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Mikovits responds to Singh Study

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by dannybex, May 6, 2011.

  1. ukxmrv

    ukxmrv Senior Member

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    Heapsreal,

    I did ask one of the researchers (Dr Holmes in NZ) but he was too sick himself to keep up with the developments and make a public comment.

    Dr Martin (Stealth Virus) did post to your thread a few times recently on this forum. Hoping he will post again.

    Dr Defeitas has not publicly commented.

    They must be feeling deja vu after the last time I would imagine. Again, like Dr Holmes I wonder if Dr Defreitas is physically well enough to answer. It would I imagine be very stressful.
     
  2. anciendaze

    anciendaze Senior Member

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    I'm still digesting the Shin/Singh paper, However, there is an idea which occurs to me at this point which I want to try out on you.

    I've described PCR as like an old-fashioned radio with two knobs for sensitivity and selectivity, in addition to tuning and volume. There has never been much doubt in my mind that turning selectivity all the way up will give you a 0/0 result. I expected more variation before the Lo/Alter results. I have come to believe variation and recombination are essential parts of the 'strategy' the virus uses to evade immune response. We have evidence of a great deal of recombination and potential for infection in the laboratory. It is hard to square this with the claim the flow is entirely one-way. These were not special containment facilities.

    If the virus is capable of playing such tricks indirectly via reagents and unintentional transfers, and possesses demonstrated ability to infect human cells, not to mention rhesus macaques, it seems highly implausible that it does not affect humans in less controlled circumstances. Every time Dr. Coffin sweeps out his garage he likely picks up enough mouse virus to contaminate a lab, since we know virions are present in droppings. (This would be a unique excuse for having someone else do the dirty work.)

    So, on the one hand, we have a problem of excluding actual mouse sequences, and, on the other, we have a problem excluding endogenous sequences. With 94% homology to MLV and 95% homology to a HERV there is a fundamental problem in detection. Concentrating on highly-conserved subsequences will likely increase the probability of matching endogenous sequences. Deliberately avoiding highly-conserved sequences increases the apparent effect of variation.

    This is not simply a laboratory phenomenon. Human bodies can't tell the difference either. Excluding antibodies which might be cross reactions extends the problem to another level.

    In the past, some percentage of ME/CFS patients have shown the anti-nuclear antibodies (ANA) characteristic of autoimmune disorders. More recently, a high percentage have shown specific antibodies to cardiolipin (ACA). Most neurological damage appears to come from a specific immune response. Immune interactions with the brain are a bigger problem in humans than any other species I'm aware of. If you check the list of diseases believed to be autoimmune disorders, you will find a surprising correlation with 'rumor viruses'. You will also find pitifully little progress on etiology over the last generation.

    In rhesus macaques the virus quickly disappeared from the blood. An immune challenge may be necessary to generate detectable antibodies. The idea that the specific sequences which started the pathological process disappear, except in internal organs, while a great deal of clutter which serves to confuse immune response continues, seems to fit.

    One technique possible with qPCR is to spike all samples with a tiny amount of a specific sequence, then subtract the effect of this after a known amplification. This can uncover highly similar sequences which would otherwise be missed. This might very well distinguish patients from controls. If so, it would tell us something important about the disease.
     
  3. liquid sky

    liquid sky Senior Member

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    Judy called Singh and the others "good scientists". She was not insulting in the least. Being polite does not require her to state her study is wrong, when she is convinced otherwise. Nor does it require her to not point out the faults of study that did not replicate either of the 2 early studies that found HGRV's in PwME.

    Looking forward to more comments from WPI and Lo/Alter.
     
  4. Andrew

    Andrew Senior Member

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    No study covers all bases. This is true of the Mikovits study and the Singh study. I feel the same way about Singh that Mikovits does. I think Singh is a good scientist. But (correct me if I'm wrong), it looks like Singh is saying that she found contamination in Mikovits' reagent. If this is the case, a possible next step is for Mikovits to replicate the method Singh used to test the reagent. For all we know, the test contaminated the reagent. Lots of possibilities. OTOH, this would not explain how a reagent could selectively contaminate more subjects than controls, but I think it would be a good step.

