Science asks authors to retract XMRV/CFS paper

[currer]

KDM gave a presentation at the Invest in ME conference last month.

A report of what he said is available on the IiME site www.investinme.org
Go to conference 2011 page and to conference report.

 

[alex3619]

If I understand the paper correctly, they say XMRV could not infect humans succesfully, because the virus gets eliminated by our immune system. A lot of people disagree with this.

Anyway, what you say could be possible as well: XMRV could be relatively harmless in itself, but our immune systems hate the life of it and start a full out war. The immune system has great difficulty eliminate a retrovirus however, which leads to us being sick all the time.

XMRV being a retrovirus however, it seems less likely it's just there for the ride. It might provoke the immune system and get stronger by its response.

Hi Jemal and eric_s, I have said for some time that one explanation that would have XMRV as benign, and still making us sick, is basically what you describe here. Our immune system is trying to kill the virus. Its a retrovirus - we can't kill it. So our immune system does not stop until it can no longer see the virus or its effects - temporary remission.

The argument that we can kill the virus so it can't hurt us is a blood argument. It is, ironically, one reason the virus is hard to find in blood. Is it true for other tissues? In particular, is it true for mucous membranes, the most likely route of infection? I doubt it.

Bye
Alex

ps This argument can be extended to other viruses that are not cleared - both herpes and enteroviruses which can persist in the tissues.

 

[Bob]

KDM gave a presentation at the Invest in ME conference last month.

A report of what he said is available on the IiME site www.investinme.org
Go to conference 2011 page and to conference report.

All the 61 people he tested came back positive for MLVs

I thought that it might just be a mistake in the wording of the article, because that would make it 100% positive.
Do you think it's correct currer?

It says:
"He had looked at 61 patients in Europe for XMRV, MLV and XMRVc and all were positive to at least one."

But it also says:
"84 CFS patients 57% +ve XMRV"

Article:
http://www.investinme.org/IiME Conf...onal ME Conference 2011 Conference Report.htm

 

[currer]

On re-reading it it looks to me as if there are references to two studies here. But it is ambiguous. It says all the 61 were positive either for MLvs XMRV or XMRVc. People can go to the link and see for themselves!

It will be nice to get the DVD and see how he presented his data.
I dont remember him making much drama out of his results though. I remember his presentation as pretty low-key.
Does anyone else who was there have another interpretation?

 

[Jemal]

Here is a long article on the Coffin paper, on the university website he works for.
http://now.tufts.edu/articles/exonerating-virus

It seems one of his students did a lot of the work. This is the conclusion:

XMRV was generated in the lab, says Cingz. Cell lines becoming contaminated with retroviruses is well documented.

That view is increasingly being accepted in the scientific community. In an editorial accompanying reports by Coffin and his colleagues, Science editor-in-chief Bruce Alberts noted that the 2009 study is now seriously in question, and that the journal is publishing whats called an expression of concern and attaching it to the original 2009 paper in Science.

The Reno scientists as well as many chronic fatigue syndrome patients and their advocates still cling to the XMRV hypothesis, despite the evidence that Coffin and others have presented to refute that. Thats not surprising, given the emotional tenor of the debate. And thats OK, says Coffin. Some good will come of this, he says. It brought chronic fatigue syndrome back into spotlight, and it will prompt more funding.

 

[WillowJ]

And thats OK, says Coffin. Some good will come of this, he says. It brought chronic fatigue syndrome back into spotlight, and it will prompt more funding.

It did bring ME/CFS back into the spotlight, but whether it will bring more funding--so desperately needed--remains to be seen. It hasn't yet, and government says no, no funding. Maybe Coffin will put his influence where his mouth is. I hope so.

 

[Jemal]

It did bring ME/CFS back into the spotlight, but whether it will bring more funding--so desperately needed--remains to be seen. It hasn't yet, and government says no, no funding. Maybe Coffin will put his influence where his mouth is. I hope so.

I think it is very easy for all the scientists to say that ME/CFS needs more research. I am also thinking most of them will forget about us. They weren't used to studying ME/CFS before and only jumped on it when it was associated with a retrovirus. Now that they think that association is dead, most will move back to their usual research.

