Discussion in 'XMRV Research and Replication Studies' started by mojoey, Oct 12, 2010.
My news alert sent me this link to Science Daily reporting on those same studies: http://www.sciencedaily.com/releases/2010/10/101012151246.htm.
I wish the prostate study had looked at healthy controls too.
Thanks for the news though.
Things are getting really interesting, there has been some compelling talk lately of the possibility that the positive XMRV finding are due to contamination and I am dieing to see some more data. I started listening to the CFSAC Science Day XMRV presentation a little late today so I missed a lot of information but the speaker made some very interesting points of the possibility of contamination. I am surprised to see no one discussing that presentation on the boards, hopefully the taping of the webcast will be available soon... Is it December yet so we can see the data?!?
There has been a lot of discussion on the issue of contamination here - on the McClure Contamination and Rumour viruses threads for example.
The consensus (amongst those who understand these things) is that there are several logical grounds for dismissing contamination as a possibility in the positive studies including the different positive rates found in PWCs v controls (assuming identical processing of samples) and the fact that the virus had mutated in the Alter patients. I'm sure that there are others.
Personally though, while its a legitimate concern, I'm getting a little hacked off with this constant raising of contamination. Are we going to spend the next 10 years totting up the number of positive v negative studies and raising the spectre of contamination every time XMRV is discussed in a seminar situation?
Either contamination is a remaining issue or it isn't. I don't believe XMRV research and ME/CFS research in general can move on until this issue is sorted once and for all.
In a way, I just don't get it. One group of researchers (WPI, Singh, Kate Bishop who surprisingly also co-authored one of the negative studies) seem to be pressing ahead on the assumption that the positive findings are beyond reproach and moving on to investigate pathology, transmission etc. Others seem stuck at the for/against/contamination stage.
They should all have access to the same published studies including, for example, the correspondence between WPI and Weiss/McClure. Do the likes of Grice et al actually read this stuff before shouting contamination or is contamination one of those words virologists like to drop into conversation to prove how open and objective they are. Could they be suffering from a case of professional jealousy or NIH syndrome? On the other hand, have they read the papers and come to different conclusions?
If WPI and the Lo/Alter team are convinced they have ruled out any possibility of contamination and can demonstrate this, then they need to be saying this very loudly and often and the critics need to put up or shut up. Only then can we move on to more productive discussions.
Assuming that the WPI and Lo/Alter studies can be shown to be watertight in terms of excluding any possibility or contamination arising from the procedures or reagents etc there only remains, in my eyes only, one possible route for contamination that I hesitate to think about let alone state publicly. That is that the patient cohort themselves have been contaminated with XMRV/MLVs. Perhaps this is what Mellor? Was alluding to at the international XMRV conference when he talked about things going on behind closed doors. Can this possibility be excluded?
There has also been criticism in some quarters that certain charities/advocacy groups have been rather lukewarm on the XMRV issue perhaps preferring to take a cautious non-committal approach. I think they need to realise that either XMRV is the answer and continuing to debate plus and minus studies and contamination only serves to delay proper research. If XMRV isn't the answer and contamination is an issue, again the continuing uncertainty only serves to delay and divert funding from other potential areas.
Surely it isn't beyond all concerned to come up with a some small study that can confirm or dismiss contamination as an issue once and for all.
If the prevalence rates of 65-95% hold up, you don't need many patients. Perhaps 10 new blood draws from the positive studies patient cohort and 10 from another well characterised (CCD) cohort. These can then be processed using a variety of methods, reagents, independent labs etc using whatever experimental design necessary to answer the question.
Perhaps the sceptical/cautious groups (CAA, MEA) should put up the money individually or collectively?
I for one, don't want to be sitting here the same time next year listening to the same is it real, is it contamination bickering ad nauseum.
maybe i missed this, but did anyone mention that Myra mc clure is co author of one of these new studies?
Failure to Detect Xenotropic Murine Leukemia Virus–Related Virus in Blood of Individuals at High Risk of Blood‐Borne Viral Infections
Eleanor Barnes,1 Peter Flanagan,1 Anthony Brown,1 Nicola Robinson,1 Helen Brown,1 Myra McClure,4 Annette Oxenius,5 Jane Collier,3 Jonathan Weber,4 Huldrych F. Gnthard,6 Bernard Hirschel,7 Sarah Fidler,4 Rodney Phillips,1,2 and John Frater,1,2
Marco, I completely agree. It is hard to distinguish professional, objective cautiousness from purposeful, ill-intentioned obfuscation. However, there are subtle differences. Primary among them is taking real action to answer the question scientifically. At its core, the question of contamination is a scientific hypothesis that can be tested. Yet so far all of the proponents of contamination seem to be doing a lot of talking and not much real investigation (aside from a few tests devised by Switzer for the PNAS paper that all failed to detect contamination). If people like McClure were serious scientists concerned about contamination, then they would be proactively conducting collaborative research to get to the bottom of the issue rather than just continually talking about it.
