Your conversation reminded me that I’ve heard people say they can smell some cancers. Usually lung cancer and usually on someone’s breath. My husband was diagnosed with colon cancer several years ago and his breath had begun smelling weird to me in the months before. He’s been an ardent vegetable hater but I would tease him that his breath smelled like brussels sprouts. Soon after he started chemo he smelled like himself again and has ever since (he’s cancer free so far since surgery and treatment). Of course that’s not scientific at all, but it was interesting to me. Ironically now that brussels sprouts are getting popular he’s begun to like them. But I haven’t noticed any brussels sprouts breath yet!
Thank you for the shows. I’ll second the person who said your Ebola information was helpful. I did a lot of spreading that information around to worried friends, too. I feel like it calmed a few fears. At least it made me feel useful. Keep up the good work.
Hi again TWiVers,
I just wanted to write in to clarify the reason for conjugating protein therapeutics, such as the soluble CD4 you discussed last week, to the Fc portion of an IgG antibody. You guys speculated that the reason might be to get killing of cells bound by the conjugate, or phagocytosis. Though these may be marginal effects, the principal reason is actually to increase the half-life of the drug in serum.
Most proteins in serum are rapidly and non-specifically engulfed by macrophages and other phagocytes. However, proteins like IgG and albumin that are meant to persist in the blood are bound by FcRn in endosomes, and then delivered back out into serum rather than being degraded (see for example this paper). When drugs (like monoclonal antibodies) need to be infused, you can’t rely on daily administration to maintain the proper dosage, so a long half-life is key.
I wonder if this will be as important with protein drugs that are expressed (produced?) from AAV vectors. Here, presumably the therapeutic is being continually produced, but I suspect that having lower expression levels with a long half-life will still be ideal
PS – No need to read this part on air, but for the future, I wanted to clarify “audiommunity” is pronounced like “autoimmunity,” just switching the i and the o. In the past, when you’ve read the name (and thank you for doing so!), you’ve read “audio-i-mmunity. Pretty sure that all of our listeners are coming from your shout-outs, and the numbers go up every time you mention us, so some people are clearly finding it, but we’ve had a couple of comments that people had trouble because they were looking for audio immunity.
re: AAV-expressed eCD4-Ig
Thanks for the excellent discussion of this exciting article. Your discussion added a much deeper understanding to what I was able to gather from the popular press and the abstract, figures and tables available on line.
4 windless rainy degrees C as Philadelphia awaits another Winter Storm Warning.
Hello TWiV Team,
I thought the recent discussion of vaccinating premature infants by Johnye was too pertinent to pass up commenting on. I started listening to TWiV many months ago because of the birth of my daughter who was born at 28 weeks gestational age. Her hospital stay was a many month ordeal, and one of the big milestones was my Daughter getting her first round of childhood vaccines. Because of her weakened state the immune challenges from vaccines were scary, and she had increased rates of apnea and bradycardia. I was also frequently warned about the impact of RSV on infants (perhaps you could do an episode on RSV one day.) All this caused me to seek out info on viruses and vaccines so I found TWiV.
She is now 9 months old, and doing quite well. Her 6 month vaccinations happened without incident. I can now turn my focus to more normal parenting activities and figuring out how to encourage my daughter to be as enthusiastic about science as I am when she gets older.
It is 60F out near the beach in San Francisco, where the fog is never too far away.
Thanks to the TWiV team for many hours of great content,
Ken Stedman writes:
Dear TWiV team,
Unfortunately I am probably a little late for follow up for TWiV 323 (great title by the way), but there are a couple of things that I wanted to follow up on for the paper that you discussed (Norman et al., 2015).
First, sorry to burst Rich’s bubble but the “presence” of “poxviruses” in their stool dataset is almost definitely due to a match to the circovirus-like rep gene which is found in canarypox virus and no other poxviruses to my knowledge. (We made the same mistake in the first analysis of our meta genome from which the “they did it in the hot-tub” [TWiV 195] virus genome came.)
