XMRV and chronic fatigue syndrome: So long, and thanks for all the lulz, Part I

Posted by ERV on May 31, 2011
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Sometimes papers make me laugh because they are so bad.

Sometimes papers make me laugh when they do or report something particularly clever.

This paper is the latter:

No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected

I literally laughed-out-loud several times while reading it.

Quick summary– Other people looked for XMRV in patients that had previously or were concurrently determined ‘XMRV positive’ by the WPI and their commercial branch, VIPDx. None of these ‘XMRV positive’ individuals were actually XMRV positive in a lab that controlled for contamination.

Long summary–


Group 1–

  • 41 patients from an Incline Village clinic.
  • 37 patients were previously tested by the Whittemore Peterson Institute and/or their commercial branch, VIPDx.
  • 26 of those 37 tested ‘positive’ at WPI/VIPDx, 11 tested negative

Scientists used the exact same primers used by Lombardi et al to look for XMRV gag and env sequences in patient PBMC. While WPI/VIPDx said 26/37 were positive, this lab found 0/41 using previously reported detection methods.

Furthermore, of the 41 patients, 19 had blood drawn by the same phlebotomist at the same time for this group and WPI/VIPDx. WPI/VIPDx reported that 10/19 were positive. This group, actively controlling for contamination, found 0/19 were positive. Same blood, same patients, same time– and when you control for contamination, XMRV disappears.

Group 2–

  • 29 patients from Petersons medical practice. The ‘Peterson’ of Whittemore Peterson Institute.
  • 26 of the 29 tested ‘positive’ at WPI/VIPDx, 3 tested negative

This time they used Lo et als primers and PCR protocols.

Still no XMRV proviruses in patients PBMC. Also no XMRV RNA in patient plasma.

No XMRV as assayed by four different culturing methods– an indicator cell line, looking for an increase in RT activity over time, looking for increase in XMRV RNA over time, or assaying stimulated patient PBMC for three weeks.

Nothing.

… When contamination is controlled for.

They then took 19 patients in Group 2 and 7 healthy controls and looked for anti-XMRV antibodies.

None, in assays using two different XMRV proteins.

And then they also found something cool… very cool…
Normal human sera hates XMRV and MLV-like-whatever viruses.

Wait, wat?

It means if I took a blood sample from you, yes, YOU, right now, and took out all the cells. Thats your sera. If I mixed your sera, right now, with XMRV or MLV-blah-blahs, your sera would neutralize the virus. Yours. Right now. This is so old school, I am like, nostalgiaing out on this little assay– its either antibody-independent activation of complement, or you (ie humans) have a generic IgM or IgG arrangement that recognizes something on XMRV/MLVugh and activates complement. This is like, a 1970s-1980s thing applied to a virus in 2011. They couldnt have made me squeal and giggle in surprise any more if they had typed ‘and btw, CARE BEARS!’ in this paper or made a pic of He-Man Figure 4.

They also just made a cute little phylogenetic tree of the WPIs sequences and the XMRV plasmid VP62 and were just like “wtf. theyre vp62.” Its a random add-on, but no ones mentioned it, so I guess they felt motivated to.

Summary–

  • WPI/VIPDxs research and commercial ‘tests’ for XMRV finds positives that are a contaminant, VP62, in patient samples that test negative when contamination is actively avoided.
  • Naked human sera hates XMRV and related Magic-Eye viruses, from healthy controls AND CFS patients. Another reason why XMRV probably isnt infecting humans, even if it had the opportunity to do so.
  • The findings in the XMRV–>CFS papers is the result of contamination events, nothing more.
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Comments

  1. #1 RRM
    May 31, 2011

    Slight repost, but there is one thing that is slightly bugging me about the Levy paper. Sending patient samples to VipDx that are negative according to Levy, doesn’t really say anything that we didn’t already know.

    I think Levy (or any other scientists with enough budget to pay for these VipDx tests) should have sent samples of HEALTY controls to VipDx, while telling them these were patient samples. VipDx finding a ‘positive rate’ of ~50% in those healty control samples would have really sealed the deal (N-ray style).

  2. #2 ghholm
    May 31, 2011

    Science has now made an “Editorial Expression of Concern.”

    Followed by a new press release from WPI…

    WPI Response to the Science Editorial Expression of Concern

    Still delusional…

  3. #3 Censored Analyst
    May 31, 2011

    I think Levy (or any other scientists with enough budget to pay for these VipDx tests) should have sent samples of HEALTY controls to VipDx, while telling them these were patient samples. VipDx finding a ‘positive rate’ of ~50% in those healty control samples would have really sealed the deal (N-ray style).

    Completely agree. However, the positive rate would have to be nearly identical to those with ME/CFS to really “seal the deal”. Why would they not do this?

