From the summer-fall 2011 issue of SolveCFS
By K. Kimberly McCleary, President & CEO
Two years ago, a gammaretrovirus called xenotropic murine leukemia virus-like virus (XMRV) was linked to CFS with a high-profile study published in Science by a team of researchers from the Whittemore Peterson Institute (WPI), National Cancer Institute (NCI) and Cleveland Clinic [1]. Today, this study by Vincent Lombardi et al. remains the only one to have shown an association between XMRV and CFS. Research groups in seven countries have tested samples from CFS patients and published 16 papers [2-17] that cast doubt on the original data. Through more than 175 publications about XMRV, researchers have documented a better understanding of its origins, life cycle and other properties, yet no links to human disease have been firmly established.
Recent Studies
While several of the early follow-up studies involving samples from CFS patients were small, used broader criteria to define CFS or had other limitations, two major studies published in May 2011 addressed many of the criticisms. The first was from Clifford Shin et al., published May 4 in the Journal of Virology [13]. Konnie Knox et al. published results in Science on May 31 [14]. Both groups tested samples from CFS patients who had tested positive at WPI, yet neither group found evidence of the virus in those samples or others they tested from well-characterized patients using multiple detection methods. Both studies attracted considerable media attention that kept CFS and XMRV in headlines for most of May and early June.
Another group at NCI led by Tobias Paprotka reported in the same issue of Science [18] that XMRV originated through a laboratory recombination of two mouse viruses in the prostate cancer cell line CWR22Rv1. The recombination event occurred between 1993 and 1996. This evidence makes it unlikely that XMRV will be shown to be the sole cause of CFS, which certainly existed before these dates. The XMRV sequences submitted by WPI to GenBank, the public DNA sequence database, are 98-100 percent identical to VP62, an XMRV clone derived from 22Rv1 and used by WPI and the Cleveland Clinic.
The other piece of evidence weighing against XMRV as a human pathogen are multiple reports of contaminants with mouse DNA in laboratory reagents, supplies and equipment that can show falsely positive results in tests for XMRV and other murine leukemia virus-like viruses (MLVs). Four papers published on Dec. 20, 2010, in Retrovirology [19-22] drew considerable attention to the issue of contamination. The two CFS papers published in May (described above) reported specific sources of contaminants that were encountered in their studies. Information posted to NCI’s website in early June states, “a sample of the XMRV viruses reported in the 2009 article has been cultivated from patient samples and was analyzed at NCI. In contrast to the original findings, the new data suggest it is unlikely that these XMRVs were derived from infected patients. Instead, like the other XMRVs that have been sequenced, they appear to be laboratory contaminants.” Robert Silverman of the Cleveland Clinic told the Chicago Tribune in March 2011 that he was “concerned about lab contamination, despite our best efforts to avoid it.” His lab is conducting additional experiments to test for the possibility. WPI has stated repeatedly that its tests for contaminants have been negative.
By the end of May, doubts about the original report had grown so strong that the editor of Science, Bruce Alberts, requested the authors retract the original paper. They declined to do so, stating it was premature. On May 31, Alberts issued an “Editorial Expression of Concern” [23] that is now tagged to the paper pending the outcome of two large multicenter studies being funded by the National Institutes of Health (NIH) (see below).
Supporting evidence for gammaretrovirus association with CFS has come from two groups who have reported finding sequences consistent with the larger family of gammaretroviruses, but not XMRV specifically. The first team, from the Food and Drug Administration (FDA), NIH and Harvard Medical School, published its findings in August 2010 in the Proceedings of the National Academy of Sciences (Shyh-Ching Lo et al.) [24]. Testing stored samples collected in 1993 for a study looking for mycoplasma, Dr. Lo found 32 of 37 samples from CFS patients positive for MLV sequences. Eight patients from that cohort provided fresh samples and seven of those tested positive again. None of the researchers involved in this study has reported any further data. However, two papers published this summer by groups working independently reported that the sequences obtained from two time points were not consistent with evolutionary changes [25, 26].
