Breaking news. The entire WPI research program has been closed by the institute’s CEO, and the facility is now locked down. It’s former principle investigator, Dr. Judy Mikovits, is in active discussions concerning institutions to which she may move to continue her grant-funded research. The institutions must remain unidentified, for obvious reasons, but it’s important for patients to know that she remains committed to continuing this critical work.
So now, on top of everything else, a divorce at the WPI. Yet to come are all the things that can happen in such messy situations. Meanwhile, there is no Mikovits-led research at the WPI or any research institution at the moment. An enormous loss of possibility. I’ve done a lot of soul searching about whether to write this blog or not. My motivation for writing all along has been to make things better, to inform, alleviate isolation, share ideas that I hoped would be useful. This is different. Writing this entry, I feel like I’ll be taking away hope, which is anathema to me. But at this time, withholding the information I have would be dishonest. I don’t know what else to do, except tell it the way I see it.
Here is the reality and the context for why I write this particular blog entry: My email inbox is filled with so much pain and confusion, as patients try to figure out what the BWG study means to them. I feel it is my obligation to both these patients and the larger community to share my opinions. I think what the BWG results mean is that all the XMRV/HGRV testing done at VIP Dx has been and is now null and void. Keep in mind that Dr. Mikovits works at the WPI research lab, which is a separate lab from the clinical, commercially-oriented VIP Dx lab. She believes that she has reproduced her original work many times and found evidence of infection in the patients who were previously found XMRV positive. But she never found any single patient positive on every date tested by every assay. So there has been an assumption that there were false negatives in the WPI research lab for some time. Another important thing to keep in mind is that WPI routinely used several tests on each sample, whereas VIP Dx used different, more limited testing, on the samples they received, testing that apparently was never truly validated against WPI methods or performed with appropriate controls. I personally don’t know why this was the case or how it happened. Obviously the decision to sell a test was a very poor one, hindsight being 20/20. It left the institute with a difficult conflict of interest.
I have watched this whole thing unfold and kept quiet because I hoped that management at the WPI would come to their senses, before it was too late. They have not, so I now feel obligated to share what I know.
Dr. Mikovits is a personal friend of mine. We’ve spent time together in Reno. We were excited about our collaboration. We still speak and email regularly. Because I know her so well, I can tell you first hand that she never thinks of or spares herself, and instead gives her all to the research and the patients who need it so badly. She has been criticized for the unorthodox step she took of allowing patients to gain access to her, a step that was life-saving for some, though it turned her into the ME/CFS hotline.
In terms of the BWG: I was told that the BWG specimens were being run in both the WPI research lab and the VIP Dx clinical lab. Though the labs were kept separate, and cooperation between the two labs was already very troubled, Dr. Mikovits believed that VIP Dx would succeed, and everything would be doubly validated.
When the results of the BWG were uncoded and revealed to all nine labs (but not yet made public), in early August, WPI was left in a bad place. Dr. Mikovits says that at that time she asked WPI management to stop offering the XMRV test at VIP Dx. But the testing was not stopped. Why?
Then, when the BWG results were finally made public on September 22, Dr. Mikovits was quoted as saying, “VIPdx lab will NOT continue XMRV-testing because it hasn’t been shown to be reproducible in [the] BloodWorkingGroup”. Shortly after she said this, cooperation between the two labs ceased completely and the research lab was closed. Why?
It is important to know that Dr. Mikovits stands by her work at the WPI research lab, which is all she can vouch for. She cannot account for what happened at VIP Dx. It was in a different location, under different leadership: Dr. Lombardi was in charge at VIP Dx.
Now it appears the WPI research program is getting thrown under the bus, but VIP Dx is still up and running, now minus XMRV testing. None of this means that we don’t have HGRV’s, or that some of the work that came out of the Mikovits-led research lab wasn’t correct. What it does mean is that there is no validated test for clinical, commercial use. And it means we are now at risk of losing all the gains we’ve made because of poor managerial decisions.
My next blog will be to repost Dr. Mikovits’ slides from Ottawa, this time with her comments and a summary from me, making the case for HGRV’s. Culture contamination with VP62 doesn’t explain away her findings. She was finding variants of XMRV. The serology test used in the BWG and published in Lombardi et al is picking up something that is at least very close to, if not antibodies to, MLV proteins. Someone needs to find out what those proteins are. There were electron micrographs from patients showing retroviruses. Pictures. Frank Ruscetti has been studying retroviruses since the beginning of the field and he believes he has been looking at something real. And there have been clinical responses to antiretrovirals, including ours, that are hard to explain away, other than that they are doing what they are supposed to do, inhibiting the replication of retroviruses. Please read Dr. Snyderman’s posts and comments again: A Reason For Hope.
