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The Race to Retract Lombardi 2009...

Discussion in 'XMRV Research and Replication Studies' started by jace, Oct 10, 2011.

  1. kurt

    kurt Senior Member

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    I disagree, there is no trouble for the 0/0 studies in the Silverman sequence problem. If everyone had just run gag and env sequences, as WPI did,then maybe this would cause some issues. Fortunately, most of the 0/0 studies used broader, and more sensitive tests, including the pol gene, which MUST be present in a viable virus, even if it is integrated in the host DNA. And the pol gene is stable in the entire MLV family (it is the 'conserved portion' of the viral genome that is required for replication and can not mutate or the virus loses viabillity). Therefore, the specific VP-62 MLV sequence that was retracted is not changing the general conclusions. The 0/0 studies overwhelmingly demonstrated that there is no MLV family in ME/CFS patient samples, contradicting the WPI hypothesis.

    Not true, the negative findings are still valid, they were testing more than what WPI had tested, these labs used more sensitive and more modern tests than WPI, and they tested for the conserved portion as I mentioned above, which WPI did not. This is false logic, Silverman's primers are not the only variable here, and you can not conclude that their failure invalidates all the 0/0 studies, just not true.

    That gel showed nothing significant and is far less important than the PCR testing which has conclusively ruled-out MLV species infection in ME/CFS blood.

    Maybe in the 1990s that would have been true, with older PCR test designs like those WPI used. However, modern PCR testing, like was used in most if not all the 0/0 studies, takes this into account, they know about the G & C rich areas, their triple hydrogen bonds, and can extract the DNA sequences successfully.

    As just mentioned, the DNA was properly amplified, and some of the studies tested against live XMRV viral samples, so in fact they had no trouble detecting MLV integrated into human cells, including in the G&C rich areas. And again, unlike WPI the outside labs tested the pol gene, so does not matter whether VP-62 was 'recalled' or not, its pol gene is the same as the rest of the MLV family, by definition it has to be, or it is not in the family.

    I've already disproved this claim. There is ABSOLUTELY NO TRUTH to the above statement and nothing has been invalidated except the original WPI hypothesis and the Science study.

    So there is a conspiracy here? Why on earth would these people conspire against us? They would not, and have not, and the facts can speak for themselves to those who know the science, or have access to credentialed researchers, which I was lucky to have two years ago.

    I realize some people want to continue propping-up their hopes for XMRV, or now for some other MLV/HGRV, but they need to look somewhere else than what was presented here. The argument that Silverman's retraction invalidates the 0/0 studies is not based on fact.
     
  2. kurt

    kurt Senior Member

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    I don't think the Science paper can be rescued and expect a full retraction at some point. And fraud is not the only reason for retraction, if researchers can find alternate explanations for most or all of the findings, then they should retract the paper. That is what will probably happen in this case. Personally I think the excitement about the gels is excessive as those were not very important to the primary issue, which is whether PCR can detect the sequence of XMRV in CFS patient blood. Even though I don't believe XMRV, MLV, or HGRV have a prayer of a chance of explaining ME/CFS, I think we need to leave WPI and Mikovits alone at this point, let them re-trench. We don't need to set a vindictive precedent in ME/CFS research. What will that tell future researchers?

    BTW, I think your statement about retracting all the nonsense studies, particularly the psych studies, is brilliant. We seriously should have a campaign to get those out of the literature.
     
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  3. barbc56

    barbc56 Senior Member

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    Kurt, I'm not sure that a campaign to do this would actually be fruitful or were you saying this tongue in cheek?

    Better, would be a another study, designed around the criticisms of the PACE study. This is not saying going in with a set of preconceived assumptions but a hypothesis building upon the existing research, using different criteria or methods to see what results would occur.

    Probably wouldn't happen, but certainly food for thought.

    I certainly agree about not setting a vindictive precedent. Whether based on fact or not, the notion that we are all out for blood will not help the research continue.
     
    Firestormm likes this.
  4. Angela Kennedy

    Angela Kennedy *****

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    Thanks Citybug,

    The only thing I would say that I believe V99 was NOT saying the slides were different. V99 was saying at least aspects of the slides were the same but that this was not in itself a problem.

    But I believe there is also concern about 'doctoring' of the images put up by ERV? Just to confuse matters even more!

    I do think it's funny now that some people are trying to deem other people's position unreliable on the basis of whether they judged a poor, fuzzy image 'the same' or 'different' (not you citybug).
     
  5. jace

    jace Off the fence

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    Hi Esther, you said
    But that is not the case, V99 is a young woman, often posting in a hurry from a smartphone (and not always so that her meaning is clear) and Gerwyn is an older man, housebound and as sick as any of us. They are not the same person, and cannot be conflated, so my points stand.

    Angela pointed out

    removed wrong information.

