A transatlantic battle rages over the role of a newly discovered retrovirus in patients
with Chronic Fatigue Syndrome
Last fall, a group of American researchers published a study in
Science that offered hope to the 17 million patients with Chronic Fatigue Syndrome (CFS) worldwide. Identifying what may turn out to be an important clue to the illness, the researchers found that 67 percent of 101 patients were infected with a newly discovered retrovirus called XMRV. More sophisticated testing later showed that 98 percent were infected.
The XMRV study has already had global consequences. Concerned that the retrovirus may contaminate the blood supply, health officials in Australia,
Canada and
New Zealand announced new policies banning patients with CFS from giving blood. The U.S. government has stopped short of prohibition, but the National Cancer Institute has advised CFS patients against blood donation.
Despite these significant actions worldwide, XMRV’s role in CFS is still very much in question. In fact, the New Year ushered in a severe blow to patients when British XMRV researchers
published a study that didn’t find the retrovirus in even one of 186 CFS patients—and the XMRV momentum was stopped dead, if temporarily, in its tracks.
Each XMRV camp blamed the other for flaws in methodology. Pundits took potshots at CFS patients for defending the U.S. findings. In
Psychology Today, rheumatologist Mark Borigini christened CFS patients “terrorists of health, in full jihadist mode.” More than a hundred patients fired back comments, several asking Psychology Today editors to delete his article (they did not) and one comparing Borigini to Nazi physician Josef Mengele. But most responses were like this one: “Please, please tell me you did not actually compare legitimately chronically ill patients, desperate to find relief from their pain and disability, to violent radical extremists?”
Clearly, this is no run-of-the-mill scientific dispute. These new studies are just the latest twist in a quarter-century saga of backbiting and infighting, politics and money, accusations of flawed studies and covert alliances, allegations of patient abuse and blood-supply contamination, charges of paternalism and sexism, culminating in two XMRV studies that pit a longstanding cohort of British psychiatrists endorsing a psychological cause for the disease against a longstanding cohort of American researchers endorsing a physiological one. The antagonists include the parents of an adult daughter seriously ill with CFS facing off against an influential British psychiatrist and medal recipient from the Royal College of Physicians, who has long been a bête noire of the CFS community.
The feud between the physical and psychological camps simmered in the 1980s and ignited in 1991, when a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas
discovered a retrovirus in the blood of CFS patients. Whether XMRV and DeFreitas’s retrovirus are one and the same is not known with certainty, though preliminary evidence indicates that they are not. Twenty years ago, newspapers and TV news shows latched onto DeFreitas’s finding, spreading the word that the cause of the debilitating disease had, perhaps, been found.
The jubilant atmosphere was short-lived. The Centers for Disease Control (CDC) failed to find DeFreitas’s retrovirus in patients and controls (without using DeFreitas’s protocol) and British researchers found the retrovirus in all the controls and the patients—again without using her protocol. Given the diametrically opposed findings, DeFreitas reasoned the problem was rooted in the methods. But by that time, retroviral disbelievers outnumbered believers, media interest flagged and the CDC took the unusual step of publicly chastising DeFreitas. Tangling with the U.S. government proved costly to the researcher, which scared off likeminded scientists for nearly 20 years, silenced patients and split the research community into two nonintersecting camps.
Over the years, their disparate positions have only become more entrenched, evidenced by the inevitable exclamatory XMRV headline posted on one patient forum: “The fight is on!”
Contaminated blood supply
XMRV—which stands for xenotropic murine leukemia virus-related virus—is the human version of a mouse gammaretrovirus. The last retrovirus to jump species was HIV—from monkeys to humans. XMRV could impact us all. In the U.S. study, 3.7 percent of a control group of healthy subjects tested positive for the retrovirus. If those numbers hold up on subsequent studies, that will translate to 10 million people in the U.S.—nearly 10 times the number living with HIV/AIDS. How many may become ill as a result, no one yet knows. But since the host’s DNA becomes inextricably intertwined with the retrovirus, an XMRV infection lasts for life.
How did so many people become infected? Although the mode of transmission has not been established, the Japanese Red Cross issued a
disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply. In the U.S., the National Institutes of Health (NIH) is investigating the blood supply; results are expected by the fall.
In animals, XMRV can cause serious neuroimmune problems as well as blood cancers, which afflict CFS patients as well. Few are aware of the seriousness of CFS, though the severe abnormalities it causes—including
seizures,
heart failure and
serious infections from a damaged immune system—have been documented in two thousand Medline articles. That’s partly due to the disease’s trivial name, coined by the CDC.
U.S. studies: XMRV link
The first report of an association of XMRV with human disease came in 2006—from U.S. researchers studying a virulent form of prostate cancer, not CFS. But then a German study found no such association, echoing the conflicting findings of the CFS studies.
