Stolen Notebooks and a Biochemist in Chains
How did the study of chronic fatigue syndrome come to this?
By Julie Rehmeyer|Posted Friday, Dec. 2, 2011, at 5:58 PM ET
Two years ago, Judy Mikovits and the Whittemore-Peterson Institute for
Neuro-Immune Disease were triumphant. Mikovits had just published a
report in Science pointing to a retrovirus called XMRV as the possible
cause of chronic fatigue syndrome, a little-understood illness
characterized by debilitating flu-like symptoms that worsen with
exertion. A wealthy woman whose daughter has the disease had started
the institute in 2007 to study CFS, fibromyalgia, and Gulf War
illness—and it wasn't long before its researchers appeared to have
shown they could succeed where two decades of government-led research
had produced little.
Best of all for many CFS patients, the work seemed to offer undeniable
proof of what they had long hoped to establish: that their disease has
a physiological cause, not a psychological one.
But as of mid-November, the XMRV retrovirus research had been
discredited and was suspected of being fraudulent; Mikovits sat clad
in a blue jumpsuit in a California jail, accused of stealing lab
notebooks and computer files from her former employer; the research
program at the Whittemore-Peterson Institute was in disarray; and CFS
patients were as confused as ever about the source of their illness
and how to treat it.
Mikovits and her employer share blame for this mess, having at the
very least hugely oversold the certainty of their result and allowed
an intellectual property dispute to get out of control. But a large share of the responsibility goes back to the National Institutes of Health, the Centers for Disease Control, and the researchers who engaged in the weak research those agencies funded. For decades, both agencies have propagated the idea that CFS probably isn't amenable to any physiological treatment, that psychologically healthy people aren't likely to get it, and hence that it isn't an important threat to the general public. Many CFS patients came to feel abandoned by the scientific establishment. This created a climate of mistrust that
breeds hero-worship and conspiracy theories and that can cast a
scientist simultaneously as a savior and a villain.
The Reno, Nev., institute itself was formed as a response to the
despair CFS patients felt. Annette Whittemore, its co-founder, saw
privately funded research as the only hope to save her daughter, who
at times was homebound and was suffering from frequent seizures.
Simply allowing the wheels of science to turn, she had concluded, was
unlikely to lead to effective treatment anytime soon.
The first problem was funding: The NIH spends $5 per patient on CFS research each year, compared with $400 per multiple sclerosis patient and $3,000 per HIV patient. (Disclosure: I myself have CFS.) Even leading researchers have difficulty getting funding, especially for
research on the hypothesis that CFS is caused by an infectious
agent—which is exactly what Whittemore believed to be true. The CDC's
reluctance to fund biological studies of chronic fatigue syndrome was
so great that between 1995 and 1998, agency officials diverted half
the funds allocated for the illness to other diseases and William
Reeves, the head of the research program at the CDC, got
whistle-blower protection when he testified that officials had lied to
Congress to cover up the misappropriations.
Worse, much of that paltry funding has been wasted on questionable
science. Soon after the outbreaks of CFS in the 1980s, government
officials suspected that it was psychosomatic, because its
manifestations were so bewilderingly diverse. Stephen Straus, head of
the CFS research program at the NIH, said that he believed it was the
same illness that was once called neurasthenia, "a neurosis
characterized by weakness and fatigue." Officials stuck to that position even as a large body of evidence accumulated that CFS patients have characteristic patterns of immune, autonomic, neurological, and endocrine abnormalities.
Scientists funded by the CDC published a stream of research to support
the idea that CFS is psychosomatic, but their work has some troubling
flaws. Last year, for example, a study by the former director of the
agency's CFS research program pointed out that 29 percent of diagnosed
patients have a personality disorder, compared with just 7 percent of
healthy controls. The paper concluded that "this might be associated
with being noncompliant with treatment suggestions, displaying
unhealthy behavioral strategies and lacking a stable social
environment." But the study ignored the fact that having a chronic
illness, particularly a highly misunderstood one, itself takes a toll
on mental health. In 2003, by contrast, a non-CDC study found no difference in neuroticism and depressive symptoms between patients with CFS and those with multiple sclerosis.
An additional problem with this study and many others was that they
used a definition of the disease that most researchers consider overly
broad. Because there is not yet a blood test or other clear diagnostic
marker for the disease, any definition has to rely on a set of
symptoms. A 1994 definition required that patients experience six
months of fatigue that isn't helped by rest along with several of a
set of other symptoms including concentration problems, sore throat,
pain, and increased symptoms after exercise. Many researchers argued
that the requirements needed to be tightened to ensure that the
definition would capture only CFS patients, and not those with
depression or some other ailment. In 2005, the agency offered a new
"empirical" definition, but rather than tightening the criteria, the
new definition quadrupled the number of people considered to have the
disease. The included symptoms were unchanged, but the empirical
definition required that the symptoms have lasted only one month
rather than six and established a low threshold for the intensity and
frequency of these symptoms. One study showed that 38 percent of
people diagnosed with clinical depression qualified as having CFS
under the new guidelines but not the old ones. But broadening the pool
of patients in this way has only made it harder to find physiological
abnormalities and easier to find psychological ones, and it casts into
doubt whether any new results would apply to CFS patients as defined
by a more specific definition.