The other group, led by Cornell University researcher Maureen Hanson, has presented data at meetings, but its findings have not yet been reported in the literature. The WPI has presented positive data from a study of patients in the U.K., but that has not yet been published, either. News about other unpublished data has circulated through the community and some have charged that positive studies are being unfairly declined by journals, but no specific incidents have been made public.
Clarity Ahead?
To bring greater clarity to the issue, NIH is supporting two studies that involve some of the labs that have published conflicting data.
The first is being coordinated by the National Heart, Lung and Blood Institute and is known as the Blood XMRV Scientific Research Working Group study (SRWG). It is a four-phase study [27] designed to evaluate XMRV detection assays in analytical and clinical samples and to make an initial estimate of XMRV prevalence in blood donors.
- Results from Phase I were reported in July 2010 at a meeting of the FDA’s Blood Products Advisory Committee (BPAC). They showed that six participating labs (CDC, Gen-Probe, NCI-Drug Resistance Program, WPI and FDA-Lo and FDA-Hewlett) had comparable sensitivity in their testing methods using coded analytical samples spiked with XMRV.
Phase II results were presented at a BPAC meeting in December 2010. The presentation was repeated days later during a webinar hosted by the CFIDS Association. In Phase II, samples were obtained from four subjects whom WPI indicated were positive for XMRV on multiple occasions and one pedigreed negative control (tested in Phase I). Samples were collected in the same manner and then split into three groups for immediate processing and processing after two days and four days to compare results. Five labs (CDC, Gen-Probe, NCI-Drug Resistance Program, WPI and NCI-Ruscetti) tested the samples under blinded conditions using the assays from Phase I. Results from three labs (CDC, Gen-Probe and NCI-Drug Resistance Program) were all negative. WPI had at least one positive result for three of the four XMRV-positive subjects as well as the negative control. NCI-Ruscetti reported positive results for three of four XMRV-positive subjects, as well as the negative control. The results from WPI and NCI-Ruscetti agreed on two of the XMRV-positive subjects and differed on the other two. One of the aims of Phase II was to determine whether processing time affected testing results; the data indicated that it did not. In spite of the other conflicting data, it was deemed that Phase III would proceed.- This spring, samples were collected from 30 subjects who previously tested positive for either XMRV or MLV sequences, two pedigreed negative controls and 12 blood donor controls. Five analytical controls were included in the panel as well. Eight participating labs (CDC, Gen-Probe, NCI-Drug Resistance Program, WPI, NCI-Ruscetti, FDA-Lo, FDA-Hewlett and Abbott) tested blinded samples according to approved protocols and each has submitted its results to the Blood Systems Research Institute for decoding and analysis. Results will be presented at meetings this fall and submitted to a peer-reviewed journal.
- The need for Phase IV (focused on blood donors) will be based on the outcome of Phase III.
The second large study is being sponsored by the National Institute for Allergy and Infectious Diseases. W. Ian Lipkin, M.D., of Columbia’s Center for Infection and Immunity, a renowned pathogen hunter, is coordinating the collection of samples from 100 well-characterized CFS patients and 100 matched controls from four sites around the country. Samples will be processed, blinded and sent to labs at the FDA (Lo), CDC and WPI. Dr. Lipkin will break the code and reconcile the results. Although the study was expected to wrap up before year-end, delays in securing required institutional approvals may push the conclusion of the study into 2012.
Other studies continue as well:
The American Red Cross is collaborating with Gen-Probe and Abbott Laboratories to test samples from 10,000 healthy people in six geographic areas. They will also test samples from 120 recipients of blood donations from more than 4,000 donors. Both donors and recipients will be tested for evidence of XMRV and MLVs. [28]
The NCI has evaluated CFS patients who had been previously tested for XMRV at one of its clinics for a study of the different assays used to detect XMRV.- The FDA’s Center for Biologics Evaluation and Research has conducted a study of the transmission and infection processes of XMRV to address potential safety concerns in cells used to produce vaccines and blood products; results have been submitted for publication.
Based on presentations made earlier this year at the 18th Conference on Retroviruses and Opportunistic Infections (March 2011) and the 15th Conference on Human Retrovirology, HTLV and Related Viruses (June 2011), there are other reports in the publication pipeline.
