Today in the journal Science, two articles were published about xenotropic murine leukemia virus-related virus (XMRV), a retrovirus that was first associated with CFS in a study published in Science in October 2009 by Lombardi et al. These studies add to the mounting number of publications that challenge the reliability of the initial report. Science’s editor-in-chief, Bruce Alberts, issued an “Editorial Expression of Concern” that accompanied the two papers and will be attached to the Lombardi publication. According to Ivan Oransky, executive editor of Reuter’s Health and publisher of the Retraction Watch blog, Science has issued four Expressions of Concern and 10 retractions since mid-2007.
The first study, “Recombinant Origin of the Retrovirus XMRV,” by Tobias Paprotka et al., builds on presentations made in March 2011 at the 18th Conference on Retroviruses and Opportunistic Infections (CROI). It provides data to show that XMRV is a laboratory recombinant of two endogenous murine leukemia viruses that arose during the development of a prostate tumor cell line called 22Rv1. The authors conclude that XMRV originated in the laboratory and does not readily infect or pose a risk to humans. This conclusion is supported by a number of published studies that have used serology to look for evidence of an immune response to XMRV infection. John Coffin, PhD, of Tufts University and the National Cancer Institute, is one of the senior authors on this study. He is a member of the National Academy of Sciences and is considered one of the leading authorities on retroviruses.
The second study, “No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected,” by Konstance Knox et al., tested newly collected samples from 61 CFS patients diagnosed by Daniel Peterson, M.D. Of the 61, 43 had tested positive for XMRV by the Whittemore Peterson Institute or its commercial laboratory, VIP Diagnostics. This team used a variety of methods to detect XMRV and did not detect XMRV in any of the freshly collected samples. Following on reports from other laboratories, they tested a variety of reagents used to perform polymerase chain reaction and found 9 of 17 to be contaminated with mouse DNA similar to sequences reported by Lo et al. in the Proceedings of the National Academy of Sciences. They conclude, “We believe that the detection of MLV in human blood in previous studies reflects contamination of reagents used to assess their presence and/or contamination of human samples during laboratory manipulation of the infectious XMRV clone, VP62.”
The senior author on this study, Dr. Jay Levy of University of California at San Francisco, is head of the Laboratory for Tumor and AIDS Virus Research. He discovered xenotropic murine leukemia viruses (X-MLVs) and is one of the co-discoverers of HIV. In the early 1990s, Dr. Levy and colleagues published two papers about immune activation in CFS and he was affiliated with a CFS clinic at UCSF, as was Dr. Daniel Peterson, the physician who collaborated on the study published today and on the Oct. 2009 study.
These two studies are the result of months of diligent effort by top experts in the fields of virology and retrovirology to understand the origins of XMRV and its potential role in human disease. Multiple collaborators at multiple institutions were involved in the experiments described in these papers published in one of the world’s top journals.
As Alberts states in the Science Expression of Concern, “The U.S. National Institutes of Health [NIH] is sponsoring additional carefully designed studies to ascertain whether the association between XMRV and CFS can be confirmed. Science eagerly awaits the outcome of further studies and will take appropriate action when their results are known.”
Alberts’ statement is consistent with the statement made by CFIDS Association CEO Kim McCleary at the May 10, 2011, meeting of the Department of Health and Human Services Advisory Committee: “The CFIDS Association stands for rigorous research that leads to better care for CFS patients. The results of NIH-supported research into XMRV will provide answers about whether XMRV is a route to better care. We will support the outcome of those studies, whichever way they lead. We will continue to foster the engagement of scientists interested in viral hypotheses and other well-reasoned approaches to improving diagnosis and treatment.”
The CFIDS Association issued a Request for Applications on April 6, 2011, and letters of intent are due on Friday, June 3, 2011. All proposals, including those that may relate to the role of XMRV and MLVs in CFS, will be peer-reviewed for scientific and strategic merit and funding decisions will be made in early 2012 at the conclusion of the thorough application and review process.
We will provide additional analysis of the Knox et al. paper and will closely follow further developments and news coverage about these studies and XMRV with updates to our XMRV resources page and the Media Coverage section and blog at Research1st.com.
References:
Alberts B. Editorial expression of concern. Science. 31 May 2011: 10.1126/science.1208542.
