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Cleaning up after XMRV

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by Ecoclimber, May 18, 2012.

  1. ukxmrv

    ukxmrv Senior Member

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    Esther,
    I'd like you to provide evidence that Mikovits could not "identify her own" in the BWG study. We have yet to hear from her what went wrong and that's a tragedy for patients, especially when people make unsubstanitated claims.

    We've discussed on other threads the danger of patients making claims that there is no evidence for,

    Due to the legal action there is not much coming out from the WPI and from Dr Mikovits but from the small amounts released it appears that Dr Mikovits became concerned about the VIP I and their tests being unable to detect XMRV in the BWG patients. Whether this is true or not is something we will have to wait and see. Until then it is simply not reasonable for us to claim that is not the case when we have no proof.

    It would be a pity for patients to keep repeating their assumptioms. We want to know the truth and until then we simply do not know what happened.
    SOC likes this.
  2. Mark

    Mark Acting CEO

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    In terms of turning back to the bigger picture, that's always important as well, of course, you're quite right. And what you say in this quote is not unreasonable, though I would be cautious with some of those conclusions.

    I would agree that without doubt it has unexpectedly emerged that XMRV is a widespread contaminant.

    I don't however think there is any evidence that it is not potentially harmful, thought clearly if it's so widespread it isn't casually affecting humans and causing them to die in some new and obvious way. But the question of whether it may be harmful if it did get into humans, or whether it may have got into some humans and may have been harmful (in short or long term), is not resolved. We can't detect it by most conventional means, in the blood, and results that seemed to do so now seem questionable. But it's still quite possible that it's infected people, been quickly cleared from the blood, and taken up residence elsewhere, either harmfully or harmlessly. There's literally no evidence either way on that point. But if it hasn't ever infected a human, then how can we possibly say it wouldn't be harmful if it did? What would happen if you got injected with it, or a derivative, in a vaccine cultured in a contaminated environment? Unknown. You can't have it both ways on infectivity and potential harmfulness: If it has never infected anyone, you can't say it wouldn't be harmful if it did.

    Whether it is related to CFS/ME/PC in any way, I am still not certain that question is laid to rest. Science has swung that way and is pointing that way, and there's no question that contamination is a more significant factor than anyone ever realised, and this confounded many of the results. There's a strong case that all the detection was due to contamination, but there is still much to be explained - like why the batch contamination always affected patients rather than controls? Nobody (to my knowledge) has reporting finding loads of XMRV in controls and none in patients: the odds of the results I am aware of being so one-sided due to chance are less than 1% (flipping a coin 7 times and every time it's heads), so an explanation of that is required. I prefer to wait for Lipkin's results, and I also prefer to not make overly definitive statements even then.


    Barb, I'm sorry that this discussion, or argument perhaps, has felt like a personal criticism to you at times. I can see why, because I have been pretty relentless on it in the last couple of days, I happen to have a day off and I so rarely get time to post, which I enjoy. And I don't want you to feel like I'm having a go at you personally, I don't mean to. I don't have anything against you personally, and I quite accept that the fogginess doesn't help matters and it's frustrating for us all to have to function well below our capabilities. I'm also sorry that I've been relentless on the facts of the matter and haven't been a bit more friendly and conversational too, along the way.

    But I have tried very hard to just state the facts, and I think that for the vast majority of the time, at least, I have done so. You accuse me of defensiveness, but actually I have simply mentioned points on which you were wrong, and when I did so - repeatedly - you didn't accept that. To me, it seems that you have been very defensive yourself, because I have pointed out where you were wrong, clearly, with evidence, repeatedly, and you've still continued to disagree.

    That has been extremely frustrating for me as well. I appreciate that you've accepted some of those points now, and I do understand that it might be difficult for you to think these things through and it takes time. But if you're struggling like that, please understand that it can be very frustrating for others too, to state corrections like these and have them disputed, and it might help if you take a little more time to look at what I've said, try to understand it, and decide whether I'm actually right, before posting to say you still think I'm wrong and you want that to be an end of it. To be honest, it has felt rather disrespectful at times, because I have only been trying to explain where you were in error, and you didn't seem to entertain the possibility that I might actually be right, you just argued back. That did feel like you didn't think it was worth listening to what I was actually saying.

