Nature: Lombardi XMRV Paper Retracted in Full

[Firestormm]

22 December 2.45pm: http://blogs.nature.com/news/2011/12/xmrv-paper-withdrawn.html

The controversial paper that linked chronic fatigue syndrome to a virus has been withdrawn by Science.

Multiple laboratories, including those of the original authors, have failed to reliably detect xenotropic murine leukemia virusrelated virus (XMRV) or other murine leukemia virus (MLV)related viruses in chronic fatigue syndrome (CFS) patients, says the retraction notice. In addition, there is evidence of poor quality control in a number of specific experiments in the Report.

Unusually, Science has decided to retract the paper without the full agreement of the authors. We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement. It is Sciences opinion that a retraction signed by all the authors is unlikely to be forthcoming. We are therefore editorially retracting the Report.

The 2009 paper had already attracted an editorial expression of concern in May that noted that replicating the findings had proven difficult, and it was partially retracted in September after contamination of some samples used was detected.

The full retraction is not unexpected, but will still be a blow to advocates of a link between the virus and CFS, notably Judy Mikovits (whom we profiled in March; see Fighting for a cause). Some scientists have been harshly critical of the original paper and of the way that debate around the research has descended into a furious argument (see, for example, the Nature editorial Cause for concern).

Mikovits has since become embroiled in a legal case with her former employers, the Whittemore Peterson Institute for Neuro-Immune Disease research centre in Reno, Nevada (see Embattled scientist in theft probe). Other questions have also arisen over accusations that she misrepresented data (see Integrity issue follows fired researcher).

Jonathan Stoye, a retrovirologist at the National Institute for Medical Research in London, said it was no surprise that the paper had been retracted. The writings been on the wall for a time and the fonts been getting larger, he said. From the time the first contamination papers came out there were suggestions that was the explanation for everyones inability to find the virus when they looked for it. I dont think it can be a surprise that they finally retracted it.

He added, Mistakes will happen and science does tend to be self-correcting. It has done that, and actually its done that remarkably efficiently [in this case].

Nature is seeking comment from Mikovits, several of her co-authors, and the Whittemore Peterson Institute.

 

[oceanblue]

A little odd in that I thought Science had said it was waiting on the outcome of the Lipkin study. Maybe they have new information?

Multiple laboratories, including those of the original authors, have failed to reliably detect xenotropic murine leukemia virusrelated virus (XMRV) or other murine leukemia virus (MLV)related viruses in chronic fatigue syndrome (CFS) patients, says the retraction notice. In addition, there is evidence of poor quality control in a number of specific experiments in the Report.

 

[Firestormm]

Bloomberg: http://www.bloomberg.com/news/2011-1...e-journal.html

Chronic Fatigue-Virus Link Research From 2009 Retracted by Science Journal

A 2009 study on chronic fatigue syndrome that tied it to a mouse virus and led to a blood- donation ban has been retracted by the journal Science because it hasnt been replicated and had poor quality control.

The journal has lost confidence in the report and the validity of a potential link between the mouse virus XMRV and chronic fatigue, said Bruce Alberts, Sciences editor-in-chief, in a statement. The statement will appear in the magazines issue dated Dec. 23.

In December 2010, the American Red Cross stopped accepting blood from people diagnosed with chronic fatigue because of the risk it carried XMRV. The syndrome is characterized by severe, continued tiredness not relieved by rest. In October, scientific reports from the American Association of Blood Banks in San Diego indicated that XMRV isnt transmitted through blood.

At least 10 trials since the study have failed to replicate the results, and subsequent research has indicated the blood samples used in 2009 were likely contaminated by the virus in the laboratory. While the majority of authors agreed to the retraction, they have been unable to word a statement on their own, the journal said. Science decided to retract the report itself since a retraction signed by the authors is unlikely to be forthcoming, the journal said in a statement.

We regret the time and resources that the scientific community has devoted to the unsuccessful attempts to replicate these results, Alberts wrote.'

Virology Blog: http://www.virology.ws/2011/12/22/science-retracts-paper-on-detection-of-xmrv-in-cfs-patients/

Bruce Alberts, Editor-in-Chief of Science magazine, writes that the journal is retracting the 2009 paper describing the detection of the retrovirus XMRV in patients with chronic fatigue syndrome:

Science is fully retracting the Report Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.