It remains to be seen whether XMRV will provide the answers to better methods of diagnosis and treatment that were heralded in October 2009. There is no question that the original report of an association has attracted remarkable scientific talent, increased engagement by health agencies and unprecedented awareness of the devastating impact of CFS. No other report among the 5,000+ peer-reviewed articles about CFS has attracted this much attention or such sustained effort to investigate more thoroughly. The debate over XMRV has been polarizing at times, but there is no longer dispute about whether CFS is worthy of scientific endeavor; that, in itself, is progress.
References:
[1] Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA (2009). Detection of an infectious retrovirus, XMRV, in blood cells of patients with CFS. Science. Vol. 326(5952), 585-9.
[2] Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, Cleare A (2010). Failure to detect the novel retrovirus XMRV in CFS. PloS ONE, 5 (1).
[3] Groom HCT, Boucherit VC, Makinson K, Randal E, Baptista S, Hagan S, Gow JW, Mattes FM, Breuer J, Kerr JR, Stoye JP, Bishop KN (2010). Absence of XMRV in UK patients with CFS. Retrovirology: 10.1186/1742-4690-7-10.
[4] Van Kuppeveld FJM, de Jong AS, Lanke KH, Verhaegh GW, Melchers WJG, Swanink CMA, et al. (2010) Prevalence of XMRV in patients with CFS in the Netherlands: retrospective analysis of samples from an established cohort. British Medical Journal 2010;340:c1018.
[5] Switzer WA, Jia H, Honn O, Zheng HQ, Tang S, Shankar A, Norbert N, Simmons G, Hendry RM, Falkenberg VR, Reeves WC, Heneine W. (2010) Absence of evidence of XMRV infection in persons with CFS and healthy controls in the United States. Retrovirology.
[6] Ping H, Jinmong L, Li Y. (2010) Failure to detect XMRV in Chinese patients with CFS. Virology Journal. 7:224.
[7] Heinrich TJ, Li JZ, Felsenstein D, Kotton CN, Plenge RM, Pereyra F, Marty FM, Lin NH, Grazioso P, Crochiere DM, Eggers D, Kuritzkes DR, Tsibris AMN. (2010) XMRV prevalence in patients with CFS or chronic immunomodulatory conditions. Journal of Infectious Diseases. DOI: 10.1086/657168.
[8] Hohn O, Strohschein K, Brandt AU, Seeher S, Klein S, Kurth R, Paul F, Meisel C, Scheibenbogen C, Bannert N. (2010) No evidence for XMRV in German CFS and MS patients with fatigue despite the ability of the virus to infect human blood cells in vitro. PLoS ONE 5(12): e15632.
[9] Satterfield BC, Garcia RA, Jia H, Tang S, Zheng HQ, Switzer WM. (2011) Serologic and PCR testing of persons with CFS in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses. Retrovirology 2011, 8:12doi:10.1186/1742-4690-8-12.
[10] Erlwein O, Robinson MJ, Kaye S, Wills G, Izui S, et al. (2011) Investigation into the presence of and serological response to XMRV in CFS Patients. PLoS ONE 6(3): e17592. doi:10.1371/journal.pone.001759.
[11] Furuta RA, Miyazawa T, Sugiyama T, Kuratsune H, Ikeda Y, Sato E, Misawa N, Nakatomi Y, Sakuma R, Yasui K, Yamaguti K, Hirayama F. (2011) No association of XMRV with prostate cancer or CFS in Japan. Retrovirology. Mar 17;8:20.
[12] Schutzer SE, Rounds MA, Natelson BH, Ecker DJ, Eshoo MW. (2011) Analysis of cerebrospinal fluid from CFS patients for multiple human ubiquitous viruses and XMRV. Annals of Neurology. 69(4): 735-738.
[13] Shin CH, Bateman L, Schlaberg R, Bunker AM, Leonard CJ, Hughen RW, Light AR, Light KC Singh IR. Absence of XMRV and other MLV-related viruses in patients with CFS. Journal of Virology, 4 May 2011.