    Now: to be fair to you, I think it is entirely understandable and forgivable why you formed those incorrect impressions about what Singh's criticisms applied to. This is very complicated and technical. The criticisms were presented all mixed up together in the paper, and they didn't distinguish between which applied to positive and which applied to negative studies. Some of them were actually quite complex to distinguish, I found, and one or two were ambiguous or undetermined. Yet it was quite possible to read that paper as you did, and assume that the first section criticised the negative studies and the criticisms then moved on to focusing on flaws in the positive ones - it does read a bit like that and I think it's been valuable to pick that all apart and distinguish them because the final analysis was a little surprising even to me. It's actually quite damning of the methodology of the other negative studies, much more so than of Lombardi et al and Lo et al, and it wasn't presented that way at all. Furthermore, Racaniello's bullet point summary doesn't highlight that point either, and it does leave the reader open to imagine that those criticisms are really a criticism of those nasty, bad, weak, load of old rubbish positive studies that have been winding everyone up - if that's what one believed, then that's how one would tend to read it. But the opposite is in fact the case. I think that's really interesting to notice and analyse, how that sort of thing happens - it happens all the time.

    So I can quite see how you got to thinking that, but really I honestly do think it would be well worthwhile for you to take a step back, take some time, and think this one through honestly and fairly and observe how you misinterpreted this, and how unfair that misinterpretation was to the positive papers. I do think you should do that really, because we are indeed all only human, we all make mistakes and get things wrong, and if we can recognise and admit that then we can learn an enormous amount in doing so. There should be no shame in that, and certainly no hard feelings from me over it. And please try to understand that if you post on threads like this stating that black equals white and stick to your guns relentlessly when clear evidence is presented to the contrary, then it's inevitable that there are going to be people who keep arguing with you: I was only arguing with you because you were wrong on a few points of fact, and there was no matter-of-opinion about it, even if we disagree on the matter of opinion on the wider picture, and despite the fact that you may well be right in your conclusions.

    In that spirit of admitting where we are wrong, I'll try to ask myself what I've done wrong myself on this thread. Well, for a start I've let myself get carried away writing, which I enjoy and rarely get the chance to do, but there are still other things I should have been doing instead. And I've not managed to take enough time to be gentle in saying what I've said. So I do want to stress that, although you were wrong, that doesn't mean I'm angry with you about that, or that I want to give you a hard time. So I'll try to make space to be more sensitive to that in future.

    Indeed we are, and please don't think there are any hard feelings in this from my side. I'm sorry if I was tough on you. :)
    jace likes this.
  3. barbc56

    barbc56 Senior Member

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    Nah, Mark, I am fine. TBH, now that I look back, it seems all rather silly getting stuck on the interpretation of the minor details. I don't know how off I was or how off you were or if either of us was as off as the other thought. Maybe it doesn't matter as I think there were far more important things on this thread that could have been discussed.

    I bet in the long run most of us on this forum would agree more than disagree on issues as we are all dealing with a chronic illness and just want to get well. What a boring world it would be if we all had the same opinions.

    No hard feelings here. Don't worry about being hard on me. I can take it. :D

    Thanks.

    Barb C.
  4. Esther12

    Esther12 Senior Member

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    We have heard from Mikovits. Her name was on the BWG paper and she conducted the testing, as we discussed at the time, I think it was in this thread, or maybe another?: http://forums.phoenixrising.me/inde...etract-lombardi-2009.12666/page-5#post-215153
  5. ukxmrv

    ukxmrv Senior Member

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    Sorry Esther there is nothing on any previous thread and you seem to have forgotten the earlier debate.

    Dr Mikovits has never spoken about what went wrong at the BWG post that paper apart from what has come out in the legal reports and even that is uncertain in meaning.

    Being named on the paper isn't the same as carrying out all the experiments in it or even agreeing that the experiments are done in the right way from start to finish.