With each passing day and each new half-baked, unsubstantiated claim of contamination it's looking more and more like a case of "If we say it loud enough and often enough it will become true." The sad thing, as you allude to, is that this method is painfully powerful when it comes to stifling real research and progress.
What Marco said...
I agree with a lot of what Marco said, and found this conclusion particularly important:
"In an accompanying editorial, Frank Maldarelli, MD, PhD, and Mary Kearney, PhD, of the National Cancer Institute, pointed out that differences among various studies may be related to a variety of factors, including geography, patient selection, and detection techniques. They noted that these three new studies highlight the need for standardization of detection assays, prospective epidemiological surveys, and sharing of reagents and samples among investigators. Only when this is done in a rigorous fashion will it become clear what role XMRV or related viruses have in human disease. "
Sheesh...how long can they keep this farce up?
One thing that jumped straight off the page for me, and made me think "remember that name: Barnes" was this quote:
What utter crap. Putting aside all questions of methodology, contamination, retrovirology etc, the results of the study simply do not support the conclusions. This is completely illogical, which is par for the course with a majority of the negative studies. So no surprise to find McClure's grubby paws all over this one as well.
To point out what should be logically obvious:
"if XMRV is a human pathogen..." ... then all the studies in both PC and in CFS that have detected it, have found it in 3-8% of healthy controls. And those results are statistically significant enough, and confirmed in the UK also by Dr Mikovits' study, that it is simply the case that if all those positive studies are correctly detecting human XMRV infection, and are not due to contamination, then this study that finds zero XMRV anywhere in all of 230 patients...must be failing to detect XMRV in vivo. ERGO, "if XMRV is a human pathogen", then this study is not able to detect it. And in this case, then we cannot draw any conclusions about whether XMRV is "spread though sexual or blood-borne routes in the UK and Western Europe". It's totally irresponsible and illogical to suggest that any scenario can justify the idea that this research shows that XMRV can't be sexually or blood-borne in the UK and Western Europe.
The results do not support the conclusions. Either XMRV is there at about 5% general population infection rate, and they can't detect it; or it is not there, and their results that consistently find that There Is No XMRV are simply wrong. In neither case can we pass comment on whether it is or is not sexually or blood-borne in the UK and Western Europe.
And purlease....do the authors intend to leave open the possibility that XMRV may be sexually transmitted in some countries, but not in this neck of the woods? What have they been smoking?
No, I'm sorry, but they have once again shown that they draw completely illogical and unjustifiable conclusions from their results, and choose to ignore the central questions which demand to be urgently resolved. On that basis, just as when McClure's first study predicted they would fail, failed, and then suggested in the press that this meant XMRV wasn't in the UK, I dismiss them utterly. If they can't be trusted to draw rational conclusions from their own results, why should we trust any other aspect of their work? Seems to me they are just indulging in the favourite English hobby of getting very well-paid to consistently deliver nothing whatsoever.
On the other hand, Dr Kimata, it would seem, is carrying on doing science regardless of all this. Finding XMRV in 22% of 144 patients with prostate cancer. Well what a coincidence! 22% yet again. All this contamination shows remarkably consistent percentages! How come none of these 'contaminated' prostate cancer studies find different rates of 'contamination', I wonder? The mind boggles...
Yes, for sure, it's an ever so slight shame this one didn't waste any more time comparing to healthy controls, Esther12. Why not? Because it would be a waste of money proving that which is already clearly established. Instead, they are refusing to get dragged down into the debate over why some people can't collect their samples and test effectively: they are simply pressing on and actually extending the science: looking in both normal and tumour tissue, and thereby finding evidence that suggests that the XMRV infection preceded the prostate cancer. Useful science.
Kimata restricts his engagement with the fruitless question of whether human XMRV infection is real or not, to a plea: to "continue discussions about XMRV detection assay methodologies, so that discrepancies in the findings of different research groups can be addressed."
If those who insist on not seeking, and thus not finding, refuse to engage with those discussions, then scientists like Dr Kimata are quite right not to waste valuable money on yet more control comparisons, and instead, to press on with finding stuff out. Which is exactly what we pay these guys for - and not to suppress inconvenient truths.
And Dr Tsibris' analysis is no more impressive.
"Researchers did not detect XMRV in any of the 293 patients tested, and the investigators did not find an association between XMRV and patients with CFS, chronic immune suppression, or medical conditions associated with chronic immune activation."
If they didn't find any XMRV at all, then indeed, they didn't find an association with CFS...
"Researchers were surprised that they did not detect XMRV in any of the study participants, despite the high prevalence previously reported."
Really? Were they unaware of the failure of so many others? Did they take on board all the advice of those who are finding it? I wonder...
