Have You Been Served?
Two years ago, when Science published the first study linking the retrovirus XMRV to ME, how many of us yearned to fast forward a few years to see if Dr. Judy Mikovits’s findings would be validated and the cause of ME finally nailed, as we hankered to do 20 years earlier when Dr. Elaine DeFreitas published her landmark study linking ME to another retrovirus?
This heady time around no one could envision the spate of nightmarish events that have been plastered in the media since October 2009: shouting contests on both sides of the Atlantic about the rightness of this study or that study and intimidating researchers in Europe and the U.S. for daring to research the retrovirus XMRV, until they switched sides, washed their hands of ME or were booted out of research altogether.
Blood Working Group
More recently was the failure to distinguish patients from controls in the Blood Working Group's XMRV study, and the relabeling of slides, which caused an uproar. That was followed by a spate of jaw-dropping disclosures, for which I've coined the phrase "the specificity of the crazy"—though that phrase applies to much of ME research during the past 30 years. As many readers know, according to court affidavits by Mikovits's research assistant Max Pfost, Mikovits asked him to take documents from the Whittemore Peterson Institute (WPI), which he stashed in a Happy Birthday bag. His affidavits also state that Mikovits hid out on a boat to avoid being served with papers from WPI and that the duo created secret email accounts—an oxymoron if there ever was one.
Then, during Thanksgiving week, in a quintessential Upstairs, Downstairs moment, WPI gave public thanks for getting back most of its property.
British researchers Simon Wessely and Myra McClure, who published a negative XMRV study, and the CDC, which did the same, must be licking their lips as they watch the critical XMRV players implode in the media. Under extreme stress, many people become reptilian, but still…. To paraphrase singer Annie Lennox, how long can the ME community go on living in this same sick joke?
Pulling strings
Scientists are supposed to ask: What do we think, what do we know, what can we prove?
I don’t know what to think about most of these events—let alone reflect on what we know and what we can prove. At this point, there are far more questions than answers. Here are some of mine: After working several years on XMRV, did anyone at the Whittemore Peterson Institute know that there were reliability issues with the XMRV assays before the Blood Working Group began its studies? After all, when you conduct scientific experiments, you check known positives at the same time to make sure everything is copasetic.
Another question: Who was pulling the strings? Did Mikovits see a problem early on—perhaps even before the Science study was published? If so, did she share her concerns with Harvey and Annette Whittemore or Daniel Peterson, or did she sweep her disquiet under the proverbial carpet? And if Mikovits voiced unease, what was the response? Did they insist she soldier on, and they’d all figure it out in the rinse cycle—or could that have been, perhaps, Mikovits’s expectation? At any time was there deception? Was there self-deception?
Do the right thing
Contending that the retrovirus is hard to culture from blood is reasonable, but how long can you then confidently rely on that assay? You have to develop an antibody test that works consistently or a better way to find the virus—or something. You have to take a step back and figure it out—because if you don’t, the problem will bite you in the ass—and not in a good way. And with this disease the bite always seems to be particularly vicious, the kind that leads to, say, a methicillin-resistant staph infection, several years in the wilderness, and slashing ME’s already dangerously low street cred.
What should the key players have done if they knew there was a problem? A psychiatrist friend of mine is fond of saying: “Unless someone is planting a cattle prod to your genitals, you walk away when someone is pushing you to do something you find objectionable.” You stand up, you refuse, you do the right thing.
Could that be why Dr. Daniel Peterson left the Whittemore Peterson Institute so abruptly—back when things were ostensibly going along swimmingly, only a few months after the Mikovits study was published? He wasn’t a bit player in this yarn: He’s the Peterson in the Whittemore Peterson Institute. None of the explanations for his abrupt departure have made a whole lot of sense, at least to me.
Intellectual property
Why did Mikovits want her notebooks and other data that research assistant Max Pfost allegedly took at her request? Did Mikovits believe the materials belonged to her? Indeed, Mikovits attorney Lois Hart told Science reporter Jon Cohen, “She [Mikovits] is entitled to a copy of the information she created.”
According to law, does that data legally belong to Mikovits or WPI or to both? In the U.S. and Europe, the institution usually owns the intellectual property, though every contract is different. (In Japan, it’s usually a 50/50 split between the institution and the inventor.) Is keeping a copy of the material different from owning the material?
Did Mikovits or WPI want the material to continue the current research, or to foster other important scientific discoveries and to help patients? Did Mikovits want the data to prevent WPI from continuing its research? Does the WPI want to prevent Mikovits from continuing her research? Where, exactly did the XMRV research go wrong—and is the key to it all in those notebooks? What role did money have in all of this? What role did fame play?
Who the hell knows.
Versions of the truth
In a November 11th post on the Wings of Hope blog, Annette Whittemore wrote: “WPI immediately asked to have the materials returned, but to no avail.” If the Whittemores made that request, how did Mikovits and her lawyers respond? What other options could the Whittemores and their lawyers have utilized short of humiliating Mikovits and leaving her to stew in jail for five days without the possibility of bail? Did the Whittemores need to resort to Draconian measures?
Or did the Whittemores have the fiduciary duty to report to the police that property was taken from its institution and once they did, was the chain of events that followed pretty much out of their hands? Did the Whittemores consider the negative repercussions of putting Mikovits in jail on scientists interested in studying this disease, in the press and on the patients?
Or did the Whittemores have the fiduciary duty to report to the police that property was taken from its institution and once they did, was the chain of events that followed pretty much out of their hands? Did the Whittemores consider the negative repercussions of putting Mikovits in jail on scientists interested in studying this disease, in the press and on the patients?
I want to know the answers to these questions, instead of blindly pledging allegiance to anyone’s version of the truth. As I’ve commented on this blog in the past, and with apologies to Voltaire for messing with his quote, reason consists of seeing things as they are, not how we want things to be.
However you cut it, the last few months have been a terribly sad coda to such a promising start. I think of all the excitement, good will and hope that floated up the day the prestigious journal Science published Judy Mikovits’s study. Judy Mikovits, Daniel Peterson and the Whittemores seemed an invincible team. But most relationships end, and many end badly—though most not as badly as this. As Dr. Phil is fond of saying, “The person you marry isn’t the same person you divorce.”