That brings me to my next point which is how those datasets were generated. As is true for most metavirome studies, Norman et al. needed to amplify their DNA before sequencing. The amplification process which they used, phi29 DNA polymerase-based multiple displacement amplification, generates lots of DNA but preferentially amplifies circular ssDNA viruses (like the circoviruses mentioned above) and small dsDNA viruses with circular genomes. (see Kim and Bae, 2011: http://www.ncbi.nlm.nih.gov/pubmed/21926223).
Norman et al apparently used the same amplification protocol for all of their samples, so they should be comparable, but any assumptions regarding actual and possibly relative abundances must be made very carefully.
Unfortunately amplification, particularly of environmental samples, (unless you have a skid loader full) is a necessary evil. All amplification generates bias, it just needs to be acknowledged. That being said, I completely agree with your assessment of the paper and agree that we need a lot more data like this.
I have a couple of picks of the week if you have not yet picked them. One is Forest Rohwer, Merry Youle and Heather Maughan, and Nao Hisakawa’s : Life in our phage world book http://www.amazon.com/Life-Phage-World-Forest-Rohwer/dp/0990494306, also available online and http://2015phage.org/art.php. There are also all of the talks from the meeting/release party (http://2015phage.org/program.php) and a bunch of other cool stuff. The other is the (hilarious in my opinion) spoof of it’s all about that base (bass) from Lynn Zechiedrich’s lab (https://www.youtube.com/watch?v=gwy2lD1reos&feature=youtu.be). Full disclosure, I wrote a chapter in the book, spoke at the meeting and Lynn is a friend from graduate school.
The temperature in Lincoln Nebraska this (Feb 27, 2015, just in case it takes you a while to get to this e-mail ;-)) morning was -6F. in Portland, Oregon when I got there 56F.
In episode 321 the discussion of experiments having hyper-pathogenic potential was interesting, but I think it misses a larger and far more significant point.
I am not so worried about the activities of a few responsible, leading-edge virologists today, but I am greatly worried what happens when, 20 years from now, biotechnology has advanced to the point that any intelligent high school student can create hyper-transmissible or hyper-pathogenic organisms.
We can’t rule this out. Forty years ago, humans could not splice DNA. Twenty years ago, sequencing a genome took national-scale resources, but today it costs less than an iPad at full retail. What will off-the-shelf kits allow in 20 years?
Given biotechnology’s current trajectory, the genie is already effectively out of the bottle. So we must act now, because, as your colleagues in the world of computer viruses have painfully learned, betting the fate of civilization on the sound mental health and law-abiding nature of teenagers is unwise. RNA hacking will become the new computer hacking.
That’s why this is a golden opportunity for virology. If 20 years from now, it’s straightforward to engineer a terrible offensive virus from the chemical elements found in a handful of dirt, there is really only one possible response: the defensive side of virology has to be as good or better than the offensive side.
So if I were a virologist, I would call for a massive increase in research funding in the name of homeland security — but it would really be “species security.” As a specific goal, I’d suggest the world’s industrial nations aim to develop, within 10 years, the ability to detect, characterize, and counter, on a national scale, any new viral or bacterial threat within 30 days of its appearance.
This will be hard — enormously, insanely hard — and far more complex and challenging than either the Manhattan Project or the Apollo program. It may be argued that the threat is speculative, and doesn’t merit a response of this magnitude. But I would say the threat is when-not-if, and even if the threat never develops, the benefits of the program would be immense and would accrue as the project progresses, not just at completion.
Virology today strikes me as a cottage industry of a couple thousand people. Given the materializing threats, it cannot remain so. Virologists may find it distasteful to support the state’s goals so openly, but they are worthy goals. Importantly, I’m not saying academic freedom should be curtailed — just the opposite. Let’s do all the experiments, but let’s do them in plentiful BSL-4 labs (if necessary), with well-trained, plentiful personnel. Increased funding will enable far greater academic explorations than are possible now. (Example: NASA had freedom to fund development of nuclear rockets in the 1960s, but could never do so now.)
This proposal does not solve the problem of what knowledge to keep secret and what knowledge to spread, but I believe it identifies the bigger problem wrapped around the gain-of-function controversy.
I’ll look forward to your thoughts.
