developed for flu vaccines as explained here

http://news.discovery.com/human/vaccine-virus-particles.html

It seems somehow magical that you can build something that is structurally a virus on the outside, but is essentially an empty shell. And that VLPs may be better than inactivated vaccines because you get the all of the outside of the virus rather than perhaps just broken parts (split virion flu vaccine) or selected parts (sub unit flu vaccine).

Thanks

Sheldon

Toronto

Eric Delwart writes:

Dear TWIV

whiie not strictly speaking a virology story the paper describing a laboratory selected bacteria able to replicate in the absence of phosphate but with arsenic appears to show that even the basic structure of DNA can rapidly evolve to a new shape. That rather remarkable and surprising conclusion, if confirmed, indicates just how flexible our genetic material can be not only in sequence but in actual chemical composition. Amazing conclusions require amazingly strong evidence and at this point skepticism is probably warranted but it would certainly be interesting to see what a double helix or a tRNA with its phosphate replaced by arsenic look like and how they can possibly function. On face value the NASA researcher appear to have selected a life form stranger than all those previously known whose genetic information is encoded by a different form of DNA. It does remind us that viral RNA and DNA genomes can also be extensively chemically modified and yet still function perfectly well although a modification of their backbone forming phosphate connections has never been reported.

http://www.sciencemag.org/content/early/2010/12/01/science.1197258

Jing writes:

Dear virologists,

I’m a graduate student at boston university department of biophysics and I work on structure basis for poliovirus replication. I love your podcast show, great work and I really appriciate the time and effort you put into it.

The topics of whether viruses are alive or not has occured in your show multiple times. I’d like to view life in the structual prospect: that is anything has the ability to decrease its entropy is alive. Since viruses encode proteins that self-assemble into highly organized capsid (turn randomness into order), they have the glory of life.

Jing

Luke writes:

Hello TWiV hosts,

I know that there is a fair amount of work being done looking for therapeutic molecules in both plants and bacteria. Considering that viruses have to modulate the host response, I would imagine that they would also be a good source for such molecules. Are people looking into viruses for these kinds of things and if so, what’re the ways they go about it and what kinds of pitfalls are encountered. Thanks for the entertaining show – you hear a lot about how scientists don’t do enough to communicate their work to the general public and this podcast format is a great way to remedy that problem.

Best,

Luke

TWiV 117

Martin writes:

Listen to this…it’s incredible.

The pharma establishment is stomping on Dr. Andrew Wakefield in the same way they stomped on Peter Duesberg of UC Berkeley. In both cases Dues and Wakefield got it right, and the pharma establishment is shielding gross scientific error because of money.

Wakefield’s study was not fraudulent and accurately reported that all 12 kids had MMR vaccine associated digestive track viral illness that brought on autistic symptoms. The virus doing the damage in the kids’ guts years later was found to be the same Measles strain that was in the vaccine.

The recent news stories slamming Wakefield come from reports by a single corrupt pharma paid science writer, which the American media has jumped on without checking for accuracy.

Be sure to listen to the end of the program where the mother of two of the kids in the study tells how she tangled with the corrupt science writer.

Go to iTunes store

In the search box enter The Gary Null Program

Click on the Jan 12 show and listen at your computer

Wiki on Gary Null: http://en.wikipedia.org/wiki/Gary_Null

Null’s website: http://www.garynull.com/

Martin writes:

Dear TWIV,

In your last discussion about thimerosol, you seem to be unaware that mercury is a nerve poison. Please check out this letter from the American Academy of Environmental Medicine.

http://www.aaemonline.org/images/GreenOurVaccineRallySupport.pdf

They are opposed to the use of mercury in any material that is injected into the human body, specifically vaccinations.

Do you know which common vaccinations include mercury, especially for children?

Best as always, and I never miss a show,

Martin

Donghoon writes:

Dear Doctors

I was so much thrilled when I listened you read my email (Episode 106) about High Throughput Screening program funded by NIH (MLPCN). At the same time I apologize I did not spelled out SAR: Structure Activity Relationship. Chemists usually research SAR to make a better compounds by looking at “Chemical (target protein as well if its structure is available) structure” and activity of the compounds.

Anyway, I would like to have your comments about evolutionary benefit of natural hosts if you don’t mind. A lot of zoonotic viruses are carried by natural hosts; hantaviruses by rodents and influenza viruses by wild birds etc..Most them are asymptomatic in their natural hosts. My question is why the natural hosts carry the viruses instead of removing them. There might be some evolutionary benefits for the hosts? I appreciate your thoughts on this.

I really enjoy TWiV everyday and I have to admit that TWiV inspires me so much not only with science in virology but also with my social responsibility and attitude as a young scientist.

Thank you again for your great work.

Hoon

Donghoon Chung, Ph.D

Center For Predictive Medicine

Assistant Professor

Department of Microbiology College of Med. University of Louisville

https://louisville.edu/research/cpm

Jamie writes:

Dear TWiVers,

I love your show and am one step away from wearing a sandwich board to push it. For now, though, I just recommend it by word-of-mouth.

I have a comment regarding Vince’s assertion on episode #105 that there is not a functional envelope for HERV-K. In fact, a group at the Pasteur Institute (Thierry Heidmann’s lab) found that one member of the HERV-K family–HERV-K108– codes for a functional Env protein, and when the env sequence is cloned into an expression vector and used to co-transfect cells along with an SIV helper, the HERV-K108 pseudotyped particles mediate infection of a number of cell types (including cat brain cells, ewww), though at a very low level.

The same group later reconstructed a full-length HERV-K provirus (Phoenix), from a consensus sequence (the envelope region was that of HERV-K108), and was able to show infection of a few cell types, again, at very low levels.

Identification of a receptor is probably just around the corner (or, “au coin de la rue”?).

Jamie

Jessica writes:

Hello Dr Racaniello or the lucky grad student that is scanning his emails for him,

I am currently taking Virology at Montana State University, it is being co-taught by Dr. Mark Young an Dr. Michele Hardy, They are great! I have enjoyed your podcasts as an added reinforcement to our lectures. I recently listened to podcast #19 about cap-snatching, and in the introduction you mentioned a photo of a chinese chicken farmer sleeping with his chickens. You mentioned that there was a high chance of viral exchange via aeresol transmission. Now I have to admit that my dog does like to sneak up onto my bed and she is a cuddle bug, my question is should I be worried that we could be swapping viruses? Should I get my dog a flu shot?…just joking. Maybe a good podcast would be how house animals, especially exotic animals, are affected by the viruses that we introduce them to.

Thank you Jessica

Atila writes:

Dear Twivers,

After the mail I wrote asking for mitochondrial viruses, I have found some interesting things.

There are mitochondrial viruses in Fungi! They are mitoviruses, small 2 to 3kb dsRNA viruses of the Narnaviridae family:

http://apsjournals.apsnet.org/doi/abs/10.1094/PHYTO-96-0468

Chloroplasts may also be infected by viruses, and there is a cool story behind it. There is a sea-slug capable of making photosynthesis, Elysia chlorotica is capable of stealing chloroplasts from the algae it eats and keeping them under the skin making photosynthesis for months.

This solar-powered sea slug keeps the chloroplasts functional much longer then they should last outside the algae cell, since they need specific proteins that only the algae have genes for. But Elysia chlorotica has stolen these genes and incorporated in its nucleus. And the sea-slug has an endogenous retrovirus that has been found both in its nucleus and the chloroplasts, which may have helped to transfer the genes between species. This virus may also regulate the sea-slug life cycle, as its found in great numbers when the host dies.

This is the reference:

Rohwer, F., & Thurber, R. V. (2009). Viruses manipulate the marine environment. Nature, 459(7244), 207-12. doi: 10.1038/nature08060.

Alan Dove also mentioned that chloroplast’s polymerase seems to have a viral origin. Well, our mitochondrial DNA polymerase too. It is very similar to T4 polymerase:

Shutt, T. E., & Gray, M. W. (2006). Bacteriophage origins of mitochondrial replication and transcription proteins. Trends in genetics : TIG, 22(2), 90-5. doi: 10.1016/j.tig.2005.11.007.

Congratulations again for the great podcast,

Atila

TWiV 116

Sky writes:

Hey Vince, Dick, and the gang. I just wanted to get your thoughts on the current state of an issue that came up in an old television production that I just watched. I had always heard that the usage of phage particles to treat bacterial infections was impractical, since the virus particles could only spread so long as there was enough of a density of host cells in an area that they could continue to replicate. That is, it made sense that a phage could not successfully kill off every living bacterial cell in a natural environment (i.e., within an organism, rather than in a fluid suspension or a petri dish) since they could only spread by brownian motion and not “hunt down” the bacterial cells. But then I watched this show on phage treatments, which made a lot of sense, but it’s quite old and I’m sure that a lot of work has been done since then. Could you tell all of us what the current state of this work is?

Also, I recently read about the transmission of HIV through viral bridges, and realized that virus particles didn’t necessarily depend on brownian motion to propagate. That also seems to make the possibility of using a “hunter-killer” virus (rather than a “naval mine” I suppose), more likely. That is, the spread of the virus there seems much more active than the image I usually have in mind.

Please let me know your thoughts! This is a subject that has been on my mind increasingly since a MRSA infection drilled a fascinatingly neat little hole in my back a few weeks ago.

Love both the shows! Keep ’em comin’!

–Sky

Discuss3 writes:

I was a computer programmer for 40 years. During that time I created some things from scratch (editor, computer language, etc.) But I also found some other programs written by others which I modified so much you could hardly see the origins anymore. Some of those “hacks” were more useful than the programs I wrote from scratch.

So, that “empty” bacterial shell is simply some old code that Venter decided to hack rather than write from scratch. Some of the programs I hacked, I later went back and studied, eventually writing new code from scratch to do the same thing, but with cleaned up algorithms. I also moved to larger computers along the way.

When I first starting hacking code, I couldn’t see how anyone could write huge programs. Then I learned about modularization. Then I learned about the division of labor and interfaces.

Almost everything I ever learned about computers has some parallel in cell biology. With millions of brilliant minds reverse engineering everything inside that “empty” shell, we’ll simply create programming libraries (or dll’s) of all the components in a cell. I probably won’t live long enough to see it, but sans self destruction, I’d say in 30-50 years we’ll be building living cells from parts the same way we build new computer chips and drivers. In fact, it’s all pretty much software nowadays.

I think we should call it “Visual Biology” since our tools will be pretty high level by then. Want your microbe to have a propeller – just click on add genetic component…

Brett writes:

I’ve been a fan of TWiV since I learned about it at this year’s American Society for Virology meeting in Bozeman, and I very much enjoyed a conversation I had over lunch with Vincent at that meeting. In recent TWiV-casts, two people independently asked whether viruses infect muscle cells and whether they infect mitochondria. Flock House virus (FHV) does both (myocytes are rich in mitochondria). FHV is a positive-strand RNA virus (a nodavirus) that primarily infects the muscle tissues of insects and reorganizes the outer mitochondrial membrane to assemble the viral RNA replication machine. Some beautiful tomographic images of these machines were published a few years ago by Paul Ahlquist’s group. Other notable features of this virus are that it encodes only three proteins: a replicase, a capsid, and an RNAi-inhibitor, it replicates to very high levels (ribosomal RNA levels), and that it has been shown to replicate in a wide variety of cells from diverse eukaryotic organisms: insects (its natural host), mammals, and even brewer’s yeast. FHV gets its name from the Flock House agricultural research station in New Zealand, where it was discovered. Apparently there was a plot of land that lost its grass except in large circular patterns where the grass continued to grow. It turns out that a grass grub was eating the roots of the grass and destroying it, except in these large patches where the grubs were being killed by a virus, FHV. So, this virus was discovered by a very large colony forming assay where the diameter of the colonies was measured in meters.

The high levels of FHV RNA replication remind me of a thought experiment, one that cannot be done under our prudent biosafety policies and NIH funding, but one that I find entertaining nonetheless. I imagine that it would be fun for virologists to trick out their favorite viruses, gather together for a Friday night fight, complete with beer and pipettes, and set their viruses against one another in a “cage match” for fitness dominance. The winner of course would be the one who has the most genomes at the end of the match. Trickier virologists would design their viruses to specifically target their competition or to inactivate cellular pathways needed by their competitors. In particular, I wonder how poliovirus would stack up against FHV. Vincent? I further wonder what would happen if the competition were relatively equal and if the match was allowed to continue, would a new virus be created, an amalgam of the two competitors? Well, just some crazy thoughts to entertain me between writing grants and running my lab here at Yale.

Thanks for the great podcast, and keep up the great work.

All the best,

Brett Lindenbach, PhD
Assistant Professor
Section of Microbial Pathogenesis
Yale University School of Medicine

TWiV 115

Vinayaka writes:

Some additional info that I gathered on viruses on the verge of elimination (may or may not be new to you):

It appears that the next virus on the list of FAO to eradicate is PPR virus (Peste des Petits Ruminants). In fact, I heard from an Indian virologist friend that the Government of India will begin its campaign this year. It is a burning problem in South Asia, the middle east and equatorial Africa.

[See http://www.fao.org/teca/content/genetically-marked-vaccines-improved-control-or-eradication-rinderpest-and-antigenically-rel]

Laura writes:

Dear Drs. Racaniello, Despommier, Dove, and Condit,

I was listening to twiv #104 today which discussed recent research on Colony Collapse Disorder, a topic of obvious immense significance to everyone. You mentioned the work of Dr. May Berenbaum et. al. on increased r-RNA fragmentation among bees of affected hives. Then you went on to mention the lack of consistent correlation with the picorna-like viruses those researchers gave as a likely explanation for the finding. You followed w/ the pathogens du jour–IIV and nosema–which don’t account for the r-RNA evidence.

You expressed your “gut feelings” that something, possibly environmental, as yet undiscovered may be the unifying explanation for the bees’ susceptibility to so many pathogens. But you remained puzzled why an environmental factor would create an illness that arose abruptly and spread like an epidemic.

As ribosomes are intimately related to prions*, it is both puzzling and disturbing that there has been no visible interest (going by published articles) in seriously examining a possible prion cause. Researchers at the University of Malmo, Sweden have made great strides in amplifying prions and identifying them from tiny samples. Their techniques could be applied.

The finding of r-RNA fragmentation could be the smoking gun of an apian prion disease.

Ignoring prions is such a glaring omission that it makes me wonder if this direction of inquiry is for some reason being suppressed. Possibilities include the lack of known treatments for such diseases; the huge expenses associated with the potential need to destroy hives all at one time in large areas to contain such illness and start afresh w/ colonies from the few unaffected areas like Montana and Australia after burning and replacing all the current housing and perhaps most equipment; and the public’s possible rejection of honey at the very time beekeepers would most need income.

People often avoid explanations that demand very difficult solutions. However scientists are a group who include more than the average percentage of “pragmatic” individuals. You understand that as insecure as a difficult solution may be, the only thing worse is no understanding and no solution at all.

Could it be that research money is only available to find palliative answers to allow colonies to hang on for the pollinating season with yearly replacement w/o eradicating the underlying cause?

If it turns out to be the case that the only promising explanation that has not been eliminated is “the kiss of death” to a researcher’s funding, would there be any point to investigating further without speaking out?

I would very much like to hear your thinking.

Sincerely,

Laura

* Yeast as a model and tool to study neurodegenerative diseases (prion-based diseases)

http://www.genetic-brest.fr/index.php?rub=theme_2_neurodegenerative_diseases

“The chaperone network controls proper folding of newly synthesized proteins, assists assembly of macromolecular complexes and promotes clearance of protein aggregates. The protein chaperone activity is carried out by soluble chaperones and ribosome-associated chaperones. In addition, the ribosome itself was found to possess an intrinsic protein folding activity (Argent et al., 2000; Chattopadhyay et al., 1994; Chattopadhyay et al., 1996; Chattopadhyay et al., 1999; Das et al., 1996; Das Gupta, 1999; Kudlicki et al., 1997; Sanyal et al., 2002; Singh and Rao Ch, 2002). In yeast, prion propagation was demonstrated to be critically dependent on the chaperone machinery”

Todd writes:

Hi Guys, I have listening to all the previous Twiv and Twips since hearing you on Futures in Biotech (currently at twiv #90) and have been intrigued with your discussions on Junk DNA.

While growing up in Canada, the highlight of my Saturday morning was listening to the CBC Radio science program Quirks and Quarks. It has had a few wonderful hosts over the decades, giving me a regular science booster until I moved to the US several years ago. I missed it greatly until I found it again as a podcast, giving me a taste home while living here in Denver.

This weeks 35th Anniversary show was recorded in front of a large audience in Toronto and one of the guests discussed Junk DNA…here is her segment.

I’d love to her your ideas on this and apologize if you have gone over this since episode 90.

Vince, Dick, Alan and Rich…you feel like old friends by now, and though you don’t hear me, I’m constantly poking my comments into your conversations!

Keep Twiv and Twip going, you are an incredible source of information and entertainment!

Take care and and Happy Holidays, Todd

sent http://www.twiv.tv/quirks_quarks_nov_13.mp3

David writes:

Dear Twivers

I discovered TWIV this summer and am doing my best to catch up! I have a short 15 min walking commute to work so it takes some time to get through all these episodes but I look forward to it every day.

With Rich Condit on the show, this comment is probably unnecessary. Yesterday, Frank Fenner passed away and he was a key player in the eradication of smallpox and made many important contributions in poxvirology. Although I never met him, I consider him one of my science heroes, someone who’s work has greatly influenced my career and interest in virology. It would be great to hear some discussion on TWiV about his contributions to science.

It has also started me thinking about the people who influence us in our careers and stimulate our interest in science. Of course our teachers and advisors are among them, but then there are the other scientists who’s work or life stories influence our decision to go into science. Certainly he was one for me. Another was Linus Pauling, who died when I was in high school and my chemistry teacher wore black for several days after his death. I wondered who this guy was so I read his biography and it remains one of the most influential books I have read. Luckily, another of my heroes, David Suzuki, is still alive. Your Canadian listeners will know him well. I am curious about who the most influential people have been in your careers especially in terms of stimulating your interest in science or virology or who’s work has had a major impact on your careers.

Cheers

David

Kimberly writes:

I was listening to the Futures in Biotech episode 71 where you described the recent PNAS paper on TRIM21. You had mentioned that this antibody/TRIM21-mediated virus destruction may be why viruses such as Polio and Flu only need a few antibodies for neutralization. This could work for Polio, but probably not for the Flu as it is an enveloped virus. The paper states many times that this can only work for un-enveloped viruses, and it took me a bit to realize why as they didn’t spell it out. If the antibody is directed to the viral glycoprotein (or any other protein on the outside of the virion) and binds the virion outside of the cell (as the paper describes), then upon membrane fusion the antibody would remain outside of the cell and inaccessible to TRIM21. I think only time will tell if there is a similar mechanism for enveloped viruses.

Thanks for the podcasts!

Kim

TWiV 114

Jean writes:

I am at present suffering from [what] I have been told will be a virus.

Symptoms:- a dry continuous hacking cough. Unable to get much sleep. No cough medicine seems to soothe it. An uncontrolled loss of urine when coughing. Otherwise no flu symptoms.

History:- I harvested 12 rows of potatoes some of which were scabby, 5 days before the onset of these symptoms.

Could there be a connection to the Adean Potato mottle virus which you state is a plant virus of the family COMOVIRIDAE.

Any comments would be most helpful

Jean

Sophie writes:

Hello to all the great twiv hosts and guests.

I found this story and find it quite intriguing, but I really want your opinion on the matter, will it work, when they only vaccinate the high-risk kids? And if they use the attenuated vaccine (I don’t know if the “dead” vaccine also is a oral-drop vaccine), will the risk of the vaccine-strain regaining pathogenicity and infecting the non-vaccinated kids or adults be high?

I would really like you to get the veterinarian, who wrote last week, on – that would be great, I can hear we’re a bit behind the US on that field (it’s still recommended to get your dog vaccinated once a year in Denmark).

And don’t you worry, I still love the show of course:)

Sincerely Sophie

Annamaria writes:

Good Morning,

I truly enjoy listening to your podcast and often find myself laughing out loud at some of the jokes.

I am a graduate student currently working on my thesis, unfortunately I seem to be in the common position of most students: I need more data. As I was searching through the plethora of information out there I had an idea. Well a question really.

Is there anything out there for scientific papers that resembles wikipedia? Let me see if I can explain this properly, if there was a website where members could post their current work, negative data, or even papers that were rejected for various reasons. Then other members could go in, look at the work, maybe comment.

This would be an opportunity to get feedback on your work, also a way to see what other people had done. For example, I am currently looking to see if certain proteins are packaged in a specific retrovirus. It would be nice to be able to see if others had already tried looking for these proteins and had been unsuccessful. It would also be nice to see if there are better methods for purifying virus other than the one I am using.

When we read articles on various topics in our lab we tend to “tear them apart” as my advisor likes to put it; but all that work that we put into trying to understand the paper and finding flaws in some of the reasoning is lost as soon as we leave the lab. In my opinion it would be amazing if we could go and give feedback on papers or current research where the writers or even other members would be able to see. It would also be amazing if we could ask questions. I don’t know if this would be good for some of the larger institutions but amongst the smaller ones it would be a way to communicate with your peers.

My husband, who is a computer programmer, tells me this is completely doable in terms of programming; the only problem he sees with it is how it would be payed for (servers cost money).

My only concern is as competitive as some science gets sometimes people would not want to share, but I think it has been shown how much more information can be generated when you share.

So is there anything like that out there? And if not, who would I talk to about trying to start it?

Thank you for your time.

Respectfully,

Annamaria

Don writes:

Vincent, Dickson, Alan, and Rich,

I just heard a fascinating interview with Barry Marshall on ABC’s The Science Show Podcast. It seems that he was not content to establish helicobacter as a cause of disease, now he wants to find/create more benign strains as a way to vaccinate against other microbes.

Follow this link and click on “Eating bacteria as a vaccine.” (30 October 2010):

http://www.abc.net.au/rn/scienceshow/stories/2010/3044922.htm

Don

P.S. Long time lister to TWiV and TWiP. Can’t get enough. Bravo!!

James writes:

I saw that you had a link to NLM at http://www.twiv.tv/ so I thought you might want to know about a new biomedical search engine:

http://www.BioMedSearch.com

BioMedSearch contains PubMed/MedLine publications (including some data that NIH chooses not to display), plus additional journals and a collection of theses and dissertations that are not available elsewhere for free, making it the most comprehensive biomedical search on the web.

A link would be great if you have a place for it.

Cheers!

James

Didier writes:

Dear all,

look at the second comment that follow the new of polio eradication!!!!: how not to despair?!

(taken from; http://www.scientificamerican.com/article.cfm?id=polio-in-retreat)

Polio in Retreat: New Cases Nearly Eliminated Where Virus Once Flourished

New cases in key Indian states are hovering near zero—unprecedented, historic lows—suggesting that a long-time goal of eliminating the virus is within reach in parts of world where it has long been considered intractable

1. tfmcvey 01:38 PM 10/28/10

This reduction in cases is a testament to the work of Rotary International and its partners in the Global Polio Eradication Iniatitive. Local and religous leaders in Nigeria have played a key role in reducing the number of polio cases to only eight this year compared to 382 at this time last year. The new bivalent vaccine has also played a vital role in achieving this amazing progress. Rotary members from around the world are going to be delivering this vaccine to children in Africa and Asia in the coming months:http://pitch.pe/92093

2. SpoonmanWoS 04:11 PM 10/29/10

Yes, we might’ve save a lot of lives, but how many Indian kids now are autistic? Another win for Big Pharma at the expense of kids…

TWiV 113

Trevor writes:

Hi Vince, Dick, Alan and Rich,

My name is Trevor Stewart, a PhD student at the University of Toronto (in my final year!!) in Physics. I’ve been listening to TWIV (and TWIP) since last Xmas when my twin brother (who is a graduate student studying mass-spec determined protein sequences with massively parallel computer systems) recommended the show to me. I’ve enjoyed every moment of the show, which has helped deepen my understanding of viruses and topics related to them (such as public health).

I had a comment on Alan Dove’s response to the letter about the media and dissemination of scientific results. While agreeing with Alan, I think he may have missed the exact point of the letter (or my interpretation of it) by discussing the results of study in such detail. While the XMRV studies seem much more credible than the Wakefield study… I think there are similarities in how the studies are being used my advocacy groups, and individuals in the public. Some people in the CFS community have pounced on the original result in the same manner that the autism/anti-vaccination jumped on the Wakefield study. One only has to do a quick search on youtube to find videos for XMRV to see this (eg. http://www.youtube.com/watch?v=vz8pwuDa8aM ). In these cases, I’d suggest that the link has become an article of faith, rather than a reasoned interpretation of the data… and that no negative article will change this. In this way, XMRV is quite similar to the MMR vaccine autism link.

Is there a better way to spread scientific discoveries and encourage critical thinking? Maybe it will take a complete re-tooling of education systems to help people better understand how science ‘works’.

Cheers

Trevor

Germany

Shannon writes:

Hello Team TWiV,

I’m writing today because I am in the midst of listening to episode 100 and your discussion of why young people don’t go into careers in science. I’m forwarding an email from venture capitalist Larry Bock to a good friend of mine who is very involved in science outreach to young people and the general public. You can read more about the USA Science and Engineering Festival that Larry is organizing in the email below but the key line that I wanted to share is, “Society gets what it celebrates! As a culture, we celebrate movie stars, rock stars and athletes and we generate a lot of them, but we don’t celebrate science and engineering.” A great way to start celebrating science and engineering is this 2 day festival being held on the Washington Mall October 23-24, 2010 See: http://www.usasciencefestival.org for more details. I think it would be a great event to publicize to TWiV listeners so they can attend the event or forward the information on to people in the DC area who may be able to attend.

Congratulations on reaching 100 episodes!

All the best,

Shannon

Graduate Student at the Salk Institute/UCSD

Mitchell writes:

Hello TWiV:

I was just catching up on some back episodes and heard your conversation in TWiV 51 regarding vaccination of fish and how there is some poor guy in Chile inoculating 300,000 fish by hand. I recently learned of this company, Microtek, which has a machine for doing just this. The company was recently acquired by Pfizer, so they obviously have something good. There is still a lot of manual labor involved, but the machine does the heavy lifting.

Be sure to check out the video that is linked in the last sentence on this page.

http://www.microtek-intl.com/vc-intro.html

-Mitchell

Durham, NC

Yasmine writes:

Hello,

I LOVE virology and although I am not a virologist I constantly read about it and recently I read an interesting article, and not quite sure I understand the whole mechanism:

Question: I read an article about using cyclotriazadisulfonamides (CADA) compounds to down regulate CD4 receptors (up to 90%!) and therefore block HIV adhesion to CD4+ cells. It’s been shown to be very effective in decreasing HIV infectivity and also works synergystically with other anti-HIV meds. Here’s what I don’t understand… So one would have to take this med continuously to prevent new virions from attaching and the drug will never get rid of already infected cells? If this is the case would it be a practical tx for patients to take for the rest of their lives? Plus, I’m sure CD4 receptors are there because they serve a role in binding substances…blocking them would not affect health?

Thanks

Yasmine

Rick writes:

Hello Dr. Racaniello et al.,

I enjoyed listening to episode 103 with Dr. Tan. I appreciated his explanation of Flumist. Pretty cool. So if I understand correctly, the attenuated virus in FLumist is engineered to produce HA from the H1N1 pandemic 2009 strain, HA from H3N2, and HA from type B virus?

Also, a second question kind of off-topic, why do adeno-associated viruses, when used as a gene delivery vector, require a helper virus, and what is the role of the helper virus?

I appreciate you and your colleagues taking the time to put this awesome podcast together. TWIV and TWIP (the parasite podcast not photography) help my commute go by quickly.

Well one more question, perhaps for Dr. Condit. Many TWIV’s ago, Dr. Condit described the antiviral mechanism for acyclovir and gave a nice discussion on viral TK. I have read that acyclovir can irreversibly inhibit viral DNA polymerase in addition competitive inhibition and chain termination. Any insight as to how this drug can irreversibly inhibit DNA polymerase?

Thanks much,

Rick

[sent “Acyclovir Triphosphate Is a Suicide Inactivator of the Herpes Simplex Virus DNA Polymerase” JBC 259:9575]

Julia writes:

Hi all

Been listening to the podcasts on my dog walking sessions! A quick question about a throw away comment from, I think, the CFS podcast. There was a mention of CCR5 gene therapy for BMT in HIV. I cannot find anything on this being a reality just a theoretical concept but the comment came across as if it was actually being done. Can you clarify at all?

Best wishes

Julia

Consultant Paediatric Immunology and Infectious Disease

Newcastle General Hospital

Neil writes:

Dear TWIV,

Thanks for the great podcast. I am catching up on recent episodes and was just listening to episode 103 with Dr. Tan talking about flu vaccine. I used to work at Medimmune (while it was still called Aviron) and so could not resist writing to correct an error which was Dr. Tan saying that flumist is an engineered vaccine. In fact it was attenuated “the old way” by serial passage in vitro, at low temperature. My project was actually to engineer a separate vaccine strain but this was shelved once the flumist strain (aka “cold-adapted”) was licensed by Aviron from the NIH.

Anyways since some folks get nervous about genetically engineered organisms, I thought it would be important to let listeners know about this error.

Sincerely,

Neil

TWiV 112

Jennie writes:

I love your show very much and this is not my first comment. I load firewood and paint as I listen to you guys, thanks so much for the inspiration over what is becoming years. I’m not an audio learner, though my mind is quite stimulated by what I hear. I’ve purchased Dick’s book which I love.

(2 parts: Reader pick and Question.)

(FIRST) I have a reader pick for you. I’m an RN with an interest in science, I’ve been trying to teach myself about the immune system. I’ve gone through some books that were too complicated (Roits) and too simple, and kept shopping for one that had it all…I seem to have found it and want to recommend it to you and your listeners:

The Immune System by Peter Parham (third edition) put out by Garland Science. He is on faculty at Stanford University where he is Professor in the Departments of Structural Biology and Microbiology and Immunology. This is an excellent book, good structure, knowledge building moves logically and progressively. He doesn’t get stuck with pet ideas, nice pictures (for visual folks like me). And, at the end of each chapter is a test…I recognize now that open book tests really help my brain to grab the new information.

(SECOND) OK, here’s a QUESTION from a person who is really not qualified to ask the question (me!)

Regarding the TWiV 87: A PHIREside chat with Professor Graham Hatfull…GREAT episode by the way, I SO enjoyed it.

A person named Jason sent a link to “Scientist Infected by a Computer Virus”.

OK, WAIT A MINUTE! Infected with the virus? And not only “infected” but his body became a conduit for (replicated?) viral information so that it could be transferred to his computer?

There must be some leap over basic rules of viral infection going on here. So…what are the rules? Don’t viruses have to bind to human sialic acid receptors? Don’t they have to have specific mechanisms for making the cell do their bidding in generating copies of their genetic information?

1) Does what happened to this scientist constitute “infection?

2) Does that article seem a little too simple to you, and is the TechWorld site reliable?

3) Last but not least: what would be the mechanism by which binary computer information could (replicate???) infect a wet human body…I’m not getting it at all. I don’t even understand how it could be released by the chip (as a particle?) or picked up by the computer (as a particle…or as digital information….how would it be assessed?)

Another related question: we are not “infected” by the phage viruses that infect our gut bacteria…? In other words, a virus can be present in our body somewhere, but not infecting our own human cells…because “infection” is a specific process. True or what would you say on this?

Love your show and look forward to enjoying your answer on your podcast.

Yours with warmest regards

Jennie of Oneonta, NY (Read below for article)

“A British scientist claims to have become the first human to be infected by a computer virus, in an experiment he says has important implications for the future of implantable technology.

Dr Mark Gasson from the University of Reading infected a computer chip which was then implanted in his hand with the virus and then transmitted it to a PC to prove that malware can move between human and computer.

Chips that can be implanted into the body have been around for a while, and Gasson uses one in place of a security pass to gain secure access to the building, and to activate his mobile phone. But he says the implications for computer viruses in implants are far-reaching, and could potentially affect those with pacemakers and other medical devices.

Speaking to the BBC, Gasson said someone with an infected chip implant could potentially infect someone else, while a person with two devices under the skin could run the risk of viruses passing between the two chips.

“With the benefits of this type of technology come risks,” Gasson told the BBC. “We may improve ourselves in some way but much like the improvements with other technologies, mobile phones for example, they become vulnerable to risks.”

Brent writes:

Hi guys, love the podcasts. Esp the history behind the discoveries. When I was at primary school there was an animated movie that showed the immune system fighting the germs they looked like blobs with steel helmets and guns fighting the nasty germs. It was shown around the second half of the 1970s. Do you have any idea what it was called and if there are any copies available.

