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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 180 Letters

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 Letters

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 Letters

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 oneimage 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 Letters

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:

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.

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 175 Letters

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.

TWiV 174 Letters

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 Letters

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.

Read more: TWiV 173 Letters

TWiV 172 Letters

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,

mb

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 Letters

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 Letters

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

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