‘science’ Magazine Calls For Retraction Of The Original Paper On Xmrv And Cfs

‘Science’ magazine calls for retraction of the original paper on XMRV and CFS

From the Wall Street Journal health blog, 30 May 2011 (Story by Amy Dockser Marcus.
Editors of the journal Science have asked the co-authors of a 2009 paper that linked chronic fatigue syndrome to a retrovirus called XMRV to voluntarily retract the paper.
But in written response Friday, study co-author Judy A. Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease said “it is premature to retract our paper.” The letter was reviewed by the The Wall Street Journal.
The study raised patients’ hopes that if a virus was linked to chronic fatigue syndrome, a treatment might be found. Public-health officials were alarmed by the possibility that supposedly healthy people might unknowingly be infected with a contagious retrovirus. The federal government began an ongoing effort to evaluate whether the nation’s blood supply was safe, work that continues.
In the May 26 letter to Dr. Mikovits and her co-authors, also reviewed by the Journal, Science editor-in-chief Bruce Alberts and executive editor Monica Bradford cited concerns about the validity of the findings, saying other scientists hadn’t been able to replicate them, among other reasons.
Dr. Mikovits, who confirmed the letters, said she hadn’t received a response in return. Dr. Alberts and Ms. Bradford at Science couldn’t be reached for comment.
After the 2009 study, other published studies showed that some anti-retrovirals approved for use in HIV might also be effective against XMRV. Some doctors began prescribing anti-retrovirals for chronic fatigue syndrome patients.
The concern about the blood supply led blood banks to bar patients with chronic fatigue syndrome from donating. An advisory committee to the federal Food and Drug Administration recommended last year that the FDA bar people with chronic fatigue syndrome from donating. The FDA hasn’t weighed in on the recommendation.
The Centers for Disease Control and Prevention, among other groups, published studies reporting they didn’t find XMRV in chronic fatigue syndrome patients. Other papers found that substances used as part of the process to detect XMRV might be contaminated, raising the possibility that this may explain the positive findings in the 2009 Science paper.
In the letter to the study authors, Dr. Alberts and Ms. Bradford suggested the paper be withdrawn “in light of the growing number of research papers from independent investigators who have either failed to replicate your original finding that XMRV is associated with chronic fatigue syndrome and/or who have provided evidence that laboratory reagents are widely contaminated with the virus.”
The letter added that two additional papers that “cast further doubt” on the 2009 paper’s findings will be published on June 2 in Science, and that Science will be publishing what it called an editorial expression of concern about the 2009 paper. “At this juncture, Science feels that it would be in the best interest of the scientific community” for the co-authors to retract the paper, the letter stated.
An editorial expression of concern, while falling short of the journal outright retracting a paper itself, raises a red flag to the scientific community that serious doubts exist about a paper’s findings and can make it harder for researchers to obtain funding or publish papers, says R. Grant Steen, a medical communications consultant. He has published papers analyzing 742 English language research papers that were retracted from the PubMed database from 2000-2010.
The 2009 study in question, led by investigators at Whittemore Peterson in Reno, Nev., and including researchers from the National Cancer Institute and the Cleveland Clinic, generated enormous attention among scientists and patients. The researchers reported they found the retrovirus XMRV in a majority of 101 patients with chronic fatigue syndrome, a debilitating condition that involves cognitive dysfunction and severe pain. The authors also found the virus in nearly 4% of 218 healthy people used as controls in the study.
Dr. Mikovits said it was still too early to know the reasons for the differing results in different labs, and that the Institute was looking forward to participating in a major study under way by the NIH and led by Columbia University scientist Ian Lipkin to help clarify the matter.<br style=""> <br style="">

Write to Amy Dockser Marcus at amy.marcus@wsj.com

Source: http://www.sciencema...t/333/6050/1694

Science 23 September 2011:
Vol. 333
no. 6050
pp.1694-1701
DOI:10.1126/science.333.6050.1694

