Retrovirology Publishes Five Papers on XMRV and Contamination

[Jemal]

Maybe it's because XMRV doesn't in fact cause CFS. Nothing so far has shown that it does, at least. I know many people want to believe it does, but believing in something doesn't make it true. At this point the most we can say is maybe it does, and maybe it doesn't. The best the strongest proponents can even show is that it's possibly associated. Personally I doubt any direct or sole causation will be found - it just doesn't seem likely given the complexity of CFS. And it might still play some minor or additive role, so that treating it where it exists improves symptoms. But the weight of the evidence so far suggests that it doesn't cause the disorder.

Not sure why people would be upset with research just because it doesn't show what they want it to, other than the initial disappointment that will come when we find out XMRV doesn't cause CFS, which is understandable. We're best served in the long run by finding out what really causes CFS, not by clinging to false hopes despite the evidence to the contrary.

I think most of us are just tired about the continuing controversy. I like to believe XMRV is an important cause for CFS (either directly or indirectly) and there is evidence for it. There's also evidence against it though and if this virus is to be eliminated as contamination, so be it. I just don't want the controversy to continue. I want to know what's wrong with us and I want a treatment. Basically I want the insanity to end.

 

[Tia]

Yeah right, trying to cover it up again. :Retro mad:

 

[Esther12]

I don't think this counts out XMRV yet... but there's no way those scientists would be promoting their work like this unless they thought they were right. No way this is a cover up. There's too much other work going on with XMRV for them ot hope to get away with something like that - it would just ruin their reputations.

They're sure of themselves. So are the WPI. Whoever gets the most compelling evidence behind them wins. It's a shame we're unlikely to get a reply from the pro-XMRV camp before x-mas.

 

[urbantravels]

Please, folks, let's check to see if a thread already exists before starting multiple new ones. Thanks!

 

[eric_s]

The composition of that TMG really is ubelievable.

While i don't mind the papers i don't like the role Retrovirology is playing. But like some have said before, now it's time for the authors of the positive papers to prove their results are true. Nobody can keep them from doing so and if they manage to do it, things will be looking fine.

 

[Cort]

There were actually only four studies (thank god) and one review paper. This last paper is the least substantial of them all; it points out that this Japanese group did find contaminants in a primer that Lo used but it also picked them up in their negative controls and Lo reported that they did many negative controls and nothing ever showed up. Still they do question one of Lo's procedures....

An Endogenous Murine Leukemia Viral Genome Contaminant in a RT-PCR kit is Amplified Using Standard Primers for XMRV - Sato et. al.

This paper relates the experiences of the Japanese Red Cross in their search for XMRV and appears to apply to the Lo study mostly. In their pilot studies they discovered a positive band in their negative control. (Negative controls are always included for just this reason. The WPI and Alter and presumably everybody else ran them and reported that they were clean). Further testing lead them to suspect that Taq DNA polymerase in one of the kits from Invitrogen was contaminated with endogenous MLVs.

They stated that the results raised the possibility that the MLVs found in the Lo study were produced by the Invitrogen products they used (one of which was similar). They did note that the Lo study did not find any positives in the negative controls but they also stated that it wasn't clear if the control samples were assay simultaneously with the positive samples in a blinded, randomized way

 

[Esther12]

The forum's big and busy. It's easy to miss something.... good to have all the conversation in one place though.

 

[dannybex]

I think most of us are just tired about the continuing controversy. I like to believe XMRV is an important cause for CFS (either directly or indirectly) and there is evidence for it. There's also evidence against it though and if this virus is to be eliminated as contamination, so be it. I just don't want the controversy to continue. I want to know what's wrong with us and I want a treatment. Basically I want the insanity to end.

The controversy/"insanity" certainly is tiring, at least for me.

This is just my uninformed opinion, but I think even if someone is XMRV positive, there will never be one single treatment, as we all have other different issues -- possible mold, environmental or heavy metal problems, not to mention other co-infections -- all of which may affect immunity and health in some of us.

 

[Jemal]

Yeah, I hope I didn't sound cranky, because that wasn't my intention. It's easy to miss stuff, just wanted to direct everyone to the big thread.

 

[Cort]

I was a little relieved as I got to the end of the papers. For me, the Hue was really the major one. Two of the others cite the importance of using the IAP test to search for contamination which I do not think has been done.

The Huber paper is certainly a warning about contamination and highlights the need for both the patient and control samples to be treated exactly the same. That has not happened, I don't believe, remarkably enough, in any of the positive XMRV studies....

Singh is doing that; the BWG did and will do that....

