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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« Pharma and the Health Care Bill: Value For the Money? | Main | Drug Patents in India »

February 16, 2010

XMRV and Chronic Fatigue Syndrome: More Negative Data

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Posted by Derek

Update: fixed formatting problems with the post. Not sure what happened!

The wrangling over this issue has been fierce, and now it's even more so. Here's another paper from the UK, just coming out today, that has found no association between patients diagnosed with Chronic Fatigue Syndrome and xenotropic murine leukaemia virus-related virus. The bottom line:

In summary, we have studied 299 DNA samples and 565 serum samples for evidence of XMRV infection. We have not identified XMRV DNA in any samples by PCR, however, some serum samples were able to neutralise XMRV reactivity in our assay. Only one of these positive sera came from a CFS patient, implying that there is no association between XMRV infection and CFS.

I have, as they say, no dog in this fight, so I'm going to sit back while things get sorted out. But something clearly needs to get sorted, because there are claims in this area that seem to be completely irreconcilable.

Comments (11) + TrackBacks (0) | Category: Infectious Diseases


COMMENTS

1. Anonymous on February 16, 2010 1:53 PM writes...

Well look, its not enough of a surprise even to mention. It was obvious to any expert molecular biologist that the entire initial paper was one big artifact of a non-specific PCR with lots of non-specific background bands. They had no good positive and negative controls (they claimed to use "positive" samples as the positive control -positive samples that were deemed positive by their shitty PCR assay - talk about circular reasoning). I mean the review process for that initial paper must have lacked any serious experts in PCR.

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2. Bob on February 16, 2010 2:11 PM writes...

Agreed, I don't know why Science ever ran that paper... The 'budding' virus in the LNCaP cell is by no means XMRV - it could be any virus (in a good electronmicrograph, you'd be able to tell it was a retrovirus!) The lab who produced the original PCR assay (which as far as I can tell, no one has been able to replicate - although the fact that they've copyrighted the assay, so that no one can use it without paying them, might explain why other labs don't want to use it...) have themselves dropped this test for testing patient samples - they now only use culture, because they couldn't get positives.

VIP Dx are just preying on the vulnerable.

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3. retread on February 16, 2010 4:15 PM writes...

It probably won't ever happen, but it would be fascinating to see what would happen if the two labs gave each other their serum samples (blinded of course and with a few ringers thrown in). At this point, we're at the my assay is better than your assay stage.

As noted in an earlier comment, the very high rates of positivity for the XMRV virus in what is almost certainly a heterogeneous condition didn't pass the smell test.

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4. passionlessdrone on February 16, 2010 7:41 PM writes...

Hello friends -

I arrived on this blog sort of by accident, but have been lurking for a while because it is so interesting, though I'm even more out of my league than most places I visit.

Anyways, as I'm in Internet training to cure autism, I've got lots to learn, but one of the things that I thought I had figured out was that you could count on a journal like Science or Nature to get the shit right. According to the long thread on XRMV that got posted here a month or two ago, this paper was in peer review for six months in Science. Here, we have people saying that a competent PCR person would have immediately known the WPI paper had big holes.

If we can't be sure that a large paper in Science has a better handle on things that a Brief Communication in NeuroLetters or whatever low impact journal, what can we be sure of? Are there so few experts that Science couldn't get ahold of one or two for such a seemingly important finding? As with autism, the question could be seen as a choice between things having gotten worse, or have we simply gotten better at seeing the faulty conclusions.

Any thoughts are appreciated.

- pD

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5. dearieme on February 17, 2010 2:03 AM writes...

"I don't know why Science ever ran that paper..": given the rubbish they've carried on Global Warming over the years, why should this be unexpected?

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6. Morten G on February 17, 2010 3:11 AM writes...

I put the same comment on the Science NOW thing about this but I like repeating myself.

If CFS onset is usually associated with viral infection but no-one has been able to pinpoint the actual virus it could be a disorder of the innate immune system, interferons etc. Then both articles could be right. XMRV that transfers readily from mice to humans is probably geographically limited. They should be testing each others samples like someone said. And they should be using the same technique that identified Israeli Paralysis Virus as the culprit behind the recent American honey bee Colony Collapse Disorder (think I got the names right).

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7. Petros on February 17, 2010 8:50 AM writes...

The 6 month review by Science suggests that the first two referees disagreed on the MS. Science then puts it out to a third referee, who in this case said yes.

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8. milkshake on February 17, 2010 11:08 AM writes...