    When I used to do data analysis and two people were getting different results, we did not assume one or the other were correct. We figured out why the results were different. I think this needs to be done with XMRV research. IOW, not speculate on the difference, but rather, identify the cause of the difference.
     
  5. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    thanks ukxmrv, deja vu exactly!!
     
  6. shannah

    shannah Senior Member

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    Stoye is joining with Coffin in criticising the WPI but seems to be taking it a step further.

    Researchers stand by findings linking XMRV to chronic fatigue syndrome

    By Trine Tsouderos, Chicago Tribune / For the Booster Shots blog

    May 11, 2011, 6:35 a.m.
    Researchers who remain convinced that a retrovirus is linked to chronic fatigue syndrome say they have proof their findings are correct, dismissing a recent comprehensive study that found no evidence of the link.

    That paper, published last week in the Journal of Virology by a team led by University of Utah researcher Dr. Ila R. Singh, is just the latest in a long line of studies conducted by scientists who have looked for evidence of the retrovirus XMRV in the blood of chronic fatigue syndrome patients but failed to find any.

    The scientific communitys consensus is that the original findings, reported in the journal Science in 2009, likely were the result of lab contamination, not a real infection in people.

    But researchers from the Whittemore Peterson Institute for Neuro-Immune Disease, which led the team that published that report, say they are confident of their findings.

    One reason, they stated in a written response posted online Monday, is that they have isolated XMRV from one chronic fatigue syndrome patient and decoded its genetic sequence. That sequence, they write, is different from the genetic sequences of two known XMRV samples.

    Those differences indicate they found something growing and changing in a person, not the same lab contaminant over and over again, they say. Sequence data demonstrates that this virus is clearly distinct, the researchers wrote in their statement.

    But the three sequences published in a federally maintained genetic database known as GenBank are nearly identical, several retrovirologists pointed out. The differences among the sequences amount to very few bases among more than 8,000.

    Thats about the amount of difference I would expect to accumulate during one or two tissue culture passages, wrote Tufts University retrovirologist John Coffin. Given what we now know about this virus, I don't see how it can be anything but cross contamination of cell cultures.WPI also stated that many of the patients tested positive for antibodies to a XMRV indicating that these patients had an immune response to a XMRV.

    But virologist Vincent Racaniello of Columbia University said that cant be true. There is no way they can say that the antibodies are specific for XMRV, Racaniello said.


    In an email, retrovirologist Jonathan Stoye suggested that if the methods described in the original paper dont hold up, it should be retracted.

    Sooner or later they are going to have to face up to the fact that [their] paper is almost certainly flawed beyond repair, wrote Stoye, head of the Division of Virology at the UK Medical Research Council's National Institute for Medical Research. What is more, WPI cannot simply blame others for failing to reproduce their protocols.

    Rather they must ask themselves whether the protocols they have described, if followed to the letter, can yield the data they have reported, he wrote. If not, the original paper should be retracted.

    http://www.latimes.com/health/boostershots/la-heb-xmrv-chronic-fatigue-20110510,0,1125656.story
     
  7. currer

    currer Senior Member

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    You know, I get a cold chill when I read the word "retract".

    Why? If they can DISPROVE the research they are welcome to do it.
    But why should anyone "retract" a paper, even if it is wrong? Science can learn from mistakes as much as from successes.

    I feel very disturbed by this. Why this attempt to "erase" research? What is so threatening about it?
    Do they want to close down this line of research? Are they afraid of what it may reveal?
     
  8. asleep

    asleep Senior Member

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    That LATimes article is atrocious!

    It misrepresents the WPI response.

    It gives uncritical air to Coffin, Racaniello, and Stoye who are so transparently desperate to make this go away.

    The Stoye quotes are just surreal. Even if the Science paper were conclusively shown to be wrong (which is sooooo far from being the case as to be laughable), calling for retraction just reeks of heavy-handed politics.
     
  9. Angela Kennedy

    Angela Kennedy *****

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    To be honest, I've called for retraction of the PACE paper (and the accompanying editorial) in my complaint to the Lancet. My reason for doing this is because, as it stands, it is directly dangerous to patients because it claims 'safety' for GET, in particular, when it should not have.