Cheers and keep up the good work

Brent

Jamie writes:

ss (+) RNA W/ DNA intermediate

Why is the replication of this virus type so different from ss(+)RNA? Where is the DNA intermediate coming from?

Charles writes:

Dear Twiv,

I have been posed with the question “Do Viruses ever encode the ability to decode mRNA” and am unsure how to answer it. Could you please provide clarification on the explanation?

Thanks!

Charles

Jon writes:

I’m not sure I am happy with this one – Dickson looks a a little too evil for my liking =)

Anyway if there are better photos I should use let me know =).

www.twiv.tv/dick_d.png

Jeff writes:

Hi guys,

I’m a postdoc working in a virology lab who recently discovered your show. I really enjoy it and got another grad student in the lab hooked on it too.

I have been listening to some of your archived shows and heard a question in TWiV #73 about applying drugs targeting reverse transcriptase to the treatment of cancer causing viruses. You guys mentioned that HBV has RT activity and could possibly be targeted with the same drugs, but did a quick search to find that AZT (or zidovudine) doesn’t work. It’s true that AZT doesn’t work, but there are 2 HIV inhibitors that are effective against HBV and have been approved by the NIH for this purpose: lamivudine (or 3TC) and tenofovir (which made headlines as the first moderately successful topical anti-HIV gel).

You also indicated that RT inhibitors are unlikely to be effective against other viruses that don’t have RT, but I thought it worth mentioning that nucleoside analogs are often effective against diverse viral polymerases. Adefovir, another approved treatment for HBV, is quite similar to tenofovir and has been shown to have anti-HIV and anti-herpesvirus activity. As you probably know, many of the approved treatments for herpesviruses, hepatitis C virus, and other viruses are nucleoside or nucleotide analogs that are not so different from RT inhibitors. Like RT, viral DNA polymerases are more likely to be inhibited by these analogs than cellular polymerases, making these types of compounds so useful as antivirals.

Just thought I would add my two cents. Keep up the good work.

Jeff

Chad writes:

Greetings,

I just recently started listening to your podcast after hearing about it so much on Futures in Biotech. I was a bit resistant at first. Though I am grad student in molecular biology, I work with plants, not viruses, so I wasn’t sure how much I would really get from it. I have to admit I enjoy it greatly and have learned quite a bit. So thanks for putting out one of the best science podcasts around. Listening to you’re latest podcast (# 100), I was very much interested in the discussions regarding science education. Of course I agree that more is needed, but I was wondering, how much is enough? Its already known that many students lack sufficient understanding in even more basic and essential skills like mathematics and reading. As much as a greater scientific literacy is needed amongst the general population, reality is that there is only so much that can be taught in elementary, middle school, and high school. Given the breadth of topics in Science that must be covered (physics, chemistry, biology, etc) what is essential and what can we do without? I don’t want to come across as skeptical/critical of the calls for more or better science education, but when these calls are made, rarely do I see anyone answer the necessary question of what is critical for students to learn.

Chad

TWiV 111

Scott writes:

Hi,

I am based in Hong Kong and there has been a local outbreak of dengue among the international community here. This is the first local transmission of dengue in 7 years! Several students at my children’s school have taken off of school with apparent dengue symptoms such as rash and muscle pain. After listening to Twiv #3 I feel much more informed about dengue. Even though you are now in the ‘100s’ it would be great if you could continue to occasionally produce educational podcasts. I really appreciate these episodes as well as those of Twip.

http://www.mb.com.ph/articles/278536/hong-kong-reports-first-local-case-dengue-fever-7-years

Scott

Peter writes:

Gentlemen,

I thought this might be interesting for you, since Chikungunya was at least glanced at a few times in twiv. Sadly, though, the blog post itself is in German. It seems that many factors are at work here: Travellers brought Aedes albopictus to southern Europe, The Chickungunya virus successfully adapted to that new host, Climate change opens up new habitats for the insect. This should be an interesting progress to watch.

http://www.wissenslogs.de/wblogs/blog/fischblog/klima-und-umwelt/2010-10-05/das-chikungunya-fieber-kommt-nach-mitteleuropa

Here’s the google translate that is, in most parts, not all that bad:

http://translate.google.com/translate?js=n&prev=_t&hl=de&ie=UTF-8&layout=2&eotf=1&sl=de&tl=en&u=http%3A%2F%2Fwww.wissenslogs.de%2Fwblogs%2Fblog%2Ffischblog%2Fklima-und-umwelt%2F2010-10-05%2Fdas-chikungunya-fieber-kommt-nach-mitteleuropa

and an older publication on ChickV in Europe:

http://www.virologyj.com/content/5/1/33

Before I found twiv (that is: before Twiv #1) I didn’t know much about virology. Yes, I knew that it’s an interesting field, but accessible knowledge was’t widely accessible for a layman like me. Now, not only do I know about the virus, I also know about the vector and can watch it get closer to where I live.

I havn’t seen Aedes albopictus here, close to Frankfurt in Germany, but according to the maps, it’s creeping up the Rhine valley, which is no surprise since the upper Rhine valley is the warmest part of the country.

It’s going to be interesting to see, how the distribution will change in the next 10 or so years.

Thanks for the education you provide, there’s so much in it, from beautiful intricacy of the biochemical interaction between virus and host to the real life implications of an insect carrying it to new parts of the world.

Keep ut the good work, I keep looking forward to a new TWIV every week (and, I have to say, I do look forward to a new TWIP every week, too).

Jim writes:

I found your podcast several weeks ago on iTunes. I really enjoy it. I learned to love science, biology and more specificaly immunology back in the late 1970s and early 80s. I had a very heavy dose of microbiology because in those days immunololgy was a part of the microbiology departments where I studied. Anyway, your podcast reminds of that time and my abiding respect for those who can do science. I was too impatient. I loved the ideas of science but not the doing of science. The book that got me interested in science was titled “The Eighth Day of Creation”. I am on podcast number 8 or 9 and look forward to many interesting hours ahead. I did skip ahead and listened to your last podcast yesterday and was pleased to hear that you had discussed retroviruses in one of your previous podcasts. I do not know whether it is appropiate to describe retroviruses as “way cool”, but the idea of them certainly is to me. My coworkers think I am a bit nuts when I start telling them about the polio vaccine and why there was an outbreak recently in Africa (as you guys predicted) and also congratulations in predicting the avian virus would not be the cause of the next flu pandemic but that more likely H1NI would be the cause.

Thanks a lot for your work and your contributors.

Jim

Alfred writes:

TWIV gang:

A bit behind on my listening, but the question came up a few episodes back of why an endogenous retrovirus does not seem to become active and replicate.

My question would be the opposite, is there any advantage to the virus becoming active again? If the goal of viral infection is to propagate it’s genome then what better way to do it than to incorporate it into the genome of a successfully reproducing organism. Once the genome is in the germ cell line, each time the organism reproduces the genome is reproduced.

Any activation of the genome in that organism is going to lead to an infection in the organism. This will force the organism to divert resources to support the growth of the virus and to the development of an immune response to the viremia. Both of these may decrease the organisms chances of successful reproduction and decrease further passage of the virus’s genetic material.

I can think of two instances that might justify activation of the virus.

1. If having the ERV’s genome leads to a mild infection then activation and communication of the virus might weaken competitors without the ERV and give the organism with the ERV a reproductive advantage.

2. If the ERV has some type of monitor to recognize when an organism is dying (or stressed beyond reproductive capacity) the virus would benefit by becoming active again and transmitting its genome to other organisms through more traditional means. I know of some trees that only go to seed when the tree is stressed but I’m sure there are other examples of infectious processes that bail out when their hosts no longer appear viable.

You guys are still the best podcast on the web. Keep up the great work.

Alfred

Ken writes:

Dear TWiV,

Your netcast is one of the highest quality science netcast available, and my favorite. I was wondering if you have any advice for people in science who would like to follow in your footsteps.

Netcasts are an amazing tool for education, both to a expert audience and the general public. However, I have noticed that there is a distinct lack of health related netcasts that are both evidence based and accessible to non-experts.

Several popular health netcasts are dedicated to naturalistic or homeopathic medicine, complete with stores selling their cures, and a general disregard for science. Scientists and physicians need to use this form of media to provide a rational voice that is friendly to lay people and covers pertinent topics.

I will likely be attending medical school next year, and was thinking of starting a netcast and interviewing available experts. Thoughts or suggestions?

On an unrelated note, I will be interviewing at Columbia P&S. Any chance I could meet either of you? I do not have an exact date yet, but it will hopefully be in late October.

Ken

Judi writes:

Hi guys – nice to have the 3 of you back together again!

You were discussing textbooks…. A pet peeve of mine. I am a high school science teacher in California. Our textbooks are large, expensive, poorly written doorstops that don’t even really follow the California state standards, so if the publishers are cow-towing to us in California, I feel really sorry for teachers in the smaller states.

But there is an interesting change coming – the Common Core Standards

http://www.corestandards.org/

The state governors started this mvoement, supported by ideas of change with the Obama presidency. 40 states have ratified that they will adopt and use the common core standards, unifying what information students should get in k12 education.

Once kids are all to be taught the same thing, publishers will put money into online and virtual texts and classes…. It is moving that way now – but…. To have digital texts and online classes, kids need to have ipads or netbooks. Right now, the only thing we can spend textbook money on is BOOKS – physical paper books – so laws will have to change to bring education into the 21st century.

I was listening to NPR – Freaknomics radio podcast, I think, and I heard the following.

If we went back in time 100 years, we would recognize very little, except the classroom with one teacher and 30 kids.

Scary. I have hope we will apply all the thing we know now about how the brain learns and the conditions we need for learning to occur.

“I did then what I knew how to do. Now that I know better, I do better.”

— Maya Angelou

Thanks for all I learn from you – and all the bad puns!

Judi

TWiV 110

Jay writes:

Looks like the polio outbreak in the Congo is pretty bad.

http://www.google.com/hostednews/afp/article/ALeqM5jpSHvrTg3sqCZs9hPXwYsuwAjXNA?docId=CNG.29d0fd00722f6f7964062dad40b4f107.ca1

http://www.unicef.org/media/media_56792.html

Over 120 deaths and 280 AFP cases so far.

Looks like this variant is related to the Type 1 circulating in Angola, which was originally derived from India (most likely from migrant workers).

Interestingly the average age is between 15 and 29 years old which is outside the usual AFP surveillance guidelines of <15 years of age. This is probably due to the vaccination gaps in the past when this age group were less likely to have been exposed to either wild or vaccine virus.

Pretty depressing really.

Cheers,

Jay

Senior Medical Scientist

Poliovirus Reference Laboratory

North Melbourne, Australia

www.vidrl.org.au

Jaakko writes:

Hello dear TWIV hosts.

Few weeks ago I made a search in iTunes for XMRV and found your pod cast. I listened to one episode on that topic and I really liked it. So I decided to listen some more and before I knew it, I was hooked. I really like how you can keep the conversation so natural and casual, still being very educational and interesting. Now I’ve finally reached the last episode and have to get used to getting just one TWIV in a week =)

Here are two articles about a possible connection between the swine flu vaccine and narcolepsia in Finnish and Sweedish children. They are google translated so it’s a bit rough read, especially the Finnish one 😉

first article

second article

Basically, what they say, is that there has been a rise in narcolepsy cases in children between 12 and 16 years during last spring. The vaccine linked to this possible connection is called Pandemrix. From what I can tell, the connection is made only via the close timing between the vaccination and the children getting the disease. Also, in the articles the doctors emphasize that they don’t still know if there is any connection between the two. Nevertheless, Finnish health officials are now considering if they should stop giving Pandemrix to children.

I would also like to suggest a tip of the week. It’s called Khan Academy and is basically an on-line school for everyone. It’s totally free, and consist of over 1600 videos covering math, physics, chemistry, some biology and economics and even a little bit of history. The guy making these videos is called Salman Khan and his education style if very accessible. And that’s not all, the site also has a browser based math application, which covers math from first grade to most of the high school stuff. You can find KA at khanacademy.org or at youtube.

Lastly I just wanted to thank you guys for doing this every week. Having CFS, listening to stuff is some times all I can do. So finding your pod cast, and after that, some other very interesting pod casts, has brought so much interesting content in to my life.

Jaakko, from Finland.

P.S. Here’s a virus joke I came up with… A virus goes in to a bar and orders a drink. The bar tender takes a good glance at him and asks; are you sure you’re old enough? To which the Virus replies, are you joking? I’m so old that you could even call me retro! —laugh/cry here—

Tim writes:

Alan/Vince:

I am a fan of the podcast “This Week in Virology”. I really love how Vince does the podcast.

I am a chronic fatigue/fibromyalgia/whatever patient. Been that way for over 15 years. Not much fun, to say the least. Why do some science research? Check out the suicide rate among the fibromyalgia/chronic fatigue patients…

My past history is as an exploration geologist for metals and minerals, River geomorphology, and a host of other areas, including teaching. Then I had a 10 year or so career as a electrical engineer in industry of designing and manufacturing ASIC microchips. That’s career ended when I developed my symptoms.

I like science. I like stories. (I also like art). I also think one of the more important problems in our society today is that the common person is not educated in science and the more science education we can give people, the better they can understand our complex society and its trials and tribulations. So my heroes are people like Vince, Ginger Campbell, Lorimer Mosely, ……

I have two suggestions. #1: (this is for Alan) please listen to in the recent TWIV podcast with Dr. Singh. Contrast her and Vince’s responses to the listeners e-mail versus t your responses. then toss me an e-mail back or give me a phone call with your thoughts.

I really do not think that either of you are well educated on the history of chronic fatigue syndrome and the government research agencies. It’s an unbelievable story. The following is by no means a complete history — it’s just some tidbits that you can use to partially educate yourself or use to dig further into the story.

////////////////////////////////////////////////

Let’s start with the beginnings of the CDC/CFS controversy. Here Is a Link to a 1996 ABC “PRIMETIME” episode on the CFS/ME saga:

Then there’s the history of the United States federal agencies research on CFS/me, let’s start you off with a very short summary, and assume you can do your further research. (Hillary Johnson is THE source for info on this subject):

http://www.nytimes.com/2009/10/21/opinion/21johnson.html?pagewanted=2&_r=2&emc=eta1

The CDC and CFS research it is a fascinating story. Hillary the book and website are both entitled, Osler’s Web. Here’s a short list of news reports from the late 90s when the CDC finally had to admit that it was diverging and misappropriating funds that were earmarked for chronic fatigue syndrome:

http://groups.google.com/group/sci.med.diseases.lyme/msg/159a4396e6bf0853

if you dig into it, you will find all sorts of twists and turns in the saga of federal government research monies and chronic fatigue, and the truly sad thing is that it hasn’t changed, or at least hasn’t changed until very recently ….

http://behindthesurface.blogspot.com/2008/11/cdc-research-funding-scandal-20.html

I also suggest that you check out Dr. Judy Mikovits, of the WPI, statements concerning her desire to share samples, information, etc. with other researchers. From what I can tell, most of the other researchers looking for XMRV, with some exceptions like Dr. Singh, ignored Dr.. Mikovits. And I’m sure you remember from your TWIV interview with Dr. Singh, she said, “XMRV is very hard to find”…. I’m paraphrasing there – you understand what I’m getting at.

Not enough? How about this statement from Dr. Vernon, a respected former CDC virologist:

http://www.cfids.org/xmrv/070110study.asp

How bout outside the USA? It may be worse in the United Kingdom, where the “it is all in their head” and “they just need to gradually build up their endurance via exercise” predominates (this is pretty important to people in the United Kingdom because the government insurance will only cover certain procedures with chronic fatigue patients…) :

http://www.investinme.org//Article-358%20The%20MRC%20and%20Secret%20Files%20on%20ME.htm

in addition, let me warn you — everyone associated with CFS/ME, the patients, the researchers, the clinicians, etc. all absolutely HATE the term, “Chronic Fatigue Syndrome”. They have tried and tried and tried to eliminate the term, but in the United States the term still lingers. In some other areas of the world it is referred to as Myalgic Encephalitis. The only way that the name can change is via the press, scientific and otherwise. So if you guys keep using the term, “Chronic Fatigue Syndrome”, and then everybody else will. Actually, to me – it’s not a big deal. But it sure is for everybody else that is involved in this messy physical ailment.

Finally, I will leave you with this quote from Dr. Nancy Kilmas. Dr. Klimas is (was? – I think she just changed jobs…) a director of the Department of Immunology of the University of Miami School of Medicine and Director of Research for Clinical AIDS/HIV Research at the Miami Veterans Affairs Medical Center.

…..But I hope you are not saying that C.F.S. patients are not as ill as H.I.V. patients. My H.I.V. patients for the most part are hale and hearty thanks to three decades of intense and excellent research and billions of dollars invested. Many of my C.F.S. patients, on the other hand, are terribly ill and unable to work or participate in the care of their families.

I split my clinical time between the two illnesses, and I can tell you if I had to choose between the two illnesses (in 2009) I would rather have H.I.V. But C.F.S., which impacts a million people in the United States alone, has had a small fraction of the research dollars directed towards it…..

thank you for taking the time to read this. As I said, I’m a fan. I’ll still stay a fan. I’ve learned so much for your podcast!! The world needs more like it. Educating the public about science is just so important! Sometimes educating the science about the public, is necessary also amounts what I was hoping to do with this letter/email.

Regards,

Tim

Fort Collins, CO

PS> please excuse the potentially garbled nature of this document. Part of my symptoms, besides unrelenting fatigue and feeling like I have the flu all the time, is that I have basically no ability to hand write more type. Handwriting — a couple sentences cause excruciating pain. The type and use the computer — I use voice dictation. I’ve used voice dictation for over 15 years — and I can tell you one thing — got better but it still sucks. Either that or I just mumbled too much. Thanks again for your time and patience in getting through this document.

Jon writes:

I’m taking Vincent’s call for a group drawing – so here is my “Alan Dove” =). This was drawn on a 21″ wacom cintiq which is somewhat more accurate than the iPad =).

Ok now a word about beards – they are a pain to draw – so please give Rich my regards as the least facial-haired PHd on the show =). Seeing I am going to redraw Vincent and sketch Dick I’m looking forward to draw Rich (well, as he appears on the “about” page of the blog =) ).

(View it at http://www.twiv.tv/about)

TWiV 108

Zephyr writes:

Hello everyone, dear doctors Racaniello, Despommier, Alan Dove and Rich Condit,

I’ve been a devoted listener since April 2009. Like many others listeners then I quickly caught up with all previous episodes (I’ll never forget that memorable one devoted to the recent West Nile Virus epidemic) and since then I haven’t missed one. I really enjoy listening to your program, it combines an invaluable source of information and knowledge about Virology extending to more general subjects on science and research, with a highly entertaining and educative format, a dynamic discussion between colleagues about a specific topic, something I always felt missing during my undergraduate years.I also appreciate many of the recommendations you’ve given during the programs such as the podcast Meet the Scientist, that Carl Zimmer’s program is another example of a podcast on science of very high quality with well made interviews, good guests and interesting topics like yours.

What moved me to write this letter is that in this week’s TWiV episode No.107 Doctor Racaniello seemed to regret having overlooked for more than 2 years the news about the development of a new recombinase that can specifically recognize and excise from the host genome the HIV-1 LTR flanking sequences (actually for more than 3 years since the 1st results were published in June 2007 in Science).

That overlook must have been a quirk of fate since the topic had been already around the program in the past: In episode No. 66 another listener asked about the possibility of excising the HIV integrated virus in a letter read during the program. The question made me remind of the article published in Science I had read not so long ago. That same week I wrote a brief description of the work and bibliographic reference in the Comments section of ‘TWiV 66: Reverse Transcription‘. It has been the only comment I’ve ever written in TWiV so I couldn’t forget it. After nobody else commented those results I assumed that those experiments were considered as devoid of any practical value for the treatment of HIV infections in humans.

In spite of that, since I first read that article I’ve firmly believed that the development of new enzymes and other proteins by means of some directed-evolution strategy will eventually become a powerful tool in research and bioengineering. Since then I’ve also heard from the use of a similar directed-evolution strategy in the development of new tRNA-aminoacyl-tRNA synthetase pairs that have been successfully expressed in bacterial and eukaryotic cell systems. As a result these cells can incorporate to nascent peptide chains new unnatural amino acids encoded by either a particular barely-used stop codon or one or even more tetrads, specific sequences of 4 nucleotides specifically recognized by those evolved tRNAs. This new unnatural amino acids can be used to develop enzymes capable of catalyzing new types of reactions never handled by enzymes before, to specifically label proteins in vivo, and in the study of the 3 dimensional structure of proteins as site-specific NMR landmarks.

Thanks for your program and keep up with the good work,

Zephyr

Raphael writes:

I am a student in Dr.Isern’s Virology class at Florida Gulf Coast University (Can’t wait for you to T.W.I.V. it up here in Fl, December 6th). Recently I watched T.W.I.V. #66, Reverse Transcription, in which you were talking about integration of HIV-1 into the host’s genome. At 49 minutes and 45 seconds you mentioned that you “Do not know much about chromosomal structure,” with respect to why HIV-1 generally integrates into the exposed area on a nucleosome. It would make sense that HIV-1 would integrate into “exposed area on a nucleosome” because, as I understand from genetics, the unwound/more exposed areas of DNA are being/about to be actively transcribed [euchromatin] and otherwise the DNA is too tightly bound to the core histone proteins. Secondly, I was wondering if you can do a T.W.I.V. on cancer associated viruses in general (I.e. which ones have a more definitive association with causing cancer, some mechanisms of their viral replication cycle, receptor pathways affected, what exactly do anti-viral anti-cancer drugs target, etc). Sorry if this sounds vague, yet I am purposefully wording it as such to give you leeway as to what you wish to speak about with respect to cancer causing viruses. Can’t wait to see your next T.W.I.V. as well as see you live December 6th.

Sincerely,

Raphael

Career Goal:Cardiopediatric Diagnostician with specialty in infectious diseases/autoimmune disorders

James writes:

Hi Vince,

I heard you ask Dick why DNA viruses need their host cells to be replicating for them to be able to duplicate their genome and you guys concluded that the replication machinery is always off when the cells are not replicating and thus the viruses can’t access it. I remember we pondered over that in my virology class last year and we concluded that when the cell is not dividing, the nuclear envelope is still intact hence the virus can’t access the replication machinery which is usually inside the nucleus. On the other hand, the nuclear envelope is degraded in replicating cells and hence the virus can access the replication machinery in the nucleus. I thought that could be another reason.

James

Daytona Beach, Fl

Øystein writes:

Dear Professor Vincent Racaniello and the rest of the TWIV crew

My apologies for not having emailed you before! I am 32 year old physician currently undergoing training as a medical microbiologist in Norway. Since first discovering TWIV in the spring of 2009 I have been following every episode with enthusiasm. You’re on my headphones when I’m walking, skiing, biking, driving, and especially when doing house and garden work! I listen because it’s fun, and because I enjoy the spirit of discovery and discussion that your show is full of.

Almost as a side effect I have also had lots of help from TWIV in my daily job, helping , amongst other things, to inform my views during the influenza pandemic, during my work with diagnosing hepatitis B and C, and , lately , when trying to make sense of the proposed link between XMRV and chronic fatigue syndrome.

On that last note, if you haven’t received it yet, I thought you might be interested in this latest article on MLV-related viruses in CFS-patients. Yes, the Harvey Alter article is finally out in the PNAS ,and I just got hold of it today:

http://www.pnas.org/content/early/2010/08/16/1006901107.full.pdf+htm

I am sure you will find an occasion to comment on it, so no pressure yet! I still retain a (hopefully!) healthy scepticism about the CFS / XMRV/MLVrV (?)-link, but have to admit the detective work and debate is intriguing.

I’ll send you a separate TWIP email one day, as it deserves separate and positive, attention!

Best regards,

Øystein

Norway

Jon writes:

Heya Vincent and gang – my quick twiv contribution:

(‘digital finger painting‘ iPad using brushes app)

Raihan writes:

Greeting TWiVerrs.

I’m Raihan, a big TWiV fan in Singapore. You guys rock!!

Anyway i just wanna share with you some local news regarding the release of genetically modified mosquitoes in some states in Malaysia (Singapore’s neighbour) to combat dengue.

I find this move really bold and potentailly contrevisial, but i’ll leave the judgement to you guys.

http://www.channelnewsasia.com/stories/afp_asiapacific/view/1077780/1/.html

Hope this is relevant to your discussion

Keep up the amazing work,

Raihan

(Alan, ever thought of writing a joke book?)

Stephen writes:

Pertaining to your interview with Dr. Ila Singh in TWiV94, I wanted to clarify some language you and a guest used that adds to the confusion about Chronic Fatigue Syndrome. During the broadcast, you refer to CFS in shorthand as ‘chronic fatigue’. Since you are a scientist that appreciates precision, I will point out that this characterization of CFS is incorrect because the phase refers to two general, distinct descriptions of different things:

1. ‘Chronic fatigue’ used by itself in a medical context refers to idiopathic chronic fatigue, fatigue that cannot be explained using any clinic definition of disease or disorder;

2. ‘Chronic fatigue’ is also generally used by the patient population as a symptom of any physiological human dysfunction.

As you dive into the morass that is CFS, I can sense through your broadcasts that you are becoming aware of the historical, high-level problems related to the disease, specifically the taxonomy and clinical definition of CFS. The CDC made a mess of things by choosing such a nonsensical name as CFS, perhaps betraying an institutional culture dismissive of the disease or not. But it did serve to confuse researchers for a generation and set back the entire field up to this very day.

BTW, your shows are a great public service.

Regards,

Stephen

TWiV 107

John writes:

Dear Doctors et al,

I’m writing to request a podcast or a discussion on colony collapse disorder. It seems that new evidence is pointing to a combination of fungus and a newly discovered virus (from a combination of academia and the military!). I know the previous primary suspect was Israeli paralysis virus but I didn’t see that mentioned in this article. I’m sure that the story has come across your desks but in the event that it hasn’t, here’s a link to the NYT article:

http://www.nytimes.com/2010/10/07/science/07bees.html?partner=rss&emc=rss

Much thanks, great podcasts!

Sincerely,

John

MSA student, URI

[TWiV told him we had done this episode as #104. Here is his reply:]

Doctors in Residence of TWiV,

Yes it was a good show. I’m glad that there was discussion of civilian/military cooperation in science research. Although I think Dr. DePalmier is incorrect in his claim that bumbles don’t sting.

John

PS After Dr. Dove left Dr. Racaniello’s lab did the latter train at the former’s school of comedy in preparation for TWiP

Ebrahim writes:

Hello Everybody

I was watching your ‘Emerging Viruses’ lecture a day after listening your HERVs TWiV epsisode, in the lecture you stated that Polio is probably present since the time of the Egyptians! (actually Egyptians still exist, I am one! – Pharaohs are the ones who do not exist any more!) and my question is ‘why did not humans endogenize Polio! yet, since it was probably present before the Egyptians!, so it is probably very ancient, and why polio still causes symptoms after infection, it is shed in faeces and can transmit easily among humans in a stable cycle, why is it still showing symptoms and sometimes killing its hosts (paralysing lung muscles or so!), wasn’t it better for Polio to shift to being silent and endogenous!, so is it a tendency of the virus to be silent with time! that some viruses do not choose this option?, or a tendency for humans to endogenize some viruses! but not the others?, since I understand from the lecture and the TWiV episode that stability in virus-host relationship is the ultimate GOAL!

Keep up the good work

Thanks

—

Ebrahim

Microbiology Department, Faculty of Science, Ain Shams University, Cairo – Egypt

Ricardo writes:

Hello Vincent.

I just saw your video about “Social media in microbiology education…”.

Very interesting.

In the end when you were asking for future evolution, and you mention students blog as part of their grade. I started a wiki page for my students. Each had to explore a theme.

The good things that came out of the experience were:

An increase in interest throughout the semester.

I could control if the students were doing their work or not

Some competition which led to improvements on their wikis (students could see all wikis)

Nice set of skills

IT knowledge

improved graphic presentation

Rich bibliographic search (no www.google.com or wikipedia bibliographic entries)

More interest than just a regular report.

About TWIV and TWIP… Well I just have the best commute I could have.

My best regards.

p.s. I think I will try to include TWIV or TWIP for extra credit on my classes.

Ricardo

Assistant Professor of Microbiology

Faculty of Health Sciences of Fernando Pessoa University

Portugal

Sue writes:

Dear Virologist:

The Tre recombinase people think that in 10 years, they might be able to use their method in a clinical setting to attempt to remove retrovirus from host. Are you as optimistic?

Thanks

Sue

Geoffrey writes:

Gentlemen:

I was listening to TWIV 82 about Dengue fever and the host’s changed response upon re-infection. It occurs to me to ask: could this changed response be a factor in other diseases that have differing short- and long-term infectivity symptomology? In particular, I was wondering about measles / shingles. Is it possible that the original measles infection stimulates an immune response that works fine over the host’s lifetime for most tissues but actually makes some tissue types more sensitive to subsequent infection (whether by the same or similar strain). It is in these cells that the “shingles” viruses reside and activate their different symptomology.

Perhaps I am making this too complicated. Perhaps measles virus doesn’t need the original infection’s “priming” action and the difference in tissues types is enough but I, in my ignorance, thought it worth asking.

Keep up the good work!

Geoffrey

James writes:

Do they seem promising to you guys? And is the theory sound or with the Influenza virus point or shuffle out of it.

James, MD

[the subject line of the email was ‘universal influenza vaccine’]

Jim writes:

Vince,

In case you haven’t seen this,” ClearLab is being developed by Muzzy Lane Software, Inc., in partnership with the Federation of American Scientists, curriculum developers from K12, Inc. and science teachers around the country. The project’s primary goal is to develop games that improve student performance on standardized assessment and that foster lifelong passion for science.”

Go to the ABOUT tab at this link, http://clearlabproject.com/ to see the page with that quote.

Jim

Smithfield, V

Jim writes:

Can you lead me to any place that offers a simple discussion of the protein portraits or cartoons so commonly used in your lectures, text and every other professional discussion of the entire microbiological field? As an old retired guy I’d much prefer a Classic Comics version, if such a thing exists.

Bluefaze writes:

I love the podcast. A special thanks to TWIV team for doing an amazing job. Since in lot of your podcasts you have discussed so much about flu viruses, I thought you might like this one on FLU-GFP virus?

http://www.pnas.org/content/107/25/11531.full

Keep up the Great work!!!

Thanks,

Bluefaze

Rich writes:

Dear Twiv Guys,

Love your show. Actually I’m chronically infected with TWIV. Just wanted to add an update to TWIV #80 on hepatitis B. It is true that up until about 1986 the hepatitis vaccine was quite expensive and developing countries were not able to afford it. Then, a group of people that I had the privilege to work with (The International Task Force on Hepatitis B Immunization) set about to make the vaccine affordable in developing countries. Since that time the vaccine has dropped in price and today UNICEF can get it for less than $0.20 per dose. Price is no longer a barrier to availability of the vaccine.

I have listened to every show up to #80 and am looking for every spare minute to get current. I have arranged for a link to your show to appear on my organization’s web site: http://www.pdvi.org. I hope every person interested in how viruses affect human health can listen to your superb podcast.

Rich

Andre writes:

Hi, I love your TWIV podcasts! I find the honest and witty banter among the TWIV cast/crew and guests to be most refreshing, entertaining and educational. It’s addictive! I’m a PCR scientist in a provincial government veterinary diagnostic lab (Manitoba, Canada). We routinely test by PCR for several viruses and microbes in livestock animals (> 30,000 samples/year). Back in 1997, despite being swamped with diagnostic PCR samples during a BVDV outbreak, using PCR we were able to identify and sequence a new virus in pigs, now known as porcine circovirus type-2 (PCV-2). As diagnostic technologies rapidly evolve it can be overwhelming to keep up with recent advances. Can you recommend any online molecular diagnostics forums specific for veterinary diagnostic labs? I’m familiar with various Bionet newsgroups, but find they’re too general for our needs. Keep up the great work and having fun and for fellow listeners please assure us that you plan to continue beyond 100 episodes! Sincerely, Andre, PCR Scientist, Virology Laboratory, Veterinary Diagnostic Services, Manitoba Agriculture and Food.

Merry writes:

Vincent et al.,

EXCELLENT program, and not just because you read my letter (thank you). Far more important were the ideas you presented to counter the prevailing notion that all viruses are bad. The agricultural implications mentioned by Marilyn Roossinck were expecially interesting for me.

