Article: Retrovirology: Five Papers on XMRV and Contamination

Comments

Amy Dockser Marcus' Blog on the Findings

http://blogs.wsj.com/health/2010/12/...contamination/

Four papers published today in the journal Retrovirology—and a fifth one commenting on the papers—demonstrated how easy it is for mouse contamination to skew lab experiments involving the virus XMRV.

But they are unlikely to resolve the debate over whether XMRV is linked to diseases like chronic fatigue syndrome or prostate cancer, especially since the authors of the papers disagree on the interpretation of their data.

XMRV has been the topic of much debate since a paper was published last year in Science, linking the virus to chronic fatigue syndrome. The virus was also found in smaller numbers of healthy controls, raising the possibility that the blood supply might be infected. XMRV had previously been linked to prostate cancer. But some other groups have not been able to find XMRV in either CFS or prostate cancer patients or in healthy people.

Greg J. Towers from University College London, a senior author of one of the papers, told the Health Blog that his group’s findings indicate that ”XMRV is not a human pathogen.” Tests used to detect XMRV are also able to detect mouse DNA, and even if a tiny bit of mouse DNA gets in a lab sample, the test can be positive even if the patient is not, he explained. He added that he was not intending to criticize the work of other scientists. ”They published their observations in good faith and we have simply reexamined their findings and made new observations and come to a more likely conclusion.”

But John M. Coffin, a retrovirologist and a co-author of another of today’s Retrovirology papers, told Health Blog that while his group’s study demonstrated that mouse DNA is everywhere in labs, none of today’s published papers ”definitively show that any prior study is wrong.”

Robert A. Smith, a research assistant professor at University of Washington in Seattle who wrote a commentary in Retrovirology summarizing the studies, told Health Blog that the possibility of contamination means that future studies must be done very carefully before conclusions about disease association are made. But he said he is unwilling to state that the reported link between XMRV and CFS or prostate cancer is no longer viable.

The papers focus on various problems associated with a specific kind of test used to detect XMRV but does not examine every method used to detect XMRV. Smith pointed out that some of the previous papers on prostate cancer found XMRV integrated into the patients’ DNA and ”I can’t come up with a mechanism where there would be contamination there.”

Judy Mikovits, who led the team of researchers that published the link between CFS and XMRV in Science last year, said her team was able to culture XMRV from the patients’ blood and show antibody responses indicating they had been exposed to XMRV at some point. ”You will not make an immune response to a lab contaminant,” she told Health Blog.

Dr. Coffin said the debate over XMRV will continue. ”This is not the end of XMRV,” Coffin said, ”but it is a warning we have to be very, very careful.”
 
Great summery as always Cort. I think everyone needs to except the possibility that XMRV does not exist in CFS patients and keep the pressure on the government for research into the cause. Every time a negative finding or the possibility of contamination is discussed many people have a knee-jerk reaction to attack the author of the paper or article as being bias but maybe we are the one who are overly biased.
 
What about the findings done by the NIH,FDA, Emory University,Utah University, Dr De Merlier in Belgium who has tested positives all over Europe, what about those samples that were frozen for 15 years and tested positive now, how can they be contamination?
what about the study done by Emory University, where they infected macaques with XMRV and after the autopsy they showed the XRMV was in blood,pancreas,spleen,liver,brain what about this studies how come they are not published anywhere?

These guys are making it sound like the debate is over and in fact XMRV does not exist in Humans, what a bunch of pseudo scientists.
 
Amy Dockser Marcus' Blog on the Findings

http://blogs.wsj.com/health/2010/12/...contamination/

Four papers published today in the journal Retrovirology—and a fifth one commenting on the papers—demonstrated how easy it is for mouse contamination to skew lab experiments involving the virus XMRV.

But they are unlikely to resolve the debate over whether XMRV is linked to diseases like chronic fatigue syndrome or prostate cancer, especially since the authors of the papers disagree on the interpretation of their data.

XMRV has been the topic of much debate since a paper was published last year in Science, linking the virus to chronic fatigue syndrome. The virus was also found in smaller numbers of healthy controls, raising the possibility that the blood supply might be infected. XMRV had previously been linked to prostate cancer. But some other groups have not been able to find XMRV in either CFS or prostate cancer patients or in healthy people.

