Rituximab: The Big Guns For ME/CFS

I appreciate all the good wishes I’ve received from readers. I want to assure everyone that the anonymous personal attacks don’t really bother me. It comes with the territory for hanging it out there as I have. I chose controversy consciously. This type of harassment is what happens when you step out of line and threaten the status quo. I actually kind of like the free-for-all in some ways. It lets us know what we are up against. Too much agreement makes for complacency. To people who have written that it makes you sick, please don’t internalize it. I don’t. I suspect the harassment is in fact a very few individuals. Don’t let it get you down. I do think things will calm down a bit now naturally, since I don’t foresee a great deal of retrovirology forthcoming on our behalf in the near future. I anticipate the discussion will now turn to treatment and how best to live with the disease. We should be on much more stable ground, since it is much harder to take pot shots at my medicine than my retrovirology. I’m sure someone will try though; wouldn’t it be wonderful if the criticism was considered rather than knee jerk?
The little mystery play we just witnessed, courtesy of Jason, exemplified the pitfalls of science as a religion unto itself. Operating under the guise of “science” creates a safety net for its practitioners, satisfying the need for self-aggrandizement, simultaneously providing excuses for not going the extra distance to look outside the box. Very much the same as the medical profession. The Health Director of Norway just apologized to patients for decades of neglect and abuse. I’d like to see a similar apology from the Surgeon General of the USA. An apology tied to some serious restitution. 
Personally, I was abused in every way possible due to CDC/NIH incompetence, from being unable to find adequate care to being denied entitlements, private disability to the SSDI system, all compounded by incompetent doctors, lawyers and now scientists. When I was first disabled in 1995, I had occupation specific disability insurance through Provident, meaning, if I couldn’t be an ER doctor, they had to pay, even if I could be some other kind of doctor, $6000/month for life. They harassed me with IME’s and other invasions into my life, literally forced me into psychiatric treatment I didn’t want, until I settled with them. For the sake of entertainment and telling the whole story, though it has no bearing on the discussion, my lawyer stole the money; he went to jail, after I spent a bunch more money to expose him, but I never recovered what he stole. When I was disabled the second time, I didn’t apply for SSDI right away, because I couldn’t believe I wasn’t going back to work. I applied after my first near death experience at our local Santa Fe hospital, with a thousand pages of records. But it turns out my last “date of insurability” was before that, so it was over before I knew I needed to build a case. Since I didn’t have a correct diagnosis for 15 years, I’m completely screwed, case sitting in appeal for 2 years as I write this. All because I didn’t have a diagnosis. And the new ICC wouldn’t have helped. It is coming to light now, that although I didn’t know what was wrong with me, Provident, in fact, did know. There is a class action suit about those policies, sold before so many yuppies were becoming disabled early in life, but since I settled, I can’t participate. A cluster fuck, as they say in the military. 
The observations that my behavior is not in line with what is considered “professional” has me thinking about what professionalism means to me now that I am reinventing myself yet again. According to Wikipedia, the criteria for a professional are: 
  • Expert and specialized knowledge in field which one is practicing professionally.
  • Excellent manual/practical and literary skills in relation to profession.
  • High quality work in (examples): creations, products, services, presentations, consultancy, primary/other research, administrative, marketing, photography or other work endeavors.
  • A high standard of professional ethics, behavior and work activities while carrying out one’s profession (as an employee, self-employed person, career, enterprise, business, company, or partnership/associate/colleague, etc.). The professional owes a higher duty to a client, often a privilege of confidentiality, as well as a duty not to abandon the client just because he or she may not be able to pay or remunerate the professional. Often the professional is required to put the interest of the client ahead of his own interests.
  • Participating for gain or livelihood in an activity or field of endeavor often engaged in by amateurs b : having a particular profession as a permanent career c : engaged in by persons receiving financial return.
  • Reasonable work morale and motivation. Having interest and desire to do a job well as holding positive attitude towards the profession are important elements in attaining a high level of professionalism.
  • Appropriate treatment of relationships with colleagues. Special respect should be demonstrated to special people and interns. An example must be set to perpetuate the attitude of one’s business without doing it harm.A professional is an expert who is master in a specific field.

I admit to difficulty with the last two at this point in my career. My disgust with most physicians and ‘the profession’ is profound and being ‘appropriate’ is low on my list of priorities. But I certainly can live by the rest of it. Personally, I would have been better off with a good village witch doctor than any of the so-called professionals who ‘took care’ of me for the first 15 years of my disease, all of whom did great harm to my mind, body and spirit. In fact, one of my goals in life is not to need a doctor or a lawyer:).

