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January 11, 2011
XMRV: It's Ugly, But That's Science
How's the XMRV / chronic fatigue syndrome connection holding up? Not real well. Science has a roundup of the latest news in the area, and none of it looks encouraging. There are four studies that have come out in the journal Retrovirology that strongly suggest that earlier positive test results for the virus in CFS samples are just artifacts.
For one thing, when you look closely, it turns out that the sequences from cell-cultured XMRV samples are quite a bit more diverse than the ones taken from widely separated patients at different times. And that's just not right for an infectious agent; it's the opposite of what you should see. A number of supposedly XMRV-specific primers that have been used in such assays also appear to amplify other murine viral sequences as well, and samples that show positive for XMRV also appear to have some mouse DNA in them. Finally, there's reason to believe that some common sources of PCR reagents may have murine viral contaminants that blow up this particular assay.
Taken together, these latest results really have to make you cautious in assigning any role at all to XMRV based on the published data. You can't be sure that any of the numbers are what they're supposed to be, and the most parsimonious explanation is that the whole thing has been a mistake. To illustrate the state of things, you may remember an effort to have several labs (on both sides of the issue) test the same set of samples. Well, according to Science. . .
Some had hoped that a project in which several U.S. labs are testing for XMRV in the same samples would clear up the picture. But so far this effort has been inconclusive. Four CFS patients' blood initially tested positive for XMRV at WPI and the U.S. Centers for Disease Control and Prevention but not at an NCI lab. When all three labs tested new samples from the same patients, none found XMRV—for reasons that aren't yet clear, says Coffin. The group now plans to test blood from several dozen CFS patients and controls.
No, this isn't looking good at all. It's pretty typical, though, of how things are out at the frontiers in this business. There are always more variables than you think, and more reasons to be wrong than you've counted. A theory doesn't hold up until everyone who wants to has had a chance to take some big piñata-shattering swings at it, with weapons of their choice. So, to people outside of research: you're not seeing evidence of bad faith, conspiracy, or stupidity here. You're seeing exactly how science gets done. It isn't pretty, but it gets results in the end. Circumspice.
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