[14] Knox K, Carrigan D, Simmons G, Teque F, Zhou Y, Hackett J Jr, Qiu X, Luk KC, Schochetman G, Knox A, Kogelnik AM, Levy JA. (2011) No evidence of murine-like gammaretroviruses in CFS patients previously identified as XMRV-infected. Science. Jul 1;333(6038):94-7. Epub 2011 May 31.
[15] Oakes B, Qui X, Levine S, Hackett J, Huber BT. (2011) Failure to detect XMRV-specific antibodies in the plasma of CFS patients using highly sensitive chemiluminescence immunoassays. Advances in Virology. doi:10.1155/2011/854540
[16] Jerome KR, Diem K, Huang M-L, Selke S, Corey L, Buchwald D. (2011) XMRV in monozygotic twins discordant for CFS. Diagnostic Microbiology and Infectious Disease. doi:10.1016/j.diagmicrobio.2011.06.003
[17] Cool M, Bouchard N, Massé G, Laganière B, Dumon A, Hanna Z, Phaneuf D, Morisset R, Jolicoeur P. (2011) No detectable XMRV in subjects with CFS from Quebec. Virology. doi:10.1016/j.virol.2011.08.018
[18] Paprotka T, Delviks-Frankenberry KA, Cingoz O, Martinez A. Kung HJ, Tepper CG, Hu WS, Fivash MJ Jr, Coffin JM, Pathak VK. (2011) Recombinant origin of the retrovirus XMRV. Science. 2011 Jul 1:333(6038);97-101. Epub 2011 May 31.
[19] Hue S, Gray ER, Gall A, Katzourakis A, Tan CP, Houldcroft CJ, McLaren S, Pillay D, Futreal A, Garson JA, Pybus OG, Kellam P, Towers GJ. (2010) Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology 2010, 7:111
[20] Sato E, Furata RA, Miyazawa T. (2010) An endogenous murine leukemia viral genome contaminant in a commercial RT-PCR Kit is amplified using standard primers for XMRV. Retrovirology, 7:110
[21] Oakes B, Tai AK, Cingoz O, Henefield MH, Levine S, Coffin JM, Huber BT. (2010) Contamination of human DNA samples with mouse DNA can lead to false detection of XMRV-like sequences. Retrovirology, 7:109.
[22] Robinson MJ, Erlwein OW, Kaye S, Weber J, Cingoz O, Patel A, Walker MM, Kim W-J, Uiprasertkul M, Coffin JM, McClure MO. (2010) Mouse DNA contamination in human tissue tested for XMRV. Retrovirology, 7:108.
[23] Alberts B. (2011) Editorial expression of concern. Science. 1 July 2011: 35. Published online 31 May 2011 [DOI:10.1126/science.1208542]
[24] Lo S-C, Pripuzova N, Li B, Komaroff AL, Hung G-C, Wang R, Alter H. Detection of MLV-related virus gene sequences in blood of patients with CFS and healthy blood donors. Proceedings of the National Academy of Sciences. 10.1073/pnas.1006901107.
[25] Coffin JM and Cingoz O. (2011) Endogenous Murine Leukemia Viruses: Relationship to XMRV and related sequences detected in human DNA samples. Advances in Virology. 7 Jul 2011.
[26] Katzourakis A, Hue S, Kellam P, Towers GJ. (2011) Phylogenetic analysis of MLV sequences from longitudinally sampled CFS patients suggests PCR contamination rather than viral evolution. Journal of Virology. JVI.00827-11.
[27] Simmons G, Glynn SA, Holmberg JA, Coffin JM, Hewlett IK, Lo S-C, Mikovits JA, Switzer WM, Linnen JM and Busch MP for the Blood XMRV Scientific Research Working Group. (2011) The Blood XMRV Scientific Research Working Group: mission, progress, and plans. Transfusion. 1 Mar 2011. DOI: 10.1111/j.1537-2995.2011.03063.x
[28] Bergoth T, Salminen M, Escriva A-B. Risk assessment on XMRV implications for blood donation. European Centre for Disease Control. 06 July 2011. Page 18.