In general, CFS patients get better care if they don’t tell doctors what they have. Many patients have told me this. Have chest pain or a belly ache and need to go to the ER? You will get better care if you just talk about the chief complaint. Sad, but true. Maybe it is finally changing? XMRV, however it plays out, has brought us into the spotlight at last. We are finally worthy of study, not only because of numbers of affected people, but because maybe, just maybe, we are sick. And not because of our wrong thoughts. We don’t tolerate stress, because we have diffuse hormone receptor insensitivity and depletion, including stress hormones. The response to stress is abnormal, and not because of distorted thinking. Viruses hi-jack cellular machinery, and retroviruses do it on an evolutionary level, using the organism’s own DNA to replicate, either by reverse transcription and assembly of new viral particles or mitotically. Stress is an inevitable consequence of life, and some retroviruses have evolved a strategy to take advantage of this, hormone receptor elements that, when activated, turn on virus: Glucocorticoid Regulation of Murine Leukemia Virus Transcription Elements Is Specified by Determinants within the Viral Enhancer Region. Celander. Note interesting evidence that steroid responsiveness of MLV’s may be competitively inhibited by progesterone.

And now we have the Rituxan study from Norway:

An unintended effect of treating a patient for cancer was remission of CFS symptoms and the patient’s doctor actually noticed. The entire CFS community owes the doctors who pursued and published their study a debt of gratitude. Whether Rituxan pans out for CFS or not, Drs. Fluge et al gave CFS patients big guns, and reported scientifically (though blinding doesn’t seem possible since the patients could probably mostly tell who got the drug).

Rituximab is not the only chemotherapeutic drug to result in temporary remission of CFS symptoms. The question is why and who might be helped by it enough to justify the risk. Given that it is possible to die from a trial of the drug, it isn’t an academic question, or mostly about money and politics, as with arv’s. If you want to look at the disease as an immune disorder of unknown etiology, rituximab, might help a subset of patients by depleting CD20 expressing B cells. However, even for rheumatoid arthritis patients, 40% or so don’t respond to B cell depletion, even though B cells are clearly involved in the pathogenesis of that disease. Rituximab also selectively depletes certain T cell and NK cell populations. Most cytokines/chemokines are made by T-cells, but under certain circumstances, B cells make proinflammatory cytokines also. Here are some hints:

And the argument against: The drug cripples immunologically on purpose and we may be more at risk than rheumatoid arthritis patients for the worst possible outcome:

Take a look at this paper, addressing the question of why some RA patients respond to B cell depletion and some don’t: New Insight in the Mechanism of Action of Rituximab: The Interferon Signature Towards Personalized Medicine. Verweij. It suggests that particular levels of gene expression, disease phenotype, low IFN signature, predicts response to treatment. This paper also talks about the effect of the drug on macrophages, shifting them to a more mature, less proinflammatory stage, possibly suggesting some mechanistic overlap with the positive clinical effect observed in some patients with GcMAF. Since a course of treatment, 2 infusions 2 weeks apart, costs $9000, generally needs to be repeated every 6 months, and includes significant risk of morbidity/mortality to the patient, it is important to predict response to treatment. There are over 8000 papers on PubMed about rituximab (a search for ‘chronic fatigue syndrome’ brings up 5430 papers). The arthritis literature seems to find the risk acceptable. The risk of hypotension, anaphylaxis from the infusion itself, can be ameliorated with skilled administration and/or concurrent treatment. The increased risk of infection, deemed mild to moderate, in the arthritis literature, is anecdotally significant, according to doctor friends of mine who have treated complications of the drug. There is a small risk of sepsis, fulminant hepatitis B reactivation and PML (progressive multifocal leukoencephalopathy). It does appear that the risks decrease for a particular patient with time, though the longest patients have only been followed for 5, to at most 10, years. Longterm Safety of Patients Receiving Rituximab in Rheumatoid Arthritis Clinical Trials. Vollenhoven.

Although I am enthusiastic that someone is talking about big guns for CFS, my initial reaction was, I’ll sit this one out until we know a lot more. It scares me. But when I answered Ali’s questions about why I’m not more interested, she said, “I’d take a small risk of death every 6 months for a complete remission.” So Russian Roulette. I have a patient with a high Rheumatoid Arthritis Factor, degenerative arthritic changes on MRI and clinical synovitis. She could probably get it covered, a problem for most CFS patients. Though I wouldn’t prescribe it at this time, this patient could seek treatment from any number of rheumatologists who have vast experience with the drug.

