‘The painstaking way science really works’, The Independent, 3 June 2011

From The Independent ‘Commentators’ section, 3 June 2011 (story by Steve Connor, science editor).

Science is a messy business. We like to think that it can give us clear-cut answers to difficult questions, but like any human endeavour it can frequently lead us up the wrong path. This week two scientific reports were published that more or less end a long-running dispute over whether an obscure mouse virus was the cause of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis or ME. These studies are the latest to suggest that it is not after all caused by a mouse retrovirus with the confusing name of murine leukaemia virus-related virus (XMRV).

The story of XMRV goes back many years but most people would have heard about it first in late 2009 when scientists led by Judy Mikovits of the Whittemore Peterson Institute in Reno, Nevada claimed in a study published in the journal Science to have found it in the blood of 67 per cent of patients with CFS. It was strong evidence, but not proof, that she had found the cause of the mysterious condition that leaves people chronically tired.

Up to then I had never heard of XMRV, but realised these findings were of huge potential significance. If true, and it was being published in a highly prestigious journal, then this could answer one of the most vexing questions in medical science: what is behind CFS, which affects about 250,000 people in Britain alone and has never had a satisfactory explanation?

While writing up this report I remember the profound scepticism of some experts in this country who just didn’t believe the link had been shown. So trying to get the balance right between this disbelief and the excitement of the findings was never going to be easy, or indeed satisfactory for both the scientists and the patients.

Soon after that initial report, further studies in Britain failed to establish a link. Professor Myra McClure, a distinguished virologist at Imperial College London, even suggested that Science had been premature in publishing the study. Half a dozen other groups also failed to replicate the findings and now a seminal piece of work by Tobias Paprotka and colleagues at the US National Cancer Institute has revealed that the XMRV allegedly found in the blood of patients with CFS was not actually there at all but present as a laboratory contamination in the animal cells, or reagents, used to test their blood.

In a remarkable piece of detective work, Paprotka discovered through genetic sequencing that the XMRV virus is a “hybrid” of two mouse leukaemia viruses that infected the same mouse cells used to grow human prostate tumour cells. This hybrid then infected a cell line known as 22Rv1 widely used as a laboratory reagent. Dr Mikovits and her team appear to be the unwitting victims of a universal problem for virologists. These modern-day sleuths use such sensitive techniques for detecting new viruses that they can often be misled by contaminants that get into their reagents.

In December, Professor Greg Towers of University College London showed in another study questioning XMRV that it was highly improbable for the virus to be the cause of the illness precisely because it appears to be a laboratory contamination. No one has so far provided convincing evidence to the contrary, which is why Science has taken the unusual step of asking Dr Mikovits to retract her paper.

She is reported to have said that this is “premature”. In the meantime, Science has published an “editorial expression of concern”, which amounts to a hazard warning to any others working in the field. A full retraction of the paper is surely not far away, and will probably come after a further study by the US National Institutes of Health, which is expected later this year.

This is all of little comfort to those with CFS. The XMRV affair looks like it was a wild goose chase. But, as one fictional sleuth is prone to say, by eliminating the impossible we can eventually arrive at the truth.

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