(sorry about the commenting issues the past couple of days– dunno what that was, fixed now!)

So, they finally retracted Lo et al, which should have never been published in the first place, as it turns out their findings were contamination, and they should have been aware of that if they BLASTed their goddamn sequences or did some basic evolutionary biology before they tried to publish.

Again, via Retraction Watch:

Another shoe drops as authors retract PNAS chronic fatigue syndrome-virus paper
The authors wish to note the following: “Although our published findings were reproducible in our laboratory and while there has been no evidence of contamination using sensitive mouse mitochondrial DNA or IAP assays or in testing coded panels, we have the following concerns:

1. The original chronic fatigue syndrome (CFS) patient samples were of insufficient volume to distribute to other laboratories for independent confirmation.
2. Only one (1) of many laboratories has found a similar association between polytropic murine leukemia viruses (pMLV) and CFS and a careful study of 100 CFS patients (2), as well as a coded panel recently constructed by the National Heart, Lung, and Blood Institute (NHLBI) (3), have found no evidence for either xenotropic murine leukemia virus-related virus (XMRV) or pMLVs in CFS patient samples.
3. Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.
4. While recall of eight patients from the original cohort 15 y later showed pMLV gag sequences in seven, the copy number was very low and phylogenetic analysis showed these sequences were not direct descendents of the original dominant strains (4). Still later samples from four of these patients tested negative in the NHLBI panel. While this result could be explained by viral clearance over time, it fails to support a sustained retroviral infection in human cells.

Although a more definitive, National Institute of Allergy and Infectious Diseases (NIAID)-sponsored, coded panel of samples from 150 well-characterized and geographically diverse CFS patients and controls is being assembled for further study, in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article.

Gee, thanks. I hope your sloppy (but high-profile!) publication was worth wasting everyones time and money, and jerking around patients. Thanks.

But hey, at least you all were grown up enough to retract this yourself and didnt have to have Bruce Alberts do it for you.

Comments

  1. #1 Jack
    December 26, 2011

    Go Vincent!

    ‘As for the Lipkin study – the more I think about it, the less compelling it seems. Many laboratories have failed to find any retrovirus in CFS patients. The story is over. Why do we think that the results from one laboratory will clear the matter up further? On the contrary – if the Lipkin study is positive, I would not believe it, in the face of all the other negative results we have seen. As I always say, trust science, not scientists.’

  2. #2 Tony Mach
    December 26, 2011

    The Lipkin study is not done for YOU Jack, it is certainly not done to further science or retrovirology (I guess the “we” you talk of), it is done so that patients can have peace of mind. Thank Darwin (or god, if that is your inclination) if you are healthy and non-brain fogged so you don not have to depend on other people getting your disease right – and seeing for decades that these people you depend on get it wrong.

    So from a scientific point of view, is it a waste of money? Fuck yeah, big time. But the problem is that medical science didn’t took the disease serious for decades – this is tying up loose ends, dotting i’s and crossing t’s. You might understand what it means to get certainty if it were your life that depended on it.

    Gee, I look forward to hopefully discussing (non-retroviral) medical science in the future.

  3. #3 RRM
    December 26, 2011

    Problem is, will the Lipkin study convince those patients that are not yet convinced?

    I can see where Lipkin’s coming from, but I feel that his intentions will probably not lead to the desired results (get “emotional” closure on this). At this moment, his “agnostic approach” and disagreement with the retraction is already being seen by some as evidence that other scientists have jumped the gun. Thus, his approach is only leading to more distrust in science. Also, there are certainly already indications that some will feel that negative Lipkin study results will mean that this was an orchestrated effort to shut down research forever…

    It seems the only way to convince that small group of people would be for saint Mikovits (and Ruscetti) to admit she was wrong all along. I don’t know how much of the 2.3M USD has already been spent but, at this point, it seems smarter to take your losses (i.e. accept that a small but vocal group of people will cry foul but will probably be unable to turn this into some hype, even with the help of teh crazies at AoA) and cancel the study, although I’m pretty sure it will not happen.

  4. #4 Grant
    December 26, 2011

    RRM – My thoughts are somewhat similar, but I think the thing with these sorts of things is that you have to focus on those who you can reach and not worry too much about the (admittedly vocal) few who will keep on ‘overlooking’ the evidence against their point of view.

