Robin writes:

Dew points:

Oldest rodent

From the Wikipedia:

Evolution and History

“The fossil record of rodent-like mammals begins shortly after the extinction of the non-avian dinosaurs 65 million years ago, as early as the Paleocene. Some molecular clock data, however, suggest modern rodents (members of the order Rodentia) already appeared in the late Cretaceous, although other molecular divergence estimations are in agreement with the fossil record.[18][19] By the end of the Eocene epoch, relatives of beavers, dormice, squirrels, and other groups appeared in the fossil record.”

Human transferrin receptor evolution:

If viruses latched onto the active site, wouldn’t they be killing the goose that laid their golden eggs? Hence no such geese are found because they die off quickly? Perhaps a corollary to the Anthropic principle?

Asian human arenaviruses not found in spite of the variation in their transferrin receptor: maybe the fossils are present in the genomes?

Viral diseases of trees

Again, if viruses wiped out trees, then those trees wouldn’t be around: the Anthropic principle again. Also, a tree has much more internal autonomy of its parts than animals. If one part is killed off, other parts might survive; beneficial mutations could be selected for within regions of the tree itself.

Dickson may no longer be a cash cow, but when it comes to information and ideas, he’s a stud bull.

Running backward (as suggested to the uSN MSC officer in letters) is actually a valid sport:

Backward running

Why is there only one species of humans?

The hominin lineage (the lineage leading to humans after divergence of the lineage leading to chimps & bonobos from the common hominid ancestor) has had almost two dozen species, depending on whether one is a lumper or splitter. Even more recently, there has been many members qualifying for the genus Homo: habilis, erectus, heidelbergensis, neanderthalis, denisovanis, and the TWIV team. The last two extinct species have actually been our contemporaries for most of our 200,000 years. But they did not display the rapid innovation and improvement in tools and implements that characterised us since our migration out of Africa about 50,000 years ago. Innovate or perish.

Prior to more complete gene sequencing, the Neanderthal branch was studied on the basis of mitochondrial DNA and seemed to have no overlap with humans. Since mitochondrial DNA is matrilineally inherited, it means no Neanderthal ladies were imported into the human tribe. However now that we know that some Neanderthal DNA was imported into our tribe, it would have been through our ladies.

Checking Email functionality:

One way to check if one’s email accounts are functional would be send an email from one’s gmail to one’s yahoo mail or hotmail or account or the other way around.

DJ writes:

Dear Vincent Racaniello and TWIV co-hosts,

May I point to a section of your podcast group discussions on TWIV# 242, “I want my MMTV”?

The dialogue I refer to sounded like a digression into political hysteresis and pseudo-scientific proselytizing. I focus on the discussion revolving on autism and vaccination. The listener was treated with an iconic ad hominem attack on a celebrity who’s apparent crime is apparently to have a disagreement with the scientific majority as it concerns the immunization/vaccination controversies of the notable recent past.

Acting as scientific authorities, a few TWIV members took turns publically diminishing a celebrity named Jenny McCarthy. For example, we were told that she was a “Playboy Bunny” and had other dubious credentials prior to becoming a spokeswoman for requesting investigation on the link between autism and commonly administered immunizations/vaccinations against certain disease causing agents; especially in young children.

While Ms. McCarthy’s employment history may be a matter of public record, I see no justification to initiate what sounded like a verbal assault on her by front-loading information meant to diminish her activities concerning a controversial issue. This is a political tactic if I am not mistaken. Certainly not a leading scientific approach when discussing research controversies even when the public gets involved.

Whatever the intentions of the podcast crew members may have been, this publically offered discussion could have benefited from editorial excision prior to broadcast.

Rather than acting even-tempered and open-minded, certain members of the TWIV podcast seemed to suggest they found Ms. McCarthy to be at best a “zealot” as this term was used pejoratively to define a person who believes in something the majority find absurd. At least this was the interpretation I made while cringingly listening to the tirade against this woman and her opinions.

While I will not weigh in on this controversy in this email, I will stand on scientific historical grounds by admonishing others for allowing emotions to rule over rational judgment.

However, I will offer that whatever the scientific literature says on this subject, it will remain an open question whether the practice of sweeping vaccination/immunization has an epigenetic effect on the human population.

Finally, it comes as an unfortunate result that members of the scientific community make the decision to transition from hypothetico-deductive experimentation to seemingly dogmatic hyperbole in the public domain.

These are my personal opinions and do not necessarily reflect any other faculties of reason I may or may not possess and/or chose to articulate in this correspondence.