I know, you hear this all the time but I’ll say it, too. Important work you are doing here. Excellent job. Keep up the good work. etc. etc.

Merry Youle

Small Things Considered

Pritesh writes:

Has any research been done on the distribution of envelope glycoproteins on viral surface. Especially in the context of viruses that use specific receptors from the many they have. But I guess each one is present for some definite function.

Thanks,

Pritesh

Georgia State University

Benjamin writes:

I’m a student at Grinnell College on the cusp of finishing a degree in Biological Chemistry. I found your podcast this summer via the advertisement you made in one of the episodes of ASM’s Meet the Scientist podcast. I was able to finish all 92 (so far) episodes of TWiV this month. I’ve found your podcast deeply interesting and it has put virology on my radar as a possible career path.

One concern that is somewhat tangential to most of your discussion is the occasional mention of telomeres and aging. While I don’t think I heard anything that was outright incorrect, I would often hear mention of telomerase, toned as if it caused aging, which it does not. In fact, telomerase is what helps maintain the “youth” of a cell line by allowing it to replicate for a longer period of time. As such, the cells in humans that most often express telomerase are germ-line cells. Cancers also tend to express the gene, since it removes the limits to the number of times a cell can divide. One of the reasons that HeLa cells are so useful is because they have this gene switched on, meaning that they can be cultured indefinitely without the typical result of culturing non-cancerous human tissue, which is an inevitable halt in division.

As far as I know, most if not all eukaryotes (I’d be intrigued by a counterexample) have linear chromosomes and thus use telomeres as a protective measure against the loss of coding sequence caused during every replication of a linear chromosome. Most prokaryotes have circular DNA, thus avoiding the shortening effects of replications. Telomerase itself just extends the telomere, which is merely a repeating noncoding sequence, thus increasing the cell’s reproductive longevity by delaying the inevitable cleavage of important genetic material that would occur if a cell line were to replicate without expressing telomerase.

Another topic that came up repeatedly was the discussion of viruses as “living” or “non-living”. I’ve discussed my thoughts on the matter in a comment on your “The virus and the virion” post at your virology blog (http://www.virology.ws/2010/07/22/the-virus-and-the-virion/). The comment I’d like to make in this email is with regard to vaccine terminology. Often the topic of whether to use words like “activate” and “inactivated” in place of “live” and “killed” because viruses fail to meet the classical criteria of life. Personally, I prefer “live” and “killed” both because they require fewer syllables and because they are more intuitive. A “killed vaccine” doesn’t carry the same connotation of being ineffectual that “inactivated vaccine” does and it doesn’t take as long to say it. Further I would like to point out that those two words are not exclusively used with reference to entities that are living by the classical definition. Live grenades and killed microphones are perfectly acceptable phrases in the English language. So regardless of your thoughts on the living or non-living nature of viruses, I think that you can feel free to say live and killed as modifiers for viruses and viral vaccines without stigma.

Viral evolution is a topic that really piqued my interest and I am looking forward to checking out Luis Villarreal’s book from my college’s science library when the new semester starts. So, without much background in the topic, I have a couple of questions of a speculative nature that I was wondering if you could discuss. One of the interesting things about organisms is the universality of DNA as the genomic medium as well as the near-universality of the genetic code (and the alternative codes are only slightly different than the cannonical code). Is it possible that dicers played a key role in the demise of RNA based organism in the primordial sea? I also remember hearing on your podcast that mimiviruses package some of their own transfer RNA, which made me wonder if the viral tRNAs of this monster virus in any way acted to modify the genetic code for the virus.

To wrap up, I’d like to suggest two websites to check out. The first is one of the blogs at Seed Media’s ScienceBlogs called ERV, which, as you can guess by the name, is about endogenous retroviruses. It’s written by Abigail Smith, a graduate student from University of Oklahoma who studies retroviruses. The writing can be a bit informal at times, but she often writes about interesting topics.

The second link, I’d like to send on is to Hans Rosling’s Gapminder. He’s talked at TED before, and his first talk is here (within that link is a link to a follow-up talk). Their Gapminder World software is a great source for visualizing the relationships between various national indicators and a few of them under the Health section have direct relevance to virology, though the data covers a broad array of domains and can keep you busy for hours looking at different relationships.

Ben

http://mengbomin.wordpress.com/

Jennie writes

Dear Dr. Racaniello and TwiV guys,

I am a patient with Chronic Fatigue Syndrome, and I found TWiV when you discussed XMRV on the show. My background in science consists of the PhDs held by my parents and brother (none in virology), but I love TWiV! Your discussions are informative and (usually) easy to understand. I am learning a lot from the show, and will keep listening. Using the podcast to make science more accessible to the general public is brilliant.

I would also like to thank Dr. Racaniello for giving a webinar on XMRV for the CFIDS Association. The CFS community needs to understand how science will solve the XMRV question, even if the pace is too slow for us as individuals. You perform a great service in sharing a scientist’s point of view of the topic. Full disclosure: I am a member of the Association’s Board of Directors, but I know many patients appreciated your perspective and participation.

Thanks for your terrific work!

Jennie

Richard writes:

Dear Guys,

I did it. With a start at about May 1, I caught up through all 92 TWIVs. TWIV has become a very important part of my work. I want to tell you about what I do because it is a new profession, and I think the several people who do what I do would benefit as much from TWIV as I have. I am the Director of Vaccine Access for the Pediatric Dengue Vaccine Initiative, a program of the International Vaccine Institute. The organizations like the Dengue Initiative are called Product Development Partnerships (PDPs). They are like small non-profit drug and vaccine development companies. All of them are supported by the Bill & Melinda Gates Foundation and other donors. They always work in partnership with one or more private companies. For example, we have worked with sanofi pasteur, GlaxoSmithKline, Hawaii Biotech, and Inviragen. We collaborate in different ways with each organization. With Hawaii Biotech and Inviragen, we paid for the production of the clinical lots they needed to get into Phase 1 testing. A core function of a PDP is to help plan for the introduction of the new product into developing countries and reach the poor in those countries; that is basically what I and my access colleagues do. When friends ask me what I do, I say that I am like the Vice President for Global Marketing of a vaccine company except my market is the poor in developing countries. At any rate, there are about 12 PDPs and several are concerned with vaccines: TB, malaria, AIDS, hookworm, cholera, shigellosis, rotavirus, typhoid fever, and pneumococcal disease. Not one of the access directors is a trained virologist or vaccinologist, as far as I can count. However, to do our job we must understand viruses and “how they make you sick.” So, I’d like you to know that your program is contributing to making vaccines available to the poor in developing countries. Your discussion of dengue has been very good and helpful, and I have learned a great deal from all the other episodes. I hope all my access colleagues will listen to TWIV, and I have written to them separately suggesting they do.

I wonder if you would consider doing a program on the vaccine PDPs. I attach a paper by Mary Moran and colleagues that will provide more information.

With congratulations for a truly amazing science breakthrough.

Rich

Director, Access

Pediatric Dengue Vaccine Initiative

International Vaccine Institute

Seoul, Korea

Judi writes:

First – thanks to all you for the wonderful education you are giving us. I am a high school science teacher and you are great professional development for me, especially since there is no funding for conferences.

And, as an educator, I know the amount of work it take to prep a lesson. I am amazed at the amount of work you all do for the commin good. You are truly educators.

I would like enlightenment, please, about gel filtration. Gel filtration a]was described as beads in a column that size=separated materials.

I thought gel filtration as size separation by molecules in a agarose or acrylimide media by electrophoresis. The procedure with beads with pores is, I thought, size exclusion chromatography.

Chromatography can also be ionic, hydrophobic, or affinity columns.

Can you clarify? What is the difference between filtration and chromatography anyhow?

Once again – thanks so much – can I vote for more TWIP?

Judi

San Diego, CA

Elio writes

Hi, TWIVers:

Please see the attached letter. I love TWIV, by the way.

Regarding your discussion of the term prokaryote in TVIW # 93, I want to pipe in as a combatant in the “P word” wars. I am firmly in the camp of the users of the term. Although the term has carried a phylogenetic burden, meaning that it originally implied a close evolutionary relationship between the Bacteria and the Archaea, no one I know uses it in that sense now. Among biologists, the three domains model is widely accepted, in fact, not even discussed. It’s true that there are leftover people who think that the prokaryote/eukaryote divide denotes a single evolutionary cleft, but that’s simply because any concept of science takes time to filter out.

I maintain that the term, used in a broad sense, is extraordinarily useful. In a college textbook I co-authored called “Microbe”, we used the P word some 300 times. How come? Had we not used it, we would have had to say “Bacteria and Archaea” that many times (and being parsimonious of verbiage, we eschewed that). This usage illustrates the reality that these two groups of microbes, though they likely diverged very early on in evolution, share a large number of common properties. They sizes tend to overlap, their overall body plan is generally very similar, they often occupy the same habitats, they share many homologous genes. Presented with an EM thin section, you could not tell a typical bacterium from a typical archaeon. So, dissimilar as they may be in one sense, they are very similar in a number of important attributes. Saying “prokaryotes” is much like saying “animals” or “plants,” large groups that are extremely heterogeneous and that diverged a long time ago (although certainly not as far back as the prokaryotes and eukaryotes). I agree, there is danger in the P word being misunderstood out in the big wide world, but there is none within the family of biologists.

Anyhow, the battle has been met and, yeah!, the victors are clearly the users of the word prokaryote. The term is found all over the place, notwithstanding the astonishing campaign waged against it. Just look at titles of recent articles in major journals.

There is a more serious issue. Making phylogeny the overarching master of relatedness is readily justified if one thinks in these terms only. But isn’t ecology just as important to understand biological behavior and relatedness? There is a tyranny to phylogeny, which demands that you view the world of living things in terms of where they came from, not what they are doing now.

Elio Schaechter

Co-host, Small Things Considered

Atila writes:

Dear Twivers,

I have already written for the show, but forgot to present myself. My name is Atila, I’m a Brazilian graduate student working with HIV evolution at Universidade de São Paulo. After listening almost all shows, I can say that TWiV is a great way to keep in touch with general virology instead of just reading articles in my narrow area. Also, you have made my dish washing time much more pleasant.

During the TWiV 90, Dave wrote about the difference between organisms mutations and computer program mutations. I would like to add another point of view. For me, the most important difference between computer programs and living organisms is redundancy. While computer have strict instructions to realize tasks, we have many metabolic pathways and even important genes may be knocked out with virtually no effects. So we can afford changes in our code with much more flexibility than computer programs. I suggest an open access PNAS article comparing the differences between E. coli genes and Linux OS code, showing that their set of instructions, composed of regulators, middle managers and workhorses, have a very different distribution. Also, the bacteria has more autonomous modules of genes controlled by one master regulator, so that the loss of one module does not affect others. On the other side, Linux has many overlapping and interdependent modules, and if one crashes, so do all.

Yan, K., Fang, G., Bhardwaj, N., Alexander, R., & Gerstein, M. (2010). Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks Proceedings of the National Academy of Sciences DOI:10.1073/pnas.0914771107

Also, Dave ends the letter asking if there is any biological entity that self-mutates. I want to add that viruses can self mutate to, and not only via its nucleic acid polymerase. In the last years, it has been found an enzyme called APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) that is capable of attacking single stranded DNA at the cell cytoplasm. It deaminates cytosines mutating them into uracils, hypermutating HIV genome with many G-to-A changes. This protein is packed in the virus particles and leads to the introduction of many stop codons in HIV genome.

HIV has an accessory protein named Vif (Viral infectivity factor) that promotes the degradation of our APOBEC3G, and allows the virus to replicate in human cells. Now comes the weird part. They have found that some Vif defective viruses can replicate in APOBEC3G expressing cells, and what makes this possible is that their other accessory protein Vpr (Viral protein R) stops bringing APOBEC to virus particles. So, HIV can actively pack APOBEC within its particles, balancing Vif inactivation and Vpr recruiting, and may be using the hypermutation for its own benefit.

Haché G, Shindo K, Albin JS, Harris RS. Evolution of HIV-1 isolates that use a novel Vif-independent mechanism to resist restriction by human APOBEC3G. Current biology : CB. 2008;18(11):819-24.

Congratulations for the great podcast and sorry for my English,

Atila

PS Is there a virus that infects mitochondria? Its an organelle that has its own genetic material and polymerase, so it could replicate a virus. Does the mitochondrial double membrane and the cell membrane impose a barrier that phages cannot transpose?

Chad writes:

I found the podcast a few weeks ago, and I just listened to #63 where Alan was talking about WINE.

He commented that he didn’t know why they say that Wine Is Not an Emulator, and I didn’t know if anyone had explained this yet.

I have been into Linux for years, and the reason that the WINE team call it that is because it installs the native Windows API and uses that to trick programs into thinking that they are on a Windows PC, thus making them run as native applications.

It creates a Windows directory and labels it as drive “Z”. In non Windows systems drives are usually labeled something like “hda0, hda1, sda0, sda1, fdd0, fdd1, cdrom0, cdrom1, ect.”

I hope this clarifies things a bit.

Chad

Louisville, KY

PhD student in distress writes:

Hi Professors,

I’m a PhD student in studying influenza. I’m writing to share with you an interesting paper I found in Virology Journal. The authors discuss the possibility of influenza infection in a story from the bible. Even though I find their discussion rather interesting, I’m curios as to why something as speculative and unconfirmed as this can be published in a science journal. my guess is that something like this should be published in a science magazine or something similar. Just a thought.

On another note, I’m writing to seek advice from you guys with regards to my current predicament. I seriously enjoy my work and the prospects it brings but I am working under a supervisor who is very temperamental. He has violent mood swings and this results in us working in fear in his lab. We often have to resort to hiding bad results and doing secret experiments to get the results that he wants. I’m half way through my PhD and have often considered quitting, but the amount of data I’ve generated over the past 2 years is rather substantial and could lead to more interesting work. Most of the professors in my university are pals of my supervisor, so discussing this matter to them would not help. You guys seem to be rather nice guys, pls advice on this matter….

PhD Student in distress

TWiV 106

Christina writes:

Hi TWiV guys,

I am currently attending Florida Gulf Coast University as a biology major. I am taking molecular genetics and a virology course. I have learned that, in a eukaryotic system, histones are bound to DNA through a force attraction between the negatively charged nucleotides and positively charged histones. The disassociation of histone proteins with DNA, for either replication or transcription, is due to ubiquination, acetylation, or methylation which decreases the positive charge on the basic amino acids in the histones. Knowing this, I wonder how viral capsid proteins disassociate from viral nucleotides upon entry. Is the mechanism similar to eukaryotes or do the mechanisms differ from virus to virus? If the mechanisms differ from the eukaryotic system, what strategies do the viruses employ?

Thank you,

Christina

P.S. Looking forward to meeting you during your podcast on December 6th at our campus!

Aatila writes:

Dear Twivers,

As a Brazillian graduate student, I was very surprised to hear about the finding of vaccinia viruses in monkeys at Brazil in TWiV 95 and not finding about it in Portuguese. So I wrote to the team that made the finding, interviewed them for my blog (http://scienceblogs.com.br/rainha/2010/09/vaccinina.php) and recommended their history to the local newspapers. Fortunately, they received divulgation in local newspaper after.

I’m writing because I remember professor Racaniello asking how they came up with the idea of sampling monkeys at that point. So I asked them during our interview.

They told me that already there where records of rural workers with vaccinia at the Southeast Region of Brazil, and some old records of detection dated from 1960’s at Belém, a city really far at North region. So, they knew that the virus was somehow spreading trough the country. And knew that similar viruses like cowpox and monkeypox can circulate in primates and rodents.

Also, in Tocantis, the state where they collected the samples, a big damn was being built (for the Lajeado Hydroeletric station, that appears at the episode picture) and a large region would be flooded. So, the animals had to be rescued and transported to safe ground. A good occasion for sampling.

Visiting the TWiV site to write this e-mail I saw the video of episode 96 (I’m used to download the episodes directly to my ipod). It’s very funny to have the opportunity to see the show being made and see the faces of you all. TWiV gets greater every time, and I really appreciate how you can have every kind of participants at the show, from graduate students (and prof. Racaniello’s son) to Nobel laureates. It’s fantastic to have contact with this sort of content here at Brazil.

Keep the good work,

Atila

Donghoon writes:

Dear TWiV

I am a big fan of TWiV since I bought my iPhone4 last June. I haven’t thought a Podcast can affect me this much. The iphone was a really good buy for me that is only because of TWiV. I can make a call with it as well (:-))

Anyway, I heard you introduced HTS at Episode 95. I liked Alan’s explanation about HTS. I appreciate it.

The reason I am writing this email is that I wish you can advertise a program funded by the NIH, that is the MLPCN, Molecular Libraries Probe Production Center Network. http://mli.nih.gov/mli/mlpcn/

I would say this program as a “poor man’s HTS”, which the NIH provides all resources to screen a 300,000 compound library for YOUR ASSAY. You don’t need to buy anything. Only thing you have to do is “to develop an assay which (potentially) is compatible HTS and submit it. This is a FREE service and it uses RO3 and R21 mechanism. This is open to ANYONE even to foreign institutions. The centers in the network will screen for assay providers and still assay providers receive money for doing follow-up experiment etc.. (This is cool.) The MLPCN has done more than 200 HT screenings for public domain.

The reason I bring this to your attention is this program supports “HTS for infectious target”. Southern Research Institute is a specialized center in that aspect. The outcome of the screening is a “probe” which can be developed for a therapeutic candidate (for antiviral) or special compounds to see the effect of it in your assay. For example, if you submit an assay which can screen compounds inhibiting (or activating) a certain step (let say, inhibition of NP trans-location from/to nucleus), at the end of the screening, you will get (a) compounds with that activity. And you may want to utilize the compounds to study your basic science as well. The program accepts variety of assay formats such as a cell-based assay, fluorescence based or target oriented or phenotypic assay as well. There is a chemistry centers which work for SAR and lead optimization for you. Again everything is free once your assay is picked. I believe more virologists should take advantage of this program.

It would be great if you can read this to your listeners or pick the MLPCN site for “pick of the week” so more people can see the program.

I apologize for bad grammar (English is my second language) and please tailed it if you want to.

If you have a question about the program, I would be more than happy to answer it.

Best regards.

Hoon

Center for Predictive Medicine For Biodefense and Emerging Infectious Disease

https://louisville.edu/research/cpm

TWiV 105

Timothy writes

Dear Vince and Alan,

Being a seasoned virologist and a science writer, I was hoping you could discuss the interface between basic science, public health, the media and the general public…

While I was listening to you discuss the controversy surrounding the potential involvement of XMRV in CFS, it unfortunately reminded me of the Andrew Wakefield story.

Like the Wakefield saga, it seems as though the Wittemore Peterson study has given a glimmer of hope to a patient population suffering from a difficult to diagnose disease. As we saw with the Wakefield study, even though several studies disproved the association between the MMR vaccine and autism, many people were reluctant to believe it. Alas, pipets are no match for hope.

Is there any way to temper the media’s response to studies like these in order to send a message that is more realistic? Relatedly, the media response to H1N1 pandemic threat was especially painful to watch. The media could be one of the most effective arms of the public health machine but oftentimes instead of helping, it creates a world of hurt. What is your take on this situation? How can the scientific community disseminate more responsible and accurate information to the public? Is this even possible since the media’s business revolves around attention grabbing. Are pipets no match for the dollar?

Keep up the good work. Until next week…

Tim

Ilya writes:

Hello, Vincent, Allan, Rich and hopefully Dickson!

I write to tell you again of how fascinating and useful I find TWIV. Your ability of being descriptive and as simple as possible while talking about serious questions in virology attracts people and makes them wait passionately for each new episode. Interestingly, this TWIV FENOMENON spread far beyond virologists. You are great!

Recently I had a talk with a non-virologist on how could a non-living object multiply and influence cell so much. Another chapter of “chicken and egg question” in virology 🙂 Successfully I managed to find a decent model for explaining it to him. Now I want to share it with you.

Imagine a fine Swiss-made mechanic watch. Each gearwheel is in its place and everything works fine. Suddenly one tiny tooth slips through a chink inside the watchcase and get stuck between two gearwheels. The watch is still ticking but something goes wrong from now on. One by one teeth start to break from stalled gearwheels, damaging working ones. Now, the watchcase breaks open exploding lots of tiny teeth to other watch.

Maybe it’s a bit too mechanistic, but descriptive. It worked.

LISTENERS! Vote for MORE TWIP campaign!

Ilya

Arsen writes:

Hey! TWiV 88 gave me some pretty nourishing food for thoughts.

I’d like to thank you for bringing my attention to the article on gene therapy being a potential cure for HIV. I’ll translate and publish it in my Ukrainian blog on advances in medicine: http://laboratoria.zahray.com .

Also I have found the article on reconstruction of an ancient human retrovirus fascinating. It would be also interesting to conduct a different experiment: how about removing from human embrio’s DNA the traces of recent (since apes) retrovirus infections and observe, if there are any noticeable differences. The experiment probably wouldn’t be conducted because of the ethical considerations, however, it would be just fascinating to find out, if some of our superior human intellect was originated by retroviruses.

Arsen

Ed writes:

Hi Vincent and the Gang,

I came across a book the other day that scratches the same itch as listening to TWIV and TWIP. It’s called “Genes, Germs, and Civilization”. I’m only a little into the book, but so far it’s covered some interesting links between the origin of diseases (measles, malaria, …) versus the human population density needed to keep the infection from dying out. I wonder if you’ve read it, and what your opinion on it is.

I’ve been listening to TWIV since your first appearance on Futures in Biotech early last year. I’m an electrical engineer, and as other have mentioned in letters you’ve read on the air, there’s something compelling about viruses and their programming. The question of whether computer programs can mutate and develop successful new features came up on one of your recent shows. The biological system has an advantage over present day computers in that each cell is equivalent to a computer. In an infected individual you essentially have billlions of parallel computers each producing occassional random variations, and billions more uninfected computers each testing the outcome. Some day we may have that many computers, but so far it’s a math thought experiment.

Samuel writes:

Dear Sirs-

I love twiv and hope it becomes even more popular/famous. I read “H1N1 Lessons Learned” in April’s CIDRAP–an article in by Robert Roos in which you (Vincent) were interviewed–and I was surprised that there is not an agreement among scientists on what to expect from this upcoming flu season. Why is it that some virologists have doubts that the 2009 H1N1 will replace other subtypes as the major seasonal flu? Is it mainly b/c the cycling strains of the 1977 H1N1epidemic–and possible lab accident–muddle things so that we have no analogous history to compare to the current situation? I don’t want to sound like a pushy reporter, but I would be interested if anyone would like to place a bet on what we will see from H1N1 this autumn.

Can there only be one serotype that carries the day and becomes the major seasonal flu? I ask b/c in 2009 H1N1 seemed to have usurped the previous flus. What is the significance of “serotype”? If the 2009 H1N1 and the 1957 H1N1 have the same hemagglutinin and neuraminidase proteins does that mean they have the same antigens? Do they elicit the same immune response?

Thanks for bearing with me through all these questions.

PS: I enjoyed the article in CIDRAP and thought you did a good job explaining complex concepts concisely, and in a way palatable to the public. (I read the article as part of a course co-taught by Drs. Phillip Brachman and Jan Patterson for the University of Michigan Epidemiology Summer Sessions

Samuel

TWiV 104

Kelly writes:

I know that I am behind on this but would you please do a complete broadcast of the suspected cause of CCD (colony collapse disorder) in honey bees. I am a bee keeper and would like to know more. Please don’t be afraid to dumb it down.

Also would you explain the naming of the flu viruses strains such as n1h5, n2h3, (for example n means x and h means y and the numbers mean???) Thanks for being approachable. Many knowledgeable people are very condescending and arrogant. You are not and that is important to those who are trying to learn.

Thanks

Kelly

Timothy writes:

Vincent et al:

I just listened to your latest podcast episode (#88) on my way to work and heard you mention the new DVD, “Naturally Obsessed.” I’m wondering if you are aware of the quite similarly entitled 1999 book, “Natural Obsessions,” written by Natalie Angier on the very same topic! [vr: yes, pick of the week on twiv 71]. She was allowed into the inner workings of lab of world-famous cancer researcher Robert Weinberg at MIT, and it so happened to be around the time his lab discovered the retinoblastoma gene (Rb), which as you know is a key regulatory of cell growth and is a favorite target for many of the DNA viruses. Might this be “title/concept plagerism,” or alternatively perhaps is it obvious to non-scientists that we scientists are just very obsessive people?????

By the way, like everyone else who’s emails you read on the air, I really enjoy your podcasts. I discovered twiv when browsing iTunes for something that I could listen to when NPR turns to all of the depressing stories on war and politics during my commute. I was hooked when the first episode I listened to that I picked randomly from recent ones featured Grant McFadden discussing virotherapy for cancer, as that is my field and he gives great talks at meetings. (My PhD thesis was in virology — HPV — but I became a pediatric oncologist and now study virotherapy for children’s cancer.)

One more thing: I know the following is probably a sad statement of the times in which we live and the fact that we are all too busy, but I was delighted to discover I can listen to twiv at 2X speed on my iPod Touch and understand everything very clearly. The pitch, lilt, and cadence of all of your voices speeds up just fine, and I can get twice as many episodes in as I might otherwise be able to catch! (Note: Note everyone’s voice is amenable to fast-forward — I can’t speed up Futures in Biotech as well because Marc talks so fast!)

Thanks to all of you for taking the time to help the wonder of viruses go viral.

Tim

James writes:

Hello Professors,

I am glad you said something in episode 89 that the scientific community needs to step up its PR game. I already did something small about it. I started influencing my friends with what interests me in science. I wrote this article early June and would appreciate it if you critique it.(if you have the time)

http://www.higgens.net/amatterofscience/?s=amatterofscience-061110

Thank you,

James, ASCP(CG)

Cytogenetics Technologist

PS Keep up the great work and love your show! Thank you for answering my question about “if human cancer cells grew a resistance to viruses,” a few episodes back.

Connie writes:

Hello Vincent and Alan,

I am an avid TWIV and TWIP listener, being a Ph.D. molecular geneticist who is also a practicing veterinarian (another one of those who trained and then didn’t see herself chasing the grant dollar and waiting years for results). I love both shows and your communal erudition and humor.

However…

twice now (once on TWIP and now again on TWIV), a veterinarian’s perspective is sorely lacking (the TWIP “incident” was simply a slight misunderstanding of a parasitic zoonosis). This time the commentary was a bit offensive regarding veterinary vaccine guidelines and motivations for those guidelines. Since 2006, AAHA (as well as a number of other professional bodies) has set vaccine guidelines that define “core vaccines” for dogs and cats. 3 year duration of immunity is standard for those core vaccines (Parvo and Distemper for dogs, Rhinotracheitis and Panleukopenia for cats with Rabies durations set via a combination of manufacturer and state standards). I refer you to the synopsis http://www.avma.org/onlnews/javma/apr06/060415i.asp.

While it is true that a few practitioners have been slow to embrace the new guidelines, most have and it is mark of a high quality practice to do so. Sadly, because companion animal medicine has scant research dollars, we are left primarily with manufacturer-funded research and so had no vaccine (other than Rabies) labelled for 3 year duration of immunity until quite recently. Titers are also quite effective for Distemper and Parvo so are frequently done in lieu of vaccines. I will say also that, having spent an externship on the Navajo reservation where vaccination rates are low, the core vaccines are vitally important.

Just to let you know that the bulk of what we do consists of a high mastery of most things medical and surgical (my days are spent with congestive heart failure, diabetes and other endocrine disorders, renal failure, autoimmune diseases, dermatologic disease, urolithiasis, pneumonia, peritonitis, splenic, renal and hepatic masses, hyperlipidemia to name a few while being able to perform nearly all abdominal surgical procedures and fracture fixation, as well being pretty handy with abdominal and cardiac ultrasound in addition to trauma medicine—the caseload and variety having much to do with the fact that most purebred dogs come from tiny founder populations with an excessive amount of inbreeding as well as small animals’ prediliction to try to kill themselves with vehicles and toxins). Sadly as well, I have to keep up with the human literature (NEJM, Lancet, Annals of Internal Medicine, Annals of Emergency Med as well) since my own branch is so underfunded that much of what we do is extrapolitive.

These are 10-12 hour days for a median national salary of $75,000 per year with vaccines accounting for probably 1% of my income. To put it in perspective: I nearly choked on my biscuit when Sara Palin made fun of C. Elegans research (“millions of dollars to study worms!” I believe was the quote) so please don’t “Palin” the veterinarian. We try very hard to do good medicine at low cost.

I forgive you but do want you to be slightly sensitive to your fellow science geeks.

Connie DVM (and Ph.D.-which-is-not-on-my-business-card)

Portland, OR

Heather writes:

Dear TWiV,

I am a 3rd year medical student here at Columbia. Dr. Despommier actually interviewed me when I applied and had a lot to do with my decision to choose this school, and then he told us about TWiV during a Parasitology small group session last fall and had a lot to do with my listening to this show when I should be studying for exams!

I know that this is rather tangential to the topic of virology, but I wanted to comment on the SMN1 and SMN2 genes mentioned in the discussion of Andrew’s letter in TWiV #88. SMN1 and SMN2 are actually different genes located near each other in the human genome. Other mammals only have SMN1 – SMN2 arose due to a gene duplication in humans. Spinal Muscular Atrophy (SMA) is due to a mutation in SMN1 that causes improper splicing of the mRNA, resulting in a nonfunctional protein. The mRNA for SMN2 is spliced like SMN1 should be spliced about 10% of the time, so it can actually serve as a “rescue” for the defective SMN1. Different individuals have different numbers of the duplicated SMN2 gene in their genome, so there are different severities of SMA – those with more copies of SMN2 make enough of the “close enough” protein that the disease may be fairly mild, while those with few copies of SMN2 can have severe disease, perhaps even dying in infancy.

TWiV 103

Anttoni writes

Hi!

Thank you for your great program!

Im a material enginer/organic chemist student and i have developed a interest in virology while listening to your program. I found your program when asking around in www.reddit.com for good scientific podcasts to listen while biking to work or lectures.

I’m still listening to the past episodes of Twiv, so im not shure if you have allready digested this information.

I recollect that you spoke in your “live-podcast” about the GlaxoSmithKline vaxine Pandemrix having a new, untested adjuvant.

Now it seems that that adjuvant can cause narcolepsy in 12-16 year old children (http://www.thl.fi/en_US/web/en/pressrelease?id=22930). As there seems to be some evidence of narcolepsy being caused by a autoimmune disease (http://news.bbc.co.uk/2/hi/health/4081225.stm), is it possible that the adjuvant causes a overeaction while trying to enhace the immune responce? or could the inactivated virus be the main cause? I know this is a hard question that probably has no answers yet, but as a novice in virology id like to hear what the experts have to say.. 😉

Also, as the cases have emerged only in Finland and Sweden, whom both have quite homogenic population, could the ammount of narcoleptic symptoms (that seem to be higher then in a normal influenza) be caused by a mutation in the population or could screening in these countrys be different (both have national healthcare for all)?

Thank you for the good work you all put into this!

Anttoni (just say Anthony 😉

ps. I’d love to hear a episode about virus-free surfcaces via selfcleening coating and what is the mecanism and how these surfaces are tested/used in laboratories and in the field. Thanks!

Stann writes:

Hello Vince and company. I was listening to a previous episode of Twiv today, and enjoying a banter between yourself and Dick about virus transmission. The topic was that all viruses evolve towards increased transmission, and away from lethality. Over time, it would be safe to assume that all viruses will eventually become something akin to rhinovirus, spreading like wildfire all through their host population, but rarely, if ever, killing a host. I thought of an interesting question I would like to ask: if all viruses evolve away from lethality, why did they evolve it in the first place? What about the lethal viruses that are around today? Why haven’t they lost their lethality? Are they new viruses, that haven’t been given enough time to evolve? The only answer I could come up with when posing these questions to myself is that the viruses that can jump between species evolve to reduce lethality to their natural host, not their incidental host. That would only explain those viruses that can do so, but not viruses such as polio with only one host. I would be very interested to hear everyone’s opinion, if an answer even exists, thanks.

Stann

NS, Canada

Kate writes:

Hi, TWIV team!

I love your podcast and the wealth of knowledge you make available to the general public!

My question is about viruses that effect animals: do animals experience viral infections in the same or a similar way as humans? In humans, usually there are physical symptoms that indicate a viral infection. Is this same in all animals or at least some animals?

Thanks and keep up the excellent podcasting and “lame” jokes… I love ‘em!