Dr. Michael Snyderman’s comments of this morning:

In my practice, rituximab at 375mg/m2 causes hypotension in most patients, about 60% need downward adjustment of their infusion rates and about 25% the hypotension is severe enough to be symptomatic. I would expect the hypotensive reactions to be more severe and frequent at the dose of 500mg/m2 used in the CFS protocol. If the patients signed a proper consent form they would have been warned that hypotension would be a risk, therefore most patients would be aware that they had received rituximab rather than placebo. The physicians who administered the rituximab would have to be adjusting the infusion rate in most patients and would also be aware that they had given the active drug rather than the placebo.

Therefore the statement that the study was double blinded is incorrect; it is not possible to double blind rituximab for the above reasons. Furthermore, the results are based on subjective, “how do I feel” criteria which could be influenced by the patients knowledge that they had received rituximab. We have not proven that there is an expansion or clonal component of B-lymphocytes in CFS. There may be but it has to be proved and we have just started looking on a small scale. I believe that the MLRVs (I know this is politically incorrect nomenclature) probably integrate into a number of cell types. I and other people with CFS and cancer have clonal gamma delta T-cell expansions. Gamma delta T-cells are a more likely source of the well-known and accepted elevation of cytokines/chemokines in CFS than B-cells. I could find very little about cytokine/chemokine production by B-cells, certainly with respect to those elevated in CFS. I did a search as to the origin of IL8 and could only find that neutrophils and “macrophages” which would be derived from monocytes could make IL8. I could not find any article saying that B- or T-lymphocytes made IL8 but maybe they do, the area needs more research.

With respect to the present preoccupation with B-cells in CFS all I have seen were nebulous references to autoantibodies. What are the autoantibodies that cause CFS? This is too much of a leap of faith for me. Finally, rituximab would have no activity against the T-cells that are responsible for elevated cytokines found in many patients with CFS.

It maybe that CFS patients have a veritable zoo of clonal cell lines that interact with each other. I would not be surprised at all if there was a clonal expansion of cells derived from monocytes in CFS. Monocytes are the source of macrophages and microglial cells. This would fit Dr. Sandra Ruscetti’s belief that microglial cells are part of the problem with CFS. So, MLRV would integrate into monocytes, increased levels of IL8 would be made and rogue microglial cells would cause problems in the CNS. Rituximab would have no activity against monocytes or microglial cells.

Rituximab is very immunosuppressive and patients who receive it are at risk for opportunistic infections including the dreaded progressive multifocal leukoencephalopathy which is caused by the JC polyoma virus. I hope to soon prove that I have a unique MLRV (not “XMRV”) and it therefore doesn’t make sense to me to take an immunosuppressive drug. In conclusion, we need new treatment for CFS but for many reasons I don’t think that rituximab will be useful. 

Occam’s Razor, as applied to medicine, advocates looking for diagnostic parsimony, though patients may of course have more than one disease; the subsets of patients I think related, e.g. treatment refractory Lyme Disease and ME/CFS, may in fact have different diseases. In any case, it is a big step up to have an immune disorder rather than a psych disorder. But with respect to an explanation for all the manifestations of the disease, plus the epidemiology, I still think a retroviral hypothesis fits best. Clonality contributing to pathogenesis fits. MLV’s replicate mitotically, by clonal expansion, in addition to conventionally (as does HTLV). This is a likely explanation for the incomplete response to arv’s in people with advanced disease. The little bit of information that we have about this in CFS suggests that clonal expansion can happen with various cell lines, so B cells might be implicated in some patients, but T cell clonality more important in others. LabCorp has testing to look at both T cell and B cell clonality (southern blot and PCR).

Epigenetic factors are clearly a very important piece of the clinical picture, likely impacting who gets sick and who doesn’t. Here is an excellent article to start the discussion, illustrating where the environmental piece comes into play. As I’ve said before, I think environmental and retroviral illness are two peas in a pod, not in any way mutually exclusive hypotheses. Why Your DNA Isn’t Your Destiny. Cloud.