OPTIONAL: I don’t want the letter to be too long, but I have listened to enough TWIV to know that Alan is skeptical of the potential for engineered or weaponized micro-organisms to cause havoc. This is puzzling to me, because the responses are so numerous. If needed, therefore, I’d offer that: First, natural organisms seem to do a great job of causing havoc, and they’re not even trying (in fact, evolution tamps down their virulence). Second, there is the precedent of the 1979 Sverdlovsk accident that killed 100 Soviets downwind from a bioweapons plant — again, without trying. Third, there is the precedent of the 1977 Russian flu which circled the world after escaping from a laboratory freezer somewhere. That one is personal, because it infected me, quite unpleasantly I might add, and we don’t know if someone was trying or not. And fourth, even if all the above points are rejected, saying that enhanced bio-weapons are improbable because smart people couldn’t develop them in the 1980s is like saying airplanes are improbable because Leonardo da Vinci failed to build one. He could do it today, alone, using a kit.
A message for the anti-vaccine movement:
A couple of small notes regarding the last episode:
First, the now famous quote about vaccine-preventable diseases tracking with Whole Foods locations. Is this just a stereotype or do you know of any data that would actually support it? I tried to search online, but instead found this article:
http://prospect.org/article/vaccine-fear-mongers-are-wrong-theyre-not-ideological which links to a research paper showing that anti-vaccine beliefs are spread fairly equally across the ideological spectrum in the US.
Second, you had an intense discussion about the career implications of getting a PhD and doing a postdoc. Why not invite some people to TWiV, who are virologists, but are not working in academia? You can invite someone from a Pharma company, a biotech, CDC, FDA, funding agencies, editors from Nature, etc… and ask them whether these things were important for their career and, what is more relevant to current job market, what they are looking for when they are hiring.
Yegor Voronin, PhD
Senior Science Officer
Global HIV Vaccine Enterprise
Thank you for the sample chapter of the textbook you are writing. I found it much more readable than the “hateful texts” mentioned in my original email. I liked the straightforward style of delivery, as opposed to the obfuscation employed in the wording of many texts. I took about three days to read it, in order to do so slowly and make sure I followed the ideas presented. At first it was a bit overwhelming, (mind blown here!). The illustrations helped too. I plowed through and I can say I have a much better understanding of how different viruses are ushered into healthy cells, often by way of using many of the same functions used by normal cell life. Fascinating. Just please do not give me the final exam today!
It is currently 34 degrees in Chattanooga, clear with winds 6 mph from the Southwest.
Thanks again for the honor.
It is -10 C headed for -20 in the suburbs of Boston, I have a virus (the kind that makes you sick), and a man in my neighborhood is wielding a strange machine that looks like a 19th Century snow blower (see attachment).
On TWiV 324 you read a letter about vaccination of premature infants. Your response emphasized the safety of vaccines given on the normal schedule. The literature review you cited did say vaccination was safe, but did not unequivocally say that vaccination was effective.
According to that paper, vaccination of premature infants protects against Diphtheria, Tetanus, and Polio. It is less effective against against Pertussis, Hepatitis B, and flu, and a booster dose may be required.
Explaining this to a worried parent of a premature infant should take less than 10 seconds. “Vaccines are still safe, but we might need to give her an extra booster dose next year.”
Vincent’s pick of the week was an article lamenting the unwillingness of regulators to discipline anti-vaccination doctors. I think doctors who can not explain why a premature baby should be vaccinated on schedule should not be caring for those babies.
Dear Vincent and TWIV co-hosts,
Given your recent focus on Ebola, I thought you would enjoy viewing the webcast of a special presentation given at the recent CROI in Seattle by Giles van Cutsem of MSF. He received a standing ovation from the audience. Please share with the TWIV audience.
Hello TWIV friends.
Thank you very much for your “HARD” work (I do feel it is hard work but fun). Today I’m sending a pick that I do think it is a Great idea. Beekeeping just got a turning point.
My best regards.
p.s. For the first time I’m giving extra credits for Twix listening and info integration on a semester work for my Nurse students.
Ricardo Magalhaes, Ph.D.
Associate Professor of Microbiology
Faculty of Health Sciences of Fernando Pessoa University