Kate

Eric writes:

Hey guys, I’ve been listening to the podcast for a while now. I happened across it in itunes and have been hooked ever since. I suppose you could say I’m writing this as lay person, since my background is in nursing, and not in microbiology. This thought occured to me as you were talking about Norovirus and the routes of transmission being the fecal oral route. I have read elsewhere that the typical scent has a weight of about 760 nanograms, and I have also read that a “typical” virus wieghs in at around 10 femtograms (0.00001 nangrams). You may see where I’m heading with this train of thought….. For smell to have weight, it has to have substance…………so I guess what I’m asking is, is the amount of fecal particulate passed in flatus sufficient enough to transmit a significant viral load, and possibly transmit Norovirus? This may be the wierdest question and or hypothesis ever presented, but just like many things in life, you’ll never know unless you ask!

Keep up the great work guys,

Eric LPN

TWiV 102

Simon writes:

Hello Vince and Dick,

Thank you for your podcasts, i subscribe to both twiv and twip and find them both fascinating. I work as a truck driver here in England and listen to your podcasts whilst driving about. Currently i am study for a life sciences Bsc (hons) with the Open University and just coming to the end of my first year. I’ve just finished a module on microbes and your podcasts add to the stuff that i’ve learnt doing that. During the twiv and twip I find the questions Dick and Vince ask each other very helpful for explaining things in a more layman like way, hopefully as my studies continue i’ll be able to keep up with the more complicated aspects of the subjects. Also i have downloaded Vince’s lectures on virology from iTunes U which give me some grounding in these excellent subjects. Once again thank you for your podcasts, keep up the good work.

Many thanks, Simon

Josh writes:

Hey TWiV guys,

I emailed back in early 2009 when I first found your show to tell you how much I had been enjoying it. Since then I’ve listened to all of your episodes. I’m a medical student at the University of Dundee in Scotland. In the UK, the Medical course is undergraduate and takes 5 years. After listening to your show and hearing all about the interesting lab techniques from brilliant researchers I decided to take up the university’s offer of doing a BMSc (Hons) in a single year before returning to the medical course. It is very challenging to go straight into the final year of a course that medical students are taught little about but I decided it would be worth it for the practical lab experience.

I’ve just begun my Pharmacology degree course and have a placement in a lab working on diabetes. I’ve already treated cell cultures with various drugs and have just completed my first Western blot! Having never done any lab work before this is all very new to me, but I’m really enjoying it. I’m looking forward to using various other techniques I’ve heard you guys talk about including PCR. Just thought I’d let you know that you are the people who inspired me to do some pure science! Hopefully some day I’ll get to work with some viruses too.

Thanks a lot and keep up the good work,

Josh

Erik writes:

Since influenza virus has eight genome segments, and each segment carries a gene or genes that are vital for the virus to exist/replicate, how does a budding virion “guarantee” (I know how you feel about anthropomorphizing viruses, but I can’t think of a better word) that it will contain all eight genome segments? Is it simply that the ones that are missing one or two or have doubles of a segment will not “survive”, while those that by chance just happen to have all eight will proliferate…..a sort of ‘survival of the most complete genomes’? Or is there a different, more sophisticated method that the virus employs in order to get all eight genome segments into all or at least most of the budding virions?

Best wishes,

Jamie writes:

Dear Vincent, Dick, Alan, Rich et al,

Knowing how much you guys love bats*, and on the off-chance you hadn’t seen it yet, I thought I’d bring the following to your attention; it seems deforestation in the Amazon is causing large scale vampire bat attacks on the local population of that part of Peru, which in turn has caused an outbreak of rabies (how’s THAT for medical ecology Dick?):

http://www.bbc.co.uk/news/world-latin-america-10960389

It’s only a short news article, and I’d like to see more information, but it seems to me that if these bat swarms are spreading rabies it’s quite probably they’re spreading other nasties as well (coronaviruses spring to mind). It doesn’t mention that they are checking for anything else, and obviously vaccinating the bitten for rabies is a priority, but it seems like an ideal opportunity to measure bat-bourne viral spread to humans.

Love the show, started late but working my way back through. Keep up the good work!

Best regards,

Jamie

*Originally I wrote “Knowing how batty you guys are about bats…” but I had to change it. I made MYSELF groan.

Bradford writes:

Hello Dr’s of TWIV,

First off I’ll add to the chorus of emails and say how much I enjoy listening to TWIV and TWIP and couldn’t imagine my commute without them.

I currently work in the Virology department at The American Type Culture Collection (ATCC) in northern VA. I spend my days in the lab replenishing stocks of just about every kind of virus and enjoy every minute of it. My question for you all is, when you’re doing your research, where do you get your viruses? ATCC, being a bioresource, provides many different kinds of authenticated organisms to researchers and universities around the world, but the vibe I got from my lab leader (who recently attended TWIV, Live @ Bozeman) was that most resources in the field of virology tend to come from neighboring labs or researchers doing similar work. I’d be interested to hear how you guys get your biologicals in the academic community and how you make sure what you get is authentic.

Thanks, and I look forward to many more TWIV’s to come!

Brad

McLean, VA

Richard writes:

Hi Professors,

Thanks to Vince again, for your pod cast, and supporting materials (lectures and blog). I am still having fun following, and gaining an understanding of these things.

I have done a little work myself on phage, using samples of both bacteria, and phage from sewage treatment plants. I have not the equipment to identify all of the bacteria present, but have some interesting results. I have seen under a microscope ‘popped’ bacterium from plaques on agar plates. I have also placed phage from a single plaque onto a plate of mixed bacteria, and seen the plate cleared of a single bacterium, leaving the others to thrive.

The reason for choosing sewage treatment plants is, that it is where I work, and they are absolutely full of bacteria (and phage it would seem).

I have a few simple questions that I hope you can answer?

If phage can be selected for, and very quickly wipe out a particular bacterium, then why are they not used more in medicine? It seems that it would be possible to treat bacterial infections this way, and reduce the use of antibiotics. I think this would be more sustainable, since the bacterium and phage are locked in an evolutionary relationship, resistance should be much less of a problem. I’m sure there must be a reason this isn’t done, because it seems almost too easy?

With the recent news on synthetic life, do you see a future for synthetic Virology, and if so in what fields? I would imagine gene therapy would be one possibility, but are there others?

Thanks for your time

Regards

Richard

Levi writes:

Hi TWiV!

Here’s an interesting news article about a “vaccine patch” that delivers a vaccine through hundreds of tiny “dissolving polymer micro-needles.” They barely puncture the skin and are supposedly painless, yet a study in Nature Medicine claims that they induce a better response against influenza than a vaccine delivered by typical needle jab.

The BBC article: http://www.bbc.co.uk/news/health-10661117

The original paper: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2182.html

Do you think this technology could ever see common use, and could we ever use it to vaccinate ourselves rather than going to a doctor’s office or other vaccine clinic? I know many people who don’t like needles who would love something like this. However, there are also plenty of people who I’m sure would love to sue a manufacturer if they used the patch but still got sick.

Would self-administration be a realistic goal for future vaccines, or will we still need someone to apply the patch on our arms to make sure we did it right?

Thanks, and I look forward to your comments. As always, TWiV is excellent. Keep up the great work.

Levi

Pre-Doctoral Fellow

UF College of Medicine

Katie writes:

Hello all!

I just want to tell you that you are all my heroes, and I wish (as do many of my student counterparts, I’m sure) I could hang out with you guys during TWiV (not to contribute, obviously; merely to absorb it all in person).

Cheers,

Katie

Lowly 2nd year PhD Student

Distant Land of Montreal-ia

North of the Border

PS: sorry about all the parenthetical text. Bad habit.

Eric writes:

Hi Vincent, Dick, Alan, Rich, et. al:

After the last time I was on TWiV, I received an email from a high school biology teacher in Hong Kong who was interested in helping with the viral metagenomics project. So I sent her a data set to work with and she is blazing away. In the meantime, we have been discussing how we can bring her high school students into the project and she had some really great ideas that I hope we can implement in the next couple of months. So hopefully, we will have students at all levels hunting for viruses in a haystack of sequences! Once we have something established, I intend to reach out to our local high schools, too.

I think this story illustrates how wide spread TWiV’s influence is, and demonstrates what a powerful tool it is for science education!

Thanks for your continued effort in making this podcast a success,

Eric

Eric F. Donaldson, Ph.D. Research Assistant Professor, Ralph Baric Lab University of North Carolina Department of Epidemiology

TWiV 101

Russ writes:

I think this image from www.3d4medical.com is great!

This is a cool app for the iPad. This would make a great pick of the week

Russ

Julian writes:

Dear Vincent, Dick, and colleagues,

My name is Julian, DVM, MSC in Virology and PhD candidate fron Universidad Nacional of Colombia (South America). After some discussions with some Virologist including Dr Anne-Lise Haenni (Business Secretary from ICTV) we wrote a disscussion paper about the “Living Nature” of viruses, trying to travel from the virus history to the new concepts and findings about viruses.

This paper were published in the last number of Acta Virol (Viruses, virophages, and their living nature -http://www.ncbi.nlm.nih.gov/pubmed/20545437) and I would like to share it with the biggest team of Virologist on the web (I attached you a PDF copy of the paper).

Keep on-line podcasting, you have faithful listeners on this tropical virology area. I hope to meet you in the ASV meeting in Bozeman.

As a pick of the week, I would like to share the best Virology Book that I have ever read: “The Invisible Enemy: A Natural History of Viruses” from Dorothy Crawford, Professor of Virology from the University of Edinburgh.

Best regards

Julian

Colombia

South America

[This article was referenced in Julian’s paper: http://www.ncbi.nlm.nih.gov/pubmed/19270719]

Matt writes:

Dear Dr Racaniello and TWIV cast,

I love your show and have been listening to it since Nov 2009 , I know that the topic of viral DNA being integrated into the human genome has come up before , my question is could viral DNA that is in the genome from 100’s to 1000’s of years ago be expressed and produce a virion ? Could it be possible for a virus to aquire genes from another virus that is in our genome? Thanks for the podcast and all the great work yall put into it.

Sincerely Matt from South Carolina

Alex writes:

Hello Vincent and Dick (and all those other experts I have yet to hear on TWiV),

I am an undergraduate microbiologist and the university of Leeds and I wanted to thank you for you marvellous podcast which I discovered last night, we recently broke up for our summer holidays (or vacation as I’ve heard you say across the pond) and I am finding both TWiV and TWiP very interesting so thanks for that.

I thought I would let you know that the article in New Scientist mentioned in episode 1 titled “Welcome to the virosphere” was what initially tweaked my interest in microbiology and led me to study it in higher education. It seems only appropriate that it is mentioned again as I finish my first year of study.

You’re doing a great job with the podcasts, please keep it up!

Alex

University of Leeds

Kathy writes:

Hello!

I was so excited when I started listening to TWIV 87 because I have been a part of Dr. Hatfull’s Phagehunting program. I am a high school teacher in Illinois and was accepted to the first teacher outreach program and spent a week in the summer of 2006 at the University of Pittsburgh learning the protocols for isolating phages. The goal was for teachers to get their students involved in authentic research all over the country. That first year I had 8 students in 3 classes who found their own phage. One of them came in after school to finish isolating it and getting it ready to send to Pitt. She named the phage. It was sequenced and we were able to annotate the genome-it was then submitted to GenBank under our names. This was very exciting to me and to my students. I’ve gone back 3 summers and have trained 3 years worth of students to phagehunt.

While there, we got to listen to lectures on current research in phages and bioinformatics. We also worked closely with Steve Cresawn on bioinformatics. So they are reaching more than just undergrads and local high school students.

The grant has been re-newed so I will go back as long as they’ll have me!

Kathy

High school teacher and TWIV enthusiast

TWiV 100

Damon writes:

I’ve been having an enjoyable time on my commute lately catching up with TWiV. Today I listened to #26 (Poxviruses), which included a discussion of Tysabri and PML. I work at Millipore which sells many products that go into a MAb production train, including virus removal filters that are included in the process. When this Tysabri story broke, there was a minor hubbub here until we (the R&D Virology group) were able to advise everyone that the PML was almost certainly an opportunistic infection rather than a product contamination.

I mention this because the story made me wonder if you might be interested in biopharmaceutical virus safety as a topic for TWiV? One of the things we do is study ways to ensure that any virus that might happen to contaminate a bioreactor would be removed by the drug purification process. There are some interesting scientific and regulatory issues around this, including building of a representative scaled-down system, selection of appropriate model viruses, best methods for virus quantification, and concerns around impurities in the virus stocks distorting study results. I happen to have a “Blog” entry recently put out by my company that discusses about this last issue. ( http://bit.ly/awWInI or http://www.millipore.com/downstream/cp1/2010tour_blog )

Of course, “interesting” is always a subjective term, but if you think this might make a good topic sometime I would be happy to participate.

Incidentally, I share your interest in picornaviruses, at least a subset, having done my thesis and post-graduate work on Coxsackievirus B and the Coxsackie and Adenovirus Receptor (CAR).

Thank-you for the fantastic services you are doing for scientific and general community with both your textbook and the web-based educational initiatives . I have found TWiV and your blog to be great ways to stay dialed into the wider world of virology.

Best regards,

Damon

Cedric writes:

Dear TWiVers,

After listening to you for several months, I have become interested in viruses to the point that I chose to write my final essay in a composition course on them. Attached is the essay: “The ‘Death’ of a Virus.” It was written toward a less virology-aware audience, but I thought you might enjoy seeing one person’s view on viral “life” and his thought process leading to that conclusion.

Many thanks for your wonderful podcasts,

Cedric

[www.twiv.tv/death_of_a_virus.pdf]

Jean writes

Hi Vincent,

I wanted to write and let you know how much I rely on TWIV now for a lot of my virology news! I am not fully caught up on the TWIV episodes, but just finished the one on Dengue. You mentioned that there wasn’t any good models for Dengue in immunocompetent mice, and I was wondering if you had a chance to read a paper in PNAS that describes a dengue model in Balb/C mice (using a mouse adapted virus). It doesn’t say it in the abstract, but if you read the paper, they describe the model in detail, and the disease in these mice does look a lot like dengue in people. Perhaps you saw this paper and think this model is flawed? Could you give me your thoughts on this article?

Best,

Jean

Fred writes:

I just listed to podcast 84 on oncolytic viruses and thoroughly enjoyed it. I agree that the topic warrants additional attention on your show when time permits. I was very glad that Grant McFadden spoke about Reovirus and its oncolytic properties, I only wished he talked about it longer.

The Dearing 3 strain of reovirus is the virus used in Oncolyticbiotech’s Reolysin and is quite far along and showing great promise in cancer clinical trials when used in conjunction with existing drug therapies. The company first tried injecting Reolysin into tumors directly and they found that they were getting app a 70% response rate at the primary injected tumor and some minor responses at metastatic tumors. They then tried Reolysin alone systemically to get at all the tumor masses and were disappointed with the results getting only app a 30 to 35% response rate – the problem being that the immune system cleared out the virus before it could get to the primary and metastatic tumors. This led the company to start testing Reolysin with existing cancer therapies like cisplatin, carboplatin, taxanes and other front line cancer drugs first in petri dishes and then in animals and finally in humans. To their amazement Reolysin and the cancer drugs worked synergistically together boosting the response rates to be higher than either Reolysin alone or the cancer drug alone and boosting clinical response rates back to the 70% or so level seen in the intratumeral trials. The primary reason is probably because the cancer drugs ablate the immune system giving the virus a better chance to get to the tumors and also by making the tiumors beds ‘Leaky’ and more open to viral infection. It has taken at least 10 years for Oncolyticbiotech to get to the point where they are now in one Phase III clinical trial for head and neck cancers and most likely over the next two years to be in up to three more Phase III trials (probably for Ras+ lung cancers and Ras+ colorectal cancers and maybe sarcomas which have very poor treatment options and very poor prognosis). In addition to the Phase Three trials ongoing or to start the company has completed or is currently running over 20 clinical trials with more to start soon

http://www.oncolyticsbiotech.com/clinical.html

Some additional points – Reolysin contains Deering 3 reovirus is a naturally occurring non-manipulated wild type virus. Reolysin is easily and cheaply manufactured in up to 100 liter batches (100,000 injections) with potential to scale up to 500 liter batches.

The company holds dozens if not hundreds of patents worldwide on viral treatment of cancers with reovirus and other types of virus both attenuated and non-attenuated.

App. 400 patients worldwide have been treated to date with Reolysin and the number has been snowballing in the last two years.

Reolysin is being tested in cancer centers in the US, Canada, Great Britain and Europe.

Reolysin is showing great promise and hopefully will be an approved ubiquitious cancer therapy within the next three years.

Thanks again for that Podcast.

Fred

Jim writes:

Found the link to this (http://www.miller-mccune.com/science/the-real-science-gap-16191/) in Slashdot. Lots of comments there, and here. There’s a link in the comments here to a similar Harvard Magazine article, also with many comments. I’m saddened to see few suggestions about how to improve the situation. You’ve probably seen one or both articles, but I wanted to be sure you know about them in case they are useful. Dunno if any listeners to TWIV or TWIP would benefit by knowing where to read them. Perhaps it’s time for America to reinvent itself, again, but I don’t see how to do it, except through innovation.

Jim

Jesper writes:

Professors,

I just met with a friend of mine who recently caught dengue-fever. It’s a rather rare disease in Sweden (30-100/year – http://www.smi.se/in-english/statistics/dengue-fever/). My friend caught it in Malaysia, working as a cameraman at the recording of the most recent season of the European version of “Survivor” (known as “Robinson” over here) – http://www.dowell-netherlands.com/2010/05/dengue-stops-robinson-expedition-in.html. Some 68 people caught it in one fell swoop, and they had to evacuate the entire set.

However, I was glad to be one of the few in his circle of friends who’d ever heard of the disease and even have some cursory knowledge in the field – and no, I did not override his doctor’s recommendation on any point!. I did send him to TWIV#3 (/twiv/twiv-3-dengue/) so he too could get more info from the experts.

Thanks for your effort in producing twiw and sharing your knowledge with me!

All the best,

Jesper
Sweden

TWiV 98

James writes:

I’m just writing to clarify my question about the production of the flu vaccine if one of the other seasonal strains was removed as there seemed to be a bit of confusion about the point of it.

As I understand it one of the biggest holdups in seasonal flu vaccine production is getting enough eggs of the right quality to grow the vaccine in. This is effectively a fixed amount that gets split three ways between the three seasonal strains. So this would mean for 100 units of possible production each strain gets 33.3 units made.

What if the WHO decided that Swine Origin H1N1 had not only displaced the previous seasonal H1N1 but also one of the other seasonal strains and thus the next seasonal vaccine, for whichever hemisphere is next, only needs a bivalent vaccine instead of the previous trivalent vaccine. To my understanding this would mean that for 100 units of available production you could make 50 units of each strain.

This would have two immediate advantages. Either you can make the same number of seasonal flu vaccines as in previous in less time. Or for the same amount of time you can get more doses. The main logistical advantage of this would be that you could vaccinate more people faster then is currently possible.

This of course would require the WHO to decide that Swine Origin H1N1 to have displaced two seasonal strains which seems to be unlikely from my outside view.

Kind Regards,

James from Wellington

John writes:

Dear TWIVers,

Thanks for this wonderful podcast.

I found two of your stories in TWIV #82 really fascinating, and wanted to ask a couple questions. Forgive me if these are dumb questions–I’m a computer scientist with little formal biology background, so I may be missing all kinds of stuff.

First, from your dengue story, I was trying to get my head around antibody-dependent enhancement of infection.

How is ADE related to original antigenic sin? Is it just a worse variant of it? In both cases, you get infected with strain #1 of the virus, you develop an immune response to it, and then when you’re exposed to strain #2, you respond as though it were strain #1. In the original antigenic sin case, you produce relatively ineffective antibodies, so you don’t get as effective an immune response as you should. In the ADE case, the ineffective antibodies provide an opportunity for the virus to gain entry to macrophages via the Fc receptor, along with failing to neutralize the virus. Is that basically right, or have I misunderstood?

What I’m trying to understand is why this doesn’t happen all the time. I mean, if the viral infection is still present when my antibody response starts ramping up, shouldn’t I start having virions getting bound to by some of those early antibodies at a level where they’re not neutralized, but they can get inside the macrophages using the Fc receptor? (Perhaps most viruses just can’t benefit from being engulfed by the macrophage, but dengue can?)

How is the T-cell response involved in all this? If I already have cytotoxic t-cells that recognize what infected cells look like, shouldn’t they be killing the infected macrophages? (Or maybe that’s why the second bout of dengue makes you so sick?)

After you’ve had the second bout of dengue, assuming you survive, do you end up with antibodies that protect you from both strains you’ve been exposed to? Or are you stuck with the antibody response to the first strain?

Second, when you were talking about the different MHC molecules associated with people whose bodies control HIV for a long time without getting sick, I was curious about whether these MHC molecules were associated with different levels of autoimmune disease. On one side, I’d expect MHC molecules that don’t bind well to many self antigens to be less likely to cause autoimmune disease. On the other side, I’d expect a wider range of antigens that could be bound by the MHC to be associated with more ways for something to go wrong, leading to your immune system attacking healthy host cells. Or does the process of selection in the thymus keep those MHC differences from having much effect?

Thanks,

–John

Jim writes:

The Jul/Aug 2010 issue of Discover Magazine addresses faulty research in an article by David H. Freeedman, called “The Streetlight Effect”, which is based on his new book, entitled “Wrong”.

The NY Times had a column that discussed this book and included the following comment:

“Mr. Freedman, the author of “Wrong,” is a science and business journalist…

“He points out that most expert wisdom, especially about health issues, isn’t just sometimes but nearly always ultimately proved wrong. He is diligent about explaining the “disconcerting reasons” why this is so. He examines how the sausage that is major health studies is actually made. It’s not pretty.

“Mr. Freedman observes the way that very small (and hence unreliable) surveys, often based solely on animal testing, are used to make extravagant claims about cancer or our diets. He notes how scientists discard data that doesn’t fit their theses. He talks about measurement errors and the academic pressures of publish-or-perish.”

His concerns and those addressed by the cancer doctor about journalism seems to present issues for anyone interested in a research career might need to know about.

Jim from VA

TWiV 97

Jerome writes:

Bonjour Dear Dr.Racaniello & TWIV community,

I discover your podcasts couple months ago and love to listen them each week to learn News in virology from my country in France. I don´t have a direct question about one of the exciting topics from your recents podcast, but just ask for advices.

Background: after my Ph.D. in Germany (Heidelberg) where I start my seconde education as virologist I went as Postdoc to the gorgeous city of Portland in Oregon to work in the laboratory of Dr. Jay Nelson. Dr. Jay Nelson is known for his topics on Cytomegaloviruses and West Nile virus research. I stayed 6 years in his laboratory working at first on SARS-CoV (2003), which has to be stopped 8 months later because of deletion of funding on SARS-CoV. Then I workeded on 7 other risky projects on HCMV. Finally I get one good paper from the last project (HCMV Secretome and TVS) and had to move back to Europe because of the end of my contract and work visa: I should move one after this long period of time as Postdoc by Jay. I just want to add that despite weak publications I learned a lot during this time. Back in France I am still looking for the next post-postdoctale position as virologist or in R&D in food industry (my primary education).

Question: I am looking for advices to continue my passion for pathogen-host interactions and to combine my high interest in nutrition and chronic diseases during viral infections. Because I speak & write 3 languages (French, English & German) and love to live wordwide despite to be French, I am very flexible for relocation. However I could not meet the right people having interest on my profile at University, in industry or in non-profit organization like WHO. Which way you will look to find them in Europe, in the States or worldwide. After so many years working in virology I don´t want to abolish my knowledge and start over with some work just to pay the bills.

My Science story should not be sad but rich in adventures like my private live !

Thank for any advices or opportunities of one of your listeners.

Thank et merci for your Podcasts on Virus. I am listening only Podcasts on Science or travel in 3 languages.

best regards

Jérôme
Normandy, France.

TWiV 96

Connor writes:

My name is Connor and I am an undergraduate (soon to graduate) Microbiology student at Oregon State University. I’ve recently discovered your show and I love listening to it. Especially now that it’s featured on Stitcher, making it much easier for me to listen to when I’m walking around campus or taking a road trip. I am taking an immunology course this term and I wanted to discuss the article you brought up about HIV and HLA class 1 (which I’ll call MHC 1 from here on out, so as not to confuse myself). You expressed some confusion, and I thought I’d try to explain it. Try is the key word here since I am only a student on this and I’m actively trying to figure this out as I’m writing.

MHC class 1 molecules present peptides from a cell’s cytosol on its surface. T-cells can then bind these molecules. If the peptide bound to the MHC is recognized as self by the T-cell receptor, the T-cell will receive a negative signal and leave the cell alone. When recognized as pathogenic, the T-cell will get a positive signal that will tell it to kill the MHC presenting cell. This is pretty basic and I’m guessing you already know this but I thought I would give some background.

Now the problem with this is preventing T-cells from recognizing self peptides. The thymus is very important for this. Cells in the epithelium of the thymus express MHC 1 (and 2), and using what is known as the AIRE transcription factor, tissue-specific peptides found all over the body can be expressed by these thymic epithelial cells and presented on their MHC’s. Positive and negative selections occur to get rid of nonfunctional and self-reactive T-cells. Now here is where the paper comes in.

Since there is so much allelic diversity from MHC’s, they can vastly differ between individuals. Here the paper mentions HLA-B 57 specifically. They say this MHC can bind far fewer peptides in the human proteome than others. This should cause thymic epithelial cells to present fewer self-peptides to T-cells and decrease negative selection. As a result the diversity of T-cells would increase, and they would be able to recognize a greater variety of peptides as foreign. However, I believe this would increase risk of self-recognition and ultimately autoimmunity.

My guess is that as HIV mutates, it may begin to express sections of peptide that may be similar to some of those found in the human proteome. So in most cases a regular diversity of T-cells will recognize these peptides as self and no or little response will be elicited. But in the case of thymic cells expressing HLA-B 57, less negative selection occurs in the thymus, a greater variety of T-cells persist in the body, and your immune system has a greater chance to recognize HIV as a pathogen even after mutation.

This is purely speculation, but I’d be interested in hearing what you have to say about this. I hope I explained it well (and correctly, my immunology professor would be disappointed if I didn’t). If I confused you I apologize. You guys do an awesome job and I look forward to each new episode. Thanks again,

Connor

Sergio writes:

Dear Twivers:

This is the second time I write and the previous was like two years ago. I had stumbled on twiv searching for microbiology related podcasts for my then brand new ipod. Now the ipod is pretty worn out and twiv is one of my favorites….i never miss one. I am a plant pathologist/microbial ecologist about to finish my Ph.D. work in bacterial plant pathogens, but I am so into molecular biology that plant virology is very attractive and probably I will [do] some plant virology in the future.

Now that all of you have been showing interest in RNA interference and related topics I thought this would be the perfect moment to ask you something that has been around my head for some time. A few years ago in my plant virology class my professor explained his research on new plant varieties resistant to viral infections. There are 2 main approaches: Infection of plants by mild virus strains to generate what is known as “cross protection” (something like a “vaccine” for plants, without the immune system) and transgenic plants where a viral gene (set of genes?) is insterted into the plants. Then he started to explain the rationale and the theoretical basis of these two methods and their relationship to “gene silencing” or RNAi. That’s where he lost me!!! I have been going around this in my (little) free time and I kind of get the “cross protection” stuff, but the transgenic stuff is beyond me, needless to say I don’t get the relationship to RNAi. I know you are specilized in animal viruses but you are my best source of info on viruses so I thought I would give it a try.

Now that I am about to go back home and hopefully work as a researcher in a university I also thought you could give me some advise on getting funded. You see…I am from Bolivia and public universities there are completely free (as in beer) so there is no money for research. Most of the budget goes to infrastructure and salaries so serious researchers must get their funds mostly from foreign cooperating agencies or multinational organizations. I thought this was because we were a developing country and being so poor simply there was no money for research, but I learned that the situation is not so different in the US. Researchers have to compete very hard to get funded and if they don’t….well….it’s over. Since in Bolivia the money comes from cooperation there is a natural skew towards applied research and mostly oriented to development, but I believe (I hope I am not being naive) that if you get funded and get some materials and equipment for applied research, some basic research “made in the developing world and for the developing world” is possible. What do you think? Do you think it is better to stay in the applied field solving the many problems we have in the developing world or is it a good idea to try to perform basic research and add new knowledge for the sake of science from the developing world (would a paper be published even if it is from　a small Bolivian university?). An if you were from a cooperating agency..what would I have to write to convince you to fund some research. By the way, I forgot to mention that I am studying in Japan, where as soon as you get a scholarship the reserach is automatically funded by the Japanese Gov. and each lab has a budget directed to research that seems enough at leats to fund students’ research.

I know my questions are too detailed and probably out of the scope of twiv, but hey….better safe than sorry right. Once again tahnks for twiv and twip….and hopefully very soon for twib. Sincerely,

Sergio

Eric’s response:

This is one way post-transcriptional gene silencing was first observed: people were trying to make more intense colors of petunias using transgenes encoding pigment enzymes. What they wound up with instead were flowers with white sectors where not only wasn’t the extra pigment made, but the endogenous gene was silenced. So the same principle applies to viruses: make a transgene expressing some (but not all) virus genes. If the plant gets infected, there are already pre-loaded RISC complexes with siRNAs ready to cleave the virus’s RNA. The phenomenon of transgene-induced virus resistance was known before the discovery of RNA-interference, but the mechanism wasn’t known. What happens is that multicopy transgenes produce a sufficient amount of dsRNA to engage the RNAi machinery. Plants (and some other creatures) have the ability to replicate dsRNA via RNA-dependent RNA polymerases. (Mammals don’t seem to have RDRPs—except whatever copies Delta.) RNAs homologous to virus sequences can be maintained (and transported from cell to cell, I think) and act as siRNAs, thus conferring resistance.

I guess that’s what people mean by “immunity” in plants. The technical term used in the literature is “cross protection,” which refers to a phenomenon that is entirely RNAi-based. The persistence of the protection is due to the propagation of the virus-specific RNA by RDRPs.

TWiV 95

Jim writes:

Some listeners might benefit from reading “The Treatment; why is it so difficult to develop drugs for cancer” in the May 17, 2010 issue of The New Yorker, a nine page article (pp 68-77).

This link goes to the digital edition ( http://archives.newyorker.com/?i=2010-05-17#folio=076 ), but you have to be a subscriber ($) to access it.

One part of the article describes the mass screening of chemicals for potential compounds and points out that although industrial research labs like Kodak and Fujifilm have millions of chemicals in their vaults, Pfizer was screening only 600,000 and Merck about 500,000. One researcher obtained a grant and purchased 22,000 chemicals from Russia and Ukraine at $10 each [AD: I have an aside about these Russian libraries], then screened them ninety-six at a time and a hundred batches a day with automatic equipment to find some suitable candidates for clinical tests that eventually produced elesclomol. They never explained why Kodak and Fujifilm were not approached. Has anyone made an effort to locate where such chemicals are assembled and how they might be accessed?

Another interesting point was the importance of the Kaplan-Meier curve that is the turning point of any clinical trial in determining its success. Interesting insight.

Jim
VA

Ricardo writes:

Hello TWIV Professors,

Please read the answers or at least the winning answer of the DROBO Contest part 2 (Influenza replication in bacteria) so all listeners can learn with the winner of the contest.

Thank you,

Ricardo
Brazil

This is the winning answer (from Jeff):

Would it be possible to genetically engineer influenza virus so it could replicate in bacteria? Why or Why not?

First, this depends on the definition of “replication”. But there are lots of reasons why flu cannot infect and replicate in E. coli.

1. E. coli doesn’t have the required receptor proteins to bind flu.

2. E. coli doesn’t have a mechanism to internalize flu through it’s cell wall.

3. E. coli doesn’t have capped mRNAs which are needed to create flu mRNAs through the “cap-stealing mechanism”.

4. E. coli doesn’t have a mechanism to splice flu mRNAs to produce the full complement of flu proteins; this normally takes place in the nucleus of eukaryotic cells.

5. E. coli doesn’t have an environment equivalent to the acidic endosome needed to allow escape of the nucleocapsid.

6. E. coli doesn’t have ER/Golgi (or enzymes) to produce N-linked glycosylated proteins.

7. Flu HA and NA proteins would not be directed to inner membrane of E. coli; signal sequences wouldn’t work; therefore virus would not assemble on inner membrane.

8. E. coli doesn’t have protease to activate flu HA to make the protein competent to trigger fusion.

9. Even if flu mRNAs were made (with or without CAPs) they couldn’t be translated in E. coli (no ribosome binding sites).

