Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease… (David B. Parker/Reno Gazette-Journal )
At first, it looked like a breakthrough in the fight against chronic fatigue syndrome. Researchers said they found a mouse retrovirus called XMRV in the 68% of blood samples collected from 101 patients with chronic fatigue syndrome, while only 4% of blood samples from 218 healthy controls had evidence of the same virus. The research team said it was strong evidence that XMRV had something to do with causing chronic fatigue syndrome (CFS). The report had added credibility because it was published in the prestigious journal Science.
But the XMRV-CFS theory began unraveling just a few weeks after the study was published in October 2009. The tale reads like a whodunit and is summarized nicely in Friday’s edition of Science. That article is accompanied online by a partial retraction of the controversial paper and a multi-lab study that failed to turn up any convincing evidence linking XMRV to chronic fatigue syndrome.
When the initial report was published, virology experts were skeptical that a mouse virus could be responsible for chronic fatigue syndrome, a debilitating condition characterized by extreme fatigue, chronic pain and depression. One of the early criticisms was that the strains of the XMRV virus found in patients were unusually similar, suggesting that contamination was responsible for their presence in so many of the blood samples.
In addition, the genetic technique used to look for XMRV – called “nested PCR” – has a known tendency to produce false positives, critics said.
Still others noted that all the CFS patients in the study were from Nevada, but the controls were from all over the country. Perhaps there was something in the Nevada environment that made XMRV more prevalent there but had nothing to do with chronic fatigue.
There was also the fact that when the researchers tested the blood samples, they knew whether those samples were from patients with CFS or from healthy controls. That knowledge may have biased their results.
After the report came out, many other labs looked for XMRV in the blood of other patients with CFS and couldn’t find it. Those that did find it also turned up evidence of mouse DNA, lending support to the theory that XMRV got into the blood samples through contaminated laboratory chemicals.
In March, scientists from the National Cancer Institute and Tufts University presented strong evidence that the strain of XMRV identified in the initial Science report had been created inadvertently in the 1990s by researchers who were studying prostate cancer in mice. If that were the true origin of XMRV, it couldn’t possibly be responsible for cases of chronic fatigue syndrome, which was recognized in the 1980s. (Similar ailments were described decades earlier.)
For many, the NCI-Tufts report was the final blow. The new study in Science, published online Thursday, simply piles on.
It involved nine different laboratories, including ones at the National Institutes of Health, the Centers for Disease Control and Prevention, the Food and Drug Administration and the two labs that published the initial paper. Each lab got a collection of blood samples to test. Some of those samples were from chronic fatigue syndrome patients who had previously been found to be infected with XMRV (or a related virus), and some were from healthy controls. There were no labels that might tip off the testers about which were which.
Overall, only two of the labs were able to detect XMRV in any of the blood samples – the same two labs that worked on the original study. But this time around, these labs found XMRV in blood samples from healthy people just as often as they found it in blood taken from people with CFS. Also troubling was the fact that when the same blood sample was divided up and tested separately, the results didn’t always agree.
Ostensibly, the purpose of this study was to determine whether there was any reason to screen donated blood for XMRV, in case the virus might be spreading and causing new cases of CFS. “Blood donor screening is not warranted,” the research team concluded.
But the driving force behind the 2009 study, Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, continues to believe in a connection between XMRV and CFS. As she told Science, the new study shows only that there’s no reliable way to find XMRV in blood samples, but the virus could still be lurking in patients’ tissues or be circulating in the bloodstream at levels that are too small to detect using ordinary methods. She accused one particular naysayer of trying to play God and offered a conspiracy theory in which the U.S. government is trying to undermine her research because it fears an outbreak of XMRV.
In the partial retraction published online Thursday, Mikovits and her colleagues on the original study acknowledge that two of the researchers used blood samples that were contaminated with XMRV DNA. Two figures and a table were affected. But the retraction says nothing about the study’s overall conclusions.
The full news story by Science is available to subscribers only, but summaries are available here and here.