  5. #5 got ilk?
    December 27, 2011

    @3 RRM: So true. the true believer forums are buzzing over the “fraudulent” retractions and tirades about whether to push Lipkins’ balls to the wall and make him publish his study details NOW and/or force him to change the study in some undetermined way so it’s more to there liking. (Like they have the power to decide. Although I suppose they are the reason the pointless exercise is still on the books now.) They will not believe the outcome, just like they rejected Signh’s study when it was published and the Blood study when it came out. Still they whine, no replication attempts have been made. Still they screech, there are unpublished positive studies by DeMeirlier and Beiger. If this study is meant to win over the true believers then it is truly a waste of time and effort (and my taxpayer dollars). Lipkin himself cannot be expected to give a reasoned opinion about whether to go through the exercise or not — he will collect his whole fee only if it’s finished. WHich means he better hurry, because Judy may be going back to jail in a couple of weeks if her defense attorney is as dopey as he sounds.

  6. #6 got ilk?
    December 27, 2011

    I just noticed at the bottom of the home page of the wilddaisy/tango/v99 forum it says that the most people online ever was 128. They have gone to all this trouble and $2.3 M to please 128 people? That’s fewer people than ordered a double shot mocha latte grande with foam this morning at the Starbuck’s nearest you. Now I’m really pissed.

  7. #7 In Vitro Infidelium
    December 27, 2011

    #6 “They have gone to all this trouble and $2.3 M to please 128 people?”

    Before the “it was done to convince patients” propostion becomes a full blown internet meme, I think we should roll back a bit. Lipkin isn’t the prime motivator in this research, and although he’s now an involved apologist (he’s the one whose name is on all the bills justifying the $2.3million) Lipkin was sought out by the NIAID.Unlike the usual competitive grant bidding process, Lipkin’s work is in effect an NIAID initiative. The funds supporting Lipkin still aren’t registered on the TAGGS system http://taggs.hhs.gov/index.cfm and no study description is publicly available. From the outside it looks as though the NIAID either decided that XMRV was a good bandwagon to ride (lots of publicity re: infected blood supplies) or there was an anxiety attack about the WPI grant (the five year commitment to Mikovits) and someone was desperate to have a face saving backstop. Concern over patient views – be they miority or majority, are very unlikely to have played any role in the internal concerns of the NIAID, and it is with the NIAID that there ought be a focus on questioning about grant awarding decisions.

  8. #8 Jack
    December 27, 2011

    @Tony Mach – ?! It was a quote from Vincent Racaniello you twerp: http://www.virology.ws/2011/12/26/authors-retract-paper-on-detection-of-murine-leukemia-virus-releated-sequences-in-cfs-patients/. ‘As I always say, trust science, not scientists’. I am sure you would agree Tony even and especially as a fellow patient?

    @RRM There was a statement in the Washington Post from the NIH funding will proceed – but perhaps this latest retraction of the supporting paper will change things?

    ‘NIH will continue to support the study through its conclusion next year, said a spokeswoman for the NIH branch funding the study, the National Institute of Allergy and Infectious Diseases.

    Alberts disagrees with that decision. He said Thursday there was no reason to continue the NIH-funded study.

    “I think this whole thing has been a tragedy for science,” he said. “The scientific community has put so much time and effort into this.”’

    http://www.washingtonpost.com/national/health-science/study-linking-virus-to-chronic-fatigue-syndrome-retracted-amid-controversy/2011/12/22/gIQADvc6BP_story.html

    I don’t know what to make of the Lipkin XMRV study. There doesn’t appear to be much information available about it – official information I mean – and of course when the funding was announced the BWG had not reported and the retractions had not begun in earnest.

    Am also not sure if the quoted $2.3m applies solely to the XMRV study or also include his more general ‘virus-hunt’ using the Next Generation Sequencing – again detail is sketchy and at least one source (Nature) have said the XMRV study is $1.3m (though that could have been a typo I suppose).

    If (when) the XMRV study proves ‘negative’ or inconclusive it will serve to further undermine the associations proclaimed in Lombardi. It will never (could never) see an end to speculation over retroviral involvement and the vitriol will continue unabated I am afraid.

    However, if the likes of certain ‘players’ on certain forums have lost their ‘faith’ in science – then I don’t think science need loose any sleep over it!

  9. #9 Jack
    December 27, 2011

    Sorry I meant ‘lose’ although I expect scientists are quite ‘loose’ about the whole thing ;)

  10. #10 got ilk?
    December 27, 2011

    @7: No doubt that NIAID hand-picked Lipkin’s group and fast tracked his funding through an open grant mechanism bypassing the usual peer review evaluation and need to convince a jury of his/their peers that this was worth doing. At the time it seemed like it was. The study was announced in the press in Nov. 2010 (NYTimes by none other than Carl Zimmer), so it was in the works before that. Before the Retrovirology papers unveiled the widespread routes of contamination. Before the recombination event was documented. Before Silverman discovered his samples had been spiked SOMEWHERE else. Before the Blood study turned out to be a bust, with false positives in cases and controls, Judy’s mycoplasma problem that precluded her from doing culture and Ruscetti’s positive sequences fitted neatly among the 22RV1 contaminants. Before Judy’s slide manipulation was uncovered by Abbie. Before displaced Judy enlisted her post-doc to steal notebooks. Before we saw mug shots in the pages of scientific journals. Before Ruscetti’s samples were found to be lousy with mouse DNA. Before PNAS pressured Lo and Alter to strip their paper from the journal’s pages because it was all quite clearly a bad idea to have published it in the first place.

