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Lo and Alter respond to contamination and other methodology questions in PNAS"

Discussion in 'XMRV Research and Replication Studies' started by CBS, Oct 1, 2010.

  1. CBS

    CBS Senior Member

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    There are a series of letters published in today's (9/30/10) early edition of PNAS:

    I have not yet had a chance to read them - they appear to require a subscription - I have full copies.

    Erlwein, McClure and Co.
    Martin
    Lo and Alter
    I'm sure that as we read through and analyze these there will be more posts relatively soon.
  2. CBS

    CBS Senior Member

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    I'm going to try and break this down with brief quotes and a paraphrase or two:

    Erlwein -

    Paraphrase - It's contamination and we don't think you handled your patient and control samples in the same manner. And for good measure, we'll throw in a jab at something they claim wasn't included in their methods section.

    Martin:
    Paraphrase - Lo et al. used such a nested PCR near the limits of its sensativity and there fore we cannot rule out the possibility that everyone in society has some level of MLV infection

    Lo Atler response:
    These are the key points. Sounds like Lo and Alter are quite comfortable with their study as it was and with the acknowledge limitations.
  3. CBS

    CBS Senior Member

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    On Sept 13th, Myra McClure was interviewed by Vincent Racaniello forr his TWiV postcast. McClure was quite convinced that the WPI needed to prove there was no contamination.

    Was she aware of Lo and Alter's soon to be published response? Did she make her case for contamination after the episode of TWiV?

    Will this latest response from Lo/Alter make any difference to her on the issue of contamination? As Lo and Alter state, we are "still at a very early stage of exploration." However, continued claims that there is nothing to see ("just a bunch of CFS patients being CFS patients - complaining while we can't figure out why") are becoming harder and harder to defend.
  4. eric_s

    eric_s Senior Member

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    Thanks CBS. That's very interesting. I'm still fully behind Lo/Alter, when their study came out i said that as far as i'm concerned there is an association between CFS and HMRV.

    Here the critics really provide technical arguments, which i'm not able to understand, but i like that way. Done in such a way, i don't have any problem with people criticizing positive results.
  5. CBS

    CBS Senior Member

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    There are too many big names that have been looking at this for years and are gearing up for greater involvement (eg. Lipkin & Singh). You don't do that if you're not finding anything (if you can't find anything apparently you take your negative results and go on a speakers tour - maybe if McClure was spending more time in the lab and less time defending her absence of evidence she'd be a bit more open to changing her tune).
  6. ukxmrv

    ukxmrv Senior Member

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    CBS - is that the same Dr Martin of the "Stealth Virus" fame?
  7. Esther12

    Esther12 Senior Member

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    Thanks for that info CBS.
  8. voner

    voner Senior Member

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    cbs: thanks for the info and explanation...

    Since Dr. Ila singh used to work at Columbia, and knows Dr. Vincent Racaniello, lets hope He interviews her on TWIV when her studies are published. Hopefully, this will clarify the muddy water. I was struck by Dr. Lombardi's confidence in his results, etc when he was interviewed on the radio show .... Nevada Newsline --interviewed by Mike Hillerby... Dr. Lombardi was proceeding aggressively and didn't act as though there was ANY doubt in his mind....

    it really sounds like the research world is heading in 2 directions, one small group are agressively pursuing the XMRV connection and the rest are quibbling. Some researchers love to quibble (using the word "quibble may be a bit harsh here)...and it certainly is valid at this point.

    the big question will be::: "WHO GETS THE FEDERAL RESEARCH $$ ?????? & WHY?
  9. CBS

    CBS Senior Member

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    quantitative versus qualitative distinction?

    Lo and Alter state:

    This is an interesting comment. It has significant potential to change the meaning of detecting MLV's in controls and other disease states. It also means that dismissing MLV's as being 'passenger viruses' or co-infections may be overlooking the importance of quantitative distinctions.