10. A different codon-usage bias may interfere with protein translation.

11. Formyl-methionine would be placed at the N-term of flu proteins, may interfere with function.

12. Proteins may not fold properly in E. coli and they may interact (bind) to E. coli proteins inappropriately, reducing their effective concentration. For example basic domains used as Nuclear Localization Signals in mammalian cells may cause problems.

However, perhaps we can use a less stringent definition of “replication”.

Perhaps it’s possible to try and engineer a system to replicate the viral RNAs in E. coli. This would be similar in some aspects to the reverse genetics systems used for flu in mammalian cells.

Instead of trying to express all the proteins of flu, we could limit ourselves to the proteins required to replicate a flu genome segment. The flu proteins would need to be under E. coli transcription/translation control. For replication would need PB1, PB2, PA and NP proteins. It should also be possible to use plasmids with two promoters (opposite orientation) to get 1 or more of the flu genome strands (opposite of the mRNA) made to act as template for the replicase.

Maintaining everything in E. coli, is a little tricky; plasmids with different compatibility groups (plasmid maintenance in E. coli) and antibiotic resistance for selection would be needed. This problem would go away if an in vitro transcription/translation (still prokaryotic) were used.

One further obstacle to this system is generating the proteins in correct amounts; would need a lot more NP than replication enzymes.

TWiV 94

Kate writes:

Is it possible that disease stage makes a difference in detection of XMRV and have any XMRV studies tested patients for the virus at several different points over a period of time?

Cort writes:

How different or similar are your methods from the Science paper or the amended version of the WPI’s methods http://www.iacfsme.org/BULLETINSPRING2010/Spring2010MikovitsLetter/tabid/427/Default.aspx

Since the Science paper was published at least six papers have been published that were unable to find it and several other studies have reportedly failed. Have there been other retrovirus (or virus) studies which the scientific community initially experienced a similar degree of difficulty validating but later did validate?

What new information will your study bring to the table? When do you expect it to be published?

Are your results validated against a positive human sample?

Did you receive XMRV samples from the WPI and if so were you able to validate the presence of XMRV in them?

Our understanding is that you gathered samples from patients rather than used stored samples. Is this important and why?

Flowerancy writes:

1. Do you think that XMRV is the result of vaccines (either human or pet) contaminated with animal retrovirus?

2. Do you think that XMRV could have “dropped into” or “piggybacked onto” a herpes virus like HHV-6 or EBV, which allowed it to be spread casually?

3. How can cluster outbreaks of CFS be explained?

4. Could an escaped engineered virus be the cause of XMRV?

5. Can you please explain how XMRV affects the female urogenital system?

Gay writes:

In your studies of XMRV, what kind of tests have you found to be most successful at finding XMRV in blood? Do you think culturing the virus makes a difference?

XMRV growth is stimulated by androgen. If XMRV should be shown to be the cause or a co-factor in chronic fatigue syndrome, why are most (like 4 to 1) CFS patients women? And related to that, the macaque monkey studies showed that XMRV has a tropism for prostate tissue; do we know what tissues it prefers in women?

Could XMRV cause immunosuppression, and if so, how?

In the studies on macaque monkeys, XMRV viremia in the blood cells peaked at about day 8 after infection, and after a couple of weeks it was almost gone from the blood. Since finding XMRV in the blood seems to be difficult, is there somewhere else we should test for it? Like maybe saliva or respiratory secretions?

Kate writes:

My question for the brilliant Dr Singh is,

If xmrv is it! then when would drugs be available to treat us, if everything went to plan! (months, Years or decades?)

Jackie writes:

I was very encouraged to hear that you are engaged in a major study of the XMRV in Chronic Fatigue Syndrome with Dr Bateman and Dr Light.

1. Could you give any indication please of just how close you and your colleagues might be to proving that the XMRV causes CFS, or whether we are still at the stage of proving strong association only?

2. If strong association only, what kind of studies do you think we might need to discover whether there is causation?

3. Where in your view is the most likely reservoir for XMRV in CFS patients, other than in the peripheral blood?

4. Is the reservoir likely to be the most practical location from which to harvest XMRV samples and develop tests for use in a clinical setting (ie clearly saliva or blood tests are more practical, but what if the main reservoir is the brain or the nervous system?)

Thank you both very much!

The UK may seem a world away to you all at this present time, but I can assure you that CFS labelled patients over here are enthusiastically following all promising scientific developments in this field worldwide and are very grateful to you and your colleagues for undertaking this groundbreaking research and for your scientific curiosity.

Rebecca writes:

In treating XMRV, some of us are considering getting stem cell treatments. Do you think HAART would hurt the new stem cells we get?

Katrina writes:

What can you tell us about the XMRV assay being used for the Stanford/Columbia study?. How is it similar or different from others?

Thanks so much, and for all of your work on XMRV/CFS, especially!

Terry writes:

I was wondering if Dr. Singh could comment on your show if XMRV may be present in cancers other than prostate cancer. I am interested to know specifically if it may be a factor in the development of cervical cancer in women. Is there any chance XMRV could act as a trigger and interact with a person’s genes and HPV (and factors like smoking) to create cervical tumours? Also, if there is time could Dr. Singh comment if XMRV triggers the expression of Herv’s (endogenous retroviruses) in cancer and other disease?

Thank you for covering this important topic on Twiv. I am a new fan.

Eric writes:

– Can you provide us with a rough indication about when we can expect the publication of your XMRV/CFS study?

– In case XMRV causes CFS, to what degree do you expect people with CFS to recover, given the right treatment (not the treatment available now, but any future one)?

Michael writes:

Would it be expected that XMRV would have a similar disease effect as the related viruses in mice (SFFV, MULV).

If that is true, could we expect that the reason we see various outbreaks and susceptibility to XMRV be the same as in mice?

For example in mice (as summarized by http://jvi.asm.org/cgi/content/full/83/21/11211) SFFV vulnerability can be either genetic or affected by a co-infection. If XMRV also turns out to facilited by a co-infection could that cause the observed clusters? For example some other virus (most likely one of the ones people have thought actually caused the disease over the last 20 years) infects a bunch of people in an area and as a result a group there who are already carrying XMRV now get CFS?

Also given that there seems to be a high rate of thyroid problems and perhaps thyroid cancer in people with CFS could this also be a result of the virus. For example if certain people have a genetic variance of MET it could be activated by XMRV and cause cancer to kick off?

TWiV 93

Joyce writes:

Love the pod cast!

I once went into a very large bookstore and asked the clerk if they had any books on parasitology. She said that they did and pointed in the direction ofa large case of colorful books which on closer examination turned out to have titles such as “Unbelievable Investigations Into Ghosts”, “Area 51 Revealed” and “Recalling a Past Life” Nothing about ascarids or mosquito born disease. Oh, well.

It is wonderful to hear people who are enthusiastic about the history and future of their special fields. I listen to both TWiV and TWiP. I am decidedly a non-scientist. My science education consists of closely reading the last three editions of the Merck Veterinary Manual and raising livestock for most of my life. I appreciate any the references to remedial reading sources in Virology and Parasitology.

As a non-scientist I would love more information about lab procedures and technology. How do you “extract a protein”? What is involved in “setting up a lab”? How have these things changed?

Keep up the excellent work, gentlemen. And could you scare up a few more gentlewomen scientists?

Joyce

Peter writes:

Since I last emailed you I’ve been able to ascertain that there is a program to serosurvey imported captive Pteropid fruit bats held in American facilities e.g.zoos etc , which is being facilitated through the Lubee Bat Concervancy’s Allyson Walsh and CDC’s Tom Kiaszak.

As far as a survey of native North and South American and Caribbean bats, nothing is apparently known yet on the status of henipaviruses, but Jon Epstein from The Consortium for Conservation Medicine in New York advises that they have received funding from the NIH to survey native new world bats for unknown and known viruses including henipaviruses, in a program to be headed by Peter Daszak.

Let me know when you’re planning to do the show and I’m only too happy to talk with you on Skype. Keep up the good work.

Kind regards

Peter

Equine Veterinary Surgeon

Jamie writes:

Hello everyone!

First I want to say that you truly add an educational ray of sunshine to my day!

I’m an animal technician with a reputable university and fortunately we are allowed to listen to iPods while we work. I discovered TWiV via TWiP (I have to add that I most definitely would appreciate more frequent TWiP’s). The length of the podcast gets me through my morning of checking and changing and then I move on to iTunesU courses.

I do have a question, or rather a request.

One of the rooms that I work in is considered a biohazard level 2 (BL2). The posting on the door reads “hazardous agents: Influenza, Adenovirus, Lentivirus”. After listening to all the TWiV’s, I feel I understand Influenza. However, I don’t know much about Adenovirus and Lentivirus.

As an animal technician, I try to solicit information from the investigators about their study so that I can be sure the animals get the utmost care. I know what side effects to be prepared for (particularly with this lab’s mice), I guess I’m looking for the “why”. Of course these viri may or may not have to do with the side effects that I am mindful of, I wholeheartedly appreciate any insight.

Keep up the titillizing podcasts, I look forward them!

Regards,

Jamie

Ken writes:

During episode 87, Vince and Graham both used a word that microbiologists have been urged to purge from their vocabularies: Prokaryote.

The initiative is from Norman Pace, a pioneer of molecular microbial ecology. Pace argues, persuasively in my opinion, that, while the word “eukaryote” can be used to refer to a phylogenetically coherent group of organisms, “prokaryote” cannot. Using the word can mislead students into thinking that cellular life is divided into two main groups.

Pace gives a good exposition of his argument in a short essay published in 2006.

http://www.nature.com/nature/journal/v441/n7091/full/441289a.html

It may seem silly, but it’s a good lesson in thinking phylogenetically.

By the way, the best virus joke is attributed to comedian Brian Malow:

A virus walks into a bar.

The bartender says, “We don’t serve viruses in this bar.”

The virus says, “Now we do.”

Sophie writes:

Hello to all the great people on twiv and twip people.

I listened to the ER twiv and the question about why we don’t have any active ER viruses. Could it be because our immune system are more active/better than for example a hen’s? I’m aware that this probably wouldn’t explain the difference between us and other mammals – but could the differences between our immune systems be big enough.

At last, but not least I want to thank you for telling me about drobo – it’s exactly what we need – especially school notes and pictures – just too bad that the promotion code doesn’t work for us danes 🙂

Sincerely Sophie

Welkin’s reply:

My first reaction is that our immune systems should be no better or worse, but then there’s the caveat that most active ERVs probably come from heavily domesticated/inbred animals – chickens and mice – so maybe there’s something to it. Not worse, but less diverse.

Perhaps another, purely speculative, possibility is behavioral- humans recently developed weapons and cooking, so could we be less likely to come into direct physical contact with infectious, retrovirus-containing material from other species?

A tangential but similar question, that has bothered me for sometime, is why there are no known retroviruses of dogs? Cats have several, so do humans, horses, cows, mice, chickens, sheep – why not dogs?

Jim writes:

Will the Ipad change the way you teach and communicate by allowing textbooks that incorporate interactive apps, motion, audio files, games, and faster/more frequent revisions?

Will use of the touch screen devices, such as the Ipad, improve sanitation by promoting cleaner hands?

Will the Ipad represent sand or pebbles? – – haw, haw

Jim

Chris writes:

Dear Drs. Racaniello and Despommier:

I just wanted to thank you so much for taking the time to make my birthday gift possible–via Dr. Jean Lim. It meant more than you could possibly imagine to have so many people take the time out of their schedules over something so silly as a 23rd birthday. I know even as a first year graduate student I find that time seems to be the resource that dries up the most quickly, and it’s very inspiring to someone who is just beginning to dream of spending their life in science to have those way ahead of them take the time to lend a hand on the way up.

I know you get this sort of feedback a lot via email, but perhaps there is never too much–thanks for taking the time to do TWiV. It’s proven to be so much more than great entertainment while working out at the gym (I love that they keep getting longer, too–I’m doing much longer workouts so I can finish listening!), but has really helped me to challenge my professors actively in virology and pathogenesis–which I think they like even more than I do. Also, some of the stories and ideas you bring up on TWiV have helped to fuel entire science discussions over food and beer between groups of graduate students and post-docs here (we all follow TWiV compulsively, haha) which is where I think all the best thinking is done.

I appreciate all the time and effort you both (and Dr. Dove and Dr. Condit and guest-of the week…) do to help make our training experience so much fun, and I hope it shall continue for future students for a long time.

Chris

Peter writes:

Dear TWiV hosts (this includes Rich, since I am not regarding him as a guest anymore),

What a week!

Monday (It’s Monday for me here in Korea, when it’s still Sunday for you) the interview with Adolfo Garcia-Sastre; Wednesday FiB #56 about New Antiviral Strategies with Karla Kirkegaard and Thursday a tape worm long TWiP #6 and MTS #46 with Curtis Suttle titled It’s a Virus World and We Just Live On It

From me just four news items, I would like to hear discussed by you (if you haven’t done so already):

1.) Well, not really news, since more than a month old, I attached the 8+ min section of the interview with Harriet Robinson (Senior VP, GeoVax Labs) on a combined new two component HIV vaccine. Sounds promising to me.

2.) 2 min of Mark Crislip from the most recent Puscast for the first two weeks of March

As he says it’s cool. I remember you mentioning Rinderpest as being a potential candidate for the second eradicated infectious disease, but did you discuss the relation to measles?

As a German, of course I like you using German words like Schmutzdecke and Rinderpest.

I should have known the origin of the name of toll-like receptors, but I learned it from TWiV. Don’t ask me why, but I always associated it with (highway) toll-gates.

3.) Vaccine delivering mosquitoes

From the latest Science podcast and a potential way to keep vaccination campaigns of cattles up and running.

4.) And last but not least and always of interest to me working the biopharmaceutical industry – product safety – here ‘PCV1 virus DNA found in GSK’s Rotarix vaccine’: http://www.in-pharmatechnologist.com/Processing-QC/PCV1-virus-DNA-found-in-GSK-s-Rotarix-vaccine/?c=EhWMkLwu2mysBysCtgNUDA%3D%3D&utm_source=newsletter_weekly&utm_medium=email&utm_campaign=Newsletter%2BWeekly

Thank you for TWiV and TWiP,

Kind Regards from Korea,

Peter

Jeffry writes:

Hi Vincent-

Perhaps I haven’t listened to a specific TWIV addressing this, but what is your opinion on viruses having a role in autism spectrum disorders?

http://www.autismone.org/content/episode-8-viruses

Dr. Stewart and Lisa discuss viruses and their effect on children in the Spectrum. As always you can submit your questions for next months Podcast by sending them to questions@drkendalstewart.com

Is it possible to have a TWIV with Dr. Stewart as a guest?

Also, before you speak about the possibility from your perspective, could you also answer what we can test for to rule out viral infections? How do we know what we don’t know or test for? 🙂

Even though I do not agree with everything you speak of, I do find your twivs educational. Thanks for the info as always.

Respectfully,

Jeffry in Colorado

Amy writes:

Hi Professor Racaniello,

I’m an undergraduate student in your class, and I have a question about episode 67.

Of all the extreme sterilization methods that you discussed in this podcast, why is phenol the only one that can alter or destroy prions? What mechanisms does this chemical use to alter the particle, and do you think it is possible to use phenolic derivatives to treat prion diseases or are they too toxic?

Thanks!

~ Amy

Radhika writes:

Hi,

This really does not have to do with viruses but rather prions. How did prions originally form, is it just a mutation in peptide structure, and are there any links between prions and degenerative brain diseases such as Alzheimers?

Thanks,

Radhika

Mark writes:

Hi Vince et al,

I was interested to hear you talking about people using calorimetry to measure energies of viral processes.

On a bit of a tangent I wonder if you are aware of a paper published in June 2009 ago where researchers measured the energies required to cleave the von Willebrand’s protein by molecular manipulation using laser tweezers:

X. Zhang*, K. Halvorsen*, C.-Z. Zhang, W.P. Wong^, and T.A. Springer^, “Mechanoenzymatic cleavage of the ultralarge vascular protein, von Willebrand Factor,” Science 324 (5932), 1330-1334 (2009).

I’ve long thought that quantum approaches could be applied to biological processes, perhaps that specific frequencies of electromagnetic radiation (read photon energies) could be applied to enhance or inhibit specific biological processes. Are you aware of any research in this area?

Thanks for all that wooshing noise above my head

Mark

Adam writes:

Does the fact that Mimivirus and other similar DNA viruses that also replicate in the cytoplasm without directly sending nucleic acids to the nucleus mean that like the evolution of eukaryotic cells into different species and types of cells from one eukaryotic cell ; viruses are also one step closer to moving away and evolving into something we can call a life form? Is it possible that the virus over the course of time will keep moving farther and farther from the nucleus needing it less and eventually moving away completely from the host cell itself due to new progeny being mutated through exposure to differrent environments and by picking up more host proteins/ machinery/ nucleic acid through time?

? writes:

I thought this would be an interesting article to discuss. It covers a study where M13 virus was used to split water, which may be a potential method for production of Hydrogen for fuel cells. I know these aren’t “the kind that make you sick,” but it would be an interesting aside.

http://www.sciencedaily.com/releases/2010/04/100411143403.htm

Sheldon writes:

If you use Windows and your eyes aren’t as good as they once were, you need to zoom in on the page. But that doesn’t work for all programs.

Using itunes can be difficult

So why not change the resolution of your monitor. The problem is that you have to get all the way into monitor settings. Wouldn’t it be nice to have two quick launch icons one to lower the resolution (zooming in) and the other to reset the resolution to your normal favorite.

That’s where nircmd comes in. Search for it and read down for the command for creating a shortcut that changes the resoluton. Download it, extract it and a few minutes of playing around and it works fine.

If you accidentally create a shortcut that your monitor doesn’t support, don’t worry — nothing happens.

Now I can read itunes.

Sheldon

Toronto

Jason writes:

Hi TWIV fellows,

Firstly my congratulations on a wonderful podcast. TWIV is the first podcast I have ever listened to and now find it a pre-requisite for my daily 100klm (60mile) round trip to and from the lab. I am still listening to the TWIV archives (25 more to go) and intend to listen to them all again, just in case I missed something. I also recommend that our students sign up to your mailing list as I think it is a valuable tool for their education.

Anyway, I have been watching the Tajikistan poliovirus importation event and have to say I am concerned. Currently there are over 270 cases of AFP with more than 50 of these confirmed as wild type 1 polio with more to come no doubt. Given a conservative AFP to asymptomatic infection ratio of 1:100, there appears to be in excess of 27,000 case of polio infection in a community with a vaccination coverage of around 90%. I would really appreciate hearing the TWIV teams viewpoints on this.

Also I found this paper very interesting (and concerning), any thoughts?

Asymptomatic Wild‐Type Poliovirus Infection in India among Children with Previous Oral Poliovirus Vaccination Grassly NC et al.

http://www.journals.uchicago.edu/doi/abs/10.1086/651952

Keep up the good work, and thankyou for helping me keep up to date with viruses other than enterovirus during my daily commute.

Kind regards,

Jason

TWiV 92

Destainie writes:

Hi Vincent et Al 🙂

I am an avid listener of both Twiv and Twip and am very grateful that you all take the time each week to create these wonderful podcasts, they are a great learning tool! I did have several questions I’d like to ask. My first has to do with HIV. It is my understanding that currently doctors use combinations of three different anti-virals to treat and manage the infection and this is due to HIV ability to evolve quickly and become drug resistant. My question is why does HIV evolve so quickly compared with other viruses? Or does it only seem faster because the immune system can’t fight it off? What would happen if you increased the combination to 4, 5 or even 10 antivirals?

My second question is since we know that viruses evolve and become drug resistant is there any way to try to predict the way a certain virus will evolve such that we can try to prevent or prolong drug resistance? My guess is probably not but it would be nice if we could.

My last and final question (for now) has to do with a podcast I heard a while back where you mentioned that a lot of Immunologist and/or Virologist are retiring soon. I am in the process of studying for the GRE and I plan on applying this fall for Immunology programs… since you know the field better than I which ones would you recommend? I should mention that my interests right now would be for a Immunology program with an emphasis in virology if I could and I actually would absolutely love if I could become a double doctor and combine this degree with an MD. I find the human body’s ability to fend off invaders and heal completely fascinating, such that I would be more than happy to devote my life to studying it!

Thank you for all that you do,

Destanie

Merry writes:

Hi, Vincent & TWIV,

I particularly enjoyed this week’s chat with Graham Hatfull as I am a phage enthusiast. He certainly gave the phage their rightful due! And I appreciated the mention of the blog that Elio Schaechter and I write, Small Things Considered, as well as Graham selecting Forest Rohwer’s book (Coral Reefs in Microbial Seas) as his pick-of-the-week.

Also in the pick-of-the-week, you enthusiastically praised the great breadth of information contained in John Ingraham’s recent book, March of the Microbes. I have my own copy close at hand here. When I received it, I turned eagerly to Chapter 10, Viruses — my favorite topic. He, like TWIV, focuses on those that make us (or other animals) sick. Not a word in that chapter about the phage. Of course, he has to be selective as he is covering a vast territory in one book. However, he does not simply ignore them. On the first page of that chapter he sets the tone by quoting two Nobel laureates. First, David Baltimore, who said about viruses: “If they weren’t here, we wouldn’t miss them.” That is followed by Peter Medawar’s quip describing a virus as “a piece of bad news wrapped in a protein.” Both highly quotable quotes.

But considering the ecological and environmental role of viruses in general, and phage in particular, his view of viruses seems incomplete. Would you, Rich, and Alan care to share your thoughts about this?

All the best,

Merry Youle (Small Things Considered)

Jack writes:

Hello Vince,

I discovered TWIV recently and I have become a big fan – keep it up. I have been teaching an undergraduate Introductory Virology course for over 30 years – initially for 10 years at UC Berkeley and now at Nebraska. TWIV will become a requirement for my course this Fall. We have some excellent virology programs here. We recently consolidated all human, animal, algal & plant virology into one building – check out www.unl.edu/virologycenter. I just added a link to your Blog on our website.

I have been going through all of the TWIV episodes this summer. I am a plant virologist and I recall one episode in which the discussion focused on innate immunity. It turns out that plants have an innate immune system with toll-like receptors and MAP kinase cascades. There is also an adaptive immune layer – RNA silencing. This is what we work on. It might be a fun topic for a future TWIV.

I am also interested in Dick’s enthusiasm in “vertical farming”. I read his essays and it all sounds quite promising. What struck me, somewhat ironically, is the potential virology connection. One of the major threats to greenhouse food production are plant viruses. Commercial operations have gone bellyup because they have not been able to successfully control the spread of viruses. Most problems result because the viruses are contact transmitted through roots and soil. Interestingly, some of these viruses like Tomato Bushy Stunt (the 1st icosahedron to be structurally resolved by Steve Harrison) pass right through the human gut and become contaminates in waterways used for irrigation. All quite interesting biology.

Keep up the good work. You are doing a great service to the discipline.

T. Jack Morris
Distinguished Professor
School of Biological Sciences
University of Nebraska

Caleb writes:

Hello TWiV guys,

I’m in 6th grade and I love your podcast. I have a few questions. What is the biggest virus? What are viriods and prions and virophages? Thanks for all your time and for the great podcast.

Caleb W.

[Caleb: check out TWiV #23 on the biggest and smallest viruses and virophages, TWiV #24 on viroids, and TWiV #12 and #67 on prions]

TWiV 91

Darrick and Scott write:

Hello Professor Racaniello,

We are two graduate students from the University of Guelph in Canada studying oncogenic sheep betaretroviruses and we are big fans of the show. Part of the reason we like the show so much is that we can use it to keep up to date on the latest virology events and in addition expand the breadth of our virology knowledge. We will be attending ASV in July and we hope to see you there at the live podcast.

P.S. We have put together a few rap songs using clips from some of your past podcasts that I think you and the rest of the twiv crew will enjoy. We put together the songs using audacity and free rap beats from http://www.20dollarbeats.com/.

Sincerely,

Darrick and Scott

T-Number Index by G-Unit (mp3)
Vincent (mp3)

(the) Acrophobic Antediluvian writes:

The May 25 episode of the “To The Point” podcast from KCRW had a segment titled “Synthetic Cells: Momentous Breakthrough or Ethical Morass?” http://www.kcrw.com/news/programs/tp/tp100525is_synthetic_biology

This was a fascinating listen, and to me illuminated a problem that you have discussed before on Twiv; specifically, that it is common for Science stories to be distorted or sensationalized by the media.

This instance is however clouded by the fact that David Baltimore and Craig Ventor completely disagreed and had what seemed to me a tense argument.

One said a breakthrough in creating life occured in a laboratory, the other said it really is nothing new and is not a paradigm shift.

So, whose story do we accept? How should we listen to a conversation like this and decide who is in the right? Should we go by the credentials (number of Nobel Prizes won,etc.)? It seems as if the issue is split down the middle.

Can you comment? Is there consensus in the scientific community? Are the Twiv hosts on one side of this? I urge you all to listen.

Sincerely,

(the) Acrophobic Antediluvian

TWiV 90

Eric writes:

Hi Vincent,

After 86 episodes of TWiV, I am still loving every minute of the podcast and I am constantly impressed with how much I learn. For example, I have been mentoring an undergraduate student in the lab and we have had a rough two week stretch where none of her experiments have worked. I was racking my brain, trying to come up with some things that would help boost her confidence. On my way in to the lab on Thursday morning, I listened to you and Rich and Dr. Kiki; and Rich described how a good mentor guides the student in a direction that will allow them to succeed. I took that approach with her that morning and we had a great discussion about the project, what additional experiments she could try, and I was able to assure her that it was not her skills that were lacking. On Friday, she had two great successes that really boosted her confidence, and I felt like a good mentor! Thank you TWiV!

Tonight, I listened to Dark Matter with Eric Delwart, and I loved it. I have been experiencing many of the same things that Dr. Delwart described, and in fact I have 100s of hours of eyeball time invested in the bat virome project.

Thanks for your continued work with the podcast. I find it extremely helpful to hear about different viruses that I would normally have no exposure to.

Thanks,

Eric

David writes:

TWiV gang,

Several emails you’ve received have addressed the question, can computer viruses mutate? My take on this question is a qualified yes, but in a different way than biological viruses.

If I remember correctly, one of the emails you received answered this question as no, because randomly changing bits of a computer program almost invariably result in a broken program. I can vouch that this is true – I work in a group that designs computer chips, and any single bit change will cause the mutated program to go out into the weeds. However, mutations in biological systems, and as well as those that computer viruses undergo, happen at a different level.

By my way of thinking, changing a single bit in a computer program would be like changing a single atom in a biological compound. If you replace a Carbon atom with a Gold atom in Adenine, what you’ll probably end up with is an expensive non-functional molecule. Instead, mutations in DNA and RNA seem to happen at the molecular level, for example where an Adenine gets replaced by an Guanine, in the case of single nucleotide polymorphisms. Other mutations, such as copy number variations, occur at the level of a large collection of molecules. The point is that biological mutations occur at a higher level of organization than “bits”. This greatly increases the probability that the resulting mutants are viable (and sometimes “fitter”) than the original.

For computer viruses, I’m unaware of any comparable higher level of mutation inherent in computers. I’m not exactly how accurate computer based copying is, but I’ll hazard a guess that it is more accurate than biological copying. Errors in computer copying that I’ve typically encountered have been due to equipment failure (queue Drobo promotion here :)). Because of this, when computer viruses change, it is because the computer virus itself purposely inserts variation into its offspring as they are created.

One way antivirus programs detect viruses is to look for virus signatures, sequences of bits in viruses that are characteristic of a virus or family of viruses. To evade detection, one tactic newer viruses use is to modify (“mutate”) their children to be unrecognizable to the antivirus software. The viral code is modified at a higher level of organization than bits, such as reordering instructions (analogous to SNPs, perhaps). In this way, some computer viruses do change (mutate if you will), but they self-mutate, rather than let nature do the mutating. For some more background, see http://en.wikipedia.org/wiki/Computer_virus#Stealth.

The Tierra program mentioned in one episode, mutates at both at the bit level and at a higher level of organization (swapping segments of code). The Tierra virtual environment does the mutating in this case.

This does beg one question – are there any biological entities that you are aware of that actively self-mutate?

Keep up the good work. I listen to several podcasts, and TWiV (and TWiP) are among the few that I make sure I have time and concentration to really listen to. I get a lot out of these podcasts.

— David

P.S. I guess the moral of the story is don’t mutate the bits, mutate the organization 🙂

TWiV 89

Andreas writes:

Hello professors,

I would just like to start by saying thank you for the wonderful podcast.

Today I found this article on npr which seems to describe a remarkably effective antiviral treatment for ebola.

The article has virologist Heinz Feldman expressing concerns that the drug – though very effective – is unlikely to be brought to market due to the lack of financial incentives.

What’s your take on this?

Regards

Andreas

Ken writes:

Hello DRs.V.R.A.D,

My Name is Agyeman-Badu, a graduate student in Ghana and a regular listener to TWiV and TWiP. I came across a paper by Zhang et al and I have a question about priming of non-enveloped viruses before cell entry. If viruses are really particles before cell entry and hijack the cell machinery to act as living and replicate, how is it possible for non-enveloped viruses like the B19 viruses, Adenoviruses, Rhinoviruses, coxsakieviruses and even the Hepatitis Delta virus to prime from a dormant state to a metastable state by shedding off protective proteins before cell entry? How can a viral particle release proteins if it is not in a cell? I tried reaching the original authors but couldn’t and hope you geniuses could help me answer this question. Maybe there is something i don’t know and i would like you to fill the gap in my knowledge like okazaki fragments. Thanks and keep up the good work, you are really helping some of us now coming in the molecular research field.

Ken

Damon writes:

Dear Professors,

I am writing to more or less ask for a sanity check on the topic of flu vaccination. When my company began operation of a flu laboratory, our medical director mandated twice yearly flu vaccinations. Now, these are the normal seasonal vaccines, not the strains we are working with, but the hope is that there would be some cross-protection. That I can buy as a risk mitigation approach. However, I originally assumed that the vaccine we receive in the spring was the southern hemisphere vaccine, which would give us even broader influenza immunity. I recently learned that is not the case. In the spring we receive another shot of the same vaccine we were given the preceding fall. The justification for this is ostensively that the repeated shot will compensate for waning immunity.

I am tempted to call shenanigans on this, because I can find no evidence that flu immunity provided by a vaccine wanes, especially over a time period as short as six months. In fact, flu immunity against particular stains seems to be lifelong, as evidenced by the finding that people exposed to a similar flu decades ago had resistance to the latest H1N1.

What are your opinions on this? Is there any benefit to receiving an identical flu shot twice in a row?

A related question: Why is it that pets need to be revaccinated yearly, when most human vaccines provide lifelong immunity?

Thanks for all the fulfilling commutes provided by TWiV!

Best regards,

Damon

Dan writes:

Twiv crew:

Your recent interview with Dr. Kiki that touched on press releases and sometimes missconstrued information by the media relates well to this story in Wired Magazine. I am including the URL here as well as attaching a PDF with this email if for some reason the article ages off the site. You might want to consider a short mention of it on your program.

As a meteorologist, I now find myself in a field where the public’s perception of the science is now heavily influenced by politics and public opinion (case in point – global warming/climate change). It used to be that a meteorologist only had to worry about a forecast, improving a numerical model, or better ways to assimilate or improve data for analyses and models, but now we have to fend off a growing upset public that have received erroneous information about climate change. It is ironic that I chose this field to help humanity. I figured a better forecast could only help mankind make better decisions that would benefit everyone. But because of strong opinion, some of my colleagues are now more worried about a direct physical assault on their own person or families than the science. The improvement in communication is a two-edged sword, not only does it allow for the wonderful opportunity of “free access” to knowledge (even perhaps cutting edge information such as presented on your podcast) a dream that I share with you, but it also allows for the uneducated to voice an “equal” opinion.

We all know funding dollars for research grow more valuable to us every day. I would hate to have to spend my research dollars on PR, but it might be necessary as science becomes more political and opinions more polarized. In virology you have your own nemesis – the anti-vaccinators, look how much damage one or two unscientific articles affected many people to question real science, and in your case you don’t have the resources of giant corporations that might have something to gain if vaccines were rejected by the public fighting against your cause (or maybe there are, please educate me on that point if there is). We share a common problem even though we are in different fields. I value your collective opinion on how to best deal with this problem and your reaction to science PR. To a degree you folks are doing what this article advocates, your audience is wide open and you do a great job of taking the science to the lay-person’s level. But to what extent do we go? and what is the best way to reach those who have open minds before they meet the entity that has an apparent agenda to coerce their beliefs so they will perhaps vote a specific way in the next election that might very well have a bearing on research funding for basic science?

I value your comments, candor, and intelligent discourse; I always look forward to listening to your show during my daily commute.

