Letters

TWiV regularly receives listener email with corrections, comments, suggestions for show topics, requests for clarification, and additional information. A selection of these is archived on this page.

TWiV 183

Joe writes:

How cool is that to be listening to you all reading my emails with Peter Sandman while I am stuck in traffic.

I loved the discussion and want to send a big thank you to Michael for joining in and giving us the missing perspective of what the NSABB was thinking as they made their decisions. His efforts on the podcast are a perfect example of risk communication done well. You don’t have to have all the answers, just be able to articulate the process that went into valuing the things that created the decision in an honest way.

I apologize to Michael for my blunt technical description of them as a Nameless Faceless Government Committee, but it is an accurate description of how they were viewed by outsiders not aware of their existence prior to them making a significant decision with little public involvement in the process prior to the decision. I wrote it to reenforce the following point:

It is a critical and sometimes frustrating reality for every risk manager that when making public risk communications, if you communicate based on who you think you are things will not go well. If you communicate based on your audience’s perception of you then you have a chance to actually finish a sentence!

I was surprised to hear Michael say that there were some research that he did not think we had a right to know. I would appreciate hearing more details on his thoughts. In the world of basic science I can’t think of any that I would agree with. I agree that we should not publish the specs and construction steps for building a cruise missile in your garage, but that is different than the kind of science we are currently discussing.

Regards,

Joe

Josh writes:

Dear TWiV Doctors,

I would like to thank Dr. Imperiale from the NSABB for being on the show. It was very illuminating, and he spoke clearly about the struggles that have surrounded this situation.

He said that the WHO meeting came to a different conclusion because it was “mostly made up of flu virologists”. Isn’t that kind of the point? Experts in the field of flu virology came to different conclusion than the NSABB. Shouldn’t the NSABB defer to this group of experts on the matter? Does the NSABB dispute their expertise?

Bioterrorism is largely a fantasy of crazies and the bio-defense crowd. The real threat is Mother Nature, as Dr. Imperiale said.

Sincerely,

Josh

Mike responds:

Dear Josh,

Vincent asked a very similar question during the podcast, and I think I clarified at the time that my point was that it wasn’t surprising that the two groups might come to different conclusions. But let me answer your questions more directly.

The first thing that I want to make clear is that there is a flu expert on NSABB (Michael Osterholm) and we also consulted with other flu experts as we were discussing the original manuscripts last fall. Thus, we did not make our first recommendation in a vacuum. Second, I do not dispute the expertise of those who participated in the WHO meeting. However, they have not spent the past seven years together discussing the dual use issue, as NSABB has. NSABB’s expertise is much more broad, including microbiology, infectious diseases, biosafety, public health, veterinary medicine, plant health, national security, biodefense, and scientific publishing. One of the things NSABB has been stressing is that the scientific community needs to be more engaged in discussions of dual use.

Regarding your statement about bioterrorism being “largely a fantasy of crazies and the bio-defense crowd,” I strongly disagree. I think the Native Americans who were deliberately infected with smallpox by the British in the 1700′s, or residents of The Dalles, Oregon, who were poisoned by the Rajneeshee sect with Salmonella in 1984, or the relatives of those who died from the anthrax letters in 2001, among others, would also disagree with you. Bioterror is very real, and groups like Al Qaeda have publicly expressed their desire to use it. That is not classified information: it is freely available. Here is an example that was just reported a week ago by CNN:

http://security.blogs.cnn.com/2012/05/02/from-the-grave-al-awlaki-calls-for-bio-chem-attacks-on-the-u-s/

Best,

Mike

Kim writes:

Hello TWi hosts!

I’m studying the bachelor program in biomedicin at Karolinska Institutet, Stockholm. I found these lovely podcasts (TWiV/TWiM/TWiP) during our course called “Infection & immunology”. We were working with Semliki forest virus and supposed to do calculation involving the infected cell cultures, to which I found help from your website. I then discovered the podcasts, which I used for support when studying for the exam. From that day I was hooked. I’ve continued to listen to your podcasts, both old and new, and I absolutely love them.

Now for my question! I’m curious to what your opinions are on pre-postdoctoral studies (meaning bachelor, master and PhD studies) and their importance for someone who is pursuing and dreams about a career in research. As an example I can use myself, because I should soon choose how to continue my studies. I’m not sure if the structure is the same in the States as in Europe, but the crossroad I’m at is which master program should I choose that would help me the most in continuing my studies. I’m weighing between a program in microbiology and a program in biomedicin, both resulting in a master’s degree, and wondering what implications might this decision have for my future. I feel that I would love to study only microbiology for two years, but I also feel that it might give me a “tunnel vision” in a way because I would only focus on one thing. In contrast, biomedicin would provide a wide knowledge of many fields, but less specific and in depth. Do you think this decision really matters in the end if I aim at a career in research. I’ve heard that ones postdoctoral work is in a way the research which defines one the most.

Please do tell us about your own studies and how you feel they shaped your future resulting in a career in research or something else (depending on which hosts are present while reading this). Thank you very much for your answer and keep up the good work! And the weather has been around 5 Celsius for many weeks now, so almost summer!

Best regards,

Kim

Todd writes:

Even though it’s not something you’ll likely put on your resume, but I just wanted to congratulate Vincent on being quoted in Maxim magazine for clarifying that, contrary to the TV show Lost, you cannot disinfect a wound with vodka due to less than 66% alcohol content. (Channeling Alan) You could have enhanced your viral sex appeal if you had also mentioned that research shows cleavage is utilized in some viral reproduction.

Tyler writes:

Just as a quick FYI, I wanted to let you know that I will be staying at the Dengue Branch in a permanent position once EIS is over in June. One factor that motivated my bosses to find the money to keep me here was my TWiV interview, which garnered a lot of attention for the Branch in a variety of capacities. I therefore wanted to thank you again for offering the interview and helping to make it such a positive experience.