As sometimes happens with divorce, we now find ourselves in a position where we have to take sides. The science, not the institution, is the child that must be protected somehow in the ensuing custody fight.
For the record. As we descend back into darkness… I wrote the below text a few weeks ago, but didn’t post it. I have confronted these issues directly with WPI management and not gotten an adequate response.
Untitled blog:
If you tell the truth, you don’t have to remember anything.
~ Mark Twain
I’ve been quiet about my own personal experiences at the WPI, figuring things would unfold on their own, without disclosure from me. But something is happening that I can’t just let pass, It is this belief patients have that, could they only get to Reno and be treated at WPI, it would all be better. This dynamic is too painful to watch in silence. It hits a nerve. When my daughter got sick with “Chronic Lyme Disease,” I felt that there was information other doctors had that might help her. The memory of that feeling, of being unable to help my child, thinking that there was something to know that I didn’t know, and the poor decisions that desperate feeling led to, is driving this next disclosure of mine. Keep in mind that most of what I know about that is happening on the clinical side at the WPI now is hearsay. He said, she said. Eventually, it will all come out in the wash. But as a physician, I feel the medical carrot being dangled before the public needs comment.
I recently watched Annette Whittemore on Nevada Newsmakers imply that there is new treatment available at the WPI that is producing miraculous results. Due to patient confidences, I can only impart my reaction, not prove my case with details. But her comments were over the top, an advertisement, cobbled together from little pieces of reality, but not reality. There is one doctor working independently in the clinic space, downstairs from the WPI. He is a lovely doctor, an experienced endocrinologist with an interest in CFS. He would have made a wonderful addition to a multidisciplinary team. Does he know something that nobody else knows regarding how to treat CFS? No. There is no treatment being offered in Reno that isn’t mentioned on my blog. No secret knowledge. Nothing you need to be an insider to find out.
It has been really tough for me to decide what, if anything, to say about this next topic. Given that I promised to be truthful here, saying nothing seems almost a lie of omission. If I say something, I sound bitter, which maybe I am. And if I say nothing, I sound incompetent, which I am not. A no win situation. But the truth is, I was well on my way to getting the WPI clinic going as envisioned from day one: A team of like-minded doctors sharing ideas and generating a large patient database, an integral part of a WPI translational research institute. It would have generated enough income to support the research program. But the plug was pulled, inexplicably. A very poor decision.
The ways in which I was mismanaged and completely constrained by ineffective micromanaging when I was working at the WPI, and now this insanity, shutting down the research program, establishes a pattern of behavior. Although it is sad, the party is over, and needs to be. They were, and are, in over their heads. They started with the best of intentions. We will always owe them a debt of gratitude for the spark of genius and the increased awareness they have brought to our disease. But now, the work needs to be done by someone with the resources to do it right. They have risen to their level of incompetence. It doesn’t matter to us who wins, gets the money or what their personalities are like, as long as the research continues. We need it to happen. The WPI is now an obstacle to progress.
Tonight’s song: Square One by Tom Petty
>Gels of the same experiment should look identical. Scientists do not introduce variables into their experiments they cannot control.
It has never been made public who the reviewers of Lombardi were, and Stoye has not accused the Russcetti/Mikovits teams of anything.
Science will know about this children's game, they wont be taking it seriously as gels should look the same.
>Lombardi reviewers, whoever that person or persons are, would not have access to the original gel from the slide in Ottawa. So ERV images are artistic impressions.
>Since when do reviewed get to keep the originals? Maybe, if you say it was Coffin anon, he kept it as a souvenir. A paper that changed our understanding of human gamma retroviruses and ME.
>@Anonymous:
"Gels of the same experiment should look identical."
The why do the postives in lanes 3 and lanes 6 look entirely different from each other?
"Science will know about this children's game, they wont be taking it seriously as gels should look the same."
Picture from the ACTUAL powerpoint:
http://i56.tinypic.com/23r7fwx.jpg
Something just hit the fan…
>@RRM
Position on the gel using same test would match. ERVs new mighty big images are not from the originals. You really think they got into the WPI? Conspiracy theorist much. They don't even line up with the slide or gel anymore. The slide on Jamie's blog isn't the original either. Looks like you don't know the difference. New elements shouldn't suddenly appear as if by magic, but that is how ERV describes it. So it must be magic. Magic art.
>Why has Abbie Smith put up enlarged images that are not the gel from the paper or slide?
>Mikovits: "XMRV!!!"
Science: "Contamination"
Mikovits: "You are all wrong"
Mikovits: "XMRV!!!"
