‘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.

2 Comments on "‘It’s over’"

  1. youdontlooksick | January 6, 2012 at 1:21 am |

    It’s not over. You better check your facts.
    December 28, 2011

    Dear Colleagues and Friends in the CFS/ME Community:

    This letter is written to clarify the status of the XMRV/MLV CFS/ME study I am coordinating at the request of the National Institutes of Health. Although frequently described as the “Lipkin Study,” it is in fact the Alter, Bateman, Klimas, Komaroff, Levine, Lo, Mikovits, Montoya, Peterson, Ruscetti, and Switzer study, designed by these 11 investigators to bring their best methods for case ascertainment and characterization and state-of-the-art molecular and serological diagnostic tools to address the question of whether a retrovirus is associated with disease. My role in conjunction with Mady Hornig and Bruce Levin at Columbia University is to ensure that the study represents an appropriately powered, definitive, representative sample of CFS/ME patients across the United States; to receive and distribute samples; and to assess results obtained in individual laboratories for consistency and evidence for or against an association between retroviral signal and disease. I use the term “signal” because any finding related to a retrovirus, whether infectious or noninfectious, genetic material, protein, or antibody, may provide insights into disease or allow development of diagnostic tests even if a causative relationship is not established. My condition on accepting this charge from the NIH and the clinical and laboratory investigators is that each participant agree to unconditionally accept group criteria for defining cases to be used in this study. Laboratory investigators were also required to unequivocally endorse their results at the conclusion of the study. Several months were required to develop clinical criteria for case and control definition and to complete approvals for human subject protection. We encountered additional delays when Dr. Mikovits could no longer pursue her work at the WPI. At that juncture, some parties suggested that the work proceed at WPI without her.

    However, in my judgment, the value of this study rests in its inclusion of the original investigators who reported the XMRV/MLV findings. Thus, I was grateful when we found a way to fully engage Dr. Mikovits. At the time of this writing we have collected and distributed for laboratory analysis samples from 123 CFS/ME patients and 88 matched control subjects. We intend to complete collection and analysis of samples from 150 patients and 150 controls in early 2012.

    There is criticism in some quarters that this study is unnecessary given results obtained by other investigators with other samples. However, the participating clinical and laboratory investigators and our team at Columbia do not agree. We are fully committed to completing the work rapidly and rigorously. For those who continue to express concerns that this study is an inappropriate use of resources in a challenging fiscal environment, please be assured that more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution. Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that disease is due to XMRV or MLV infection.

    Sincerely yours,

    W. Ian Lipkin, MD, Director, Center for Infection and Immunity

  2. It’s a horrible disease. We need treatment and research.

Comments are closed.