Peter writes:

One minor point on episode 181, we’ve seen a few cases here in the UK where sheep farmers have picked up skin lesions on their hands after vaccinating their sheep against ORF. Another route of infection to add to your list. Of course here in the UK parapoxviruses are all about the poor old red squirrel.

All the best,

HCV Group : School of Immunity and Infection :College of Medical and Dental Sciences : University of Birmingham

Matt Evans writes:

Hello Vince and all the TWiV hosts,

I am interested in adding people to my lab and it occurred to me that there may be no better place to find motivated young virologists than TWiV! If you think it would be appropriate, please post this on your website or even read it on the program.

My lab studies the hepatitis C virus and how host factors influence entry and replication of this virus in host cells. I am currently looking to hire a postdoc with a strong research track record. I am also interested in hiring a technician, who will help maintain the lab and conduct their own research projects. I am sure that successful applicants will find the Department of Microbiology at the Mount Sinai School of Medicine in New York a terrific place to study viruses.

Those interested in applying can find my contact information on my Mount Sinai webpage: http://www.mssm.edu/profiles/matthew-j-evans

Many thanks,

Matt

TWiV 182

Joe writes:

Vince, here is the text of my post on Peter S site. I was disappointed in the quality of his article as I have much previous experience with his work and see him as the “David Baltimore of Risk Communication”. If you could get him on as a guest you would enjoy the discussion. He reminds me of D3 in his ability to tell a story.

Regards, etc

Joe

Peter, while I have the greatest respect for you and have been to trainings by yourself and Vincent Covello in years past, I have to tell you that this article is very flawed both in the “facts” used and in the conclusions.

About 5 years ago I did the work to prepare my global organization for responding to a potential pandemic based on my concerns over H5N1, SARS and a few other pathogens. At that time I did the work to get as complete an understanding of the state of the science that I could achieve with my background in Chemical Engineering and Environmental Science. Within a few years the public discussion caught up with risk management trade’s discussion on pandemics and we saw serious resources put into preparedness planning at the international, national and local levels. We have relatively robust systems in place and are working to improve the major deficiencies in prediction, vaccination and control.

The research and the researchers you are unhappy with have been an integral part in trying to get the answers risk managers like me need to make good decisions related to these preparation. Their emotional response to the criticism of a faceless unknown committee is very understandable to me. Their efforts to remain professional is to be praised and their lack of sophistication regarding risk communication seems to be something they are working to rectify.

I would argue that the Decide, Announce, Defend strategy you describe better describes the NSABB’s approach than the scientists. And the target of their decision was not a few papers but the fundamental process of scientific communication among peers by publishing finds for peer review. Scientists value this in a way equivalent to the 1st amendment of the US constitution. To me their outrage is appropriate and reasonably targeted.

WRT the facts:

We know the 60% number is not accurate in the way you used it. It is the % of those who sought hospital care that died. The number of people infected is certainly much larger and there are good studies that indicate that this flu is currently in or near the typical flu Case Fatality range of 0.1%- 2%.

This flu strain is not exceptional in its lethality as you characterized it. Ebola, Nipah virus, HIV, Hep B, SARS, and many other pathogens are very similar to it or worse that it in virulence.

There is little mystery in how the 4 BioSafety Levels of protection are determined for a given pathogen.

1 = not a human pathogen,

2 = human pathogen that is not airborne transmissible, (e.g.,HIV, Hep B)

3 = human pathogen with life threatening disease that is airborne and for which we have treatment or vaccine (e.g., flu, yellow fever)

4 = human fatal pathogen possible airborne transmission with no known treatment

The BSL system had been incredibly successful at stopping lab acquired infections and loss of containment not withstanding unproven speculation about the source of H1N1 (note that it has an excellent reservoir in pigs where it experiences little evolutionary pressure)

These experiments are not as unusual as you suggest. The value in publishing them is in accelerating our ability to develop an effective treatment or vaccine. To build our defenses against a natural or unnatural outbreak. Their work is totally reproducible by any competent biologist with a supply of ferrets and virus (both readily available).

My view is the NSABB did not understand the history of research in this area, made a knee jerk decision to ban the details and were caught by surprise when knowledgeable people protested the impacts of their decision on all scientists.

Warmest Regards and please keep on with the business of improving our risk dialogs.

Joe G.

EH&S Manager

Peter Sandman responds:

Thanks, Joe, for your kind remarks about my work and your thoughtful ones about upcoming risk communication challenges. And thanks for sending me your critique of my Genetic Engineering & Biotechnology News piece on the H5N1 publication debate.

I’m drafting a response to the latter, which I hope to have ready to post with your comment in a few days.

For the sake of clarity: I have posted three commentaries on this issue so far. (This Guestbook comment-and-response will be #4.) Here they are in chronological order:

“Bird flu risk perception: bioterrorist attack, lab accident, natural pandemic” (http://www.psandman.com/gst2012.htm#NSABB) – a Guestbook entry posted on January 19, 2012.

“The H5N1 Debate Needs Respectful Dialogue, Not “Education” or One-Sided Advocacy” (http://www.psandman.com/col/WHO-H5N1.htm) – the article TWiV discussed, really an email to Lisa Schnirring of CIDRAP News, posted on February 17, 2012, which she drew on for her article (http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/feb1712meeting.html) of the same date.

“Talking to the Public about H5N1 Biotech Research,” (http://www.psandman.com/articles/H5N1-1.htm) – the article you read, submitted to Genetic Engineering & Biotechnology News [ital] on March 18, 2012. (The version the magazine published [make “version the magazine published” a link to http://www.genengnews.com/gen-articles/talking-about-h5n1-research/4067/] on April 15 under the same title is somewhat shorter.)