This is definitely not the end of XMRV; the papers aren't definitive, I don't think - Hue's is the closest I would guess, but they are definite warnings.

 

[Esther12]

Is the Japanese red cross paper related to the 2-3% in Japanese blood supply study that never got published? Or is this different?

If it's the same one, then I guess we're now lacking one of the previously positive bits of evidence for XMRV.

 

[eric_s]

A good article in the WSJ blog about the new papers

http://blogs.wsj.com/health/2010/12/20/xmrv-raising-the-issue-of-contamination/

It's worth reading.

 

[kurt]

That is the antibody test - which has always been Dr. Mikovits biggest backup....So it would seem that their job now, as it has always been, really, is to show that the antibody is completely specific for XMRV; that its not cross-reacting with anything else. Dr. Mikovits and Dr. Bagni have reported progress in this area. Dr. Singh has her own antibody test....This was all about PCR.

This is a good point, does PCR contamination change antibody results? I'm not an expert but have had a lot of back-channel discussions with experts over the past year. Here is what I understand, the antibody tests used by WPI and others utilize XMRV positive DNA samples, which were (hypothetically) already contaminated. So the problem is this, if there was contamination in the PCR test, and the PCR test was used to identify XMRV antigens for use in the antibody studies, then those contaminant particles may have triggered the initial antibodies. In other words, they constructed an antibody test that detects common contaminant particles. Therefore, they essentially constructed an antibody test that will naturally have a high rate of false positives. This was actually confirmed when the Phase II BWG study when the antibody test produced a false positive on a negative control.

 

[pine108kell]

Maybe it's because XMRV doesn't in fact cause CFS. Nothing so far has shown that it does, at least. I know many people want to believe it does, but believing in something doesn't make it true. At this point the most we can say is maybe it does, and maybe it doesn't. The best the strongest proponents can even show is that it's possibly associated. Personally I doubt any direct or sole causation will be found - it just doesn't seem likely given the complexity of CFS. And it might still play some minor or additive role, so that treating it where it exists improves symptoms. But the weight of the evidence so far suggests that it doesn't cause the disorder.

Not sure why people would be upset with research just because it doesn't show what they want it to, other than the initial disappointment that will come when we find out XMRV doesn't cause CFS, which is understandable. We're best served in the long run by finding out what really causes CFS, not by clinging to false hopes despite the evidence to the contrary.

This is what I was going to say, but you said it in a more polite manner. I want to find the reason for my illness more than anyone, but the only way is through good science. Scientists that find evidence that contradicts earlier studies aren't happy that we are sick or that they cannot find a solution. Well, maybe there are a few evil or demented people out there that like to be contrarians just for their ego, but it is very small number and not this long list of scientists that show how contamination could be a problem.

 

[kurt]

I don't think this counts out XMRV yet... but there's no way those scientists would be promoting their work like this unless they thought they were right. No way this is a cover up. There's too much other work going on with XMRV for them ot hope to get away with something like that - it would just ruin their reputations.

They're sure of themselves. So are the WPI. Whoever gets the most compelling evidence behind them wins. It's a shame we're unlikely to get a reply from the pro-XMRV camp before x-mas.

I think this contamination issue will have to be discussed among researchers on both sides, and new IAP tests must now be run on samples from all of the the positive XMRV and Polytropic MuLV studies. If those IAP tests show positive for mouse contamination, then it will be time to start counting out XMRV. At the present the evidence for contamination is strong, but there are still unknowns.

The certainty of individual scientists, or their supporters is fortunately not the most important data point here. The work of many researchers has to be taken into account, and each brings different knowledge and perspective to the eventual consensus view.

 

[Cort]

This is a good point, does PCR contamination change antibody results? I'm not an expert but have had a lot of back-channel discussions with experts over the past year. Here is what I understand, the antibody tests used by WPI and others utilize XMRV positive DNA samples, which were (hypothetically) already contaminated. So the problem is this, if there was contamination in the PCR test, and the PCR test was used to identify XMRV antigens for use in the antibody studies, then those contaminant particles may have triggered the initial antibodies. In other words, they constructed an antibody test that detects common contaminant particles. Therefore, they essentially constructed an antibody test that will naturally have a high rate of false positives. This was actually confirmed when the Phase II BWG study when the antibody test produced a false positive on a negative control.

Ouch....they make the antibody test off of the agent they found. I thought they used a standard antibody test for MLV's though in the original paper??

 

[Bob]

I was a little relieved as I got to the end of the papers. For me, the Hue was really the major one. Two of the others cite the importance of using the IAP test to search for contamination which I do not think has been done.