    In Nov. 2010 the Lipkin study sounded like a perfectly good thing.
    “Dr. Lipkin is now preparing to dive into a new controversy. In October 2009, a team of scientists claimed to find a virus known as XMRV in people with chronic fatigue syndrome. A pitched debate has arisen over the findings. A number of other groups have since failed to find the same link. To make matters more confusing, a team of researchers from the Food and Drug Administration, the National Institutes of Health and Harvard Medical School reported in August that they found related viruses in people with chronic fatigue, but not XMRV itself. “I think we have to keep an open mind on this,” Dr. Lipkin said.

    In September, Dr. Fauci asked Dr. Lipkin to organize a large-scale investigation. Earlier this month, Dr. Lipkin brought together scientists from three labs that have gotten contradictory results to begin working together on a new search for the link.

    “There isn’t anybody any better at this than Ian Lipkin,” said Dr. Fauci. “If he can’t find it, it probably doesn’t exist.” http://www.nytimes.com/2010/11/23/science/23prof.html?_r=1&adxnnl=1&ref=health&adxnnlx=1324991095-v3OUovXSPPsIU6I2bOpTdw&pagewanted=1

    No doubt Fauci was trying to get past the Elaine deFrietas hangover from the early 1990s and to make sure that the activst patients couldn’t level the “premature abandonment” charge again. Now he’s trapped in a situation. Cut your losses and stop the study now? Chalk it up to a sunk cost and let it play out with the terribly flawed characters involved and prepare to live with a messy result no matter what the assays say? BTW: Who would have expected CDC’s Switzer to be the only one involved who wouldn’t have a recent retraction to his name by the time they got to the point of testing samples? (And hey, what could have taken so long to collect samples? Judy held that up in the BWG but she’s not involved with picking patients this time). The deep sequencing is financed elsewhere and Fauci could probably care less. He just wants this monkey off his back. But it’s probably not a scientific answer he’s looking for. It’s merely ass coverage now. Whatever the price, it seems too high since it won’t change what we know about CFS or XMRV or HGRV or PMLV or ZGRV or whatever the hell they are calling their pets on the forums now. And it sure as hell won’t inocculate Fauci against charges that he hasn’t done enough on CFS, from anyone – sane, XMRV-infected or otherwise.

  11. #11 In Vitro Infidelium
    December 27, 2011

    @Jack #8 Am also not sure if the quoted $2.3m applies solely to the XMRV study or also include his more general ‘virus-hunt’ using the Next Generation Sequencing – again detail is sketchy and at least one source (Nature) have said the XMRV study is $1.3m (though that could have been a typo I suppose).

    The $2.3m figure has been quoted/repeated elsewhere, so it’s possible Lipkin is working on two studies in tandem, split $1.3m and $1m, however these are large sums – Mikovits was having to make do with just $300k a year from the NIAID, and two thirds of that went on her salary ! It’s clear that Lipkin and his collaborators have actually done a large amount of prepatory work so completing the study, even on the XMRV/MLV aspects makes sense. Retraction Lombardi et al and Lo and Alter shouldn’t impact on Lipkin’s other work looking for infectious agencies in CFS patient samples. The question though is whether LIpkin’s microbe hunting will simply spawn a whole raft of similar studies chasing down ever more elusive bugs. My concern is they’ll find lots of EBV (which will produce collective yawns) and a load of weird stuff over which the microbe folks will get excited and want to study in more detail. Although we will not future XMRV type hysteria, there’s a good chance that the cardinal error of Lombardi et al will be successively reproduced – that is that the microbiology will be wholly divorced from the aetiology of M.E/CFS with the M.E/CFS patient population merely being a convenient vat of samples which carry a ‘mystery’ cache.

  12. #12 mo (one of Abbies's elk)
    December 27, 2011

    [...]in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous.

    But what about TEH HUMAN GAMMARETROVIRUSES?????

    Anyway, Merry Christmas to the Mikovits busting gang and gang-queen.

  13. #13 Jack
    December 27, 2011

    IVI – Agreed. Your conclusion especially.