He writes that the decision was reached because multiple laboratories have failed to reliably detect XMRV or related viruses in CFS patients. He also cites evidence of poor quality control in a number of specific experiments in the report, and that Figure 1, table S1, and figure S2 have been retracted by the authors. Finally, he notes the omission of information from the legend of figure 2C, specifically that the authors failed to indicate that the peripheral blood mononuclear cells had been treated with azacytidine, phytohemagglutinin, and IL-2. He concludes:

Given all of these issues, Science has lost confidence in the Report and the validity of its conclusions. We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement. It is Sciences opinion that a retraction signed by all the authors is unlikely to be forthcoming. We are therefore editorially retracting the Report. We regret the time and resources that the scientific community has devoted to unsuccessful attempts to replicate these results.'

I think Science are due to publish the full retraction tomorrow 23 December 2011.

 

[Firestormm]

Reuters: http://www.reuters.com/article/2011/12/22/us-embattled-chronic-fatigue-idUSTRE7BL14A20111222

Embattled chronic fatigue syndrome paper retracted

The editors of the journal Science have retracted a controversial 2009 paper claiming to prove a link between a virus and chronic fatigue syndrome.

"Science has lost confidence in the Report and the validity of its conclusions," Editor-in-Chief Bruce Alberts writes in the journal. "We regret the time and resources that the scientific community has devoted to unsuccessful attempts to replicate these results."

Although many in the chronic fatigue syndrome community were thrilled to have found a cause for their condition, and some began taking drugs to fight the infection, scientists started raising questions about the paper almost as soon as it was published.

A number of teams were unable to replicate the findings, and some thought the supposed link was due to contamination of the samples by the virus.

In May, the editors of Science, one of the world's leading scientific journals, published an Expression of Concern about the study along with two studies casting doubt on it. That was followed in September by the retraction of parts of the paper, although a number of authors, most notably Dr. Judy Mikovits, stood by the original findings.

What appears to have prompted today's retraction were further questions that surfaced in October, as reported by the Chicago Tribune, about whether some of the images in the paper had been inappropriately manipulated in ways that lent more credence to the link between CFS and the virus, known as XMRV.

According to Science, the authors of the report have acknowledged to the journal that they left out "important information" about one of the images.

"We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement," Alberts writes in the retraction notice.

Although the move is the nail in the coffin for the paper, it is unlikely to be the end of the virus-CFS story. A group led by Ian Lipkin of Columbia University is testing blood samples from 150 patients with the condition for XMRV and other potentially linked agents.

Chronic fatigue syndrome, which affects an estimated 1 to 4 million Americans, is characterized by "overwhelming fatigue that is not improved by bed rest and that may be worsened by physical or mental activity," according to the Centers for Disease Control and Prevention.

The story of XMRV and CFS has also had dramatic twists for Mikovits. Last month, she ended up in a Ventura County, California jail for five days after her former employer, the Whittemore Peterson Institute in Reno, Nevada, accused her of stealing lab notebooks, a computer and other materials. Earlier this week, a Washoe County, Nevada judge ruled in a civil case against Mikovits, saying that she had to return all of the materials to the institute.

SOURCE: Science, December 22, 2011.

 

[Firestormm]

A little odd in that I thought Science had said it was waiting on the outcome of the Lipkin study. Maybe they have new information?

I do seem to recall hearing/reading something similar Ocean. To be honest though the specifics are a blur. It will be interesting to see if this full retraction does affect what Lipkin is overseeing with the XMRV work I think.

 

[Wonko]

Yum!! I love the taste of steel toecaps in the morning, and timed specially for christmas as well.

 

[Vitalic]

It's about time, hopefully the ME/CFS community can move on from this now.

 

[Firestormm]

Here's the Cohen Science Insider piece and Retraction Watch follows...

http://news.sciencemag.org/scienceinsider/2011/12/in-a-rare-move-science-without-a.html

In a Rare Move, Science Without Authors' Consent Retracts Paper That Tied Mouse Virus to Chronic Fatigue Syndrome

After enduring more than 2 years of criticism that included evidence of contamination and misrepresentation of data, a Science paper that linked a mouse retrovirus to chronic fatigue syndrome (CFS) today received its last rites: Editor-in-Chief Bruce Alberts issued a full retraction. The study's 13 authors in September signed a partial retraction after one of the three collaborating labs found that a contamination had marred its contribution, but they could not agree on the wording of the full retraction, so Alberts issued it without their approval. "Science has lost confidence in the Report and the validity of its conclusions," wrote Alberts in a rare "editorial" retraction, which appears in the 23 December issue of Science. "It is Science's opinion that a retraction signed by all the authors is unlikely to be forthcoming."