Three years later,
Dr. Judy Mikovits of the
Whittemore-Peterson Institute in Reno, Nevada, led the U.S. group that connected XMRV to CFS. The National Cancer Institute and the Cleveland Clinic replicated the study before the troika published in the prestigious journal
Science.
Harvey and
Annette Whittemore co-founded the Whittemore-Peterson Institute and funded the study in support of their daughter, who has CFS. The other name on the Institute’s shingle is
Dr. Daniel Peterson who, along with then-partner Dr. Paul Cheney, was the first to contact the Centers for Disease Control (CDC) about a CFS outbreak in the tony resort town of Incline Village on Lake Tahoe, Nevada, in 1984.
The Whittemores and Peterson have a lot on the line: The Whittemores want to help patients, including their 31-year-old daughter, who’s had the disease for 20 years and requires supplemental oxygen and experiences seizures; Peterson wants to find the cause of CFS and get down to the business of researching treatments.
It’s a position endorsed by CFS sufferers, who also want to put an end to the anemic name and the 25 years of ridicule by many doctors, researchers and government agencies that treat CFS as an inconsequential affliction of whiners, hysterics and depressives. “As a longstanding patient, a parent of a son who died of CFS and an advocate who in 20 plus years has spoken to hundreds if not thousands of patients, I want the bias aired, the bigotry gone and our stories told,” CFS patient Pat Fero says. “To be the subject of laughter and the butt of a joke because of an illness I have no control over is a disgrace.”
British study: No XMRV
British psychiatrist
Simon Wessely and two of his colleagues in the psychiatry department at King’s College London, along with virologists at Imperial College London, conducted the British study, which didn’t find XMRV in any patients. Wessely’s psychiatry unit supplied the blood samples. Critics question the patient group for two reasons: First, the psychiatrist bills CFS as a biosocial disorder, in which a person’s negative “
illness beliefs” cause physical symptoms. And second, his studies often
lump CFS in with “chronic fatigue,” “fatigue” and, most recently,
“burnout,” which are entirely different entities.
On the heels of the British study’s publication came a statement from the Whittemore-Peterson Institute questioning whether the patients in the British study actually had CFS: “Significant and critical questions remain as to the status of patient samples used in the U.K. study as those samples may have been confused with fatigued psychiatric patients, since the U.K. has relegated ‘CFS’ patients to psychiatric care and not traditional medical practices.”
Former Villanova University professor and patient advocate
Dr. Mary Schweitzer, who’s had severe CFS for 15 years and is XMRV positive, puts it more directly: “There’s an old saying in computerized statistics: GIGO—garbage in, garbage out. The study is only as good as the data set.”
Wessely, however, maintains that the patients in his study “fulfill the international criteria for this illness, are quite disabled and most of them aren’t working. It has been said in some quarters,” he adds, “that the reason we did not find XMRV is because the patients at King’s College London did not really have CFS but instead had mental disorders, psychiatric illness, whatever. On the record, I do not mind people insulting me, but I dramatically and vehemently object to them insulting our patients, and you can take it from me—and every one else on this service—that whatever CFS is, these patients have it.”
Fresh blood
Columbia University virologists
Dr. Stephen Goff and
Dr. Vincent Racaniello have suggested that one way to solve the XMRV puzzle is for researchers to exchange samples. “I would be reluctant to do this,” says Dr. Myra McClure, one of the retrovirologists on the British study, a hint of a Scottish lilt in her voice. She believes contamination of the samples could result, potentially leading to false positives. “Please believe me, I’m not accusing [the U.S.] lab of contamination or anything like that. I’m sure they’re very careful workers. The way to do this cleanly, so that there’s no ambiguity, is to take fresh blood from CFS patients. And to send one part to one lab, one part to an independent lab and one part to my lab and see what results you get.”
Dr. Judy Mikovits, the U.S. study’s principal investigator, agrees that procedure would have been ideal. The problem, she says, is that the British cohort never requested fresh blood—“or anything else”—from her lab. In fact, maintains Mikovits, her lab has sent fresh blood to researchers around the world and would gladly have supplied it to the British. All they had to do, she says, was ask.
Swimming to England
Both women sport impressive resumes: McClure trained at the Institute for Cancer Research in London under Dr. Robin Weiss, a top retrovirologist in England; Mikovits trained at the National Cancer Institute under Dr. Frank Ruscetti, the co-discoverer of the first known human retrovirus, HTLV-1, and a co-author on the U.S. XMRV study.
McClure and Mikovits have been butting heads since the British group published. “Mikovits has been critical of us publishing so quickly,” McClure says, to which Mikovits responds, “McClure is the one who said we rushed to judgment.” Besides, Mikovits adds, “We didn’t judge anything. We isolated a retrovirus.”
