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Set of Contamination Studies Published in Retrovirology
Retrovirology, an online open access journal, published four new studies and one editorial about XMRV and other murine leukemia virus-related viruses on Dec. 20, 2010. The four papers identify three potential sources of contamination in previous studies linking XMRV and P-MLVs to human disease (prostate cancer and CFS). These studies address only the polymerase chain reaction (PCR) methods used by other groups to detect XMRV and polytropic MLVs.
Numerous media reports relied more heavily on a press release issued by the Wellcome Trust, but the papers themselves and statements made by experts about the data presented indicate that the headlines overstated the strength of conclusions that can be reached. The study of XMRV in CFS is just 15 months along and more study is needed, including more sharing of samples, reagents and methods used by labs that have detected XMRV and other MLVs in human subjects.
Titles, authors and links to the four research papers:
Disease-associated XMRV sequences are consistent with laboratory contamination
Stephane Hue, Eleanor R Gray, Astrid Gall, Aris Katzourakis, Choon Ping Tan, Charlotte J Houldcroft, Stuart McLaren, Deenan Pillay, Andrew Futreal, Jeremy A Garson, Oliver G Pybus, Paul Kellam, Greg J Towers
Retrovirology 2010, 7:111 (20 December 2010)
http://www.retrovirology.com/content/pdf/1742-4690-7-111.pdf
An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR Kit is amplified using standard primers for XMRV
Eiji Sato, Rika A Furuta, Takayuki Miyazawa
Retrovirology 2010, 7:110 (20 December 2010)
http://www.retrovirology.com/content/pdf/1742-4690-7-110.pdf
Contamination of human DNA samples with mouse DNA can lead to false detection of XMRV-like sequences
Brendan Oakes, Albert K Tai, Oya Cingoz, Madeleine H Henefield, Susan Levine, John M Coffin, Brigitte T Huber
Retrovirology 2010, 7:109 (20 December 2010)
http://www.retrovirology.com/content/pdf/1742-4690-7-109.pdf
Mouse DNA contamination in human tissue tested for XMRV
Mark J Robinson, Otto W Erlwein, Steve Kaye, Jonathan Weber, Oya Cingoz, Anup Patel, Marjorie M Walker, Wun-Jae Kim, Mongkol Uiprasertkul, John M Coffin, Myra O McClure
Retrovirology 2010, 7:108 (20 December 2010)
http://www.retrovirology.com/content/pdf/1742-4690-7-108.pdf
Viewpoint article:
Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses
Robert A Smith
Retrovirology 2010, 7:112 (20 December 2010)
http://www.retrovirology.com/content/pdf/1742-4690-7-112.pdf
Media stories about these papers:
- "Big Study Linking Chronic Fatigue To Virus May Be Fatally Flawed," Forbes
- "Studies point to possible contamination in XMRV findings," Science (full text available only to subscribers or pay-per-article basis)
- "Exhausted by illness, and doubts," New York Times
- "XMRV: Raising the issue of contamination," Wall Street Journal Health Blog
- "Studies cloud chronic fatigue research," Chicago Tribune
- "Studying Viruses," retraction of comment to Chicago Tribune by Vincent Racaniello, PhD
- "New study dismisses virus link to chronic fatigue," MSNBC
- "Mouse virus link to CFS is challenged in four studies," Bloomberg News
- "New challenge to link between virus and CFS," Nature.com
- "Contamination may have marred XMRV studies," MedPage Today
- "XMRV not CFS cause," UPI
- "ME, or chronic fatigue syndrome, ‘not caused by the XMRV virus,’ say researchers," BBC News
- "Scientists conclude mouse virus does not cause ME," The Guardian (U.K)
- "Chronic fatigue virus study tainted," CBC (Canadian Broadcasting Centre)
- "ME virus was actually a lab mistake study says," Independent (U.K.)
