Discussion in 'XMRV Research and Replication Studies' started by Alistair, Jun 1, 2012.
Lipkin Study (deep sequancing) to be published on 30th of June 2012
I don't think it's the deep sequencing study, but the multi-lab XMRV/MLV study.
From invest in ME conference. Twitter
#MELondon Peterson talking about the Lipkin XMRV/MLV study. It's completed. Will be released on June 30th.
Wow! 29 days to go. I hope they have some good news for us?
I wonder what sort of response we'll get from Mikovits if it's negative?
I'm assuming that it will be based on past studies, and the lack of urgent action that I'd have expected if they had come up with a clear positive result. This could just be me engaging in tea leaf reading though.
We can only hope she keeps her integrity. But given her previous statements and previous actions I'm afraid she'll take the martyr route.
She is rather boxed in at the moment with litigation pending. Also, she had to sign an agreement to support the results of the study to be allowed to participate. Lipkin must have not thought she was acting like a martyr as he had her participate in the study.
Great to hear that we get to hear the results of this study. Im more excited about the next one, because i think the results of this study are more predictable, but who knows? We dont really till we see them. Feel like we have waited for *ages*.
If its negative, then what Mitkovits does wont matter much I guess. Too late to turn anything around if it is negative IMO.
To join in the speculation, one of JM's last public utterances on XMRV was about this study where she said something like 'Well, if we can't find it, we can't find it. That's science".
Also, she may have been influenced by Lipkin who in part made his name identifyingBorna Virus (I think) which was subsequently linked with a whole load of diseases, including autism. Lipkin recently published a blinded study which failed to find any association between said virus and said diseases, and said something to the effect that he was disappointed 'his' virus wasn't associated with any human disease, but that's science for you... [I posted this biton another thread, can't find it now]
Isn't June 30th a Saturday?
Hi Firestorm. Do they not release a studies on a Saturday? Big plans for that day?
Is it standard procedure to have scientist sigh a paper that they have to agree to go by the findings? Is this a specific case? I wonder if this is even true?
i'm sure I saw a quote from Lipkin somewhere saying that unambiguously endorsing their own results was a condition of entry to the study for all researchers, along with a committment to publish the results.
I just assumed everyone knew about this information:
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.
W. Ian Lipkin, MD
Director, Center for Infection and Immunity
Barb C. :>)
So if the study is negative they have signed to say they stand by this.
.....I guess that doesn't include all the other scientists out there who are also finding MLVs in people. So if the study is negative those other scientists out side of the study will maybe want further research.
It doesn't stop them from doing further research, VillageLife, or from having further theories about MRVs.
It just means that they have to say that they don't dispute the results of that particular study.
Basically, it just stops the researchers bad-mouthing the findings of the study, and the methodology, after it is published.
Reposted from another forum with permission from Asleep:
My view on the Lipkin "XMRV" study is one of strong suspicion and skepticism. I will preface this by saying that I am hopeful that he will produce a quality study that provides scientific answers and isn't swept into town in a tsunami of self-righteous political triumph. But I would be shocked if he actually does.
The main problem is that everything Lipkin has said and done to date with regard to this study is indistinguishable from astute politicking aimed at ensuring that this study seals off this line of research once and for all. I'm not saying that this is definitely the case, merely that Lipkin has yet to do anything to logically preclude this motivational possibility. Through a lens of such politics, all of his "maverick" actions are perfectly coherent:
** Carrying on with the study in defiance of criticism: The negative faux "replications" and the BWG didn't successfully put out the political fire, so another study is necessary. However, it must be carefully framed as the final word (an absolute nonsense concept in science) and conducted by someone who has delicately jockeyed themselves into a superficial position of agnosticism. Despite patients being admonished endlessly about "following scientists instead of the science," it is hoped that they will in fact follow someone down a path of corrupted science based solely on his appearance as caring and even handed.
** Getting Mikovits and Ruscetti involved: This is necessary to give the appearance of actually trying. Someone who accepts the carefully cultivated image of Lipkin's agnosticism would likely to a double-take at any attempt that entirely excludes the primary proponents. The narrative key is to have them "involved," even using their own tools and methods, but to remove crucial elements of the process from their control (in this case cohort selection; sample collection, processing, coding; overarching study design and analysis).
** Saying a number of "open minded" things about ME: Words are free and never warrant suspension of skepticism prior to actions (in this case the actual scientific quality Lipkin produces with his study). In fact, the use of hopeful words to prime the populace for destructive action is a timeless political tool, a "fig leaf."
Again, I must stress that I'm not accusing Lipkin of being motivated in this way, nor am I attacking him. I am simply pointing out a possible motivation that is entirely consistent with what has been said and done thus far. It won't be until his study is published that we will be able to evaluate the integrity of his actions and words. It is entirely in his hands to produce research that is rigorous, logical, and measured in its conclusions.