Martin writes:

“The best data indicates that vaccine induced chronic disease is now of a magnitude that dwarfs almost all prior poisoning of humans including poisoning from agents like asbestos, low dose radiation, lead and even cigarettes. Most patients don’t even realize that they are suffering from the adverse effects of vaccines. Even more concerning patients and or their parents are being harassed, accused of practicing poor dieting and exercise habits leading to development obesity and diabetes when in fact they suffer from vaccine induced obesity and diabetes,” says Dr. J. Bart Classen.

David writes:


I’ve been listening to TWIV now for perhaps 8 months, and have listened to the last 150 TWIV podcasts on my long commute. I really enjoy the show, and have learned a lot from it. I’m a practicing pulmonary/critical care doctor, so I have considerable interest in infectious disease. I was also impressed with the role of viral disease in my specialty when the H1N1 pandemic swept through my area.

My podcast application uses feeds to organize and download podcasts. Now that I want to listen to the first 100 TWIVs, I’m stymied as I can’t find a feed that includes them. I’ve noticed that some long-running podcasts have static archive feeds for the older shows so that the main feed doesn’t get too long. For example, archives for 2008, 2009, etc. I think this would be a good addition to TWIV, so that those who want to listen to the older shows can get ready, organized access to them.

Keep up the good work.


Robin writes:

Hey guys!

First off I would like to say I enjoy your podcasts greatly and I want to thank you for putting them up! And then I just have a question on going into virology.

So I’m 16 and I will be a junior in high school this upcoming school year. I was dead set on becoming a marine biologist until recently. And now I’m really into microbiology. It started freshman year in my biology class when my teacher showed us a movie on Ebola. I fell in love instantly, as terrible as that sounds. I was disgusted and awestruck. I wanted to know more. Then sophomore year I made a game and wrote an essay about the “Black Death” for extra credit. I wanted to do my second semester extra credit assignment on Ebola, but sadly didn’t have the time. And this summer I started to read books about viruses and became extremely interested and started listening to your podcasts.

As I’m getting closer to graduation and going into college, I was wondering what kinds of classes I should take while I still can in high school (I’ll be taking AP Biology, physics, AP Calculus AB, and honors English next year along with US History and orchestra). And what kinds of things I should look for in college and what I should major in.

I planned on going to the school in my town, University of Alaska Fairbanks, because they have a great marine biology program, but they don’t have microbiology. So I’m assuming that isn’t a good choice.

Also any other advice you could give me would be great!

Thank you so much!

Shelby writes:

I have no Virology background but have gained so much information and understanding (I Hope) from listening to your podcast. As you can see I’m still working my way through back episodes but I do really enjoy it.



Indianapolis, IN

PS I always listen till the end of the episodes which prompted this email.

Robin writes:

TWHIV Vaccines

Attempting to mobilise the immune system against HIV in conventional ways is offering them lunch meat. Trying some kind of an evolutionary end run might be more interesting, particularly so since we have to live in interesting times.

A starting point may be the comparing of retrovirus fossils to their extant kin with a view to seeking some insight into the ways in which they are accommodated by their hosts. Would a fossilised HIV work? If it would, how could it be incorporated into the human germ cell line?

Joe writes:

Kathy, et al.

Had to laugh at Vince’s digression into the food value of placentas since I had recently listened to two episodes on the Moth Podcast in which a father agonizes over the politically correct answer to what to do with this emotionally charged organ. Not much biology involved but very funny and well worth a listen!

As always love the shows,

Warmest Regards,


Robert writes:

I have just finished listening to episode 245 and decided I needed to let you know how much I enjoyed it. I am a retired Ph.D biochemist/immunologist and I finished my doctorate in 1975. I met my wife at U.C.L.A while I was a postdoc and my best man at our wedding was Martinez Hewlett who was a postdoctoral student in David Baltimore’s lab beginning in 1974 to 1977. Marty and I were graduate students together at the University of Arizona College of Medicine Dept. of Biochemistry in Tucson. Marty returned to the University of Arizona and continued to do research on a number of different topics in virology. I spent 8 years at U.C.L.A. as a faculty member in the Dept. of Neurology where I did research in M.S. and human immune regulation in autoimmune diseases. I left academia and spent the rest of my career in industry.

I had to smile during the discussion about Luria’s text as I could see my copy of the book on the book shelf next to my desk (although it is a later edition with Baltimore, Darnell and Campbell as coauthors). I just purchased the latest edition of Principles of Virology and I am looking forward to reading it as I am also taking the Coursera Virology course. I agree completely with the philosophy of teaching Virology from principles rather than on a virus by virus basis.

