It’s hard, even years later, to read Laura Hillenbrand’s wrenching description of her pain. Hillenbrand, 43, is the author of Seabiscuit and the new and widely acclaimed book Unbroken, an account of the World War II bombardier Louis Zamperini. But she is also the most articulate spokesperson for chronic-fatigue syndrome, the mysterious disorder that has plagued her since college. In an essay she wrote for The New Yorker in 2003, Hillenbrand described her aching joints, swollen glands, nausea, and exhaustion. The debilitating and unproductive trek from doctor to doctor. The disregard, the shame, and the elusive quest for relief. Chronic-fatigue syndrome plunged Hillenbrand into a state of disorientation; words looked like meaningless shapes; thoughts disappeared. “I was at a sensory distance from the world,” she wrote, “as if I were wrapped in clear plastic.”
It is a metaphor for the illness itself. For decades, chronic-fatigue syndrome has been mired in layers of medical and scientific uncertainty. Since Hillenbrand’s symptoms emerged in 1987, doctors’ awareness has grown and researchers have come up with tantalizing hypotheses about how the disorder has made as many as 4 million Americans sick. But every advance seems to come with a caveat, including a recent series of dramatic and confounding discoveries. In August a team of researchers led by the National Institutes of Health and the FDA announced that they’d found evidence of a family of retroviruses in the blood of patients with chronic-fatigue syndrome. The study mirrored an earlier report, published last year, which was celebrated by patients because it raised the possibility of pinpointing a cause and a treatment. But a third major study published this summer by the Centers for Disease Control and Prevention found no such link. The big hope now is that a new nationwide investigation, directed by a leading virologist at Columbia University, will bring greater urgency and find some clarity within the next 12 to 18 months. “Cutting-edge science is often not definitive,” says Dr. William Schaffner, an infectious-disease expert at Vanderbilt University School of Medicine. “Keep your seat belts tight.”
It’s been a long ride. Since the illness first surfaced in the U.S. in the ’80s, chronic-fatigue patients have endured skepticism from doctors, who have not known what to make of a constellation of symptoms that has no known cause, no diagnostic test, and no specific treatment. Many patients, including Hillenbrand, have been referred to psychiatrists. For years the disorder was not a priority at the highest levels; in 1999 a government audit found that the CDC had diverted millions of chronic-fatigue research dollars to other programs. The complex disorder continues to baffle the medical community because symptoms can vary dramatically over time and the spectrum of patients is vast. Some hold it together during the week but collapse on weekends; the most severely affected are bedridden. “Even though chronic-fatigue syndrome isn’t a death sentence, it’s a life sentence,” says Kim McCleary, president of the Chronic Fatigue and Immune Dysfunction Syndrome Association of America, a leading funding and advocacy organization. “People lead diminished lives because of the illness.”
What patients want is scientific validation. In the study published last year, researchers led by Judy Mikovits, of the Whittemore Peterson Institute (WPI) in Reno, Nev., identified XMRV, an infectious retrovirus in the same family as the AIDS virus, in the blood of 67 percent of patients suffering from chronic-fatigue syndrome. “There’s no question it’s in the people we found it in,” says Mikovits. The NIH study detected the DNA of viruses related to XMRV in 87 percent of its patients, compared with only 7 percent of healthy controls. But other studies, including the CDC’s report and several in Europe, found nothing. Nobody knows why with any certainty. Viral testing methods differ among labs. It’s also possible that the virus is endemic to certain geographic areas and not to others. Perhaps most significant: some patients, including those studied by the WPI and the NIH, are much sicker than others. “It just highlights that there’s still a lot we don’t know about this virus,” says the CDC’s Dr. Steve Monroe.
Including: how do humans get XMRV in the first place? “No one has any idea,” says Mikovits. Researchers emphasize that it’s still not known if the virus family detected actually causes chronic-fatigue syndrome. “It could be a bystander effect,” says the NIH’s Dr. Harvey Alter. But the possibility of infection has raised concern. Earlier this year an international blood-bank association urged members to discourage chronic-fatigue patients from donating because of the potential risk of transmitting the virus. The American Red Cross goes even further, deferring indefinitely any donor who reveals she has been diagnosed with chronic-fatigue syndrome or an XMRV infection.
Today, doctors prescribe an array of treatments—including exercise programs, cognitive behavioral therapy, painkillers, and sleep medications—to relieve symptoms. But if chronic fatigue is caused by a virus, it raises the question: should patients be on antiretrovirals, the same drugs prescribed to people with HIV? Some chronic-fatigue patients are already taking them off-label, but they can have serious side effects. Dr. Andrew Mason, a virologist at the University of Alberta in Canada, says it’s time to launch a well-planned clinical trial to test the drugs’ effectiveness. It wasn’t until antibiotics were prescribed to treat peptic ulcers, says Mason, that the medical community finally accepted bacteria as the culprit. “It’s the only way to win this battle,” he says.
But, as with so many aspects of chronic-fatigue syndrome, there is disagreement here, too. Other specialists say the science needs to be on firmer ground before trials are launched. “Patients are clearly ill and suffering, and we need to address treatment as rapidly as we can,” says Dr. Ian Lipkin, director of Columbia’s Center for Infection and Immunity. “But the first order of business is to determine if the association is real.”
In early November U.S. researchers met with Lipkin, who is spearheading the next phase of research. The plan is to collect blood samples from at least 150 patients across the U.S. with similar disease characteristics, then compare them with healthy controls matched for age, sex, and geography so that scientists can sort out the confusion and establish as conclusively as possible if a viral link is valid.
Scientific discovery is never straightforward, much as we all want it to be. More often than not, it’s a tangle of hunches, studies, disagreements, false starts, tangents, and frustrations. One day, everybody hopes, the layers of wrapping will come off. The cause—or, very possibly, causes—of chronic-fatigue syndrome will become clear. Treatments will become available. And Laura Hillenbrand and millions of others can start reclaiming their vitality and their lives.