    We have some clues from the legal reports but that is all. She's not able to speak freely.

    Given that Dr Mikovits expressed concerns about the testing being done at VIP dx it's unfair to blame her or making comments about work she may not have carried out or even known the full story on at the time.

    The BWG was not controlled by Dr Mikovits and as I said earlier she was making comments about the methods being asked of her at the iIMe conference.

    I think you are being unfair. You may well be right or wrong but there is no evidence to back up your assumptoms.
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  6. currer

    currer Senior Member

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    Dr Mikovits being silenced at this precise moment so that she cannot defend or explain her work is highly suspicious and is a repeat of what was done to Dr Wakefield who was unable to defend his work whilst waiting several years for the GMC hearing.
    Denise O'Keefe is on record on her blog saying today that other researchers with positive MLV findings are unable to publish thier work.
    This is politics and not science. I wonder you can be so trusting of authority, Esther. These authorities have never accepted the reality of ME and have repeatedly diverted research and funding into "safe" areas and are still doing this today.
    The two areas that badly need to be researched today are
    1. MRVs and other known contaminants of labs and cell lines which have been used for decades.
    2. Adjuvants in vaccines and their effect on the immune system, singly and in combination.

    One or both of these could well be the cause of ME and other diseases that have increased recently.
    Until I can see that research into these areas properly funded and backed by those health agencies charged with responsibility to protect health I will continue to be very sceptical of official "reassurance" which as we have seen has always been trumpeted around with the maximum publicity.
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  7. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    It's interesting that we have some posters who claim that researchers are reluctant to get into XMRV because of pressure from patients. On the other hand we have researchers who say the pressure is coming from their peers, pressure that is not science-based, but political.
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  8. Ecoclimber

    Ecoclimber Senior Member

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    This research started as research project for detection in early stages of prostate cancer at the Cleveland Clinic by several retrovirologists way before the WPI, Lombardi and Mikovits got involved in ME/CFS association with XMRV.

    You must put this in perspective that XMRV was first found in prostate cancer patients long before its association with the ME/CFS community. Silverman hoped that this was a precursor biomarker for cancer patients. The Silverman's research was targeted in finding a cure or treatment for prostate cancer patients and was not initially intended for the ME/CFS community.

    Obviously, there is more research funding for the cause and treatment of prostate cancer patients so questioning other researcher's motives as though there was some sort of conspiracy or they didn't try hard enough is fruitless. The ME/CFS patients and the prostate cancer patient community are inexplicable drawn together in the xmrv association as a human pathogen. No conspiracies as this was a cancer research project for the cancer prostate community.

    You can not fairly determine what are the motives of researchers are without any facts or knowledge. Anything else is destructive speculation. The quote that you mentioned above is misquoting O' Keefe's blog statement. "I guarantee you that there are people with similar data whom don't want to torture themselves by attempting to publish." This is taken out of context with the meaning applied above in the quote. I know of no retroviroligist researcher that hasn't spent long hours trying to find a handle on this and are still working today to figure it out. More papers will be published.

    However, the only way this it can be resolved as O'keefe mentioned is using Next Gen, micro array assays and high throughput sequencing which will happen and is in the process of happening."And assuming this data will be borne out by other next-gen sequencing studies, what does it all mean? I guess we have to await some more next-gen sequencing to find out.."

    So, lets do away with the conspiracies and the motives of the researchers as there are two patient communities involved and the National Cancer Society is just as eager to find a cause and a treatment for prostate cancer patients.

    If patients from other countries are unhappy with U.S. researchers, then, I suggest maybe the UK patient community find some of their own retrovirologist researchers to conduct their own experiments through various funding opportunities from their various ME organizations. If they can not, then they should focus on the reason why they are so inexorably bad in financing research in their own country.

    Eco
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  9. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Hi Eco, I am not misquoting. I have made an interpretation of her comment, just as you have. O'Keefe has published her discontent with the dirty quick-fire negative studies in previous blogs. There is also some suggestion that she herself has been subjected to that pressure.

