XMRV is running out of legs to stand on. The journal Science, which published a controversial 2009 paper linking the retrovirus to chronic fatigue syndrome (CFS), has published two follow-up papers undermining the association, as well as an “editorial expression of concern” indicating that the association was probably the result of contamination.
According to the Wall Street Journal, Science has also asked the authors of the 2009 paper to voluntarily retract it.
“The request was almost inevitable at some point,” says Jonathan Stoye, a retrovirologist at the MRC National Institute for Medical Research in London who emerged as one of the staunchest critics of the link between XMRV and CFS. “It’s a bust.”
In 2009, a team led by Judy Mikovits at the Whittemore-Peterson Institute for Neuro-Immune Disease (WPI) in Reno Nevada, reported evidence of XMRV infection in up to two-thirds of people with CFS, which is also known as mylagic encephalomyelitis, and only a small percentage of healthy people. For a full rundown on the two-year saga, check out my recent profile of Mikovits and XMRV.
In that story, we reported on the two studies released today in Science. One paper, led by Vinay Pathak at the National Cancer Institute in Frederick, Maryland and John Coffin at Tufts University in Boston, suggests that XMRV was created in a laboratory in the 1990s and was unlikely to have infected people with CFS.
Pathak and Coffin’s team discovered viral sequences perfectly matching XMRV’s in two different mouse strains in which a prostate tumour biopsy was implanted to create a cell line called 22Rv1. “They just sort of snapped together like two puzzle pieces,” Coffin told Nature in March.
The second study, led by retrovirologist Jay Levy at the University of California, San Francisco, found no evidence for XMRV infection in 61 CFS patients, including some who tested positive for the virus at WPI or a company it owns that markets an XMRV test.
Levy’s team failed to detect the virus or an immune response to it using several different methods. Levy’s team also found sequences of mouse viruses related to XMRV in laboratory reagents, echoing similar findings by other groups. Notably, the patients in Levy’s study were referred by Daniel Peterson, the physician who co-founded the WPI and left the institute last year.
Based on these results, as well as a growing heap of studies failing to find any sign of XMRV, Science released an “expression of concern” from its Editor-in-Chief Bruce Alberts, a potential step towards retracting the paper.
A letter sent from Alberts to Mikovits’ team and obtained by WSJ has asked them to do just that. However Mikovits told WSJ in a statement that “it is premature to retract our paper.”
In a 30 May letter addressed to Science and forwarded to Nature by Mikovits, she stands by her group’s work and questions Science’s expression of concern and their request to retract her paper. “We feel this is an extremely premature action which is not in the best interest of the scientific community or human health and again we respectfully request that you allow the scientific process to run its course unhindered by bias,” she writes.
The latest Science papers are not the final word on XMRV. The US National Institutes of Health is sponsoring two studies in which several different labs are testing blinded samples from CFS patients and healthy controls.
One, known as the Blood Working Group, should have the results of tests for XMRV in about 30 people with CFS by this summer. While a second, larger study, coordinated by Columbia University virologist Ian Lipkin, should be complete by year’s end.
Stoye, who co-authored an enthusiastic preview of the original paper linking XMRV to CFS questions whether both studies are needed to come to an increasingly obvious conclusion. “Perhaps none of us were sufficiently critical early on, but who could tell? I think we have to move on,” he says.
Micrograph of XMRV via Wikimedia Commons