There are, however, a number of aspects to this study that would suggest this political motivation is more than a mere possibility:
** Requiring participants to pre-accept results in order to participate (i.e. gagging them): It's hard to imagine any legitimate reason why an honest study would require this. It reeks of a totalitarian attempt to control the message after publication and marks an effective continuation of gags on Mikovits.
** The very nature of the study: Why yet another "do-or-die" test under novel conditions? This is akin to demanding that because someone claims evidence of a novel phenomenon, they must immediately know enough about it to always reproduce it under any conditions presented to them. Yes, blinded and controlled reproducibility is crucial, but not at square one of understanding (unless, perhaps, your goal is to exclude additional understanding...). I think that the only honest approach to get to the bottom of things at this point is for Lipkin to sit down with Mikovits and Ruscetti and see what they are finding and then work closely with them to flesh out the many unknowns surrounding these possible viruses (e.g. better contamination controls, better understanding of viral life cycle and tropism and reservoirs, better understanding of the role of collection and processing, better understanding of methodological nuances and sequence variations). If they cannot find some agreed upon explanation such as contamination, they can at least acquire enough understanding to devise a blinded test that will reasonably control for these current unknowns, which necessarily plague this Lipkin study. Interestingly, this is the precise approach that DeFreitas recommended to the CDC, which they declined due to the cost of a plane ticket. Yet surprisingly the CDC found the funds to force upon her a series of eerily similar, premature, CDC-controlled "do-or-die" tests that "disproved" her finding.
** The secrecy of the design: Obviously the details will be known upon publication, and any criticisms levied thereafter. Obviously the study cannot begin until the design has been worked out, so why not release the details ahead of time, especially if (with a straight face) you intend it to be "definitive"? Wouldn't you want to tidy up any overlooked loose ends before starting, as it would be laughable to genuine scientists to hear of a fatally flawed study being sold as the last word? The reason for the secrecy cannot be that Lipkin is ensured of producing a flawless study and therefore it would be pointless to air the details publicly, as that would imply that the whole peer review process is unnecessary. Is the canard about "that's not the way it's done" so deeply entrenched that it cannot be put aside to make sure this all-important study is robust? Or is it just easier for criticisms to be conveniently lost in the media frenzy that will accompany a negative study?
** The possibility of this study being used to discount all retroviral involvement: In Lipkin's letter from last December, he says the study will "address the question of whether a retrovirus is associated with disease." There are already serious questions about whether this study will even adequately look for relevant MRV sequences (see below), which is a small subset of all retroviruses. The question of whether a retrovirus is involved is far far beyond the scope of this study, esp if they don't do extensive testing for reverse transcriptase, extensive searching in non-blood tissues, and extensive, unbiased deep sequencing. If the study is negative, I fully expect many "lazy" media articles to "accidentally" state that the involvement of a retrovirus has been definitively ruled out in ME.
From the perspective of patients, there is only one outcome of this study that could be devastating. That is if MRVs are involved in ME and this study renders research into this area politically infeasible and scientifically suicidal, as it would mean there will never be full understanding of or a reliable treatment for the root cause. It's far worse to seal the only path to freedom than it is to wander a bit further down a dead-end. Unfortunately, the Lipkin study seems poised to deliver this nightmare.
I think it's also worth considering some of the extraordinary implications if this study is actually positive. It would mean that Fauci (who has presided over decades of government negligence in this disease), following years of successful legal, political, media, and pseudo-scientific attacks on this finding, has inexplicably allowed his star pupil to reveal the truth just before the political finish line. It would mean unavoidable realization by the public (in an election year no less!) that not only is there a new retrovirus loose in the population, but that it has been negligently allowed to spread and destroy lives for decades by the government health agencies. It would mean catastrophic cost escalation for health insurers. It would mean that the BWG and many of the negative studies would almost have to be investigated for fraud. It would mean a fall from respectability for many of the "top" retrovirologists. It would expose the psychobabblers for what they truly are. It would mean very uncomfortable questions about viral origin and government knowledge. It would force a re-evaluation of all of the previous "rumor viruses," thus exacerbating all of these other issues. Simply put, it cannot be allowed to happen.
Lastly, I want to enumerate just some of the open questions that would have to be left on the table if this study is negative and successfully sold as "definitive":
** What about issues of cohort selection, sample collection and processing, viral life cycle and tropism adversely affecting the study? After all, the BWG failed in its duty to better elucidate these issues, so they now represent unknown variables in Lipkin's study. When you don't even know what variables you should be controlling and accounting for, your conclusions are wholly unreliable.
** What about novel sequences found by Hanson, O'Keefe, the Lithuanians, and Grossberg? None of these are close enough to VP62 to be simply written off as contamination, so leaving them unexplained (and likely un-searched-for in Lipkin's study) shows an extreme lack of scientific ingenuity.
** What about Mikovits's unsequenced isolates? It seems laughably disingenuous to claim that something is not there when you haven't even bothered to take a small step (sequence the isolates) to identify precisely what you're even searching for (the ME virus sequences). Not even Judy knows at this point exactly what sequences she found originally.
