You could be forgiven for thinking that the story of XMRV, a mouse retrovirus implicated in chronic fatigue syndrome (CFS), is over. After all, study after study has failed to replicate the XMRV-CFS link, and last year, Science retracted the 2009 paper  in which XMRV was first fingered as a cause of the elusive syndrome. Most researchers concluded long ago that those findings resulted from an accidental contamination of patient samples in the lab.
But until now, the biggest study on the topic still hadn't been wrapped up: a project funded by the U.S. National Institutes of Health (NIH) and led by Ian Lipkin of Columbia University that brought together supporters and skeptics of the theory that XMRV plays a role in chronic fatigue. Today, mBio published the results of the study, which proves that, as most scientists suspected, the XMRV theory is most definitely dead .
This time, even Judy Mikovits, the chief author of the 2009 study and the main protagonist in the twisted scientific saga, agrees. Mikovits, formerly at the Whittemore Peterson Institute (WPI) in Reno, Nevada, participated in Lipkin's study and concedes that it is "the definitive answer. … There is no evidence that XMRV is a human pathogen."
Three research groups took part in the mBio study: Mikovits, along with her collaborators Francis Ruscetti at the National Cancer Institute and Maureen Hanson at Cornell University; a team led by Shyh-Ching Lo at the Food and Drug Administration, which linked CFS to a related group of viruses called MLVs  in a study that was also retracted ; and a group at the Centers for Disease Control and Prevention, which had failed to find the virus in CFS patient samples . Each group was presented with samples from 147 patients and 146 healthy controls from six U.S. cities. Each was free to analyze samples using its own techniques; that way, no one could complain that the right methods weren't used, Lipkin says. The samples were blinded until all the analyses were done.
Mikovits's participation in the study was complicated by the fact that she was fired by WPI  in September of 2011 and later arrested, jailed, and charged with illegally taking data and related property from WPI. (The criminal charges, which came on top of a civil suit by WPI, were dropped in June .) Antibody testing for Mikovits's share of the study was done at Ruscetti's lab and PCR tests at Hanson's lab.
None of the groups found any trace of XMRV or MLVs whatsoever—neither in patients nor controls. Mikovits and Ruscetti did find that about 6% of patients and controls had antibodies that reacted to XMRV—a result that they chalk up to aspecific binding instead of XMRV infection.
As to XMRV, "it's simply not there," Mikovits said at a press conference this morning to announce the results of the new study. No previous study had tried to replicate her findings using her exact methods, Mikovits says. "I'm forever grateful to Ian Lipkin for making it possible to participate," she says. Lipkin says he is "proud" of Mikovits for accepting the outcome and asked the audience at the press conference to give her a round of applause.
The outcome isn't surprising, says Vinay Pathak of the National Cancer Institute, one of the authors of a key study last year that showed XMRV was accidentally created in the lab . Still, Pathak says, Lipkin's study is a "model" for how similar disputes can be resolved in the future. Kim McCleary, the head of the CFIDS Association of America, a CFS advocacy group, hopes the study will finally bring closure to the debate about XMRV.
Samples gathered for the new study will also be available for other researchers, which is a "silver lining for an ultimately disappointing outcome," McCleary says. "We hope that people from all over the world will use these samples," Lipkin said this morning.