"The findings suggest that in the population we tested, XMRV is not associated with chronic fatigue syndrome and suggests that differences in PCR technique from study to study do not explain the disparate results seen in XMRV studies of chronic fatigue syndrome," Dr. Tsibris said.
The findings do not suggest this. They mean that either XMRV is not in the general population at significant levels - as all positive studies have found in healthy controls - or their methodology is not able to detect it. And why is Dr Tsibris talking about differences in PCR technique? We have already moved on from that discussion: it is clearly established that methodological differences in the collection and storage of samples are the critical factor. Is it even worth digging into his study to find out what measures he took to ensure that the collection and storage procedures are consistent with those of the positive studies? Or can we just save time and assume that he too has refused to engage with that issue?
Well the picture they are painting is quite clear. OK, say the sceptics: we accept that XMRV is real, it's probably in some prostate cancers, fine...but it's not in the general population (eh? not one of your many hundreds of samples are on their way to prostate cancer? how so?), and it's definitely not in CFS - and the proof? They can't find it anywhere....
On and on we go. Roll on the findings of the Blood Working Group...resolution of this farce can't come too soon...
Yes, i'm really, really waiting for that. And Dr. Lipkin's work. Those negative studies are making me nervous. But i find it hard to believe a 0/0 result. And also that all of the positive ones have been wrong. Are there any news about the Blood Working Group? I think they should be quite far advanced in their program by now.
As has been said before, the most important thing to do at this point is get a reliable (and clinically practical) test for both the presence of the virus, and the level of viral load.
Everything else is dependent on it, and nothing about this issue will be resolved until it happens.
I hope the Blood Working Group doesn't overlook the part of the process where McClure and her ilk swap each sample for elephant blood before heating it to 3000 degrees. It's hard to find a drop of DNA in a pool if you throw out the pool and replace it with a bathtub full of freshly distilled water.
In seriousness, beyond the problems of collection, storage and processing that are likely plaguing the negative studies, have PCR differences fully been ruled out? Have any of these 0/0 studies shown that their primers are capable of amplifying wild, clinical viral strains and not just synthetic strains?
harvard used exactly the same methods as mikovits....now what?!
You have no idea how reluctant I am to post this, because I know how crazy I sound when I say it, but ....
Several years ago I read a wire service (probably AP) story about an admission by our military that in the 1950s (I think), when they were trying to figure out how illnesses caused by biological weapons would spread in the population, planes dusted some midwestern (and possibly other?) towns with supposedly harmless pathogens. I've been wondering, if XMRV is just one of a number of viruses that could be co-factors in CFIDS, whether something like that could explain why it's found in the US (and I guess Japan?) and not so much in Europe. Perhaps the presumably harmless dust was contaminated in the lab with XMRV. That might also explain why, in 1984, most people getting CFS were in their 30s and 40s -- i.e., children when the dusting took place. So many of those early patients said that although the onset of the severe illness was sudden, they had felt a little strange for a long time -- so perhaps there was something about Tahoe in 1984 that triggered a more severe form. If it was then transmitted as an STD or through the placenta, it could spread more generally throughout the population to other age groups. Perhaps in Europe co-factors other than XMRV are more prevalent.
Ehmmmm.. where did you get the impression that me/cfs it is less prevalent in Europe? That is not the case. i myself am European and got tested positive through VIP labs
You need to research the worldwide outbreaks of ME. Someone did a great Youtube one just recently (If I find the link I'll add it here)
XMRV is alive and well in Europe, well Britain anyway. Patients are being tested by private means and by the WPI
There is also a history of looking at (for examples) of how MS was related to military personnel going onto Shetland and Orkney. That was merely looking at the placement of bases and the introduction of a infectious agent by "innocent" means.
We have our own examples of military testing and experiments in europe though.
New Zealand had an outbreak though around 1984 and I'm not aware of any military dustings there.
We don't know where XMRV came from and how it spread yet. No problem with speculating.
If you go back and check outbreaks of ME over the world, they have occured in many places and particuarly hospitals.
These negative studies make me nervous. Some of them come to some outrageous conclusions however... it's like those studies want XMRV carried to it's grave sooner rather than later.
1. If anyone has a link to the Harvard study, full-text, please post. Note that "293" likely refers to ALL patients in the study and not just CFS patients. This study was done a while ago I believe so not sure how much to conclude from it. A member here tried to get into that study a few months ago and was told it was closed.
2. Not finding XMRV in HIV and HCV subjects doesn't concern me much as a negative finding in non-CFS subjects only goes to show that XMRV is not as common as we think and strengthens the association with XMRV. There have been some comments on this board that XMRV is common in healthy people and yet they don't show disease. I guess it's all in what one considers "common" but to me the 5% or so rate isn't that common in a clinical sense. To the blood people, where we're talking about possible blood borne pathogen in the blood supply, yes, that would be high.
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