- "ME virus not responsible for causing CFS," French Tribune
- "CFS not caused by XMRV virus, study finds," WebMD
- "Researchers cast doubt on virus as culprit in CFS," NPR Health Blog
- "Is XMRV A Laboratory Contaminant?" Virology Blog
- "XMRV and CFS: It's Not the End," Virology Blog
- "Alan Rein on XMRV," This Week in Virology Episode 113
- "New research shows virus previously linked to chronic fatigue syndrome is a lab contaminant," Science Blog
- "Virus previously linked to CFS was lab contaminant, not cause of disease, new study shows," ScienceDaily
Press release from Wellcome Trust Sanger Institute: http://www.sanger.ac.uk/about/press/2010/101220.html
Statements from Whittemore Peterson Institute:
http://www.wpinstitute.org/WPI%20statement%20Dec%202010%20Contamination%20Issue.pdfhttp://wpinstitute.org/news/docs/WPI_XMRV_010111.pdf
Quotations from Experts About These Studies:
“The argument for lab contamination as a source of XMRV is subtle and indirect, and not, in my opinion, conclusive," said John Coffin, PhD, of Tufts University in Boston. (MedPage Today, Dec. 21, 2010) “This is not the end of XMRV,” Coffin said, ”but it is a warning we have to be very, very careful.” (Wall Street Journal Health Blog, Dec. 20, 2010)
Judy Mikovits, who led the team of researchers that published the link between CFS and XMRV in Science last year, said her team was able to culture XMRV from the patients’ blood and show antibody responses indicating they had been exposed to XMRV at some point. “You will not make an immune response to a lab contaminant.” (Wall Street Journal Health Blog, Dec. 20, 2010)
“These data emphasize the importance of strict attention to molecular hygiene,” says Ian Lipkin, M.D., of the Mailman School of Public Health and College of Physicians and Surgeons at Columbia University in New York. “They also raise concerns about some findings in earlier studies. However, they do not exclude an association between XMRV or related viruses with either prostate cancer or CFS.” (Nature.com, Dec. 21, 2010)
“My conclusion is that these four papers point out how identification of XMRV from human specimens can be complicated by contamination, but they do not mean that previous studies were compromised. They serve as an important reminder that future experiments to identify XMRV need to be appropriately controlled to ensure that the results are not compromised by contamination. In other words, these four papers are NOT the beginning of the end of XMRV and CFS. Rather, research on the role of this virus in human disease must proceed, with large, case-controlled epidemiological studies, as suggested by others.” Vincent Racaniello, PhD, Columbia University (www.virology.ws)
“The data shown...do not justify some of the sweeping statements made,” says Ila Singh (PhD) of the University of Utah, who has reported XMRV in prostate cancer samples. (Science, Jan. 7, 2011)
“Nothing that has been published to date refutes our data.” Judy Mikovits, PhD, Whittemore Peterson Institute (Science, Jan. 7, 2011)
Statement from the HHS Blood XMRV Scientific Research Working Group about these studies (requested by the CFIDS Association of America):
“The Blood XMRV Scientific Research Working Group has discussed the findings from the four studies published in Retrovirology on December 20, 2010. These studies confirmed the importance of carefully checking XMRV/MLV related-positive results for any evidence of contamination with mouse genetic materials. The Working Group is proceeding with phase III which will evaluate the clinical sensitivity and specificity of multiple laboratory assays that test for the RNA and/or DNA of XMRV/MLVs or antibodies to these viruses. All laboratories have and will continue to apply best practices and check to the best of their ability that no contamination with mouse DNA is present before reporting any positive results. These reports also substantiate the importance of employing tests that not only detect viral DNA and/or RNA but can also detect the virus itself (culture) and/or an immunological reaction to the virus. These tests are reflected in the Working Group planned phase III study.” (Issued on Dec. 27, 2010)
(For more information about the Blood XMRV Scientific Research Working Group, view the Dec. 17, 2010 webinar recording posted at http://www.youtube.com/watch?v=0HynlkG0cVc)
Updated most recently on January 10, 2011
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