From the Wall Street Journal health blog, 30 May 2011 (Story by Amy Dockser Marcus.
Editors of the journal Science have asked the co-authors of a 2009 paper that linked chronic fatigue syndrome to a retrovirus called XMRV to voluntarily retract the paper.
But in written response Friday, study co-author Judy A. Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease said “it is premature to retract our paper.” The letter was reviewed by the The Wall Street Journal.
The study raised patients' hopes that if a virus was linked to chronic fatigue syndrome, a treatment might be found. Public-health officials were alarmed by the possibility that supposedly healthy people might unknowingly be infected with a contagious retrovirus. The federal government began an ongoing effort to evaluate whether the nation's blood supply was safe, work that continues.
In the May 26 letter to Dr. Mikovits and her co-authors, also reviewed by the Journal, Science editor-in-chief Bruce Alberts and executive editor Monica Bradford cited concerns about the validity of the findings, saying other scientists hadn't been able to replicate them, among other reasons.
Dr. Mikovits, who confirmed the letters, said she hadn't received a response in return. Dr. Alberts and Ms. Bradford at Science couldn't be reached for comment.
After the 2009 study, other published studies showed that some anti-retrovirals approved for use in HIV might also be effective against XMRV. Some doctors began prescribing anti-retrovirals for chronic fatigue syndrome patients.
The concern about the blood supply led blood banks to bar patients with chronic fatigue syndrome from donating. An advisory committee to the federal Food and Drug Administration recommended last year that the FDA bar people with chronic fatigue syndrome from donating. The FDA hasn't weighed in on the recommendation.
The Centers for Disease Control and Prevention, among other groups, published studies reporting they didn't find XMRV in chronic fatigue syndrome patients. Other papers found that substances used as part of the process to detect XMRV might be contaminated, raising the possibility that this may explain the positive findings in the 2009 Science paper.
In the letter to the study authors, Dr. Alberts and Ms. Bradford suggested the paper be withdrawn “in light of the growing number of research papers from independent investigators who have either failed to replicate your original finding that XMRV is associated with chronic fatigue syndrome and/or who have provided evidence that laboratory reagents are widely contaminated with the virus.”
The letter added that two additional papers that “cast further doubt” on the 2009 paper's findings will be published on June 2 in Science, and that Science will be publishing what it called an editorial expression of concern about the 2009 paper. “At this juncture, Science feels that it would be in the best interest of the scientific community” for the co-authors to retract the paper, the letter stated.
An editorial expression of concern, while falling short of the journal outright retracting a paper itself, raises a red flag to the scientific community that serious doubts exist about a paper's findings and can make it harder for researchers to obtain funding or publish papers, says R. Grant Steen, a medical communications consultant. He has published papers analyzing 742 English language research papers that were retracted from the PubMed database from 2000-2010.
The 2009 study in question, led by investigators at Whittemore Peterson in Reno, Nev., and including researchers from the National Cancer Institute and the Cleveland Clinic, generated enormous attention among scientists and patients. The researchers reported they found the retrovirus XMRV in a majority of 101 patients with chronic fatigue syndrome, a debilitating condition that involves cognitive dysfunction and severe pain. The authors also found the virus in nearly 4% of 218 healthy people used as controls in the study.
Dr. Mikovits said it was still too early to know the reasons for the differing results in different labs, and that the Institute was looking forward to participating in a major study under way by the NIH and led by Columbia University scientist Ian Lipkin to help clarify the matter.
Write to Amy Dockser Marcus at amy.marcus@wsj.com
They would need a scientific reason to do so and there is none. We have negative studies using unvalidated assays, how about they have their papers retracted.
If anyone is wondering why an assay that can find a low copy number of the VP-62 clone can’t find wild-type virus, the answer is relatively simple.
The chemophysical properties of the DNA are different
high levels of oxidative stress caused by HGRV infections and commonly found in studies investigating patients with ME cause oxidative modification of nucleotide bases. The most common is the addition of a hydroxyl functional group or deamination. This (for reasons involving sterochemistry and something called twisting) means that the stacking energy and hydrogen bonding which hold complimentary nucleotide bases together are dramatically reduced. This can be compensated for by using increased levels of magnesium and lowering annealing temperatures. Another strategy is to use an RNA template to begin with. MLV viruses can’t replicate in resting cells so xmrv will exist in such cells as preintegrative complexes and integrated highly methylated proviruses. ROS oxidation induces a pattern of base substitution or inversion in the provirus affecting primer annealing.The presence of certain oxidised bases or even abasic sequences can stop taq polymerase “in its tracks” leading to an absence of product.Unless PCR reagent concentrations and cycling conditions are adjusted accordingly the virus will escape detection. silverman was able to adjust his assays to find gag sequences which were already present and was fortunate enough to isolate XMRV from RNA hence largely avoiding these issues
The effect of activating PMBCs would be to allow the integration of “fresh” proviruses as the preintegrative complexes are nowhere near as prone to oxidative damage. This would also allow the creation of viral RNA
thank you JT, although I admit most of it is beyond me.
The reason I continue to believe it may be XMRV or something very similar is that I have followed the story closely. I know what very varied symptoms I have. I also have a sibling with autistic syndrome and a nephew with ME. It is like there is a scattered jigsaw on the floor but when the XMRV piece is fitted it links all these bits and pieces together. I can’t recall the exact details but when I have read that the XMRV receptors respond to such and such, every time I will think ‘Oh Yes!’ It just seems to make sense of this senseless illness.
Non of the 0/0 studies replicated the methods of Lombardi et al 2009 hence they count for relatively little – other than proving how important it is to use a proven method.
Other groups have found this family of retroviruses in ME/cfs patients and yet more groups will publish positive results before the end of the year.
The editors of “Science” will therefore come to regret their weak willed capitulation to the naysayers and those who believe science should be driven by consensus. That isn’t science, it’s politics.