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 168

Mike writes:

Hello Men (and sometimes women) of TWiV!

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

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

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

Raihan writes:

Hello TWIV hosts

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

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

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

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

Stephanie writes:

Dear Twivers,

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

Stephanie

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

Charlotte writes:

Contagion – what a dog!

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

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

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

Best regards,

Charlotte

TWiV 167

Joe writes:

Twivers

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

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

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

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

Thanks for everything that Y’all do!

Joe

EH&S Manager

Alex writes:

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

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

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

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

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

Cheers,

Alex

Bachelor of Science

Lance writes:

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

Thomas writes:

Hey gang,

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

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

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

Regards,

Thomas

MD Candidate, Class of 2014

The George Washington University

Nina writes:

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

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

Keep up the great work!!

Thanks,

Nina

Roberto Cattaneo writes:

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

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

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

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

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

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

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

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

Thanks again for discussing my favorite virus!

Best

Roberto

Kartik writes:

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

Thanks and best,

Kartik

Kartik Chandran, PhD

Assistant Professor of Microbiology and Immunology

Albert Einstein College of Medicine

http://www.chandranlab.org

Judi writes:

Hello professor TWIVers:

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

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

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

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

Thanks again for all you do…

Judi

Lori writes:

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

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

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

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

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

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

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

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

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

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

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

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

Hope this helps.

best wishes

Lori

University of Ottawa

Jon writes:

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

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

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

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

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

Jon

CSIC-IMF

Barcelona, Spain

TWiV 166

Eric writes:

Hello Professors,

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

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

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

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

Eric

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

Lance writes:

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

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

Some really interesting work dealing with the philosophy of science.

Thanks, and keep up the great work,

Lance

Nam writes:

Hello,

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

Stephanie writes:

Dear Twivers,

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

Thanks,

Stephanie

Andrew writes:

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

Eager Learner

Ewout writes:

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

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

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

best regards, thanks for all the interesting podcasts!

Ewout

MD communicable disease control, the Netherlands

Marie writes:

Greetings TWiV crew,

Thanks for your informative and entertaining podcast!

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

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

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

Thanks,

Marie

TWiV 165

Justin writes:

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

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

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

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

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

Yours,

Justin, esq.

Suzanne writes:

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

Michael writes:

Great men of TWIV,

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

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

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

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

Best wishes,

Michael

Penn State M.S. Hershey College of Medicine

Chen writes:

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

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

Sincerely looking forward to your reply and any advice.

best regards

chen

Ph.D. Candidate

Laboratory of Structural Biology

Tsinghua University

Beijing 100084

China

Saul Silverstein writes:

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

Jason writes:

Hey guys,

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

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

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

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

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

Cheers,

Jay

Senior Medical Scientist

National Enterovirus Reference Laboratory

WHO Poliomyelitis Regional Reference Laboratory

Victorian Infectious Diseases Reference Laboratory

North Melbourne,

Australia, 3051

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

Peter writes:

Dear Vincent, Rich, Alan and Dickson

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

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

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

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

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

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

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

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

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

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

Sorry for my rambling questions.

Peter

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

Saul Silverstein writes:

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

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

Atila writes:

Dear Twivers,

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

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

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

Thank you again for the great podcast,

Atila

Grant McFadden answers:

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

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

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

Anyway, I hope these points help clarify the question.

Cheers,

Grant

Thomas writes:

Hello TWiV crew!

Quick question for Dr. Racaniello et al:

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

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

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

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

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

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

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

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

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

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

he sent http://www.twiv.tv/hanahan.pdf

Tim writes:

Dr. Raceniello & Esteemed Cohorts:

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

(http://mecfscenter.com/)

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

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

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

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

Tim

Lance writes:

Dear Doctors,

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

A couple of messages to relay.

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

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

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

Peter writes:

Dear TWiVsters,

Have you seen this picture of a T4 phage tattoo:

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

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

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

Alison writes:

Hi TWiV gang!

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

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

Thanks so much for this awesome service for the public!

Kathy Spindler replies:

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

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

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

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

Cheers,

Kathy

Danielle writes:

Hello Twiv!

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

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

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

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

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

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

Richard writes:

Hi Vincent, Dick and other hosts

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

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

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

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

Looking forward to more virology

Regards

Richard

Richard writes:

Hi Vincent, dick and cohosts

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

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

Again thanks for your podcasts.