    This was her statement: "First, bravo! to the Hanson group for being able to get anything published that might go against the current dogma regarding MLV-like viruses in human samples published." The 'current dogma', I believe, is that all evidence of MLVs in humans is merely contamination.

    Lol, that would probably depend on which researchers you are talking to. Hearsay, from an anonymous source, whom I have every reason to believe is acting on behalf of anonymous researchers. You really shouldn't be making these statements.

    Could be interpreted as patronizing (certainly I saw it that way). You ignore decades of abuse, collusion and misuse of funding on both sides of the Atlantic. UK researchers such as Stoye are in NIH's pocket.

    I think O'Keefe's past references to NGS were along the lines that the contamination researchers have completely muddied the waters to such an extent that it is impossible for positive PCR studies to get any traction. After all, the Hanson study is a positive study.
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  10. Esther12

    Esther12 Senior Member

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    I do not think that we can assume the BWG went wrong - it looks like it was a well conducted study. If Mikovits thought that the BWG's paper was making incorrect claims, then she should not have put her name on it.

    I'm not trusting of anyone, Mikovits or those in authority, but I do think that testing needs to be able to hold up under independently blinded conditions before it can be treated seriously. The BWG did the sort of study I wanted done from the start, and combined with the other negative studies, it does provide good evidence that the testing used by Mikovits, Ruscetti, Lo/Alter and the WPI is not able to distinguish between samples from CFS patients previously found positive for XMRV and healthy controls. Without that, there's no reason particular to believe that CFS is related to HGRV.

    I think it's possible to get too hung up on whether it's been proven that HGRV are not related to CFS, when proving a negative is almost impossible. With the Lipkin study, there's going to be another round of blinded testing, but at this point, I don't think that we can believe that the claims made in the original Science paper about the significance of the testing used by Mikovits at al. were accurate.
  11. asleep

    asleep Senior Member

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    Nor can we assume that it went right, no matter how "well conducted" it appears. It is, after all, just one amongst many studies at this point.

    From a broad perspective of all the studies, the BWG is a rather large anomaly. The rest of the studies could generally be grouped into three categories: positive studies with more positives found in patients than controls; zero/zero studies; clear-cut contaminated studies (e.g. Huber, some of the reagent studies).

    Granted, it is also the only study with purportedly independent blinding. But as ukxmrv has concisely pointed out, there is still a great deal we don't know about this study, and you are filling in blanks with assumptions. Central blinding, while theoretically eliminating some variables, introduces many novel variables, including but not limited to: additional potential methodological pitfalls with collection, processing, and distribution; additional entry points for contamination that could obscure genuine results; methodological constraints due to study design; issues with the actual coding/blinding. Many if not all of these were not adequately controlled for much less understood in the BWG.

    You are also making a huge, ungrounded assumption here. Isn't Lipkin requiring pre-approval for all participants to have their names listed on the outcome? Who's to say something similar wasn't in play here?

    And even if it wasn't, do you honestly think that Mikovits could have grandstanded on the the attachment of her name to "unfavorable" results without being viciously raked over the coals, no matter how legitimate her concerns? That would have been political suicide.

    You are more than welcome to believe these conclusions, but make no mistake: they are built upon assumptions in lieu of evidence. As such, there is nothing scientific or skeptical about them.
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  12. Esther12

    Esther12 Senior Member

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    re: The BWG being an anomaly that cannot be grouped as 0/0, clear contamination, or more positive in patients - that is entirely what you would expect when testing different labs, some of which are claiming different results, but whose positives are occurring as a result of contamination.

    It would need to be a remarkable coincidence for those novel variables to account for the BWG results, rather than contamination affecting those claiming an association between HGRV and CFS. First we would need the collection of samples to occur in a way which somehow meant that the samples from those patients who had previously tested positive were no more likely to test positive than healthy controls - some sort of HGRV killer. Then we would also need a new source of HGRV contamination which only affected the samples sent to a couple of labs. It's very difficult to prove a negative, but that seems very unlikely. I guess that we'll know soon with the results from Lipkin due, and it's always good to be extra certain, but I don't see how anyone can expect the Lipkin study to show an association between CFS and HGRV at this point.

    re no matter how legitimate her concerns: I don't think that's true. But her concerns would need to be legitimate. If Mikovits started saying that she thought that the samples were collected in a way that coincidentally made HGRV undetectable, and then contamination took place later on in a way that made HGRV detectable, she would need to have some good evidence to support her claims, or she would be laughed at because it sounds like such a poor excuse. If she had evidence that the manner in which samples were collected prevented the corrected identification of samples from patients and control, then I think that would be taken seriously.