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I don't think the Whittemore's have given a thought to how their actions would be negatively portrayed to the patient community, neither do I think they care. Care of patients left the institute with Dr.Mikovits.
ReplyDeleteThis has been proved time and time again by the refusal of the WPI to openly communicate with the patients.
They gave us hope then snatched it away in the most cruel way.
Agreed. I too have been watching all this play out. Without having access 24/7 like a fly on a wall I cannot begin to know where allegiances (if any)should lie at this time. I'd love to have the answers to these questions....I wonder if they will ever be forthcoming?
ReplyDeleteThere are some questions I do not have to ask because I know enough about at least one of the people involved. Mindy has no answers to these questions. Neither do I. But I know that Dr. Judy Mikovits has integrity and has only ever tried to help people, in this instance, people who suffer from M.E.
ReplyDeleteI trust her and I know that she did nothing for personal gain. I cannot say the same for the other people involved.
Modify message
WPI are still looking at retroviruses.
ReplyDeleteAnnette w recently said on the news....
"Is there just one XMRV or are there several?"
Thank you Mindy! I've always appreciated your calm and rational approach in reporting...I appreciate it even more, now - amidst the total chaos the ME patient community is facing! With your specificity of the crazy, you've just about covered all the possibilities. I want the truth too, and "Do the right thing" is a phrase I cant get out of my mind - its helped me to reach my own limited conclusions. This is an awful episode in the history of ME (shameful, really...and stunningly unprofessional, on so many levels) - I hope doing the right thing eventually takes center stage with ALL the "players" in this life and death drama affecting over 17 million people worldwide - while there is still time for honor to be redeemed. IF there is still time...j. nance
ReplyDeleteWhat role do the real bad guys have in this?
ReplyDeleteMindy, the questions you ask are reasonable ones. I know that all of us wish we had answers. All I can say from my fifteen years as a lawyer is that in most disputes there are two versions of the truth, some of which agree, and others which don't. The ME/CFS and autism community both deserve answers and treatments for these very serious illnesses and the medical community has been very slow to do meaningful research. Even with all of this being said it still seems like a retrovirus explains a lot of the health problems of our two communities. The current situation is painful to watch, almost like watching two parents go through a very bad divorce. For the sake of everybody I hope they come to a quick resolution of their current difficulties.
ReplyDeleteAll the best,
Kent Heckenlively
"I want to know the answers to these questions, instead of blindly pledging allegiance to anyone’s version of the truth."
ReplyDeleteMindy, I cannot thank you enough for saying that. My precise sentiments.
We will probably never know the answers as 99% of the media has no knowledge of the events concerning M.E. these past 2 years. The only ones who know all the sordid details are us. Until we find a way to bring all this to the worlds attention, we're just going to have to continue on with blind hope. Jimbob
ReplyDeleteHi Mindy,
ReplyDeleteYou raised the issue of the reliability of the XMRV assays, as brought into question by the BWG study, and as raised by Judy Mikovits prior to being fired. But I don't know if you are aware that we are not talking about one set of assays. There were in fact two - those run by the WPI research team, which were used in the 2009 Science study, and those used by the clinical lab (VIPDx) run by Vincent Lombardi. It is important to note that the assays whose reliability have been questioned by different parties and those primarily called into question by the BWG were Lombardi's, NOT those of the research lab by Mikovits (which had been developed by Mikovits along with Frank and Sandra Ruscetti). The VIPDx assays were supposed to use the identical protocol, but there is now uncertainty as to whether they actually did, and even in they did they needed to be independently analytically AND clinically validated; we have yet to hear definitively from the WPI about the latter. Mikovits and a few clinicians who had patients tested at VIPDx became concerned that the VIPDx assays or their execution might not be reliable, yet Mikovits was never allowed to review any of VIPDx's assay validation data, protocols, test result breakdowns, etc. The BWG panels, to my understanding, were conducted mostly by the clinical lab under Lombardi, using protocols over which Mikovits had not been allowed oversight (I still don't know why all the BWG samples were not tested by the research lab instead). It seems that the inconsistency in the subsequent results confirmed her fears about the assays, and she insisted that they be immediately withdrawn from commercial use.
Another important point is that the BWG itself had a flawed study design and execution (for instance, potential problems with sample processing that could negatively impact detection were apparent in Phase II remained unresolved), and that there is a likelihood of de novo contamination from the BWG samples themselves. It is unfortunately issues like these which have been swept under the rug, and the BWG only raised more confusing questions that should have been resolved in a scientific manner rather than being ignored, as they were. As a result it is hard to know what really went on in the BWG or at VIPDx. The decision-makers of both the WPI and the BWG chose not to properly investigate these issues, with the result that it will be very difficult for us to ever learn the truth in all cases. The VIPDx assay reliability can only be addressed now through a thorough independent quality assurance review of the lab, including the review of notebooks and any other materials and data necessary to demonstrate the clinical validity of those assays. A mutual disclosure (i.e. by BOTH Lombardi/VIPDx and Mikovits) of who tested what in the BWG may also be helpful, though as I mentioned the BWG results cannot be seen as perfectly reliable themselves. The real answer to all questions of assay reliablity lies where it always has - in a true replication study.
As far as I know: Judy Mikovits was ordered by the law to stay in the county – she didn't. She went from Nevada to California, and even if it is only a short distance, those responsible for law enforcement had little choice, as she was formally running from justice. If this is how it happened, then it was a really really stupid thing to do and she has mainly herself to blame for getting herself into prison.
ReplyDeleteAnd whats with the claims by Judy that she didn't took/didn't had the material? She knew who had the material, as it was her who asked that person to take it! From my point of view, she was lying – your milage may vary.
Not that I think that the material are of any use – that the WPI believes the material is useful doesn't make it so…
Why are you speculating on the clinically validated Lombardi assays? Will you be reporting the terrible errors in the BWG paper? No Trizol used with the PBMCs, controls PBMCs not pre screened, 22Rv1 in the CDC lab with some collection tubes, Lo's team using the failed assay from Lo et al?
