Numerous individual every year file long term disability claims as a result of suffering from Chronic Fatigue Syndrome (CFS). CFS is a complex disease whose cause is not known and for which no diagnostic test or approved treatment exists. An article recently published by Trine Tsouderos of the Chicago Tribune displays the inherent conflict between patient’s need to find answers and science’s approach to finding them.
The push and pull over a chronic fatigue syndrome study
Good news is rare for sufferers of chronic fatigue syndrome so when a team of researchers reported last fall that the mysterious condition was associated with a retrovirus, it made a splash.
The paper, published in the prestigious journal Science, suggested that the virus could somehow be helping to cause the disease. Drug companies expressed interest, and patients lit up the Internet with expressions of hope. One blogger posted photos of a party, complete with hats reading “I ♥ retrovirii” and a shrine to the paper’s lead author, retroviral immunologist Judy Mikovits.
Nine months later, the joyous mood has soured. Five research teams trying to confirm the finding have reported in journals or at conferences that they could not find the retrovirus, known as XMRV, in patients diagnosed with chronic fatigue syndrome, casting grave doubts on the connection.
In response, Mikovits has accused other researchers of bias and amped up efforts to sound the alarm over what she views as an epic health crisis. Invoking the world’s slow response to AIDS, she warned that XMRV infection “could be the worst epidemic in U.S. history.” Though her published findings address only chronic fatigue syndrome, Mikovits also has publicly linked the retrovirus to autism, atypical multiple sclerosis other disorders.
Meanwhile, some people with chronic fatigue syndrome already are getting tested for XMRV and taking toxic drugs intended to treat the retrovirus that causes AIDS, an idea Mikovits does not endorse but declines to oppose.
The story of XMRV and chronic fatigue syndrome is unfolding in a uniquely modern way, highlighting the clash between slow, methodical science and a plugged-in world ready to act on a single piece of information. It also puts the spotlight on a scientist whose unorthodox statements have raised eyebrows among colleagues while finding a receptive audience among patients desperate for answers.
“Right now it is chaotic,” said John Coffin of Tufts University, a retrovirus expert who co-wrote a positive commentary accompanying the Science paper. “It is not impossible that there is something fundamentally wrong with the initial study. Everything is on the table.”
Mikovits said in an interview and by e-mail that she feels her finding is being ignored by a dithering, even hostile scientific world. A retroviral scientist with decades of experience at the National Cancer Institute, she was hired in 2006 to head the research program at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev.
In its Science paper, Mikovits’ team, which included scientists from the Cleveland Clinic and the National Cancer Institute, reported finding evidence of XMRV infection in 67% of 101 chronic fatigue syndrome patients but in only a handful of people without the disorder.
“It was an incredibly proud day,” Mikovits said of the paper’s publication. “I got calls from around the world. Dubai, China, you name it.”
For patients, such a report can seem like a long-awaited answer. But for scientists, a single paper raises questions. Are the findings correct? What do they mean? And, perhaps most important, can we confirm it?
Even the best scientists can be wrong. Findings must be tested and confirmed by other researchers before they can be trusted. And that has yet to happen for XMRV and chronic fatigue syndrome.
“Extraordinary claims require extraordinary proof,” said Dr. Pat Moore, director of the cancer virology program at the University of Pittsburgh Cancer Institute and the co-discoverer of two viruses that cause cancer. “It’s important in cases that have a lot of clinical implications like this, where there are a lot of people desperate for an answer.”
Other pathogens - Epstein-Barr virus, human herpesvirus-6, the retrovirus HTLV-II – have been fingered in the past as possible causes of chronic fatigue syndrome, but none has stuck. Proving that a retrovirus causes a specific disease is especially difficult, experts note. And contamination in the lab, which is always possible and challenging to detect, can wildly skew results.
“Once you start having contamination, then whatever disease you look at, you will find an association,” said British retrovirologist Robin Weiss.
His lab published evidence of a new human retrovirus, but it turned out that his lab had been contaminated with a rabbit virus instead. “It took four years to work out,” he said. “It was a bit embarrassing.”
Mikovits called the contamination issue “a red herring.”
“Contamination? Absolutely not,” said Mike Hillerby, vice president of the Whittemore Peterson Institute. The goal of the institute, founded by Annette Whittemore, a wealthy Nevadan whose daughter has chronic fatigue syndrome, is to develop treatments as well as do basic science.
Both Hillerby and Mikovits say the team’s paper was closely examined by peer reviewers looking for evidence of contamination, and that the researchers also found evidence of an immune response to XMRV, something they said would not occur in a contamination situation.
Other research teams may not be finding XMRV in chronic fatigue syndrome patients because they are not doing the experiments in the same way as the institute, Mikovits said.
In January, the Reno Gazette-Journal quoted her as saying one British team had “skewed” its study design to avoid finding XMRV in patient samples. “Some are not trying in completely good faith,” she said in an interview with the Tribune.
Dr. Jos W.M. van der Meer of Radboud University Nijmegen Medical Centre in the Netherlands, a co-author of one of the studies that failed to replicate the findings, told the Tribune: “I don’t like these kinds of fights. I would prefer to have scientific debates on the scientific level.”
Driven by what she says is the urgent need for action on XMRV, Mikovits has publicly tied the retrovirus to disorders including atypical multiple sclerosis, though she has not published data supporting these claims.
Last month, she spoke at the Autism One conference in Chicago about her new research on XMRV and autism, joining a lineup of speakers that included disgraced autism researcher Andrew Wakefield, who recently lost the right to practice medicine in Britain for serious professional misconduct.
Mikovits wrote in an e-mail that she realizes presenting at the conference “could destroy what is left of my career” but felt she had to accept in order to help sound the alarm.
She accused researchers and government agencies of being more interested in previously published research linking XMRV and a form of prostate cancer than in her work. Chronic fatigue syndrome affects women at four times the rate of men, according to the Centers for Disease Prevention.
“So research dollars will go for XMRV-infected men with cancer but not women with CFS,” she wrote in an e-mail. “[This] left me no recourse but to play the autism card! Will they ignore the children too?”
Virologist Vincent Racaniello of Columbia University said raising an alarm about XMRV would be premature given how little is known about the retrovirus.
“Her claim has to be validated,” Racaniello said. “Otherwise, not only is money wasted, but people can be harmed, physically and psychologically.”
Dr. Jamie Deckoff-Jones, a physician in Santa Fe, N.M., and her daughter both suffer from chronic fatigue syndrome and have been taking AZT, raltegravir and tenofovir. Deckoff-Jones said she is aware of the risks but feels ready to accept them.
“I am still a scientist at heart,” she wrote in an e-mail. “But life sometimes forces leaps of faith.”
Deckoff-Jones, whose blog about her treatment includes dosages, said other people interested in trying anti-retrovirals have contacted her. “Some of us simply don’t have the time to wait,” she said.
A risky path
Dr. Paul Sax, clinical director of the HIV Program and Division of Infectious Diseases at Brigham and Women’s Hospital in Boston, said he has “tremendous sympathy” for people with the disorder. “No wonder they are looking for both a cause and a treatable cause at that,” he said.
But, Sax said, the three drugs Deckoff-Jones is using can have serious risks that are considered a reasonable risk to people with HIV because the alternative is death from AIDS. Potential side effects include kidney damage, anemia, muscle problems and damage to the energy-producing centers of cells.
“This is not the way to answer the question of whether these meds can help people,” Sax said. “HIV therapy did have some stops and starts along the way, and we learned the hard way about these medicines in being overeager.”