Yesterday evening the long awaited and heavily anticipated study by a team the from National Institutes of Health (NIH), the Food and Drug Administration (FDA) and Harvard University “Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors” finally appeared on the website of PNAS – Proceedings of the National Academy of Sciences. Contrary to the rumors and popular belief it is neither a confirmation for, nor a replication study of the original WPI study. They didn’t find any XMRV at all.
The Facts
The scope of this article is limited to the two positive studies:
- Science: “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” by WPI (October 2009)
- PNAS: “Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors” by FDA, NIH & Harvard (August 2010)
The first study found 67% of ME/CFS patients and 3.7% of healthy controls infected with XMRV (Xenotropic Murine leukemia virus-Related Virus). The second study found 86.5% of ME/CFS patients and 6.8% of healthy controls infected with MLVs (Murine Leukemia Virus).
Lets focus on what they have in common: it looks like between 67 and 86.5% of the ME/CFS patients and between 3.7 and 6.8% of the healthy controls in the USA are infected with a MLV.
The second study only contained a small group of patients (37) and healthy controls (44). A larger scale study is urgently needed to confirm these findings. Yes, ironically enough, the second study, hoped to be the replication and confirmation study, will now have to replicated and confirmed as well. Hopefully we will not have to wait that long again.
Spin
In my opinion, the second study is neither a confirmation for, nor a replication of the first. The second study only confirms that WPI is on to something and that there might be an association between a type of retroviruses and ME/CFS.
For 10 months all we’ve heard was “it’s XMRV”. If you didn’t find XMRV you were doing something wrong: wrong selection criteria, wrong methods, or wrong attitude. Now comes this new paper which doesn’t find XMRV either and it’s heralded as the long awaited replication and confirmation study. Well, it isn’t! Nice piece of spin by Annette Whittemore and Judy Mikovits from the WPI as you can see in the videos below, mentioned in the resources section. WPI may count their blessings that the NIH/FDA/Harvard team looked at other MLVs and found them or otherwise it could have been game over. Well, probably not, but how many negative studies can you take?
Close Call
Am I the only who realizes how close we came to yet another negative study. If the team by NIH/FDA/Harvard had been looking solely for XMRV the outcome of the study would have been negative. What would this have meant for this line of research started by WPI? A blow? A deathblow? Well, at least a serious blow.
What made them look for other MLVs? Was it accidental or was it some clever out-of-the-box thinking by one of the researchers? I don’t know, but it certainly was WPI’s lucky break.
What next?
The next step, as I see it, isn’t a step forward, but a step back, back to the drawing board.
- Can WPI detect MLV in the samples from NIH/FDA/Harvard? Can NIH/FDA/Harvard detect XMRV in WPI’s samples? Can MLVs be detected in the samples from the negative studies? Did WPI wrongly identify a MLV as XMRV? Do patients who tested positive for MLV also test positive using the commercially available XMRV test, and vice versa?
- Finding the reservoir is. These retroviruse are hard to find in the blood. Some tests on monkeys indicate that larger concentrations are found in the organs (liver, spleen). This kind of research will require autopsies on human corpses and lots of animal testing.
- Development of a standard MLV test.
- Large scale studies worldwide: healthy individuals, blood donors and donations, patients with ME/CFS, AIDS, MS, FM and cancer.
- The big question: Are MLVs in humans pathogens or opportunists?
- Treatment/Cure.
Conclusion
The research is exciting, but this new paper raises more questions than it answers.
What about the existing XMRV tests? Should they be called back or destroyed? Should the patients who got tested ask their money back or are these just the risks of being an early adopter?
I am a bit disappointed, because several publications were promised (be)for this Summer, but it looks like September might have some surprises up its sleeve. In less then a month I will have to decide again whether to get tested for XMRV or not and thus far I am still stuck with the arguments I used in February: To Get Tested For XMRV Or Not. That’s The Question. Meaning that my answer is still no.
The good news: ME/CFS and the scientific research got a lot of positive media attention, thus raising awareness. A lot of articles got their facts straight, mentioning that ME/CFS is more than just fatigue. I have seen articles not only on mainstream newsmedia and science sites, but on business and open source (!) newssites as well, at least in the USA. While the new study was unable to find XMRV, both papers mentioned found a link between MLVs and ME/CFS patients. French and Canadian researchers called for clinical trials to determine whether chronic fatigue patients can be treated with anti-AIDS drugs that have been shown to block replication of the virus in a test tube. Pharmaceutical companies are also starting to show an interest.