I’m glad to hear that the next version of your book will include an electronic version.

Thanks again for taking the time to do the TWiV podcast.

Yours truly,

Robert Kelley, Ph.D.

Renato writes:


I’m sure you heard the news, the NIH and the Lacks family reached an agreement about how to proceed regarding the HeLa genome.

Some links:

The “NIH Director’s Blog” has the more concise summary I’ve found:

“We have agreed that NIH-supported researchers will deposit any DNA sequences derived from HeLa cells into NIH’s dbGAP database, and have established a process through which researchers can request controlled access to that data. Such requests will be reviewed by a working group consisting of physicians, scientists, a bioethicist, and two members of the Lacks family.”

If you take some time to drill these pages for their links, you will find some documents defining the working group, the general rules of requesting access to the databases and the “Special Instructions”, which seem the more interesting ones:

There are a couple of things in these instructions which I think are noteworthy, especially if this agreement ends being used as precedent in the future. I transcribed some excerpts below.

“Studies of ancestry or population origins are not permitted.”

“[…] researchers must agree […]” “To state whether the research is intended or could be reasonably expected to result in a patent or commercial product or service […]”

“[…] researchers must agree […]” “To respect the privacy of the family members of Henrietta Lacks by not attempting to contact them.”

“[…] researchers must agree […]” “To recognize the contribution of Henrietta Lacks […] including […] an acknowledgement when reporting or presenting scientific findings based on the HeLa genome data.”

Finally, the item “Approval Process” says that the working group reports their conclusions to the ACD and the ACD makes recommendations to the NIH Director. (Googling “nih acd” indicates ACD means “Advisory Committee to the Director”).

I find these rules quite reasonable, but I’m not a researcher trying to get funded by NIH. What do you think?

Almost forgot: Weather in São Paulo is mild ranging from 13 to 28 C. We haven’t had rain for a couple of weeks, so humidity is very low and pollution is high. Beautiful “heavy metal” sunsets.



David writes:

Vincent, et al.

My family was recently hit by a gastrointestinal illness that I think was Norovirus. We visited relatives who just had an acute gastrointestinal illness with prominent vomiting. 3 of 4 of our relatives developed vomiting which subsided after about 24 hours. After one day of intense contact our 6 year old developed vomiting all evening, and then two days later our 11 year old developed vomiting illness too.

I, a 45 year old man, had rumbly tummy (medical term borborygmi), and felt feverish at the same time that the 6 year old had his vomiting. But I had no major manifestations of gastrointestinal illness. No vomiting and no diarrhea.

Overall, it seemed like a Norovirus outbreak. I had some immunity, but my children didn’t have enough to stave off illness. During episodes of cleaning up vomit, this led me to have endless ruminations about Norovirus, and perhaps one interesting insight.

Norovirus is incredibly contagious. One spews, what, 10^11 particles per ml in vomit? As little as 5 particles are infectious. There are many serotypes, and immunity is waning after months. Then why aren’t we always infected almost continuously?

A theory: the virus is persistent in the environment. The CDC states how hard it is to eradicate it. They recommend steam treatment of textiles, and chlorine treatment of hard surfaces. In practice, very few virus particles are destroyed this way. Maybe the reason that people have long term resistance to any given serotype is exactly this persistence. After an acute infection where someone in the family spews virus everywhere, it persists, but everyone in the environment develops short term immunity. This immunity is then reinforced every time one ingests a few virus particles from the environment. Hence a laboratory one time exposure results in short-lived immunity, but in the real world, an infection leads to constant immune enhancement until the final viral particle decays in the environment.

This theory could be developed into experiments. That is, do organisms sustain immunity with repeated low level exposure? If so, what does this imply about disease control?

Perhaps the best vaccine for such a virus is to apply an attenuated multivalent virus to people continuously, say every year at a doctors visit. Or even better, to spray this multivalent attenuated virus around the home so everyone picks up some virus particles over the next 12 months, and hence maintains constant immune surveillance for the virus. If not the home, how about the doctor’s waiting room? This strategy might not be popular among the anti-vaccine woo-woos, but I’m doing theoretical science here.

If this theory is true, it implies that the virus is playing off the low chance of infecting a previously infected host with the chance of infecting a new, naive host. Doesn’t this have implications for disease control?