    I have seen the following meme about the place of late. It does concern me. Then I found a source and it wasn’t a surprise really:

    ‘We have non-HIV, non-HTLV AIDS, exactly analogous to non-A, non-B hepatitis before C was isolated…’ http://treatingxmrv.blogspot.com/2011/12/tunnel-vision.html

    I can’t but worry what such comments/beliefs will do with regards perception. Not to mention the knee-jerk responses to these retractions and the ‘analysis’ that is occurring of the various interpretations given by scientists as Racaniello.

    Lo and Alter might believe in the integrity of their original paper but they (and others) were unable to replicate. They retracted. End of that paper and its’ conclusions. Next paper please.

  14. #14 got ilk?
    December 27, 2011

    From a fellow skeptic. Seems appropriate for the topic at hand: http://webcomber.tumblr.com/post/14860158600/unpleasant-truths-or-comforting-lies

  15. #15 Reed A. Cartwright
    December 27, 2011

    ERV, can you remind me again how this paper is related to the other one?

  16. #16 OWE
    December 27, 2011

    When will Silverman and Singh follow?

    OWE

  17. #17 ERV
    December 27, 2011

    Reed
    Sorry :) Paper #1 in Science ‘found’ XMRV in CFS patients. Labs all over the world tried to replicate their findings, and couldnt. Well, then this paper is published (Paper #2), where they found ‘other’ MLVs, NOT XMRV, in CFS samples. They actually ‘found’ mouse DNA contamination, because all of their sequences were obviously mouse ERVs, they are just twats for not BLASTING their goddamn sequences before they published (others did the proper sequence and phylogenetic analysis post-publication and rightly raked these authors over the coals for their negligence).

    On the surface, the Science paper had some issues, but it initially appeared plausible. It was retracted because of numerous other issues.

    This paper (Paper #2) should have never been published, but they forced it through publication at PNAS because Alter is a NAS member. Total bullshit. How many times is PNAS going to pull this crap?

  18. #18 Andrew
    December 27, 2011

    RRM Said: “Problem is, will the Lipkin study convince those patients that are not yet convinced?”

    Many of us are already convinced and have already moved on. But I suspect a minority of patients will continue to suspect there is some sort of bias until the prostate cancer papers are retracted as well. The reality is that they are just as likely to be due to contamination.

    Those of you who are virologists need to create more awareness that those papers need to be retracted. To do otherwise would be hypocritical.

  19. #19 mary (abbie's ilk)
    December 28, 2011

    So, this is it, right? This and the Lombardi paper were the positive studies, are there any more out there that can be clung to?

    Andrew: Lots of people, even those not virologists have been screaming for a retraction..Lots of awareness was created only to be drowned out, dismissed, abused, and threatened by the lunatic fringe group..

  20. #20 OWE
    December 28, 2011

    Thinking about it I am not very happy with this retraction. Lo et al. used the Invitrogen enzyme to do their PCR. Several groups have shown that it is possible to produce pMLV sequences from this enzyme, just like Lo. So, if you are after the detection of murine sequences, this is not a very clever choice. But the retraction does not refer to this at all. Rather it talks about not having enough material to share (such a shame) or potential viral clearance (for retroviruses that could be amplified after single round PCR). So, to me this sounds like “We are still convinced that we found something. However, the others cannot repeat it and for the sake of peace we leave it…” Contamination? NOT IN OUR LAB! A bit like Judy…

    A retraction it may be, yes. But it has a taste. Something like “we used the wrong enzyme and produced artifacts but rushed to have it published without proper checks” would have sounded more honest to me.

    OWE

  21. #21 Jack
    December 28, 2011

    Yes there does seem to be an unresolved issue pertaining to the contamination. I recall and have reread ERVs first article – linked above – but also the confusion expressed by Racaniello with regards to this very point.
    It would be good to ‘dot the i’s and cross the t’s’ over the contamination source in these two papers (as well as the others) I agree even as a patient and non-scientist.
    I would also like to hear more from Silverman about that too ;)

  22. #22 Jason
    December 28, 2011

    Hi Abbie,

    Jason here – postdoc in Steve Goff’s lab. Following this saga since day one. I was probably one of the original peeps to work on XMRV. As soon as the Urisman et al. paper was published, we got the two halves of XMRV, cloned the provirus and did some simple LTR analysis along with cell host range.

    http://www.ncbi.nlm.nih.gov/pubmed/20015990

    I have to say, studying the virus back then was cool since it has a unique host range. For people that study xenos then XMRV is something interesting. However, I saw the writing on the walls long time ago and switched projects (HIV RNAi scren) as soon as I published (phew!).

