Studies cloud chronic fatigue research

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Contamination is a likely explanation for scientific data that seemed to link a retrovirus and other mouse viruses to chronic fatigue syndrome and prostate cancer, according to four papers published Monday in the journal Retrovirology.

The papers provide a possible solution to a mystery that has dogged researchers for the past year: Why have a few labs been able to find evidence of the retrovirus XMRV or related mouse viruses in patients with chronic fatigue syndrome, or CFS, and prostate cancer while many others have not?

Approaching the question in different ways, four independent teams of scientists found that contamination of specimens, the lab or chemicals used in experiments could produce results that could be mistaken for XMRV and the other related mouse viruses.

"These four papers are probably the beginning of the end of XMRV and CFS," virologist Vincent Racaniello of Columbia University wrote in an email. "They don't prove that XMRV (and related viruses) don't cause CFS, but they go a long way to explaining many of the different findings in different labs."

Retrovirologist John Coffin of Tufts University, who co-authored two of the papers, said that although the papers do not settle the question, there is now reason to be concerned about the original findings on XMRV.

Slightly more than a year ago, a team of scientists led by Judy Mikovits at the Whittemore Peterson Institute for Neuro-Immune Disease reported in the prestigious journal Science they had found evidence of XMRV in the blood of more people diagnosed with chronic fatigue syndrome than their healthy peers.

The chronic fatigue syndrome community reacted with excitement to the idea that scientists could have finally figured out what was wrong with them and to the prospect of an effective therapy, a vaccine or even a cure. Patients began sending blood samples to commercial labs claiming they could detect XMRV, and some patients started taking potent antiretroviral drugs, as the Chicago Tribune reported in June.

But several other teams of researchers, including one led by the U.S. Centers for Disease Control and Prevention and another from the National Institutes of Health and the U.S. Food and Drug Administration, have published papers failing to find evidence linking XMRV to chronic fatigue syndrome.

One of the teams, from the NIH and FDA, found evidence of other mouse viruses in the patients, but it did not confirm the original study. The new papers suggest contamination could explain that team's findings, too.

The discordant results sparked talk of contamination among virologists. Many times in the history of their field, reported links between a virus and disease have later been shown to be caused by lab contamination, a phenomenon known as a "rumor virus."

The researchers behind the new papers found various routes to contamination, confirming what virologists know well – that mouse DNA is everywhere in labs and can produce phantom results.

One team led by scientists at University College London presented genetic evidence suggesting that previously described XMRV sequences are derivatives of the ones found in a human cell line known as 22Rv1, which is often used in prostate cancer research.

"There really is no evidence for XMRV replicating in people," said Greg Towers, professor of molecular virology at University College London and a co-author of the paper. "We can explain the test results as contamination."

A Japanese team led by researchers from Kyoto University found that a reagent in one of the commercial kits used to detect genetic material is contaminated with mouse DNA. Another pair of papers showed human samples easily can be contaminated by mouse DNA, potentially leading to results that look like evidence of XMRV or related mouse viruses.

"I think this is: end of story," said Tufts professor Brigitte Huber, another author of one of the papers. "It is overwhelming."

On Monday, the Whittemore Peterson Institute released a statement forcefully denying the possibility that contamination had skewed its results, citing the multiple ways they have shown the link between the disease and the retrovirus. "The coauthors stand by the conclusions," Mikovits said in the statement. "Nothing that has been published to date refutes our data."

Researchers said a large study being led by Dr. Ian Lipkin at Columbia University should help settle the question.

Virologist Robin Weiss of University College London, has sounded the alarm about the reported link between XMRV and chronic fatigue syndrome for months. In 1997, his own team reported finding a retrovirus genome in patients with rheumatoid arthritis. Two teams — one in Sweden, one in the U.S. — "confirmed" his results. It seemed to be a breakthrough in rheumatoid arthritis.

After Weiss reported his findings, he discovered he was actually detecting contamination from a newly discovered rabbit retrovirus.

Asked earlier this month whether he think this is another case of a rumor virus, Weiss wrote, "yes."

On message boards, some chronic fatigue patients reacted to the quartet of new papers with dismay. "I've got to admit, it feels like a bit of a blow," wrote esther12 at Phoenix Rising. "We'll have to see how it all works out."

Wrote withhope on the same board: "This seems like really unsettling news at Xmas!"

ttsouderos@tribune.com

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