Silverman found that XMRV induces 30 genes in vitro within 24-48 post infection. This is the kind of quality work that isn’t being done on our behalf, because XMRV is dead. For posterity, please reread Lee/Silverman. Journal or Urology. Vol 185, No. 4S, Supplement, May 15, 2011 :

EPIGENETIC REGULATION IN INHIBITION OF PROSTATE-DERIVED ETS FACTOR, A TUMOR METASTASIS SUPPRESSOR, IN ADVANCED PROSTATE CANCER A TUMOR METASTASIS SUPPRESSOR, IN ADVANCED PROSTATE CANCER Joshua Steffan, Sweaty Koul, Randall B. Meacham, Hari Koul*, Aurora, CO INTRODUCTION AND OBJECTIVES: There is, at present, no effective treatment for intervention in metastatic prostate cancer. In our recent studies we demonstrated that Prostate-derived Ets factor (PDEF) expression is decreased, and even lost in high grade prostate cancer. Using in vitro assays we show that reintroduction of PDEF results in phenotypic reversal from aggressive to a less morbid pheno- type in prostate cancer cells. Since a common mechanism of tumor suppressor inactivation is by promoter hyper-methylation, the objective of this study was to determine if and how PDEF is regulated epigeneti- cally through promoter methylation. METHODS: LNCaP cells (Androgen dependent), LNCaP C4-2B (Androgen un-responsive) and PC3 (Androgen independent) prostate cancer cell lines were maintained in their respective growth media supplemented with 10% Fetal Bovine Serum and antibiotics. PDEF was over-expressed using bicistronic vectors and delivered by retroviral transfection. Where indicated cells were pretreated with 5-aza cytidine (5-azaC) for various time points prior to measurement of PDEF expression by RTPCR method. Cellular RNA was isolated, reverse- transcribed into cDNA, and PCR was performed using PDEF-specific primers. Migration (scratch assays and Boyden chambers without Matrigel) and invasion (Boyden chambers with Matrigel) were per- formed on cells treated with or without 5-azza-2’-deoxycytidine. RESULTS: We observed decreased PDEF expression in pros- tate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Treatment of prostate cancer cells (PC3 cells) that do not show any PDEF expression with DNA methyl transferase inhibitor, 5-azaC, led to expression of PDEF in a time dependent fashion, suggesting epigenetic mechanisms in suppression of PDEF in advanced prostate cancer. Our studies suggest that treatment with 5-azaC results in decreased cell migration and invasion, concordant with an increase in PDEF expression. CONCLUSIONS: These studies demonstrate for the first time that inhibition of PDEF expression in aggressive prostate cancer cells is modulated by epigenetic mechanisms. Based on these exciting results, we propose that epigenetic regulations are critical for progres- sion of prostate cancer to aggressive phenotype and that demethylating agents like 5-azaC may serve as effective agents to prevent prostate cancer progression. 

Since XMRV is dead as a human pathogen it makes no sense for the Lipkin study to use precious specimens collected at a cost to the taxpayers of $450,000 ($1500/specimen to the doctors for each patient and control, 150 of each) to allow WPI to try to prove that they can do what they already proved they couldn’t do, and now without a chief scientist. It seems to me that the patient community should object to that vociferously. Rather, the rest of the money should be spent on deep sequencing, looking for the actual cause of the disease. Why not allow Dr. Lipkin to look? He said in Reno that if someone gave him a million dollars he’d look. Let the virus hunter hunt look for it, not Unevx. What if they don’t find it? Then it’s really dead. It is most definitely not in our best interest to give them another shot. They should sink or swim on their own, not spending the very few tax dollars earmarked for investigating causation in our disease. We should certainly not be willing to have the WPI be our last best hope at this point.

I thought this article particularly interesting while we consider where our disease came from: Canadian researcher traces AIDS to single bush hunter from 1921. The scientific community is showing a stunning lack of concern with respect to live vaccines and other medical technology known to be contaminated with animal retroviruses. The case is growing. Too many clues. The burden of proof is on the folks selling the stuff. A little humility, in short supply in the past, is certainly in order now. The band is playing on again.

Today’s song: I Won’t Back Down

With A Little Help From My Friends

Somebody posted on FaceBook a few days ago: I love my computer, because my friends live in it. For no one has that been more true than for me, despite the trolls. I started to write, because I was so excited about what was happening and thought sharing my experiences would be useful. My selfish motivation was to move it along as quickly as possible, so we could all get on with it. I thought the anecdotal clinical responses might drive it, along with fear of a contaminated blood supply and the lure of money for the drug companies. I actually felt a twinge of regret that by the time I was ready to work, it would be all figured out. Ha!