All the best.

–Peter

P.S. I’m not sure whether it makes sense for me to participate in a future TWiV netcast or not. I’d be interested if the focus were on risk communication issues raised by the controversy … not the technical issues where the moderators are experts and I’m a novice. (Even if I were right – or more likely half-right – on a technical point, they’d still outrank me and could still out-argue me.) But given that the papers are headed for publication now, a conversation about the risk communication implications of the mooted publication debate would probably seem pretty peripheral to the TWiV audience, I think. Still, I’d be open to an invitation of the three moderators think it makes sense … and I won’t feel slighted if they think the moment has passed.

Joe responds:

Peter, it is interesting to me as we continue this dialog (and now that I have read the actual paper discussed on TWIV) that it is a perfect example of how much people can disagree even when given the same facts!

I don’t think the work that has created the ruckus is that different than similar work going on all over the world with a variety of organisms, many that I find much more concerning than H5N1. I must admit that I don’t watch TV news so I may have missed some of the drama. My view at the time was that the researcher, Dr. Fouchier, created the problem by announcing to the media that “he had created the world’s scariest virus” (assuming the facts I saw are accurate). I later heard him talk on the TWIV episode in Dublin and he seemed much more circumspect now that he has experienced some “live fire” media training. Now that I know he had to pre-mutate the wild virus to give it a starting chance to passage through the ferrets, I find the risk of a pandemic lower not higher than before. What he did actually proved just how high the natural barrier is between H5N1 and mammals.

There is a lot of research being done in BSL 3 and 4 labs that could be much more worrisome than this if it was not done with the extreme caution and rigid rules of the BSL 3 and 4 labs. Since one of my jobs is to coordinate with the safety staff that run the BSL 3 and 4 labs in the USA to allow our field service engineers to come out and repair our instruments in their labs I know just how seriously everyone takes these rules. When you say the virus is stored in a lab, that does not quite conjure up the reality of how they are stored in a double sealed container in an isolation system within at least two other isolation systems (BSL 4 labs live within a BSL 3 lab that usually are attached to a BSL 2 lab).

Has there been a lot of media coverage of angry scientists on this issue? I haven’t seen it but would not expect to if it does not show up on the web. I ask because I would not characterize most researcher in the biotech world as dismissive of public concerns. These are in fact the same folks who volunteered to put on the Asilomar conference when folks were scared of genetic engineering in the 80′s. I can’t think of many branches of research that took what could have been considered uninformed fear more seriously.

One part of this debate that has baffled me is the focus on not publishing this kind of work when that is exactly what we need to develop realistic response plans. The irony of it is that I would bet the eternal box of doughnuts that there was much scarier work being done 10-20 years ago to weaponize smallpox that was never published because we were not supposed to be doing it. You and I did not have a need to know! They are not saying don’t do the work just don’t publish the results! All the (minimal) risk with none of the valuable gain.

Regards

PS. you would have fun on the TWIV podcast. Actually the discussion that would be very worthwhile would be on how to better communicate the need for vaccines to an ever more confused public. A great venue to reach the scientists and doctors interacting with people on this critical issue. The hosts spent many episodes trying to get the science clear on CFS and the purported links to the XMRV virus as it was breaking news the last 2 years.

Joe

EH&S Manager

Josh writes:

Dear TWiV Doctors,

I have a suggestion for a listener pick of the week: Dr. Paul Offit’s course on Vaccines from UPenn on Coursera. It starts in June and is free. It does not appear to be an technical course, but rather a general examination of the history, science and use of vaccines. As such it might of more interest to lay-people than people in the field. My assessment might be inaccurate, however, since I have not taken it (yet).

https://www.coursera.org/course/vaccines

Sincerely,

Josh

TWiV 181

Spencer writes:

I would like to propose the book:

Netter’s Infectious Diseases, 1e as a listener pick of the week.

The book, filled with great explanations, is beautifully illustrated by the late Frank Netter MD, a pioneer in medical illustration. As a student, one of my classmates at Mount Sinai actually had Dr. Netter as a cadaver. Dr. Netter taught us so much in life as well as after! The sections on parasitic diseases are particularly well done.

Sincerely,

Spencer MD PhD

Richard writes:

Hi Vincent and other hosts!

I have no silly questions for you this week, but a book that I found interesting.

Germs, genes and civilisation: how epidemics shaped who we are today.

By David P Clark

Thanks again for the series of podcasts, that I enjoy learning from each week.

Regards

Richard

Andrew writes:

Good [insert appropriate distinction regarding time of day you receive this] gentlemen of TWiV,

I’ve been an off-and-on listener to TWiV for what must have been before 2009 in the middle of my undergraduate years. This podcast serves as an example of the power of the medium to deliver focused higher-level discussion on topics too complex to survive on traditional broadcast media but still casual enough for the non-scientist. So thank you for your excellent service to us, the listener!

The question/concern/comment I’m writing about is this: Graduate School is Scary. I graduated from a local state school with a BS in Biology in 2010, and have been out of school for just under two years. I’ve maintained some (probably about 5-10 hours a week) of activity in the population genetics lab I worked in prior to my graduation. Some family issues kept me tied to the area and reluctant to apply to graduate school but recently those issues have resolved themselves and now I find myself looking to take the next step. This is very frightening, and I find it difficult to proceed. How do I find what Masters or (preferably) PhD program is right for me? Am I doomed? What do I do if the program best for me doesn’t think I’m best for it? It seems too late in the year to apply to anything? Most programs have closed applications by now and those that haven’t have disclaimers stating that funding is usually assigned already. Should I bide my time and wait? In the mean time, I’m currently applying to the IRTA Postbaccalaureate Training Program which seems like a great program to get into in order to help bridge that gap between undergrad and PhD (and may even deserve a mention on the show: https://www.training.nih.gov/programs/postbac_irta ). Any advice on how to proceed when caught in this quagmire would be greatly appreciated and would likely help any listener also caught in the same post-undergraduate-pre-graduate morass.