    On an administrative note, I have asked that the title of this thread be changed. My first thought was:


    "Lo and Alter MLV smackdown with McClure and Friends in PNAS"


    Instead I'm asking for a change to : "Lo and Alter respond to contamination and other methodology questions in PNAS"
  10. anciendaze

    anciendaze Senior Member

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    Once again it sounds like "if you were doing things the way we are you wouldn't get these disturbing results."

    The possibility of many similar endogenous sequences is scarcely news, this is a fundamental problem for the entire field. It also says rather clearly that humans have been infected with very similar retrovirus over long periods in the past.

    On contamination: you need to test your reagents and equipment before you use them, not try to untangle the mess afterward. (Did the "esteemed" Dr. Weiss do this in 1997?) As for working at or near the limits of sensitivity, I must ask "are you running a research laboratory or an ordinary clinical laboratory?" (Funding can be adjusted as appropriate.)

    As I've said before, you can guarantee you will not get positive results due to contamination if you exclude all positive results, and this proposition does not require expensive research to prove. This now appears to have happened at the CDC, which has an extremely sensitive test for mouse DNA. The contamination problem in the laboratory where they were working with samples from DeFreitas went unreported in their publications. At different times the contaminant has been identified as either gibbon ape leukemia virus or murine leukemia virus. After the contaminant was completely excluded, their results turned so thoroughly negative they started fiddling with her lab. protocol until it produced garbage. (Failure of this modified protocol was believed to discredit her.) Like the contamination later plaguing Dr. Weiss, the specific route for contamination was never identified.
  11. urbantravels

    urbantravels disjecta membra

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    Can we get these letters into the Library?
  12. Cort

    Cort Phoenix Rising Founder

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    Well said!
  13. anciendaze

    anciendaze Senior Member

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    This is a case where CBS and I agree in broad outline, but differ on specific wording. We wouldn't be having this discussion if major authorities had not made major blunders many years ago. Most people simply never noticed that virtually all information came from a very small number of sources which substituted opinions for facts. Once the bandwagon was rolling, it was easy to get others to sign on to the idea. Colossal mistakes spanning years do happen.

    What has dismayed me about the whole series of responses since last October is the paucity of new ideas, (compared to those getting positive results,) and the unwillingness to grant opponents the bare possibility of having real results, even temporarily and hypothetically. I have tried to make contamination arguments work. The only place where I have had some success is with Huber's study, and there I had to assume she had an underlying set of data with modest positive results mixed in with contamination to get probabilities I could swallow. The probabilities elsewhere would make being dealt a pat hand at bridge look like a sure thing. One group might make systematic errors to cause badly skewed results, but, as more diverse groups become involved, it is less and less likely they will make the same errors without noticing.

    I have assumed the negative results came from people who were honestly doing what they said they were doing to the best of their abilities. We have now reached the point where these criticisms verge on charges of gross incompetence, fraud and conspiracy. If I am forced to make a choice between competing conspiracy theories, I know which I would choose. I will not reject data simply because someone else says "these can't be right, we got different results." (This reminds me of the bit in the book and movie MASH about "We're the pros from Dover". Assertion and bluff work better than we like to admit.) It looks more and more to me like the contamination called into question is contamination by the idea of organic causation.
  14. Otis

    Otis Señor Mumbler

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    What a great finish to that post anciendaze! And the this contamination is very widespread indeed. Anyone who would argue that science is objective doesn't have this disease.
  15. ixchelkali

    ixchelkali Senior Member

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    Yes, it's Dr W. John Martin, the stealth virus man.
  16. Cort

    Cort Phoenix Rising Founder

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  17. alex3619

    alex3619 Senior Member

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    Hi anciendaze

    I find the bolded (my bolding) bit highly disturbing. Do you have a reference for this? Taken in a particular way, it could imply that the CDC found XMRV way back then, and dismissed it as contamination, and then shut down all research in this area. So I just want to ask: can you elaborate on this? I might actually have read something on this in the past, my memory is atrocious, but it would have been before I knew about XMRV or all sorts of red lights would have been flashing in my mind.