Among U.S. scientists who work primarily on this disease, essentially
no one argues for a psychosomatic cause. Nor do any researchers use
the 2005 definition, besides the ones whose work is paid for by the
CDC. Nevertheless, the agency has had a huge influence on the opinion
of doctors and the general public, creating an attitude of skepticism
and even condescension toward the disease. Rather than focusing on
treatments, the majority of research has gone toward providing
evidence, in one form or another, that patients had some kind of
psychological problem long before they developed the syndrome.
Although public officials have acknowledged that the disease may have
a number of different causes, including physiological ones, their
public statements have alienated the patient community, without
offering any clear path to treatment or prevention.
So when Whittemore opened her institute, many patients saw it as their
hope for salvation. Whittemore used her own wealth (reportedly
contributing $5 million initially) and connections (raising $10
million from the state of Nevada, and $1.4 million from patients and
other private donors) to fund research that would be free of the
federal government's apparent bias toward psychiatric explanations.
Eventually, the NIH got behind Whittemore's effort, too, supplying a
$1.5 million grant for her institute's CFS research.
Just a few years after its founding, the retrovirus finding seemed to
justify all the high hopes. Because retroviruses can spread through
blood transfusions, the risk to the general public was obvious. CFS
was catapulted out of the backwaters of science and into the land of
When other groups' first attempts to replicate Mikovits' finding
failed, some patients waited for more rigorous studies, but some
rallied harder to defend Mikovits, sending money from their disability
checks to support the institute. (A few were said to have levied death
threats against scientists who questioned the retroviral link.)
Mikovits was deluged with emails from patients expressing their
desperation for a cure, proclaiming her a hero and pledging to stand
by her no matter what. And Mikovits herself combatively defended her
result. She even fanned the skepticism by making wildly irresponsible
claims, tying the retrovirus to autism, Parkinson's disease, MS, Lou
Gehrig's disease, and dementia. The Whittemores also went way beyond
the evidence, selling an unvalidated XMRV test to patients for around
$500 apiece through a separate lab that they owned.
Eventually, though, major studies came in showing that the infectious
agent she'd discovered was almost certainly a laboratory contaminant
and not the cause of CFS at all. And that turned out to be only the
beginning of the bad news for Mikovits and the institute. The
commercial lab stopped selling its XMRV test, but it had taken many
thousands of dollars from patients for an illegitimate test. Questions
emerged about whether Mikovits had faked data in her Science paper.
Whittemore fired Mikovits in a dispute over who controlled her lab
samples, putting into limbo the institute's $1.5 million grant, for
which she is the principal investigator. Soon after, Mikovits' former
research assistant said that he had secreted critical lab notebooks
out of the building to her and the WPI pressed charges against her for
theft, leading to her manacled appearance in a California courtroom.
She is now out on bail and the notebooks have been returned.
How did this once-promising effort to understand and treat CFS go so
far off the rails? The intoxicating effect of being lauded as the sole
defender of the theory that might rescue more than a million
desperately ill Americans probably contributed. Some CFS patients felt
so mistreated that for them, Mikovits wasn't just a researcher whose
theory wasn't yet validated; she was their redeemer. For those
patients, the legitimacy of the retrovirus research became conflated
with public acceptance of CFS as a "real" disease. Their fervor may
well have fueled that of both Mikovits and the institute, leaving each
feeling that they were the only ones left standing up for patients and
supercharging their initial enthusiasm for the work into
self-righteous certainty. For now, it's unclear whether Mikovits is a
fraud; an overambitious, careless, and irresponsible scientist; or
just a researcher who temporarily lost all perspective. But it's easy
to imagine how her sense of obligation to produce results quickly for
desperate patients, and the polarized atmosphere around CFS research,
could have greased the slide she and the institute took from cautious
science into reckless overreaching.
The failings of Mikovits, Whittemore, or the patients who trusted them
aren't the point, though. With a disease this debilitating and
marginalized, some patients are bound to make leaps of faith; some
researchers might start to believe their own press; and a mother may
overextend herself in her quest to save her child. But the alienation of the patient community only arose because of the mishandling of CFS by the public agencies. The best way to avoid this kind of fiasco would be for researchers and public health officials to follow their obligation to protect public health, be faithful to the science from the beginning, and fund and pursue the many promising avenues for research on CFS that have recently emerged.
Remarkably, despite the minimal funding, such avenues have emerged.
Researchers are making progress toward developing a test that could
definitively determine who has the disease and who doesn't—by using
either proteins in spinal fluid or alterations in gene expression
after exercise. Such "biomarkers" for CFS would show whether CFS is a
single disease or a cluster of related ones. An experimental drug
treatment has been remarkably effective and has provided evidence that
CFS is an autoimmune disease, opening a whole new area of treatment
possibilities. These scientists aren't selling testing kits or making
dramatic statements about their devotion to their patients. They're
just doing their jobs. And they need a lot more government support in
getting them done.