    If a proper investigation of the discrepancies of the PACE trial is conducted, the question then arises of what to do with a dangerously incorrect article that claims the authority of peer-review, and one which has been accepted by NICE (because of their belief in peer review as 'best quality evidence'), therefore having direct (and advers) effect upon patient care. That's even before the problems of others like wikipedia claiming CBT/GET is safe for ME sufferers based on so-called 'reliable sources'!

    That's unfortunately how serious the situation is. There may be other ways around 'retraction' as far as PACE goes, but presently that seems to be all we have as an option.

    Of course the Lombardi paper is different, because they did not make outlandish claims! From what I've seen, nor did the Wakefield et al paper, contrary to what might be claimed.
     
  10. Bob

    Bob

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    Why do I always feel like the goal posts are being continuously moved?
    The WPI provides evidence of genetic variability, but apparently it's not good enough.
    Apparently the tissue culture that the WPI is contaminated with, has undergone an extra couple of passages than the cell lines that have been studied in research papers.
    (OK, I know that I'm not being very scientific here, but it seems that the WPI can never do anything right!)

    ETA: Now I'm not sure if they were referring to sequences that have been with genbank for some time, or if they are refering to the 3 new sequences that have been submitted to genbank by the WPI. If they are referring to the old sequences, then please ignore this post! (I had assumed that they meant the new sequences.)
     
  11. Bob

    Bob

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    I suppose it's a lot of hot air really, because it will all be determined by the BWG and by Lipkin, or by any other convincing positive studies if any are ever released.
     
  12. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    its because the govt have invested so much money in the pace trial???????????????????????????///
     
  13. asleep

    asleep Senior Member

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    I don't disagree at all. It is a tricky issue, but I concur that there are circumstances where retraction is warranted. But the bar should be held very high and the process should be transparent and judicious, not reactionary and politicized.

    On one hand, we have a study that claims nothing more than a potential association. Beyond a faux frenzy (amongst otherwise unconcerned individuals) about ARV usage in a handful of severely ill patients, this study poses no risk to anyone (i.e. it poses no actual risk). It was a sound study designed to test a hypothesis and did so in a diverse, scientific, and rigorous manner. The call for retraction is being made by a clearly biased person, wearing the robe of "scientific authority", aired and promoted uncritically in the press, and without any empirical or conceptual supporting evidence.

    On the other hand, we have a study that was carefully constructed to promote a certain outcome laden with deep conflicts of interest. It has been shown to be severely flawed in virtually every way. Its conclusions are genuinely dangerous to patients. Any calls for retraction are being made by individuals with little authoritative or political power, against the tide of vested interests and media amplification, and supported by mountains of evidence that is easily ignored or brushed aside by those in a position to actually do anything.

    The gulf between these two cases is so wide I could possibly even float Stoye between them were I able to find a sizable enough barge.
     
  14. Cort

    Cort Phoenix Rising Founder

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    While I grant that Dr. Mikovits comments have rallied portions of the patient community her 'fighting' hasn't done anything in my opinion for the WPI in the professional community; in fact it's done the opposite - some of her comments, while music to patients ears, have only hurt the WPI in research circles. Stating that XMRV is worse than HIV AIDS in Africa, that XMRV is found in lupus, autism, breast milk, etc,. etc. before publishing on that, stating the negative findings are all due to 'politics' - basically impugning other researchers integrity - calling findings ridiculous....that's not fighting effectively for your institution (WPI) that's acting in a manner that loses you support in people that would otherwise support you.

    Fighting effectively, in my opinion, would be doing things like sticking rigorously to published evidence - like all other researchers do, not impugning other researchers integrity, and keeping this on a scientific level.

    The WPI cannot exist on patient donations - it needs to get grants and to run treatment trials and I think her 'fighting' has hurt them in that area - I don't see how it could not have.

    That said, if the XMRV studies were working out I don't think it would matter what she said - because the research world was primed to run with XMRV if worked out and will run with it if it does work out. They don't care what Dr. Mikovits says - they look at the Science paper and it convinced them to take a shot. In fact the fact the XMRV has gotten so much research despite her comments at times - simply demonstrates how strong that original paper was.