    I hear good things about Rich Van K's protocol. Methylation may well be one key. I'd like to see that worked on, as well as a blinded, well funded and monitored clinical trial of ARV's. All I want for Christmas is a cure that works....
     

    Attached Files:

  6. Firestormm

    Firestormm Guest

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    Morning Jace,

    I am afraid V is wrong about that. The figure in question was 2C and the legend from Lombardi et al reads:

    '(C) Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) OR from CFS patients (lanes 3 and 6) were analyzed by Western blots using rat mAb to SFFV Env (top panel) or goat antiserum to MLV p30 Gag (bottom panel). Lane 8, SFFV-infected HCD-57 cells. Molecular weight (MW) markers in kilodaltons are at left.'

    http://www.sciencemag.org/content/326/5952/585.full

    That of course is Lombardi et al. The headings were different on the Ottawa slide although the experiment was the same.
     
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  7. jace

    jace Off the fence

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    Spot on Fire. Bit too early in the morning, I should have checked my copy of Lombardi 2009. I have now. I have also removed the misleading info in my previous post.
     
  8. Sam Carter

    Sam Carter Guest

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    Hi Jace,

    To respond to one particular point in your post, I'm fairly sure the WPI/NCI did have VP62 in their labs. It's actually documented in the supporting online material for Lombardi:

    p7

    """""""""""""""
    Lysates were prepared from XMRV-VP62-infected Raji
    (lane 1), LNCaP (lane 2) or Sup-T1 (lane 3).
    """""""""""""""

    Jon Cohen and Martin Enserink also mention it in their article 'False Positive':

    """""""""""""""
    She soon enlisted Ruscetti, who had worked in Gallo's lab when it
    discovered HTLV-I, to screen blood samples from Peterson?s patients
    for viruses. Intrigued by the RNase L link to XMRV, Mikovits and
    Lombardi -- who by then had joined WPI as well -- met Silverman in
    October 2007 at a prostate cancer conference in Lake Tahoe, where
    they discussed the possible role of XMRV in CFS. Silverman was
    happy to collaborate and sent WPI a clone of the virus, known as VP62.

    The institute could use it as a reference to start hunting for the virus in
    CFS patient blood samples that Peterson had stored.
    """""""""""""""""""
     
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  9. Esther12

    Esther12 Senior Member

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    I never thought that this was an attempt to exactly re-create the conditions of any of the past papers. Seeing as the samples from patietns and controls had come from different sources, they would not want to do so.

    I assumed that the study was designed to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. To support this assumption we have the fact that the BWG said:

    It was not my claim I could see nothing in support of. You had said:

    I keep asking why you think this. I'm really interested to know. What has led you to believe this?

    They didn't want to do that. They wanted to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. It's possible that some part of the collection process needs to be done in an inexplicably specific manner, but we have no specific reason to believe this is the case, or to believe that Mikovits or anyone else had requested different collection procedures prior to the BWG test being carried out.


    The paper published was the post-mortem.

    With Mikovits's name on it, they concluded:

    If there was any identifiable problem with the process, they and she could not find it. It could still be an error, but this is the sort of study I've been wanting done since the Science paper first came out (although the size of the sample was apparently limited by difficulty getting known positives from WPI and Lo/Alter), and I can't see any reason to believe that the results are in error.

    The end result was:

    That does have a bearing on the likely accuracy of both the WPI and Lo/Alter papers.

    Why do you think that?


    V99 sometimes seemed to be posting on behalf of Gerwyn, and often writes in a similar way, so I'm often unsure who the true source is. It could be that V99 just garbles Gerwyn's opinions, but the new claim that Silverman's retraction invalidates all of the negative studies, including those like Singh who had followed up on the work from Lo/Alter, seems similarly inaccurate.

    I don't normally visit the other forum, and they stopped public access recently, but since this thread a few people have sent me some bits like this (posted by V99, but some from Gerwyn?):

    When I saw, there were images of clearly the same resault, but with different resoloutions and contrast, and people claiming that they were different. Wasn't the whole thread called something like 'ERV may be giving up virology because of XMRV mistakes'? The first few pages of it were like entering an alternative reality.

    There were claims that the images were different. There were claims that they had been doctored to look the same (even though everyone now acknowledges that they are the same). There were claims that different tests with the same results should have the same artefacts visible. There were claims that the labelling in Science only referred to the top half of the western blot. Anyone could see this stuff was wrong, and while you may have been uncertain about that, it should certainly mean that you no longer trust those who claim expertise on these matters, and got it so wrong.
     
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  10. Firestormm

    Firestormm Guest

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    Esther - that was hysterical lol x
     
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  11. currer

    currer Senior Member

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    I must admit I havent followed this area of the debate in detail, because I think the information available to us is too incomplete to support the conclusions that are being drawn for it.