A chronological listing of XMRV-related articles and publications is available at http://www.cfids.org/xmrv/resource-listing.asp.
_________________________
Links to full-text articles accompanied by the patientINFORM logo are provided courtesy of the Association’s partnership with patientINFORM.
K. Kimberly McCleary has served as the CFIDS Association’s chief staff executive since 1991.
This article will appear in the summer-fall 2011 issue of the print publication, SolveCFS: The Chronicle of the CFIDS Association of America. The issue is now at press. To obtain a complimentary copy, send your name and mailing address to cfids@cfids.org with SOLVECFS in the subject line.
(Note: This article was updated at 10:38 a.m. on Sept. 22 to reflect publication of the study by Cool et al.)
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Lombardi et al. only had 3 of the 68 sequences fully sequenced, they were XMRV, the others are unknown. XMRV is a polytropic and xenotropic hybrid.
Lo et al found xenotrpic, polytropic and modified polytropic sequences. That is the same virus. So Lombardi et al has been supported by another study, and that brings the total number of labs published to 5.
No negative paper has attempted to replicate or use diagnostically validated assays, making it impossible to make claims that the findings in Lombardi and Lo et al are somehow wrong. Clearly they are not. It will be the same if the BWG also fail to use diagnostically validated assay.
John Coffin’s last two papers were also positive. HIV was 2.7%, prostate cancer was 12%.
No studies looking a pathogenesis have been published yet, so you are jumping the gun when you say no “links to human disease have been firmly established.”
Now Paprotka et al. has been found to have left out a 3rd assay from their paper. An RT-PCR assay. They also failed to prove the existence of the virus they should not have called PreXMRV-1, without evidence it was a pre instead of a post virus.
Simon, although Lombardi et al. only fully sequenced 3 of the 68 positives they found, all three were almost exactly the same, differing only by a few nucleotides from each other. What is more, the 3 of the 68 positives Lombardi sequenced matched exactly the 3 fully sequenced examples by the Cleveland Clinic, which means that if XMRV truly did have some sort of sequence variation, then out of all this supposed variation the 6 full sequences done thus far were all somehow exactly the same virus. So it’s not just the 3 full sequences by Lombardi, it’s also the 3 full sequences by the Cleveland Clinic for 6 full sequences total.
As for the WPI and the Alter/Lo findings being distinct findings, the Wall Street Journal reported on June 1, 2011 that “Through an NIH spokesperson, Alter replies that the PNAS paper did not link XMRV to chronic fatigue syndrome but rather the larger family of polytropic murine leukemia viruses to which XMRV belongs. The paper never reported finding XMRV itself.”- http://on.wsj.com/jMj2Ax
The issue of assays being ‘diagnostically validated’ is a red herring because if XMRV is truly a contaminant then there would be no such thing as a diagnostically validated assay since XMRV would not exist in a clinical sample to begin with. It is worth noting that Mary Kearney of the NCI has developed alternate techniques which could determine the status of XMRV-infected monkeys, whereas these same techniques could not detect XMRV in samples previously reported as being XMRV-positive. This indicates that it was the tests that initially reported XMRV infection which were the ones that were flawed.
I’m not sure exactly which studies by Coffin you are referring to.
No one is jumping any guns by saying that links to human disease have not been firmly established, precisely because no studies looking a pathogenesis have been published yet. If no studies on the subject have been published yet, then by definition no links have been firmly established.
Paprotka sequenced the entire length of their Pre-XMRV 1 virus. This proves it’s existance. They explain either in the paper or in the supporting online materials why they conclude it was a pre-XMRV and not a post-XMRV.
3 of the 68 Lombardi sequences were fully sequenced. MLVs have high recombination rates. That is why other gammaretroviruses are regarded as families, not single viruses, but multiple variants. The 3 that were cloned by Silverman were 3 new strains. They were not the same as those found previously by Silverman.
The sequence variation that is present in all the isolates of human gammaretroviruses are in no way different to other viruses. To claim there is no diversity here is illogical, when other retroviruese have been shown to have less. Do some research, this is typical of other gammaretroviruses. They preferentially use mitosis to propagate, not reverse transcriptase like HIV does. Hence why the sequence variation is low or none existent. Coffin and Stoye agree that MLVs in mice can have 0% diversity between isolates.