Thank you, whether you read this or not, your podcast has been a huge influence on me. Please, never stop.

P.S. I forgot to actually include the field of study I’m interested in, because I meant to move it around, then forgot to reinclude it. My longstanding interest in genetics managed to fuse and include virology, and so ideally I’m most interested in virology (hence looking for TWiV’s perspective) with a focus on evolution and genetics.

Jim writes:

Hi Vince,

Last November you had Science360 Radio as a TWIV pick. There are now over a hundred program links there. That provides a concentration of material you can point folks towards to more easily find what they want. I hear many podcasts from these places that are good, but some sites always stand out, like TWIP/V/M. Others periodically have great shows or a segment of a digest, and some have a huge number of past programs. So if you have an interested listener, I don’t know where you send them, especially if their time is limited, such as a teacher who wants to use certain subjects.

I’m trying a blog describing selected items culled from 60 or more podcasts each week thinking it might be a way to make better podcasts easier to locate. No feedback or comment has occurred after 16 entries over four months, a short period considering the probability anyone is even looking. I now suspect blog material is read more frequently on smart phones and my efforts are too wordy for small screens, so will begin producing shorthand-type entries. It does a far better job of offering material than an alphabetized list of podcasts on my hard drive. This doesn’t address all your TWI(*) efforts, especially as their numbers increase, and only a few of them are included in this blog.

Anyway, if you contact anyone to suggest an article about use of podcasts in schools, the attached list of 92 rss feeds with podcast names might be of use. In addition, this link about listening faster might be of use, too, in light of Kathy Spindler’s comment about finding time to hear your episodes. The blog, Media Mining, is included should anyone have an interest in that approach. Suggested improvements are welcomed, of course, to include ditching it for some other approach.

Oh, I enjoyed your descriptions of daily activities; all time well spent!

Regards,

Jim

Smithfield, VA

Stephanie writes:

Dear Twivers,

I was a bit shocked when a listener wrote in last week and requested that you guys to avoid the subject of evolution in order to avoid offending anti-evolutionary Christians. I understand that, in order to reach the largest audience possible, it is important to be politically correct. But, is it even possible to discuss papers in the field of virology without understanding viral evolution? Why do viruses become resistant to drugs? Why does a virus tend to be less pathogenic in long term hosts? How did viruses develop so many ways to subvert host immune defenses? This is a sensitive subject to be sure, but this subject is something that just about every teacher of biology must face at one point. I look forward to hearing how you guys respond to this issue. You TWIVERs are role models for the scientists and educators that do not practice communicating science to a large, diverse audience on a weekly basis.

Horatio writes:

A brief comment on rabies: the genotype 1 rabies virus usually sustains itself in an endemic cycle in different carnivores according to geography and species composition. Bats may carry genotype 1 but are not needed as reservoirs; however they are reservoirs of the specific bat genotypes, which may cause disease in various animals and humans. Fortunately, the basic reproduction number of rabies virus is low, primarily due to the particular mode of transmission, restricted tissue tropism and long incubation time. Let’s hope that the path to a putative, aerogenically transmitted virus is long and with many obstacles.

Erica writes:

Hi Team TWiV!

I just wanted to write in and let you know that you did indeed discuss miR-122 and HCV in a previous podcast as Rich suspected–it was episode 97 with my PI, Peter Sarnow. Not only is Peter a fantastic mentor, but he is a pioneer in the field of virology, and his episode on your show is one of my favorites. I highly recommend it to anyone who is interested in learning more about miR-122 and HCV.

Thanks so much for a great podcast!

Rohit writes:

I was pleasantly surprised to hear our (miR-122 & HCV) paper discussed on Twiv #180. We are really glad to know that the TWIV crew liked our study. Thanks for discussing our paper.

Currently, I am a postdoctoral fellow with Dr Benjamin tenOever in the Department of Microbiology at the Mount Sinai School of Medicine where I am trying to further develop the novel technology of use of host miRNAs to engineer a live-attenuated influenza vaccine. This technology was demonstrated earlier by Jasmine Perez in the tenOever lab [http://www.ncbi.nlm.nih.gov/pubmed/19483680].

I did my PhD with Dr Stan Lemon while he was at the University of Texas Medical Branch (UTMB) at Galveston, TX. Some of the initial experiments of the PNAS manuscript were actually carried out in the Lemon lab when we were located on the 5th floor of the Galveston National Laboratory, where you are headed sometime soon to do a TWIV episode.

I thought that I would answer some of the questions that came up during the discussion of the paper. In addition to its positive role in HCV replication, miR-122 also regulates cholesterol metabolism in liver. Knockdown of miR-122 significantly reduces serum cholesterol levels in mice as well as non-human primates. Thus, miR-122 is also an attractive drug target for cardiovascular diseases. However, certain liver cancers are associated with lower miR-122 levels suggesting that long-term knockdown of miR-122 might have some side-effects.

Location of miRNA targets in 5′UTR by itself is not enough to change a miRNA from a “repressor” to an “activator” of gene expression as there are examples where miRNA targets located in 5′-UTR of mRNAs down-regulate gene expression. Thus, miR-122 effect on HCV 5′-UTR seems to be unique so far. However, there must be other such examples out there that are yet to discovered.

