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Article: Comedown at CROI: XMRV and CFS at the Conference on Retroviruses and Opportunistic Infectio

Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, Mar 7, 2011.

  1. Phoenix Rising Team

    Phoenix Rising Team

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  2. anciendaze

    anciendaze Senior Member

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    The arguments on variation are subject to two problems: creating a cell-line is an extremely selective process; you naturally see more variation where you have more data. If there were a wild-type virus population with considerable variation, running infected tissues through the long sequence of passages used to create the strain would strongly select particular strains of virus just as it strongly selects a particular strain of cells. Limited data from the two studies finding HGRVs show greater variation, unless you argue that these are completely distinct viruses. Both are gamma retroviruses and both infect human cells which should be a concern. Arguments over probability need data to work with, otherwise you are looking for your keys under the lamppost, where the light is better.

    We continue to see people busy telling the virus how it ought to behave. Viruses do not respect authority.
  3. jace

    jace Off the fence

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    Hi Cort, that's a pretty wide ranging article. Just a few points:

    The 22RV1 cell line was created by Pretlow et al in 1991, 8 years earlier than you state: http://jnci.oxfordjournals.org/content/85/5/394.short

    The paper you quote re Miller in 2010 was lead by EC Knouf, here's another quote from that paper that precedes your second one above:

    http://jvi.asm.org/cgi/content/full/83/14/7353#R14

    Note "Similar" not near identical, and note the rather less than perfect peptide match at the start of the quote. AD Miller was lead in another, later XMRV paper last year, on "Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors", which doesn't sound like he was convinced it was a lab recombinant contamination at that time.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939604/

    Moving on to Stephanie Hue, and the paper published alongside four others on the 20th December last... Gerwyn's comment, published in Retrovirology, shoots it down in flames. The incorrectly used Baysian technique Hue et al employed is enough, for me anyway, to discredit Hues' hypothesis (which certainly has not reached the status of a theory). http://www.retrovirology.com/content/7/1/111/comments

    I could go on. Cort, sweetheart, sometimes it's best to leave scientific analysis to those that understand the science (not me, I hasten to add) but if not, please give references in future so lay people can check quotes out, and see them in context. Fair enough?

    We are a long way from the hypothesis that XMRV and other HGRVs are implicated in ME/CFS being disproved. A very long way.
  4. pine108kell

    pine108kell Senior Member

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    Wow, that is really a condescending manner of trying to make a point. Why not leave out the "sweetheart" and "those that understand science" part and just stick to your other points and links.
  5. jace

    jace Off the fence

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    Gee. I was just trying to make a friendly suggestion. Sorry you didn't approve.
  6. anciendaze

    anciendaze Senior Member

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    My criticism of the hypotheses of recombination and contamination is separate from personal criticism of Cort. With limitations on my ability to attend scientific conferences and hear what is being discussed off the podium, even when video is available, I have to depend on others to report what they hear. I do not want him to filter what I hear to avoid upsetting me. The arguments being presented give considerable insight into the politics taking place out of sight. These trends are ugly, but I can't counter them if I don't know about them.

    Research on APOBEC enzymes is apparently off in some other world from this conference. The discovery of hypermutation, and viral sequences which evade this defense by using codons that hypermutate into synonyms is a major step forward. We are unlikely to have exhausted the catalogue of natural defenses against retroviral infection. HIV-2 was in the wild long before anti-retroviral drugs were available, and the human race has not become extinct. With one such example of host-virus interaction which can defeat PCR detection, it is unwise to assume PCR will not fail in special cases.

    The argument I've heard that PCR is good enough to cause people to be sentenced to death is specious. When positive results are presented in court they are convincing. If anyone has been sentenced on the basis of negative results, an immediate appeal is in order.

    The sophistication of the interaction of host defenses and viral sequences strongly supports the idea this is a highly-evolved interaction. Arguing that such an effective infectious agent can spring de novo from laboratory work which is now standard practice in research is to argue that all such work should be limited to containment facilities -- a point deniers are careful to avoid even thinking about.
  7. SOC

    SOC Moderator and Senior Member

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    I agree with pine108kell; that was an unnecessarily condescending way of trying to make a point. Your post was interesting, informative, and intelligent until you diminished your credibility with,

    If that's your way of making a friendly suggestion, I'd hate to hear what you sound like when you're being snide.
  8. Christopher

    Christopher Senior Member

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  9. Christopher

    Christopher Senior Member

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    Curious how her tone alters her content. Could you explain how?
  10. carolinetanderson

    carolinetanderson

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  11. Cort

    Cort Phoenix Rising Founder

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    Hi Jace, here's how found the info on 22RV1. I punched it into Pubmed and went to the first paper published on it. Here it is - notice the title....A new human prostrate cancer cell line - 22RV1.

    The paper you refer to focused on xenografts

    With xenografts they were growing prostate tumors on the backs of nude mice. In the cell line the mice are gone and they are growing prostate cancer cells by themselves in culture - much more quickly, and testing them etc.

    Of course he wasn't and I didn't suggest that he was, and I don't know that he feels that way now. As I noted in the article Miller's first stab at genetic analysis was a preliminary one. (Hue ended up doing a paper focused on a genetic analysis). I pointed out the views of the people at the conference not Dr. Miller - and I hope you will not portray the conclusions of those people as the conclusions of Dr. Miller - since I don't have any idea what he thinks about what happened at the CROI conference. I was pointing out was the chain of progression of events - not how Miller about felt them. As I noted in the article 22RV1 only gained attention as the findings started piling up. It could very well be that Miller believes else is going on and I believe he is working with Dr. Silverman to buttress his claims regarding prostate cell integration.