 

[eric_s]

The Reno scientists as well as many chronic fatigue syndrome patients and their advocates still cling to the XMRV hypothesis, despite the evidence that Coffin and others have presented to refute that. Thats not surprising, given the emotional tenor of the debate. And thats OK, says Coffin.

Coffin got pretty emotional at the SoK Worhshop himself, just to say.

It's also interesting to read what Randy Schekman, the editor-in-chief of PNAS says about the situation (maybe this has already been posted, i don't know):

Schekman says its part of the scientific process for different groups to publish findings, for other groups to try to replicate them, and for researchers to debate conflicting results. Even if the original findings in a paper dont hold up, that is an unusual situation to retract a paper under.

Since PNAS published the paper, the journal has received a half-dozen papers from other authors documenting no correlation between XMRV and CFS but we declined to publish all of them because they are not substantial additions to the literature, just more of the same, says Schekman.

http://blogs.wsj.com/health/2011/06...on-cfs-xmrv-link-what-about-related-research/

 

[justinreilly]

The argument that we can kill the virus so it can't hurt us is a blood argument. It is, ironically, one reason the virus is hard to find in blood. Is it true for other tissues? In particular, is it true for mucous membranes, the most likely route of infection? I doubt it.

Hadn't thought of that. Makes some sense to me, but wouldn't it have to travel by blood or lymph to get all around the body? It seems like it would have to to cause a multi-system disease like ME.

 

[justinreilly]

Well, it looks like the antibodies could be very telling then, so that's good. I wanted to paste this bit in as well, it's more evidence why the antibodies are not random antibodies:

The WPI serology test can only be picking up the SU protein of an MuLV. The antibody to SFFV (spleen focus-forming virus) only reacts to that protein. Mouse DNA or ERV's cannot make whole virions, so the protein will not react.

So more evidence for a new human retrovirus, originating from mice.

Am I understanding this right that they are saying they are using antibodies to SFFV they got from a monkey or somewhere to detect the SU protein of MuLVs. So these are not antibodies from the ME patients, right?

They also say that you can't make antibodies to a contaminant. So does this mean that they are doing two antibody experiments: the one where they use SFFV antibodies and another where they look for the patients' own antibodies?

 

[alex3619]

Hadn't thought of that. Makes some sense to me, but wouldn't it have to travel by blood or lymph to get all around the body? It seems like it would have to to cause a multi-system disease like ME.

Hi justinreilly, in classical virology that would be "correct". However, a major means of transmission of MLVs is direct cell to cell transfer. It is slow. Over time a few will get through via blood, and set up new colonies in new organs, and then start the cell to cell transmission.

The second issue is: cytokines and other immune factors. The cells that produce them can travel in the blood everywhere, and these hormones will cause damage - how much and of what kind I do not think we really understand.

All of this is still speculation of course - we still wait for uncontested evidence of XMRV association or causation of ME/CFS. We need the likes of the Lipkin study.

Bye
Alex

 

[In Vitro Infidelium]

The argument that we can kill the virus so it can't hurt us is a blood argument. It is, ironically, one reason the virus is hard to find in blood.

But the only reason to connect XMRV to M.E/CFS is because Lombardi et al say it is detectable in the blood of CFS patients. Without that 'blood' evidence there is no reason to consider XMRV as being relevant to M.E/CFS any more than any other randomly selected micro-organism. Certainly one can hypothesise how XMRV might 'cause' M.E/CFS and come up with convincing disease models - but why choose XMRV ? This question is important because if Lipkin and the BWG do not provide support for XMRV in blood, then there will need to be some collective 'reflection' upon the XMRV saga if M.E/CFS communities are not be at the constant mercy of every research enthusiasm that follows, following every high and low with the commitment of a sports fan.

IVI

 

[ukxmrv]

ME patients follow the science behind the disease with the committment of someone fighting for their lives, IVI
I can't see anything wrong with that
and I mean follow, as in critically examine, and not blindly follow.

 

[In Vitro Infidelium]

ME patients follow the science behind the disease with the committment of someone fighting for their lives, IVI
I can't see anything wrong with that and I mean follow, as in critically examine, and not blindly follow.