Allan was right in pointing out that RISC, as the name RNA-Induced Silencing Complex suggests, is a complex of multiple types of proteins. Argonautes are the central and canonical components of RISC. There are 4 argonaute proteins in the human genome, argonaute 1-4. Ago-2 is the best studied one and is the only argonaute with a slicer/endonuclease activity that is used to cleave the target mRNA when there is perfect complementarity between miRNA/siRNA and its target.

Thanks

Rohit

Stephen writes:

I’m a new subscriber to TWIV, and just began with #180. Richard Condit’s comments on polydnaviruses and wasps was fascinating, and I will follow up on that.

A few comments:

1. Broken link: “Viral and wasp genes involved in symbiotic replication (J Virol)” http://www.ncbi.nlm.nih.gov/pubmed/22238295

2. braconid wasps are parasitoids, not parasites. Parasitoids kill the host.

3. The layers of complexity involving parasitoid wasps are sometimes even deeper. Here’s a photo I took by accident while shooting some grasshoppers (Nisquallia olympica http://onh.eugraph.com/insects/orthop/nolympica) I casually study in the Olympic mountains. I’ve appended a comment from bugguide.net, to which I contributed a crop of this photo.

Brachymeria tegularis…

These are hyperparasitoids of common grasshoppers (through sarcophid and tachinid flies). More commonly found in western states. Great find.

See reference here.

… Ross Hill, 12 September, 2011 – 4:32pm

http://bugguide.net/node/view/575501

So the flies parasitize (or parasitoidize) grasshoppers, then Chalcidid wasps lay an egg on the grasshopper. The larva of the wasp then finds the larva of the fly and parasitoidizes it.

I have to wonder how much of a role viral genes play in all of this.

TWiV 180

Rohit writes:

Hi Dr Racaniello,

I am a long time listener of TWIV and really enjoy the informal scientific discussions. I listen to TWIV while working in the lab and am trying to catch up on TWIM and TWIP episodes too.

I have been dilly-dallying on the idea of writing to you for a while now as the paper that I am suggesting is in a way self-promotion. However, I thought that you may find this study interesting as it presents a very interesting example of a virus (HCV) using a liver-specific miRNA (miR-122) to protect its genome from 5′-exonuclease-mediated degradation (attached paper). This paper not only describes a novel way used by an important human virus to slow down the rate of viral RNA decay but also adds a novel mechanism of action to the repertoire of mechanism of action of cellular miRNAs. Usually miRNAs down-regulate expression of target genes by decreasing translation and/or enhancing the rate of degradation. However, HCV has devised ways to use miR-122 to both increase its translation, protect its genome from 5′-exonuclease-mediated degradation and potentially prevent detection of 5′-triphosphate containing viral genome by the cellular immune response.

I enjoy all three podcasts and look forward to many more episodes of them. Thanks for keeping me up to the speed on some of the interesting developments in virology and microbiology as well as fascinating discussions on parasites.

Rohit

Postdoctoral Fellow

Department of Microbiology

Mount Sinai School of Medicine

New York NY

Tanel writes:

Dear twiv team,

Very nice of you to have read my letter. Boston marathon is history for this year. Despite of the crazy heat, I made it to the finish. Took me much more than I expected (final time 3:26:39) but still, it’s done. Was great! Ahead is a new running season with new goals in my mind and new twiv episodes to spice up the time in running shoes.

Thank you again for your time and effort!

Best,

Mr. Tanel

(a typical name for boys born around 1985 in Estonia )

PhD student

Department of Virology

University of Freiburg

William writes:

Dear TWiV Doctors,

I stumbled upon your webcast this morning, and as an aspiring virologist I am looking forward to going through the archives. I particularly enjoyed this episode because I work for Dr. Kathy Hanley at NMSU doing research into dengue virus-mosquito interactions, and my eventual career goal after I get my PhD is with the PHS. An interesting thing about dengue that was outside the scope of the interview is that dengue also has an extant sylvatic cycle in both Southeast Asia and Africa. This is important because it could serve as a model system for other as yet un-emerged zoonotic viruses, as well as currently emerging viruses (chickungunya being an excellent example). Furthermore it is a potential complication should an effective tetravalent vaccine be approved for use, as these sylvatic viruses are entirely capable of spilling over into humans, and have the same epidemic potential.

It will be an interesting year for arboviruses with the early onset of the mosquito season across much of the country, along with the presence of dengue in the Keys, as well as West Nile.

Keep up the good work

William

P.S. I am not ashamed to admit that I carry Principles of Virology around with me on a daily basis.

Jesse writes:

I don’t know if you remember, but we met briefly when I was at Columbia visiting Ian Lipkin’s lab two summers ago. At the time I was a postdoc with David Baltimore. I really enjoy your Virology Podcast, and listen to it whenever I get a chance.

I have to say however, that as an influenza virologist I’ve been a bit disappointed in how you and your co-hosts have treated the H5N1 research debate. I think this issue is more complex and deserves more balanced consideration than almost all commentary, including your own, has given it. I thought of this today when I read an essay by Peter Sandman (which I have forwarded below) on the topic. The essay is the most intelligent thing I have read about the debate, and I think it has some good suggestions. I know you and your podcast represent one of the most respected voices in virology (certainly I respect it a lot!), so I thought I would forward along the essay.

Thanks,

Jesse

Assistant Member, Basic Sciences Division

Fred Hutchinson Cancer Research Center

http://labs.fhcrc.org/bloom/index.html

Josh writes:

Hello future, Vincent, Allan, Rich, Dickson, and all other present contributors. I started listening to TWiV in November 2011 and am up to episode #95, so hello from 2010! I would like to express my deepest gratitude for the work that you do and the education you provide to the listener. I can say that this show has singlehandedly assuaged my fear of vaccination, which was built on hearsay and fear mongering. I would like to ask a few questions and share a video I’m hoping at least Vincent will like.