The British study was published after only three days of review in PLoS One, in contrast to the Science study, which was published after a six-month peer review. In addition, the Cleveland Clinic and the National Cancer Institute replicated the Mikovits findings before the U.S. results were published, whereas the British researchers didn’t use outside labs to confirm. The U.S. group looked for the virus with a technique called polymerase chain reaction (PCR), as well as culture and antibody testing because, says Mikovits, XMRV is difficult to detect through PCR alone. In contrast, the British researchers used only PCR. And unlike the U.S. study, the British study didn’t include healthy controls.
“If we had found one positive, we would have had to go for controls,” McClure explains. “It was because we didn’t find any that there was no need.” To which Mikovits responds: “That is unscientific and not worthy of comment.”
McClure says the British scientists published swiftly because they “wanted to put a stop to this stampede of patients who were demanding antiretroviral therapy.” Despite its speed, McClure is confident of the study’s conclusions.
Still, given that the U.S. and Japan have found XMRV, it seems odd that the British researchers didn’t find the retrovirus in even a few patients. Certainly the numbers in England could be far lower than in the U.S., but zero?
“We wondered about that, too,” McClure admits. And she and Wessely concede a XMRV background rate of about 1 to 1.5 percent is possible. “Our study doesn’t mean XMRV doesn’t exist in Britain,” Wessely acknowledges. “It might. But clearly our study would be incompatible—if our study is correct—with a high prevalence in this country.”
Using the U.S. study’s assays, the Nevada-based lab
VIP Dx has already found, in a different cohort, XMRV in eight out of 20 British CFS patients, triggering one CFS blogger to quip: “Apparently XMRV can swim!”
Fainting couches and hate mail
Far more heated than the Mikovits-McClure face-off is Simon Wessely’s roiling feud with CFS patients that’s finally reached boiling point.
“I’m aware that some people feel that because I am by background a psychiatrist that these patients [in his XMRV study] therefore suffer from imaginary psychiatric conditions and not Chronic Fatigue Syndrome,” Wessely says. “That is a disgraceful and disgusting suggestion, which I find insulting on behalf of our patients who have Chronic Fatigue Syndrome. And you can quote me on that.”
Wessely’s critics point to the more than one hundred CFS papers he’s written over the course of 20 years as evidence of his underlying beliefs about the illness. In 1989, he gave six books a mostly thumbs-down review because instead of focusing on psychological problems, they chronicled neurological and immune dysfunction in CFS—or ME, short for the malignant-sounding Myalgic Encephalomyelitis, as it was known in England for 40 years until Simon Wessely and England’s Royal Colleges of Physicians, Psychiatrists and General Practitioners
favored a name change to the benign-sounding CFS a decade ago. In his review, Wessely maintained that the disease is an updated name for neurasthenia, a 19
th century affliction of hysterical women swooning on fainting couches, clasped hand to furrowed brow.
The Golden Girls
In
another article that same year, Wessely takes issue with the conclusion of a two-part
Golden Girls episode in which a doctor gives a relieved Dorothy (Bea Arthur) a CFS diagnosis—after two other physicians write her off as lonely or in need of a change in hair color and suggest she visit a psychiatrist. “Most of us believe it’s a virus, it just has not been identified yet,” the third doctor tells her. At the heart of the CFS “movement,” Wessely asserts in his paper, “is the rejection of any form of psychological causation or treatment.” Patients say it’s articles like these that cause the CFS community—two-thirds of whom are women—to label Wessely as sexist and paternalistic.
Critics also note Wessely’s uncanny ability to affirm both sides—or neither side—of a debate, sometimes in the same maddening sentence, as if he’s
Lewis Carroll and they’ve tumbled down the rabbit hole: “What lies behind CFS is neither a virus nor psychiatry, but our idea of what constitutes a real illness, what doesn’t, and what we do to make something real,” Wessely told
The Independent in 1997.
Penned British investigative journalist
Martin Walker in
Cultural Dwarfs and Junk Journalism, “Professor Wessely should be granted a dictionary of his own, so far has he stretched the meaning of the English language while attempting to explain that ME although a ‘real’ illness, is often first imagined.”
Wessely gets his share of hate mail, and, in turn, his quarrel with the CFS community sometimes seems curiously personal. “If one reads the angry responses to any article that mentions Chronic Fatigue Syndrome and psychiatry in the same breath, it is clear that the drive to find a somatic biomarker for Chronic Fatigue Syndrome is driven not so much by a dispassionate thirst for knowledge but more by an overwhelming desire to get rid of the psychiatrists,” Wessely
wrote in 2009.
Offering counsel to me a few weeks after publishing the XMRV study, Wessely suggests, “My advice to you—which of course you will not take—is to wait a little [before publishing]. I think your piece might be more informative in the coming weeks as other groups begin to publish.”
This article, “Blood Feud,” Part 1 is copyright © CFS Central 2010. All rights reserved. You may quote up to two paragraphs from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is from CFS Central.
Next week: BLOOD FEUD, Part 2. As Dr. Simon Wessely forecasted, a second group of British CFS researchers weighed in within weeks with a study that didn’t find any firm evidence of XMRV in CFS patients.
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