Science for the win!

A paper claiming a viral link to puzzling Chronic Fatigue Syndrome has been withdrawn by Science.  Since publication in October, 2009 it had been met with controversy by scientists and hope by patients. Chronic fatigue syndrome affects millions of people worldwide with physical and mental fatigue that does not improve with rest but its causes remain unclear. Many people say their illness started after a viral infection so that is where the 2009 research focused and a paper by researchers at Whittemore Peterson Institute for Neuro-Immune Disease in Reno detected Xenotropic murine leukemia virus–related virus (XMRV) in two thirds of patients with chronic fatigue syndrome, but could not prove a direct (causal) link between the virus and the disease.

In January 2010, another research team found no evidence of XMRV in 186 patients with chronic fatigue syndrome in the United Kingdom. Another study also failed to identify XMRV in 170 patients and a study in Holland shortly thereafter examined the DNA from XMRV in the blood cells of 32 patients with chronic fatigue syndrome and 43 healthy controls, matched by age, sex and geographical area but found no evidence of XMRV in any of the patients or the controls, adding to the negative evidence in the two previous studies.

XMRV has been the subject of many studies since its discovery in 2006; some reports suggest a possible link between XMRV and prostate cancer but other links involving chronic fatigue syndrome, HIV infection, or hepatitis C virus (HCV) infection have been invalidated - the retraction of the original paper in Science effectively removes it from the scientific record.  The issue is that follow-up studies did not detect XMRV in quantity, or sometimes at all, in study participants, despite the high prevalence reported in the 2009 paper, which found evidence of XMRV DNA in 67 percent of subjects with chronic fatigue syndrome (CFS), compared to 3.7 percent of healthy controls. No subsequent studies in Europe were able to demonstrate the presence of XMRV in CFS subjects or healthy controls.

One study even found that cell samples used in previous research were contaminated with the virus identified as XMRV and that XMRV is present in the mouse genome.  "When we compare viral genomes, we see signs of their history, of how far they have travelled in space or time," said Dr. Stéphane Hué, Post Doctoral Researcher at UCL. "We would expect the samples from patients from around the world, collected at different times, to be more diverse than the samples from within a cell line in a lab, where they are grown under standard conditions. During infection and transmission in people, our immune system would push XMRV into new genetic variants. Viral infection is a battle between the virus and the host and XMRV does not have the scars of a virus that transmits between people."

It's a disappointment to chronic fatigue syndrome patients but sometimes science advances by eliminating dead ends and XMRV may turn out to be important in the pathogenesis of other diseases. More importantly, it shows the public that the moment a bold claim is made efforts are on to both duplicate the result and to invalidate it; that's how solid science works.  If the researchers in 2009 had claimed 'the science is settled' they would have been ridiculed and journalists reported it as fact but that's okay.  Our skepticism was enough that our coverage of XMRV and chronic fatigue syndrome was limited to how CFS patients took out a full-page ad to insist the 2009 study was correct; ironically just a few weeks ago. The folks behind the ad were primarily looking for more study funding, something all of the NIH would agree with; they cite that $5 million for CFS research is in the NIH budget compared to $144 million for multiple sclerosis research and $121 million for lupus.

“As far as virologists go, the story ended a long time ago,” Vincent Racaniello, a virologist at Columbia University, told the Washington Post. “There’s no evidence at the moment that any virus is associated with chronic fatigue syndrome.” 

Kim McCleary, president and chief executive of the CFIDS Association of America said CFS patients are “certainly disappointed and discouraged that this did not pan out the way it was initially promoted. But they understand there’s no point in pursuing a dead end.”

The American Red Cross continues to ban blood donations from chronic fatigue patients.