I wrote because it was all I could do at the time, and it didn’t matter what anyone thought about me. Work was an impossibility, a fantasy. Now I’m working part time and taking care of a very small number of patients. I am caring for them in a very hands on way, like they are all Ali:). I will be max’ed out very quickly. I am not selling a protocol or seeking patients on this blog. That will take care of itself word of mouth, as it did in my last practice. I am writing to share with people who could never get to me. Many readers are on the other side of the world. My approach to treatment is very moderate and non-invasive, having learned from the mistakes of the past. Primum non nocere. Why should that threaten anyone? Unless you disagree with my question authority point of view. Honestly, the idea that what I’ve been saying has ignited such a firestorm is a puzzle. You would think that people would be happy that a doctor is willing to share openly, not to mention hearing that someone is making progress. Instead the whole thing has spun into some weird parallel universe where the critters all have big, sharp teeth. That’s what has me scratching my head. The response is so off kilter to the message.

My interaction with Jason was a personification of the problem. After insulting me on my own blog to the point that I thought he was a troll, he sent me a request to review the science and post his thoughts. I responded as warmly as I knew how. The only thing I asked was that he learn something about the disease. I offered to share with him, so that the time he put into it would be meaningful. He said he would review the literature. Period. End of discussion. If it isn’t in the literature, it doesn’t exist. Below is my second letter to Jason.

Dear Jason, 

I deeply appreciate your coming forward as yourself, and not an anonymous poster. I will publish what you write without editing. I will only state that it is opinion, not fact, and that I think you were brave and generous to do it. If I disagree, I’ll blog my thoughts after. The only way I wouldn’t post is if it was clearly written from a place of needing to prove me wrong. I am asking you to come to this project with a “beginner’s mind”.

“In the beginner’s mind there are many possibilities, but in the expert’s mind there are few.”
~ Shunryu Suzuki

In your quest for objectivity, please don’t forget that there are real people with a horrible disease, many trapped in their beds with no medical care and no hope. I am the CFS suicide hotline. The shoulder to cry on. I take calls and email regularly. I am not exaggerating the importance of what you write. Please take that responsibility very seriously, even if it makes you somewhat less “objective”. Think about why the hypothesis might be right, not just why it’s wrong. Don’t decide going into it what the answer is, even though I have attacked some of your heroes, you think unfairly, but I think they have shown an incredible lack of compassion, cruelty to oppressed people. 

I don’t think that you can fully consider the hypothesis without understanding the pathophysiology of CFS, autism, Gulf War Illness, Lyme Disease. Also human and animal retroviral disease. The veterinary literature is very telling. What you will find when you start to look into viral etiology of CFS is literature proving it isn’t EBV or HHV-6. There is nothing but the recent furor to connect CFS to retroviruses. Other than Michael Snyderman’s data, published as a poster presentation. So the only choice is to start with a hypothesis and work backwards. Please bear in mind, I am a doctor, not a scientist. I sit in a room with people who want to die because they have lost everything, are suffering unbelievably and are laughed at by doctors and scientists. Imagine having the worst day of flu of your life and having it never go away (not the way I got sick btw). Then maybe a hundred other horrible symptoms, pain, nausea, intractable headache, chronic cramps and diarrhea, sleep deprivation. Then your doctor sends you to a psychiatrist who says you are too focused on your symptoms. Cowboy up. Only you can’t even sit up. Then your kids and husband start getting sick too, and nobody cares. 

 
I have never claimed to be ‘objective’. It was an ah-ha for me. A 15 year mystery, that almost cost me my life (transfusion, emergency surgery, small bowel resection at midnight, TPN), beginning to give up its secrets. A mystery that ended any chance for a normal life for my beloved daughter at 13. I am tearing up as I write this, thinking of what she was like when she was the size of your precious baby. Not that she isn’t wonderful now, but her life is so diminished compared to the one she could have had. I was 41 and a successful doctor, so I had something to fall back on each time I’ve recovered enough to do something, but the kids who get sick in adolescence never get to live at all. The second generation is sicker. The youngest person I’ve heard of with CFS is 4, not autism, CFS, 3rd generation. Grandma is very sick. Mother, a doctor, a little sick. Doctors and nurses are over represented in the patient group. Also vets. You should be able to share in my outrage at the lack of epidemiological studies, since it doesn’t impact your field, once you start to hear what the patients are saying about their families (some on my blog). I am looking forward to your figuring out how little money has been spent on a disease that affects so many and causes so much disability. You wouldn’t believe the untapped talent in my mail. 


