The big XMRV news last week was that the NIH had confirmed the original WPI paper regarding XMRV and CFS. Or, as sue so eloquently put it:
HA read it and weep you stupid cunt
Unfortunately for the oh-so-civil sue, I wasnt entirely surprised at someone else in the US finding the XMRV-CFS connection (see my October 23, 2009 post on the topic). I am completely open to the idea that XMRV is endemic in the US, and is better able to infect certain immunocompromised citizens, which may or may not cause or perpetuate diseases of some kind. However, replicating the WPIs results in no way justifies the reasons I have written negatively about WPI in the past– Judy accusing other researchers of fraud/collaborating with snake-oil salesmen/supporting anti-vaxers, Annettes shockingly inappropriate behavior, or people randomly experimenting on themselves with antiretrovirals.
So, okay, I was patiently waiting for this paper to come out… when Grant Jacobs, a blagger in New Zealand alerted me to some ‘controversy’. Really? Controversy and stupid drama in XMRV research? Oh I just dont believe it!!!
But the story wasn’t as simple as that. Science has learned that a paper describing the new findings, already accepted by the Proceedings of the National Academy of Sciences (PNAS), has been put on hold because it directly contradicts another as-yet-unpublished study by a third government agency, the U.S. Centers for Disease Control and Prevention (CDC). That paper, a retrovirus scientist says, has been submitted to Retrovirology and is also on hold; it fails to find a link between the xenotropic murine leukemia virus-related virus (XMRV) and CFS. The contradiction has caused “nervousness” both at PNAS and among senior officials within the Department of Health and Human Services, of which all three agencies are part, says one scientist with inside knowledge.
Sooooo… the ‘positive’ paper was submitted by Harvey Alter to PNAS. Harvey Alter is a NAS member, so this paper had, um, ‘a different peer review history’ than you all are accustomed to. Normally, you send a paper to a journal, and they send the paper out to three reviewers, and they give the journal editor a thumbs-up or thumbs-down. When you are a NAS member submitting to PNAS, you pick your own reviewers and send in your own reviews. So, you could, like Lynn Margulis, send a controversial paper out to seven people to get two ‘good enough’ reviews, and be accepted for publication.
Just to be 100% clear, Alter isnt doing anything ‘wrong’, even if he sent it out to 50 people to get two good reviews. He wouldnt be doing anything ‘sneaky’ and its not ‘cheating’, thats just the way things work at PNAS. Which he must understand is a valid concern for Average Joe/Jane scientists who also know how PNAS works. And considering the crap PNAS got for publishing that insane ‘caterpillars and butterflies are two different species!’ weird ass paper for Margulis, I dont blame them at all for being ‘nervous’ about not looking-before-they-leap into this controversy.
But I do think this is funny considering the holy hell that was raised over the first negative study at PLOS: “WARBLEGARBLE IZ NUT REVIEWEDED! PLOS SUX!”
EDIT 07-02-10– Yup.
… the journal’s editor-in-chief, cell biologist Randy Schekman of the University of California, Berkeley, sent the paper out for further review after government agencies requested the publication delay. That review came back with requests for additional studies, the scientist says.
Again, this does not mean Alter did something sleezy or wrong. It also doesnt mean that Alters reviewers are idiots or gave him softball reviews. But people are more critical with anon reviews than in non-anon reviews for colleagues. The PNAS editor didnt want to jump into anything before they sent it out to a few reviewers of their own, and the reviewers wanted a few more experiments. No big whoop, no massive government conspiracy, just exactly what would have happened if Alter sent the paper to a non-PNAS journal.
Anyway, now the ‘held up’ paper in Retrovirology from the CDC, was actually published this morning.
And its fine.
Western Blot– They looked for antibodies to XMRV in 51 CFS patients and 53 matched controls, 121 random blood donors, and sera from 26 people infected with a retrovirus (HTLV, HIV-1, and/or HIV-2). Their positive control sera lit up the appropriate bands for Gag and Env. None of the other samples had any antibodies to XMRV.
ELISA– They also sent the CFS + matched samples off to another lab for blinded testing– this other lab had no idea which samples were from CFS patients, and which were from the matched controls. With ELISAs, you put a LOT of the protein of interest (Gag, Env) into a well, instead of just a band in a gel in a Western, and look for reactivity. They found a couple weakly positive samples for Gag (not Env), one CFS, one control– but those couldnt be confirmed with a different test. They were also sent positive and negative controls, which they were also blinded to, and they properly identified them.
PCR– They used the same damn PCR as WPI, and then a separate primer set they designed. They could see 10 copies of XMRV diluted in human genomic DNA for their controls. They couldnt find it in whole blood or PBMC from the CFS+matched set, or 41 totally different (not the ones used in the Western test) blood donors.
They also sent their stuff to another lab for blinded testing, with blinded positive and negative controls. Positive were positive, negative were negative, and none of the experimental samples had any XMRV.
They used the same definition of CFS (1994 CDC Fukuda Criteria) as the Science paper. They used the same PCR conditions. They had two different labs blindly double check their findings two different ways. They couldnt find XMRV in healthy blood donors to an appreciable degree, much like BigPharma (WPI also did not find antibodies to XMRV in healthy donors, but for some reason is sticking with their 3.7% PCR number).
So what did this paper do ‘wrong’?
Whats the excuse now?
And what did Alter do that was so magically different that his lab could replicate the Science paper?