    However, the point that I want to make, and maybe you should in another post, is the ultimate retraction of the Plos pathogens Urisman paper. I jsut can’t see how this man made (well mouse-made) virus can infect RNaseL “null” prostate cancer to such a high degree. More likely Silverman had a contaminated line (22Rv1 or CWR derivations) along side prostate tissue samples on the day they isolated RNA. Even the RNaseL connection is tenuous at best. That mutation described in the paper (R426Q) is not a null mutation. It reduces the catalytic activity of RNaseL by 3-fold tops. There are plenty of other IFN induced antiviral genes (900 and growing) around to mop up wayward viruses.

    I think you could make a strong case for the retraction, or cause for concern, on your blog since you get alot of traffic.

    Best,

    Jason

    ps – heading to the CSHL retro-meeting this year?

  23. #23 In Vitro Infidelium
    December 28, 2011

    Taking ERV in vain – there’s a wonderful array of burning stupid in the comments at:

    http://treatingxmrv.blogspot.com/2011/12/tunnel-vision.html

    where a couple of Abbie’s posts from 2009 re:MS and HERVs, have left the ARV advocates confused over ERVs versus replicant competent RVs. Meanwhile Mikovits, despite the lifeline given her career by Lipkin, has thrown her lot in with with the chronic Lyme crew http://lymebook.com/vogan-blog/?p=130 A gold star to the first person who comes up with a genunely funny joke about bad poetry (Douglas Adams ref)

  24. #24 herr doktor bimler
    December 28, 2011

    Lo has made a career of headline-grabbing contamination-related blunders, going back two decades when he announced that AIDS was actually caused by a new strain of mycoplasma (there is now a sub-industry within the ME/CFS conspiracy factory that attributes CFS to mycoplasma bio-weapons created in Lo’s research).

    If Lo hasn’t been discredited yet, there is hope for Mikovits.

  25. #25 Poodle Stomper
    December 28, 2011

    Hilarious!

    My current situation is horrendous and while I can say that I did not expect a bed of roses when I started working in the CFS community, knowing full well how other scientists and physicians have been treated poorly, I did not expect to be jailed. If this can happen to me without any wrongdoing, it can happen to anyone in the field and we all must stick together and make certain that our government knows that neither the patients nor the physicians/scientists find this acceptable.” – Dr. Judy Mikovits, 12/27/11

    Yep, there you go; coercing someone to steal notebooks for you, hiding to escape being tracked down, falsifying data, lying about having the notebooks in the first place, lying about why you had the notebooks after admitting to having the notebooks, ect… but no “wrongdoing”. Priceless!

  26. #26 RRM
    December 28, 2011

    Lipkin’s public statement is (luckily) more sensible (added some more para breaks):

    Dear Colleagues and Friends in the CFS/ME Community:

    This letter is written to clarify the status of the XMRV/MLV CFS/ME study I am coordinating at the request of the National Institutes of Health. Although frequently described as the “Lipkin Study,” it is in fact the Alter, Bateman, Klimas, Komaroff, Levine, Lo, Mikovits, Montoya, Peterson, Ruscetti, and Switzer study, designed by these 11 investigators to bring their best methods for case ascertainment and characterization and state-of-the-art molecular and serological diagnostic tools to address the question of whether a retrovirus is associated with disease.

    My role in conjunction with Mady Hornig and Bruce Levin at Columbia University is to ensure that the study represents an appropriately powered, definitive, representative sample of CFS/ME patients across the United States; to receive and distribute samples; and to assess results obtained in individual laboratories for consistency and evidence for or against an association between retroviral signal and disease. I use the term “signal” because any finding related to a retrovirus, whether infectious or noninfectious, genetic material, protein, or antibody, may provide insights into disease or allow development of diagnostic tests even if a causative relationship is not established.

    My condition on accepting this charge from the NIH and the clinical and laboratory investigators is that each participant agree to unconditionally accept group criteria for defining cases to be used in this study. Laboratory investigators were also required to unequivocally endorse their results at the conclusion of the study. Several months were required to develop clinical criteria for case and control definition and to complete approvals for human subject protection. We encountered additional delays when Dr. Mikovits could no longer pursue her work at the WPI. At that juncture, some parties suggested that the work proceed at WPI without her. However, in my judgment, the value of this study rests in its inclusion of the original investigators who reported the XMRV/MLV findings. Thus, I was grateful when we found a way to fully engage Dr. Mikovits. At the time of this writing we have collected and distributed for laboratory analysis samples from 123 CFS/ME patients and 88 matched control subjects. We intend to complete collection and analysis of samples from 150 patients and 150 controls in early 2012.