Judy Mikovits heard the pain of the patients. Too much for her own good. She took all the desperate mail and was terribly affected by it. She visited horribly ill patients in the UK and Norway, who are being abused by their doctors and governments. Patients lying in dark rooms with ear protection and feeding tubes, for years; too weak to roll over, begging to be let out of their bodies. I kid you not. I got involved with the WPI because Judy was answering all this mail, from people who were writing to me also, and she was really bad at it, while it was a reflex for me. Judy Mikovits is a gifted scientist, with human frailties. She was working in an impossibly toxic environment with no help and the entire old boys network coming down on her. She did lots of things wrong from a PR point of view. What she did or didn’t do right scientifically will all come out in the wash. It is the finding the novel pathogen, or more likely pathogens, the theory that matters now and that must be investigated. Even though you prefer deductive reasoning, genius requires induction. There is an enormous opportunity here for you, both as a scientist and as a humanitarian. It is possible to be both. 


I have brainstormed with Frank Ruscetti. He thinks it’s real. Sandy Ruscetti thinks it’s real and she understands the murine retrovirology better than almost anyone. I had dinner with Ian Lipkin. He said “it smells viral”. He was clearly very interested. It isn’t one of the known pathogens… 


I know you are in the lion’s den and need not to get eaten. But always question authority:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/?tool=pubmed 


The ‘souless freak’,
Jamie 


PS. I didn’t send any letters.

PPS. Another Suzuki Roshi quote: 

If you want to enjoy the movie, you should know that it is the combination of film and light and white screen, and that the most important thing is to have a plain, white screen.
~ Shunryu Suzuki

Jason 
Jamie

I sent our correspondence to five trusted friends for reality testing, two of whom are well known advocates, before I answered Jason’s response to my letter. Complete consensus. One of them called him a ‘snot’ and I did pass it on to him, I confess. If the shoe fits. I suggested he start his own blog. I’m sure, in fact, Jason is a very nice young man, with a young family, trying to get by, like all of us. He doesn’t even really know what hit him, removed as he is, working in an ivory tower environment. He was unwilling to take off the blinders and my readers don’t need any more negativity. Plenty of that to go around. Patients, with no medical help, have to decide what to do, in real time, with incomplete information, in a very imperfect world. And I have to treat patients in the here and now.

The attacks are an energy suck. Not just my energy, but readers’ precious energy. Any suggestions about how to deal with it are greatly appreciated. It is very strange to be judged by anonymous people. It’s not just me that they are judging, but the uppity patients who agree with me. If nobody was reading, they wouldn’t bother with me. It is the growing sense of community that is spooking them, not lil ol me. Being forced to defend myself again and again, to prove I’m right, when I’ve never said that I am, serves no one. Being right is the booby prize.

I want to get better. I want my daughter, my patients and my readers to improve. If somebody has better ideas, please share them. The name of the blog is X Rx. I think it is still appropriate. Virologists call an unknown pathogen X. Elaine De Freitas called her virus X. I concede the URL is obsolete. But the point is, it does me no good to be right if it doesn’t result in treatment, at least an approach to the illness. We can start to look at our NK cells, number and function, as well as cytokines. There are many things that can be done for AIDS, in the alternative medicine world, in addition to HAART. Let’s look at those. One of the reasons we are better is the excellent help we’ve had from our FP, Russ Canfield, a smart, young doctor in Santa Fe, who has a profound understanding of the functional medicine piece, which I didn’t find cost effective when I was in practice last time, but which, he is slowly convincing me, has made progress since then. I have a longstanding interest in herbs. Trying to put it all together, like everyone else. The blog is an assist, bilaterally, except for anonymous attacks and gratuitous insults. I will persevere, as the vast majority of the feedback I get is positive, even from people who disagree with me.

Today’s song: With A Little Help From My Friends
by Joe Cocker

Null Result

“Appeal to ignorance – the claim that whatever has not been proved false must be true, and vice versa (e.g., there is no compelling evidence that UFOs are not visiting the Earth; therefore UFOs exist – and there is intelligent life elsewhere in the Universe. Or: there may be seventy kazillion other worlds, but not one is known to have the moral advancement of the Earth, so we’re still central to the Universe.) This impatience with ambiguity can be criticized in the phrase: absence of evidence is not evidence of absence.” ~ Carl Sagan. The Demon-Haunted World: Chapter 12 – The Fine Art of Baloney Detection.