Recently you gave away a Drobo after judging essays entered for the competition. As one who submitted an entry, I would at some point enjoy learning the desired essay response (if I missed the episode in which this was divulged, please share, but I only recall the announcement that there was a winner). Maybe I could learn from my mistakes since the lack of a Drobo on my desk is evidence I didn’t “get it right.”

Regards,

Dan

TWiV 88

Sharon writes:

Hello fellow virus lovers,

I first want to comment about Vincent’s pick of the week a few weeks back, the book “Polio” by David Oshinsky. I am currently studying poliovirus in Julie Pfeiffer’s lab (as you revealed many moons ago with a previous email I sent), and I received this book as a gift from my mother. David Oshinsky was in San Angelo, TX (my home town, and in the first sentence of the book) speaking about his book and receipt of the Pulitzer Prize and doing a signing. My mom attended the event and subsequently purchased a book for she and I. I love it! This is a wonderful historical perspective of the societal impact of poliovirus and impending vaccine “arms race” between Salk and Sabin that you don’t necessarily get from Pubmed. This book has been circulating in our lab for a while now and I recommend it to anyone.

I would like to recommend a pick of the week that I think hasn’t been suggested yet. It’s a PBS special called “Naturally Obsessed” (http://naturallyobsessed.com/). The film (~1 hour long) is a documentary that follows 3 graduate students in the pursuit of their PhDs and the divergent routes they take. We watched the video for a lab meeting, and all sympathized with the students in the video in regards to the rigor (and dissapointments of mountains of negative data) of graduate school. It does have a happy ending!

One more short mention. I have listened to every TWIV podcast and have heard you all ask several times if anyone is studying gastrointestinal (commensal) bacterial effects on viruses. No one to date has published on this subject, but keep an eye out. 🙂

As always, I love the podcast! Thank you for broadening my virology knowledge!

Best,

Sharon

Andrew writes:

Dear TWiV,

I’m an second year undergraduate in Genetics at the Queens University in Belfast, Northern Ireland. I’ve been listening to TWiV for about a year now and I find it fascinating! I had not been much interested in viruses until I discovered your podcast and took a introductory virology module this year, but now I’m considering the field of virology as a long term career.

What caught my eye the most within my Virology course is the idea of virus-mediated gene therapy, something that (and I could be wrong) I don’t remember you talking about on the show. My sister is affected by Type 2 Spinal Muscular Atrophy, a condition which is caused by the loss of the SMN1 (Survival Motor Neurone 1) gene and my question is,

How far away are we from being able to successfully carry out gene therapy for genes such as this?

My thoughts are: that one of the main problems would be the size, from my basic knowledge I know we have successfully put GFP (Green Jellyfish Protein) into a measles virus and had it express GFP in ferrets etc, but genes like the SMN1 gene are considerably bigger (28kbp as supposed to the 1kbp GFP) so, what are the current and theoretical limits of gene size we can integrate into viral genomes?

And finally, what would be stopping us from simply building our own viruses to deliver the genes? I’ve heard about the poliovirus which was built from scratch because the sequence was known and it was simply ordered as primers and put together to create a live virus, but with lots of different strains of different viruses being sequenced and publicly available, wouldn’t it be possible to engineer and build a fit to purpose virus? It seems locigal to me that you could take different sequences from wild viruses and create a viral genome of your own. A capsid protein from here, a reverse transcription enzyme from there, a replicase enzyme from somewhere else and so on. Could it be possible that we could greate a virus that would give a persistent infection of the appropriate tissues that shows little or no harmful cytopathic effect and delivers your missing gene?

I would love to hear you talk about this on the show, look forward to my TWiV fix every week,

Sincerely,

Andrew in Belfast, Northern Ireland

Brent writes:

Hi Guys, excellent podcast for IT business analyst with no virus knowledge. Just wondering about flu/cold transmission in the household. Would sharing toothpaste be a valid way to transmit easily. I figure it would ie person with cold , toothpaste tube to brush, mouth to brush, next person has toothpaste tube to brush, brush to mouth. or it this paranoia :). or does tooth paste kill it? interesting 🙂

Would it be a high chance of catching the cold?

thanks

Brent

James writes:

Hello Twiv,

Thank you for putting together a great podcast. My question refers to the podcast “Gators go Viral,” in which you talk about viruses attacking cancer cells (jaw dropper). I was wondering and it might be a little early to talk about this but is there any chance of evolution/resistance in these cancer cells when you expose them to this virus treatment.

Thank you,

James

TWiV 87

James writes:

Dear TWIV,

I’ve really enjoyed hearing about the paths you and your guests took to enter the fields of virology and parasitology.

I was wondering if Dr. Dove could talk for a few minutes about how and why he decided to transition into science journalism. Does he have any advice for PhD students who are considering making the switch? And how bad is the job market considering all the cuts media companies are making as of late?

Many thanks,

James in Japan

Marcie writes:

Dear Vincent, Dick, and colleagues,

I love both your shows and would strongly encourage you to increase the frequency of TWIP if possible!

I was volunteering in my son’s second grade classroom this morning reading a book about the human body with a student who needs extra practice reading. This student has struggled to be engaged by things he reads but this morning he was full of questions and this is why I am writing to you. Two pages of this short book were about blood and germs and there was a photo of some red blood cells next to a photo of some “germs” that I assume were rod shaped bacteria. These photos spawned a lengthy session where the student asked many questions about germs including, do they move?, how do they move?, how do they get inside our bodies?, what shapes do they have?, and a host of others. I drew him some examples of different shapes (paramecium, amoeba, ebola), and told him that paramecia swam using little hair-like things (I could not think of the word cilia at the time) and amoeba moved by oozing little feet-like things forward and then oozing the rest of itself into that “foot-like” projection. We also discussed more passive forms of movement like being blown on the wind, or being forcefully pushed by air as in coughs or sneezes. The student really wanted to know whether any germs had hair-like projections that the could deploy to facilitate being carried by air/wind like dandelion seeds. I told him that I was not aware of any but that I knew some very smart scientists who knew a lot about microbes and I would ask. So, are there any microbes (or other parasitic things) that can deploy hair-like projections to help them to travel?

Are there any books with good photos of microbes that you could recommend for early-elementary kids? I am hoping for a book with a picture of a microbe that simply says something like, “Here is a picture of the bacteria X. X is helpful/harmful to animals because it does Y and Z. X moves by (flagellum) and is passed from person to person by (touch). More complicated explanations would also be fine as I could translate them into simpler words, but something he could read himself would be ideal.

Thank you for your help!

Marcie

Jason writes:

Hi Guys,

I thought you might like this article. You have to love the headline anyway. I have heard that malware/viruses could potentially be transmitted to pacemakers before, but it looks like Gasson has a proof of concept.

http://news.techworld.com/personal-tech/3224739/scientist-infected-with-computer-virus/?cmpid=TD1N1&no1x1&cmpid=sbslashdotrplant

Keep up the good work,

Kind regards,

Jason

TWiV 86

Stann writes:

I found your podcast through the Microbe World website. Thanks to Microbe World, I’ve been unable to sate my thirst for knowledge about the microscopic organisms that act as the foundation for our planet. So, I stumble across a podcast about viruses? Hells yeah. Until recently my RSS feeds have only been filled with skeptical podcasts, making me the residential expert on why homeopathy is bunkem, but now I get to amaze my roommates with fascinating info on viruses and their ilk.

When I first discovered your podcast, I jumped head first into the latest episode, and was kind of lost, and almost bored. Not one to give up so easily, I decided to take it slow and go through your previous episodes. Clearly this was the best strategy, because your first episode on West Nile was so jam packed with information on a virus that I knew almost nothing about. Ever since, I’ve been hooked. In a world where ignorance is praised and brainless celebrities reign over cable television, people like yourselves, whose only agenda is to educate, give me hope for the human race.

In summary, I love the show and wish you best of luck in the future. Of course, my best wishes are somewhat selfish, as I hope for more episodes every week. 😀

-Stann

Darnelle writes:

I am studying virology at Columbia University and would like to pose a question to the expert panel of virologist @ twiv. In the most recent lecture we were introduced to vaccines, and my question pertains to such.

It is my understanding that the same virus that causes the ‘chickenpox’ that we get when we are younger also causes the ‘Zoster rash’, yet two different vaccines are given to treat these diseases. Why is this the case? Are the degrees of the vaccines different, given that they are delivered to different age groups? Why doesn’t the immune response developed after chickenpox protect you against zoster rash?
Darnelle

Sheldon writes:

The likely culprit for the PCV contamination of the rotavirus vaccine
is trypsin. I came across this statement in a document that
described the manufacturing process for Rotateq.
“Rotateq manufacturing process
—————————————-
“The applicant has put adequate measures (EVCP for pre-master seeds,
gamma irradiation of bovine serum and porcine pancreatic trypsin) in
place to ensure absence of adventitious agents for the above materials
and the virus removal or inactivation steps have been validated.”
at page 10 of
http://www.ema.europa.eu/humandocs/PDFs/EPAR/Rotateq/066906en6.pdf
So did the gamma irradiation quote kill unqote the PCV viruses in the trypsin?

The document I referred to had trypsin irradiated before use in
production. Could the problem be that the trypsin used at the very
start of the process was not irradiated?

I really enjoy listening to your podcast.
Sheldon

Paddy writes:

Dear Professors
I have been a loyal listener since late 2008 and sent an e-mail at around TWIV #15 asking for clarification on the definition of “infectious” and “contagious”. At that time I had just enrolled in a virology course after work and now, after having completed several of the courses, I am now enrolled in the MSc Virology program – at 43 years and with a couple of kids I did a great deal of thinking about this but I am thoroughly enjoying it and am occasionally mesmerized by the beauty and complexity of viruses as well as awed by the devastation they can cause.

I enclose my last assignment (complete with the marker’s comments and spelling mistakes) which I dedicate to you guys – obviously it is relatively rudimentary as far as you guys are concerned but late nights of listening to TWIV definitely have helped me get through the courses so far.

One problem that I have encountered is that getting my hands on pertinent recent publications that explain concepts at a level that would be completely useful to me is, at this stage, quite hard. The publications in Pubmed etc. are very often a bit hard to decipher and very focused on specific issues. I understand why this is so but finding references for assignments is quite hard – but I am sure that it gets easier over time especially when listening to TWIV.

I have a question – what are the steps to uncover a virus that has not previously been identified ? I have enclosed a brief description of one such suspected virus known as RRV or rodent respiratory virus – I have thought about looking a bit closer at this because it has some relation to my current job. I have enclosed the tech sheet from this – as yet unknown virus. Insofar as the pulmonary lesions are concerned it would look (from the pathology) that it could seem to be something like the RSV (SS RNA from a subfamily of Paramyxoviridae) that human neonates can sometimes get.

I understand the principles of PCR and multiplex PCR but I can’t see how you identify something entirely new with them. Can you at some point discuss this and perhaps also how they have uncovered some in the past.

Best
Paddy

Joe writes:
While I was listening to your discussion of the antibodies we have to the Alpha 1,3 sugar group and how it could be used to target disease agents I had a thought. It struck me that it would seem to be very much easier to use this as the ultimate bio-weapon and target a key functional group in our bodies than to try to target HIV which is always mutating. As this is not my area, I hope I am wrong. It seems that one could target a surface feature on heart cells or lung cells or liver cells and cause the body to attack itself in a way similar to the “cytokine storm” discussed related to the 1918 flu. As I said, I hope there is a technical reason that makes this impractical. If not please do not read this on air as I don’t want any knuckleheads to get any ideas!

Love the shows.
Regards,
Joe

Alaina writes:

Hey guys,
I have a job assisting a medical professor in doing literature searches and compiling information for the new edition of a book he is writing. The other day he asked me to gather some information on the XMRV virus. Having listened to the episode of TWIV you did on XMRV a while back, I was able to converse knowledgeably with him about it right away. So, I guess I just wanted to say thanks for helping me impress my boss!
Virally yours,
Alaina

Welkin writes:

Dear Vince and Dick;
Congratulations on producing a brilliant series of podcasts. I have been
hearing about TWiV almost since you began podcasting, to the point where I
had come to believe I was a fan without having actually listened to a single
episode. I even deluded myself to the extent of recommending it to others.
With the recent purchase of an iPhone, I have made up for this fraud, and am
working my way back through all the episodes.

I especially enjoyed the episode on Reverse Transcriptase, and the
discussion on endogenous retroviruses – HERVs were the topic of my thesis
when I was a graduate student in John Coffin’s lab. Dick was amazed that we
(humans) haven’t gotten rid of all those “useless” retroelements from our
genomic DNA. In point of fact, we have jettisoned them by the bucketful
over the course of evolutionary time. The sheer abundance of these elements
is all the more amazing, then, once you realize that the ones we know about
are just a tiny fraction of the whole. These are the pernicious few that
made it through the evolutionary grinder and still cling tenaciously to our
genomes.

The most obvious evidence for loss comes in the form of solitary LTR’s, the
element left behind when recombination between the two identical ends of the
ERV loops out the intervening retroviral genes. Solo LTRs vastly outnumber
intact proviruses in our genomes, indicating that large chunks of them are
more frequently lost than not. There are other mechanisms of loss, and
probably a majority of integrations that land in germline DNA simply don’t
survive down the generations, so we don’t know about all the stuff that was
there once upon a time. It is staggering to realize that retroviral
epidemics like the current HIV epidemic have a constant presence throughout
evolution.

Keep up the great work, and if you get a chance, check out “Small Things
Considered”, Elio Schaechter’s blog on microbes and viruses (yours truly is
an associate blogger).

Thanks again for all the great listening
Welkin

TWiV 84

Matthew writes:

Hi Twiv,

Firstly, love the podcast, I listen to it on my way to work. Don’t change a thing!

I recently wrote to you asking about the possible link between a high-arginine diet and herpes simplex outbreaks in humans (does lysine prevent outbreaks?). While researching I found this study which to my untrained eye seems to be saying that HSV-1 DNA in the neuron nucleus is histone-bound and folded into chromatin when it is it latent. This suggests an epigenetic control pathway via HDAC inhibitors. Perhaps diet could play a role in the suppression of HSV-1, as diet is linked to epigenetic silencing of genes in animal DNA.
Please could you talk a little about the epigenetics of viruses ?

Cheers,
Matthew

Jesper writes:

Dear professors,

A while back you discussed the idea of applying mutations to computer viruses to see how they evolved. Someone wrote in and explained that it simply doesn’t work that way in machine code.

I am currently reading The Red Queen by Matt Riddley. Great book, I must say. On the discussion of sex as a means to out-evolve the threat from parasites he mentioned a computer program named Tierra.

Tierra is a virtual environment where programs compete for resources (mainly by copying themselves and thus their ‘species’ would occupy more of the environment). The author of Tierra threw in a small randomization in the copying algorithm, to simulate mutations. As in the biological world, most mutations were detrimental and caused program malfunctioning and thus death, but somewhat to his surprise, some mutations appeared that didn’t kill the host. First, they had no impact at all. Then suddenly “parasitic” programs came into being. These programs had no code for reproduction, but used the required instructions from other programs. Some of the initial mutated programs were immune to the parasites. And on it went.

I found a nice article on the project on http://www.infidels.org/library/modern/meta/getalife/coretierra.html (continues onhttp://www.infidels.org/library/modern/meta/getalife/epgp.html and http://www.infidels.org/library/modern/meta/getalife/resources.html).

All the best, and I thoroughly enjoy both twiv and twip. In terms of podcast competiveness for attention resources, you rock!

Keep up the good work!

–Jesper
Sweden

Jim writes:

Wanted to make sure you didn’t miss this.

Jim

New handheld HIV detector fits into your iPod case
By Bryan Nelson
The portable device takes less than 10 minutes to perform the test, and it could revolutionize how HIV is monitored in remote regions of Africa.

Bill writes:

Journal of Clinical Investigation — Antiangiogenic cancer therapy combined with oncolytic virotherapy leads to regression of…

Drs: I’m still hooked on TWIV. Are you still thinking about a TWIV episode focused on this cool emerging virus based cancer therapy?

The company is now about to enroll its first patient to a Phase 3 “registration” trial focused on head and neck cancers, but there are many studies being conducted in and around the principal discovery that reovirus exploits the RAS flaw that is common to 70% of all tumor cell lines….It is shaping up to be a huge story…time for you guys to get on it.

Best Regards,

Bill

Lenn sent:

EQUINE HERPESVIRUS – USA (02): (NEW JERSEY) SUSPECTED
*****************************************************

Date: Thu 1 Apr 2010

Source: APP.Com [edited]

A total of 6 New Jersey non-racing horse farms, including 5 in
Monmouth County, were under quarantine Thursday [1 Apr 2010] because
of a possible outbreak of a deadly equine virus.

Except for a farm in Millstone, the Monmouth County farms are all in
Howell according to the state Department of Agriculture, whose
Division of Animal Health announced the quarantine Thursday [1 Apr
2010]. The 5th farm is in Gloucester County, according to the
agriculture department.

The disease, called the [equine herpes], is not harmful to humans and
other animals, but it can spread quickly to horses and is often fatal
to them, according to the agriculture department.

“Quarantines are necessary to ensure that this serious disease does
not spread,” said state Secretary of Agriculture Douglas H Fisher.
“Our investigation is continuing as we work to protect the health and
safety of horses in New Jersey and other states.”

The agriculture department noted tests, so far, have not confirmed the
disease. But the quarantines went into effect after 2 horses showed
clinical signs of the disease and were euthanized and another with
similar signs died, according to the department.

One of the farms is connected in some way to all the other farms under
quarantine, Lynn Richmond, an agriculture department spokeswoman. The
quarantines were put in place over various days within the last week
or so, and are expected to remain in place for weeks, Richmond said.

[Byline: Joe Sapia]

—
Communicated by:
ProMED-mail

[Equine herpesvirus 1 (EHV-1) and EHV-4 comprise 2 antigenically
distinct groups of viruses previously referred to as subtypes 1 and 2
of EHV-1. Both viruses are ubiquitous in horse populations worldwide
and produce an acute febrile respiratory disease upon primary
infection, characterized by rhinopharyngitis and tracheobronchitis.
Outbreaks of respiratory disease occur annually among foals in areas
with concentrated horse populations. Most of these outbreaks in
weanlings are caused by strains of EHV-4. The age, seasonal, and
geographic distributions vary and are determined by immune status and
horse population. In individual horses, the outcome of exposure is
determined by viral strain, immune status, pregnancy status, and
possibly age. Infection of pregnant mares with EHV-4 rarely results in
abortion.

Outbreaks with specific strains of EHV-1 infection result in
neurologic disease. Clinical signs vary from mild incoordination and
posterior paresis to severe posterior paralysis with recumbency, loss
of bladder and tail function, and loss of sensation to the skin in the
perineal and inguinal areas. In exceptional cases, the paralysis may
progress to quadriplegia and death. Prognosis depends on severity of
signs and the period of recumbency. Neurologic disease associated with
EHV-1 is thought to occur more commonly in mares after abortion
storms, but it has been reported in barren mares, stallions, geldings,
and foals after an outbreak of EHV-1 respiratory infection.

For prevention and control of EHV-4- and EHV-1-related diseases,
management practices that reduce viral spread are recommended. New
horses (or those returning from other premises) should be isolated for
3-4 weeks before commingling with resident horses, especially pregnant
mares. Management-related stress-inducing circumstances should be
avoided to prevent recrudescence of latent virus. Pregnant mares
should be maintained in a group away from the weanlings, yearlings,
and horses out of training. In an outbreak of respiratory disease or
abortion, affected horses should be isolated and appropriate measures
taken for disinfection of contaminated premises. No horse should leave
the premises for 3 weeks after recovery of the last clinical case.

Parenterally administered modified live vaccines are licensed in some
countries but banned in others. An inactivated vaccine is the only
product currently recommended by the manufacturer as an aid in
prevention of EHV-1 abortion. Vaccine should be administered during
moths 3, 5, 7, and 9 of pregnancy. Humoral immunity induced by
vaccination against EHV-1 and EHV-4 generally persists for only 2-4
months. Antigenic variation within each virus type means that
available vaccines do not cover all strains to which horses can be
exposed. Vaccination should begin when foals are 3-4 months old and,
depending on the vaccine used, a 2nd dose given 4-8 weeks later.
Booster vaccinations may be indicated as often as every 3-6 months
through maturity. Vaccination programs against EHV-1 should include
all horses on the premises.

Gary writes:

The original version of the “I’m positive!” joke (TWIV 78), as I heard it, is an atomic physics joke:

Two atoms are talking and one says to the other, “I think I lost an electron.”

“Are you sure!?!”

“I’m positive!”

Thanks for the excellent podcasts!

Gary

TWiV 83

PJ writes:

TWiV gets weird

Well, not really weird, but allow me some criticism:

I just listened to the “Darwin gets weird” episode, which was again a real treat! Thinking about Prions as non-mendelian inheritance factors seems logical, albeit the question is: how much information is carried by them? Do they belong to the general assortment of “stuff” in the zygote (which, with it’s chemical gradients, also carries some information like orientation iirc) or should they be considered a 3rd factor?

However, and this is why I used the “TWiV gets weird” headline: you’ve ventured into an area that I’m rather passionate about when you mentioned a possible TWiV iPhone app. This might sound a little strange, but:

The whole Apple i-Ecosystem is built in such a way that it keeps stuff in, that is, it’s a closed system. A native iPhone app will only run on Apple’s iPhone, iPod and iPad, so everybody wanting to use it would have to buy one of those products. That’s quite the opposite of what I call open access. Luckily, there’s an alternative that has been invented by Tim Berners-Lee a while ago, called “The Web”. Data available on “The Web” is usually open access by definition (unless the information owner wants to monetize or protect it). Now, a native application has the advantage that it can store data locally on the device, and here’s the good news: HTML5 on most browsers (WebKIT as used on the iPhone and Safari but also as part of Google’s Android and Palm’s WebOS and Google Chrome, Firefox should not be far behind) have everything you need to write applications using JavaScript and persistant storage methods (using a local database). Those applications are basically websites on steroids that can work off-line. They are, by their very nature, cross platform, you can distribute them without having to go through the iTunes Appstore or Google Android Store, use them both on mobile devices and on the desktop.

I have been an open source advocate for many years now, and the trend towards closed platforms away from “The Web”(or, euphemistically “walled gardens”) seems worrying to me. Many people seem to be willing to trade “freedom of access” for “ease of use” – even though this trade off is not really one we need to make.

So, if you do do such an application, please don’t feed it to a closed platform, it would be a pity to have the data just there.

Thanks for the show

ps: just to throw in my hat: a weekly TWiP would be highly appreciated 🙂

Howie writes:

Dear Professors TWIV and TWIP,

Awesome podcasts! This is science education at its very best. I am a mathematician who has started to work on population modeling. I listen to both podcasts regularly, and have watched about half of your virology course lectures.

Two comments:

1) For bacteria transfered from one medium to another, there is an initial lag phase where the individual bacteria are synthesizing RNA, enzymes, and other molecules they need for growth, prior to their resumption of division. Then comes the exponential growth phase which is eventually limited by the exhaustion of available nutrients and accumulation of inhibitory metabolites or end products. Thus at first the bacterial population is not growing.

2) The mathematical epidemiology world seems to believe that pathogens evolve to increase their fitness measured by their R_0 (basic reproductive rate), thus to become more easily transmitted, make individuals sick longer, and to decrease virulence (host mortality). I sometimes get a little confused by your discussion of this.

Keep up the great work!

Howie

Kara writes:

As I was listening to the episode of Futures in Biotech that Vincent was a guest on, I had a question. There was a philosophy towards antivirals you discussed on the show. Generally, antivirals should be used very cautiously avoiding monotherapy. I completely agree with you in the case of HIV and HCV and viruses that cause infections like those. That is the only way to go in that case, but I don’t know that it is as practical current drug development market for other infections.

My question is about tamiflu and the other influenza drugs with similar targets. Isn’t the fact that influenza is a self-limiting illness the reason we do not attack it with multiple drugs like we do with HIV? In an influenza infection, our bodies can often clear the flu without drugs and we come out without any lasting ill effects. HIV and HCV cause chronic diseases that ultimately kill their hosts.

Thank you for taking the time to read this and I look forward to hearing your thoughts. Thank you for making such entertaining thought provoking educational podcasts for geeks like me to listen to!

Kara

Levi writes:

Hi Vince, Dick, Alan, and the the rest of the TWiV team!

This email got a bit longer than I expected, so if you use it on the show please feel free to cut to the important parts.

I’m a grad student at the University of Florida and I study HSV-1 latency. My advisor is Dr. David Bloom, and I am also lucky enough to work right next door to Dr. Rich Condit. He recommended TWiV during our spring virology journal club and it has often been a source of material for our discussions. I wanted to give a little something back by suggesting that you all have a look at a film preview for a recent documentary about HIV/AIDS. I’m still catching up on my TWiV episodes, so I hope this isn’t a repeat of something you have seen already.

As an avid moviegoer, I frequently go to Apple Trailers (http://trailers.apple.com/) to watch movie previews. While viruses in films are often subject to extreme artistic license, I recently saw a trailer for a film called “House of Numbers” that may make a more serious error. It is a documentary about HIV and AIDS, and it supposedly includes interviews with many of the heavy-hitters in the field. Unfortunately, the preview for the film had a heavy overtone of AIDS denialism of the kind promoted by Peter Duesberg and others. I have not seen the entire film so I don’t know if it really pushes this agenda, but I hope not. The attitude of AIDS denialism can only hinder our efforts to counter the AIDS pandemic.

As you have mentioned in previous episodes, there are controversies and conspiracy theories surrounding many diseases, viruses, and vaccines, perhaps none more than HIV and AIDS. Hopefully this film takes an honest, objective look at HIV research and is not just a piece of sensationalism intended to stir up controversy or enhance a filmmaker’s career. I will try to get my hands on a copy of the film so I can judge for myself. Perhaps the TWiV team can do the same.

Here is a link to the trailer: http://trailers.apple.com/trailers/independent/houseofnumbers/ Here is a link to the film website: http://www.houseofnumbers.com/ Here is a link to the Wikipedia article about the film:http://en.wikipedia.org/wiki/House_of_Numbers

According to the Wikipedia article, it appears that my fears may be well grounded. You can judge for yourself. These controversies and conspiracy theories can only be fought with quality research and education of the public at large. Hopefully, virologists like myself and those of the TWiV team can be a part of the process of separating fact from fiction.

I’ll close by saying that I look forward to meeting you during your visit to UF this summer. As always, thanks for a great podcast, and keep up the good work!

— Levi

TWiV 82

Erik writes:

Yesterday I sent my Skype audio question again, and I think it worked this time. In my question I mentioned a particular youtube video. Here’s the link if you want to see what I was referring to. It’s only 5 minutes long. I’m not sure if what I was saying even made sense, so I guess if you see the video then you’ll understand at least what I was trying to say.

Regards,
~Erik

Joseph writes:

Dear TWIV,

I am a graduate student in the computer science department of the University of New Orleans studying Bioinformatics. I only recently discovered that Biology is nothing like what was presented to me in high school and have found this an excellent service to fill those knowledge gaps I have naively created. I am emailing both a response and a request.

At some point you requested your listeners provide what other webcasts they listen to, so I created a list of them in three orders: favorite, density, and discovered; all from least to greatest. Hopefully this helps. I’m not much of a list person but I figured it would be more useful than just a list of what I listen to. For your reference, I generally listen while doing non-critical tasks at work, driving commutes to work and campus, and walking/biking commutes to campus.

FAVORITE:
1.Software Engineering Radio
2.Machine Structures (Berkeley)
3.This Week in Virology
4.omega tau
5.This Week in Parasitism
6.Structure and Interpretation of Computer Programs (Berkeley)
7.Futures in Biotech
8.NPR: Science Friday
9.Molecular and Cell Biology (Berkeley)
10.Dave’s Psych Classes (Berkeley?)
11.Berkeley Speakers
12.Security Now!
13.This Week In Google

DENSITY:
1.omega tau
2.Software Engineering Radio
3.This Week in Virology
4.Machine Structures (Berkeley)
5.This Week in Parasitism
6.Structure and Interpretation of Computer Programs (Berkeley)
7.Futures in Biotech
8.NPR: Science Friday
9.Molecular and Cell Biology (Berkeley)
10.Berkeley Speakers
11.Dave’s Psych Classes (Berkeley?)
12.Security Now!
13.This Week In Google

DISCOVERED:
1.Security Now!
2.Futures in Biotech
3.Software Engineering Radio
4.Dave’s Psych Classes (Berkeley?)
5.NPR: Science Friday
6.Structure and Interpretation of Computer Programs (Berkeley)
7.omega tau
8.Machine Structures (Berkeley)
9.Molecular and Cell Biology (Berkeley)
10.This Week in Virology
11.This Week In Google
12.This Week in Parasitism
13.Berkeley Speakers

With that aside, I have a question/request. I’m new to the biology field and am working with a bioinformaticist this summer. Specifically, we are corrolaborating with some biologists who have some information (which they published as Human T-Cell Leukemia Virus Type 1 Integration Target Sites in the Human Genome: Comparison with Those of Other Retroviruses published in Journal of Virology June 2007) on preferred integration sites of HTLV-1 in a HeLa cell line. This is contrasted with other virus families’ preferred integration sites. Specifically, our goal is to create a model from the HTLV-1 preferred integration sites, hopefully find other studies using HTLV-1 with different cell lines, and incorporate that information into a model which will predict integration sites of HTLV-1 in a T-cell line. Natuarlly, the ultimate goal is to have a general enough model so that, given a virus’s phylogeny, we can predict its preferred integration sites. Do you know of any similar studies with HTLV-1 integration sites and, as a complete amateur, what material/tools would you recommend I review? I am currently familiarizing myself with the UCSC Genome Browser and tackling any vocabulary issues I have in the aforementioned paper.

Thanks, I love the show. Maybe shoot for more metaphors when explaining processes or comparing/contrasting things.
~Joseph

P.S. I encourage TWIP on a bi-weekly basis, but I have a lot of TWIV to catch up on, so no rush from me.

José writes:

Hi Dr. Vince, Dick, Alan and Rich

My name is José, I´m a PhD student in Mexico City and i´m
working with innate immunity against dengue virus infection.
First of all, thanks for the great job with the cast, before i became a
fan of TWIV, i knew your work with RNA detection and innate immunity and i
never thought that doctors of your level were so enthusiastic with the
academic part of science, making it so fun and interesting.

i have some comments and questions.

1. there´s any viruses that we know that are transmitted in sea water
(seaborn), since there are so many of them in the sea my guess is that
some of them are capable to infect human, do you think that some of these
viruses actually uses the sea water for spread. Might be very interesting
evaluates the stability of the particles since they are resistant to high
concentrations of salt.

2. There are many reports of exclusive detection of viral PAMPs by TLRs
and RLHs, appears to me like the mechanism of detection depends of the
cell type, the genotype of the virus and the genetic aport of the host,
not just by the PRR involved. Since almost all of these kind of receptors
activates the IRF´s and NFkB families of transcript factors, these
differences in the specific combination of elements in the detection part
can give to the activation of a specific kind of dimer in the case of NFkB
(c-Rel, Rel-b, p50, etc) and for IRF´s (IRF3,7,1, etc) given to an
activation of different sets of genes in each case, given by the
differences in the affinity for the promoter sequences and the quantity of
the transcription factor. So the response it´s more complicated that just
“activated the IRF family and NFkB pathway”.

3. About the T cell specific retroviral therapy question in TWIV 71 one of
the obstacles is that the region were the specific epitope it´s loaded in
the MHC, is not lineal in sequence it´s formed by the spatial structure of
the MHC. So if a virus have to integrates the sequence that codifies to
the specific CTL or Th must do it in fragments that have to fit exactly in
the gaps of the MHC and have to leave the sequence in open reading frame…i
think that’s very difficult.

[the original question in twiv 71: Is possible to use gene therapy to insert genes into the major histocompatibility complex that could encode protien expressed on T-cells for a certain virus? ]

take a look at these microscopy technique that allows visualize in the
range of 40nm!!!!! so cool.

Thank you for the great show and sorry by english it´s very precarious.

TWiV 81

Jesper writes:

Dear Professors,

Having upped my daily dose of podcasts I stumbled upon This Week In Science. The latest show (http://www.twis.org/audio/2010/03/09/438/) they mentioned something that probably comes within your sphere of interest, namely the finding that viruses are a possible triggering factor to gluten allergy. A brief report is available on http://www.eurekalert.org/pub_releases/2010-03/aof-vim030510.php.