Researchers from the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, led the controversial study, teaming up with investigators from the National Cancer Institute (NCI) and the Cleveland Clinic in Ohio. As they reported online in the 8 October 2009 issue of Science, they found evidence of a mouse virus known as xenotropic murine leukemia virus-related virus (XMRV) in the blood of 67% of the 101 CFS patients they analyzed. Alarmingly, 3.7% of controls also tested positive, leading to fears that XMRV could be widely contaminating the blood supply in many countries.

Soon after publication, researchers around the world began reporting that they could not find the virus in CFS patients. One group discovered that XMRV was likely created in laboratory experiments with mice that made an immortalized cell line to study prostate cancer, and another showed that variants of this line had evolved more than isolates of XMRV, exactly the opposite of what would be expected if the mouse virus truly infected humans and was subject to immune pressure. The U.S. Department of Health and Human Services organized a nine-lab study to assess whether the blood supply was at risk from XMRV or related mouse retroviruses. This so-called Blood Working Groupwhich included the researchers from WPI and NCI who co-authored the original Science study using whatever assays they chosereported online 22 September in Science that no one could reliably detect the virus in previously positive samples from patients.

Alberts says the Blood Working Group finding was the final straw that led Science to request the full retraction. "The blood group study to me was dramatic evidence of poor science," says Alberts. "It gave us absolutely no confidence in the ability of the major labs involved to do the assays. I find that enormously disturbing." NCI's Francis Ruscetti, a prominent retrovirologist and one of the co-authors, attempted to coordinate a retraction with his colleagues but a dispute arose over wording that suggested some of the findings in the original paper were still valid. "We tried to get all of the authors to agree, but it got endless," says Alberts. "The responsibility that Science magazine has to the scientific community is to make a strong statement that we don't think anything in that paper can be relied on."

WPI's Judy Mikovits, who led the study with Ruscetti, says she and two of her contributing lab assistants refused to sign the retraction. The day after the publication of the Blood Working Group study, Mikovits presented new data at a CFS meeting in Ottawa, Canada, that purported to show evidence of human gamma retrovirusesthe family XMRV belongs toin patients. She essentially argued that the original paper focused too narrowly on one variant of XMRV. (She also showed a slide at the meeting that led to Science to discover that the original paper had a mislabeled image, which factored into the full retraction.) "We were confident of our data," Mikovits told ScienceInsider, explaining why they wanted to include a line in the retraction that said they still trusted their data and conclusions. Ruscetti refused to comment about the full retraction.

Mikovits was fired by WPI a week after the Ottawa meeting for insubordination and then accused in a civil suit by her former employer of misappropriating laboratory notebooks and computer data about her studies. Police at the University of Nevada, Reno, then filed a warrant for her arrest in relation to the allegedly stolen material, and she was briefly jailed. Both the civil and criminal cases are now being adjudicated.

Mikovits and Ruscetti are currently taking part in a multilab study coordinated by pathogen sleuth Ian Lipkin at Columbia University in New York City that will look for XMRV and related viruses in many more CFS patients than were analyzed in the Blood Working Group study. Mikovits says this $2.3 million study, funded by the U.S. National Institute of Allergy and Infectious Diseases, also factored in to the decision not to sign the full retraction. "We think it's premature to do anything before it's complete," says Mikovits, who estimates they will have results within 2 months.

Alberts strongly disagrees. "I think they should cancel that study," says Alberts. "It's over. They can't do the assays, so what's the point? Why should that give any different result than the blood group study? Maybe us retracting will help them scale back how much money they've spent on that. It seems like an incredible waste."

Researchers who have closely followed this saga and invested their own efforts into finding XMRV in CFS patients commend Science for issuing a full retraction. "It's very sad, but the writing has been on the wall for some time nowand the font size has gotten bigger over the course of the year," says retrovirologist Jonathan Stoye of the Medical Research Council in London, who co-authored an editorial in Science supporting the original paper. John Coffin, a retrovirologist at Tufts University in Boston who wrote the editorial with Stoye, says the full retraction could have happened much earlier. "It's kind of a surprise that it took so long," says Coffin.