** What about Dr. Snyderman's results? If Lipkin is the maverick some claim, and the deep sequencing expert some claim, and he's serious about getting to the bottom of this disease, how could he possibly not take on such a straightforward case that others have turned down out of fear?
** What about an ARV clinical trial? Putting aside all the disingenuous "concern" from non-patient onlookers, it would be completely trivial to find very willing volunteers. Dr. Snyderman's data alone is more than was necessary to launch trials of Rituximab, a far more dangerous drug.
** What about the PC and BPH results? If the ordained ministers of Science have proclaimed that MRVs don't exist in ME, it would be rather incongruous for these studies to persist.
** What about searching for reverse transcriptase? Seems odd to say you found no sign of RVs when your search was limited to specific--but unknown--sequences and never extended to more generic markers of RV infection.
** Why has no attempt been made to test tissues? Evidence from the macaque study as well as behavior of MRV-like viruses in other animals would strongly suggest that blood is not the ideal place to look, esp until more is understood about the virus.
** What about all of the still-unexplained non-PCR results (serology, IHC, FISH)? These cannot be simply written off as contamination, and the explanations to date (cross-reactivity, etc) have not be supported by anything other than desperation and guesswork.
** Philosophically and practically, could the axioms of modern retrovirology ever permit the discovery of a slowly replicating exogenous retrovirus with some vague semblance to human or animal ERVs? I believe this is essentially the question that anciendaze has been positing for some time. In essence, the axioms and assumptions that rule the field exclude any MRV-like virus from ever being "found" in humans as any MRV-like virus would have enough similarity to endogenous sequences and be close enough to limits of detection to always be reflexively dismissed as contamination.
Doesn't fit Gerwyn's model since 'when' is never invoked on MRV's, HGRV's or pathogens such as a retroviruses.
From another post:
The XMRV study will NOT be published on June 30. Rumors associated with this release date are false.
We have begun composing the manuscript/compiling the data. Follow @CII722 for updates. Cheers!
It was reported at the #CFSACmeeting that the XMRV results will be published as a white paper in a few weeks. Can you confirm?
@CII722: Another false rumor. XMRV paper will be peer-reviewed. Will announce on Twitter when it is submitted/accepted/published.
*Update 12:25pm – The Center for Infection & Immunity contacted via Twitter to clarify:”Hi! 2 corrections. Our Twitter is run by the CII’s science writer, not Dr. Lipkin. More accurate to say “the CII tweeted” & “CII’s response”
**Update 6:14 pm – Dr. Lee a the timing of the results she responded, “I do not know when the XMRV results will be released. I too have heard conflicting information. It will happen when it happens. I must have patience.”
So there is apparently confusion as to the date of release and in what format.
The way you've posted your comment to Asleep's post is confusing, Eco. It makes it look like your words are integral to the post, and you've just bolded, which is not the case.
I don't think Asleep's English, I am though, but nationality is irrelevant anyway
This is an opinion piece, an opinion that is shared by many of us. Of course there is no proof - it wouldn't be very astute politicking if there was.
Asleep says The narrative key is to have them "involved," even using their own tools and methods, but to remove crucial elements of the process from their control (in this case cohort selection; sample collection, processing, coding; overarching study design and analysis).
We have no proof either way, your statement is not backed up either.
It's really hard to know what is truth and what is spin sometimes. The full paper will help us to unpack the details, of course.
DeFreitas was crucified. I'm sure Lipkin knows what he's doing, we're not so sure, but will be delighted if it turns out that this was an 100% honest scientific endeavour, totally open and above board.
There is no proof of conspiracy unless proof is shown. We are not talking proof here, rather concerns and possibilities.
Who knows what goes on? We do know that there is still a civil suit outstanding against Mikovits. Thank heavens the criminal case was dropped. Dangerous field to be working in, no? Vis DeFreitas, as above.
Is that Him as in God or him as in Grossberg? He did name his sequence as a murine leukemia related gamma retrovirus. No idea what it's called now. What are you describing as XMRV?
(re Snydermans results - this is the earlier info)
Scuse us for speculating. Is that not allowed? It is indeed curious though, that a senior oncologist with CLL should gain so much remission from his ME aka CFS by taking anti-retrovirals. It is a shame that this has not been followed up. I do hope someone picks up Dr. Snyderman's banner in the future.
The Morris/Maes paper you are referring to does not rule retroviruses either in or out. It is neutral on that subject. Here, we are talking about the Lipkin study. This is a separate matter.
Yes, we know that Peterson was either misunderstood or was wrong re the release of the Lipkin study, on 30th June. It will be as it is. I do hope they publish open-access.
Bottom line: If any of the researchers participating in the Lipkin research study, voiced any concerns regarding any of the issues raised by Gerwyn/Asleep comments above in reference to the Lipkin study, then they had the obligation to object and state those objections publicly. Furthermore, they then should have refused to participate in this study. No one forced them to participate. To date, I have not encounter any objections by any of the researchers on this project.
Separate names with a comma.