‘It’s over’

A controversial 2009 paper that linked a mouse retrovirus to Chronic Fatigue Syndrome (CFS) has been through dozens of criticisms and a partial retraction. Now, after a nine-lab study showed that the retrovirus could not even be reliably detected in the original experiment’s patients, the journal Science has issued a rare full retraction without a signature from the paper’s authors.

The original experiment, led by Vincent Lombardi of the Whittemore Peterson Institute in Reno, NV, detected the mouse retrovirus XMRV in 67 per cent of patients with CFS. According to the paper published in Science, these results raise the possibility that XMRV contributes to the pathogenesis of CFS, a debilitating disease of elusive origin.

Sufferers face persistent tiredness that is not relieved by sleep, forgetfulness, joint pain and unusual headaches. Epstein-Barr virus, human herpes virus six, and inflammation of the nervous system have all been cited as possible causes.
The results, which apparently showed a viral link to CFS, thrilled many CFS sufferers and patient advocates. But many others advised caution. “Here we go again,” said Kimberly McCleary, president of the CFIDS Association of America, a North Carolina patient group, when she first saw the headlines. With more than 20 years in her position, McCleary has seen a number of infectious agents suggested as causes of CFS, and each possibility has been ruled out as scientists looked closer.

Research on the subject continued, and in early 2011 two new papers were submitted to Science arguing that the original findings were most likely due to contamination. One of these studies failed to find XMRV in 61 confirmed CFS patients, 43 of whom had been told by the Lombardi et al team that they were infected with the virus. Judy Mikovits, one of the coauthors of the Lombardi et al paper and the team’s spokesperson, maintained that neither study invalidated the original research.

But the editors at Science privately requested a retraction. Mikovits declined, saying that a retraction was “premature.” Eventually, given the growing amount of evidence calling the paper into question, the editors published an “Editorial Expression of Concern” about the research.

A nine-lab study called the Blood Working Group was formed by the US Department of Health and Human Services to test the result, and in September of 2011 they found that none of the labs could even reliably detect XMRV in randomly coded blood samples. At the same time, a lab contributing to the original study found evidence of contamination in their materials. A partial retraction, of that lab’s section of the study, was run in Science.

After the Blood Working Group study was published, the Science editors lost confidence in the Lombardi et al paper’s validity. “The blood group study to me was dramatic evidence of poor science,” said Editor-in-Chief Bruce Alberts, “I find that enormously disturbing.” Francis Ruscetti, one of the original authors, attempted to coordinate a retraction, but some members of the team refused to sign in a dispute over the wording.

Alberts eventually lost patience with the arguing and published the retraction anyway. “We tried to get all of the authors to agree, but it got endless,” he said, “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.”

Judy Mikovits and two contributing assistants from her lab refused to sign the retraction. “We were confident of our data,” she said, “We think it’s premature to do anything before it’s complete.” She and others are currently conducting a $2.3 million study looking for XMRV and related viruses in CFS patients.
Alberts disagrees: “I think they should cancel that study. It’s over.”

Other scientists in the field believe the retraction should have happened earlier. “It’s kind of a surprise that it took so long,” said John Coffin, a retrovirologist at Tufts University in Boston.

The only other paper supporting a link between XMRV and CFS was published in the Proceedings of the National Academy of Sciences. Shortly after the Lombardi et al retraction, the authors of the PNAS paper retracted their work, citing the Blood Working Group study and others.

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