JON COHEN, 30 SEPTEMBER 2011 VOL 333 SCIENCE, www.sciencemag.org:
The Waning Conﬂict Over XMRVAnd Chronic Fatigue Syndrome
Less than a day after anew study dealt what many consider a lethal blow to the controversial theory that a newlydetected virus, XMRV, is linked to chronicfatigue syndrome (CFS), proponents and skeptics of the theory squared off in a meet-ing here.In one corner was Judy Mikovits, researchdirector at the Whittemore Peterson Institutefor Neuro-Immune Disease (WPI) in Reno, Nevada, and the main champion of the ideathat XMRV and its relatives play a role in CFS. Her opponent, an erstwhile supporter,was heavyweight retrovirologist John Cofﬁn of the Tufts Univer-sity Sackler School of GraduateBiomedical Sciences in Boston.When Mikovits and Cofﬁn took the stage at the meeting, whichwas organized by IACFS/ME (an international associa-tion devoted to the disease)and attracted 460 researchersand patients, they sat on oppo-site sides of the lectern.
Dur-ing their introductions, Cofﬁnclasped his hands in front of hismouth, looking like a man in prayer who wished this would all stop. Neither addressed theother 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 inScience that made the startling link betweenXMRV, a mouse retrovirus, and CFS (23 Sep-tember, 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 ﬁrsttime convincingly showed that not one of nine labs, including WPI, could reliably ﬁnd XMRV or its close relatives known as murineleukemia viruses (MLVs) in people who pre-viously had tested positive for them.Both Mikovits and Cofﬁn were amongthe 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 discov-ered that a contaminant—as many critics criticshad asserted—explained the XMRV DNA itfound in some patient samples.In Ottawa, Mikovits came out swing-ing. But she didn’t make the case for XMRV,which stands for xenotropic murine leukemiavirus–related virus. Instead, she offered newevidence that people with CFS (known asmyalgic 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, Mikovitsrevealed only partial viral sequences that she shesaid were from the XMRV and MLV familyknown as gammaretroviruses. She said her team, which includes Francis Ruscetti of theU.S. National Cancer Institute in Frederick,Maryland, also had preliminary data thatsuggest these gammaretroviruses may travelthrough the air.
“That’s pretty scary,” she said.Cofﬁn began by stressing that he initiallythought the XMRV-CFS theory “was a won-derful hypothesis.” But it rested on three legsof a stool. After removing blood from CFS patients, Mikovits and co-workers had used the polymerase chain reaction to pluck outDNA from the virus and sequence it, found antibodies to XMRV, and shown that the iso-lated virus could infect cells in lab experi-ments. All the legs have now been kicked outfor both XMRV and MLVs, he said. “To claimthat there’s more than one XMRV, you’re goingto have to show a virus that has a sequencethat’s different from XMRV,” he said.Mikovits’s presentation underwhelmed several of the scientists attending. “With-out the full sequence, it’s hard to judge,” said Graham Simmons, who presented the data datafor the Blood Working Group. Simmons, whoworks at the Blood Systems Research Insti-tute in San Francisco, California, also said hewas “dubious” about her claims that the viruscan be aerosolized. Virologist KonstanceKnox of the Wisconsin Viral Research Groupin Milwaukee said Mikovits was “just reach-ing.” Knox, who once consulted for WPI and had a falling-out with the institute, added that“this is obfuscating what the community ﬁndsto be obvious.” Jonas Blomberg, a retrovirolo-gist at the University of Uppsala in Swedenwho like Knox has failed to ﬁnd XMRV in hisown studies of CFS patients, said it’s “hard tohandle” Mikovits’s morphing theories. “It’slike the argument follows the availability of the data,” Blomberg says.
Two other presentations offered somesupport for gammaretroviruses in CFS patients, but both detected justantibodies and not the virusitself. One study, led by KennyDe Meirleir of Vrije Universit-eit in Brussels, had WPI run itsassays. When asked whether the new findings invalidated his data, De Meirleir said,“I’m not going to say yes or no.” The other report camefrom Maureen Hanson, a plantgeneticist at Cornell Univer-sity, who collaborated withCFS clinicians. “Even thoughthe XMRV sequences may bewrong, it’s still certainly possi- ble 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 rea-son. “It was as if the medical gods, after yearsof neglect, had bent down and offered up anapology in the form of a simple answer thatcame gift-wrapped with hundreds of eager researchers.” Nancy Klimas, a CFS clinician at the Uni-versity of Miami in Florida, stressed that theBlood Working Group had analyzed samplesfrom just 15 people who had tested positivefor gammaretroviruses in earlier reports. “Iwould be much more conﬁdent putting these putative retroviruses to rest if I had a larger,more powerful study,” Klimas said. Sim-mons agrees that a larger study would havemore power, but he says the 15-person studyis enough “to make conclusions about theassays being totally unreliable.” Results of alarger study of 150 CFS patients are expected early next year.Mikovits said she hopes to have fullsequences of her new viruses “in a couple of weeks.”