People with chronic fatigue syndrome exhausted by illness, doubts

From The NY Times:

Chronic fatigue syndrome causes a host of debilitating symptoms: profound exhaustion, disordered sleep, muscle and joint pain and severe cognitive problems, among others. But what causes the syndrome itself?

Since the first cases in the United States were identified in the 1980s, scientists have been divided over that question. Some have suspected that one or more viral infections are likely to play a central role.

But many other researchers — not to mention relatives, friends, employers, doctors and insurers of the million or more Americans estimated to suffer from the illness — have dismissed it as stress-related, psychosomatic or simply imaginary.

Now recent back-to-back announcements have highlighted both the volatility of the issue and the ambiguity of the science, and have alternately heartened and dismayed patients.

On Dec. 14, an advisory panel suggested that the Food and Drug Administration ban blood donations by people with a history of C.F.S., as the illness is often called. The goal was to prevent the possible spread of viruses that two high-profile studies had linked to the condition.

But then, on Dec. 20, the journal Retrovirology published four papers suggesting that key findings in those studies could have resulted from laboratory contamination.

The F.D.A. is not required to accept the opinion of its advisory panel. Yet patients still hailed the recommendation as a sign that their illness was being taken seriously.

“When an F.D.A. panel suggests that patients with C.F.S. not donate blood, that’s going to impact the way doctors think about it,” said Mary Schweitzer, a former history professor at Villanova, who has frequently written about living with the illness. Dr. Schweitzer said she has been unable to work for 16 years because of the syndrome, which was diagnosed after she suffered from a series of flulike illnesses.

The studies that concerned the F.D.A. had reported that people with the syndrome, which is also called myalgic encephalomyelitis or myalgic encephalopathy in Europe, showed higher rates of infection with the virus XMRV or others from the same category, known as MLV-related viruses. (These viruses are all relatives of mouse leukemia viruses, some of which can infect species other than mice; their role in human disease, if any, remains poorly understood.)

But several other research teams in the last year have found no connection between chronic fatigue syndrome and these viruses, although none tried to replicate the exact methods used by researchers who reported an association.

The new papers in Retrovirology reported that contamination of tissue samples or other laboratory items with mouse DNA or viral genetic material could lead to false positive results for XMRV, and by extension other MLV-related viruses, specifically when using polymerase chain reaction technology. The technique rapidly produces millions of copies of genetic segments, so even minute traces of genetic contamination can skew results.

“Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome,” said the senior author of one of the studies, Greg Towers, a professor of virology at University College London, in a statement released by Wellcome Trust Sanger Institute, the British research center that co-sponsored it.

Other scientists and advocates for patients have sharply criticized such certainty as unwarranted, noting that the Retrovirology papers themselves expressed their findings in more cautious terms. The critics agree that contamination can be a serious issue when using polymerase chain reaction technology. But the new papers, said Eric Gordon, a doctor in Santa Rosa, Calif., who treats many patients with the illness, do not evaluate other strategies besides P.C.R., as the technique is known, for detecting the MLV-related viruses, like testing for an immune response and culturing the viruses in cell lines.

“The articles make the point that P.C.R. doesn’t work that well for these viruses, and then they act like that disproves the whole idea,” said Dr. Gordon.

XMRV was first identified in 2006 and has been detected in prostate cancer patients in some studies. It was linked to chronic fatigue syndrome in October 2009 in a paper in the journal Science by researchers from the Whittemore Peterson Institute for Neuro-Immune Disease at the University of Nevada, Reno, the National Cancer Institute and the Cleveland Clinic.

The researchers relied on P.C.R. technology to show that about two-thirds of patients but less than 4 percent of control subjects harbored XMRV. Using other technologies, however, they also documented an antibody response in some chronic fatigue syndrome patients, and reported that XMRV in human blood could infect other human cell lines.

In a statement responding to the new papers in Retrovirology, Judy A. Mikovits, director of research at Whittemore Peterson and the senior author of the Science study, said her team took extensive steps to rule out P.C.R. contamination and also focused on other approaches to finding XMRV. “Nothing that has been published to date refutes our data,” she said.

Even some specialists stumbled over the meaning of the new findings. Vincent Racaniello, a professor of microbiology at Columbia not involved in the research, apologized on his Virology Blog for having stated that it was likely to spell “the beginning of the end” for the proposed connection between the viruses and chronic fatigue syndrome.

After reviewing the issue more thoroughly, he wrote, he realized that the new studies “show that identification of XMRV can be fraught with contamination problems, but they do not imply that previously published studies are compromised.” He added, “If I had difficulties interpreting these papers, how would nonscientists fare?”

Federal agencies have come down on different sides of the issue. In a paper published in The Proceedings of the National Academy of Sciences in August, researchers from the National Institutes of Health and the F.D.A. found a link between the fatigue syndrome and MLV-related viruses (although not specifically XMRV). In contrast, a study from the Centers for Disease Control and Prevention was among those not reporting a link.

Federal health officials have organized two research efforts to resolve the inconsistencies, determine whether XMRV and MLV-related viruses are possible human pathogens, and identify reliable ways to detect them. Patients hope the increased attention will quickly lead to research on treatments, including clinical trials of H.I.V. drugs, some of which have been shown in lab studies to inhibit the replication of XMRV.

The unsettled situation has created a quandary for patients with chronic fatigue syndrome and the doctors who treat them. Some patients are seeking to be treated with H.I.V. drugs, which doctors can legally prescribe even though the F.D.A. has not approved them for that purpose.

Many doctors and researchers say it is too early to prescribe the drugs for chronic fatigue because of possible side effects, like bone marrow suppression, gastrointestinal problems and liver or kidney dysfunction, among others. But Michael Allen, a writer and a former psychologist in San Francisco who has been disabled for more than 15 years, said he wouldn’t hesitate to try the medications if he found out he was positive for an MLV-related virus.

“It feels patronizing when the medical establishment says the side effects are too risky and we should keep waiting,” he said. “What that says to me is they have no idea whatsoever how sick people like me have been with this disease.”