    Ever since the paper came out its really been out of the WPI's hands - which is what Dr. Peterson said from the beginning; what he hoped for was that the research community would run with it - and it has. There have been over 30 studies looking for XMRV in all sorts of diseases.
     
  15. Bob

    Bob

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    I think it's hard for us to know what would have happened if Judy had been a meek and quiet scientist who didn't rock the boat.

    I think it could have gone one of two ways... Either other scientists might have been more willing to work with her and institutions more willing to give grants to the WPI... or... Vested interests would have succeeded in getting it all swept under the carpet, and XMRV research would have been swiftly closed down. Also, ME might not have got half so much publicity over the past year and a half if Judy wasn't so vocal.

    Look at what happened to Jonathan Kerr... It has been said that he didn't leave CFS research voluntarily but was forced out just because he was doing CFS research... And Jonathan Kerr is as quiet, pleasant and uncontroversial a scientist as you can get... We lost a valued researcher... He had researched enteroviruses, he was carrying out very interesting genetic studies, and he wanted to trial certain treatments.

    So, maybe there are reasons why Judy has been so vocal, that we are not aware of.
    Maybe Judy has seen the vested interests in action, first hand, and has decided to be vocal to fight against them.
    The WPI has said that it has been surprised at the amount of politics at play.
     
  16. Jemal

    Jemal Senior Member

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    Yeah, it could have gone a lot of different ways. Somehow I think we need a bulldog for this and not a chihuahua.
     
  17. liquid sky

    liquid sky Senior Member

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    Now they want a retraction? They must be scared of something or else they would just let the science play out. If they were so completely sure that there was no retrovirus affecting PwME, they would not be this upset about this particular study.

    I smell fear. I know scientists have big egos and big money is at stake, but this kind of reaction goes beyond that. I smell fear.
     
  18. acer2000

    acer2000 Senior Member

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    Agreed, retraction seems a bit extreme. There are plenty of papers published on scientific theories that don't work out. Almost none of them are retracted. Thats how science works, people publish and others try the same (or in this case similar) experiments and theories are confirmed or not. There is no need for a retraction... sheez these people are worked up. I wish they'd just focus on figuring out what causes CFS, whatever that may end up being.

    The lack of cooperation among these scientists and the stupid statements going back and forth make it so painfully obvious that they are ignoring that there are really sick people involved here. Scientists who are convinced by the current level of evidence this point that the xmrv association hasn't held up - great, good for you... *but*, don't just pat yourselves on the back that you shot something down - actually *do* more research to figure out what *is* causing the illness.
     
  19. currer

    currer Senior Member

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    There is nothing to retract.
    The recent CDC paper showed that XMRV is a replicating, variable, human retrovirus, and is not contamination, just as Dr. Mikovits said.
    The CDC called for further research on this virus and its effect in cells.

    How can that make Dr. Mikovits study "flawed beyond repair"?
    What is going on here?
     
  20. anciendaze

    anciendaze Senior Member

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    The crux of the matter may lie here. Grants were rejected starting immediately after the Science paper, before anyone had evidence. Sequencing a few more isolates could have advanced understanding quickly.

    Stoye's comment about following their protocol to the letter is wrong. Singh used different primers and different temperatures. As I understand this, her assays would tolerate less variation than WPI's in some regions, while allowing several different sequences overall. The question is not the amount of variation overall, but whether those variations would prevent detection. I still think large variations are being missed.

    The problem I see is that avoiding endogenous sequences, IAP sequences, etc. pretty well eliminates all possibilities. Cells can't tell these sequences apart. Detection should not depend on threading an impossibly narrow channel between self and other because we already have evidence of autoimmune responses in this disease.

    Failure of culturing is disturbing, but there are millions of ways to go wrong -- in either direction.

    Singh has cleared away some of the appalling diagnostic confusion, and sharpened criteria. She has avoided several kinds of risk. This is of paramount importance in institutional science today. It is not enough to advance the state of the art very far.
     

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