XMRV: False Positive in chronic fatigue syndrome

4 Oct

Xenotropic murine leukemia virus-related virus (XMRV) has been suggested as linked to chronic fatigue syndrome and autism. This has been rather controversial in both cases.

Before we get to the “false positive” report, Science published one of the papers on XMRV and chronic fatigue syndrome

Murine leukemia viruses (MLV), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.

Reminds me of the Hornig study trying to find measles RNA in autistic children’s intestinal tissues. Multiple laboratories. No link found.

But, what of the older studies claiming a link? Well, Science also has a short article from some of the authors in an earlier paper. They reexamined samples from their study and found that their samples were contaminated with XMRV plasmid DNA:

Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study.

In our 23 October 2009 Report, “Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome,” two of the coauthors, Silverman and Das Gupta, analyzed DNA samples from chronic fatigue syndrome (CFS) patients and healthy controls. A reexamination by Silverman and Das Gupta of the samples they used shows that some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA.”

Again, this is very reminiscent. In testimony for the Omnibus Autism Proceeding, Stephen Bustin discussed contamination (and other) problems with the laboratory searching for measles virus in the samples provided by Andrew Wakefield’s group.

Science ran another article, False Positive, on the XMRV/chronic fatigue story:

For the past 2 years, a controversy has roiled around the purported link between a mouse retrovirus, XMRV, and chronic fatigue syndrome (CFS), a baffling, debilitating disease with no known origin. An October 2009 paper in Science found XMRV in the blood of two-thirds of the CFS patients examined, but more than a dozen labs have failed to replicate it to date. Millions of dollars have gone into clarifying the question, which has had far-reaching consequences for people with CFS and, if the virus lurked in the blood supply, the public at large. A nine-lab study published online this week by Science found that none of the labs could reproducibly detect XMRV or relatives of the virus in blood samples distributed under a blinded code. Science is also running a partial retraction of the original paper, as a contributing lab found that it in fact had a contamination.

More discussion can be found at the blog A Photon in the Darkness as Mikovits XMRV Study “Partial Retraction” and at ERV as XMRV and chronic fatigue syndrome: For your enjoyment– A magic trick.

Other studies have already looked closely and found no evidence of a link: PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism. The current articles in Science do not directly address autism, but they show the serious difficulties involved with studying XMRV and help us to understand how these potential links were made in the first place.

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7 Responses to “XMRV: False Positive in chronic fatigue syndrome”

  1. brian October 4, 2011 at 21:58 #

    Scientist who led XMRV research team let go:


  2. brian October 4, 2011 at 23:05 #

    High-profile 2009 chronic fatigue syndrome study in dispute: Lead researcher fired as journal, institute investigate alleged figure manipulation


    Thanks for the link to the ERV blog. (I rarely visit it, and I probably would have missed the discussion there without your pointer.) The discussion there indicates (and the Tribune article notes) that there may be THREE differently-labeled versions of the same gel scan in circulation: that from the Science paper and two others from different conferences. Oops.

    As daedalus2u noted at the ERV blog, “If this is fraud, it is millions of dollars and go to jail kind of fraud.”

    • Sullivan October 5, 2011 at 01:12 #

      Hey ERV,

      don’t you write a “snarky blog”?

  3. ERV October 5, 2011 at 04:49 #

    I prefer the term ‘irreverent’ ;)

  4. Tsu Dho Nimh October 7, 2011 at 00:33 #

    Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement and reactivity was similar among CFS subjects and negative controls.

    OUCH! Did they never do any self-testing to make sure their results were at least repeatable?

  5. brian October 7, 2011 at 01:09 #

    Tsu Dho Nimh asked: “Did they never do any self-testing to make sure their results were at least repeatable?”

    Perhaps a better question would be this: “Did they never do any BLINDED self-testing to make sure that their results were at least repeatable?”

    The competition for AoA’s next Galileo Award may be heating up–until now I thought that Mark Geier was a lock.

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