    There is criticism in some quarters that this study is unnecessary given results obtained by other investigators with other samples. However, the participating clinical and laboratory investigators and our team at Columbia do not agree. We are fully committed to completing the work rapidly and rigorously. For those who continue to express concerns that this study is an inappropriate use of resources in a challenging fiscal environment, please be assured that more than 85% of the funding associated with this initiative is invested in patient recruitment and characterization and sample collection, archiving, and distribution. Thus, irrespective of study outcome there will be unprecedented opportunity to explore hypotheses other than that disease is due to XMRV or MLV infection.

    Sincerely yours,

    W. Ian Lipkin, MD
    Director, Center for Infection and Immunity

    Good to know that most of the money has already been flushed down the toillet.

  27. #27 Grant
    December 28, 2011

    RRM,

    Do you have a source for Lipkin’s statement? – it’s not showing up on google, so I presume wherever it is it’s not being indexed.

  28. #28 Grant
    December 28, 2011

    Eventually found another source that provided a link to what appears to be the original: http://cii.columbia.edu/blog.htm?cid=CalAzy

  29. #29 Grant
    December 28, 2011

    @25 (Poodle Stomper):

    Immediately prior to the quote you offered, Mitovits is cited as having written:

    “I am committed to moving forward this work and am working as the PI on the Lipkin study […]” (Source: http://lymebook.com/vogan-blog/?p=130)

    Presumably Mitovits meant the PI of her team that is part of the ‘Lipkin study’, not the PI of the ‘Lipkin study’ as a whole – ?

  30. #30 got ilk?
    December 28, 2011

    I think another retraction is order – of all the bad things anyone posting to ERV has ever said about Dr. Judy. She is, after all, the Shine “reader’s choice” Woman of the Year for 2011. The female soldier and the First Lady did not even rate as highly.

    http://shine.yahoo.com/healthy-living/shines-woman-2011-she-210200472.html (scroll all the way to the bottom)

    Take it back, ya’ll.

    (Makes sense that it’s “Reader’s Choice” and not “Readers’ Choice. That means it was only one reader to have chosen. Let me guess which one…)

  31. #31 herr doktor bimler
    December 29, 2011

    My role in conjunction with Mady Hornig and Bruce Levin at Columbia University is to ensure that the study represents an appropriately powered, definitive, representative sample of CFS/ME patients across the United States

    Mady Hornig of the much-ridiculed and egregiously bad autistic mice study? That is not encouraging.

  32. #32 herr doktor bimler
    December 29, 2011
  33. #33 Andrew
    December 30, 2011

    I second Jason’s suggestion that Abbie should make a blog post about the flaws of the original Urisman et al. paper.

  34. #34 RRM
    December 30, 2011

    Although the Urisman paper is clearly the most important still “out there”, I guess the paper that is “most eligible” for retraction at this moment must be that rather weird Lombardi et al. 2011 cytokine study (http://goo.gl/Jdxyi). There are several severe flaws IMO:

    - The paper compares 118 “XMRV positive” CFS patients with 138 healthy controls (with unknown XMRV status). Now that the XMRV findings are retracted and WPI couldn’t differentiate between patients and controls in the blinded BWG study, this finding of 118 (out of 118 tested – OMG it’s 100% clinically validated!) positives, without the use of negative controls let alone blinding, there is no way that these patients can still be regarded as XMRV positive.

    - This paper is not about 118 randomly selected CFS patients, as it seems the paper wants to make one believe. A Powerpoint presentation from May 2009 showed that all 118 patients came from a single outbreak, the so-called Lake Tahoe/Incline Village outbreak, which has been long been suggested to have been caused by a viral infection (see http://goo.gl/VMDWS). Therefore, it is a major error to omit this information from your paper. You don’t suggest that your results are generalizable when they come from a single outbreak.

    - Following from the previos point, it was really Dr. Peterson that provided the ‘Lake Tahoe outbreak’ cohort for this study. He was also mentioned as a collaborator in the Powerpoint presentation (mentioned above) of this study. However, Mikovits/Lombardi omitted his name from the authors’ list. Deja fucking vu, because they omitted his name from the Science paper too, before a reviewer caught (and questioned) this omission. I doubt this is a grounds for retraction, but at the very least it shows you Mikovits is a petty person (from the 9/22 ‘slidegate’ presentation, just check the font sizes on the slide of her collaborators if you don’t believe this). It doesn’t matter if you don’t like the person that provided the cohort or that he/she was no longer working with you at the time of publication – if the person deserves credit as an author he/she should get credit as an author.

    - ERV has mentioned other problems with the study, e.g. why only compare ‘XMRV positive’ patients with healthy controls with unknown XMRV status? Surely you can find a group of ‘XMRV positive’ healthy controls (when 4-7% of the general population is infected) and a buch of XMRV negative patients. Now, even if the results are true, it’s unclear whether they are caused by XMRV status, by CFS status, or by XMRV/CFS status.