    I trust the integrity of Mikovits and Ruscetti and I prefer to wait until I hear more from them to clarify what went on in the BWG trial.

    I would just like to ask where retraction of Lombardi would get us? And why some here want a retraction of this paper?

    As I have said on a couple of other threads, even retraction of HGRVs/XMRV in ME will not resolve all the problems created by the discovery that these viruses infect humans, unless Silverman is planning a complete retraction of his prostate cancer findings.

    So are Ruscetti and Mikovits just the beginning? Are all findings linking HGRVs to human disease going to be retracted?
    And how safe will that be, considering that we are poised to release gene vectors based on these very viruses, with all the danger of recombination and spread into the human population that will entail.

    It seems to me that there must be powerful financial interests at play which stand to loose massively if HGRVs are confirmed. So it is all the more important not to rush to judgement, but to wait and evaluate the science impartially, and that means all of it, not only the link to ME.

    Personally I think that investigating other viruses will not take our cause very far, because none of them could be shown to cause all cases of ME. We will be left with the same problem of proving that ME is a biomedical disorder, the insurance firms will be able to refuse to compensate those sick, and we will be led round the circle of psychogenic explanations all over again.

    Politically it is much better for us to support the HGRV hypothesis, until we can be certain that it is mistaken. We have no idea where this science may lead. We are looking into the unknown and other unexpected causes may yet emerge from the retroviral investigations. I find it incredible, given Dr Snydermen's data that a retrovirus is not involved.


    Surely we as a community are politically astute enough to realise that some interests will massively loose out should ME be accepted as it is - as a biomedical disorder. How much would it cost the insurance companies in the US to pay back all the compensation denies to sufferers for their disability over the past twenty years?

    We need to be alert to attempts to divide our community, to confuse us as to where our best interests lie.

    What is so wrong in allowing the science to continue? Investigation of HGRVs is in its infancy. This call for retraction makes no sense and is highly sinister.
     
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  12. ukxmrv

    ukxmrv Senior Member

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    Esther,

    I have been through your long reply but I still cannot see any facts to back up your assumptions about the BWG. It's just more opinion, opinion and opinion. Quoting from the paper and then interpreting any hint of an ideas to support your feeling just simply isn't going to work. All the comments you have reproduced have holes in them and could be argued any way. That what committee or group produced reports can look like.

    I can't see how you would see a paper published at the last phase of the BWG to be a post-Morten of the entire event. It's obviously not true. It's a paper published by a group and doesn't contain comments from each author on what went right and wrong. That's what I would like to see.

    The BEG was never designed to be a test of the Lombardi paper or the Alter/Lo paper so I am still at a loss to see why you think that it should influence any thoughts or the validity of the published work.

    It may be your opinion (which is fine of course) but it is not a fact and was not the intention of the BEG.

    The BEG results have a bearing on any tests used under their conditions and at that time only. It would be illogical and unscientific to argue otherwise.

    Changes to a published protocol such as specifying a new condition creates a new protocol.

    You don't know what was agreed, specified and laid down as an absolute requirement in any part of the process do you? Keeping an open mind (and remember I heard Dr Mikovits speak at IiME) would make this an important question and one to determine before judging a process.

    These are the important questions we need answers to and it may be a wise idea to suspend any judgements until it is done.

    Once again if you have any new concrete evidence to support these feelings of yours please present them here as I am interested in getting to the bottom of what happened.
     
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  13. Esther12

    Esther12 Senior Member

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    Oops, but thanks? I really don't mean to be too hostile on any of this. I know that there's still some uncertainty here, and I also know how difficult it is to be detached about things which affect ones own health. Even if I think that some people are really clearly wrong, I don't want to be bullying about it - I just think that we need to do more to reject some of the errors being made on this forum and the other - the 'debate' over the slide was a bit of a wake-up call to me.

    Personally, I think it would be a bad mistake to retract the paper now, prior to Lipkin. Especially if the authors do not think it should be retracted, and the prostate cancer papers are not retracted. The paper explicitly links XMRV to CFS, and it seems that everyone know accepts that this is false - so there is a good reason for retraction, but I don't think doing so will bring any benefit, and could mean that some people will then be less likely to trust the Lipkin study, and ignore the results from that if they are negative.

    To me, it now looks very likely that the prostate cancer studies were the result of error. They've been less controversial, have not had the sort of blinded testing we saw under the BWG, and so their may not be the same drive to retraction. I wouldn't be surprised if the authors themselves decided to retract their own work.

    I really disagree. I can't think of anything more likely to encourage scientists and doctors to believe that CFS is the result of abnormal illness beliefs than a bad a patients insisting that they have evidence of a virus that only Mikovits can detect.

    As ever, it's best for us to try to look dispassionately at the evidence, and to allow that to guide our beliefs. It could well be that we would be treated more fairly if it was believed that CFS is caused by XMRV, but campaigning on the belief that CFS is caused by HGRV despite evidence to the contrary is going to be entirely harmful.