  4. #4 RRM
    May 31, 2011

    Actually, the final response to Science retraction request is much crazier:

    http://www.wpinstitute.org/news/docs/FinalreplytoScienceWPI.pdf

    “The critical question which remains is not simply whether gammaretroviruses play a role in CFS or cancer but in how many other human diseases?”

    Oh, boy.

  5. #5 Censored Analyst
    May 31, 2011

    And I have only read the abstract, but perhaps the XMRV+ patients came from Peterson (so they didn’t have to spend money on testing)?

    And I am pretty sure Peterson was involved in this study. Why the hell isn’t his name on the top of it?

  6. #6 Levi
    May 31, 2011

    ERV,

    A relatively tasteful gloat. Would you be willing to posit as to how this development will affect future desire to research biological causation of CFS by virologist/retrovirologists? Do you think the Lipkin study will be pulled now?

  7. #7 Richard Jefferys
    May 31, 2011

    “Without the participation of Drs. Alter, Lo and the WPI, who have proven gamma retroviral detection methods, it may be impossible to discover whether or not gammaretroviruses are a threat to human transfusion and transplantation medicine.”

    Messianically crazy. I don’t think Science is exactly blameless in this though, you could argue they have a tendency to publish dubious publicity-magnet papers, see the recent controversies around the arsenic life and RNA editing studies.

  8. #8 Sili
    May 31, 2011

    Naked human sera hates XMRV and related Magic-Eye viruses

    Yeahbut – it’s not like you have naked human serum flowing in your veins, so that’s besides the point and completely irrelevant to anything real!

    Also :phlrrrrrt:

  9. #9 Andrew
    May 31, 2011

    The thing is, all of the positive XMRV results in human samples are likely to be due to contamination. So it is not just the Lombardi paper that should be retracted, but all the papers from Urisman onwards with positive results.

  10. #10 scramton
    May 31, 2011

    The contamination result is on the regular local news! Cool!

  11. #11 ERV
    May 31, 2011

    RRM– I do not think Levy et al paid to have any of these people tested at WPI/VIPDx. I got the impression that the same-draws, different-labs ‘test’ was done by the patients, of their own accord, and this is what happened– not that it was Levy actively ‘testing’ WPI/VIPDxs methods.

    Levi– Not ‘gloating’. The science is what it is, and Mikovits is what she is (crazy bitch). I figured these things out early, but I could have been easily wrong about the science. I cant see why anyone who had evidence that CFS was caused by a virus of some kind would stop just because Mikovits is a nut. Nor do I see why Lipkin would stop what hes doing. I doubt there will be any grants written re: XMRV and diseases will be funded in the near future, though, unless someone pulls a rabbit out of a hat.

    Richard Jefferys– Yup. Enough crow to go around for everyone.

    Andrew– Probably.

    scramton– heh, cool!

  12. #12 Jack
    June 1, 2011

    Erhmm… are we back to talking about lawsuits then? Say I had been one of those reported number ‘prescribed’ ARVs… or happened to blog about the ‘benefits’ of taking ARVs because I was convinced I was ‘positive’… or was prepared to speak to some fellow ‘believers’ that ARVs were the answer…

    I mean in all seriousness there are people out there who have been ‘coerced’ into a belief that they are responsible for spreading a dangerous retrovirus through having sex and giving blood for fuck’s sake.

    What all this has meant to them for the past two years can be seen most readily on some of the ‘forums’ out there – as if ‘CFS/ME’ wasn’t already bad enough to deal with every day.

    This is not their fault – not in all cases – and now their refuge is in the welcoming arms of the conspiracy nuts.

    Here’s the latest from NCI – not saying they are nuts you understand:

    ‘While studies now cumulatively and convincingly exclude a role for XMRV in prostate cancer and CFS, they do not rule out the possibility that some other virus or viruses might play a role in either disease. It is known that a variety of viruses contribute to about 15 percent of known human cancers.’

    http://www.cancer.gov/newscenter/qa/2011/xmrv_qa?forumid=331851

    So there you have it, ‘cumulatively and convincingly exclude a role for XMRV in PROSTATE CANCER’ AND ‘CFS’…

    I would imagine – but what do I know – that Singh and Stoye will be addressing this statement specifically in relation to their own previous findings, but is it likely they will stick to their own guns when they employ similar methods as have been used in the study yesterday?

    So back to the question about suing VIP.dx and the perpetuators of this damaging and protracted mess – and I don’t refer to the natural scientific process you understand – but the spurious claims that have inflated the weakest side of it…

  13. #13 Jack
    June 1, 2011

    My mistake, I didn’t mean Stoye did I? Apols. It’s what happens when a layman like me starts getting annoyed :)

    ‘Dr Jonathan Stoye, virologist at the Medical Research Council National Institute of Medical Research, said: “It comes as no great surprise, in fact it was inevitable since a series of studies failed to reproduce the original results.”