Greg J. Towers from University College London, a senior author of one of the papers, told the Health Blog that his group’s findings indicate that ”XMRV is not a human pathogen.” Tests used to detect XMRV are also able to detect mouse DNA, and even if a tiny bit of mouse DNA gets in a lab sample, the test can be positive even if the patient is not, he explained. He added that he was not intending to criticize the work of other scientists. ”They published their observations in good faith and we have simply reexamined their findings and made new observations and come to a more likely conclusion.”

But John M. Coffin, a retrovirologist and a co-author of another of today’s Retrovirology papers, told Health Blog that while his group’s study demonstrated that mouse DNA is everywhere in labs, none of today’s published papers ”definitively show that any prior study is wrong.”

Robert A. Smith, a research assistant professor at University of Washington in Seattle who wrote a commentary in Retrovirology summarizing the studies, told Health Blog that the possibility of contamination means that future studies must be done very carefully before conclusions about disease association are made. But he said he is unwilling to state that the reported link between XMRV and CFS or prostate cancer is no longer viable.

The papers focus on various problems associated with a specific kind of test used to detect XMRV but does not examine every method used to detect XMRV. Smith pointed out that some of the previous papers on prostate cancer found XMRV integrated into the patients’ DNA and ”I can’t come up with a mechanism where there would be contamination there.”

Judy Mikovits, who led the team of researchers that published the link between CFS and XMRV in Science last year, said her team was able to culture XMRV from the patients’ blood and show antibody responses indicating they had been exposed to XMRV at some point. ”You will not make an immune response to a lab contaminant,” she told Health Blog.

Dr. Coffin said the debate over XMRV will continue. ”This is not the end of XMRV,” Coffin said, ”but it is a warning we have to be very, very careful.”
 
Great summery as always Cort. I think everyone needs to except the possibility that XMRV does not exist in CFS patients and keep the pressure on the government for research into the cause. Every time a negative finding or the possibility of contamination is discussed many people have a knee-jerk reaction to attack the author of the paper or article as being bias but maybe we are the one who are overly biased.

I guess in such a high stakes subject that is expected. Science at its best is ruthlessly objective - which can make it so hard to take. I think of people with incurable deadly disorders just praying that a drug will pass the FDA trials...its rough stuff, that's for sure..
 
C
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Even if xmrv turns out to be 100% contamination, it doesn't change my opinion on how obvious it seems that many of these negative studies over the last year were authored by people defending vested interests rather than practicing true science.
 
Even if xmrv turns out to be 100% contamination, it doesn't change my opinion on how obvious it seems that many of these negative studies over the last year were authored by people defending vested interests rather than practicing true science.
Exactly. I have no leaning either way regarding the outcome & only want the truth. It's just how much this whole process reeks of politics over science that bothers me.
 
It's obvious the brits are all wrong again. too bad McClure suck it!
 
WPI statement on XMRV research and PCR contamination

The Lombardi et al. and Lo et al. studies were done using four different methods of detection. They were not simply PCR experiments, as were the studies by McClure et al. and others who have recently reported their difficulties with contamination. Experienced researchers such as Mikovits, Lombardi, Lo and their collaborators understand the limitations of PCR technology, especially the possibility of sample contamination. As a result, we and Lo et al. conducted rigorous studies to prevent and rule out any possibility that the results reported were from contamination.

In addition to the use of PCR methodology, the Lombardi team used two other scientific techniques to determine whether, in fact, we had found new retroviruses in human blood samples. We identified a human antibody response to a gamma retroviral infection and we demonstrated that live gamma retrovirus isolated from human blood could infect human cells in culture. These scientific findings cannot be explained by contamination with mouse cells, mouse DNA or XMRV-related virus-contaminated human tumor cells. No mouse cell lines and none of the human cell lines reported today by Hue et al. to contain XMRV were ever cultured in the WPI lab where our PCR experiments were performed.

Humans cannot make antibodies to viruses related to murine leukemia viruses unless they have been exposed to virus proteins. Therefore, recent publications regarding PCR contamination do not change the conclusions of the Lombardi et al. and Lo et al. studies that concluded that patients with ME/CFS are infected with human gammaretroviruses. We have never claimed that CFS was caused by XMRV,only that CFS patients possess antibodies to XMRV related proteins and harbor infectious XMRV, which integrates into human chromosomes and thus is a human infection of as yet unknown pathogenic potential.