XMRV is a hybrid, it is not xenotropic. Lo found not only xenotropic sequences, but also polytropic and modified polytropic sequences. There is no basis from which to claim that they found a different virus. The both found xenotropic sequences. They both found polytropic sequences. The WPI and NCI reported several months before Lo et al. was published that they were also finding modified polytropic sequences, as Lo et al. also did. Alter agrees, Lo et al. backs the findings of Lombardi et al. He and Lo said this in person at the telephone conference after the paper was published. We are looking at a family of viruses, they will continue to create recombinants in people.
The issue of assays being diagnostically validated is one for the FDA. You would quickly land yourself in jail if a scientist failed to do this before creating a HIV assay. How else can you know an assays works if you fail to prove it does. Take a look at the regulations of any western country.
Assays developed to detect viruses in monkeys are not optimised or validated for humans. They abandoned such research for HIV as the immune response in monkeys is nothing like that in a human and an artificial inoculation is nothing like a natural infection. It is a red herring to claim otherwise. There are many many papers published on these issues that have been known about for decades. Discrepant data will always exist with every virus, when people fail to diagnostically validate their assays. There are many new assays for other pathogens that are shown not to work, but they then choose to diagnostically validate instead of backing away.
When we start to see papers published on pathogenesis, then it will be correct to discuss that research, but trying to discuss it before is jumping the gun. At this time the issue is association. All studies so far strongly support the association of human gammaretrovirsuses with ME and prostate cancer.
PreXMRV-1 was never isolated from a single source, something I’m sure you are aware of. The name is also irrelevant as it has no relationship to evidence and is only a belief. As PreXMRV-1 has not shown to exist as a complete virus from a single source, the evidence only points to the XMRV variant being precent in the early xenografts.
In Coffins last two positive papers, he arbitrarily altered the requirement for a positive result and failed to use all assays on all the participants and instead tested only a fraction of them with some assays. It is in error to believe that assays just work without proof. You cannot put two together and declare your preferred results to be the winner. Otherwise the suggestion is that anyone with basic training can discover new viruses and that there is no need to develop new assays, regardless of our limited understanding of a virus we were unaware of. This approach would definitely declare HIV a contaminant. It is inappropriate.
Thanks for sharing your perspective.
Regarding the finding by Dr. Lo’s group, the Wall Street Journal reported on June 1, 2011 that, “Through an NIH spokesperson, [Harvey] Alter replies that the PNAS paper did not link XMRV to chronic fatigue syndrome but rather the larger family of polytropic murine leukemia viruses to which XMRV belongs. The paper never reported finding XMRV itself.” (Dr. Harvey Alter is the senior author on the PNAS paper.) See http://on.wsj.com/jMj2Ax.