“Virus infections may be contributing factor in onset of gluten intolerance

Recent research findings indicate a possible connection between virus infections, the immune system and the onset of gluten intolerance, also known as coeliac disease. A research project in the Academy of Finland’s Research Programme on Nutrition, Food and Health (ELVIRA) has brought new knowledge on the hereditary nature of gluten intolerance and identified genes that carry a higher risk of developing the condition. Research has shown that the genes in question are closely linked with the human immune system and the occurrence of inflammations, rather than being connected with the actual breakdown of gluten in the digestive tract.
“Some of the genes we have identified are linked with human immune defence against viruses. This may indicate that virus infections may be connected in some way with the onset of gluten intolerance,” says Academy Research Fellow Päivi Saavalainen, who has conducted research into the hereditary risk factors for gluten intolerance. […]”

I presume this may open up a huge field of both treatments and preventions.

As for This Week in Science it’s a general science news pick kind of show with an attitude. Not as in depth/subject focused as twiv, and no doubt satisfying a different need, but anything helping the scientific project is worth trying! I think Vincent may appreciate their music selection, but that’s mere speculation.

All the best,

–Jesper, Sweden

[here is the paper: http://www.nature.com/ng/journal/v42/n4/abs/ng.543.html#/]

Jason writes:

I was listening to the most recent episode of TWIV (episode 72) and was delighted to hear you discuss RNA silencing and viruses. It happens to be what I’ve devoted the last 6 or so years of my life to so it’s a topic that I am fairly familiar with and I just wanted to shed a little light on some things. First a brief background on myself – I defended my dissertation at the end of last May, graduating from NC State University where I performed research on a fairly obscure plant virus, Red clover necrotic mosaic virus. My research surrounded the role of plant RNA silencing as a host defense mechanism, and of course how the virus might circumvent this defense. Towards the end of my research I knew I wanted to transition out of plants and into animal virology so I applied to a variety of labs and ended up getting a Post doc position at Duke with Bryan Cullen. It’s been an interesting transition, and I’ve absolutely loved listening to your podcasts which I think do a great job providing digestible information for everyone from the common layperson to PhD’s like myself. Anyway at one point in the past episode you made a comment that all vertebrate viruses are surely chopped up into siRNAs. Rich wasn’t so sure about that, and he is definitely correct. I won’t say that it is a completely settled subject, but at this point it does not appear that RNA silencing is a general feature of viral defense in vertebrates, although some exceptions may exist. Certainly there is interplay between small RNAs and viruses, but a generalized antiviral link is pretty tenuous at this point. You mentioned how it would be useful to do some deep sequencing on infected cells to see if you could detect virally-derived siRNAs. Our lab has done that for a number of herpesviruses, and, along with other labs, has found that herpesviruses actually encode their own miRNAs. In fact, EBV encodes 25 miRNAs, while KSHV, HSV-1, and HSV-2 all encode multiple miRNAs as well (I can’t recall the number off the top of my head). A much broader study was recently published by Andy Fire and colleagues in PLoS Pathogens which you might find interesting: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000764

Keep up the good work!

Ewout writes:

Dear TWIV-staff,

Thanks for answering my mumps question! Great fun (and honour) to be cycling back from work and suddenly hearing my email on the iPhone!

Me and my colleagues would like to read the CDC response mail, with the references named in the podcast.
Would you be so kind to forward it to me if possible?

Hope you are able to continue this great podcast for a long while, I will advise more colleagues to listen to you.

I sent him the email, and he replied:

Thanks! We (Nat Inst Publ Health and MHS) are planning to go deeper into the mumps issue, since vaccination related diseases (measles/mumps etc) are an ongoing issue because of areas with low vaccination coverage (due to protestant reformed religion). Genotype G suddenly seems to hit vaccinated (non religious) students. I also contacted Israel a few weeks ago, thanks to your former TWIV about their outbreak.

TWIV is more than just an interesting podcast. It enhances science.

Bree writes:

Hello again,

I just wanted to say thank you once more for taking the time to answer my question on your podcast. It’s very exciting for me and the other members of my class to be able to have our questions answered after listening to your podcasts!

And to answer the question you asked during the last podcast – I have mixed feelings about podcasts as a learning tool. For someone like me, who only has a very basic grasp on the principles of virology, understanding everything that is being discussed by people who are very advanced in the field can be difficult. However, when I do understand the subject matter (and hopefully I will after completing this course!), I find that it’s relatively easy to follow and understand what is being said; I also find that listening to what someone other than my professor has to say about the topic being discussed is not only refreshing, but provides me with more than one viewpoint from which to understand and look at certain topics and new material.

Again, I greatly appreciate all of you taking the time to read and answer my question, and I look forward to hearing more questions answered on future podcasts!

Thank you.

Jim writes:

The Canadian Broadcasting Corp podcasts are my only connection with Canadian activities. Too bad we don’t hear more about our neighbors. I’d not heard about the Summit Awards until this podcast fromt http://www.cbc.ca/podcasting/pastpodcasts.html#ref14 . Not much about viruses, but listeners to TWIV might still be interested from the standpoint of career development and jobs. Here’s a summary of the 46 min program: Science at the Summit

“Two leading Canadian medical researchers – Benjamin Neel, and John
Wallace – discuss what it takes to rise through the ranks and
ultimately arrive at the lofty pinnacle where true scientific
advancements are made. Both received the $5 million 2009 Premier’s
Summit Awards. John Dirks, President of the Gairdner Foundation,
moderates the discussion, recorded at the MaRS innovation centre in
Toronto.”

In case I’ve not said so, all the TWIV podcasts have excellent sound quality and levels.

I’ve heard several references to online videos of lectures from places like MIT at http://www.academicearth.org/ . After viewing a dozen or so on chemistry, math, biology, computer science and physics I must say how much more enjoyable the TWIV podcasts are. Lectures do not appear to have changed from the last I attended 25 yrs ago. I expected to see more. In several there wasn’t even any chalkboard work, just a lecturer talking. Just a comment…..

[the podcast can be found at http://www.podcastdirectory.com/podshows/5624750]

Mike writes:

I just started listening to the show (after downloading every episode) and I’m really enjoying it. I have no science background, but I’m a geek and enjoy listening to Futures in Biotech so as soon as I heard about TwiV and TwiP I knew I’d have to check the shows out.

A worthy find, indeed! I shall be recommending it to other science minded friends. Keep up the great work!

Richard writes:

Thanks for posing the question, it has proved interesting to research, and think about. (referring to the flu/bacteria question).

I have a pick for you, this is a webpage that provides information for experimenting with phage at home. It gives info and experiments that require little or no equipment to be purchased. http://www.disknet.com/indiana_biolab/p.htm

Thanks again for the interesting and informative podcast.

Regards

Richard

Thomas writes:

Hello,
Love the podcast. Wish everyone was an enthusiastic about what they do as you guys are. I have some questions and clarification:
1. On TWIV 65 a pick of the week was Rebecca Skloot’s book “The Immortal Life of Henrietta Lacks”. The HeLa cells are infected with HPV18, but I cannot find any discussion about what makes these cells immortal. Certainly “experienced” virologists such as yourself can help in my quest for an answer to this question.
2. There are 2 current rotavirus vaccines (and one previous). Here is a history and a question (you can omit the history if it gets too long):
ROTASHIELD-FDA approved in 1998-a lyophilized tetravalent rhesus-human reassortant rotavirus. It is postulated that because it is rhesus and not bovine based, that the closer genetic similarity allowed it to replicate in the intestine and lead to intussussception.
ROTATEQ-a pentavalent human-bovine reassortant rotavirus vaccine. It has been wonderful for us primary care pediatricians-reduced RV related gastroenteritis hospitalizations by over 98%. The intussusception correlation has not been reported, but this vaccine is given to infants less than 6 months old and if you are 12 weeks old, you are too old to start it. These restrictions were put in place because intussusception after RotaShield correlated with increasing age of first vaccine and increasing age when getting any dose. Hard to imagine that at 12 weeks of age you are “too old” for a vaccine (no jokes about the experienced virologists in this podcasts at this point), but that is what we have to tell parents.
ROTARIX-just today the CDC reported that there is porcine circovirus type 1 (PCV1) present in RotaRix and has withdrawn it from the market. This is NOT swine in origin, just seen in pigs. They do not know if there is intact virus present or just DNA segments or whether this causes human disease, from what I can tell. They also do not report how this virus was detected. Can you dig into this and enlighten the masses? Let the second coming of swine flu begin in the media (they get things wrong a good part of the time) so that we can work at undoing their mistakes.

Here is a good tag line for those who want answers now that we don’t know: SLOW PROGRESS IS BETTER THAN NO PROGRESS.
Have a great day.

Joel writes:

Hi Vincent, Dickson, Alan, and Rich,

TWIV episode 72 was great. I had a few quick comments.

1) The original high profile paper describing CRISPR as an adaptive-type immune response in bacteria was from a research group at a dairy company. Apparently there are some common bacteriophage that are the scourge of cheese and/or yogurt production. I found it interesting that these phage are such a problem that the company funded basic research like this. (http://www.ncbi.nlm.nih.gov/pubmed/17379808)

2) While it is well documented that plants and insects use RNAi (siRNA-mediated) as a defense mechanism against viruses, RNAi (either miRNA- or siRNA-mediated) as a defense against viruses in animals with more complex immune systems has been contentious. An interesting exception is in germ cells. A novel class of small RNAs called Piwi-interacting RNAs (piRNAs) are highly expressed in germ cells and are thought to defend these cells against the replication and re-integration of endogenous retroviruses. Stringent defense against the replication of endogenous retroviruses is important to prevent ever-expanding genomic “junk” from being passed on to future generations.

3) If you are interested in discussing archaeal viruses, I would recommend having Dr. Mark Young from Montana State University as a guest on your show. His group has been spending years finding viruses in what amounts to boiling acid in the hot springs of Yellowstone park. (http://mbprogram.montana.edu/faculty.asp?per_id=101&in_id=12)

I received my Ph.D. studying rotaviruses and have moved on to a postdoc studying Leishmania, so I enjoy both TWIV and TWIP. Keep up the good work.

-Joel

PS Dickson, any chance you’ll be at the Woods Hole Immonoparasitology meeting in a month?

Henrik writes:

I really enjoy your show and am slowly starting to get the hang of basic virology. I like the way you revisit topics
from different angles. It helps to hear things again in a different way, so it doesn’t become boring.

And don’t forget the 101 stuff. Even if I’d rather learn about the sophisticated topics, the devil is usually in the detail, so understanding the basics is vital for really following your trains of thought.

I just watched a nice talk on fora.tv about an expedition to New Guinea.

You may find it interesting as they did a lot of virus sampling in the birds there.

http://fora.tv/2010/03/17/Expedition_Papua_New_Guinea_with_Jack_Dumbacher#fullprogram

http://www.calacademy.org/blogs/jdumbacher/

Keep up the great work!

Cheers,

Henrik

Dan writes:

Your recent episodes have again discussed aspects of H1N1 and influenza. Given advances in gene sequencing (deep techniques or
whatever) it seems that if these techniques became economical, swine populations (or birds) could be monitored for new influenza strains
on a regular basis. Once a new, say “novel” infection is discovered in the swine (before the virus becomes zoonoic, did I say that right?)
or transmitted to humans, an inactive vaccine could quickly be made from the swine virus through say for instance plant or insect
techniques (common by that time) that could be administered to humans along with the annual flu shot. I don’t think the vaccine
would be harmful to humans (inactive vaccine), but it could be an intelligent “shot in the dark” to head off a potential nasty pandemic
(via “cross reactivity”, did I state this right?). Is this idea science fiction, or does it have potential? Until a true “vaccine for all flu types” becomes reality, it seems this could actually be a way to protect our growing population from a devastating infection with high virulence.

Remember, when you end your podcast with “another twiv is viral”, I am the one who was just infected.

Yours sincerely,
Dan, the meteorologist in Colorado.

Ps: give my 3’s to Alan, he will understand

Anthony writes:

Dear heroes,

Iterations of flattery and humility. A question: does an individual who is infected with HSV-1 and who chronically develops lesions become newly infected with each outbreak? I.e. if retroviruses insert their DNA copy with impunity, would not each outbreak produce new virus to peruse the body and infect other cells? or even the same cell twice? It is my understanding that HSV-1 infects neurons in the face/neck. Do viruses, newly produced during an outbreak infect other nearby neurons? Do they insert many copies into the same infection-susceptible cell? My guess is no, because this would eventually be horribly detrimental to the host. If my guess is inaccurate, how many outbreaks must one go through before a secondary infection induces cancer or apoptosis in these rarely regenerated neurons?

Another question: How can a lowly research technician get money to study a brilliant idea he or she had? Then, how can said technician get the IP if his or her brilliant idea works?

Godspeed,
Anthony

Sophie writes:

Hi Vincent and cohost(s).

I have a question about HIV/AIDS. You always say that virus have a tendency to get less virulent, because it lets the host transmit it to more people. Could the reason for the prolonged life of HIV patients be due to the virus is adapting to us, or is it just the antivirals?
Furthermore could it be possible to find the mechanism that control whether it is HIV or AIDS you have (I’m thinking of something like the bacteriophage Lamda, with Cro and cI)? Or is it simply, when a high enough number of T-h cells are infected you will get AIDS?

Still love your podcast.
Sophie

Ken writes:

While discussing the evolution of H1N1 2009 pandemic influenza virus, Alan dropped the line, “Be a virus, see the world.” Which is, of course, a Far Side caption.

When teaching introductory microbiology courses, I used to disclose to the students, at the beginning of the virology lectures, that I understood they had, coming into the course, very little knowledge of virus biology. I understood this because one can get a sense of what Americans learn in high school and introductory college biology courses by scanning The Far Side. A high proportion of Gary Larson’s humor played on shared popular knowledge of biology. And the fact is (I know this because my beloved partner bought me the complete collection) that, in fifteen years of daily panels, there are exactly two that make any reference to viruses, and neither addresses virus biology.

I no longer do that bit, because my current students don’t know who Gary Larson is. And more of my students will already know something about the biology of viruses because they’re growing up around people who listen to TWIV.

Duncan writes:

This is the second time that I have emailed you and I have no desire to be considered a stalker, but I thought that I should let you know about the impact that TWIV and TWIP is having on at least one of your listeners.

Last time I emailed you I told you that I was planning on leaving my IT job to attend university and study for a degree in medical laboratory science. That was probably a year ago and I still haven’t left my job. Why I hear you say.

Well, I’m writing to tell you that it is pretty much your fault. You see originally I wasn’t even considering getting into research and that is why I was looking at the lab science degree. After a year or so of listening to your wonderfully podcasts, I discovered that my passion for microbiology runs much deeper than I had previously thought. After much thought I decided that if I was going to follow my dreams, I should follow them all the way and I am now going to be studying for a bachelor of biomedical science majoring in genetics and molecular pathology.

I’m not entirely sure what I will do after I’ve completed my degree but I have an open mind and deep fascination in viruses, parasites, bacteria, genetics, disease and what makes life tick at the cellular level. I may go on the do a PhD, I might even decide that after all that time at university I’m satisfied with my level of knowledge and go back to IT, but I very much doubt it. Whatever happens, I thought that you would like to know that you guys played, and are still playing, a major part in helping me to achieve my dreams with your inspirational shows. Thank you very much and keep on doing what you’re doing.

Cheers
Duncan
New Zealand

Belle writes:

I am appalled at the lack of sanitation in manicure salons. Even those salons that claim to disinfect and sterilize seem to cut corners. Has any study been made to determine viral transmission in these establishments? Many women have cuticles cut and pushed back, basically a surgical procedure done under non-sterile conditions. In addition to the well know viruses, other retroviruses including XMRV, might possibly be transmitted. There have been clusters of diseases in many neighborhoods of different illnesses. It would be tantalizing to explore the unsanitary conditions of these salons as sources of infections.

Years ago, it was said that upper-middle class women had higher incidences of breast cancer. I am not sure of the status of this statistic. Has anyone ever questioned these women about their attendance at manicure salons? beauty salons?

If you want to satisfy your curiousity of how unsanitary these establishments are, simply visit one and observe. Instruments are either not sterilized, sterilized inadequately, or reused from person to person. One establishement had their instruments in some kind of sandy material which they heated to 135 degrees F (they were proud to show this to me). Others have instruments soaking in liquids. Nail shavings are left on paper towels from person to person.

I am sorry if this email seems eccentric, but it is very disturbing to see the mess that goes on in most manicure salons. I do have some substantial medical knowledge. In addition, my nails look very ungroomed .

Sincerely,
Belle

Matthew writes:

I just discovered TWIV and have been devouring episodes. The one on the 7 types of virus genome was the best one yet. I will have many more questions to come but for now I have a somewhat practical question as I’m currently recovering from a recurrence of herpes simplex in my cornea. It’s interesting to think that I’m actually looking through herpes simplex viruses as I type this! It’s ok – I have acyclovir on the case.

What I’d like to know is: is there any truth in the idea that eating foods rich in arginine can trigger a recurrence of herpes ? The idea is that eating more lysine-rich foods can prevent recurrences by blocking absorption of arginine.

Thanks for doing the TWIV podcast. I love the episodes with you and Dick talking in technical detail. I think that viruses are beautiful, enigmatic things. Surely they hold clues to some of the profound mysteries of cellular life.

Cheers,
Matthew

Laura writes:

Dear Vince, Dick, Alan and Rich,

Thank you so much for the wonderful podcasts as both TWIV and TWIP are my favorites. They frequently make me laugh out loud getting me strange looks on public transport and at the gym. I teach High School Biology in Hong Kong and am currently doing a distance learning MSc. in Infectious Disease so all your info. is invaluable. I am writing to recommend a pick of the week which is Arno Karlen’s “Plague’s progress” which is both informative and a very easy-to-read stroll through the history of disease.
If any of you are ever over in Hong Kong and are at a lose to what to do send me an email and I will happily show you around to say thank you.

Regards,

Laura

James writes:

Hello all,

I was flicking through my RSS feeds when I came across this story about the New Zealand Blood Service moving to stop people with CFS from donating blood. This seems to be a precautionary measure until the science becomes settled as it is remarked in the story that the science is shaky at the moment.
http://www.stuff.co.nz/national/health/3607226/Chronic-fatigue-donors-face-rejection

And a quick question. If H1N1 Swine Origin is found to displace the H3N2 seasonal strain would you expect the WHO to switch their suggestion to a bivalent vaccine and thus instantly increase the amount of seasonal Flu vaccine that could be produced by a third? Just an interesting public health logistics though I had.

Kind Regards,
James
New Zealand

Stephen writes:

I was listening to your story about researchers who bought an assortment of groceries in Marseilles for testing. I wonder if they bought any Koala brand tea. This is important because “The Koala tea of Marseilles is not strained” 🙂

– Stephen

TWiV 80

Ricardo writes:
Again and again, You do it over and over. Your podcast is everything about teaching. I’m expecting every monday morning for the download to finish so I can have my “pleasure drive” to Ponte de Lima (a secondary campus from UFP). Episode 72 was really good, the CRISPR and the iRNA sequencing was very interesting. But, another thing made me wish my entire group of students could listen to you four. During the last episode I found myself thinking “… look how this guys learn…”. You are all grate teachers but you are also grate learners. During your 90″ talk we get questions, chains of events, summaries, research (google) it’s almost like a fight for knowledge.
Sorry for my English and congratulations.

Just an interesting software I herd about “Tableau Public”. http://www.tableausoftware.com/public/.

Ricardo

Etienne writes:

Hello Vincent Racaniello and TWIV panelists,
I was listening to twiv 72 and it was mentioned that archea only live in extreme environments ( hot vents, salt lakes, and extremely low ph for example). Tho it is true that they are well known to be the dominate life in those environments, it has been shown that they can be found in much more mundane settings. They even seem to play a major role in the production of nitrites and nitrates from ammonia in top soil.

For examples, here are 2 articles about DNA sequencing revealing the presences of archea genes in top soil. I tough that you might find them interesting.

Archaea predominate among ammonia-oxidizing prokaryotes in soils: http://scholar.google.ca/scholar?hl=en&as_sdt=2000&q=archaea+bacteria+in+soil
Molecular phylogeny of Archaea from soil

Etienne

Cedric writes:

Hello TWIV gang, I’m currently listening to TWIV #72 and just heard the discussion of viral infections in Archaea. One of the questions that came up was how viruses could survive the extreme conditions that archaea inhabit. I agree with Alan’s assertion that if archaea can make proteins that survive such extremes, viruses can too, but it is also worth pointing out that archaea do not only live in extreme environments. They tend to thrive in nutrient-poor ecosystems and at extremes of pH, temperature and other environmental parameters, but they are also found alongside bacteria and eukaryotes in soil and other mundane habitats. Like bacteria, archaea can also live inside other organisms, including humans, and as you know this is an excellent environment for horizontal gene transfer, including virus-mediated transduction. The section of the Wikipedia entry on archaeal habitats is well-referenced and talks a bit about their ecology: http://en.wikipedia.org/wiki/Archaea#Habitats.

I love the show and always enjoy the discussions. Keep up the good work!
—
Cedric

Angie writes:

Hello fellow Virologists,

Just wanted to drop you a line to say I LOVE, LOVE, LOVE your podcast! I just discovered it last month and I can’t get enough of it. I am a former Virologist (I worked on Herpes and Parvovirus), who is now a forensic scientist. Although I love my new job, I miss reading and discussing the newest papers/research on Viruses. This podcast fills that void. The way you discuss papers and answer email questions is great. It reminds me of journal clubs or informal discussions at lunch or conferences.

Thanks and Keep the podcasts coming. They are infectious!

TWiV 79

Ben writes:

I really enjoyed your podcast about reverse transcription. I was wondering what makes retroviruses like HIV impossible for our bodies fight off. Are there any retroviruses that can be eliminated from the body?

Paula writes:

I was browsing on the “Chronic Wasting Disease” website when I read that prions not only occur in the brain and spinal cord according to the TWiV #67 program, but also in the saliva, blood, muscle, urine, and antler velvet of symptomatic animals with the late-stage disease. So being that this prion has been found in all mammals including humans (again from the website), we do have the potential to become infected by prion exposure if we handle or consume the meat of an infected deer?

Sarah writes:

What is an enterovirus?

Heather writes:

Dear Dr. Racaniello,

I’m responding to your question regarding the usefullness of podcasts as a learning tool. The traditional classroom provides a forum to discuss and explore new concepts which gives depth to the learning experience. But I feel the podcast has several advantages as well which makes them worthwhile. Students can get exposure from a larger pool of experts who bring their unique background and expertise. Material can be instantly repeated if a section is missed or not understood. The podcast can be interrupted if the student wants to check out links related to the topic, look up terms or whatever may increase their understanding and interest. They can then return to the podcast at their convenience. Finally, there is the possibility of the two-way exchange of ideas, such as this email. Although this feature is not inherent in a podcast per se, it can provide the tools to open the door. I wouldn’t be sending you this email if it weren’t for your kind invitation. So Thank you.

Michelle writes:

I wanted to say “Thank you” for answering my question about viral resistance to antiviral drugs. I have studied microbiology, but virology is a new field for me. I have learned about bacterial resistance and the development of new drugs that combat resistance, so I was interested in knowing about this for viruses too. (As a side note, I learned from my veterinarian that the same thing is happening with certain parasites and drugs used to kill them.)

To answer your question…I think that podcasts are an effective way to learn. I have only listened to twiv, but I enjoy listening. The one thing I would caution is that if podcasts are used specifically for student education, that the presenters would have to be careful to stay on topic because it may be easier to stray when not in a classroom setting.

Ken writes:

I‘m reluctant to be seen as chastising such a distinguished group of scholars, but I know that you are committed to basic virology education.

Toward the end of the episode, y’all handled a question about what distinguishes the most complex viruses from the simplest bacteria.

Listening to the discussion, I was dismayed that I did not hear what I regard to be the critical word.

That word is Eclipse.

David writes:

I believe in TWIV #70 where someone asked the question, is there a virus that alters human behavior to facilitate transmission. Would rabies qualify?

I recall years ago speculation that rabies was the basis for the vampire legend. If I remember correctly, rabid people would try to bite other people, spreading the infection. If that is true, and if rabies can be spread by biting, then rabies could be considered a virus that spreads through altering its host behavior.

http://en.wikipedia.org/wiki/Vampire#Rabies
Gómez-Alonso, Juan (September 1998). “Rabies: a possible explanation for the vampire legend”. Neurology 51 (3): 856–9. ISSN 0028-3878. PMID 9748039.

Vincent writes:

Drs. Racaniello, Despommier, Dove, et. al.,

Thanks for the wonderful podcast. TWiV and TWiP are at the top of my pod-cast favorites! I recommend them to everybody, and have posted a thread at Student Doctor Network, a community of pre-med, medical, and professional doctors.

A few comments and questions:

1) You have mentioned several times that Fugu Fish have a compact genome virtually free of “junk” DNA. First off, does this include LINE or retrotransposons, or just endogenous retro-viral material? You guys repeatedly use this fact as supporting evidence of why this ‘superfluous’ DNA may not be essential for the host, which is very fascinating to me. Forgive my rudimentary understanding of this subject, but I instead want to ask WHY does Fugu not have any? I understand that we have such a small set of data, but is this an otherwise unique finding in animals? That is, are there other known examples of “junk-free” species?

In past episodes Dick asserted that ocean water contains very high levels of genetic material. This indirectly implies that it is a very diverse – and yet unexamined – biologically significant reservoir of viruses. I would expect their to be a plethora of viruses that could potentially infect a fugu fish, including retroviruses.

But at the same time, you have likened the existence of endogenous retroviruses to a ‘fossil record’ of ancient retro-viral infections in an animal’s germline? What does the lack of such a fossil record suggest?

So Fugu’s compact genome begs many questions: Have there never been any endogenous retro-viral infections of their ancestors’ germlines? Or does the Fugu possess some extreme type of cell defense mechanism that leads to super-efficient clearing of these potential infections in their germ cells? Are there any known retroviruses of Fugu fish? If so, has anybody investigated if they indeed can infect fugu germs cells? What is the next nearest fish species, phylogenetically speaking, to possess a “normal” amount of “junk” DNA?

2) I am a non-traditional student who will attend the Cleveland Clinic Lerner College of Medicine this summer, returning after almost 12 years as a research medical device engineer. It’s a five-year Master’s/MD program that focuses on research as well as medical training and I am very excited! CCLCM’s mission is to create Physician – Investigators and as such I am keen to learn more about potential virology (or parasitology) related research career paths with a formal medical training beyond the obvious Infectious Disease specialty. Any thought would be appreciated.

3) Just wanted to comment on Alan’s mention of micro-fluidic devices many podcasts ago. He brought up the possibility of “lab-on-a-chip” products for doing complex, but predictably repetitive lab techniques like PCR. As a former MicroElectroMechanical Systems (MEMS) engineer working with micro-fluidics, I had to smile. While the field looks promising, I think it is safe to say it has yet to live up to it’s hype. Given the amount of time and money invested into the core technologies of MEMS, it is my opinion that beyond very specific applications (such as accelerometers in your kid’s Wii and your car) it has fallen flat on its face. If I had to guess, I would bet that a novel and disruptive technology will obsolete the lab-on-a-chip within the next decade or so. Now, that of course is just my two cents, but I couldn’t resist.

4) And finally, if you haven’t seen the following basic science research publication, I just think is is really cool. It is a paper that details the detection of glycine of extra-terrestrial origin that was capture from a sample taken in 2002 from the comet Wild-2. What is personally very exciting for me is that I have known the lead investigator, Dr. Jamie Elsila, since high-school. We were both members of a radio astronomy team (RATs) that built our own radio-telescope (a la SETI, which you have also mentioned). That core group of geeky high-school students have all gone on to successful and interesting engineering and science careers. RATs is a poignant example of how early mentoring and exposure to advanced sciences can have a direct impact on society in very, very positive ways. http://news.bbc.co.uk/2/hi/8208307.stm

Sorry for the long e-mail. Keep up the good work. I look forward to every episode.

All the best,

-Vincent

TWiV 78

Michael writes:

Hi guys really like the show even though some of it (not much) goes over my head. I also listen to twip and hope there will be a matching number of episodes to rival twiv. My name is Michael and I was talking to my dad the other day and he mentioned that he took parisitology from Dr. Brown (Stoolie) when he was at Columbia. Small world. I was also interested in checking out some classes at UCLA, I live in LA, and wanted to know if you had any recommendations as far as instructors or classes.

A couple of things I was wondering how your iphone app is coming along. I know lots of programmers and artists and would like to produce one of your ideas.

Secondly you guys mention all the time about the dearth of research being done. How would you like to start your own non profit? And is there a website that tracks current field studies or lists proposed studies? I have a great plan for a virtual corp. that could direct and help synergize field research. You guys would get to do the fun part i.e. plan the protocols and general aim of the project, and approve the personnel, take all the public credit. I would do what I do best which is organization and logistics. I think Field Studies International sounds good.

Well enough of your time for now thanks for the great podcasts.

Michael

Mary writes:

As much as you guys are adamant against engaging in political discussion, I know you also feel strongly about exposing the truths behind alternative medicine, anti-vaccination campaigns, and so much other medical and scientific disinformation espoused by quacks all over the world… so maybe this is something you might feel like passing onto listeners? I’m not sure if really counts as “politics”, anyway.

As you may know, science writer Simon Singh is being sued essentially for bringing debate on alternative medicine into the public forum, and the millionaire- and corporate-backed British libel laws, among the most repressive in the world, are allowing this to happen to responsible journalists, writers, anyone—even outside Britain, thanks to the thriving “libel tourism” the laws have given rise to. There is a movement sponsored by journalists and others, including scientists, to reform these laws, and it includes a petition, for which they are inviting signatures from around the world, because even those of us outside the UK are at risk for litigation.<

http://www.simonsingh.net/

http://www.libelreform.org/sign

Just food for thought. (Please excuse me if this is wildly inappropriate.)

In a separate (or maybe conceptually related?) vein of thought, here is a good essay from the Journal of Cell Science a year or so ago (attached) on the importance of admitting and even embracing our own stupidity as scientists.

Thanks for the great shows!

Mary

Cedric writes:

Dear This-Week’s-TWiV-Crew,

I heard in a lecture from Prof. Steven L. Goldman of Lehigh University that atmospheric/wind currents can pick up dirt, bacteria, and viruses and transport them across entire oceans. I was wondering if this can or could have been a means of viral spread. Can a virus survive in the upper atmosphere, or would radiation render it inert? Is this a phenomenon that can be of significance in today’s world of human-created interconnectivity?

Many thanks for your podcast. I am a high school student working part time as an intern at a national lab and I love to listen to TWiV and TWiP while doing the menial chores.

Salubrious Salutations,
Cedric

John writes:

Listening to your show reminds me of the excitement I felt as a child reading Paul DeKruif’s “Microbe Hunters.” As a physician living in North Carolina, you are making me nostalgic for my days as a resident and intern at Columbia. Your show reminds me of what a great institution it was and is.

Benhard writes:

Dear TWiVers and TWiPers,

Since I’ve discovered TWiV (and TWiP), I’m addicted to virology (and parasitism), well, at least during my commute to work and back home. It took me quite some time to catch up but it was definitely worth it!

Although I’m working as a software designer for medicinal chemists in a pharmaceutical company, I’ve always been interested in the big picture of biology. Listening to TWiV (and TWiP as well) gives me a glimpse into how biologists work and think, which helps me communicate with them. There are many other podcasts which I’ve since also subscribed to but TWiV and TWiP are special in how well they match what I would be interested in from the respective fields and how entertaining the subject is presented.

The second reason I write is to suggest a Pick of the Week:

Last year, I learned about ‘Sustainable Energy – without the hot air’ (http://www.withouthotair.com/) by David MacKay. I knew his previous book ‘Information Theory, Inference, and Learning Algorithms’ as a treasure trove, but it’s probably too heavy reading for general consumption. Sustainable Energy, however, is fairly easy reading, full of facts and figures, surprising calculations, provides a big picture, and shows how the world might be able to escape it’s current agony. It provides a sober view on (British and world-wide) energy consumption and production with real figures and personalized measures. It could arguably be the most important book on the topic written to date. So, have a look and decide for yourself.

Keep up the good work (including the jokes)

Bernd

Dave writes:

Hi DrsVAD,

When GRID computing is promoted, the usual suspects mentioned are Seti@Home and Folding@Home. At least of equal merit and more germane to TWIV should be:

www.worldcommunitygrid.org (WGG)

I found the following factors (listed on the WCG website) more compelling than Folding@home:

“World Community Grid harvests the unused computing capacity of volunteer PCs around the world, creating a secure virtual supercomputer available at no charge to scientists engaged in not-for-profit humanitarian research.”