"The coauthors stand by the conclusions of Lombardi et al. Nothing that has been published to date refutes our data." Judy A. Mikovits
 
Exactly. I have no leaning either way regarding the outcome & only want the truth. It's just how much this whole process reeks of politics over science that bothers me.
Yep. And the elephant in the room is the interest in keeping ME or CFS 'unexplained' so that psychogenic explanation by default can be promoted.
 
I am not a scientist, doctor or expert by any means.
I am just a logical thinking person.

What I don't understand is, if as they claim, the study has been contaminated by mouse XMRV why is it that the blood of ME/CFS patients have been contaminated at a much greater percentage than healthy controls?

If it's a problem of contamination in the lab, there should be an equal amount of contamination no matter who the blood donor is.

Nielk
 
What I don't understand is, if as they claim, the study has been contaminated by mouse XMRV why is it that the blood of ME/CFS patients have been contaminated at a much greater percentage than healthy controls?
You might be interested in this explanation I posted on the full thread about the retrovirology papers
Robert Weiss - arch-XMRV sceptic - argues that generally patient samples are handled more than negative controls that are often just water. The sample might be handled multiple times in collection, in storage, in retrieval (I think the WPI samples were frozen and drawn some time ago). And this is his explanation for why patient samples could end up with a higher positive rate than controls if contamination is the real cause. I think he's also saying that such different handling of samples and controls is quite common place, not just in the case of XMRV testing.
 
That is actually ALL the positive studies thus far; none have handled the healthy control and patient samples in the same way. I finally got how important this could be when I read the Huber study; her findings were just the opposite - high rates of XMRV in the controls and low rates in the CFS patients; she noted that both groups were initially processed at different times - and concluded that the contamination snuck through a reagant or something in the healthy controls at that time.

This is why the BWG and the Singh study and the Lipkin studies are so important - because they are handling both samples in exactly in same way.
 
C
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Yep. And the elephant in the room is the interest in keeping ME or CFS 'unexplained' so that psychogenic explanation by default can be promoted.
Well put Angela!

It would be interesting to know the source that coordinated all these studies being published the same day, in the same journal, at this time, and immediately splashed across UK media as proof that xmrv does not cause CFS.

To me, the elephant has consumed the entire room.
 
You might be interested in this explanation I posted on the full thread about the retrovirology papers
Hi oceanblue, (like your name)

Thanks for your reply and explanation.
I was under the impression that to get a true study result, all samples would be (should be) handled exactly
the same way. How else can you get true values? The results would be meaningless.

As per Cort Robert Weiss says: "Robert Weiss - arch-XMRV sceptic - argues that generally patient samples are handled more than negative controls that are often just water. The sample might be handled multiple times in collection, in storage, in retrieval (I think the WPI samples were frozen and drawn some time ago). And this is his explanation for why patient samples could end up with a higher positive rate than controls if contamination is the real cause. I think he's also saying that such different handling of samples and controls is quite common place, not just in the case of XMRV testing."

Wouldn't then this be a problem with ANY studies being done in ANY lab for ANY diseases?
There should be then a higher positive rate for patients of any illness being studied.
 
Hi oceanblue, (like your name)

Thanks for your reply and explanation.
I was under the impression that to get a true study result, all samples would be (should be) handled exactly
the same way. How else can you get true values? The results would be meaningless.

As per Cort Robert Weiss says: "Robert Weiss - arch-XMRV sceptic - argues that generally patient samples are handled more than negative controls that are often just water. The sample might be handled multiple times in collection, in storage, in retrieval (I think the WPI samples were frozen and drawn some time ago). And this is his explanation for why patient samples could end up with a higher positive rate than controls if contamination is the real cause. I think he's also saying that such different handling of samples and controls is quite common place, not just in the case of XMRV testing."

Wouldn't then this be a problem with ANY studies being done in ANY lab for ANY diseases?
There should be then a higher positive rate for patients of any illness being studied.
Yet another great point. We really need to insist that all the studies that have been completed be published. This thing has become so political that ALL studies need to be publish. The journals are picking and choosing. That includes information on the animal studies that are being done. If all of the studies done to date were published then there would be much more information to work with. Reasonably there should be many more studies published on this than there have been. To date we have only the original study and two others that comes close to replicating. The rest seem to have been a exercise in futility.

There is now more information on the problems with PCR and specifics regarding the limits of detection from the BWG and those too need too publicized.