Of course I agree with critically examine and not blindly follow but is that something achievable by people who see themselves as fighting for their lives ? At the very least such an attitude suggest a likely preference for ready answers rather than the posing of fundamental questions. To suggest that XMRV wasnt latched onto with undue expectations is denying what has to be obvious to anyone who has read the M.E/CFS forums in the last two years. That wanting XMRV to pan out is understandable, but the group attitude has been unhealthy and unrealistic and has not involved a general critical appraisal of all the available science. My suggestion is that now is the time to learn from the XMRV saga, and for those involved in the forums to start a more considered approach to science because the odds are against XMRV being a single answer, and M.E/CFS affected people are going to need positive engagement with a broad range of medical science for many years to come.

Of course another ten, twenty, thirty years without effective treatment would be really crap and at that range some of us will never enjoy the benefits of research, but given that there may well be a genetic element to M.E/CFS, we should IMO not focus just on our individual 'fights to survive' but on what the long term propects are for our, children, grand children, nephews, nieces etc. Saving the world from an XMRV plague had a great ring to it, but even if what we are stuck with is plain boring old M.E that's been around for forever, we can at least 'achieve' a quiet personal herosim by being part of the reasoned deconstruction of the elements of a confusing illness.

IVI

 

[ukxmrv]

That's just your poor opinion of other patients, though IVI. In fact most of your post was just your judgement of other patients. Nothing more.

Patients who have an interest in XMRV also are looking at the future. They see possible future generations who could possibly have a retrovirus. They see possible children infected. These are no short term goals.

It is a "quiet personal heroism" that they would consider the horror of having a retrovirus and yet be unselfish enough to consider their family members and the ongoing potential misery and harm that could occur.

I've been posing "fundamental questions" for nearly 30 years. Not going to stop now.

Not interested in easy answers. Never have been. Lots of patients considering XMRV are like that.

 

[Bob]

But the only reason to connect XMRV to M.E/CFS is because Lombardi et al say it is detectable in the blood of CFS patients.

Not really... There is also Alter and Lo... And now there is Hanson, De Meirlier, and Beiger.

Without that 'blood' evidence there is no reason to consider XMRV as being relevant to M.E/CFS any more than any other randomly selected micro-organism.

The virus might have an afinity to certain tissue types, and might replicate easily in these tissues, even if it is quickly cleared from the blood.

Certainly one can hypothesise how XMRV might 'cause' M.E/CFS and come up with convincing disease models - but why choose XMRV ?

Wanting XMRV to be fully investigated is not the same as 'choosing' XMRV.

This question is important because if Lipkin and the BWG do not provide support for XMRV in blood, then there will need to be some collective 'reflection' upon the XMRV saga if M.E/CFS communities are not be at the constant mercy of every research enthusiasm that follows, following every high and low with the commitment of a sports fan.

IVI, I think you misunderstand the science, otherwise you would not have these patronising and insulting opinions about the ME community.
You call it an 'XMRV saga', but I would call it an ongoing investigation into a scientific discovery.
I think that most ME patients are happy to watch XMRV research run its course.
Things only get heated when we perceive that certain establishment figures are trying to shut down the research for no valid scientific reason.

And even if XMRV proves not to be associated with ME, the WPI have still discovered an antibody biomarker.
That's an enormously interesting and significant discovery in itself.

 

[eric_s]

But the only reason to connect XMRV to M.E/CFS is because Lombardi et al say it is detectable in the blood of CFS patients. Without that 'blood' evidence there is no reason to consider XMRV as being relevant to M.E/CFS any more than any other randomly selected micro-organism. Certainly one can hypothesise how XMRV might 'cause' M.E/CFS and come up with convincing disease models - but why choose XMRV ?

Not really... There is also Alter and Lo... And now there is Hanson, De Meirlier, and Beiger.

Also there have now been stomach biopsies where they have found XMRV.

 

[Bob]

Also there have now been stomach biopsies where they have found XMRV.

Have you got a link for that please eric?

 

[eric_s]

No, but i could try to look for one. I know that Dr. De Meirleir is analyzing (i guess at RedLabs) stomach biopsies from at least some of his patients. I have personally met one of these patients.

 

[Enid]

Thanks for your input eric - the current work being done by K de M and Beiger (and treating) is very exciting.