The Huber paper is certainly a warning about contamination and highlights the need for both the patient and control samples to be treated exactly the same. That has not happened, I don't believe, remarkably enough, in any of the positive XMRV studies....

Singh is doing that; the BWG did and will do that....

This is definitely not the end of XMRV; the papers aren't definitive, I don't think - Hue's is the closest I would guess, but they are definite warnings.

I agree with your overview of the papers, Cort.
They are all just warnings about the risks of contamination.
The Hue paper definitely brings something new to the contamination arguement, but like you say, it is not definitive...
Even their own conclusion admits that...

... our observations cannot conclusively prove that XMRV is not a human pathogen...

 

[free at last]

A good article in the WSJ blog about the new papers

http://blogs.wsj.com/health/2010/12/20/xmrv-raising-the-issue-of-contamination/

It's worth reading.

Thanks for tha Eric, its lifted my spirits a bit, Im surprised about Coffins response, as i would have expected more agreement with the london researchers, As Coffin has seemed lets say a bit dubiouse on occation.This article seems to suggest our london friends might be blowing there trumpet a little harder than the instrument was capable of doing, im encouraged this is not the death of xmrv being associated in ME /CFS as much as our london friends ( not sure they are our friends take a vote ?) seem to be ever so strongly stateing.

it reminds me of a group of psychitrists, that have had enough of this nonesense, and said right, time to put this baby to bed. If this is so, and there science is not sound on all the testing methods used, and thats what these other researchers seem to be suggesting, i hope in time the likes of Frank Ruscetti tear this group apart. because finding something that means caution should be used in future testing is fine ( thanks for that ) but absolutely stating this is the end, we have found the reason for all this, and XMRV is not associated with ME/CFS period is another. It striks me as unproffesional biased, misleading, even outright lies,

Just feels like wessleys hand is up ther arse controlling these puppets, if this research is shot down, it will be another reason i will never forgive some of my countrys so called proffesionals, for behaving in this biased exagerated damaging way. Its not them that has had there life turned upside down to the point where they are too scared to go out of there door in winter 6 months a home prisoner , for fear of catcing flu
The more i find out there wrong, im sorry the more i will just plain hate them, just like the shrinks. I hope one day there world comes crashing down, if they have tried to do what i think you knew, and now im just catching on might really be happening here, Feels like Mr simon syndrome all over again doesnt it. Go Coffin, that really surprised me. The BBC sucks we need to protest when we learn more if the science of these papers do not stand up to there oh SO CONFIDENT CONCLUSIONS
I was down, im cheering up

As for mr Kite i think XMRV fits my symptoms and life quite nicely actually. Though of course i cant be sure, none of us can yet. Lets hope as Dr Alter says the truth should be found
some opinions here Eric not as good as yours though

http://niceguidelines.blogspot.com/

 

[Jemal]

It seems the Washington Post is the only serious news outlet that actually went a bit farther than the press release / standard reporting and also contacted a few of the major players. I like that article a lot.

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.

”This is not the end of XMRV,” Coffin said, ”but it is a warning we have to be very, very careful.”

I might actually like the role Coffin is playing.

 

[acer2000]

The finding that one of the prostate cancer cell lines produces XMRV without combining it with patient blood in culture is an interesting one. But I think people need to look at this in two ways.

1) It could mean what these recent papers seem to suggest - namely the XMRV positive results in CFS patients after culture tests are due to the virus actually already being in the PC line to begin with and not the patient blood. Seems unlikely because the studies ran both CFS and controls through the PC line, and pretty much only CFS patients came back positive. If the line itself was the source of contamination, you'd think it would show up equally in both types of samples.

2) It could just be further confirmation that XMRV is associated with prostate cancer cells. Sort of re-confiming the obvious. Then it would make sense that XMRV would be in a PC cell line, because well, it caused that line to become cancerous to begin with. It seems this problem could be settled by ensuring the PC line is free of XMRV before trying to culture it with CFS pt blood in a study, or using another type of cell line altogether.

Perhaps the most intriguing thing is that its possible both of these groups are right. Meaning... XMRV is found in mice, its found in labs, and its also genuinely found in humans (and isn't a bystander). It can cause disease in both mice and humans. Perhaps its directly transmitted from mice to humans like the hanta virus.. (ie the mouse is the vector - or an insect that feeds on both mice and humans) or maybe if its as common of a lab contaminant as these people seem to claim, perhaps it was unknowingly transmitted into humans by doctors who use the products of those contaminated labs.