Paprotka T, Delviks-Frankenberry KA, Cingoz O, Martinez A, Kung HJ, Tepper CG, Hu WS, Fivash, Jr. MJ, Coffin JM, Pathak VK. Recombination origin of the retrovirus XMRV. Science. 31 May 2011. 10.1126/science.1205292
Knox K, Carrigan D, Simmons G, Teque F, Zhou Y, Hackett, Jr. J, Qui X, Luk KC, Schochetman G, Knox A, Kogelnik AM, Levy JA. No identification of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science. 2011 May 31:10.1126/science.1204983.
Lo SC, Pripuzova N, Li B, Komaroff AL, Hung GC, Wang R, Alter HJ. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Proceedings of the National Academy of Sciences. 23 August 2010. 10.1073/pnas.1006901107
Levy JA. Xenotropic viruses: murine leukemia viruses associated with NIH Swiss, NZB, and other mouse strains. Science. 1973 Dec 14;182(117):1151-3.
Barker E, Fujimura SF, Fadem MD, Landay AL, Levy JA. Immunologic abnormalities associated with CFS. Clinical Infectious Diseases. 1994. Jan:18 Suppl 1:136-41.
Levy JA. Viral studies of CFS. Clinical Infectious Diseases. 1994. Jan:18 Suppl 1:117-20. Review.
Landay AL, Jessop C, Lennette ET, Levy JA. CFS: Clinical conditions associated with immune activation. Lancet 1991 Sep21:338(8769):707-12.
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Thank you for providing this summary! It’s a challenge for me, as a patient and non-scientist, to keep up with every development in the XMRV story. Whichever way the research leads, there is no doubt that this is a monumental time in CFS history.
When us the CFIDS Association of America going to join the chorus of outrage?! Science’s ‘EEC’ is completely uncalled for as these two studies HAVE NOT proven that anything with the WPI/NCI/CC 2009 Lombardi study is wrong! This is a vicious attack against the WPI !! (please read the WPI’s 3 press releases/responses to ‘Science’ or perhaps TreatingXMRV.blogspot.com for much needed context)
This is just like the pre-Christmas farce of 4 studies concluding no more than scientists must be careful when doing this type of work as contamination ‘can’ occur – every high school science student is familiar with that warning…. although the PRESS RELEASE took the liberty of saying there is no connection between XMRV and ME/CFS; COMPLETELY LACKING PROOF!!
I certainly hope the CAA has sent/will be sending a letter of complaint to SCIENCE, as there has been nothing revealed in these two studies to warrant such an extreme measure – the ‘EEC’ that is!
If a strong worderd letter is not being sent to the journel Science, and a “more appropriately” worded response put up for the ever diminishing membership, detailing these studies for what they are worth, the CAA will have lost the last modicum of respect and scientific & moral authority it has left. We dont want to see another meek and non-committal response like that to the “PACE Trial” fiasco!
Show real leadership and make us believe you DO REALLY CARE ABOUT RESEARCH & THE MILLIONS SUFFERING UNBRIDLED TORTURE RIGHT NOW – LEAD THE CHARGE (to alert the media, investigative journalists, politicians & lead by example by representing US, the very very sick and very very angry!!!) and help this egregiously naked attempt to destroy the WPI & XMRV, which is our only chance to LIVE AGAIN in the nearest future.
ARE YOU, CAA, GOING TO ALLOW 1990 & THE HISTORY OF THE INITIAL RETROVIRUS DISCOVERY TO REPEAT AGAIN??!
IMHO the CDC, WHO etc. are doing what is called “Damage Control” and or “Deny, Deny, Deny”(compared to the recent nuclear incidences at Three Mile Island, Chernobyl and now in Japan)until they can no longer contain the truth.
The last thing the we need, in their way of thinking,is another threat to the blood supply in which we have no cure much less no credible test in our blood supply.
“These two studies are the result of months of diligent effort by top experts in the fields of virology and retrovirology to understand the origins of XMRV and its potential role in human disease. Multiple collaborators at multiple institutions were involved in the experiments described in these papers published in one of the world’s top journals.”