    The BWG results were exactly what one would expect if the labs at the WPI and NCI were reporting positive results because of contamination. The Lipkin study is now having one final look at this, but I think that it's entirely reasonable for scientists to now be talking as if it has been shown that the initial Science paper was flawed, and that there is no good reason to believe that CFS and HGRVs are associated.
  13. asleep

    asleep Senior Member

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    You are missing the point of why the BWG is an anomaly. You are focused on the story that can be told using the BWG, not the place of the BWG in the overall accumulation of data.

    You will note that when categorizing the other studies, there is no group for "positives found statistically more often in controls", nor is there a group for "positives found with no statistical difference between patients and controls". Barring obviously contaminated studies (Huber), the BWG is the only study that falls into one of these groups.

    But the first group I mentioned above ("positives found statistically more often in patients") is a rather robust group at this point (including something like 7 or more studies spanning ME and PC, as pointed out by others).

    It is far more parsimonious to believe that the single BWG study (with numerous novel variables) is anomalous than it is to believe that all of the positive patient studies were skewed in precisely the same statistically relevant direction by independent errors. Speculative reasons have been given as to why some of these positive patient studies might have been skewed, but the more recent ones have largely controlled for these potential early issues.

    What you mean is that the BWG tells a nice story if you are willing to overlook probability analysis and substitute speculation for parsimony. And it is not just the WPI and NCI who have reported statistically positive results that would need to be independently explained as contamination. It is also Singh, Hanson, Alter, Silverman, and now possibly O'Keefe. And these independent (but uniformly patient-centric) "contamination" events would need to account for more than just PCR results: serology, viral proteins, IHC.

    I wholly agree that your story about the BWG is plausible, but it is by no means certain or even likely at this point. The Lipkin study will certainly add more evidence for or against your story, but it will by no means be "final."
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  14. Esther12

    Esther12 Senior Member

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    re 'there is no group for': I really don't think that this point is of any significance. If someone was running a replication attempt of the Science paper, and found more XMRV in controls than patients, then they would assume it was contamination, and hunt for the source. This is what is meant to have happened with Huber study (I think... I'm starting to forget a lot of XMRV details at this point). The other studies which reported having problems with contamination, and then tracking down the source, would also have been equally likely to fall in to one of these groups. The studies which found contamination weren't obvious contamination from the start, but became so after exhaustive hunting for contamination to explain peculiar results. Studies which came up with the expected results for CFS and PC would not have been so careful. For a long time McClure thought that she had done a positive PC study, and it was only after the CFS controversy that she went back to re-check her results and found sources of contamination. I don't think that this is at all surprising. It does show how researcher's expectations can cause problems in science, but this is fairly widely accepted anyway.

    re needing lots contamination with lots of labs: I agree. But it seems like this is the lesson most virologists have taken from this - that contamination is far more of a problem with these sorts of studies than had been realised. Silverman seems to be gradually picking apart his own XMRV work, and I've not heard anything from Singh about it from some time. I've not been following XMRV stuff closely for a while though.
  15. ukxmrv

    ukxmrv Senior Member

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    Eco, you said

    If patients from other countries are unhappy with U.S. researchers, then, I suggest maybe the UK patient community find some of their own retrovirologist researchers to conduct their own experiments through various funding opportunities from their various ME organizations. If they can not, then they should focus on the reason why they are so inexorably bad in financing research in their own country.

    ====

    Sadly, the problems with retrovirology research into ME is an international one and won't be solved by simply funding the colleagues and ex-mentors and ex-students of the same people who happen to live elsewhere. They are a fluid group who move around a lot.

