The Waning Con=EF=AC=82ict Over XMRV And Chronic Fatigue Syndrome
OTTAWA, CANADA=E2=80=94Less 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 Cof=EF=AC=81n of the Tufts University Sackler School o=
f
Graduate Biomedical Sciences in Boston. When Mikovits and Cof=EF=AC=81n too=
k
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, Cof=EF=AC=81n 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 =EF=AC=81nding, heralded by many patients as t=
he
long-sought cause of their baf=EF=AC=82ing 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 =EF=AC=81rst time
convincingly showed that not one of nine labs, including WPI, could
reliably =EF=AC=81nd XMRV or its close relatives known as murine leukemia
viruses (MLVs) in people who previously had tested positive for them.
Both Mikovits and Cof=EF=AC=81n were among the co-authors of the paper by t=
he
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=E2=80=99s collaborators discovered that a contaminant=E2=
=80=94as many
critics had asserted=E2=80=94explained the XMRV DNA it found in some patien=
t
samples.
In Ottawa, Mikovits came out swinging. But she didn=E2=80=99t make the case
for XMRV, which stands for xenotropic murine leukemiavirus=E2=80=93related
virus. Instead, she offered new evidence that people with CFS (known
as myalgic encephalomyelitis in some countries) had a virus =E2=80=9Chighly
related=E2=80=9D 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. =E2=80=9CThat=E2=80=99s prett=
y scary,=E2=80=9D
she said.
Cof=EF=AC=81n began by stressing that he initially thought the XMRV-CFS the=
ory
=E2=80=9Cwas a wonderful hypothesis.=E2=80=9D But it rested on three legs o=
f 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. =E2=80=9CTo claim that
there=E2=80=99s more than one XMRV, you=E2=80=99re going to have to show a =
virus that
has a sequence that=E2=80=99s different from XMRV,=E2=80=9D he said.
Mikovits=E2=80=99s presentation underwhelmed several of the scientists
attending. =E2=80=9CWithout the full sequence, it=E2=80=99s hard to judge,=
=E2=80=9D 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 =E2=80=9Cdubious=E2=80=9D about her=
claims
that the virus can be aerosolized. Virologist Konstance Knox of the
Wisconsin Viral Research Group in Milwaukee said Mikovits was =E2=80=9Cjust
reaching.=E2=80=9D Knox, who once consulted for WPI and had a falling-out w=
ith
the institute, added that =E2=80=9Cthis is obfuscating what the community =
=EF=AC=81nds
to be obvious.=E2=80=9D Jonas Blomberg, a retrovirologist at the University=
of
Uppsala in Sweden who like Knox has failed to =EF=AC=81nd XMRV in his own
studies of CFS patients, said it=E2=80=99s =E2=80=9Chard to handle=E2=80=9D=
Mikovits=E2=80=99s
morphing theories. =E2=80=9CIt=E2=80=99s like the argument follows the avai=
lability of
the data,=E2=80=9D 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, =E2=80=9CI=E2=80=99m not going to s=
ay yes or
no.=E2=80=9D The other report came from Maureen Hanson, a plant geneticist =
at
Cornell University, who collaborated with CFS clinicians. =E2=80=9CEven tho=
ugh
the XMRV sequences may be wrong, it=E2=80=99s still certainly possible that
there=E2=80=99s a virus in these patients that we need to identify,=E2=80=
=9D she said.
Cort Johnson, a CFS advocate, says many patients have held fast to
XMRV for good reason. =E2=80=9CIt was as if the medical gods, after years o=
f
neglect, had bent down and offered up an apology in the form of a
simple answer that came gift-wrapped with hundreds of eager
researchers.=E2=80=9D
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. =E2=80=9CI would be much more con=EF=AC=81dent putting these putat=
ive
retroviruses to rest if I had a larger, more powerful study,=E2=80=9D Klima=
s
said. Simmons agrees that a larger study would have more power, but he
says the 15-person study is enough =E2=80=9Cto make conclusions about the
assays being totally unreliable.=E2=80=9D 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 =E2=80=9C=
in
a couple of weeks.=E2=80=9D
=E2=80=93JON COHEN
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