Science Executive Editor Monica Bradford says the journal always prefers authors to sign retractions. "It's the authors' work, and it's a very clear signal to scientific community that there can't be accusations of other agendas," says Bradford. Alberts says they simply had been "spun" by the authors too many times for too long. "If our editorial reaction helps to end the resources to go into this fruitless endeavor, I think we've made a contribution to the scientific community," he says.


Retraction Watch:

Chronic fatigue syndrome-XMRV paper retracted by Science, completely this time

The editors of Science have fully retracted a study they published in 2009 alleging a link between chronic fatigue syndrome (CFS) and the virus XMRV.

'The notice begins with a nod to the reasons that the paper has already been partially retracted:

Science is fully retracting the Report Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome (1). Multiple laboratories, including those of the original authors (2), have failed to reliably detect xenotropic murine leukemia virusrelated virus (XMRV) or other murine leukemia virus (MLV)related viruses in chronic fatigue syndrome (CFS) patients. In addition, there is evidence of poor quality control in a number of specific experiments in the Report. Fig. 1, table S1, and fig. S2 have been retracted by the authors (3).

It also refers to evidence of image manipulation that was described by blogger Abbie Smith and then reported in the Chicago Tribune:

In response to concerns expressed about Fig. 2C [summarized in (4)], the authors acknowledged to Science that they omitted important information from the legend of this figure panel. Specifically, they failed to indicate that the CFS patientderived peripheral blood mononuclear cells (PBMCs) shown in Fig. 2C had been treated with azacytidine as well as phytohemagglutinin and interleukin-2. This was in contrast to the CFS samples shown in Figs. 2A and 2B, which had not been treated with azacytidine.

The notice also makes it clear just how contentious a process it has been to sort all of this out:

Given all of these issues, Science has lost confidence in the Report and the validity of its conclusions. We note that the majority of the authors have agreed in principle to retract the Report but they have been unable to agree on the wording of their statement. It is Sciences opinion that a retraction signed by all the authors is unlikely to be forthcoming. We are therefore editorially retracting the Report. We regret the time and resources that the scientific community has devoted to unsuccessful attempts to replicate these results.

Despite the retraction, you can be sure you havent heard the end of this story. For one, one of the authors, Judy Mikovits, is embroiled in a legal battle with her former employer, the Whittemore Peterson Institute in Reno, Nevada, over whether she has the right to lab notebooks and other materials. She recently spent five days in a Ventura, California jail as part of the case. And she is also part of an ongoing study by Columbia Universitys Ian Lipkin of 150 blood samples from people with CFS, to figure out if anything including XMRV can be considered a cause of the disease.'


Hopefully we will get a statement from Lipkin in the next few days about the project he is working on and whether it will be scrapped.

 

[Esther12]

Even though I've thought it was very unlikely there would be a link between XMRV/HGRVs and CFS for some time, I'm worried that this retraction could be a bad thing politically.

There are already a few CFS patients who think that there is some cover-up around XMRV/CFS, and having the CFS paper retracted alone, when the evidence against the association between XMRV and prostate cancer looks just about equally compelling, could end up fanning the flames of that conspiracy theory.

It's annoying that so much goes on behind the scenes, and we can't know exactly what was said in all the discussion about this at Science, and between the authors of the paper. It does seem like we've got confirmation that the figure used in the paper was mislabelled in their original submission, when some from the other board have claimed that information was removed in the editing/peer review process.

 

[currer]

So History repeats itself.

Christmas. A convenient time for burying embarrassing research.

A stitch-up.

 

[Firestormm]

Even though I've thought it was very unlikely there would be a link between XMRV/HGRVs and CFS for some time, I'm worried that this retraction could be a bad thing politically.

There are already a few CFS patients who think that there is some cover-up around XMRV/CFS, and having the CFS paper retracted alone, when the evidence against the association between XMRV and prostate cancer looks just about equally compelling, could end up fanning the flames of that conspiracy theory.

It's annoying that so much goes on behind the scenes, and we can't know exactly what was said in all the discussion about this at Science, and between the authors of the paper. It does seem like we've got confirmation that the figure used in the paper was mislabelled in their original submission, when some from the other board have claimed that information was removed in the editing/peer review process.