I'd like to know exactly what the British government has done that they feel so guilty, that they are working so hard to year after year to stifle research into CFS. The attack last year was well coordinated and this years seems even more so. We as a community are going to have to get equally coordinated to fight back. Two Disinformation campaigns in two years starts to set a pattern.
 
Yet another great point. We really need to insist that all the studies that have been completed be published. This thing has become so political that ALL studies need to be publish. The journals are picking and choosing. That includes information on the animal studies that are being done. If all of the studies done to date were published then there would be much more information to work with. Reasonably there should be many more studies published on this than there have been. To date we have only the original study and two others that comes close to replicating. The rest seem to have been a exercise in futility.

There is now more information on the problems with PCR and specifics regarding the limits of detection from the BWG and those too need too publicized.

I'd like to know exactly what the British government has done that they feel so guilty, that they are working so hard to year after year to stifle research into CFS. The attack last year was well coordinated and this years seems even more so. We as a community are going to have to get equally coordinated to fight back. Two Disinformation campaigns in two years starts to set a pattern.
you are absoultely right george we have to fight, in many many ways, protests, sending letters to the FDA,NIH,calling the Univertities that have so far replicated the study, sending letters and calling congress and even the president, there's is a phone number where we can call and leave a message to the president, there is also the white house webpage where you can send messages to the president, if we all do it specially those who are very well spoken and know and believe that XMRV and MLVs are real, somebody will pay attenion eventually, somebody will, send links of everything and anything that regarding the WPI findings and how the CDC has been covering this up for decades, again you can contact many people, and the media as well, there's millions of people sick with CFS in the world, we need to be more organized and do something about it, they got away with it before not only once but twice, this time they stand no chance, past generations didn't have the internet available back then, but now we can stay informed and maybe coordinate some plan of action...is juist surreal and criminal how the CDC has been treating thousands of Americans treating them like second class citizens and many times labeling them as hysterical people, im am so full with rage right now...millions of lives are at stake because of the actions of the CDC, the blood supply has been contaminated for a long time by now and there's no way around it, it's so obvious that there is something infectious going around among the American people i have lived in other coutries, and never but never i have heard of ME/CFS,Fibro,Autism and even MS, too bad that now i am infected with something too, in my family nobody has a history of CFS,Fibro,Autism,MS Lupus not even cancers and i have quite a large familiy and now i have brain demyelination after having a broken condom incident back in May and many other symptoms that resemlbe HIV, but yet i have tested negative for HIV,HTLV and every other know to man stds out there, to me there is no doubt and will never be any doubt that there is another retrovirus out there and XMRV and MLVs fit exatcly the description and the symptoms that i have.. simple as this, to rule out ME/CFS and even MS you have to rule out first many many other conditions including HIV and HTLVs, you don't need to be a scientist to figure this things out, it's obvious that there's something else out there.
 
"Robert Weiss - arch-XMRV sceptic - argues that generally patient samples are handled more than negative controls that are often just water... I think he's also saying that such different handling of samples and controls is quite common place, not just in the case of XMRV testing."

Wouldn't then this be a problem with ANY studies being done in ANY lab for ANY diseases?
There should be then a higher positive rate for patients of any illness being studied
.
Good point, but it would only apply if contamination was an issue for the disease in question. If there wasn't a danger of contamination from the lab then different handling of samples and controls wouldn't be so critical.

It matters in this case because XMRV is a mouse-derived retrovirus, and there are likely to be mouse retroviruses all over the place in many labs because mice (and their dna) are used so widely in genetics. Robert Weiss was saying this is particularly an issue when trying to identify new retroviruses in humans. And he should know - he 'found' one in the 90s that turned out not to be a new or indeed a human retrovirus at all.

glad you like the name!
 
Good point, but it would only apply if contamination was an issue for the disease in question. If there wasn't a danger of contamination from the lab then different handling of samples and controls wouldn't be so critical.

It matters in this case because XMRV is a mouse-derived retrovirus, and there are likely to be mouse retroviruses all over the place in many labs because mice (and their dna) are used so widely in genetics. Robert Weiss was saying this is particularly an issue when trying to identify new retroviruses in humans. And he should know - he 'found' one in the 90s that turned out not to be a new or indeed a human retrovirus at all.
But again - wouldn't this apply for MANY diseases where mice and their DNA are used?