Regards

Richard

Juanjo writes:

Dear Vincent (and Dick, Alan and Rich),

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

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

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

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

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

With warm regards,

Juanjo

Peter writes:

Dear Doctors

I am sure others will send you these links

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

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

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

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

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

Essa writes:

Dear TWiV team,

Happy holiday and happy new year.

Thanks a lot for the great virology blog.

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

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

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

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

Sincerely,

Essa

Joe writes:

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

Tom writes:

Dear TWIVians:

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

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

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

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

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

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

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

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

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

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

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

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

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

Vincent, I fear that you may be right.

Tom

Austin, Texas

Jim writes:

Hi Vince et al

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

This has shifted my vote to thinking viruses are alive.

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

73 ( Best Wishes)

Tim writes:

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

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

pretty darn good storytelling……

Mary writes:

Hi all,

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

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

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

thanks! mary

Jimmy writes:

Hey Guys,

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

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

http://scienceexchange.com/

 

TWiV 164

Garren writes:

Hello Vincent

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

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

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

Cheers…

Judi writes:

Hi TWIV, TWIM, AND TWIP Persons of Note!

HHMI has a new video magazine

http://www.ibiomagazine.org/

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

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

Judi

(High school teacher and FOT (follower of TWIvmp)

Mike writes:

Hello,

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

Kathy Collins replies:

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

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

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

Best,

Kathy

Marie writes:

Hello TWiV crew,

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

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

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

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

Thanks!

Todd writes:

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

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

Sarah writes:

Hi Rich,

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

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

Sarah

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

Justin writes:

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

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

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

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

TWiV 163

Ronnie writes:

Hello Professor Vincent,

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

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

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

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

Greetings and happy holidays!

Ronnie

Michael writes:

Dear Twivome,

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

Junio writes:

Hello, TWiV crew.

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

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

Thanks.

Josh writes:

Dear TWiV Doctors,

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

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

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

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

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

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

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

Thanks,

Joshua

Johan writes:

Hi,

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

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

Thanks

Johan

Sweden

James writes:

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

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

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

Grant McFadden responds:

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

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

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

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

TWiV 162

Sarah writes:

Hello to the TWiV crew,

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

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

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

(Quote is from Table 1)

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

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

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

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

http://www.onehealthinitiative.com/

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

Keep up the great work – and keep having fun!

From justanotherkinase on twitter:

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

Gary writes:

Dear Wonderful TWiV People,

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

All the best,

Gary, MD

Sebastopol, California

Thomas writes:

Dear TWIVers,

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

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

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

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

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

Sincerely,

Thomas

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

Kathy writes:

Hi Vincent, Rich, Alan, and Dick,

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

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

Cheers,

Kathy

Ayesha writes:

A few questions on on HPV.

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

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

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

Michelle Ozbun replies:

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

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

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

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

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

TWiV 161

Ayesha writes:

Honourable TWIVnesses!

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

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

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

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

@neilfws via Twitter:

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

what do we think about this?

Raphael writes:

Hi, Dr. Racaniello.

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

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

Thank you very much.

Matt writes:

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

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

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

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

Yours Faithfully,

Ann writes:

Dear TWIV community,

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

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

Thanks for all your great work!

Ann

Virology Graduate student, Harvard University

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

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

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

TWiV 160

Neva writes:

Hi fellas,

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

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

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

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

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

Thanks for your fabulous podcasts.

Godfried writes:

Dear Gentlemen,

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

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

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

Godfried

ps i did the listeners survey

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

Volker writes:

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

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

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

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

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

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

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

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

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

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

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

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

Hope you can send me some clues..

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

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

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

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

So I would love to hear your second thoughts.

Volker Stollorz

Wissenschaftsjournalist

Köln

TWiV 159

Jenny writes:

Hi Vince and the rest of the TWIV-cast!

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

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

Thanks and have a Happy Thanksgiving!

Jeremy Luban writes:

Hey Vincent,

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

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

Jerm

Wes Sundquist writes:

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

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

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

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

Best,

Wes

Matt Evans writes:

What do you think of this:

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

Matt

anonymous writes:

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

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

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

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

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

PS. Did you ever do a part about Chikungunya?

Danielle writes:

Hello!