  35. #35 herr doktor bimler
    January 1, 2012

    In the unlikely event that there are virologists out there with spare time on their hands… the usually-reputable “Behavioral and Brain Sciences” journal has put out this paper, inviting commentary:
    http://journals.cambridge.org/images/fileUpload/documents/Charney_BBS-D-10-00240_preprint.pdf

    The author seems to be keen to announce a new neo-Lysenko paradigm of human inheritance, and to that end he has cherry-picked the literature looking for any discrepancies from the neo-Darwinian consensus. Among other things, he is under the impression that ERVs in the human genome are vigorously rearranging chromosomes within the course of individual brain development… so that each neuron in your hippocampus ends up genetically different from all the others (“ongoing retrotransposition resulting from neurogenesis in the hippocampus”).
    is this paper as dubious as it seems to me?

  36. #36 John
    January 2, 2012

    RRM, I contacted the lead author of the ‘XMRV’ cytokine/chemokine profile study and was told that not all patients came from the Incline Village outbreak, although some of them did if I remember correctly, and that that description was mostly about another study in the presentation. In an interview though, he did say that the patients were selected prior to XMRV’s ‘discovery’, therefore a patient’s putative XMRV status had nothing to do with their inclusion in the study.

    On a side note, I’ve basically forgotten the amount of logical fallicies and/or misunderstandings that have been introduced since the beginning of the whole XMRV debacle, but it would be neat to do a compendum of XMRV fallicies. For instance I just read on the messedupforums where someone was still going on about how ‘XMRV status’ changes from day to day, with this person apparently still not realizing that this is much more indicative of sporadic contamination than genuine infection. Like how if you were to test and test and re-test samples, as the WPI was reported to do, yet not count the negatives and once a sample tested positive then that individual was then placed in the positive category, of course you’re going to have higher rates of ‘positivity’ in patients than controls. I don’t recall ever hearing any mention of WPI testing controls in this manner, ie over and over and over. The fucking sloppiness of the whole thing is just astounding.

    On another side note, here’s a public service test for individual irony meters. Can anyone guess what pre-emptive rebuttal has been readied for takeoff by individuals who are preparing to ignore the results of the Lipkin XMRV study? You can take your time and think about it, because it’s pretty rich. The pre-emptive rebuttal against the likely-to-be negative results from the Lipkin study is that ‘no single study can ever be called definitive’, ie one needs to look at the broader evidence base when interpreting scientific findings instead of relying on the results of a single study. Enjoy that little caramel with your morning cup of joe.

  37. #37 RRM
    January 2, 2012

    @John

    Thank you for the information.

    It doesn’t add up though. Yes, they discussed two studies in one presentation, but the slide about the cohort being from the Lake Tahoe cohort came before either one of theese studies. Moreover, this slide specifically stated (emphasis mine):

    Between 1984 and 1987, a cluster of 300 cases of
    CFS was identified in Incline Village Nevada.

    [..]

    For these studies, we isolated RNA, DNA and plasma From ~100 of this cohort at two time points Sept 06 and July 07

    I take it you have those slides (I might even stumbled upon then through you), but here is that presenatation again:

    http://www.wpinstitute.org/news/docs/Invest_in_ME_20090529_Mikovits.pdf

    - Slide 3 is about the cohort
    - The cytokine study starts at side 15

    Like I said, it doesn’t make much sense. And in the light of their other cohort controversies (e.g. the Dutch group reporting the Science cohort was also from a single outbreak, and the possible inclusion of patients with cancer in that study), I simply don’t believe them anymore.

    I mean, when you look back at the retracted 2009 study:

    - Mikovits submitted an abstract in 09/2009 about a study showing XMRV to be associated with CFS and cancer.

    - The Wall Street Journal (ADM) reoprted that in July of 2009, “Dr. Mikovits also presented preliminary data showing that 20 patients of the 101 in the study have lymphoma, a rare form of cancer”.

    - Peterson presented in late Oktober of ’09 that several patients from the Lombardi study had cancer.

    - When the CAA started researching this, Mikovits came up with a story that re-blinding of samples (to already existing patients?!) had confused everyone, apparently including Peterson.

    Why didn’t Mikovits check Peterson’s slides beforehand, or at least tell him she had changed patient numbers? Perhaps Peterson had already communicated information about the study’s results to patients according to his understanding of the patient numbers?

    Like I said, it doesn’t add up and I wouldn’t be surprised if the patients of this study were similarly “relabeled” to existing Lake Tahoe patients.