Do you mean it would be 'easier' or 'better' to have the prostate cancer/XMRV papers retracted also Esther? Sorry I am not following. This retraction is about this particular paper and whether or not it stands up i.e. the association proclaimed between XMRV and CFS and it clearly doesn't.

I don't do politics I am afraid but yes it would appear some are already claiming the retraction is about politics. Whatever the heck that means.

Be interesting to hear from Lipkin and his sponsors I think especially after the comments above from Alberts.

 

[currer]

http://www.mecfsforums.com/index.php/topic,10933.0.html

Read what DR YES says.

 

[Esther12]

Do you mean it would be 'easier' or 'better' to have the prostate cancer/XMRV papers retracted also Esther? Sorry I am not following. This retraction is about this particular paper and whether or not it stands up i.e. the association proclaimed between XMRV and CFS and it clearly doesn't.

I don't do politics I am afraid but yes it would appear some are already claiming the retraction is about politics. Whatever the heck that means.

Be interesting to hear from Lipkin and his sponsors I think especially after the comments above from Alberts.

I'm probably not expressing myself well, perhaps because I'm trying to explain beliefs which I do not hold.

I'm worried that this retraction could mean that those who still believe XMRV/CFS are associated will be more likely to believe that there is some sort of cover-up.

Because:

1) The history of quackery and CFS, most importantly from those seen as a part of 'mainstream medicine'.
2) The CFS, and not PC, paper has been retracted, even thought the evidence against XMRV/PC seems almost equally compelling.
3) They did not wait for the Lipkin study, which was supposed to be definitive. The retraction coming now could also mean that people are less likely to think that the Lipkin study will be done fairly.
4) They weren't able to get the support of the authors for retraction, yet don't seem to yet be ready to be truly condemning of them.

I'm not sure that the retraction brings any benefits at this point, and it might just make things worse. I'd be interested to know what made them decide that now was the time to do this.

 

[Wonko]

IMO christmas.

 

[Esther12]

IMO christmas.

lol - could be: "Lipkin's taking too long, and I want a clear desk for the new year! - let's whack it out now."

I'm a bit worried that they're just concerned about their own reputation, and want to distance themselves from a paper which is almost certainly wrong prior to a definitive answer from Lipkin in order to protect themselves politically, without being terribly concerned about how this may affect things politically for patients.

Who knows?

 

[xrayspex]

If you look at the big picture, historically, yeah, I do think its sketchy how the research on CFS has gone down the last 25 years and this is just more of the same. XMRV per se may not be the answer but there is research linking auto immune stuff to viruses etc and HTLV is a retrovirus and I know someone with CFS finally dx with HTLV and then get cancer....so yea I think its fascinating I never heard of htlv until the last couple years and its not routinely tested for when you have FMS or CFS....something is definitely connected with CFS, AI, cancer and viruses, I am not saying viruses the only thing but its pathetic they havent dug deeper into all of it.


oh, just looked at Dr Yes post-----exactly, they had figured out the invalid Silverman part and gave it the boot, frustrating they don't acknowledge this....really does seem like either ignorance, good ole boys club, or perhaps back room lobbying from health insurance industry to prevent this all from coming together in timely honest fashion

 

[currer]

If you look at the big picture, historically, yeah, I do think its sketchy how the research on CFS has gone down the last 25 years and this is just more of the same. XMRV per se may not be the answer but there is research linking auto immune stuff to viruses etc and HTLV is a retrovirus and I know someone with CFS finally dx with HTLV and then get cancer....so yea I think its fascinating I never heard of htlv until the last couple years and its not routinely tested for when you have FMS or CFS....something is definitely connected with CFS, AI, cancer and viruses, I am not saying viruses the only thing but its pathetic they havent dug deeper into all of it.

Not pathetic. Deliberate.

 

[xrayspex]

yea "pathetic" is just a side note, an adjective in this case, going right before evil and deliberate

 

[SilverbladeTE]

"The trouble with science is that it can be perverted"

Deliberate perfidy is not even needed, merely

...the inflexibility of inferior minds.

The world is a dangerous place to live; not because of the people who are evil, but because of the people who don't do anything about it.

 

[Jenny]

Does anybody know how common it is for a paper published in a scientific journal to be withdrawn? It seems a bit odd to me - science proceeds by confirming and disconfirming previous work, so there are bound to be papers which turn out to be 'wrong' or misleading. In my field (psychology) I've never heard of a paper being withdrawn.

Jenny