• News Focus

Virology

False Positive

• Jon Cohen,
• Martin Enserink

For the past 2 years, a controversy has roiled around the purported link between a mouse retrovirus, XMRV, and chronic fatigue syndrome (CFS), a baffling, debilitating disease with no known origin.
An October 2009 paper in Science found XMRV in the blood of two-thirds of the CFS patients examined, but more than a dozen labs have failed to replicate it to date. Millions of dollars have gone into clarifying the question, which has had far-reaching consequences for people with CFS and, if the virus lurked in the blood supply, the public at large.
A nine-lab study published online this week by Science found that none of the labs could reproducibly detect XMRV or relatives of the virus in blood samples distributed under a blinded code. Science is also running a partial retraction of the original paper, as a contributing lab found that it in fact had a contamination.

Source: http://www.chicagotr...0,6792877.story

By Trine Tsouderos Tribune staff reporter 6:47 p.m. CDT, October 3, 2011


Manipulation alleged in paper linking virus, chronic fatigue syndrome

The journal that published a high-profile paper linking chronic fatigue syndrome to a retrovirus is now investigating allegations that a figure in that report was manipulated.

The appearance in Science of the 2009 paper caused an immediate sensation among patients who have yearned for an explanation for their condition. Its authors said they had found evidence of a retrovirus called XMRV in the blood of people with chronic fatigue syndrome more frequently than in the blood of their healthy peers.

The report included a figure purporting to depict lab test results from seven blood samples, including two from chronic fatigue syndrome patients whose blood appears to show evidence of XMRV and five from healthy people whose blood does not.

But the leader of the team that authored the 2009 paper, researcher Judy Mikovits, apparently presented the same figure -- carrying different labels and supporting a different point -- in a talk given at a conference on Sept. 23 in Ottawa.

A copy of her PowerPoint presentation circulating among an email group also reveals an apparent third version of the image, with a third set of labels, when formatting is turned off.

"As is our policy in cases of alleged figure manipulation, we will follow up with the research authors as soon as our own review of the allegation is complete," the editors of Science wrote in a statement. "In particular, we will request additional information from the authors as one of the next steps."

Attempts to interview Mikovits were unsuccessful, and her employer, the Whittemore Peterson Institute for Neuro-Immune Diseases in Reno, Nev., announced Monday that she had been terminated.

Institute president Annette Whittemore said in a statement that the institute was also looking into the allegations.

"It is our understanding that some patient ID numbers may have been changed to a new set of coded numbers during the research to protect their privacy before publication," Whittemore said. "We will work with Science in hopes of addressing their concerns and to gain a full understanding of the cause of any potential discrepancies."

Almost immediately after the 2009 Science paper, researchers from across the globe, including the U.S. Centers for Disease Control and the U.S. Food and Drug Administration, initiated follow-up experiments but came up with no evidence XMRV was infecting people. Instead, most evidence pointed to XMRV as a laboratory contaminant.

Even so, some patients paid for non-FDA-approved blood tests for XMRV, and some reported taking antiretroviral drugs.

A day before Mikovits' Ottawa talk, several other figures associated with the Science paper were retracted after scientists discovered lab contamination associated with part of the study.

That same day, Science also released the results of a study in which nine independent labs, including the Whittemore Peterson Institute, tested blinded blood samples from patients and healthy people for evidence of XMRV. Seven labs found nothing. Results from the other two, including the institute, were inconsistent.

The reappearing figure came to light after an Oklahoma graduate student in retrovirology, Abbie Smith, compared Mikovits' presentation with the original Science figure.

"Ladies and gentlemen, a magic trick," Smith wrote Friday on her blog, ERV. "I am going to take two pieces of data, from two independent experiments, establishing 'proof' of two different concepts, presented in two different formats and two different events. ... And turn them into the same figure."

Patients in online forums reacted swiftly. "I have been a big supporter of WPI, sending them a lot of money whilst having only little. But this is very serious. At best they are incredibly sloppy and disorganized," one person wrote on the Phoenix Rising forum.