Lo/Alter: "Blimey, we have MLV"
Mikovits: "We have MLV too"
Science: "Contamination"
Mikovits: "No, you are all wrong. I am the only one who is right"
BWG: "No XMRV"
Science: "Contamination"
Mikovits: "na na na na I have HRGVs"
*facepalm*
Mikovits gone, I say "good riddance".
Hopefully the hype will die out and we can go back to science. Trust science, not scientists.
>@Zappa are you are sick?
Abbie Smith's images could never have come from the paper or slide. They are art at best.
>There is only one word to describe WPI and Mikovits: FUBAR
A very small group of patients, the cult of WPI with Saint Mikovits, dominated the debate for almost 2 years to the embarrassment of patients who do have some common sense.
>Zappa, have you had too many bangs on the head?
Mikovits, Ruscetti and the group have not manipulated anything in Lombardi et al. That is a false allegation.
Abbie Smith however does have images on her site that have not come from the paper or gel. What is she playing at using art to make false accusations?
>it is bad news for everyone. Too strident Zappa, Judy tried hard , maybe she was premature in the news releases.
Judy seemed to question the tests done at RED lab/ renamed VIP lab/ then renamed again . This lab was a for profit investment of Harvey Whittemore . Many patients were charged hundreds of dollars for a possibly inaccurate test. They must refund this money.
What has happened to all the money that WPI collected ? This includes $200,000 from a recent write in campaign. If Judy was locked out who will do the research? Lombardi is a post doc not capable of running the lab.
Maybe Judy asked too many financial questions in a time when Mr Whittemore was being pressed. WPI should disclose these financial contributions .
Chris
>@Chris
That is false. Mikovits has never said there is any problem with the VipDx assays. The assays in the blood working group are different to those used by Lombardi et al. and VipDx due to the interference of the BWG. The PBMCs were not treated with Tizol and culture times were slashed. Even worse the controls were not PMBC screened. So they could never have been declared negative.
Lombardi et al used multiple assays, with VipDx you get what you pay for. As it is very difficult to find gammaretroviruses in blood, due to their preference for tissue, there will always be an issue with false negatives with blood assays, but a positive is a positive. Simply, yhe proviruses integrate into CpG islands. So it is pretty much makes them impossible to amplify using normal PCR. So why have they been using standard PCR?
>Just to clarify the controversy about the images, as it currently stands, given the events of the last 12 hours:
First, look at the image found in this link: http://i56.tinypic.com/23r7fwx.jpg
(was originally posted here by RRM a few posts above)
This is purportedly the full image behind the segment shown in the Powerpoint of the Ottawa presentation, and includes the labels that state what was run in each lane of the gel (and patient numbers). I will assume that this really is the full image (and conspiracy people can run with the opposite if they'd like). ERV *proved* that the image in the talk was the same one from the Science paper. (And BTW, anyone who disputes that is ignorant about the technique.)
At first the issue seemed to be that by using the Science figure to illustrate something different in her talk, it cast doubt on the conclusions JM made in her talk. Speculative explanations ran the gamut from worse case "intentionally deceiving the audience at the talk", to a simple innocent error by her or an assistant when preparing the presentation at the last minute.
But it turns out that it is, in fact, much (much) worse. Because what the full image shows is that, in fact, what she presented in the talk was (kinda sorta) what the actual experiment was. Which means that the figure in the Science paper was not what is was claimed to be.
It's hard to imagine a simple innocent explanation: the patient numbers were different, the treatments were different, and factors like "rushing to prepare a presentation at the last minute" are no longer available.
Maybe the countdown timer at the top of this blog, which current tracks elapsed time since the publication of JM's Science paper, should be changed to "the amount time research into CFS currently has been derailed".
>Gels of the same test will look alike. The gels in Lombardi and the slide are not in full. The are copies of copies and out of focus. What Abbie Smith has posted is a larger image that could not ever have come from those sources. And it is impossible for her to have had any access to the originals so they are manipulated.
Amount of time until ERVs blog is shut.
>http://scienceblogs.com/erv/2011/09/xmrv_and_chronic_fatigue_syndr_29.php#comments
Here is a (hopefully clear) summary of the recent events in XMRV:
1) XMRV itself was found to be a laboratory artifact; a virus made when human prostate cancer cells were repeatedly inoculated into different mice. It does not exist in nature, and did not exist at all prior to the early 1990s.
2) Some of the analysis (the PCR experiments) in the original Science paper were found to be the result of contamination of some of the samples with an artificial plasmid DNA encoding XMRV. The source of the contamination is not clear, but given the circumstances and the extreme care that the Silverman group went through to reduce contamination, it is likely that the contamination originated at WPI. Why this contamination was only found in "patient" samples and not in normal controls is unknown, but highly suspicious.