The two latest papers on which John Coffin is an author conclude with these statements:
From “Prevalence of XMRV Nucleic Acid and Antibody in HIV-1 Infected Men and in Men at Risk for HIV-1 Infection,” Spindler J. et al., Advances in Virology, Aug. 22, 2011: “We hypothesized that the prevalence of XMRV infection would be higher among men who have acquired HIV-1 infection than among seronegative controls. The negative data from our study clearly refute this hypothesis. Individuals at risk for HIV-1 infection and sexually transmitted infections are not at risk for XMRV infection.” (See http://bit.ly/oAG2SB)
From “Nucleic Acid, Antibody, and Virus Culture Methods to Detect Xenotropic MLV-Related Virus (XMRV) in Human Blood Samples,” Kearney M, et al., Advances in Virology, Aug. 27, 2011: “If we had used less rigorous criteria basing an overall diagnosis on a single, non-confirmed test and not requiring all replicates to yield the same result, then our two cohorts would have given rise to an apparent, and in our view almost certainly incorrect, reported XMRV prevalence rate of approximately 12%. These considerations may explain conflicting prior reports for the prevalence of XMRV and are consistent with claims that XMRV detection is likely the result of laboratory contamination (2, 8, 12, 32). Particularly given the potential for false positive results in PCR and serological assays for XMRV, our results suggest that applying multiple diagnostic methods including measuring levels of proviral DNA in blood cells, provides a more reliable approach for investigating the prevalence of XMRV. These results also demonstrate that XMRV nucleic acid and antibodies are undetectable in the blood of patients with prostate cancer.” (See http://bit.ly/qucMhW)
There is discrepant data about the association of XMRV to CFS and prostate cancer among the 170+ articles about XMRV now in the medical literature. In addition, evidence of infection with XMRV has also been looked for in samples obtained from men with HIV, men at risk for HIV infection, individuals with ALS, MS, spondyloarthritis, rheumatoid arthritis, hepatitis C infection, fibromyalgia, lupus, B-cell lymphoma, common types of lymphoid malignancies, transplant patients, fathers of children with autism and children with autism and idiopathic diseases. So far, in these limited studies, no XMRV has been found. A group of researchers in Germany reported finding XMRV-specific sequences in 2-3% of 168 samples from immunocompromised carriers and about 10% of samples from 161 immunocompromised patients. In a study of autistic children in Italy in which all of the autism subjects were negative, 3/97 control subjects were positive by PCR for MLV sequences. Hence, my statement that “no links to human disease have been firmly established.” Certainly, many media outlets made more definitive declarations after the pair of publications in Science in late May.
As has been stated in numerous venues over the past several months, 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.
Lo et al. found the same viruses. Lo had xenotropic, polytropic and modified polytropic sequences.
XMRV is a xenotropic polytropic hybrid. Only three of the Lombardi 68 sequences were fully sequenced. That is the same virus. They are the same family of viruses. Why do you imagine they are different? Did someone mislead you?
Interesting. So we all have to have patience, very hard when one is sick every single day with several symptoms, and housebound most of the time.
Why isn’t there more attention to the studies by Komaroff at Harvard Medical School using eeg spectral which found brain differences between people with CFIDS and healthy people?
And why isn’t there more attention to the study at the U. of Utah about the changes in genetic expression in people with CFIDS after exercising vs. healthy controls?
I know that the CFIDS Association has written about these studies, but where is the follow-up? Where are other scientists furthering these studies? Where have they been publicized other than here?
Why can’t different studies and findings get the same attention as the XMRV/MLV contradictory studies?
This is why people with CFIDS get frustrated and upset. We are ill. The one concrete possibility for causation is being slammed, although not all study results are in or published?
Yet other avenues and studies are not getting publicized to either CFIDS patients, doctors, medical journals and the mass media?
If the Komaroff and Light studies were written about in the mass media, including influential papers, it would help to give credence to this disease as a physiologically caused illness with objective tests and findings? Patients, friends, families, doctors, etc. would be more enlightened, and it would help take this disease out of the Dark Ages and put it into the period of Enlightenment.
Kathy, we agree it’s frustrating that the research reported by the Lights and by Dr. Komaroff and Dr. Duffy have not received more attention from the media. Amy Dockser-Marcus, who initially reported on XMRV and has written more than 30 articles about the research as it has unfolded, got front-page attention for CFS on the Wall Street Journal. In March, three articles appeared in the weekend edition of the paper, March 5, 12 and 19 (2011), including this article, “Unlocking Chronic Fatigue Syndrome,” at http://on.wsj.com/eZnXEi. Fox News picked up on the WSJ story and ran this on March 22, 2011: http://fxn.ws/eUAQfV. The research from Univ. of Med. and Dentistry of NJ from Dr. Steve Schutzer’s group got a lot of media attention in February when they published potential spinal fluid markers that could separate CFS, post-treatment Lyme disease and healthy controls. Katie Couric introduced the story on the “CBS Evening News” on Feb. 25. You can find a comprehensive recap of the year’s media coverage of CFS research here on Research1st at http://www.research1st.com/media-coverage-about-cfs-research/.
And meanwhile all the CAA is doing is sitting on the sidelines waving their CDC pom-poms.