“The World Community Grid team helps scientists prepare research projects for grid computing, process results and reconfigure work for further computation. In return, research partners must commit to open publication of their results”.

Highlighted below are three research projects with a virology connection:

Current WCG Research:

Help Cure Muscular Dystrophy – Phase 2

Help Fight Childhood Cancer

Nutritious Rice for the World

Help Conquer Cancer

Human Proteome Folding – Phase 2

FightAIDS@Home

Influenza Antiviral Drug Search

Discovering Dengue Drugs – Together

Help Cure Muscular Dystrophy

Genome Comparison

Help Defeat Cancer

Human Proteome Folding

It would be good if you could give WCG an honorable mention along with Seti and Folding.

I am an Information Technology (IT) professional with no formal training in any of the sciences, but I really wanted to make a contribution to scientific research. My charitable cause is WCG.

Since 2004, I have donated 88 CPU years to WCG projects. This is equivalent to turning on a PC in the year 1922 and having it run 24 x 7 x 365 uninterrupted to present day, computing work units for the Current WCG Research Projects previously mentioned.

As you’re probably doing your goszinto’s right now, this involves 10 multi-core PC’s (9 quads and a dual for a total of 38 CPU cores) running pretty much at 100% load. Yes, my power bill does take a hit.

As for the TWIV and TWIP podcasts, thank you immensely DrsVAD for devoting your time and effort on the podcasts and especially for enthusiastically sharing your knowledge on virology and parasitism. I was hooked from episode 1 on both podcasts.

I suspect I’m not your average listener type since I don’t work in any scientific field and I’m circa Vincent’s age. My career ship has sailed, but in my next incarnation I hope I come back as a microbiologist or virologist. After finishing Volume 1 of Principles of Virology, it became obvious to me that to obtain a competent knowledge of viruses, I needed to take a deep plunge into biochemistry, cell / molecular biology and immunology. I’m just coming up for air, but what a fascinating journey. Science fiction pales in comparison to reality. Ready for Volume 2 of PoV.

For me, I love that you don’t dumb down the podcasts too much. There is delectability in the details. For example, when you were talking about a membrane lipid, you use the actual terminology phosphatidylinositol. This is helpful so I can do further investigation and also very useful to hear how terms are pronounced. Having no contact with scientific types, I have to guess at how some terms are pronounced. This can be problematic since often online audio dictionaries will not have technical terms. Now if we could just get Marc Pelletier (FIB podcast) to quit calling them [ am I no ] acids, life would be good.

My hope is that you continue to enjoy doing the podcasts as much as we, your audience, enjoy listening to them.

Keep it viral!

Dave

TWiV 77

Wladimir writes:

In regard to your question as to cases of known alteration of host behavior by virus that increases the rate of contact among hosts (Twiv 70), the most dramatic example is given by rabies. This extraordinary virus can convert a neurologically and behaviorally complex organism like a dog (or a person) into a vehicle that is behaviorally dedicated to increase the transmission of the virus. This seems to be done mainly by a sophisticated process of selective infection of particular neural structures that makes the host more aggressive and cause it to salivate more (increasing the load of viruses to be transmitted in the bite of the so-converted furious animal). I am copying to you below a fragment of the paper by Dr. Benjamin Hart “Behavioral adaptations to pathogens and parasites – 5 strategies” published Neuroscience and Biobehavioral Reviews in 1990, in case you want to provide to listeners further details of the elegantly macabre transmission tricks of the rabies virus.

all the best,
Wladimir

Effects of rabies virus on mammals. This is probably the most well-known example of a virus altering animal behavior. The virus infects domestic dogs and other canids and can turn a calm and placid animal into a wandering and vicious animal that attacks almost any target in sight. The rabies virus cannot survive except in living organisms, yet it is virtually always lethal in man, canids and many other hosts. In these instances, to be propagated the virus must be transferred to another animal before the host dies. In the furious or vicious form of rabies the virus usually enters a wound through a bite by an infected animal. The virus, which is in the attacker’s saliva, enters the open wound created by the bite, moves into exposed peripheral nerves and then travels up inside peripheral nerves to the brain. The virus then multiplies in several areas of the brain of the new host, but particularly in limbic system structures such as the amygdala, hippocampus and pyriform lobes. The limbic system is known to control emotional behavior, including aggressive and feeding behavior and damage or experimental electrical stimulation of this area can lead to rage and undirected, unprovoked attacks. The greater localization and multiplication of the virus in the limbic system compared with the neocortex is apparently what causes abnormal behavior, including wandering aimlessly and attacking and biting anything encountered. While the virus is multiplying in the brain, it is also descending back down peripheral nerves including those innervating the salivary glands. The virus enters the salivary gland tissue and saliva. The nerves supplying the laryngeal and pharyngeal muscles are often affected as well and the ensuing paralysis of these muscles makes swallowing difficult. This causes pooling of saliva, and when the infected animal bites a new victim the pooled saliva is a reservoir of virus to be injected into the new victim. When transmission of the rabies virus does not depend upon abnormal viciousness for transmission, such as in vampire bats where the animals naturally bite each other rather frequently, or where the virus may be transmitted by the airborne route, abnormal viciousness for transmission from neurological alteration does not occur. In vampire bats the rabies virus reportedly does not necessarily produce acute death and may not be fatal.
from HART, B. L. (1990). Behavioral adaptations to pathogens and parasites – 5 strategies, Neuroscience and Biobehavioral Reviews 14(3): 273-294

Jessica writes:

Regarding the question you received in TWIV #70 about why a person might get a cancer-causing virus, such as HPV, but not actually develop cancer, I thought I might add a bit to your discussion. It is generally believed that 5-7 events are required for a cell to become cancerous. There are many checks and balances present in our cells designed to prevent the formation of wacky cells, and generally when a cell starts displaying bad behavior, such as uncontrolled growth, it will go through apoptosis. In the case of HPV infection, the presence of the virally-encoded oncogenes contribute to cancer formation by counteracting these checks and balances. However, infection alone is not sufficient for cervical cancer formation, and many cofactors have been demonstrated to contribute, such as age, smoking, parity (the number of times a woman gives birth), and other genital infections. Without such cofactors, the virus can lay dormant in the cells, causing no apparent disease. Additionally, as you mentioned, a large portion of HPV infections are initially cleared by the immune system.

Why do I know all this? Well, I did my graduate work on papillomaviruses–not the cancer part per se, but I listened to enough seminars on it to pick up this much at least. I have since moved on to work on flaviviruses, including (gasp!) West Nile virus. I am an avid listener of your show, it helps me through my daily public transit commute. Thanks and keep them coming.

Jessica
PS I also love TWIP, can I put my vote in for higher frequency here?

Sophie writes:

Still love your show, but I have a question about the discussion about viruses and their status: Why is it so important wether they are alive or not? I don’t think many people really know when something can be called alive and would it actually make a difference if it was alive? As far as I know it would not make a difference (it’s not like bacteria has rights), so why is everybody so interested in this question, when people cannot even agree on a definition of life?

Thanks for all the information.
-Sophie

Christine writes:

I was listening to podcast #69 today and was interested in the comments about mmr vaccine and it’s effectiveness wearing off over time. I am in Australia and being 35 I got 2 doses of mmr as an infant and a rubella vaccination at 13. At 25 when I had my first child my immunity to rubella was considered “equivocal” or something like that and so after her birth I was again given a dose of mmr. Before getting pregnant with my second I was tested again and was “eqivocal” again and given another vaccination (less than 2 years since my last). When I came to have my third child, same thing with a gap of three years. My best understanding is that although I have some immunity it is not sufficient for protection from this disease. My doctor was concerned about me returning to teaching high school while preg. Luckily I was probably not exposed in my first preg and was kept too busy in later pregs to fit in work and kid(s).

I wonder how many other people there are like me out there contributing to outbreaks.

Christine
Avid twiv and twip listener.

Kurt writes:

I’m surprised at how few comments there are on iTunes. I’ve been listening for a long time, and figured huge numbers of others listen too. I gave you a nice review, but don’t know how to twitter. I hope your next contest has rules suitable for a technophobe. I came to you from iTunes, and never got around to looking at your website. The contest got me there, and I really like some of the links. Good work.

Your podcast is pitched over my head, but like any technical topic, just hearing the words lead to some level of understanding. The jokes need some work. I sometimes feel punished. Overall fun to listen to.

I appreciate what you are trying to do with distance learning. I listen to podcasts as I drive around Florida selling paint. I enjoy science, and lately have been listening to Physiology lectures by Gerald R. Cizadlo, Ph.D. Department of Biology The College of St. Scholastica. Take a look at http://faculty.css.edu/gcizadlo/ his lectures are on podcasts, and he puts his blackboard notes up on his website. That’s what I’d hoped for in your Virology 101 classes, since they are too dense for idle listening. I expect you will get to putting up lecture notes sometime. I like the pretty pictures of viruses.

Thanks for your good work. If I knew some arcane question I’d ask it, but, well, I don’t.
Kurt

Gary writes:

Just in case you haven’t seen this yet: here is an article describing measurement of the driving energy released as individual bacteriophages inject genetic material into bacterial hosts — I.e., the kinetic energy driving the process has now been quantified!!

http://pda.physorg.com/_news184588836.html

All the best,
Gary
PS: Again thanks for all your instruction. Your enthusiasm for, and love of virology is – without question – infectious.

Subbaro writes:

It was a good program on Reverse transcription of retro viruses. At least in a simplified way most of the aspects of it were explained. I would like to add that in addition to Cauliflower Mosaic Virus (CaMV), a plant Pararetrovirus of caulimoviridae, there are 20 different plant viruses belonging to BADNAVIRUS (Bacilliform virus with a dsDNA genome) group which show (para)retrovirus characters. Half of them are fully characterized now.

The following: Banana streak virus (BSV); Cacao Swollen Shoot Virus (CSSV); Citrus yellow mosaic virus (CYMV); Pineapple bacilliform virus (PBV); Rice tungro bacilliform virus (RTBV); Sugarcane bacilliform virus (ScBV) are economically very important viruses, especially RTBV which is associated with tungro disease of rice causing loss of millions of dollars. RTBV along with RTSV (Rice tungro spherical virus) a picorna virus produces lethal symptoms

Thanks
Subbarao

Jaturong writes:

I am a Thai doctor who is now doing Ph.D. study in Molecular Virology and Microbiology program at Baylor College of Medicine, Houston, TX. I know the show year ago from my fellow graduate student who sent out an e-mail to recommending TWiV to all students in our department and since then, I have become a big fan of the show. I am working on a mouse model system using mouse gammaherpesvirus to study the role of promyelocytic leukemia nuclear bodies (PML NBs) as host intrinsic immunity in acute infection and viral latency and the mechanism that the gammaherpesvirus uses to counteract these nuclear bodies.

Everything relates to viruses is always interesting to me, so I love every topic that has been discussed on the show. The show also encourages me to keep on working on my experiments even on days that things in the lab seem not to turn out as I expected. I also use the questions asked in the show to test my knowledge about virology by comparing mine with yours and the show’s guesses and I realized that there are many things I am supposed to know but I do not know. I do not have specific virology question right now but just wonder how do you manage your time to keep update of all virus-related articles and news, teach in classes, projects in lab, recording TWiV and response to those e-mails? After I graduate, I will be having my own lab and teaching virology in the medical school in Thailand as well.

Thank you for having a fantastic show for us and please keep it up. I really appreciate your input to educate people about viruses and am always looking forward to the next episode of TWiV.

Regards,
Jaturong

TWiV 71

Jennie writes:

I wonder whether we have entered a new chapter in the book of human knowledge sharing. I’m often working physically when I listen to my favorite science podcasters (TWIV, TWIP and Mark Crislip)…. so your entertaining program is intertwined with raking leaves, loading wood, washing dishes (but NOT vacuuming). I hope that learning and moving can be merged in this decade through a more thoughtful use of tech.

I love the unveiling of your subjects over the course of time…the interaction of the two of you is very important in peeling the layers…both of you ask each other good questions and your model is VERY important – neither of you is afraid of appearing ignorant by either asking questions or not knowing an answer.

Other aspects that you are modeling: the power of synergistic professional/personal friendship and the sublimation of professional rivalry that can humanize science and extend knowledge boundaries.

For years as an RN I’ve taught health care to people with a high school education (maybe not HS sometimes)…the wedge (or funnel?) of narrative is by far the best way of getting the information into their skulls. Stories, pictures and practice actually.

Your stories are the best!

Take good care of yourselves: walk where you want to go this year, eat more vegetables, have fun in the physical world and….GO GET EM IN 2010!

Your listener
Jennie

TWiV 70

Tom writes:

I just finished listening to the Original Antigenic Sin episode where you were talking about Wolbachia’s protective effect against virus infection in Drosophila. I was delighted that you were speculating about the effect in bees because Wolbachia has been one of my favorite subjects for years.

Some key things to know is that:

1. Beekeepers have used (overused) tetracycline routinely since I think the 1950s against a bacterial disease of the brood called American Foulbrood. This usage has almost certainly cleared any Wolbachia infections in domestic bees, if they once had it. Interestingly, we now have developed bees that are resistant to that disease, which make antibiotics unnecessary, though unfortunately they are still widely applied.

2. Wolbachia has been found to be very common in African bees (but only in Africa) in at least two subspecies. One of these races, Apis mellifera capensis, has the unusual trait of worker bees producing diploid (female) offspring parthenogeneticaly, possibly due to an effect of Wolbachia. Our European workers can only produce haploid offspring, which are always male.

3. Another well studied Wolbachia effect is something called cytoplasmic incompatibility. This can result in sperm produced by infected males killing eggs of uninfected females. Infected females on the other hand produce viable offspring using either infected or uninfected sperm. This gives infected females a huge reproductive advantage. Wolbachia is very selfish, and since it is passed on only maternally, in the cytoplasm the egg, it uses the genetically dead end male to kill off the competition.

My own pet hypothesis is that this could explain how descendants from 26 African honeybee queens released in Brazil in 1956 were able to make a nearly complete genetic sweep all the way to the southern US. Supporting evidence for this hypothesis is still lacking, since Wolbachia has yet to be found in this hemisphere, we are actively looking though. If found, it could be very useful not only for the possible protection from virus, but also for driving good genes into the population.

A person who we are working with to find Wolbachia in bees is David Schneider at Stanford. Here’s a quote from his article in Science last year,

“One might guess that an insect would be safe from having its microbiota altered. Honeybees are an exception, however, because we’ve been dosing commercial colonies of bees with antibiotics for decades. Before the rise of colony collapse disorder, one of the most important honeybee diseases was American foulbrood, caused by the bacterium Bacillus larvae. To deal with this threat, many beekeepers prophylactically treat their hives with tetracycline derivatives—the same antibiotics used to cure flies of Wolbachia. If these treatments cured queen bees, then all hives descending from these queens would also be Wolbachia free, because the microbe is transmitted maternally. A Wolbachia-virus sensitivity experiment may have already been performed on honeybees nationwide and may change the way bees interact with previously characterized pathogens.”

I find you and Dick brilliant in the way you come up with great ideas on the fly. It’s a pleasure to listen to such intelligent people bounce ideas around. Thanks for such interesting program.

Sincerely,

Tom

TWiV 60

Eric asked for “advice on how to bridge the gap between clinical medicine, public health, and virology research.” I asked Scott Hammer MD for his thoughts on this question. Here is Dr. Hammer’s response:

Hi Vincent:

Thanks for forwarding this comment. In response, I’d inform your interested listener that the career opportunities in Infectious Diseases are broad and include – fundamental laboratory research, clinical/translational research, clinician/teacher role at an academic center, epidemiology and public health (both domestic and international), private practice, and industry. A substantial proportion of Infectious Disease Fellows are pursuing Masters degrees in Epidemiology at their colocated Schools of Public Health so that they have formal training in both ID and epi/biostats/study design/global health, etc. For more information, I’d refer him to the following websites: the Infectious Diseases Society of America (www.idsociety.org), the American Society for Microbiology (www.asm.org) and the Association of Schools of Public Health (www.asph.org). In addition, he could surf the websites of some of the individual fellowship programs (Columbia, Partners (MGH and Brigham in Boston), Johns Hopkins, the University of Washington in Seattle, and the University of California San Francisco.

Hope this is helpful.

Best regards,

Scott

TWiV 59

Nick writes:

I’m a bit behind in my Twiv listening, but I’d like to comment on something you said in Twiv 47. You have reminded us several times in the past that “viruses are not alive” and you embellished on this during Twiv 47 by saying that if they are not alive, they can’t be killed. Actually, viruses can be killed, by treatment with formaldehyde or chlorox, boiling, or irradiation with x-rays or UV light. These are commonly-applied treatments that “kill” viruses. Were they alive before having been killed? Perhaps that is just a semantic question, but it seems to me that you cannot kill something that is not alive!

I think there may be some confusion in our minds about what a virus is. We most often think of viruses as being the virus particle, or virion, which carries the viral genome, wrapped in a protein and sometimes a lipid coat, from one cell to the next. This looks inert and not living. But this is a bit like saying that an oak tree is an acorn, or a sunflower is a sunflower seed. Viruses actually exist not only in the form of virus particles, but also in their intracellular forms, during which they carry out the many intricate and complex activities that lead to their reproduction. Sure enough, they need lots of things that cells provide, including energy, the machinery that makes proteins, and basic building blocks such as amino acids and nucleotides. But if you mean that “being alive” implies coding for those proteins and RNAs needed to synthesize proteins, produce energy, and make amino acids and nucleotides, this becomes a bit of a techical argument.

What about other “obligate intracellular parasites” such as chlyamydia and rickettsia? They can only reproduce inside cells, in part because they cannot synthesize certain amino acids and nucleotides. These organisms do make their own ribosomes and protein-synthesizing machinery, and reproduce by cell growth and division once inside an appropriate host cell. But are chlamydia elementary bodies (the infectious form that transports the chlymadia genome from cell to cell) alive? Are acorns and grains of wheat alive? The answer is yes, because they can reproduce under the right conditions; within certain cells, for chlamydia, and under certain conditions of humidity and temperature, for acorns and grains of wheat.

I argue that viruses are just as alive, simply that they have less of the equipment of life and depend more strongly on the host cell to provide this equipment. The recent sequencing of the genome of a monster virus, mimivirus, as well as the genomes of a number of other big viruses, brings viruses even closer to cellular life. Some of these viruses have more DNA and more genes than the simplest forms of cellular life. Mimivirus has genes for amino acid and nucleotide metabolism and for some parts of the protein-synthesizing machinery (but not ribosomes or energy production).

At any rate, I’m not comfortable with the notion that viruses are not alive. They are certainly part of the “biosphere” of living things. They share with other organisms the basic mechanisms of replication and expression of their genomes. They can reproduce themselves (with a little help from host cells), control many cellular processes, and undergo mutation and Darwinian evolution. Viruses have sex: they can recombine or reassort their genes. They can even have sex with cells, in both directions: viruses can insert their genomes into the cell’s genome, and they can pick up genes from host cells and integrate those genes into the viral genome.

Viruses may have originated from cells, or alternatively could have played a role in the origin of life, before cells as we know them existed. RNA viruses and viroids may even be evolutionary relics of the RNA world, which is thought to have preceeded the present world in which all known cellular organisms have DNA genomes. DNA viruses could have played a role in the transformation of cells from RNA to DNA genomes, by having introduced DNA genomes into RNA-based cells. For a fascinating argument in favor of this theory, see “Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domains” by Patrick Forterre [PNAS March 7, 2006 vol. 103 no. 10, 3669-3674].

If you can kill it, it must have been alive!

I just listened to Twiv 48: your further discussion of this topic was interesting but sort of stalled. I got the impression that Rich agrees with me!

TWiV 57

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TWiV 56

Joe writes:

TWIVERS,

Guys, what a great podcast. I am a chemical engineer with a MS in Environmental Management. I have been doing EH&S work in industrial settings for about 20 years after some years in R&D and manufacturing positions. I have always had a strong curiosity for all branches of science (physics, astronomy, electronics and biochemistry), as well as math and history. Emergency response and risk communication functions have always been part of my job over the years. Virology was relatively new to me when I found your podcast. I had spent quite a bit of time learning the state of the science related to avian flu and SARS so that I could gauge the level of preparedness my company should have for responding to a pandemic. I eventually concluded that we needed a plan and should be ready but that the H5N1 virus had some ways to go before it became a general threat to humans. That research had left me with an interest to learn more of the broader field of virology. When H1N1 hit this year in Mexico, I found your topical podcasts very helpful.

I have been rapidly catching up on your episodes as I drive (about 1 episode per weekday) and will be sad when I am forced to slow down to real time speeds. I don’t suppose you all have considered doing “Today in Virology” so that I will have a new episode each day!!!

To the point:

I strongly agree with your assessments of the limited value of face masks with respect to providing protection from airborne flu infections. Actual user practices leave many infection pathways open. Beyond just not getting a good seal, how do you train users to remove the mask without contaminating their hands and face. If you reuse the mask which would be necessary in an emergency, how do you keep the inside clean. When do you wear it and when do you take it off? I train people to wear respiratory protection in accordance with the OSHA requirements for fit testing, medical surveillance, industrial hygiene testing, etc. It will not be easy to translate those practices to an untrained inexperienced population.

I agree with Dick that the whole “hot and humid stops the spread of flu” dogma seems inconsistent with the facts. How do we know that flu does not show up in human stool? Do we have actual data? In Asia, could the transmission mechanism be airborne particulate avian feces? Could the reason the pandemic strains violate the seasonal rules be a function of increased intestinal transmission or conversely that their envelopes are more robust in withstanding environmental stresses? The great thing about science is that the more we learn the more questions we generate.

With respect to the study on flu transmission and absolute humidity, If I heard you correctly when you quoted the summary hypothesis of the paper, the authors proposed that the aerosol droplets float longer when dry. This set off my engineering “I doubt it” alarm! So I spent some time reviewing the basics of psychrometry and humidification. I have a new theory on why low absolute humidity correlates with transmission. I think the critical parameter is actually droplet temperature. Droplet temperature will be controlled by the Wet Bulb Temperature for any set of conditions. Wet bulb temp is the temperature of a wetted surface that is experiencing steady state evaporation into the local air conditions. The lower the Relative humidity, the faster the evaporation and more heat lost resulting in a cooler surface. Think swamp cooler in Phoenix vs. New Orleans. Let me give some data to elucidate:

(All data interpolated from Figure 12-2 of Perry’s Chemical Engineering Handbook 5th edition)

Take a volume of air with an absolute humidity of 30 grains of H2O per pound of dry air. (7000 grains = 1 pound) Sorry for the units, but I think in Fahrenheit!

@ 35 F = 100% Relative Humidity (RH) and the Wet Bulb Temp. (WBT) = 35 F (i.e., No cooling by evaporation)

@50 F = 55% RH WBT = 43 F

@80 F = 20% RH WBT = 55 F

As long as the absolute Humidity is low, the particle temperature will stay low until it dries out. In higher humidity, there will be little evaporative cooling and so a higher droplet temperature will be reached more quickly. My amateur virologist guess would be that the lipid coating has an upper temperature limit beyond which it loses strength and/or integrity. At higher temperatures and higher humidity the particle temperature gets too high for the virus to survive shear stresses related to contact with surfaces. In engineering terms it doesn’t bounce well if it is too hot! This would also be consistent with avian transmission routes via cold water bodies. I would expect drying rates at higher temperatures with low RH to be much faster and once the particles dry, their temperature would equilibrate to the bulk air temperature. This would be consistent with the data showing reduced transmission at higher temperatures. Do we have any data that would indicate if dried viruses are still infectious? The physics of these small particles is not straightforward. Also, none of this addresses how the properties of spit differ from pure water. If there is someone out there with the experience and the computer power, this could be an interesting research topic. Please include me in the Et. Al. part when you publish.

A couple of recommendations:

A great website for non biochemists wishing to understand the basics of DNA and RNA is DNAi.org. Great history, clear explanations and the coolest videos of translation and replication I have ever seen! When you watch an animated ribosome at work it makes you proud to be a DNA based life form!

A book for Dick: “The Great Mortality” by John Kelly; “An intimate history of the Black Death, the most devastating plague of all time” I found this when researching H5N1 and was struck by how it captures the social and environmental influences on the development of the plague and then the impacts of the plague on societies and their reactions. It puts some of the current responses to swine flu in perspective.

Future Topics:

Why all the differences in nucleic acid structures within viruses? What are the pros and cons of ssDNA vs. dsDNA vs. ssRNA+ vs. ssRNA- vs. dsRNA?

How does an encapsulated virus survive in the digestive system? My vote is for Hydrogen Bonding (the universal answer for all chemistry exams!)

Dick’s list of top ten vectors throughout history.

How and why retro viruses change our DNA. What’s in it for them? (yes I know I think they are alive!)

How about a session on rhino viruses since we can all relate to their impacts. Why so many, are the different strains new each year or just new to me, etc.?

PS. Doesn’t the Zoster vaccine qualify as one you take after infection like rabies?

Love the show and the latent humor

Joe

TWiV 55

Kevin writes:

Dear TWIVvers,

I was listening to TWIV episode #50, concerning the recent article from Ila Singh’s group about the prostate cancer – XMRV connection, on the same day the NY Times reported a study from Judy Mikowitz et al., finding an association between XMRV and chronic fatigue/immune dysfunction syndrome, aka CFIDS. The CFIDS story has been getting even more attention, due in part to the eagerness of patients and advocacy groups to contradict the common stereotype of CFIDS as a psychosomatic illness – what some people used to call the “yuppie flu”. I have no doubt that CFIDS is a “real” physical illness, and that it involves some kind of chronic infectious process; but as a computational biologist and professional skeptic, I suspect that the relationship between XMRV and disease is *much* more complicated than the people reading these stories are likely to believe.

Although the Singh and Mikowitz groups found strong evidence that prostate tumor cells and peripheral blood cells from CFIDS patients were more likely to harbor XMRV than controls, it’s still premature to assert that XMRV causes cancer or CFIDS. It’s equally probable that patients with both diseases have an immune deficiency, due to genetic or environmental factors or an infection with some *other* agent, that allows the virus to proliferate. Even if XMRV can be said to “cause” one or both of these diseases, the question remains: what is it that allows the virus to establish a foothold in some people but not others? This is of course something we understand poorly, for almost all viral pathogens, including your beloved poliovirus.

So I was intrigued when your guest Jason mentioned a mutation in RNAse L that he said was present in a large fraction of the prostate tumors, that could make the cells more susceptible to viral infection. I went online that night to look up the Singh and Mikowitz papers, and find out if the RNAse L mutation was found in the CFIDS patient’s cells also. It wasn’t – but as it turned out, Ila Singh’s group didn’t find the RNAse L association either. This was a larger, better controlled study than the 2006 paper from Joe DeRisi’s lab that did find the association, but I still have to wonder how the two groups came up with such diametrically opposite results. Any comments on this?

Also, I suspect I wasn’t the only listener who was confused by Jason’s statement that the mutation was found in the tumors, and thought this meant either that the virus was causing the mutation, or that the mutation was specific to the tumor cells. Since most listeners aren’t going to run home and read the original papers, perhaps you could clarify: the mutation we’re talking about is a variant of the RNAse L gene that some prostate cancer patients are born with and is a possible susceptibility locus – not something that’s specific to malignant tumor cells.

To end on a more positive note – I’ve been listening to TWIV for a few months now and have recommended it to many of my friends and colleagues. It makes my 45-minute commute to Livermore seem to go by in no time at all. I have lots of ideas for podcast topics – for one, it would be great if you did an episode focusing on viral strategies for evading our immune response. I would also love to hear your ideas about iPhone apps for virology research; I feel it’s really important to have ways to visualize and manipulate biological data that are both intuitive and beautiful. Thanks for all your hard work on the podcast.

Ben writes:

Hi,

I am not a scientist, researcher, or health professional, just a closet science-nerd who loves your show. I just had a few questions about viruses that I can’t seem to find answers for that I was hoping you could answer.

Are there virus-receptors on cells themselves? If so, why would a cell evolve a receptor to something harmful? How did viruses evolve in general if they kill off their hosts, that certainly couldn’t be a beneficial trait right?

How are viruses so infectious and damaging when they are merely an envelope of genes? Since they aren’t alive like bacteria I can’t imagine why they would exist just to kill things. The same goes with prions. There can’t seriously be an “infectious protein” can there? Proteins are just amino acids folds.

Hope you can answer some of these either by email or on your show. Thanks a bunch!

TWiV 48

Rodney writes:

Hello, I have been an avid listener of TWiV over the last 9 months or so and have very much enjoyed the podcast. It is always great to hear a broad, informed discussion on virology, and your recent podcast on viral classification was of particular interest to me. As a Viral Genome Curator at the National Center for Biotechnology Information (NCBI), I am currently working with the International Committee on Taxonomy of Viruses (ICTV) and several virology research communities in an attempt to address longstanding and emerging issues of viral classification. Your podcast provided a concise primer to this topic, but I thought it worth mentioning a few additional issues.

First off, all viruses are classified by nulceic acid, dsDNA, ssDNA, dsRNA, ect…, both by NCBI and ICTV. Although these divisions are given no rank, they provide functionally relevant handles with which to globally group viruses. Second, the way in which viruses are classified is somewhat variable. You might be surprised to know that despite developments in genomics, many viruses are still classified by morphology, using electron microscopy. This is particularly true of bacteriophages, and NCBI and ICTV are working hard together to develop more portable, computer based methodologies. However, it is worth noting that even when computational tools such as Blast and PASC are used to classify viruses, the line of demarcation that separate different “organisms” vary widely amongst different viral families. This variability may actually be a good thing as it allows different research communities to tailor taxonomy, making it more relevant to a specific group of viruses.

Perhaps the more pressing issues in virus classification arise as the traditional, isolate, passage, and physically characterize approach to viral discovery is altered by modern molecular techniques. In the past, viruses have been characterized by a number of criteria including host and disease. Yet, the proliferation of environmental sampling, emerging direct sequencing methodologies, and a greater appreciation of the broad host range of some viruses, creates a number of classification problems. For example, how does one know if a novel candidate genome gathered from a sewer or a biopsy is actually a virus? And for that matter, how does one know that the sequence at hand is a full-length, fully functional viral genome? The relevance of these questions grows every day as databases are filled with an increasing number of novel “genomes” obtained through these methodologies.

Of course, these direct sequencing projects do have a number of advantages. There is no need to passage the prospective viruses over host cells, so there is no laboratory adaptation to a particular cell line. Such open ended approaches also recover multiple isolates from a single sample, allowing one to track naturally occurring genetic diversity, and it is likely that the proliferation of new techniques, combined with good old fashion bench work, will fundamentally change our view of viral evolution and adaptation.

Take care and keep up the good work,
Rodney

Elliot writes:

The International Committee on the Taxonomy of Viruses (ICTV) web site at www.ICTVonline.org provides access to a database of the current taxonomic classification of viruses as well as the definitions and guidelines used by the ICTV to make the classification. The taxonomic ranks used to classify viruses are the Order, Family, Subfamily, Genus, and Species. (There are 5 orders currently recognized: the Caudovirales, Herpesvirales, Mononegavirales, Nidovirales, and Picornavirales.) All viruses are classified into species (including plant viruses), and investigators who study every recognized virus family are represented on the study groups that participate in the classification process (including plant virologists).

A viral species as defined by the ICTV is:

“… a polythetic class of viruses that constitute a replicating lineage and occupy a particular ecological niche”. A “polythetic class” is one whose members have several properties in common, although they do not necessarily all share a single common defining property. In other words, the members of a virus species are defined collectively by a consensus group of properties. Virus species thus differ from the higher viral taxa, which are “universal” classes and as such are defined by properties that are necessary for membership.”

Note that Poliovirus is no longer a species! It has been renamed Human enterovirus C.

As for how “different” a virus isolate needs to be to create a new species, this varies according to the virus family and varies especially according to the genome composition (DNA viruses vary much less than RNA viruses). Each ICTV Study Group provides species demarcation criteria specific for each virus family that define the criteria for establishment of a new species for that family.

Thanks for providing the opportunity for clarification. Love the program!

TWiV 47

Jesper writes:

Dear fellows of Twiv,

It is my understanding that us humans live in peace and symbiosis with some bacteria. Is there any such arrangement with any virus?

Another way to phrase the question; if all viruses were to be removed from the world, would we be better off?

A follow-up question, even more abstracted from the lab bench; if all viruses were gone, is it reasonable to believe that new ones would come into existence? How fast? From where? In one of the twiv episodes someone said “Any suffciently complex system has parasites”, so I assume given time something is bound to fill the niche of viruses.

All the best,

Jesper

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