3) Multiple other groups, including the Blood Working Group, have found no evidence of XMRV in any of the samples. Even the groups trying to link XMRV to CFS can't get a positive signal if they are blinded to the origin of the samples (that is, they don't know which sample is which).
4) Now, it seems as though some of the other data in the Science paper is fraudulent. The immunoblot that was shown in Fig. 2C is actually an image of a completely different experiment, one that artificially manipulated the samples in a way that would induce expression of endogenous retroviral proteins.
Taken together, it is now very difficult to trust any data in the original Science paper. It appears to be a deliberate attempt to manipulate data, in a way that takes a laboratory artifact and makes it into a bona fide result. My guess is that the Mikovits group found some provocative preliminary data, as they ran some PCRs on their original samples and found (the contaminating) XMRV. They were so excited about the possible implications of this that they ignored/underestimated the possibility of contamination, and in the rush to publication they manipulated their data so as to look more robust and impressive and get the paper into Science. Everything since then has been a house of cards, built upon a very shaky foundation.
So, XMRV has nothing to do with CFS. While it is not out of the realm of possibility that some other viral illness, possibly even an endogenous human retrovirus, may have a role, any XMRV findings are likely artifactual. (And, while I am not an expert on this, the epidemiology of the disease makes a transmittable viral illness unlikely as the cause of CFS).
I know that the majority of the scientific community is sympathetic to your cause, and would like to determine the cause/origin of CFS. We are frustrated by this apparent case of scientific misconduct, and regret all of the time/energy/money wasted on this. Hopefully, one benefit of all of this will be to bring increased attention to CFS, and direct more scientific interest into actually finding the cause(s) of this disease.
>Others' Comments:
I guess most fraudulent scientists don't make up everything. They usually find something that is wrong, become convinced it is right but then cannot produce the additional data in support of their finding.
That is when they start to make things up – because they "know" they're right and they believe the doctored results are actually true and further research will confirm this, they are confident the fraud will not see the light of day.
I know that as an European leftie I shouldn't get all political, but I guess it's a bit like making up evidence in support of Iraq owning WMD's in order to justify an invasion. They thought they would find them anyway, in which case nobody would have questioned the incorrect evidence.
*
Aside from fraud and contamination, an underlying reason for this whole affair seems to be that Mikovits desperately wanted to find a retroviral cause for a serious disease other than HIV.
Here is how it happend: Mikovits worked for some decades in a HIV lab. Her expertise is therefore, strictly, retrovirology. But just 3 retroviruses were ever shown to cause human diseases: HIV (and all its many subtypes), HTLV-1 and HTLV-2. And while there are many retroviruses known, most of them can't infect real, complete, humans and many more infect humans, but don't cause any diseases. If you want to get a job in retrovirology, you are almost required to work with HIV, because it causes the most prominent disease out of these 3. Mikovits became interested in CFS solely for the retrovirology. She heard from Lombardi that RNAse L is a biomarker for CFS, and from Silverman that his prostate cancer cells express RNAse L and are infected with XMRV (which is a contamination, see ghholms post). She specifically began to work on CFS to prove that XMRV causes CFS and that bias led to the mess we have now. If you view her motivations in this context, some of her actions, like blaming other CFS researchers who can't reproduce her data of fraud and don't admitting to mistakes to the finding of XMRV/HGRV in patients, make more sense. But that XMRV causes CFS was a highly unlikely hypothesis from the beginning, as it was just based on the expression of a single biomarker.
*
read this article:
http://www.sciencemag.org/content/333/6050/1694.short (free registration required)
>Others' Comments:
I guess most fraudulent scientists don't make up everything. They usually find something that is wrong, become convinced it is right but then cannot produce the additional data in support of their finding.
That is when they start to make things up – because they "know" they're right and they believe the doctored results are actually true and further research will confirm this, they are confident the fraud will not see the light of day.
I know that as an European leftie I shouldn't get all political, but I guess it's a bit like making up evidence in support of Iraq owning WMD's in order to justify an invasion. They thought they would find them anyway, in which case nobody would have questioned the incorrect evidence.
*
Aside from fraud and contamination, an underlying reason for this whole affair seems to be that Mikovits desperately wanted to find a retroviral cause for a serious disease other than HIV.