    There's no way that there is a cover-up of an identifiable retrovirus circulating in the blood supply.

    When the first negative paper came out from Wessely, I could not have been more certain that this was not a cover-up. No-one would be stupid enough to intentionally try to hide evidence of an identified retrovirus causing CFS and circulating in the blood supply, it would be certain to come out in the long-run (this is also why I don't think it's at all likely that the positive papers were the result of intentional deception). A new retrovirus circulating in the blood supply would pose a risk to 'real people', not just mere CFS patients! Pharmaceutical companies would want to make fortunes by providing life-long ARVs. People would not want this thing to keep spreading!

    CFS is usually treated badly. But retroviruses are treated seriously, and I don't see any reason to think that a political desire to hide the association between HGRVs and CFS is the cause of the growing evidence that they are not associated.
     
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  14. Bob

    Bob

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    I am bracing myself for a full retraction, but I don't think it will be related to the gels either.

    Thanks Kurt, I think that's a helpful thing to say. Researchers and institutes should be allowed to make mistakes, if they are honest mistakes.

    I'm all for this! Let's start it here, on PR, now!
     
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  15. Esther12

    Esther12 Senior Member

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    You posted after I started typing my last reply... which means I was typing for 30 mins! *gulp*

    I don't see how you can argue away the fact that this quote supports my assertion that the BWG wanted to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility:

    You've not be providing any countervailing evidence for your claim that:

    I don't see why this claim would be made about the BWG - particularly as the key problem I have with the study is that it looked at such a small number of samples!

    I don't know what you mean by post-mortem, but the paper was an attempt to present and asses the results from the BWG.

    I don't think that anyone will ever try to recreate every exact condition of either of those papers. It would probably be impossible to do so. If the WPI had thought that a particular form of collection was necessary, they could have requested it.

    Sure - there are things we don't know. From what I've seen though, it seems like the study was well done, and designed to evaluate XMRV detection assays in terms of sensitivity, specificity and reproducibility. Just because some things are unknown does not mean that we should avoid making any judgement - some things will always be unknown, but we still need to try to decide what is most likely to be true.

    There is no more evidence than the paper. I do not know why you think they were only examining bulk testing methods.
     
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  16. Firestormm

    Firestormm Guest

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    Hi Sam,

    I hadn't actually noticed that mentioned in Lombardi et al. Wonder why it hasn't been mentioned before now? How very strange. I thought they were denying ever to have had the stuff. Or maybe that was the supporters? I don't know. I did see it in Cohen's article of course - think I posted his comments re-confirming it also - somewhere on here :)

    Lombardi Supplementary Online Material: http://www.sciencemag.org/content/suppl/2009/10/08/1179052.DC1/Lombardi.SOM.rev.pdf

    It refers to Figure S3. Not that I understand what it means or can ascertain if this was done at the WPI. I assume it was from what you said.

    Thanks
     
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  17. Bob

    Bob

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    Interesting info thank you Kurt.

    One thing that hasn't been focused on much is the WPI's serological results.
    The anti-body research is worth following up, whether HGRV's are involved or not.
    It has the potential to lead to further insight into ME, and to be used as a biomarker, whether HGRV's are inolved or not.
    And as far as I can recollect (which doesn't mean much) the negative studies haven't addressed the serological results.
    (Does anyone know if I'm right about that?)
     
  18. Sam Carter

    Sam Carter Guest

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    Hi Bob,

    Multiple groups, including the WPI itself and NCI/Ruscetti, have been unable to replicate the serology findings presented in Lombardi.
     
  19. ukxmrv

    ukxmrv Senior Member

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    I'm not really sure why you posted that reply Esther.

    You didn't respond to any of my points. For example I stated what I would like to see as a post mortem but you typed words but didn't address it. You then stated as a reply to a further point that it appeared like a well designed study. Once again demonstrating that you are basing your judgements on your opinion and cannot provide a scientific argument.

    Once again you admitted that you did not know what restrictions that the WPI was under but unlike me you don't seem interested in knowing what they were or importantly with-holding judgement until you know.

    As far as I can tell you are unable to provide any data or specifics on why the BWG should have any bearing on the Lombardi Science paper or the Alter Lo paper.

    You seem to be arguing that because there was no enough data in the BWG to make this distinction clear for you in providing an argument, then you are still happy to hold the opinion that the BWG could be used to judge these two different papers.

    Once again I would state that you are entitled to your opinions but that you cannot provide a basis for this. For me there are too many unknowns and I will be following further data and information as it develops to fill in the holes.
     
  20. Bob

    Bob

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    Yes, I think that Dr Singh looked for antibodies, didn't she?
    And did they do serology work in the BWG?
    (Sorry, brain like a sieve as usual!)
     

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