New XMRV Studies Bring Closure—And Fresh Dispute
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NEWS & ANALYSIS NEWS & ANALYSIS What went wrong? Robert Silverman had to fi gure out how XMRV contaminated his samples. CFS patients had become so emotionally invested in the XMRV theory. “Now, it’s clear to everybody that it is really over,” Fauci says. Three groups took part in Lipkin’s study: Mikovits, formerly at the Whittemore Peter- son Institute (WPI) in Reno, Nevada, and INFECTIOUS DISEASES her collaborators Francis Ruscetti at NCI and Maureen Hanson at Cornell University; a team led by Shyh-Ching Lo at the Food and New XMRV Studies Bring Drug Administration, which in 2010 linked CFS to a related group of viruses called MLVs (Science, 27 August 2010, p. 1000); Closure—and Fresh Dispute and a group at the Centers for Disease Con- trol and Prevention that had failed to fi nd any new virus in CFS patients. The samples Most of the scientifi c community long ago their 2006 paper. Indeed, two high-impact were blinded, and each team chose their own pronounced dead the theory that a newly dis- journals gave the new paper a thumbs-up methods to analyze them so no one could covered gammaretrovirus, dubbed XMRV, but refused to publish it unless the authors complain that the right procedures weren’t was linked to chronic fatigue syndrome retracted their original work, says UCSF’s used, Lipkin says. (CFS). The idea, launched in a Science paper Charles Chiu, who didn’t participate in the This time, none of the groups found any on January 26, 2017 in 2009, quickly garnered headlines because 2006 study but whose lab did most of the evidence of XMRV or MLVs in 147 patients it might explain the baffl ing disease and sug- analyses for the new paper. or 146 controls. Mikovits and Ruscetti did gest ways to treat and prevent it. But since Lipkin’s study is one of two similar fi nd that about 6% of patients and controls then, study after study has demolished the projects NIH funded after Mikovits pub- had antibodies to XMRV, a result they chalk claim, and last year, Science retracted the lished her 2009 paper. One, by the Blood up to aspecifi c binding effects rather than paper (23 December 2011, p. 1636). XMRV Scientifi c Research Working Group, XMRV infection. No previous study had But the results of the biggest study of set out to discover if labs could reliably detect tried to replicate her fi ndings using her exact all had yet to come out. Funded by the U.S. XMRV infection in people and whether methods, Mikovits says. “I’m forever grate- National Institutes of Health (NIH) and led the U.S. blood supply was in danger. The ful to Ian Lipkin for making it possible to par- by Ian Lipkin of Columbia University, the Lipkin study, which used 10 times the ticipate,” she says. Lipkin says he is “proud” $1 million multicenter project finally pub- number of samples, was designed to get a of Mikovits for accepting the outcome. http://science.sciencemag.org/ lished its results on Tuesday in mBio—and not defi nitive answer on the link to CFS. The controversy around CFS had its ori- surprisingly, it concludes that the XMRV the- To most scientists, the blood study, in gins in the 2006 study by Silverman and the ory is really, really dead. What is surprising, which Mikovits scientists say, is that Judy Mikovits, the main also participated, author of the 2009 paper and the staunchest definitely ruled ; (BOTTOM RIGHT) CENTER FOR INFECTION AND IMMUNITY defender of a role for XMRV—or something out XMRV as a closely related—is won over. Mikovits, who pathogen—even Downloaded from SCIENCE participated in Lipkin’s study, concedes it is more so because a “the defi nitive answer. … There is no evidence 2011 paper by John that XMRV is a human pathogen.” Coffin and Vinay Meanwhile, another group has also Pathak of the wrapped up some unfinished business. National Cancer XMRV was fi rst reported in PLoS Pathogens Institute (NCI) had in 2006 by Robert Silverman of the Cleve- shown that the virus land Clinic in Ohio, along with colleagues at was a hybrid of two the University of California, San Francisco mouse viruses, acci- Final answer. Judy Mikovits (left) says she’s “forever grateful” to Ian (UCSF); at the time, they linked the virus to dentally created in Lipkin (right), who led a big study of the link between XMRV and CFS. prostate cancer. A new paper by many of the the lab in the 1990s same authors, published in PLoS ONE this (Science, 23 September 2011, p. 1694). UCSF team that first reported XMRV in week, soundly refutes that link as well and As a result, NIH received an “enormous prostate cancer patients. As the link to CFS describes their