ReplyDeleteResearch into MLV-related viruses is on hold while this property claim is sorted, it could take decades. That is unnaceptable.
@Tony
ReplyDeleteMikovits had left Nevada weeks before any civil or criminal case started. Try getting your facts straight. You also don't know what materials have been returned and who returned them. Nor do you know who own any materials relating to the research. Your silly comment about the usefulness is pathetic. What would you know?
"I want to know the answers to these questions, instead of blindly pledging allegiance to anyone’s version of the truth."
ReplyDeleteYou mean unlike your reporting during the last 2 years?
Seriously, I don't mean to be glib or snarky, as it would truly be refreshing and very much appreciated if you were more objective. Ever since the paper in Science was published, your columns have instead have pandered to the most desperate among us, and been very biased towards Mikovits, as even this one leans.
I sincerely hope you'll be a lot more objective in the future.
Respectfully,
Rebecca
“However you cut it, the last few months have been a terribly sad coda to such a promising start. I think of all the excitement, good will and hope that floated up the day the prestigious journal Science published Judy Mikovits’s study.”
ReplyDeleteTherein is the very block to getting to grips with the answers that are posed in this Blog. Science magazine may be ‘prestigious’ but the articles it publishes are only as good as the research on which they are based, even the old duffers at Science occasionally pick a turkey. Lombardi et al by no means impressed everyone and it was a very long way from being ‘promising’ in terms of relevance to M.E/CFS. The process of science is not predicated on ‘good will and hope’ which frankly sound more like religious characteristics than reasoned thinking.
Even if people were excited by the 2009 article, had there been a modicum of respect for the processes of science rather than a religious fervour for Mikovits and Whittemore as some kind of saviours, then by 2010 it would have been obvious there were fundamental problems with the WPI research and in all likelihood the WPI itself. That 'Lombardi et al 2009' didn’t pan out is not a problem, science as process absorbs wrong directions all the time, everyone just dusts themselves down, has a beer and moves on.
If the WPI, Whittemore, Mikovits, Lombardi and a proportion of M.E/CFS affected people (please remember some of us ‘told you so’) had not become unreasonably invested with the notion of XMRV/HGRV = M.E/CFS, then the Whittemore/Mikovits drama would be of no consequence to anyone other personalities involved in a workplace squabble. Certainly there are questions that need to be answered – but many of those questions have been relevant for at least 18 months. Self declared advocates who vehemently attacked anyone who raised those questions or denied the relevance of the questions, have culpability in prolonging misapprehension on the part of many M.E/CFS affected people over the validity of the WPI research, and of the robustness of WPI as an institution able to deliver the results that were unreasonably being promised. What M.E/CFS affected people need to do now, is not agonise over 'what might have been' because scientifically speaking 'it was never going to happen' the key thing is to learn and 'let's not do it this way again'. Even those who want to go down the HGRV route, need to acknowledge that a wholly new start is required and that, that is going to have to be without Mikovits or the WPI. For more "I told you so" see: http://cfsmirror.blogspot.com/2011/11/chronicle-of-embarrassment-foretold.html
great summary.
ReplyDeleteThe politics, the media, lack of authentic advocacy organization, and lack of governement support(funding etc) adds to the complication of research in our field.
Mark
"Your silly comment about the usefulness is pathetic. What would you know?"
ReplyDeleteSo you know? Then are you interested in some nice presentations about a pathogen of your choice? I will make them for you. With pretty images, nicely labeled. Just send me $500. I think you will find them equally useful as the work of either Dr. Mikovits or the WPI.
According to her lawyer Scott Freeman, Judy M is baffled by the criminal process and they will be arguing there was never any ciminal intent in taking the property.
ReplyDeleteand
He said any delay in producing the materials—which Mikovits initially denied having—stemmed from her failure to fully understand the workings of the legal system.
Pants. Fire. Or something like that, as you say in your country. Dr. Mikovits is serially misrepresenting reality. In my country we call this lying. In her defense, I would accept that she has deceived herself – confirmation bias can seriously ruin everybody's critical thinking. It happened to big minds. A little bit of fudging of data here. A little bit of misrepresenting of lab results. After all, we "know the *real* answer already". Wink, wink.
Only, the really big minds realized when they are doing this and correct their view of the world. It is sad to see when people are unable to critically examine their own work.
With the partial retraction of Silvermans full sequencing the only part of the viruses sequenced thus far is polytropic. That is also what lo et al found. Every other negative paper failed to look for the viruses Dr Ruscetti and Dr Mikovits found. They looked for a different variant called VP62/XMRV that has never been found in nature. All the negative papers also failed to clinically validate their assays, so for arguments sake we can say those asays do not work. In conclusion we have two papers that have the same finding in people with ME and no negative papers.
ReplyDeleteTony, In Vitro you need to learn the facts before you can have an opinion. It is a fact that nothing at all refutes the findings. When is there going to be a replication study?
Where are the new sequences that the WPI, now without the talents and skills of a principle investigator, were said to still be adding to the genbank?
ReplyDeleteWith regards to Dr. Mikovits' whereabouts, I have to correct myself. She was "was hiding out on a boat to avoid being served papers by the WPI." So she accidentally became a fugitive from the law, by "hiding" from the WPI she probably didn't get the notification from Washoe County.
ReplyDelete(I thought I have seen a reference, that claimed that she has apeared before a judge before fleeing the county – but can't find it…)
But as she had the material (as admitted now by her lawyers), she was actually guilty of what the WPI charged her. Not only that, she lied to the public when she claimed she didn't had the material. And all of you who "know" the "truth" fell for it. Yeah, how can we call her a thief! Truly, what audacity to say she had the material from WPI and lied about it!
All you anonymouses need to learn your facts.
She lied about possessing the material from the WPI. This is not the first time, in her work she "misrepresented" a image from the 2009 Science paper. I would not trust her to tell me what time it is.
From my point of view, Dr. Mikovits is more concerned with giving out "the right message", than with reality. And because she gives out a message you want to hear, you believe her. Again, confirmation bias, this time on your side.