    “It should be made as definitive as possible that XMRV is not linked to chronic fatigue syndrome. It is a myth.”

    He said the implication was that the samples were contaminated, however this had not been definitively proven.

    He added: “Science could have gone one step further and withdrawn it off its own bat. In football this is somewhere between a red and a yellow card.”‘

    http://www.bbc.co.uk/news/health-13604050

  14. #14 Jack
    June 1, 2011

    And here comes one of the principle perpetrators herself…

    http://treatingxmrv.blogspot.com/2011/05/sad-day-for-patients.html

    The WPIs ‘Clinical Advisory Board’s response is linked in the above, though not on the WPI website (?) and I quote:

    ‘Clinically, the disease is moved by antiretroviral therapy with HIV drugs, shown to be effective in vitro against XMRV.

    We will be submitting case studies for publication soon and are proceeding with an IRB for an open label pilot study to look at the effects, safety and tolerability of tenofovir for
    ME/CFS patients…

    …The world cannot afford another infected generation. This is not just another EEC. Your concern as editors should be for the patients, or in this case, the health of the species.’

    The blog and this ‘response’ are riddled with emotive crap and it makes me want to puke… ‘scientists’ my arse!

  15. #15 SAWells
    June 1, 2011

    Jack D. Ripper, no, the WPI want to protect your precious bodily fluids from fluoride, no, mercury, no, vaccines, no, XMRV…

  16. #16 daedalus2u
    June 1, 2011

    I think it is telling that Mikovits characterizes the release of information on the paper before the Science embargo as a

    “gross disregard for the integrity of the scientific process by the apparent willful breach of your embargo”

    Pre-publication embargoes have nothing to do with the integrity of the scientific process. Embargoes are about for-profit journals as entertainment; trying to get everyone more excited and fluffing up journal sales to generate a bigger money shot. It has nothing to do with the scientific process, other than it being the unfortunate price that scientists have to pay to publish and to read what is published. Most scientists (all?) prefer open access journals. Pay walls inhibit scientific progress by limiting and taxing the flow of information.

  17. #17 Mu
    June 1, 2011

    I love how the commentators on the Xrx blog are upset a scientist would supply samples to other scientists for verification. They also don’t seem to grasp that the contamination might be in the analytical set-up and not in the samples.

  18. #18 Censored Analyst
    June 1, 2011

    Let me first state this very clearly: It looks to me like XMRV will not be, and will never be associated with CFS.

    However, if you’ve seen graphs it’s very clear that antiretrovirals do something very positive – at least initially. But then there are cases will all the abnormal cytokines will go back to normal, and then other cytokines will spike very high (this part is anecdotal and from my observations and I haven’t seen anyone present this information).

    I don’t think it’s unlikely that it’s another retrovirus, but that being said, even though there are huge shifts in certain cytokines, overall, antiretrovirals don’t seem to work as there is not much change in the patient’s well-being.

    I do think it’s possible that patients are on the wrong cocktails or that there aren’t antiretrovirals effective against the possible retrovirus.

    Remember, ruling out XMRV does not mean it’s not a retrovirus, and does not mean antiretrovirals will not be needed to address ME/CFS. They suspected a retrovirus since the early days, and this hunt is nothing new. It’s basically history repeating itself.

    Now here comes Ampligen trials again… (just guessing trials will be done again since I expect history to repeat itself)

  19. #19 mary
    June 1, 2011

    @ levy…no, no.. not gloat. I think that everyone (scientist and lay person alike) realize that behind all these papers, there are alot of pretty ill people.

    Despite being told by the me/cfs community that those of us who doubted the XMRV connection were fools who didn’t know how to follow the scientific method..there is no gloat in any of this.

    I do wish you and any other me/cfs patients well. I myself, knew very little about this condition, when that science article was published in 09. So, if nothing else, I think this has brought some attention to the me/cfs condition.

  20. #20 GFPmonkey
    June 1, 2011

    I’m going to miss Gerwyn and his unique take on PCR as well. For sheer entertainment value I think he should be invited to CSH as a warm up act. He’ll get a bigger cheer than ‘no parking on the Bungtown Rd”!

  21. #21 ERV
    June 1, 2011

    GFP– Geryyyyyyynnnn did bring up some valid points. Like, I too wonder if Bruce Alberts consulted a biochemist before he asked Mikovits to retract. And I too am wondering when all these biologist virologists are going to start learning some chemistry!

  22. #22 GFPmonkey
    June 1, 2011

    That and wondering whether Dusty Miller knew anything about retroviruses. Classic. The man is a comic genius! I see he’s blogging on Nature still obsessing about annealing temperatures. I guess the first time he ever performs a PCR will be quite an emotional (and probably sticky) moment.

  23. #23 Smurfette
    June 1, 2011

    I read a pun in here: “Final reply to science”.