From the FAQ at http://www.cfids.org/about/faq.asp#2a:
“The Association has been very public in its criticism of the CFS Research Program at CDC. You can read a summary of our recent efforts at http://www.cfids.org/cfidslink/2009/050607.asp. The Association does not support use of the CDC’s empirical definition of CFS in federally funded research and has repeatedly urged that CDC discontinue selecting CFS cases for its studies using these guidelines. The Association has never funded any research based on the empiric definition, nor has any education supported by the Association been based on the empiric definition. Review the Association’s applicant research guidelines for defining cases (http://www.cfids.org/profresources/grants-guidelines.asp) and its current eligibility criteria for the BioBank (http://www.solvecfs.org/SOLVECFSBIOBANK/CURRENTSTUDYCRITERIA/tabid/117/Default.aspx).
“The Dec. 17, 2010 announcement by CDC that the CFS Research Program will be led by Elizabeth Unger, MD, creates the possibility for expanded opportunities for collaboration and progress toward shared goals. However, we will continue to insist upon rigorously conducted CFS research regardless of who manages the program at CDC.”
Perhaps Chris, you’re referring to the post this morning on our Facebook page (http://www.facebook.com/CFIDSAssn) that read: “From the CDC’s CFS research group, results of a genomics study that found two genes, GRIK2 and NPAS2, to be associated with CFS. http://bit.ly/qvZvHR.” If so, other readers should know that we regularly post links to new research studies that document the biological basis of CFS.
If you are interested in research all of a sudden, then you need to hire a scientist who knows about other retroviruses that are no different to human gammaretroviruses. Both in terms of diversity and in how they are near impossible to detect in the blood. They should also know why you cannot disprove results without replication or diagnostic validation of new assays. That is if you are serious.
What exactly is the CDC’s problem here in studying CFIDS and going outside the box. The CDC could do something with the Komaroff, Lights’ and Duffy studies, like get involved, validate them, try to figure out ways to study this on a national scale and then incorporate the findings into testing and disease criteria.
It seems as if the CDC has been obstructionist to finding the causes and treatments for this disease all along. Tne, as a friend has said to me over the years, “A leopard never changes its stripes.” Is it possible for the CDC to “change its stripes?”
Thankfully, the NIH and even the NCI and FDA seem to be a bit more independent of the CDC.
What will cause the CDC to wake up and smell the coffee and not keep propagating years-old, no, decades-old disease criteria.
There must be political overtones on this, in terms of limiting research funding, insurance funding, disability funding. Or else why would the CDC be obstructionist?
I’m hoping Harvey Alter, Dr. Lo, and, of course, Ian Lipkin, figure this out with the viruses.
People are suffering, losing jobs, families, finances, friends, quality of life and more. Yet the CDC fiddles while Rome burns, it seems.
In the medical research system here, it seems as if all of the labs and scientists, with some exceptions, are not collaborating. This would be extremely constructive, if they cooperated, shared information, worked on building on the research, so it’s not just isolated individual scientists in their own labs researching, but a big “Manhattan Project” only for the promotion of good health.
On of the prongs of the Association’s research strategy is to address this problem you identified, Kathy. The lack of collaboration, data sharing and hypothesis generation among researchers was clear at the NIH State of the Knowledge meeting. But once the researchers get together and start sharing this information, advances are made. The Association recognizes this and requires its funded researchers to share data. We foster collaborations and partnerships. And we are working to transform the way CFS research is done by creating more opportunities for collaboration and data sharing. Researchers working in isolation has not moved the field far enough ahead. We want to change that.
The field hasn’t moved forward because you don’t insist that science is conducted according to the scientific method. You cannot dismiss the joint supportive findings of Lo and Lombardi et al. unless you either replicate or diagnostically validate new assays. None of the negative studies have bothered to do this. Why?
Correction above: “A leopard never changes its spots.” Tigers have stripes. Another CFIDS symptom: mixed metaphors.
Jennie — That is very good to know about what the Association is doing to foster collaboration among researchers, to pool findings and promote information sharing of all kinds. This is so necessary with CFIDS and other diseases.
One just gets impatient dealing with this darn disease every day and hoping for answers — causes and treatments.