And all the while she knew that the VIPdx tests for XMRV were worthless, still she talked about XMRV ("HGRV") without even hinting that it might be, I don't know, too early (or some other euphemism) for patients outside of studies to test for XMRV. So she can stand up to the mighty NHI and not address this? Truly, a heroine in our fight to find out what is causing our disease.
And you want to tell me, that I need to learn the facts? Yeah, right.
@ Anon. December 1, 2011 10:19 AM
ReplyDeleteEven were your assertions to be correct, no one who matters (i.e scientists ) are going to listen to you or anyone else who vocalises with such inanity.
Whichever side of the Whittemore/Mikovits squabble one chooses, there now exists for multiple reasons a huge credibility gap for both the WPI and Dr Mikovits. All the rest of science may be wrong, but with a body of people (scientists) who are going to make judgements on the basis of probability, the WPI and Mikovits have put themselves into ‘research Siberia’. For an article which effectively captures an ‘insider’ view see: http://arstechnica.com/science/news/2011/11/how-the-collapse-of-a-scientific-hypothesis-led-to-a-lawsuit-and-arrest.ars?comments=1&start=40 .
If there really is such a thing as an HGRV (as opposed to plain old ERVs), research that demonstrates such thing will need to come from an institution untainted by association with the WPI or Dr Mikovits, for that research to be widely accepted. The WPI has grant funding commitment from the NIH for a further 3 years, it may be that if the NIH agrees that the funded projects remain (post BWG) valid, then its just possible that with Lombardi in the lead that the WPI might be able to regain some credibility, although it seems unlikely. In the mean time M.E/CFS research is heading in other directions involving institutions that are well established and likely to gain credibility for publication based on their research. Continuing to ‘shout at the ether’, about how HGRVs are the answer is unlikely to engage much scientific authority.
The full answers to the questions above may never be known.
ReplyDeletePerhaps now is the time for the ME/CFS community to heal, abandon blame and move forward with the science.
Nothing in the past can be changed, but the future is still being written.
Mikovits has been said to have been on a boat, she may not have been, she was however found at home not a boat. How can she have been a fugitive when there was never a restriction on her movements? So what if she worked from a boat?
ReplyDeleteThe person or people who returned unnamed materials have not been named, neither has what Mikovits provided. Was it only a statement, we're there other materials? Besides who is entilted to the materials? We don't know. Mikovits hasn't misrepresented anything. Science used one gel and changed the labels to simplified labelling for publication. Those experiments were not even performed by Mikovits.
Mikovits didn't know if the ViPDx assay was clinically validated, but has asked for evidence that it is. The BWG suggests it is not, if it wasn't for the mess with contamination in the CDC lab and no controls being in the study. The Lombardi et al. assays are clinically validated. The assays we know are not clinically validated are those from all the negative papers. Good to know you are picking and choosing when this crucial step is required. Tony learn the facts.
I don't doubt that Judy Mikovits is well intentioned, even after recent events, but I can't subscribe to the blind faith and declaration of integrity shown by Wildaisy given how things are unravelling.
ReplyDeleteWe're working from snippets of information picked up from all over, and it may take time for the truth to fully surface. It does seem now, however, that the initial letter to the WPI refuting knowledge of the notebooks, was utterly dishonest. Reading it again I feel complete disappointment.
The WPI currently have their notebooks back, and Mikovits attorney is making the bizarre defense that the delay in producing the material was based on Mikovits failure to fully understand the workings of the legal system!? So yes, she had them and has now returned them.
Let's not forget that the Lois Hart letter was introduced to the cfs community by Lilly Meehan, who was 'outraged' and 'astonished' by the accusations, stating 'It is impossible for her to have stolen the items'. She then points attention elsewhere stating 'Patients need to ask themselves who had the motive to remove and destroy the notebooks. Who had a motive to remove incriminating evidence? Who stood to lose with the revelation of misappropriation of funds and materials? It was not Dr. Mikovits.' Unfair in hindsight, and it's not as if the militant members of the community need an excuse to go after the WPI and give them a good drubbing at the moment.
And on the tail end of this Lilly was publicising a 'legal defense fund for Dr. Mikovits' for people to donate to. Looking back, this makes me extremely uncomfortable and angry. I don't know whether Lilly was complicit, or perhaps not told the whole truth by her friend Mikovits. The fact remains that the community was asked for money while likely being fed untruths. Would we have been helping to support a dishonest legal defense had Max Pfost not torpedoed it with his affidavit? The whole thing stinks.
Two years ago we were living with so much hope. To think it's come to this circus.
Tony - "Hiding out" is a subjective characterization of motive as communicated in an affidavit by one of Mikovits former employees. We don't know how accurate the statements in that affidavit are, or under what circumstances they were collected. She could have just been on a boat because she has a boat and she was trying to relax after a couple years of dealing with this mess. Also a subjective judgement... the point is, maybe she was on a boat - but don't assume that her being on said boat was for her to "avoid" anything because there isn't any evidence it was.
ReplyDeleteThanks Mindy for sharing your questions on the not-unexpected establishment frenzy to discredit any retroviral link to the disease they refuse to admit is ME, on the absolute power they have to destroy anyone who finds evidence of any retrovirus in patients with ME, FM, Autism, Lyme Disease, Gulf War Syndrome, and probably MS. Then there's the "upstairs, downstairs" mentality of the WPI, the 1%, and their condescending treatment and villification of Judy Mikovitz, as thanks for making their 1% daughter well.
ReplyDeleteThe findings of Lombardi et al and Lo et al for polytropic MLVs (minus VP62 contamination) stand uncontested, JM's follow-up research is denied publication (its not the policy-based-evidence they prefer), but the rush of bad science negative "validation" studies and the political BWG "negative despite the positive results" study all accepted without question. The establishment always gets the results they want! Look at what they did to destroy Wakefield, yet the truth of his research is finally breaking through.