    It is the profession and the "old boys network" that extends past geographical border that is compounding problems.

    Plenty of USA based CFS patients are not happy with the quality of RV research being done in their own country.
  16. ukxmrv

    ukxmrv Senior Member

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    Hi Esther,


    I don't know why Dr Mikovits put her name on that study and it's I don't think it is reasonable to judge her because of this. I think differently to you. It's not due to blind faith - it's lack of evidence that she was the designer of that study and should therefore be held responsible.

    I began to consider that there may be problems with the BWG when Dr Mikovits spoke about it at the IiME conference. That's a consideration of evidence. More doubts emerged when Dr Mikovits expressed concerns about the way VIP dx was testing. That's more evidence.

    There is no smoking gun. You are making a judgement on evidence and I don't think the same evidence adds up. That's fine we don't all have to think alike.

    It would help though if you stopped bringing up the same claims as facts in different threads on this forum. You know others have examined the same evidence, there is nothing new and there are different opinions because none of us were there and know the whole story.

    That is unless you really do want the arguments to go on and on. I'm simply at a loss to understand why you would do this.
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  17. Ecoclimber

    Ecoclimber Senior Member

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    It would be very hard to pick it up in PCR even Mikovits stated this fact in the BWG study. It needs to move to more sophisticated technology which are in only a few labs.

    Eco
  18. Esther12

    Esther12 Senior Member

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    I don't think that I've unreasonably presented any claims as facts. You first disagreed with me with this post:

    The quote wasn't quite right, but I assumed it was reffering to this post:


    I'm happy to defend the claims that I made there. The BWG did provide Mikovits (and others) a chance to validate their work under independently blinded conditions - and they failed to do so. They were involved with the design of the study, and while there are always going to be possible coincidences and problems which could have occurred, there's not been any evidence that there were problems which meant that the results from the BWG were flawed.

    People often do have different beliefs, and sometimes on-going discussion and debate is not worthwhile - sadly, CFS often means that we are less able to engage with one another's ideas as rigorously as would otherwise be the case. However I do not think that I have said anything unreasonable, and am happy to go on defending what I have said against criticism which I believe is unjust.
  19. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    So you have mentioned a few names, researchers who confidentially mentioned to you, an anonymous poster, of their concerns about pressure from patients. So you haven't shifted from my observation that it depends on who you (an anonymous poster referencing unsubstantiated comments from a select group of researchers) talk to. Oh wait, you want me to actually ask them what they said to you. Seriously? So I need to badger these people to verify what they said to you?

    Unless you can prove what they said to you, it is unsubstantiated. The onus is on you to substantiate your claims, not me.

    Lets not forget, Silverman et al were working for themselves, not us. The number of hours they put in is irrelevant. Many of the studies these people conducted were efforts to validate their own assays, not disprove the accuracy of Mikovits assay. The objective was to make a dollar.

    Jonathan Stoye, National Institute for Medical Research, UK, was appointed to The Organizing Committee 1st International Workshop on XMRV held in the US (ostensibly to ambush Mikovits & co - my personal observation). Wessely has been employed or grant-aided by both the British Ministry of Defence and the US Defense Department for decades. Wessely is embedded so far into the US system, he goes to bed with the stars and stripes under his pillow. The links are very strong. Odd that you didn't know this. FYI, similar linkages occur in other countries. Lloyd, one of the principal CFS researchers in Australia, has worked extensively with the CDC and has been grant-aided. A few minutes googling will bring up instances of these studies. All instances are documented.

    I also note the use of the term 'we' in the above quote. You are not one of us - you are not a patient. I am not sure whose interests you are serving.

    Do you forget most of the posters on this forum are very ill? You are not.
  20. Ecoclimber

    Ecoclimber Senior Member

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    Just as I assume, mere assumptions, idle speculations with no found proof of evidence. RustyJ you are the anonymous poster. You claim that they did not work long hours. It has nothing to do with me. So email them and calculate the hours worked in the lab. It has nothing to do with me. You make the assumptions so verify them! I didn't think you could!

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