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TWiV 163 Letters

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!


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"?


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



Johan writes:


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 :)




James writes:


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.


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