Tony Mach, like the establishment, is no friend of ours. He is only here to stir up trouble, because no-one cares enough to ever comment on his bland and misinformed blog. He claims to have ME/CFS, but on his entry about the ICC he admits he actually does not know who the authors are besides Klimas and Bell? That he has only heard the name of Kenny de Meirleir? Pffft! There's nearly 80 years of "facts" he appears to be missing. Helpful if you are on a witch-hunt to destroy the very caring Judy Mikovitz while conveniently ignoring the malfeasance of the establishment, and the upstairs lot burning so much talent so quickly.
There are so many questions we need answers to, but Mr Mach-o (?) can't think beyond his "burn the witch" mentality. 20 years ago they "burned" Elaine de Freitas, she has not spoken publicly since then. It would be tragic if Judy is to be consigned to history with a gag order, we simply cannot let this injsutice happen again.
Dangerous times ahead. Keep us posted Mindy!
xxx
The facts about what happened at WPI and what went wrong with the research there are not likely to be made public in the future. Neither Annette Whittemore not Judy Mikovits have any interest in disclosing any mistakes that were made by them or those they managed. The CFS/ME community will be left to speculate. The scientific community will move on with younger researchers having even more reasons to avoid the field. The Lombardi paper will never be retracted if that depends on Mikovits agreeing to do so.
ReplyDeleteWE NEED Tissue Studies and a Tissue repository. This leaves the Blood. Breaks through Blood Barriers. More studies...YES....more blood studies-No. Just my opinion. Julia Hugo Rachel.
ReplyDelete@ Anon. December 1, 2011 3:20 PM “Mikovits didn't know if the ViPDx assay was clinically validated, but has asked for evidence that it is. The BWG suggests it is not, if it wasn't for the mess with contamination in the CDC lab and no controls being in the study. The Lombardi et al. assays are clinically validated.”
ReplyDeleteClinically validated ??? How ? Clinical validation applies to treatments and testing procedures applied in a clinical setting – a disease would have to have been established and the test to have gone through rigorous clinical trials. What disease or biological process relevant to a clinically identifiable condition were the WPI/VIPdx tests, designed to identify ?
The VIPdx website carries a statement fom Lombardi which makes it clear the only validation of the test being offered was that carried out by VIPdx itself. Mikovits was reported to have claimed that the VIPdx test was not validated to the same self referenced standard as the tests used to support ‘Lombardi et al 2009’, Lombardi’s VIPdx statement disputes that reported claim. What is not in dispute is that the BWG study fundamentally questions the validity of the of XMRV testing at WPI/VIPdx. The argument which is being accorded to Mikovits, is that the assays used in ‘Lombardi et al 2009’ were sound, and the assays used by Lombardi in the BWG study and VIPdx are somehow different and not sound.
In whatever way the differences between the argument accorded to Mikovits and the VIPdx statement of Lombardi are represented, the overriding issue is: – No external, independent validation of testing used in any of the published work of the WPI, nor of the test sold by VIPdx has ever been made. For research purposes, independent validation only becomes an issue where published research is in question. For commercial testing, independent validation is the only means by which the purchaser can have any confidence that the test is in anyway meaningful. The sale of unvalidated tests to M.E/CFS affected people was misguided and given the context in which those test were being promoted, grossly irresponsible. The issue of the VIPdx sale of XMRV testing is not primarily a scientific issue, it is a consumer rights issue in which the role of the WPI is deeply questionable. What Annette Whittemore, Mikovits and Lombardi individually knew and at what point does need to be explained as matter of credibility for those individuals, but as an institution WPI appears damned on the basis of its relationship with VIPdx and the marketing of a test which was without any intrinsic value for those who were encouraged to purchase it.
That there are people who, having invested both financially and emotionally in the VIPdx tests, do not want to give up on the idea that the test has ‘told them something important’ is not surprising. Sadly that does not imbue the tests with scientific meaning, which without external validation, is wholly absent.
@anon 12:05
ReplyDeleteNothing has gone wrong with Mikovits or Ruscettis research. This mess looks to be partly about ViPDx and Lombardi. There is no reason based in science or anything else to retract Lombardi et al. Lo et al supports the findings. There are no negative papers because those optimising to VP62 and not clinically validating their assays don't count.
Lombardi et al used a previously clinically validated assay and used multiple other assays and experiments to clinically validate the positives and other assays. Clinical validation is the only way to prove an assay works.
ReplyDeleteIla Singh
"It’s just not sufficient to show that something can detect something in a plasmid template. It’s hard to know if it’s going to detect something in a matrix that’s as complicated as blood or cellular DNA. So I think that’s probably one of the biggest reasons for why people find different results.."
Vincent Racaniello
ReplyDelete"In my view the CDC paper should not have been published without a proper positive control, eg patient samples known to contain XMRV. If I had reviewed the CDC paper that's what I would have asked for."
@invitro
ReplyDelete"Mikovits was reported to have claimed that the VIPdx test was not validated to the same self referenced standard as the tests used to support ‘Lombardi et al 2009’, Lombardi’s VIPdx statement disputes that reported claim. What is not in dispute is that the BWG study fundamentally questions the validity of the of XMRV testing at WPI/VIPdx. "
Mikovits asked for evidence that the assays at ViPDx were clinically validated. The assays in Lombardi et al are clinically validated. Annette Whittemore has stated they are different assays used at ViPDx to the WPI. The BWG was done by Lombardi at the BWG.
The flawed BWG paper is hard to miss. Contamination was easily introduced by the CDC lab experimenting on 22rv1 and collection tubes. And the absence of real controls due to the failure to pre test PBMCs of controls, invalidates the paper regardless.
Well put, Mindy. A very comprehensive analysis of the situation. We would all love to have answers to those questions.
ReplyDelete@ In Vitro Infidelium
ReplyDelete@ DzD
and @ all you Anonymice :
My question is sincere albeit maybe very naive: Is it coincidence that a retrovirus very similar to (or the same as) the one found by Mikovits in CFS patients, and similar also to those MLVs found by Alter and Lo in CFS patients, happens to be contaminating the assay used by VIP Dx? Were the assays used in the negative studies also contaminated by XMRV? Or was XMRV simply not found at all in the negative studies (which didn't precisely replicate Mikovits' study)?