meticulous detective work to amount of criticism” for continuing his study, unraveled, Silverman realized that his work explain how the spurious fi ndings arose. Lipkin says. But Anthony Fauci, director of might also have problems, he says, and the But these authors have sparked a new the National Institute of Allergy and Infec- 2011 paper by Coffi n and Pathak convinced controversy by saying that XMRV remains tious Diseases, says it was worth going the him his results were due to contamination. CREDITS: (TOP) COURTESY OF CLEVELAND CLINIC; (BOTTOM LEFT) J. COHEN/ CREDITS: (TOP) COURTESY a potential pathogen and refusing to retract extra mile to disprove it, especially because From then on, “I felt like I couldn’t rest until www.sciencemag.org SCIENCE VOL 337 21 SEPTEMBER 2012 1441 Published by AAAS NEWS&ANALYSIS I fi gured out how it happened,” he says. ASTRONOMY The researchers took tumor samples from 39 new prostate cancer patients and tested Warped Light Reveals Infant Galaxy them for XMRV using three different tech- niques; they also went back to tumor tissue On the Brink of the ‘Cosmic Dawn’ still available from the 2006 study. This time, they found no XMRV in any of the samples. (Science, 19 November 2010, p. 1028). They did fi nd it in archived RNA extracts from From studying the image, the research- the 2006 study, indicating that contamination ers estimate that the galaxy is less than had happened during sample processing. 200 million years old and formed more than Further studies—some using tech- 300 million years after the big bang. Its niques unavailable at the time of the original estimated 100 million solar masses’ worth study—revealed that the virus originated in of stars makes it just 1% as massive as the LNCaP, a cell line infected with XMRV that Milky Way. Silverman’s lab used for other studies. The In the timeline of cosmic evolution, the LNCaP cells, in turn, had become contam- galaxy represents an era that is still fi lled inated by 22Rv1, another widely used cell with mystery. The universe was a soup of line that also harbors XMRV. hot plasma for a few hundred thousand Silverman’s group “deserves a medal,” years after the big bang. Then the elec- says Kim McCleary, head of the CFIDS trons and protons in the soup combined to Association of America, a patient advo- form hydrogen. The fi rst stars and galax- cacy group. In the long history of pathogens ies are believed to have been born some falsely blamed for CFS, McCleary says she’s 300 million years after the big bang. Over never seen scientists so scrupulously retrace the next 700 million years or so, something their steps. “These scientists put their egos re ionized the universe, breaking its hydro- on January 26, 2017 aside … to get to the truth,” Pathak adds. gen back into electrons and protons. But others are less charitable. In the dis- Magnified. Thanks to gravitational lensing, Studies of the cosmic microwave back- cussion of the paper, the authors say that astronomers have glimpsed a galaxy from the ground have broadly confi rmed this time- XMRV is still a “genuine infectious agent” very early universe. line. But key early details are missing, with “as-yet undefi ned pathogenic poten- including what led to the reionization. tial”; they point out that the virus is able to Many astrophysicists have suggested that infect two primate species and mice and has Sometimes nature gives you free of charge ultra violet (UV) radiation from early galax- interesting biological properties that may a discovery you expected to cost billions of ies may have played an important role. be useful, for instance, in cancer research. dollars. Just ask Wei Zheng and his fellow Zheng and his colleagues say that their Lipkin says he’s “astonished” by that claim. astronomers, who recently spotted a galaxy discovery of the faint galaxy supports that An accidental lab creation not occurring in dating back to a mere 500 million years idea. Because the magnifying glass that http://science.sciencemag.org/ nature is not a genuine infectious agent, he after the big bang. helped bring their galaxy into view covers says, and he worries that the language may The galaxy, some 13.2 billion light-years only a small volume of the sky, Zheng says, inspire new hope in XMRV believers: “I from Earth, sets a new record for most dis- it is possible that many other such galaxies thought we were really done with this.” tant object sighted by astronomers. Such were around at the time. Both Lipkin and Coffin say the 2006 distant, ancient images are technically “Theoretical models of reionization paper should be retracted because its fi nd- beyond the reach of existing telescopes.