TWIV #92 discussed plant viruses making plants resistant to drought and other adverse conditions. Is it possible that there are similar viruses conferring resistance to people living in extreme climates, such as Saharan Africa, or the Arctic Circle? Or for that matter could there be microbes, or parasites that help people in these extreme climates manage to live there? For example Dickson has mentioned that the Inuit and Yupik peoples are nearly 100% infected with toxoplasmosis and perhaps other meat borne parasites. Is it possible that these people have given an advantage in dealing with the extreme conditions present in the Arctic Circle by the viruses, microbes, and parasites present there?

On a different note rabies seems to have been around humanity and with humanity for a long time. I realize that the natural host for rabies is bats, however my question is more homo-sapiens-centric. Does its current disease cycle in humans maximize transmissibility? If it does how do hydrophobia, manic mood swings, and whatever other signs and symptoms exist aide in transmission? If not, why hasn’t the virus mutated to a form that can better transmit in humans? If it doesn’t transmit well from humans, could the lack of mutation be because of the limited amount of human borne infections comparative to viruses that mutate much more quickly to maximize transmission?

My third question is related to viruses used to construct things. I think you guys mentioned that viruses can be used to construct batteries. Could a virus be used to construct the most basic structures inside a cell. As an experiment would it be possible to create any, if even the simplest, structures that make up a cell using viruses as the building agent? I realize this idea leads to a “were viruses the root of the tree” type of argument, but frankly I’m not as interested in that question.

As for the video, Vincent mentioned that he liked the Abbot & Costello skit “Who’s on first?”. This is a modern rendition of that skit that I think uses a really clever twist. I should point out that I do not watch sports so I have no idea how current or valid the content is.

http://comedians.jokes.com/slovin-and-allen/videos/slovin—allen—abbott—costello

Thank you all for your excellent work, and ditto to Rich on what to tell everyone if you had 5 minutes to talk to them. I apologize for the length of this email. I generally save up questions until I am overwhelmed and need to write. Please feel free to read or omit whatever you feel like.

Sincerely,

Josh

TWiV 179

Ebrahim writes:

Dear Dr. Racaniello

I was watching the conference in Dublin and I wanted to thank you for sharing my e-mail with the people in the panel, since I saw how nice it was for me to reach the specialists with that ease through TWIV.

As a footnote actually my name is Ebrahim not Laurence but anyways thanks again!

Kind Regards

Josh writes:

Dear Dr. Racaniello,

Thank you for reading my email on the air on TWiV 178. It’s always nice to be included on my favorite podcast, even if you guys did disagree with me.

Would you mind an outsider’s perspective on the situation? And although TWiV is my favorite podcast, I am an outsider: I’m not an academic, and I don’t know any of the people involved.

I am apprehensive about the entire role of the NSABB, and fear that the biological community will soon be subject to the same levels of restriction and classification that currently affects the physics community. I think that in almost every case, things that fall into the category of classified information are almost always done for reasons that have nothing to do with the science, and everything to do bureaucratic nonsense. Restricting information about nuclear weapons, for instance, hasn’t prevented many countries from acquiring them.

Which disappointed me when you read my letter on TWiV, not because you disagreed with me but because I wonder if you are seeing the larger picture. I agree that it should be about the science, but it’s not. Once you remove the scientists(and there are lots of non-scientists on the NSABB) from the equation, it’s about politics and the bureaucrats. So they are going to either restrict the information or they are not. If they do, we agree that this is a bad thing. If they don’t, this is a good thing. In this instance, it’s kind of a zero-sum game.

A game that I believe TWiV played a large part in winning, because week after week you applied pressure to the scientists and other members of the NSABB by calling them out on their nonsense. It’s one thing to be rebuked for your actions behind closed doors, and quite another to be publicly reminded that you are not following the science by your peers. You had an issue that you are passionate about, you skillfully applied public pressure, and your side won the day. That’s not only how you play the game, it’s how good policy wins out over bad policy.

The next policy fight that is coming is that those people on the other side want to change the entire scientific publishing system in the US and Europe. They want to have a system where those people “on the list” get the papers, and everyone else does not. Those people “on the list” will not be able to discuss it either. Anthony Fauci said as much on that NPR story. It’s not only bad policy, it’s bad science. TWiV can either be in the middle of this policy fight, or it can be on the sidelines. I know what I would prefer.

I know it’s distasteful. I know you don’t want these public dust-ups. But what choice do we have? If you don’t engage, then they will not be any opposition to the plans. And that’s an outcome I don’t think our country can afford.

Sincerely,

Josh

P.S. On a personal note, TWiV and your online virology course inspired me to sign up for MIT’s new online course offering, 6.002x, Circuits and Electronics. It’s week 5 and so far, so good. The math is hurting me since I haven’t had calculus in 20 years, but I’m mucking through it

Tanel writes:

Dear Twivoners (twiv + marathoner),

I’m a grad student from Freiburg, Germany (originally from Estonia though), who has been listening to twiv as long ashas been running. On Monday 16th I will run the Boston marathon and no matter how it goes, I would like to use the opportunity to thank the twiv team for the support throughout the training season. Research and graduate studies can often be frustrating and running has been a way to keep a clear mind. Running 6 times a week and between 8 to 30 km a day, means quite a bit of time in running shoes.

Twiv (but also twip) has made those hours also entertaining and educative!

I’m sure there are many researchers in running shoes and maybe even those who will join me on Monday in Boston. Good luck fellow twiv listeners and marathoners!

All the best,

Tanel

PhD student

Laboratory of Prof. Stäheli

Department of Virology

University of Freiburg

Maximilian writes:

Hello TWIVers!

I discovered your netcast today, and I am hooked!