What thoughts have you, oh virus gurus? I’ve had this bug in the past, and I grow weary of it. It kills few (though I’ve seen at least one critically ill patient who started with it), but it makes many miserable. I’d like to take advantage of its evolutionary strategy to defeat it.

Dave Risher, MD

Stephanie Karst replies:

Where to start?! Brilliant ideas and I do think there is something to the continual exposure inducing some level of protection – people shed virus for weeks after their symptoms resolve so even if they are not persistently infected in the classical sense they are surely seeing virus antigen for prolonged periods. The biggest problem with the questioners idea is that noroviruses evolve so efficiently that presumably antigenically distinct strains arise frequently. So yes the vaccine formulation will have to be multivalent and frequently remodified. This is the hope with VLP based vaccines in clinical trials. The other issue of note is that we can’t generate attenuated vaccine strains because no cell culture system. That is my short answer :).

Judson writes:

TWiV folks,

(This was originally posted to Vincent’s virology Coursera forum, but after a week or so I figured I’d send it out to TWiV as well)

First of all congrats to Vincent on the ASV news! Also, of course I’m not a virologist (I just recently got into TWiV on the advice of a friend who is), so I apologize in advance if this question is known or obvious. In TWiV 243, if I understood correctly, Christiane talked about how difficult it was to get Norovirus to infect human cells, and how the immunity to norovirus fades in 6-12 months. However, I didn’t hear (or may have missed) any discussion about how the virus interacts with the human microbiome. So my question – is it possible that norovirus co-infects (or even primarily infects) the gut microbial cells instead of focusing on human cells? That might explain the fading immunity over a year, since I could imagine that the human microbiome population would turn over fairly quickly. That also might help explain why different people are immune to different strains of norovirus, since the microbiome varies so much from person to person. On a more general level, even if I’m way off base with norovirus, are there other known viruses that are zoonotic from bacteria or protozoa? I assume that must be a very difficult jump due to the large difference in host genotype, but given the sheer numbers and statistics I could imagine it might happen.

Thanks very much!


PS – the weather here in downstate NY is currently 69F (21C), partly cloudy, with a dewpoint of 64F (18C).

Daniel writes:


I know this was a brief aside in the show, but I was nevertheless disturbed by Vincent’s comment calling Prius vehicles a ‘fraud’ in episode 242. The comment sounds like a dive into the typical counterfactual misinformation about hybrid and electric technologies. It dismays me to hear such a swing from rebutting anti-vaccine claims down to bashing some of the better vehicles available in terms of multiple environmental concerns. Too much of the automotive industry wants to maintain the status quo and simply produce outdated, inefficient, and dangerously-polluting vehicles. This kind of attack usually seem to be based on misinformation from their old PR campaigns attempting to avoid criticism of their reticence to innovate.

Perhaps I misunderstand and you’re coming from an entirely different direction, but that hasn’t been my experience with such comments around the Internet and other media. Nothing warranting the descriptor ‘fraud’ has ever turned up in my research into this or similar vehicles though it has for many other types of vehicles such as a lot of vehicles using nothing more than hyped-up traditional technologies which supposedly produce efficiency but are basically a step backwards, diesel and some alternative fuels which sacrifice emissions to obtain efficiency, and weak hybrid vehicles which provide almost no benefit other than to PR.

I know this is off-topic for your show and probably not of much importance to you, but please clarify when broaching such topics or look into this further before saying something so strong that appears to align with common greenbashing or greenwashing misinformation.



Nissan Leaf and Toyota Prius owner

Joe writes:

Could the diabetes epidemic be caused by a virus, or is that just lazy thinking?

It’s 75 degrees with 45% humidity in Seattle as I pose the question to the experts.

Edward writes:

Dear Vincent,

I’ve just listened to yourself and the other authors of Principles of Virology talking on this week’s TWIV. It’s a textbook I very much admire and it was interesting to hear the processes – and the enormous amount of work – that go into writing it. In particular, I was very interested by the debates you had about precision and clarity in scientific writing. Good scientific writing is a difficult skill to master, but in my experience it is barely taught (and rarely practiced). As a public/educational service, I wonder if you and your colleagues would consider making a Principles of Virology ‘Style Guide’ available? It sounds as if you have already codified a lot of your discussions, and I’m sure I’m not the only person who would benefit from a virological Strunk & White.

Thank you all for the work you put into Principles of Virology and, of course, for the podcasts.