The sequencing of the viruses found by Mikovits/Ruscetti and Lo/Alter are identical as both are this far polytropic.
ReplyDeleteWhat do you contamination in the ViPDx assays? Do you mean 22rv1 having been experimented on in the CDC lab with a selection of the tubes?
The 00 papers found nothing, the assays were not clinically validated so can be assumed to not work. There have been a few papers finding one or two positives, but they never demonstrated it was due to contamination and not the fact they had not optimised to a clinical positive. Those authors only assumed it was and did not investigate sufficiently to even suggest contamination. Several papers had mouse contamination, but these are human gamma retroviruses, so those were poorly controlled. No study has replicate Lombardi et al. Not even lo et al. And the EM image of the budding maturing virions plus the serology assay detecting MLV viruses are indisputable. They cannot be contamination and are heavily avoided by the immaculate contamination brigade.
@Anon. December 2, 2011 4:26 PM
ReplyDeleteYou ask several questions which are not necessarily consistent with each other and also impose a couple of conditions which are not necessarily correct – it’s difficult therefore to give a simple answer.
Science doesn’t progress on the basis of ‘who got what right’, it progresses on the basis of experimentally reproducible effect – this is referred to as ‘replication’. Effective replication does not require, and frequently abjures, exact copying of previously used methods, there usually being more than one way to create and ‘observe’ an experimental phenomenon. The more ways you can observe something, the more certainty that is likely to apply to the reality of the phenomenon.
There is no way of knowing what was causing the ‘positives’ in testing done by either the WPI or VIPdx, what is scientifically significant is that no one else could reproduce the observation. The validity of the WPI and VIPdx testing would come from someone else (ideally numbers of laboratories) being able to consistently replicate the test observations. No one has done that. It doesn’t matter how much is argued about what is and what is not a contaminant and what is and what is not proper replication – without independent validation, testing, whether experimental or supposedly clinical has no scientific meaning.
Given the above, it is simply not possible to answer any questions as to what Mikovits ‘found’ because no else has been able to reproduce the observation in any meaningful way, same with Alter and Lo, and Alter and Lo differ from Lombardi et al to a degree that means these two can’t be mutually supporting (even if there are those who wish that to be true). I’m not aware that anyone has looked at ‘contaminant’ within the VIPdx testing regime, Lombardi simply states that it is the same as that employed in the research behind the 2009 Science magazine article – which is what no one else has been able to reproduce. In scientific terms it’s all a non event, one can choose to make a great mystery out of it, or a CSI story or invoke whatever version of ‘conspiracy’ takes your fancy – but scientifically it’s a ‘no score’. Maybe down the line some other researchers will come up with a different way of looking at the ‘problem’ (if there actually is one) and come up with something that throws light on the remaining questions, but for now there’s no where to go scientifically that would provide categoric answers to the questions you pose.
My questions would also include: Why didn't WPI fully staff and open the clinic? Are they being led by the lawyers? What are the new royalty income and the larger government grants for in 2010? Kathy
ReplyDeleteMy whole family is sick and there is no denying the facts. Here are some facts. My father get's to drool all over himself and can't walk anymore. He also has botox injected regularly into his eyelids so they work properly enough so he can actually feed himself. He has late stage parkinson's. His wife has had MS for about 25 years now. My mother has constant pain in her left breast that has hurt since the cancer and lymph nodes were removed. Her life was saved. My sister an I both have fibromyalgia. She recently diagnosed along with congestive heart disease, mine 18 years ago along with severe tachycardia. My brother has Graves which brought on a heart attack at the age of 44. His thyroid was recently scanned for cancer. Luckily none was found. My oldest brother is dead from Leukemia. He died alone in the hospital because my parents decided to check on their 4 other children for one night. There is no prior history of any of these illnesses in my family. I am positive both sero and culture by research lab methods. All a coincidence? I don't think so.
ReplyDeletei am just waiting to die and i feel like no one cares.
ReplyDelete"Effective replication does not require, and frequently abjures, exact copying of previously used methods, there usually being more than one way to create and ‘observe’ an experimental phenomenon. "
ReplyDeleteReplication is using the exact same methods. There is not a special dictionary for the word. In science you can try to do something a different way, but the only way to disprove a hypothesis is to replicate the experiment. It is also false to say no one produced the exact same results. Lo et al. did. They both found viruses that are polytropic. In Vitro really doesn't like that fact.
In Vitro would like you to then think others have replicated the Mikovits/Ruscetti methods. No one has, it is a lie. Again the finding has been reproduced by Lo et al. Annette Whittemore has also admitted the ViPDx test is not the methods used in Lombardi et al.
In vitro wants you to think it is not possible to know whatilovits and Ruscetti found. Wrong wrong wrong! We know from the serology assays it is a human gamma retrovirus, MLV related, as that assay cannot detect anything other than those viruses and not endogenous. We know from the EM of the maturing virion it is a gamma retrovirus that was integrated into human cells and replicating. For prostate cancer XMRV again there is evidence that cannot be contamination. There are sequences of polytropic MRVs. Multiple sequences. There is a list of further experiments as long as your arm that can now be used to move forward. Including tissue and bone marrow studies. Deep sequencing, if you know the target sequence. In vitro wants to stop this happening, but they are not a patient are they.
@ December 4, 2011 6:27 AM
ReplyDeleteI care.
@december 4, 2011 6:27am. so very sad. been sick for 40 of my 60 yrs, sometimes i feel as you do - hard not to...but i care.
ReplyDelete"Effective replication does not require, and frequently abjures, exact copying of previously used methods, there usually being more than one way to create and ‘observe’ an experimental phenomenon. "
ReplyDeleteThis statement is wrong. This isn't the same thing as replication. When scientists don't use the exact methods prescribed in the original paper when trying to verify a finding, they introduce new variables into the process. Only once an experiment is verified (or not) using the exact methods of the original paper are scientists able comment on the finding's validity. Then, if confirmed, it becomes important to move on to studying the phenomenon using from multiple angles using different methodology.