I am currently a pre-frosh at Duke University’s Pratt School of Engineering, with an intended major in Biomedical Engineering. I have two questions for you, which I’ve been thinking about for the past few weeks while I finalize my intended major/double major.

1) Is there a possibility of working on viruses/immunology if I were to focus on protein engineering? I ask because my first love in biology was virology/immunology and that love has always competed with my more prevalent interest in BME.

2) Would it be more prudent to double major in Chemistry (conc. on biochemistry) or Biology (molecular/cellular) if I want my double major to focus on my interests in virology and immunology?

Thanks so much,

Maximilian

TWiV 178

Josh writes:

Hello TWiV Doctors,

Two short things:

1. You probably already heard the TWiV shout-out you got on NPR’s Morning Edition on Friday, March 30th. It’s here: http://www.npr.org/2012/03/30/149664035/policy-on-high-risk-biological-research-tightened

2. Since the NSABB caved (and it was more like a rout) you can put one in the Win column against the forces of darkness. I know you are scientists, but high-fives are appropriate.

Ayesha writes:

Dear TWIValians,

I submitted my thesis last Monday and wanted to share Acknowledgements page with you. Please skip to end for the relevant acknowledgement.

Cheers everyone, you made a big difference to me!

Acknowledgements

I am extremely lucky to have many people to thank. Thanks are due to:

Dr Julian Naglik for his help, his patience and consistent encouragement throughout this process. He is truly a remarkable person and supervisor all around! I have been very fortunate to work with his group on this NIH funded project with further support from King‟s College for the Overseas Research Studentship (ORS).

Dr Celia Murciano for advice on figures, experiments, extensively proofreading the thesis, for performing last minute Luminex assays and conquering troublesome westerns. She is a giver of love, kindness and understanding that helped me get through.

Dr David Moyes knows everything about everything and is always willing to chat about it with anyone. His generocity and advice were always welcome especially for anything to do with fungus, qPCR, microarray, the thesis and computer savvy.

Dr Arinder Kohli for the Cat 3 training, most HIV techniques and so many moments that now make for very entertaining stories.

Manohursingh Runglall for his friendship and sharing his fantastic lab know how.

Dr Chengguo Shen and King‟s College Genomics Centre for performing the labelling, microarray protocol and producing the gene list for analysis.

Dr Simon Jeffs for UG21 protein and antibody for its detection.

Carlo Scala for performing p24 ELISA for my samples alongside his own and Professor Charles Kelly for ordering ZM96 from NIBSC on my behalf.

Dr Trevor Whittall, Thomas Seidl, and Dr Yufei Wang (from Professor Tom Lehner‟s lab) for help with flow cytometry, experimental design and trouble shooting.

Professor Stephen Challacombe for his wisdom, good humour and gentle guidance. I greatly appreciate the time he spent with me.

To Dr Abigail Tucker my postgraduate coordinator.

To my parents, Anne Senécal-Islam and Dr Shamsul Islam for encouragement.

To my husband Angel and daughter Aurora, who allowed me to finish this degree. It would not have been possible without their full cooperation and help.

Thanks are also due everyone at This Week in Virology (TWIV) podcast for re-infecting me with enthusiasm for science.

Johan writes:

I love This Week in Virology, and I just wanted to give my appreciation of the latest episode. So long time since the last video episode!

Thanks

Johan

Sweden

Sasha writes:

Hello, symbionts and hosts of TWiV!

I am a high school sophomore (from western Maryland,) and am writing to you for the first time in the three (or four) years that I’ve been listening to you. Admittedly, by now, you all seem like old friends whose voices would be sorely missed if I went a day without hearing a fascinating and entertaining conversation about viruses. What inspired me to write might come as a bit of a surprise, but I’ll get to that in a moment.

On TWiV 142: Viral oinkotherapy, you discussed a paper involving microfluidics. The details are a bit hazy to me, as I often listen to TWiV while preparing for bed, but I remember the concept very clearly. Having always been interested in circuit design, and since my discovery of TWiV, virology, it occurred to me very recently that microfluidics and microarrays, (and I’m not quite sure which is a subset of the other,) are a very nice marriage of my two primary interests.

That being said, perhaps in the future you could spend a bit of time on some papers regarding those topics. (I’d also be interested to hear your thoughts on them!) It seems to me to be a very promising emerging field, particularly for use in fast-testing and analysis where relatively little sample material is available. I also found a blog/website by the name of Microfluidic Future, which I suppose will be my listener pick of the week.

Now, on to the less virus-related, but still interesting part, which caused me to write in the first place. Back in 2008, a comic was posted on xkcd.com. It detailed a method for determining a number of random locations, at least one of which was guaranteed to be within a relatively small number of miles for any given location. This was termed “geohashing,” and was imagined as a means to select a location for, say, a local meetup. There is a relatively active community centered around this concept, and they’ve demonstrated that it is quite possible for people to use these random locations for meeting places.

This could be relatively easily applied to meetings surrounding TWiV! Using this tool, anyone can find the geohash for their latitudinal and longitudinal zone. If some members of your wide and ever expanding audience became interested in this, we could begin to plan meetups at these locations. After all, networking is what viruses are all about, isn’t it?

Anyway, thank you for reading my lengthy and geeky letter, and I hope you enjoyed my comments!

Alexander

(alias: Alexander help I’m trapped in a username database)

Lawrence writes:

I just wanted to express my appreciation for your podcast, and to tell you that I find your discussions fascinating. I am trained in engineering, but have a wide range of interests in all things scientific and am now turning my attention towards microbiology. Listening to your discussions of scientific publications and hearing the scientific mindset at work is soothing balm to my psyche in our world awash with banality, scientific illiteracy and anti-science. I keep a notepad with me as I listen and jot down words with which I am unfamiliar, and spend time afterwards researching their definitions which opens up new horizons and broadens my perspective in areas that I likely would never have encountered were it not for your podcasts. Thank you all very much for your time and effort.