    Got it -Gerwyn is an amazing guy. He's able to find problems with many studies and he seems to have wider breadth and depth of knowledge about PCR and genetic analysis and other subjects evem than the professionals in the field who make their living at it. (I admit the sarcasm - sorry...Time will tell all......and hopefully he's right - XMRV working out helps everybody...)

    Thanks Hon. I will put the citations in the paper - good idea.

    Something we can agree on! Much more work needs to be done - I agree!
  12. Cort

    Cort Phoenix Rising Founder

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    Thanks Caroline - that was Miller's or rather Knouf's first XMRV paper. Jace is correct that the lead author - the one that actually did the study - is usually the one referred to. Miller is the senior author of the study as Dr. Mikovits was in the Lombardi et al Science paper. They oversaw the study; ie Miller oversaw Knouf's study and Mikovits oversaw Lombardi's study. Sometime I just pull out the most well known -author and call it 'their' study. I did that with the Silverman integration paper. Silverman was neither the lead author or the senior author actually. In fact he was apparently the least significant author of the paper - according to the position in the citations he appeared in. :eek:

    Calling the Lombardi study the WPI's study isn't correct either because the NCI and Cleveland Clinic and VIP Dx all contributed to it but it's easier and it gets the point across as they were the main participants. Still its always better to be accurate.
  13. Enid

    Enid Senior Member

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    Can I add a little aside about Viruses - 2000 comotose one of our Biologists ( ? Dawkins) saying this will be the Century of the Virus. And all this research and findings show he is not far out. Sussing out going well ahead.
  14. Cort

    Cort Phoenix Rising Founder

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    The news right now is tending in the wrong direction but don't count out XMRV. Silverman has years invested in XMRV in both prostate cancer and ME/CFS. Dr. Ruscetti had been involved with XMRV for at least 2 years. He was the second author of the Science paper. Dr Alter is very publically associated with XMRV.

    These are all major figures - they presumably have large labs and the resources available to them to rebut these charges and they are undoubtedly working very hard to do that. This is the most visible topic either of them have been engaged in a long time.

    Coffin seems to have decided but as Ruscetti and Silverman are in the game - and the big studies are unresolved - there is much work left and much more to learn about XMRV. Dr. Klimas said there would be hills and dips - this could be a dip. I imagine we'll be pretty clear on XMRV by the Fall.
  15. Christopher

    Christopher Senior Member

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    The news according to some sources is trending in the wrong direction. The people actually studying XMRV and related retroviruses are certainly not stopping their work.

    Also you did not mention positive XMRV presenters requested permission to speak at the conference, but they were denied. Only the contamination studies were presented.
  16. Enid

    Enid Senior Member

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    And we can wait for this is a very complex area for brilliant minds as we follow them through unravelling (and for the whole of science) - the Virus - cause of so much disease including mine. No easy answers for us yet maybe. They will come. Off thread thanks to you Cort and all for revealing the pathetic and dead end PACE.
  17. SOC

    SOC Moderator and Senior Member

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    can't because I didn't say her tone alters her content. What I said was that her tone and language choices diminished her credibility.
    That I can explain.

    When a writer is attempting to make an objective, scientific argument, personal digs and other unnecessary emotional commentary call into question the objectivity of the writer. Ask any English/Rhetoric teacher. Tone affects how the argument is perceived. That is part of it's purpose, to indicate the emotional environment from which the writer is presenting his/her argument -- professional, objective, scientific, humorous, ironic, angry, snide, emotional, etc. Concluding a supposedly rational and objective commentary with snide remarks aimed at the reader diminishes the writer's credibility as an objective reporter of facts. It suggests that the purpose of the argument was more to demean or insult the reader than it was to objectively present factual information.
  18. kurt

    kurt Senior Member

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    Thanks Cort, for helping sort out the arguments a bit for us.

    We are indeed a long way from the XMRV to CFS connection being disproven. But we are also still far away from there being a proven connection. These new developments don't help that much at all, each new scientific doubt can add years to the process of developing a consensus opinion.

    Has anybody else noticed (with dismay) how the debate amongst the professional researchers here is all about retroviruses, and not about CFS? They are retrovirologists after all, and that is their primary interest.

    I think we need to find a research field that will embrace CFS itself as a serious problem to solve. Not just a single hypothetical pathology.
  19. Jemal

    Jemal Senior Member

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    I immensely enjoyed this recap. Thanks.
  20. SOC

    SOC Moderator and Senior Member

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    Well said, Kurt.

    I wonder if there is a research field that will embrace ME/CFS until the pathology is known.

    While we have some wonderful researchers in a number of fields working hard to solve ME/CFS, they are experts in their own fields. Should research into ME/CFS turn away from their areas of expertise, their organizations are unlikely to continue to investigate the disease. And so it should be -- experts focusing on their own areas of expertise. But it is a big benefit to have an organization that will follow the story wherever it leads. Another reason to maintain support for the WPI, the only research organization (that I'm aware of, anyway) devoted to solving the mystery of ME/CFS regardless of the direction research takes.

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