Here is how it happend: Mikovits worked for some decades in a HIV lab. Her expertise is therefore, strictly, retrovirology. But just 3 retroviruses were ever shown to cause human diseases: HIV (and all its many subtypes), HTLV-1 and HTLV-2. And while there are many retroviruses known, most of them can't infect real, complete, humans and many more infect humans, but don't cause any diseases. If you want to get a job in retrovirology, you are almost required to work with HIV, because it causes the most prominent disease out of these 3. Mikovits became interested in CFS solely for the retrovirology. She heard from Lombardi that RNAse L is a biomarker for CFS, and from Silverman that his prostate cancer cells express RNAse L and are infected with XMRV (which is a contamination, see ghholms post). She specifically began to work on CFS to prove that XMRV causes CFS and that bias led to the mess we have now. If you view her motivations in this context, some of her actions, like blaming other CFS researchers who can't reproduce her data of fraud and don't admitting to mistakes to the finding of XMRV/HGRV in patients, make more sense. But that XMRV causes CFS was a highly unlikely hypothesis from the beginning, as it was just based on the expression of a single biomarker.
>What the heck is wrong with you people…You cannot control Prion proteins…Wake Up! Why do you think Wakefield was crushed? You cannot predict what jello on the wall will do..Stem Cells for all!!! LOL
>One more:
read this article:
http://www.sciencemag.org/content/333/6050/1694.short (free registration required)
>XMRV has never been shown to be a contaminant. The viruses discovered by the WPI and NCI are human gammaretroviruses. Silverman only gave them the wrong name after he sequenced the VP62 plasmid contamination samples that was only in his lab. The WPI and NCI samples have been proven to be VP62 plasmid contamination free. The data now shows they found what Lo and Alter did. HGRVs.
Abbie Smith has posted images that have not come from the paper or gel. Quiet an artist made them.
>"And, while I am not an expert on this, the epidemiology of the disease makes a transmittable viral illness unlikely as the cause of CFS"
Yet we now see an effective transfer of human alzheimer's tissue (not just prion) to Mice with consequent disease.
http://www.sciencedaily.com/releases/2011/10/111004113757.htm
So don't rule out transmission yet. There are too many spouses share this illness.
>It is far better to participate in telling your truth and hope that others do the same. Few people will risk it. MY HOPE is that all patients understand that no matter what, we are better off because of WPI efforts. In addition it is not ever over in scientific pursuit as technology grows.
I agree with Pat Fero below,
"I am not making a choice over this. I prefer to view all that has happened in the last 2 years as a catalyst, reaction, ACTION, reaction…..and so it goes as fuel for patients to keep pressing forward. I have spent more than 1/2 my life sick and I lost my son in a CFS related attack. I will not stop working to support better science. Thank you"
Too many people have been lost, Medical Professional have lost one more to ME (mistakenly called CFS) and the world lost an incredible advocate about 6 weeks ago Gurli Bagnell fron New Zealand. I will not stop supporting WPI, Dr. M., Dr. Peterson (whose name is part of WPI) and others who are looking
at this.
NONE of us knows what is really going on between WPI and Dr Judy M in the current situation I know she is still speaking in the UK next week and has labs that are doing her work. WPI will continue. Just as Dr. Peterson has continued to be the physician who cares for the people who are so sick. He is a great diagnostician. We will never know why he left WPI either. Between him and the institute. we have a lot more going on and I Know that the eqq has cracked and more information will come out. Look at Norway and their leading role, Belgium/Demeirlier too.
I like what Liz willow said, as well. We keep going. We don't do what that chicken did and cry "the sky is falling…." Thank you Meghan Shannon
>By HGRV, I assume they are still in the mouse-related family of viruses.
This would fit the history of all the testing that has gone on. Not XRMV but a related virus. Anti-Retroviral efficacy. Lo and Alter's work confirming a mouse related virus. Coffin says he would accept another retrovirus that wasn't Xmrv.
I'm hoping Dr. Mikovits and the WPI both end up doing very well.
Oh yeh, they must run the research lab tests, and not the partly validated commercial lab tests when it comes to studies in the future.
>Abbey Smith, did you read the link I posted about the risk of lab transmission of MLVs? You should be afraid, very afraid. They are contagious to human lab workers.
>gerwyn Morris to Annette
Aug 2
Hi Annette
Thanks for getting back to me.The trouble is that you are an honest honourable lady who is genuinely concerned about patient welfare.The people in the other organisations however such as Pandora PR CAA etc are nothing more than self interested lying shysters who will stop at nothing to bury HGRV research and destroy the WPI. If there is anything I can do at any time all you need to do is ask. Take good care
Gerwyn
>Ah yes, our guys are the good guys, all those other guys are the bad guys. Nothing is our fault, it's their fault for pointing out our own actions. Trust us. So glad someone posted that enlightening little communiqué.