The Waning Conﬂict Over XMRV And Chronic Fatigue Syndrome
OTTAWA, CANADA—Less than a day after a new study dealt what many
consider a lethal blow to the controversial theory that a newly
detected virus, XMRV, is linked to chronic fatigue syndrome (CFS),
proponents and skeptics of the theory squared off in a meeting here.
In one corner was Judy Mikovits, research director at the Whittemore
Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, and
the main champion of the idea that XMRV and its relatives play a role
inCFS. Her opponent, an erstwhile supporter,was heavyweight
retrovirologist John Cofﬁn of the Tufts University Sackler School of
Graduate Biomedical Sciences in Boston. When Mikovits and Cofﬁn took
the stage at the meeting, which was organized by IACFS/ME (an
international association devoted to the disease)and attracted 460
researchers and patients, they sat on opposite sides of the lectern.
During their introductions, Cofﬁn clasped his hands in front of his
mouth, looking like a man in prayer who wished this would all stop.
Neither addressed the other by name, and they avoided eye contact.
The controversy began shortly after Mikovits and colleagues published
a paper (http://scim.ag/mikovits) 8 October 2009 in Science that made
the startling link between XMRV, a mouse retrovirus, and CFS (23
September, p. 1694). But the ﬁnding, heralded by many patients as the
long-sought cause of their bafﬂing disease, soon met a barrage of
criticism as lab after lab failed to replicate it.
The new study published by Science (http://scim.ag/xmrv-cfs) on 22
September and presented at the conference for the ﬁrst time
convincingly showed that not one of nine labs, including WPI, could
reliably ﬁnd XMRV or its close relatives known as murine leukemia
viruses (MLVs) in people who previously had tested positive for them.
Both Mikovits and Cofﬁn were among the co-authors of the paper by the
so-called Blood Working Group. At the same time, Science also ran a
partial retraction (http://scim.ag/R-H-S) of the October 2009 paper
after one of WPI's collaborators discovered that a contaminant—as many
critics had asserted—explained the XMRV DNA it found in some patient
In Ottawa, Mikovits came out swinging. But she didn't make the case
for XMRV, which stands for xenotropic murine leukemiavirus–related
virus. Instead, she offered new evidence that people with CFS (known
as myalgic encephalomyelitis in some countries) had a virus "highly
related" to XMRV.
Unlike the original study that appeared in Science that showed entire
sequences of XMRV and infection of fresh cells, Mikovits revealed only
partial viral sequences that she said were from the XMRV and MLV
family known as gammaretroviruses. She said her team, which includes
Francis Ruscetti of the U.S. National Cancer Institute in Frederick,
Maryland, also had preliminary data that suggest these
gammaretroviruses may travel through the air. "That's pretty scary,"
Cofﬁn began by stressing that he initially thought the XMRV-CFS theory
"was a wonderful hypothesis." But it rested on three legs of a stool.
After removing blood from CFS patients, Mikovits and co-workers had
used the polymerase chain reaction to pluck out DNA from the virus and
sequence it, found antibodies to XMRV, and shown that the isolated
virus could infect cells in lab experiments. All the legs have now
been kicked out for both XMRV and MLVs, he said. "To claim that
there's more than one XMRV, you're going to have to show a virus that
has a sequence that's different from XMRV," he said.
Mikovits's presentation underwhelmed several of the scientists
attending. "Without the full sequence, it's hard to judge," said
Graham Simmons, who presented the data for the Blood Working Group.
Simmons, who works at the Blood Systems Research Institute in San
Francisco, California, also said he was "dubious" about her claims
that the virus can be aerosolized. Virologist Konstance Knox of the
Wisconsin Viral Research Group in Milwaukee said Mikovits was "just
reaching." Knox, who once consulted for WPI and had a falling-out with
the institute, added that "this is obfuscating what the community ﬁnds
to be obvious." Jonas Blomberg, a retrovirologist at the University of
Uppsala in Sweden who like Knox has failed to ﬁnd XMRV in his own
studies of CFS patients, said it's "hard to handle" Mikovits's
morphing theories. "It's like the argument follows the availability of
the data," Blomberg says.
Two other presentations offered some support for gammaretroviruses in
CFS patients, but both detected just antibodies and not the virus
itself. One study, led by Kenny De Meirleir of Vrije Universiteit in
Brussels, had WPI run its assays. When asked whether the new findings
invalidated his data, De Meirleir said, "I'm not going to say yes or
no." The other report came from Maureen Hanson, a plant geneticist at
Cornell University, who collaborated with CFS clinicians. "Even though
the XMRV sequences may be wrong, it's still certainly possible that
there's a virus in these patients that we need to identify," she said.
Cort Johnson, a CFS advocate, says many patients have held fast to
XMRV for good reason. "It was as if the medical gods, after years of
neglect, had bent down and offered up an apology in the form of a
simple answer that came gift-wrapped with hundreds of eager
Nancy Klimas, a CFS clinician at the University of Miami in Florida,
stressed that the Blood Working Group had analyzed samples from just
15 people who had tested positive for gammaretroviruses in earlier
reports. "I would be much more conﬁdent putting these putative
retroviruses to rest if I had a larger, more powerful study," Klimas
said. Simmons agrees that a larger study would have more power, but he
says the 15-person study is enough "to make conclusions about the
assays being totally unreliable." Results of a larger study of 150 CFS
patients are expected early next year.
Mikovits said she hopes to have full sequences of her new viruses "in
a couple of weeks."