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

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

Thanks,

Danielle

Chris C responds:

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

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

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

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

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

Simon writes:

Hi Prof Racaniello

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

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

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

Simon

UK

Trudy writes:

[first part read on TWiP]

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

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

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

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

TWiV 158

Ricardo writes:

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

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

Ken writes:

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

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

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

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

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

(links to a Word document)

Jen writes:

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

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

thanks!

jen

Don writes:

Vincent, Dickson, Allen, and Rich,

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

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

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

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

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

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

Thank you for the great podcast,

Don

James writes:

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

James, Ph.D.

Tim writes:

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

Tim

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

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

Professor of Pediatrics

Division of Oncology

Cincinnati Children’s Hospital Medical Center

TWiV 157

Robert writes:

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

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

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

Nick writes:

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

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

With warm regards,

Nick Kelley, PhD

CIDRAP

Ricardo writes:

Hello TWIV members.

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

What is the reason for the lack of efficacy?

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

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

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

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

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

R i c a r d o M a g a l h ã e s

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

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

Peter writes:

Headline reads -

Horse euthanased with Hendra virus

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

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

Article…

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

TWiV 156

Kevin writes:

Dear Professor Racaniello,

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

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

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

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

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

Once again, many thanks for your patience and understanding.

Kind regards,

Kevin.

Janet writes:

Hi TWiV gang,

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

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

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

Keep up all the good work!

Grüße aus Deutschland,

Janet

Zachary writes:

Dr Racaniello and company,

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

-Zach

Kathryn writes:

Dear Twivers

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

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

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

Thanks for your show and keep up the good work.

~Kathryn

TWiV 155

Kim writes:

To the TWiVerati Intelligencia,

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

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

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

Kim

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

Luiza writes:

Hi, Professor Racaniello,

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

Best wishes,

Luiza

Laboratório de Genética e Imunologia das Infecções Virais – IMPPG

Universidade Federal do Rio de Janeiro

Rio de Janeiro, RJ – Brasil

Vinayaka writes:

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

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

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

- Prasad

——————————————————————————————–

Vinayaka R. Prasad, Ph. D.

Professor, Department of Microbiology and Immunology

Director, AIDS International Training and Research Program

Albert Einstein College of Medicine

David writes:

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

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

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

Thanks for the podcasts, learning much,

Not A Virologist

Antonio writes:

Hello there, acTWiVists!
Thank you so much for these podcasts. I’m a Filipino programmer / tech geek who’s been following the three of you since the Nile River virus episode. I’ve been absolutely captivated by this window you give the world into biology and the life sciences.
Your other student listeners might find the Nature Video covering the 2011 Nobel Laureates’ Meeting in Lindau fascinating. There’re five short films there featuring one-on-one dialogue between a student and a Nobel laureate who’re both working in the same field – shedding insight on the passing of the torch between generations in science.
All the best,
Antonio

TWiV 154

Gabriel writes:

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

Gabriel

Faleye writes:

Hi TWiV crew,

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

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

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

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

I look forward to hearing from you.

Faleye

(photos at VirusTalk)

Dan writes:

Hello,

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

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

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

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

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

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

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

Please keep up the good work.

Thank you,

Dan

Ricardo writes:

Hello Vincent and the rest of the twiv gang.

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

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

My best regards to all of you.

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

Ricardo Magalhaes, Ph.D.

Associate Professor of Microbiology

Faculty of Health Sciences of Fernando Pessoa University

Portugal

Geoffrey writes:

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

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

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

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

Geoffrey

Timothy writes:

Dear TWiVers:

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

Tim

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

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

Professor of Pediatrics

Division of Oncology

Research Director, Musculoskeletal Tumor Program

Medical Co-Director, Office for Clinical and Translational Research

Director of Pilot and Collaborative Clinical and Translational Studies Core,

University of Cincinnati Center for Clinical and Translational Science and Training

Cincinnati Children’s Hospital Medical Center

Georganne writes:

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

Thanks.

TWiV 153

Jim Pipas writes:

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

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

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

Michael writes:

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

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

~Michael

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

Jamie writes:

Hello Gentlemen (and Alan),

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

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

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

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

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

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

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

Jamie

Tim writes:

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

Thanks, virology want-to-be

Tim

Tony writes:

Hi TWIVers,

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

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

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

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

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

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

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

Regards,

Tony

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

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