In the furious debate over whether chronic fatigue syndrome is linked to a mysterious retrovirus called XMRV, scientists can at least agree on one thing: the whole thing is a mess.

In the year and a half since researchers first claimed they had found the virus — which resembles viral sequences in the mouse genome — in people with the disease, nothing close to consensus has emerged. Several groups have tried to verify the results using different methods, and most have found nothing, leading them to suggest that the initial, promising experiments were simply an artefact of laboratory contamination.

But the few scientists who have found evidence to link the virus to the syndrome, also known as myalgic encephalomyelitis, are rigorously defending their data (see page 282). Led by Judy Mikovits at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, they blame patient heterogeneity, the geographical distribution of the virus and methodological issues among the reasons for the failure to verify a link.

Clarity is urgently needed, both by the scientists and by patients desperate for an answer. Owing to the difficulty in diagnosing a chronic disorder with diffuse symptoms, many people with the disease feel they have been marginalized by the medical community — told that there is no help for them, or even that they are imagining their symptoms. It's not hard to see why patients and advocacy groups have come to Mikovits' defence. XMRV provides legitimacy, and the hope of a treatment.

Given the long and convoluted history of infectious agents proposed and later disproved as a cause for chronic fatigue, this debate could continue for some time. Among the researchers searching for a definitive answer are several high-profile groups commissioned by health officials in the United States; they also aim to determine whether XMRV is floating around in the blood supply and being passed from person to person. There is a lot at stake. Hypotheses that are later discarded by science can linger on in the minds of the public: witness the supposed link between the measles, mumps and rubella (MMR) vaccine and autism, which has refused to die years after the weight of evidence should have squashed it. Patients who latch onto XMRV as the cause of chronic fatigue syndrome are likely to find it hard to let go, even if most scientists eventually conclude that the evidence is against it. Some are already being tested for the virus and starting to take potent, antiretroviral drugs if they test positive, all on the basis of an unproven hypothesis.

The challenge for scientists in this field, as in any other that involves patients, is to understand and be motivated by the plight of the patient community without letting their research be swayed by it.

Mikovits has worked with her critics to identify and pursue the research needed to resolve the debate. She is right to engage in debate about her science and defend it where necessary. But Mikovits and her critics need to maintain an open mind.

Scientists are taking the risk of XMRV seriously, as they should. The National Institutes of Health and others examining the link should see their studies through. A thorough, well-funded effort to get to the bottom of the situation should help to ensure that time, money and the careers of young scientists are spent effectively. But if the association is not borne out by these studies (and the preponderance of evidence thus far suggests that it may not be), will the spotlight on chronic fatigue syndrome endure or dim?

Many scientists who have waded into the debate are experts in viral disease, and they say they are unlikely to pursue work on chronic fatigue. This is a pity but, given the pile-up of criticism that was Mikovits' reward for diligently following up her data, perhaps no surprise. Several lines of evidence suggest that chronic fatigue has an infectious origin. It is to be hoped that one day scientists will manage to pin it down once and for all.