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TWiV 123 Letters

Sven writes:

Dear TWiV Captain and Officers,

I am a Swedish listener in my fifties, with a neolithic MSc in computer science and nowadays active within software quality (and yes, that's an oxymoron...). I found TWiV in September 2010 and I have now soon listened to them all. I am, as you understand, deeply hooked by TWiV and TWiP, and look forward to TWiM! Like so many others I listen during my commute, possibly to the detriment of my driving ability (no comments, please...). While sometimes much of the biochemical details are beyond my comprehension, the general structures and phenomena within the field are very interesting and stimulating. I also agree wholeheartedly with the majority in praising your style and tone!

Now and then you touch upon the subject of evolution of this or that mechanism in cells, and several times you have used the approximate phrase "evolution makes use of whatever it can get hold of". There are, of course, many examples of that in nature as you have mentioned, but also (at least) one artificial that I find very instructive. In a paper by Adrian Thompson ("Exploring Beyond the Scope of Human Design: Automatic generation of FPGA configurations through artificial evolution.", 1999 I think, unfortunately I can only find an "extended abstract") he describes how "evolution" was used to produce an integrated circuit capable of discriminating between tones of two frequencies. Even though the circuit was, to an engineer, too small, and also digital rather than analog, the evolutionary process used managed to achieve the goal. At first glance this may not seem so surprising. One of the more intriguing aspects, however, was the fact that although some parts of the chip appeared not at all to be connected to the "core" of the developed function, they could nevertheless not be eliminated. The author assumes that these parts still contributed through other means such as "[...] electromagnetic coupling, or interaction through the power-supply or substrate." The author continues "Evolution was able to exploit this physical behaviour, even though it would be difficult to analyse." So, the evolutionary process actually found, and exploited, phenomena an engineer would consider parasitic and unwelcome - to wit, phenomena an engineer would not look for and certainly would (should...) not dare use. But as evolution is blind to what we term "purpose" it had no such qualms! I find this very intriguing, as I see clear parallels in the microscopic world of cells as well as in the macroscopic world of ecology - there are so many intricate dependencies and mechanisms that, because they have evolved rather than been designed, are not fully analysable and are completely devoid of intentional "purpose".

Let me finally suggest as a POTW a book, unrelated to the previous subject: "The Ghost Map: A Street, an Epidemic and the Hidden Power of Urban Networks" by Steven Johnson. A fascinating tale about the cholera in London in 1854 and how John Snow traced the source of the outbreak - a combination of detective story and science mind, if ever there was one!

Thanks for a great show and service to the public.

Live Long and Prosper!

/Sven-Urban

Sweden

Ed writes:

Dear TWiV,

Your tongue-in-cheek discussion after Alan’s pick of the Avian Vocalization Center on TWiV 112 that suggested recoding the sounds of viruses reminded me of an email I received from a friend of mine that pointed to that fact that this is already being done. I also heard mention on a Nature Medicine podcast that a grad student in Georgia, Alexandra Pajak, composed a symphony using the HIV sequence.

Here are the links: http://www.hhmi.org/bulletin/nov2010/centrifuge/scientific_artwork.html

http://www.scientificamerican.com/blog/post.cfm?id=what-does-hiv-sound-like-2010-10-27

I think it would be really interesting to find out what each viral symphony would sound like, and the result of viral evolution on each score. I understand that Ms Pajak also converted the amino acids and not just nucleotide sequence into music. Thus, silent mutations in the nucleotide sequence would obviously result in no change to the amino acid score. Do you think this could be utilized as a way to analyze sequences in the future by immediately converting it into notes that correspond to each nucleotide and comparing the music by listening? It would obviously have to be free of artistic interpretation in that case as both artists I linked to here adjusted rhythm and tempo to make the pieces more pleasing to listen to.

Thanks again for your fantastic podcast.

Ed

Multiple Sclerosis Research Center of New York

Dan writes:

Hi TWIV,

Thank you for your podcast. Please don't feel the need to read this email on the show; I don't want to turn TWIV into TWICFS.

Listening to TWIV and reading virologists discuss a potential XMRV/CFS link, I'm impressed by the thoroughness and caution which virologists take about drawing conclusions.

This makes a striking contrast with earlier CFS research. Take this paper* asserting a link between early childhood abuse and CFS. The link between the paper's findings and conclusions involved a complex chain of causal links, none of which were investigated. Many of the limitations of the study aren't discussed, including similar limitations which are frequently discussed in XMRV research (difficulty identifying patients, contradicting results of other groups, lack of blindedness). This study appears to me to be much weaker than virtually any virology study. Yet, at the time that it was done, the study was uncritically hailed in much of the news media. There has been no gauntlet of studies attempting to poke holes in the hypothesis, as there are in virology. And this is just one example of many.

It seems to me that the bar of evidence required in different areas of science is quite different. I believe this creates a systemic bias, where the least cautious areas of science will have their results most broadly accepted until another area contradicts it. I don't really know what could be done about this, but I'm curious about your thoughts. It has a real and large impact on people with CFS, as bad research often leads to bad policies.

Thank you again,

Dan

Austin, TX

*http://archpsyc.ama-assn.org/cgi/content/full/66/1/72

Heather writes:

Hello, TWiV guys,

In response to Ken's podcast idea on TWiV #111, I say go for it! I'm a medical student at Columbia University P&S, and I disagree with Alan about how much time you'll have while you're in school. Here at P&S, activities outside of our regular curriculum are actively encouraged, especially in the first two years (that's actually when you'll have the most free time). Students play sports, do art, put on concerts and plays, volunteer at free clinics, and still have time to study and learn medicine. When you start school, ask around and you'll likely find several people who would be interested in helping you start a podcast, especially if you also talk to students in other programs or years at your school. You'll probably even find that working on the podcast will help you learn the information you need for classes better!

Heather

P.S. Alan, you'd be surprised at how much effort goes into the plays and musicals we do here at P&S. The students involved put in hours and hours on many rehearsals, set design, sound and lighting, even during exam periods (and yes, we do still manage to pass all of our exams) and we invite everyone on campus to the multiple performances we do. Not to brag, but the students and faculty are almost as proud of our extracurricular achievements as we are of our medical knowledge.

Jeff writes:

Hi TWIV guys,

I was just listening to your show with Alan Rein on XMRV. Both you and Dr. Rein seemed to think that identifying junctions in samples between XMRV and human genome from tissue and mouse genome IAP controls would be good evidence for legitimate XMRV infection in patients.

Both of these seem like they would address contamination with mouse genomic DNA, but my reading of the Hue et al. Retrovirology paper was that they were asserting that false positives could be from contamination with human cell lines such as 22Rv1. Do you think such contamination could be responsible for some false positives for XMRV in patient samples? If so, is there a way to control for such contamination?

I'd be interested in your thoughts.

Jeff

 

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