If you put the cart before the horse and do it the other way around (new experimental methods before an exact replication), it breaks the scientific method and you then can't come to any conclusions about the original study's validity.
There may be *other* reasons why scientists doing follow up studies don't use the same methods as the original paper (politics, resources, researcher expertise/preferences, etc..), but that doesn't change what these follow up studies do or don't say about the original paper's validity in that case.
Thanks anon @ 6:34 AM "Replication is using the exact same methods. There is not a special dictionary for the word." The special pleading for not replicating Lo/Alter is very telling.
ReplyDelete@Anon7:52
ReplyDeleteReplication is not special pleading, it is a fundamental of the scientific method.
Replication: "the ultimate test of truth in science"
http://www.saltinstitute.org/News-events-media/Salt-Sensibility/Health/Replication-the-ultimate-test-of-truth-in-science
Why has no one replicated the proven single methods, not those that failed, in Lo et al. is also important. However, this is a gamma retrovirus. They are not easily found in blood as they preferentially propagate in tissue. As Dr Frank Ruscetti said "We do not know at the moment what the differences is, if it's processing or what not, but I stand on the recommendation I made. Until we understand it better, negative PCR is not a stand alone assay for detection of this virus in clinical samples." Scientist aim to identify as many positives as possible.
We have always known VP62/XMRV was never found in nature. We now know it was wrong of Silverman to have named the viruses found by Mikovits and Ruscetti as "XMRV". They are polytropic, with tropism still to be sequenced. Studies optimising to VP62/XMRV were not looking for the viruses and they all failed to clinically validate their assays. The assays used in those papers are unable to do the job.
@ Anon.December 4, 2011 7:30 PM
ReplyDeleteYou are confusing 'validation of method' with 'reproducibility of observation'. Of course the means of investigation has to be valid, but to suggest that 'replication' requires unwavering copying of method is absurd. If a method is flawed, copying it exactly should indeed reproduce the same results - the same flawed results.
These ridiculous and oft repeated memes about those studies which did not support Lombardi et al 2009, seem to have there origin with statements from Mikovits about the need for exact matching of her prescribed methodology. The problem is no one else working in the field could understand why the Mikovits method was necessarily so finely tuned, and Mikovits has never taken up the challenge to explain this point in any comprehesive way. This Blog article poses questions about why things have turned out as unsatisfactorily as they have - one answer is that Mikovits, whether or not intentionally, encouraged undue certainty on the part of M.E/CFS affected people, when far greater caution was necessary. In science, taking the view that everyone else is wrong is only rarely a smart move. Mikovits hasn't been smart.
I don't see anyone asking for a confirmation paper on Paprotka et al. Coffin and Pathaks paper that claimed to have found the origin of XMRV. The absence of anyone asking for that to be validated is very telling. Then again what would they be validating? One assay used is absent from the paper, but used, which is an automatic retraction. The other two assays could not detect less then 2000 copies of VP62/XMRV. The paper had no substance.
ReplyDelete@Anon11:28 - I agree... people should be scrutinizing Coffin's work on this as much as they do the other studies. I mean why do people care so much what he thinks? He hasn't done any work on this illness/virus and his papers haven't been replicated or validated.
ReplyDeleteAnon @4:24, you missed the "not" - the special pleading for NOT replicating Lo/Alter is very telling. Oh well it happens to the best of us :)
ReplyDeleteAnyway onto Next Generation Sequencing, today there is a Co-Cure post from the Cheney Clinic discussing this. www.cheneyclinic.com /changing-status-of-xmrv-hgrv-research-2/843
More on this please Mindy?
xxx
"Anon @4:24, you missed the "not" - the special pleading for NOT replicating Lo/Alter is very telling. Oh well it happens to the best of us :)"
ReplyDeleteWhere do you think a not should be?
Anon @12:18 I was agreeing with you but it got lost in translation apparently.
ReplyDeleteIn response to In Vitro you said "Replication is using the exact same methods. There is not a special dictionary for the word."
My response could have been clearer: "Brilliant comment anon @ 6:34 AM. The special pleading by In Vitro for not replicating either Lombardi/Mikovits or Lo/Alter is very telling."
I am sorry for the misunderstanding.
Tony Mach, like the establishment, is no friend of ours. He is only here to stir up trouble, because no-one cares enough to ever comment on his bland and misinformed blog.
ReplyDeleteFrankly, I would hate it I would get all these mindless anonymous comments about VP62 that go on like a broken record and that I would have to delete from my blog.
And thank you for declaring me a foe. Will you go on a with hunt against me? Please? Then I can present myself as a martyr! That would be sweet!
He claims to have ME/CFS, but on his entry about the ICC he admits he actually does not know who the authors are besides Klimas and Bell? That he has only heard the name of Kenny de Meirleir? Pffft!
I think people who have an definitive answer to everything are very suspect – both you and Dr. Mikovits fall into this category.
There's nearly 80 years of "facts" he appears to be missing.
Like what? And how does it relate to any research (or "research") into XMRV?
Helpful if you are on a witch-hunt to destroy the very caring Judy Mikovitz while conveniently ignoring the malfeasance of the establishment, and the upstairs lot burning so much talent so quickly.
Yeah, because the establishment treats me nice and cosy.
And because the fact that Dr. Mikovits is caring says *ANYTHING* about the quality of her research.
And go ahead, alienate anybody contesting that you are wrong. That is the scientific method!
There are so many questions we need answers to, but Mr Mach-o (?) can't think beyond his "burn the witch" mentality. 20 years ago they "burned" Elaine de Freitas, she has not spoken publicly since then.
"Anyone who says this is a lab contaminant has drawn the wrong conclusion and has done a disservice to the public"
– Judy Mikovits
Compare to:
"In retrospect, I say I did the disease a disservice. I might have done the patients a disservice, and I might have done the field a disservice."
– Elaine DeFreitas (page 682 "Osler's Web")
To all people posting about VP62!