After the negative studies we’re back in the game. Anything that helps giving ME/CFS patients back their lives is welcome, even if the XMRV and MLV link turns out to be a wild goose chase.
| Science never solves a problem without creating ten more. |
| George Bernard Shaw |
Resources
- Science: “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” by Vincent C. Lombardi, Francis W. Ruscetti, Jaydip Das Gupta, Max A. Pfost, Kathryn S. Hagen, Daniel L. Peterson, Sandra K. Ruscetti, Rachel K. Bagni, Cari Petrow-Sadowski, Bert Gold, Michael Dean, Robert H. Silverman, Judy A. Mikovits
- PNAS: Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors” by Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L. Komaroff, Guo-Chiuan Hung, Richard Wang, and Harvey J. Alter
- CFS Patient Advocate: Annette Whittemore & Judy Mikovits press videos on Alter study
- Enterprise Open Source Magazine: Presence of Murine Leukemia Virus Related Gene Sequences Found in CFS Patients
- ScienceBlogs: XMRV and chronic fatigue syndrome: Scientific Blue Balls by ERV
- Bloomberg Businessweek: More Evidence Virus Plays Role in Chronic Fatigue Syndrome
- Los Angeles Times: Study reignites debate over virus’ role in chronic fatigue
- ScienceNOW: Second Paper Supports Viral Link to Chronic Fatigue Syndrome
- The Wall Street Journal: New Hope in Fatigue Fight
- The New York Times: Study Links Chronic Fatigue to Virus Class
- PNAS: Mouse retroviruses and chronic fatigue syndrome: Does X (or P) mark the spot?
{ 6 comments… read them below or add one }
I think the Lo/Alter study is a great advance, and, although not a ‘replication’ study, it certainly offers great support for WPI’s pioneering work.
Virologists certainly never considered one type of ‘XMRV’ to be the ‘one and only’. Viruses are not ‘stable’ things, they change and adapt all the time, different viral sequences recombine, etc… WPI already found different strains, or have I got that wrong?
One commenter on a blog today, who reacted on the statement ‘They did not find XMRV’ explains as follows: “….Dr Alter hypothesizes that the various taxa may largely have common properties, whether or not those include causation of CFS. Not that they are all quasispecies with each other, I think, but rather sister taxa. Perhaps a good mental model would be the ‘parallel’ taxa HTLV-1 and -2….”
New serology testing might well be able to detect several related MLV-strains, who knows…
Apparently WPI found a Xenotropic MLV and the NIH/FDA/Harvard team found Polytropic MLVs. Guess they should be looking for MLVs for starters.
Amy Dockser Marcus today in WSJ Health Blog:
http://blogs.wsj.com/health/2010/08/25/does-x-the-virus-that-is-mark-the-spot-in-chronic-fatigue-syndrome/
“…The leader of the research team behind the Science paper, Judy Mikovits, director of research at the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, tells the Health Blog that when that work was published, researchers did not recognize the diversity of the viruses, nor did they understand that X was part of a larger family of MLV-related viruses. “Science evolves,” she says.
But in the months since then, they have continued to study the CFS patients included in the Science paper and Mikovits says that almost all of them are positive for one or more MLV-related viruses, including X and P….”
with X standing for xenotropic, and P for polytropic MLV’s
forgot this:
I read today that the new serological testing (by VIPdx, later through REDLabs) picks up(?)/will pick up(?) antibodies to several strains of MLV’s (source: ESME)
XMRV, MLV, stealth virus, or whatever the cause(s), if a body donor card existed to offer my over ten year Chronic Fatigue Syndrome ravaged body to be shipped fresh to a particular college to be studied, if I should happen to die for whatever reason (i.e. car accident), I would gladly sign it. It seems entirely reasonable to learn the cause of this disease by studying a large number of diseased cadavers and determining what is different about them. Are certain of my organs repositories of particular retroviruses? Are there other differences? What about my Cerebral Spinal Fluid? I wouldn’t know, but I will not allow a biopsy of each of my organs while I am alive!
I am a bit puzzled by that as well. What if they find out that the reservoir is in one of the organs? There are probably means to test it, but I guess we will have to wait what the research of dr. Ila Signh and others reveals.
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