Yours illiterately,


University of Oxford


Andrés writes:

Hi, my name is Andrés, i’m from Colombia, i just want to say thanks for your lessons on “virology I: How viruses work”, your blog, podcasts and especially for the transcript of them. I must admit that my writing-listening english skills are not good, but thanks to your transcripts i have been able to keep your classes at the same time that i improve my english.

Thanks from Colombia, you are a really nice teacher, Mr Racaniello

Peter writes:

Massively enjoyed this! I’m an ardent fan of Principles of Virology which I use for everything I teach, it simply makes sense to me. Just wish someone could do the same for Immunology!

Your news that PoV 4th edition will be electronic is exciting news, but triggers a question:

Are open licensing permissions such as Creative Commons likely to apply to PoV images?

In the “good old days” (2 years ago) there were simple rules about what we could and couldn’t do with the sheafs of paper from copyrighted sources we gave to students, for example the 5% rule for copying from textbooks allowed me to use your images in student handouts. But online electronic teaching material is a whole new world, where every single image has to be cleared before we’re allowed to use it.

So our teaching is likely to look very different in the future as we will be prevented from using any material that isn’t compliant by these strange new copyright rules.

Just to really mess with your head, I’m told if you’ve used a PoV image in a TWIV podcast,- we CAN use it! As I said,- weird.

If you need any review of HCV content in the new text – happy to help! (which is a pathetically transparent attempt get an early view of the good stuff).

All the best,


James writes:

Kia ora folks,

Vaccines are a topic that pops up routinely on TWiV and one thing I’ve wondered about is how can we test new vaccines for efficacy without actually exposing the person to the pathogen?

It’s a long time since Edward Jenner was exposing children to smallpox to show cowpox worked as a vaccine. I couldn’t see even the worst of ethics boards letting a researcher do that today.




New Zealand (Aotearoa)

Bryan writes:

Dear Vincent, Rich, Alan, Kathy, and Dickson,

I thought the following paper would be of interest to the TWIVerse:

“Signatures of mutational processes in human cancer” (Alexandrov et al., 2013) (doi:10.1038/nature12477)

The authors (many) cataloged the somatic mutations occurring in over 7000 human cancers of 30 different classes to sort out the mutational “signatures” arising from different mutational processes. Of interest to Virologists, mutational signatures associated with APOBECs were found in 16 cancer types with a prevalence of 16.6% in samples (see Figure 3). The authors suggest that “because APOBEC activation constitutes part of the innate immune response to viruses and retrotransposons it may be that these mutational signatures represent collateral damage on the human genome from a response originally directed at retrotransposing DNA elements or exogenous viruses”. Although morbid, it’s a pretty compelling idea that each of us pays a price (cancer) for surviving a lifetime of viral warfare.

Sincere thanks for producing this podcast. Great job!

Jason writes:

G’Day TWIV team,

I hope you are all well.

I’ve held off giving my somewhat simplistic opinion on whether viruses are living for a while, but I thought hey, why not put in my two cents worth.

I believe that the majority of viruses can be considered living. I view them as a seed that springs to “life” when undergoing replication in the host cell. But there are of course caveats.

For me, a virus is an entity consisting of nucleic acid encapsulated in a protein coat (with or without lipids). But more importantly, for me to consider a virus “living”, is the requirement that the nucleic acid encodes for proteins that “do something” that requires energy, for example enzymes that use ATP. Also, those enzymes must be able to be adapted to suit the host cell environment, in other words they must evolve in response to change.

This means that for me there are some viruses that don’t conform to my view of what I considered to be living. This is why I could never give you a straight answer on your internet poll.

Keep up the good work.



Jason A. Roberts

Senior Medical Scientist

National Enterovirus Reference Laboratory

WHO Poliomyelitis Regional Reference Laboratory

North Melbourne, Australia

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2 comments on “TWiV 252 letters

  1. Varun C N Oct 3, 2013

    In response to a question “Could the diabetes epidemic be
    caused by a virus, or is that just lazy thinking?” The following thought
    occurred. Several examples such as Coxsackie
    and Adenovirus are known for their interactions. Adv36, more known for its link
    to obesity can serve as proof of concept. Adv36 has potential effects in enhancing
    differentiation of preadipocytes. The mechanism
    was traced to viral RNA expression pattern by M Rathod etal. Another paper by Wang etal demonstrated
    adv36 infectionincreases glucose uptake in cells via Ras-activated PI
    3-kinase pathway in an insulin-independent manner. Of
    course, conditions such as obesity, diabetes or obesity have to be considered
    under environmental and genetic influence also. Antiviral is not advocated for
    diabetes or obesity.
    I had blogged about it earlier.