ReplyDeleteI challenge the person (all those anonymous VP62 posts seem the same to me) to provide me the following:
1. The gene-sequence of XMRV/(P)MLV/"HGV", as supplied from the WPI
2. The primer/probe sequences, as supplied by the WPI
3. The gene-sequence of VP62
4. The primer/probe sequences which are supposed to match only VP62
5. A explanation (using the material above) why the primer/probes from (4) work only with regards to VP62 (3) – and why they should not work with XMRV (1).
As a bonus, explain why the primer/probe used by the WPI are better (or the only "true" ones to be used).
Yet, somehow, I guess none of those anonymoses (if there are more than one) who goe on and on and on why VP62 will be able to provide this material. Prove me wrong.
He claims to have ME/CFS, but on his entry about the ICC he admits he actually does not know who the authors are besides Klimas and Bell? That he has only heard the name of Kenny de Meirleir?
ReplyDeleteI'm sorry for my behavior. In my country, CFS is barely recognized and ME is not. Practically all doctors here work with a psychosomatic model for these kinds of disease. So I need to apologize that I don't know more about my disease, despite the fact that it seems to be psychosomatic according to the doctors here.
And I need to apologize for gathering what I learn publicly on my blog. In future, I will keep all my information for me and leave all public speculations to those who dominate the discourse. The epic shootout between those whose confirmation bias leads them to XMRV and those whose confirmation bias leads them to psychosomatic models – I'm sure I will benefit from this very shortly.
Thirdly, I am sorry that I blogged about what I know and what I don't know. This will not happen again in the future. I will exclusively pretend to know everything. I will never admit to failures or missing knowledge. Dr. Mikovits and all those anoymouses here will be my guide in how to achieve an public "No fault" image. After all, as I can see here, one will be attacked for admitting to not knowing something and one becomes a saint by having an answer to everything and pretending to know everything.
@ Anon December 4, 2011 7:30 PM
ReplyDeleteYou are confusing ‘validation of method’, with ‘replication of observation of phenomena’. Of course a method of investigation must be effective, which is why replication without challenge to method risks simply repeating methodological failures. Replication in science does not mean simply doing the same thing someone else did – it means achieving observation of the phenomena that has previously been reported, relative to the described conditions. Contending that words don’t have ‘special meaning’ in science is patently false.
@ Anon December 7, 2011 11:20 PM
see above: replication doesn’t mean what you think it means. You want someone to copy what Lombardi and Mikovits did – fine. Your problem though is that no, but no one, is going to do that; no one thought it was worth doing before the BWG study, and unless some part of the Lipkin study is to be specifically directed to doing that, then it seems very unlikely that any grant funding is going to be poured down the drain simply copying what has all the hallmarks of a dead end.
For anyone interested in what went down the WPI drain: http://cfsmirror.blogspot.com/2011/12/myth-money-and-self-delusion.html
@Tony
ReplyDelete"1. The gene-sequence of XMRV/(P)MLV/"HGV", as supplied from the WPI"
Only the gag and partial pol of the MLV-related viruses has been sequenced at this time. That is polytropic not VP62/XMRV.
"2. The primer/probe sequences, as supplied by the WPI"
In the paper Lombardi et al.
"3. The gene-sequence of VP62"
In the GenBank
4. The primer/probe sequences which are supposed to match only VP62
VP62/XMRV has never been found in nature by anyone.
"5. A explanation (using the material above) why the primer/probes from (4) work only with regards to VP62 (3) – and why they should not work with XMRV (1). "
VP62/XMRV has never been found in nature by anyone. It is man made.
"As a bonus, explain why the primer/probe used by the WPI are better (or the only "true" ones to be used)."
Primers are not the only variable of an assay. The Mikovits and Ruscetti labs also used other experiments to support their results, such as serology and EM.
@In Vitro
ReplyDelete"You are confusing ‘validation of method’, with ‘replication of observation of phenomena’. Of course a method of investigation must be effective, which is why replication without challenge to method risks simply repeating methodological failures. Replication in science does not mean simply doing the same thing someone else did – it means achieving observation of the phenomena that has previously been reported, relative to the described conditions. Contending that words don’t have ‘special meaning’ in science is patently false. "
Replication means repeating exactly. Even children know this. This is the special meaning of replication. The only way to test a hypothesis is to repeat the experiment exactly the same way, i.e. replication. Reproducibility is getting the same results. Can you get the same results with that assay, or one of the more than 10 assays that have found these viruses in people.
Validation is where you ensure an assay works. Analytical validation only proves an assay can detect a synthetic virus spiked into blood. Clinical validation proves an assay can detect a wild-type virus in blood.
"see above: replication doesn’t mean what you think it means. You want someone to copy what Lombardi and Mikovits did – fine. Your problem though is that no, but no one, is going to do that; no one thought it was worth doing before the BWG study, and unless some part of the Lipkin study is to be specifically directed to doing that, then it seems very unlikely that any grant funding is going to be poured down the drain simply copying what has all the hallmarks of a dead end. "
You are admitting there are two positive papers using different methods, which fulfils you personal idea of what is needed to confirm the findings. The BWG study was meant to use assays that had been clinically validated and find those that are high throughput. The study failed due to no pedigreed controls, contamination exposure from 22Rv1, and labs not having used their proven assays.
The Lipkin study is over now Ruscetti and Mikovits are not involved and those taking part now use assays not shown to be clinically validated. It is interesting that you don't wish funding for future research, but you are unable to dictate what goes on in other countries. Are you connected to funding in the US? You appear to suggest you are. That rather says you are trying to stop this being researched. Again interesting.
Studies are able to clinically validate if they don't want to replicate. None of the negative papers have.
MINDY CHECK OUT THE NEWS!! MIKOVITS AND RUSCETTI ARE BACK!!
ReplyDeleteGood news. Thanks for the post. I have a little theory myself as to why we are fatigued. <a href="http://www.newworldantidote.com>Why viruses reactivate</a>
ReplyDeleteWhen will it be acknowledged that retroviruses are not cytotoxic, and are incapable of causing immune deficiency? Government-funded science (an oxymoron) puts on a wonderful charade of smoke-and-mirrors --> that CFSers oddly continue to fall for time-after-time.
ReplyDelete