I am feeling subdued. Jason contacted me back channel after our conversation in the comments of the last blog. We said what we each perceived to be a reach across the divide, but it quickly became clear that the distance was too great. I am deeply saddened by this state of affairs. ‘Scientific community’ is an oxymoron. Everybody in their own labs doing their little absence of evidence experiments, knowing nothing of the disease in question. Argumentum ad ignorantium. A false dichotomy. I own that I am one half of the dichotomy, though unlike the other side, I don’t fail to consider alternatives. The obvious third alternative here is there has been insufficient investigation to reach a conclusion. Unfortunately, it’s the folks with the above ‘vice versa’ view that we need to do the work in order to have enough information to know what is true and what is false. Deductive reasoning leads to blinders and inductive reasoning can go to religion; I acknowledge that. All valid alternatives must be considered. Hume’s Problem of Induction puts the current conundrum in a larger philosophical context.

Taking heart in the belief that regardless of the tone or outcome of our interchange, progress has been made with Jason. He will never, ever forget this and it will inform his life, even if it’s not conscious. Now he gets to decide if he is willing to see and be responsible for his assumptions and motivations. He’s just found out that there are consequences for those, even the ones you aren’t paying attention to. Especially the ones you aren’t paying attention to. It’s only a seed right now and who knows what fruit it may bear. Somewhere, somehow. Even if the only person he feels sorry for is himself, that’s a start. I articulated the ground he was standing on and he didn’t want to see it. And when it got handed to him plainly and clearly it hurt. Rightfully so, because I held up a mirror.

I didn’t even see a possibility for mediation. No common ground at all. It felt like a microcosm of the entire situation. The emperor has no clothes, but he is sighing with relief, because nobody is going to know. They aren’t going to have to deal with us. XMRV is going away. 

The divide that I was unable to bridge was our hope for reaching the promised land anytime soon. I don’t see it coming in the near future, unless it is from ‘left field’. Chronix? Andrew Mason’s lab? We can hope there are some others quietly going about their work, waiting for the dust to settle. I thought I detected real interest in Ian Lipkin when I met him. Here are Kent Heckenlively’s always incisive observations: The Wakefield Rehabilitation in Age of Autism.

I feel like a lightening rod, a lot of anger going to ground through me. Making people squirm isn’t my first choice, but I guess it’s better than being ignored. I’d rather be a lover than a fighter, but it seems it isn’t to be. I am propelled by the ‘atta girl’s I get from people who have had no voice for a very long time. It seems more important than who is pissed off or hurt.

More mail from Dr. Peterson’s patients. The jist is, he is really sad, but can’t say anything because of Annette Whittemore. And Annette Whittemore has never been willing to clear it up publicly either. These people are holding themselves out as our best hope. A little transparency is in order. I repeat. I have never met Dr. Peterson. Everything I know about him and what happened at the WPI came from the people there. Not one person, a bunch of people, but all hearsay and I plan never to repeat any of it. I believe patients first and foremost, so I apologize to Dr. Peterson. I don’t understand the apparent fixation with HHV-6 though. It seems so much less plausible than a retroviral etiology. I do admire his persistence above all else. Anyone dealing with CFS for 27 years without going insane deserves huge gratitude and congratulation for unusual survival skills and fortitude.

Like everybody, I hope the CFI gets somewhere. I’ve had a hard time getting past the name though. Seems kind of like the tee-shirt. I wish the ‘Initiative’ was not coming from the CAA, given their track record. I can’t find much in what’s been made public to suggest that resources will be spent looking for novel pathogens. We need more than a better definition of the problems, not that that isn’t important. Whether you like the CAA or not, it has managed to completely divide the patient community. Two different forums and never the twain shall meet! Very sad. Even we, the marginalized, can’t come together because so many see the powers that be at the CAA to be in bed with our captors. So ugly.
Transmission questions have been the hardest to answer, since I placed myself in the position of trying to answer questions. At this point, the scientific community has essentially alleviated you of any responsibility for transmitting a retrovirus. If my hypothesis is correct, pretty much everybody has something by now. It would appear, without the benefit of real epidemiological studies, that bad things went out horizontally at certain points, suggesting a few viruses with higher pathogenicity, or ones that combined in bad ways with what was already there; but by now, it’s pretty much of a mish mosh. What this means practically speaking for PWC’s is, sexual contact with healthy people may be more dangerous for you than them. I don’t hear that prior sexual partners of brief duration get sick, even many years later. I’ve heard occasional reports of spouses getting sick fairly quickly, but it seems to be rare. HIV precautions seem good enough for us too. 
From an internet friend who is helping me to stay positive:
Emotions run high because there is a huge reservoir of feelings and thoughts that has had no outlet for years and years. So many have suffered silently, trying to be good so they could be believed, much less helped. It’s one thing to ask for help and another to become a supplicant and plead and beg. Unfortunately pleading and begging is what we’ve been reduced to. Seems like birthing a new paradigm is just like any other birth, difficult and messy, but oh, the results matter so much. We have the old paradigm fighting tooth and nail to stop an unstoppable process. Progress will be made in strange, uncomfortable ways, but move forward we will.

