Two years ago, people with chronic fatigue syndrome (CFS) had hope that the cause of their mental and physical exhaustion, muscle pain and overwhelming tiredness had at last been found. Vincent Lombardi at the Whittemore Peterson Institute in Reno, Nevada, found a mouse virus called xenotropic murine leukaemia virus-related virus (XMRV) in blood samples from 68 of 101 people with the syndrome, compared with just eight of 218 samples from healthy blood donors.

Now, two new studies seriously undermine this finding, suggesting it arose from contamination of the samples that contained the virus. New Scientist tries to untangle the debate.

What do the two new studies show?

The first, led by Jay Levy at the University of California, San Francisco, drew a complete blank when screening for XMRV in 61 people with CFS, including 43 whose samples had tested positive in Lombardi’s study.

The second study, led by Vinay Pathak at the National Cancer Institute in Frederick, Maryland, suggests that XMRV originated in laboratory mice after the people in Lombardi’s study were diagnosed with CFS and therefore cannot be the cause.


So where did XMRV come from?

Pathak says that XMRV originated in the 1990s in labs where researchers were studying human prostate cancer. To make large amounts of tumour tissue for study, researchers grew cancers in mice that had no immune systems. While in the mice, the tumour cells picked up two mouse leukaemia viruses which combined to form a unique new mouse virus, XMRV.

The XMRV strains in Lombardi’s samples are so similar to this “recombinant” virus that it is unlikely it could have come from any other source, says Pathak. He concludes that the virus Lombardi found originated between 1993 and 1996. Yet at least a quarter of the people from whom Lombardi took samples were diagnosed with CFS in the 1980s, before the virus existed.

Why did researchers do these follow-up tests?

Because at least 10 studies around the world have failed to detect XMRV in samples from people with CFS.

One study last year did identify a mouse leukaemia virus in blood from 32 of 37 people with CFS, versus three from 44 healthy blood donors, but it was a different virus from the one that Lombardi had found, adding to confusion about what was really going on.

Lombardi, meanwhile, maintains that his results stand because no one has re-analysed the samples from his original study.

Science published all these findings – what does it have to say?

The journal’s editor-in-chief, Bruce Alberts, today issued an editorial “expression of concern” about the reliability of the Lombardi paper. It says, “The validity of the study is now seriously in question.”

It adds that the journal is eagerly awaiting the outcome of further studies investigating the validity of the association between XMRV and CFS.

What do other virologists say?

Levy told New Scientist that the studies should be halted because the case for XMRV as a possible cause of CFS is now effectively closed.

Myra McClure at Imperial College London, the leader of one of the 10 studies that drew a blank when looking for the virus, says: “Until now, Lombardi has fallen back on the argument that no one had investigated their particular chronic fatigue patients. Now Jay Levy has, and found them not to have XMRV, so this, along with all the other negative studies, buries the story.”

These are damning comments: what has the Lombardi team said in response?

In a statement issued yesterday, Annette Whittemore, president of the Whittemore Peterson Institute, expressed “disappointment” that Science had published its expression of concern. She also said that Lombardi and his colleagues stood by their study and claimed it was “premature” to change the conclusions of the original study.

What now for people with CFS?

Levy says the bottom line is that scientists have to keep looking for the real cause, or causes, of CFS.

McClure is angry because she thinks that time has been wasted on what seems to have been a wild goose chase. “Just think of all the time and resources spent in almost every retrovirology lab in the world, as we’ve all been active in proving wrong a group which failed to open their minds to the possibility that they could be wrong.”