You remember the guy who found out stomach ulcers are casued by Heliobacter infection? - no-one would take him seriously for years, and he had difficulties with publishing his results.

Journal editors + reviewers are supposed to filter out crackpots and hacks without squashing sound ideas. Sometimes it is not easy to tell unorthodox from flaky. I would rather leave the discussion to the scientific community, rather than having reviewers who are supposed to know everything. Even at risk that sometimes a patently wrong study makes it into a decent journal.
I hope that in the future the electronic journals will have a moderated comment section and links to contradicting communications, I think this is the best way to go about sorting out the validity of a disputed study.

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9. qetzal on February 17, 2010 2:17 PM writes...

In fact, both this latest paper and the previous one in PLoS ONE have an open online comments feature. As of this posting, there are no comments posted to the latest paper, but there are quite a few comments to the PLoS ONE paper, including some by the authors themselves.

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10. Anonymous on February 19, 2010 7:33 AM writes...

Exchange samples and exchange info on the testing protocols. That's what the latest UK paper concludes. Sounds good to me.

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11. Dan on February 22, 2010 2:14 PM writes...

I think I would support the opinion of National Institute of Health, The Cancer Society and work done by the world re-known and prestigious institute, Cleveland Clinic, over the prejudicial findings from the person who classifies all CFISD and Fibromylagia as psychiatric disorders.

How to make a disease disappear

PRESS RELEASE:
MEDICAL RESEARCH COUNCIL

12th February
2010
A formal complaint has been lodged by Professor Malcolm Hooper with the Rt. Hon The Lord Drayson, Minister of State with responsibility for the Medical Research Council (Science and Innovation) about the “PACE� Clinical Trial of behavioural modification interventions for people with Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS).

Since 1993, the giant US permanent health insurance company UNUMProvident has been advising the UK DWP about the most effective ways of curtailing sickness benefit payments. The PACE Trial is run by psychiatrists of the Wessely School, most of whom work for the medical and permanent health insurance industry, including UNUMProvident. These psychiatrists insist – in defiance of both the World Health Organisation and the significant biomedical evidence about the nature of it -- that "CFS/ME" is a behavioural disorder, into which they have subsumed ME, a classified neurological disorder whose separate existence they deny. Their beliefs have been repudiated in writing by the World Health Organisation.

Sophia Mirza died of CFS. Hers was the first recorded death in the UK officially attributed to Chronic Fatigue Syndrome. But in reality Sophia was killed by psychologists who stuck her in a mental institution rather than treat her illness. Sophia’s autopsy revealed damage to 80% of the dorsal ganglia in her spinal column due to widespread inflammation. (Damage to the dorsal ganglia would account for most CFS symptoms.)

Further Findings:
We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins (Envs). The envelope-mediated immunosuppression was manifested by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation specifically abolishes IS activity without affecting the “mechanical� fusogenic function of the entire envelope. Here, we genetically “switched off’ the envelope-mediated immunosuppression of an infectious retrovirus, the Friend murine leukemia virus, while preserving mutant envelope infectivity both ex vivo and in vivo, thus allowing us to test the functional importance of envelope-mediated immunosuppression in retrovirus physiology. Remarkably, we show, in vivo, that the non-IS mutant virus displays the same propagation kinetics as its WT counterpart in irradiated immunocompromised mice but that it is rapidly and totally cleared from normal immunocompetent mice, which become fully protected against a challenge with the WT retrovirus. Using cell depletion strategies, we further establish that envelope-mediated immunosuppression enables the retrovirus to escape innate (natural killer cells) and adaptive (CD8 T cells) antiviral effectors. Finally, we show that inactivated mutant virions induce higher humoral and cellular responses than their WT counterparts. In conclusion, our work demonstrates the critical role of Env-induced immunosuppression for retrovirus propagation in vivo and identifies a unique definite target for antiretroviral therapies and vaccine strategies, also characterized in the human T-cell leukemia virus (HTLV) and xenotropic murine leukemia virus-related virus (XMRV) retroviruses, opening unprecedented prospects for the treatment of retroviral diseases.

scientific director Suzanne D. Vernon, PhD, made the following assessment: “The new report from the U.K. should not be considered a valid attempt to replicate the findings described by Lombardi, et al., in the Science article. This paper heavily underscores the need for expedient, yet robust, XMRV-focused research to build upon the results reported this past fall, studies like the one being conducted by the Department of Health and Human Services Blood XMRV Scientific Research Working Group.� Vernon holds her doctorate in virology from the University of Wisconsin

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