Retrovirologist Jonathan Stoye, who co-wrote a supportive commentary accompanying the 2009 study, said of the recent events: "It is a tragedy in every respect."

Source: http://retractionwat...a-with-science/


Tracking retractions as a window into the scientific process


Why didn’t XMRV-chronic fatigue syndrome researcher Mikovits — now fired — share data with Science?
with 2 comments

The saga of XMRV and chronic fatigue syndrome (CFS) continues, with the news that Judy Mikovits, a main proponent of the link between the virus and CFS, has been fired from her post at the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno. From a blog post yesterday on X Rx:

Breaking news. The entire WPI research program has been closed by the institute’s CEO, and the facility is now locked down. It’s former principle investigator, Dr. Judy Mikovits, is in active discussions concerning institutions to which she may move to continue her grant-funded research.

We spoke to Mikovits last week, apparently within a day of her being fired, according to the sequence of events reported today on the Wall Street Journal Health Blog. We were interested in her reaction to a comment to Retraction Watch by Science executive editor Monica Bradford about why the 2009 study Mikovits had co-authored had been partially retracted — a rare move, as we noted:

While we were aware that other co-authors had tested samples and claimed to not find evidence of plasmid contamination, those co-authors were unwilling to provide their data for examination so we were unable to comment on the validity of the other experiments.

The contamination Bradford refers to had been reported to Science by two of the 2009 study’s co-authors, both of whom are at the Cleveland Clinic. According to the notice:

…two of the coauthors, Silverman and Das Gupta, analyzed DNA samples from chronic fatigue syndrome (CFS) patients and healthy controls. A reexamination by Silverman and Das Gupta of the samples they used shows that some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA (2).

We spoke to Mikovits for a while, during which time she walked us through a presentation she gave on September 23 at a CFS meeting in Ottawa. Mikovits stressed that she believes a number of XMRV relatives are linked to CFS, and that the family needs a new name: HGRV, for human gammaretrovirus.

When we asked about the samples, Mikovits told us last week:

The reason why we didn’t give the actual data to Science and start a spitting match is that the point in science isn’t to place blame. The point is to get to the bottom of what’s going on.

But in getting to the bottom of what was going on, Mikovits became convinced that, in fact, one lab was to blame:

The only conclusion is that they were contaminated in the Cleveland Clinic.

Unfortunately, three of the six samples from the Cleveland Clinic were the ones used to derive the whole sequence of the virus. But, says Mikovits:

We decided not to throw them under the bus. We don’t believe it’s in the interests of science. People make mistakes. They worked very hard to sequence the virus, and now we have to do the next generation.

She continued:

I told all the editors all this, and they agreed there was no reason to retract the whole paper.

By not providing the data, however, Mikovits has left everyone wondering about her samples. And what led to her firing seems to have been a similar situation. From the WSJ Health Blog report:

In a letter from Whittemore Peterson President Annette Whittemore to Mikovits, which was reviewed by Health Blog, Mikovits was terminated after refusing Whittemore’s direct request that cell lines be turned over to another scientist at the institute who wanted to do research on them.

In a letter of response, Mikovits said that the cells were for use in a specific NIH-funded project and that it would be inappropriate to use them for another purpose without her knowledge and consent.

We’ll of course keep an eye on this rapidly evolving situation.

Update, 7:30 p.m. Eastern: The Chicago Tribune’s Trine Tsouderos, who has been covering the XMRV-CFS story for years, just tweeted the following comment from Science, apparently in response to questions about a story she’s about to file:

“We are aware of allegations of mislabeled images in 1 of the figures in the 2009 Science paper + in meeting slides.”

Tsouderos’ story comes on the heels of a post by Abbie Smith alleging such image manipulation.

Update, 8 p.m. Eastern: Here’s Tsouderos’ story, with details and a response from WPI.