This is emotive. They have lost months of time by refusing to validate their assays. No evidence that those tests therefore work. We already know HGRV are associated with two diseases. That is not in question, as nothing remotely like evidence has been presented to show otherwise. These two papers are not up to the previous standard of Science magazine.
Could it be that this retrovirus has left the blood and plasma and moved into the Tissue? In which case, it would not be found in blood, plasma, spinal fluid, but rather in the tissue. In which case, it would “No Doubt” exist. Perhaps XMRV or MTLV’s are not the causation of CFS….yet perhaps, XMRV plays an important role in the development, progression, initiation or reactivation of other viruses and pathogens scientifically proven to exist in CFS and GWI and LYME and Autism and other associated diseases. To take a “soundbite” and use the word “Doubt” is potentially throwing 4-20 million people off of a ship and watching them drowned. Is this what humanity has come to? If so, It seems as if we have just regressed into the dark ages. Even worse, up to 10% of anyone, anywhere and anyplace reading thse words could be one of the folks getting shoved off the boat.
It is possible, Julia, but the original report by Lombardi et al. was based on analysis of blood samples (not tissue), so the follow-up studies have focused there. The positive findings in prostate cancer have focused on tissue but have been inconclusive as to whether the tumor tissue or tissue surrounding the tumor is the more robust site of infection. CFS doesn’t (yet) have a target tissue that would be the focus for such a study. One study of cerebrospinal fluid samples also turned up negative results.
I think a lot of this stuff is related to TMS. TMS is a repressed pain disorder discovered by Dr. John Sarno. It’s worth checking into. If you’ve suffered from a disorder with no known cure, why not take a different approach for a limited period to see if Sarno’s methods work. I had nothing to lose and I’m sure glad I did!
This is about science, Facts and Proof not about ego, likes & dislikes or any other human emotion. Pure research and science, to believe the entire scientific community has been brainwashed to confirm or deny any results in this day and age of Technology is just a bit of a stretch. I have met with many of the researchers involved with not just XMRV research, but with various research into the cause or causes of ME/CFS and they are committed to finding answers. One such researcher working to prove a link to XMRV stated ” Don’t worry, if this is not the cause I promise to keep working until I find it”. Just because you see a published paper by researchers that has not given you what you want, it does not mean they have stopped looking, they may be looking at several areas at once and working through the process. To attack them is to cut off your Nose….. CAA is trying to make the published science understandable here to all, so we can be well informed without returning to College to decipher the papers. Yes there are many who can do it on their own, but some including myself like it in layman’s terms. Researchers and scientist are looking for answers to ME/CFS and as individuals they select what they see in their labs to follow through with in their research. Is that not what patients want, different researchers looking at all the possibilities to come to a conclusion on the cause or causes, not all researchers looking at only one possibility. Where would HIV and Cancer research be if that was their approach and where would the treatments be using the same approach.
Excellent post, Bob. Scientists don’t reach consensus that easily. If reputable researchers don’t think that this is the cause, I want their effort (and funding) focused on other possibilities. I think many patients hold this view, I only wish that we received more attention in the press. I believe that advocating for the “best” science will enhance the credibility of CFS patients. Theoretically, we shouldn’t have to do that. But given public perceptions about CFS, we are forced to care about how we are viewed. If we want scientific solutions, we need to rely on the scientific method and peer review.
Thank you Bob, you are right on. I know that Dr Alter has said publicly that he has been moved by the suffering he has witnessed and is committed to carrying on this work. I have heard Dr Lipkin say something similar. Dr Levy is an extraordinary virologist, if we have his interest again it can only be a good thing. These are scientists of the highest caliber, aware of your suffering and keen to help. What ever happens next, understand that this past 18 months have put a focus on the illness in a way we would not have achieved if the XMRV question was not on the table.
I applaud WPI’s efforts and passion, just as I applaud the other fine investigators and clinicians who want to understand the illness and press forward towards studies of potentially effective therapies. I look forward to the completion of the studies underway including the Lipkin study that will allow investigators from WPI, the Alter/Lo group, the CDC retrovirology lab, and Dr. Coffin’s group to study blinded and randomized identical samples from the CFS/ME subjects and controls. A bit more time, a bit more patience please. In the meanwhile we are all working long and hard on other avenues with a focus on the prize: an effective treatment. Faith.