The chronic fatigue virus: de-discovered?

One of the most important things that virus-hunters do is “de-discover” links between viruses and diseases. In other words, they follow up on studies that indicate a link and see if it can really hold up. Last year, a team of scientists published a paper in Science in which they reported that 67% of people they studied who suffer from chronic fatigue syndrome carried a virus in their system known as XMRV. Only 3.7% of healthy people did. That association then morphed into the idea that XMRV actually causes chronic fatigue (a condition that afflicts an estimated 60 million people worldwide). Some people with chronic fatigue have sought anti-viral medicines based on the finding, declaring that they’ve felt better as a result. But when a lot of other scientists tried to find XMRV, they failed to do so.

Today Science itself is publishing two papers that cast even more doubt on the link. In one study, scientists looked at 61 samples from the same medical practice where the original samples had come from. They couldn’t find any XMRV in people with chronic fatigue.

Another study supports what a lot of experts have been saying recently: that XMRV was not actually infecting the cells of people with chronic fatigue, but merely contaminated the samples once they were in labs. The researchers came to this conclusion through some evolutionary detective work.

XMRV was first discovered in 2006 in a line of human prostate cells, and since then it’s been reported to be present in 6 to 27% of human prostate cells. Before the link to chronic fatigue was claimed last year, some researchers argued that XMRV can also cause prostate cancer.

XMRV belongs to a family of viruses that infect mice and can sometimes even integrate their genes into their host’s genome. Yet Vinay Pathak of the National Cancer Institute and his colleagues could not find XMRV in mice. What they did find, however, were two previously unknown viruses that were strikingly similar to parts of XMRV. In fact, XMRV looks like a hybrid of the two viruses.

How could the viruses come together? And how could they end up in human prostate cancer cells? A crucial clue is the fact that scientists who study prostate cancer cell lines have to inject them into mice to keep them alive. They then “passage” the cells from one mouse to another. Pathak and his colleagues went back to the prostate cancer cells that scientists reared in mice in the early 1990s and couldn’t find XMRV. But they did find one of the two precursor viruses. Only in later generations of the cancer cells did they find true XMRV.

The scientists concluded that as prostate cancer cells were injected in mice, viruses migrated from the mice to the cancer cells. Then the viruses were carried to the next mouse inside the cancer cells.  At some point during these passages, two different mouse viruses recombined in the human prostate cells to produce XMRV. Thus, rather than being a virus that naturally circulates in humans or mice (or both), XMRV is a virus that emerged in human cell cultures in labs and can contaminate samples that scientists bring into their labs.

These two papers have prompted Science editor-in-chief Bruce Alberts to publish an expression of concern.” He writes that the initial findings of an XMRV-chronic fatigue link are “now seriously in question.” Amy Docker Marcus of the Wall Street Journal reports that Science asked the authors of the initial study to retract the paper, but they’re not backing down.

The next (and perhaps final) stage in this saga will come in the next few months. As I reported in the New York Times last fall, the National Institutes of Health launched a replication study in which the original XMRV team and other researchers who failed to find the virus will all search for the virus again, using exactly the same set of agreed-upon protocols.

For more on this story, check out Marcus’s excellent reporting over the past few months for the Journal, plus this piece in Nature.