    Bye
    Alex
  18. anciendaze

    anciendaze Senior Member

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    There is a quote in "Osler's Web" which appears to be have taken from a recorded interview with Tom Folks referring to possible Gibbon Ape Leukemia Virus. He also says that the decision to end the lab. work came from upper floors in the administration building. Leonard Jason has made statements about the CDC contamination being MLV in published interviews, but I don't have a good reference.

    I want to make it clear I am not describing this as a clear conspiracy. This is the kind of unchallenged assumption I've found in organizational mistakes big enough to kill people in completely unrelated situations. Another clue is Folks' statement that the test started jumping on endogenous material after they changed the protocol. With 94% homology to MuLV and 95% homology to an endogenous sequence, it would be easy for them to set up criteria for test assays which would also exclude XMRV. After enough people have accepted such criteria it is virtually impossible to get an organization to change them. The circular reasoning has been expanded to the point the circle passes over the horizon for individuals with limited authority and responsibility. Those higher up the hierarchy don't have the time and interest to challenge detailed assumptions originating at a lower level. About 80-90% of their time goes to internal politics and funding battles.

    When the fertilizer hits the turbofan, you can expect to hear that "mistakes were made" without any personal responsibility for those mistakes.
  19. alex3619

    alex3619 Senior Member

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    Hi anciendaze, If this is true, then I agree its not a conspiracy. Its a case of total stuff up and incompetence. It doesn't mean they aren't trying to cover it up now though if they've realized what they have done , we simply don't know one way or the other. I've read "Osler's Web" but that was many years ago. Maybe its time I got it down off the shelf again. Bye, Alex
  20. natasa778

    natasa778 Senior Member

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    when the fertilizer hit the turbofan on the BSE/CJD story, these were the conclusions of subsequent enquiry:

    [replace BSE with XMRV and insert spooky music for full reading experience]

    http://collections.europarchive.org...iry.gov.uk/report/volume1/execsum2.htm#669592

    # BSE has caused a harrowing fatal disease for humans. As we sign this Report the number of people dead and thought to be dying stands at over 80, most of them young. They and their families have suffered terribly. Families all over the UK have been left wondering whether the same fate awaits them.
    ...
    # BSE developed into an epidemic as a consequence of an intensive farming practice - the recycling of animal protein in ruminant feed. This practice, unchallenged over decades, proved a recipe for disaster.

    # In the years up to March 1996 most of those responsible for responding to the challenge posed by BSE emerge with credit. However, there were a number of shortcomings in the way things were done.

    # At the heart of the BSE story lie questions of how to handle hazard - a known hazard to cattle and an unknown hazard to humans. The Government took measures to address both hazards. They were sensible measures, but they were not always timely nor adequately implemented and enforced.

    # The rigour with which policy measures were implemented for the protection of human health was affected by the belief of many prior to early 1996 that BSE was not a potential threat to human life.

    # The Government was anxious to act in the best interests of human and animal health. To this end it sought and followed the advice of independent scientific experts - sometimes when decisions could have been reached more swiftly and satisfactorily within government.
    ...
    # At times officials showed a lack of rigour in considering how policy should be turned into practice, to the detriment of the efficacy of the measures taken.

    # At times bureaucratic processes resulted in unacceptable delay in giving effect to policy
    .
    # The Government introduced measures to guard against the risk that BSE might be a matter of life and death not merely for cattle but also for humans, but the possibility of a risk to humans was not communicated to the public or to those whose job it was to implement and enforce the precautionary measures.

    # The Government did not lie to the public about BSE. It believed that the risks posed by BSE to humans were remote. The Government was preoccupied with preventing an alarmist over-reaction to BSE because it believed that the risk was remote. It is now clear that this campaign of reassurance was a mistake. When on 20 March 1996 the Government announced that BSE had probably been transmitted to humans, the public felt that they had been betrayed. Confidence in government pronouncements about risk was a further casualty of BSE.

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