Paul writes:

TWiVarians,

I just thought you might be interested. I donated blood today and as I was signing in, I had to read a paper that would disqualify me if I had ever be diagnosed with Chronic Fatigue Syndrome. The most interesting part of the paper was that it said a virus called XMRV was linked to CFS and since they didn’t have a valid test for XMRV, I couldn’t donate if I had been diagnosed with CFS.

I’m an IT guy by trade, so I was really surprised when I read their paper, completely understood the “link” that had been made between XMRV and CFS, and knew that it had already been proven false… all thanks to the TWIV podcast! Your podcast has always been interesting, but I had never been able to directly use anything in it.

I just wanted you to know that TWIV is also enjoyed by those of us that are not in field. Keep up the great work!

Paul

Taylor Ridge, Illinois

John writes:

Dear Dr. Racaniello,

I enjoyed TWiV 171, especially your lively discussion on our study of virus production from single cells (Timm and Yin, Virology).

Your discussion touched on what might happen if cells were infected with single virus particles or how virus yields might depend on the cell cycle. In previous work* we infected single cells will single virus particles (using a GFP virus, that allowed us to detect and sort single infected cells before the start of virus release); we found that in most cases ‘high-yield’ or ‘low-yield’ growth phenotypes did not persist from one virus generation to the next, suggesting the variation in growth behavior does not reflect viral genetic variation. Our population-level measures of virus yields on synchronized cells suggested some of the growth variation could be linked to the cell cycle — on BHK cells VSV made on average about six-fold more virus during G2M compared to cells in early S phase.

If you are interested, I’d be happy to discuss further. The ASV meeting will be in Madison this summer. If you attend, I would be happy to meet you and introduce you to my co-workers.
Best wishes,

John Yin

Systems Biology, Theme Leader

Wisconsin Institute for Discovery

University of Wisconsin-Madison

http://discovery.wisc.edu/discovery

Professor

Department of Chemical and Biological Engineering

University of Wisconsin-Madison

Cedric writes:

Dear TWiV Crew,

I read this article in today’s Wall Street Journal which discusses the growing number of pediatricians refusing to work with families who will not have their children vaccinated. It seems to me that this is an appropriate response on the part of physicians who do not want their other patients contracting preventable diseases in the waiting room just because one family has chosen not to vaccinate their child.

I was reminded of the Australian story, where families lose their tax breaks when their children are not vaccinated. Because I cannot see that scheme working in the U.S., it seems that this would be one of the few effective means left to physicians who can no longer persuade their patients of the importance of vaccination.

http://online.wsj.com/article/SB10001424052970203315804577209230884246636.html

Thank you all for the many hours of work you put into this podcast. As an undergraduate biology student, I really appreciate the head start it gives me in many of my science classes.

James writes:

Dear Prof. Racaniello,

I have been enjoying TWIV, TWIP & TWIM for some time. I am on faculty at a smaller institution and these podcasts have become my “journal club”. I have also begun to share the information and, in some cases, the podcasts themselves with my students – asking them to listen to the podcasts and then discuss what they’ve learned.

This past weekend, a thought occurred to me that, as a virologist, you might be able to provide some practical information for me. When I joined the faculty, I inherited glassware and other supplies. Among them were these pipettes. I’ve attached a couple of photographs of one (image one, image two). They are all 10 ml pipettes with a smooth plastic or Teflon tip. To me, it looks like they were designed to have removable/disposable tips. Since the lab I inherited had been previously used by someone with a virology background, I thought perhaps these were for tissue culture – something that transitioned between glass pipettes and disposable plastic pipettes. Have you or your colleagues ever seen/used pipettes such as these? I don’t suppose tips are still made for them, but I’m curious as to their history.

Sincerely,

James Masuoka, Ph.D.

Assistant Professor

Department of Biology

Midwestern State University

TWiV 177

John writes:

Dear TWIVvers,

In TWIV 173, you talked about a study on antibody levels to bird flu (H5N1) in various populations, and related this to infections that don’t cause serious enough illness to send someone to the hospital, or perhaps to get them tested for H5N1. I was curious whether some of the people with antibody to bird flu might have been exposed to the virus, but not ever infected. It seems like people who worked with poultry could be exposed to enough virus particles that even if they don’t replicate in the human body, they might still develop antibodies to them. Is this plausible? Since this is a gastrointestinal virus in birds, would droppings from infected birds be the main source of virus particles someone might be exposed to? If this explains some of the antibody against bird flu in the population, it should affect the estimate of how lethal the virus is when it does manage to infect a person.

A related question is: if we are worried about a potential H5N1 pandemic, would it make sense to add a related strain to our yearly flu virus, so that if it did start to spread, there would at least be some level of cross-reactive antibodies in people who’d been vaccinated?

Thanks again for your wonderful podcast,

–John

Lawrence writes:

Ebrahim writes:

Dear Dr. Palese, Dear Dr. Racaniello

I am a young student working on viruses in Heidelberg university, I am interested in Influenza and in viruses in general. I was watching the recent academy of sciences meeting in New York, and I just wanted to thank you so much for the position you took in the meeting, and I just could not convince myself against the idea that the real reason behind camping against the publications is anything but scientific, it might be political or whatever reason but I feel it is not based on scientific basis, since from my small experience in virology at least there are lots of experiments that might be far more dangerous than what have been done, and it might be helpful for me if you could give me your thought about that – of course if you have time for that

Thanks again

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.

Letters read on earlier episodes of TWiV can be found on this page.