  38. #38 daedalus2u
    January 2, 2012

    herr doktor, no, it is pretty much correct but over-hyped. Way too much effort at trying to incorporate failed and non-physiologic ideas like Lysenko, and way too much hype about changing paradigms and a Sokal-like incorporation of quantum mechanics and relativity.

    Maybe some people believed the straw-models he is tearing down were absolutely true and correct (actually some people did and still do and will fight for the rest of their careers to preserve their misconceptions about genetics, disease and evolution, but I don’t consider them to be “real scientists” no matter what their credentials), but real scientists only ascribed tentative and contingent validity to models.

    People have assumed way too much, and still do. People have assumed that the genome in each cell in an organism is “the same”. Real scientists might take that as a premise, but realize it is a premise and something that at some point needs to be tested. Now that it is just starting to be tested, low and behold they are different. Real scientists say “ok, what does that mean”? Real scientists don’t need to tear down paradigms they never had and never used.

    Using metaphors like Newtonian Physics, Quantum Mechanics and Relativity to describe how to understand biology is simply muddled thinking and wrong.

    It has been the massive over-hyping of genetics that has lead to the current state of attributing everything to genetics and using GWAS to find the genes for XYZ. It isn’t that simple, but the gene jocks said it was and they now have been pretty much discredited because they can’t find “the gene” for condition XYZ.

    If the brain is mosaic due to retrotransposition in neural cell precursors (and it is very likely that it is), then a genetic approach to neuropsychiatric disorders is not going to be successful.

    People are not going to like this because it pretty much proves that intelligence is pretty much non-genetic. Yes, genes are important, but if you don’t have a “broken” genome, then the genetic details don’t matter much. The racists and bigots are not going to accept that intelligence is not genetic, intelligence is not race-based and that people with brown skin are not intellectually or genetically inferior. So what else is new?

  39. #39 Jack
    January 2, 2012

    TWiV was pretty cool in it’s round-up of XMRV/CFS/MLVs I thought:
    http://www.virology.ws/2012/01/01/twiv-164-six-steps-forward-four-steps-back/

    Rich seems to have tracked down some further detail (or rather the only detail) regarding the ‘Lipkin Study’ on NIH Reporter I believe something about ‘north-east bio-defense centre’ and it being tacked onto another of his studies?

    It’s been particularly difficult finding anything out about this study as it hasn’t been through the normal review process or revealed in the normal places. Anyway, I have requested a link.

  40. #41 herr doktor bimler
    January 2, 2012

    Thanks, daedalus2u.

  41. #42 TCC
    January 12, 2012

    I’m late for the party…but Lombardi and Lo/Alter studies being retracted is cause for celebration…Happy New Year, everyone!!
    I think a few prostate cancer studies should also be retracted ASAP, starting with Urisman et al and the Ila Singh PNAS paper.

  42. #43 TCC
    January 12, 2012

    I’m late for the party…but Lombardi and Lo/Alter studies being retracted is cause for celebration…Happy New Year, everyone!!
    I think a few prostate cancer studies should also be retracted ASAP, starting with Urisman et al and the Ila Singh PNAS paper.

  43. #44 Jack
    January 12, 2012

    @TCC you happen to have seen this from Nature Reviews Urology: http://www.nature.com/nrurol/journal….2011.225.html
    Karen Sfanos et al. review the XMRV and Prostate work along with XMRV/MLV/CFS. Only became available yesterday.

  44. #45 TCC
    January 12, 2012

    @Jack#44
    Yes, I agree with this paper on all major issues. There are a few papers that showed positive evidence for presence of XMRV, which strongly indicates contamination from 22Rv1 cells. I think these papers should be retracted to correct the literature. The authors that retract first and voluntarily win by saving their reputations.

  45. #46 Jack
    January 12, 2012

    @TCC It is interesting – is it not – that Silverman has thus far made no comment about his XMRV/prostate work. Of course the retraction he made in the Lombardi paper is different and maybe he is working on those other findings I suppose – scientists as a rule are a quiet bunch aren’t they? Still I would have thought he might have spoken out about it by now. Maybe Sfanos has kicked the ball rolling…guess we shall have to wait and see. But then the XMRV/prostate cancer work was not as ‘in your face – scary – exciting’ as the Lombardi association was it?

  46. #47 TCC
    January 14, 2012

    @Jack…
    Retracting a paper must be a painful experience…I think Silverman and others would probably do nothing and hope they can just go on with their lives without having to retract, regardless of what they now think about the prostate papers. They will say nothing unless there is external pressure from the science community, editors,coauthors, etc…..
    I think it’s not that scientists are too shy or polite, but this is just not a high priority….not much to gain and plenty of time wasted if you get into a pissing contest…