Today’s song: World on Fire


Some answers…

Although the personal questions in the comments of the last blog were asked very rudely, I will try to answer them anyway. I have represented myself as an open book, and I truly am, even though it gets me in trouble, as witnessed by the tone of the questions. Most of this has been said before, but things have changed, and perhaps it needs to be said again, from our current vantage point. So, I’ll give it a go.
I am not trying to persuade anyone to take anything. I share my reasoning, with references, within the limits of my writing ability. I intentionally report before I know the outcome so that it won’t be seen as my pushing a particular protocol. I am in the same boat as everyone else. I don’t know what to do to fix it. I don’t believe that anyone else does either. Arv’s are only one of the treatments I have written about here. I am sharing my thoughts and experiences in real time. 
This is a blog. Opinion. If you read it carefully, there are inconsistencies. I even reserve the right to change my opinion from time to time. I try to summarize occasionally, but yes, a “casual” reader might come away with something I didn’t intend. I am not sure what to do about that. I cannot recapitulate the entire blog each time I write. It is an ongoing discussion, not “the truth” at a moment in time. Almost everybody gets that, I think.
I am endlessly surprised that my opinions are so controversial and can evoke such ire. Most of it seems common sense to me. It is incredible, and very telling, that there are actually people that want to restrict my freedom of speech! Why does anyone care if others find my musings useful? I am not telling anyone else what to think. I have said repeatedly that I could be wrong about anything. If I were to say nothing until everything is scientifically validated and I was positive, I would never say anything at all. I am learning as I go, as is everyone. For some peculiar reason, I seem to need to write, and some people find it helpful. The blog is the best I can do, with the limited energy and time I have left, and I am grateful for it. When Ali suggested I write a blog, I didn’t know what a blog was:). The patients who comment and write are very sophisticated and opinionated all on their own, not needing me to tell them what to think. They ask for my thoughts so they can put the information into their own equations, not take it as some kind of truth written in stone. The reflex to restrict what I say so that the poor gullible patients won’t hear it is patronizing. And to the conventional physicians who might be reading, why the sudden concern for our well being? There are many useless things that you are willing to prescribe that are much more dangerous than arv’s.
I have never claimed to be anywhere near “well” and I have said all along that there were confounders with respect to our treatment with arv’s. As noted in the comments, gamma retroviruses replicate by clonal expansion, so we need specific drugs, but transcription of viral proteins and the assembly of new viral particles may be involved in pathogenesis, if the hypothesis is correct. I am endlessly reevaluating everything with new information as it becomes available. I am not in fact a “true believer”. I would love to hear any alternative hypothesis that fits close to as well. Anything at all that might suggest a direction to turn for efficacious treatment. I am dismayed that we are back to having an idiopathic immune disorder, albeit repackaged to sound like good news. Redefining it as a syndrome, yet again. 
There is no way to know if arv’s are helping us at this time, as I have said several times. I expected viral load measures and other ways to monitor that didn’t pan out. I did monitor several likely parameters which showed trends, but not convincingly enough to be useful. There are specimens sitting at the WPI that might contain valuable information. I certainly hoped it would be less ambiguous than it turned out to be. But there are others that experienced what we did, apparent cause and effect improvement from starting arv’s (often after an initial mild symptom flare). Some of them have written on this blog. I am NOT saying anyone should take arv’s, and never have, only that they shouldn’t be forbidden. The main problem I have recommending it as an option now, is that because it isn’t being studied, anyone starting will likely find themselves where we are, not knowing what to do for the long haul, and no help coming anytime soon. I actually think it is probably mostly a moot point now; the forces against have essentially won, shut it down for all practical purposes. The important thing isn’t really even arv’s, which at best only help incompletely, but our inability to get any help at all due to the attitude displayed in the reaction we have seen to the idea.
There are many drugs that are used because they work, even though the mechanism is unknown. One would think that for a debilitating disease which affects millions of people, for which there is no meaningful treatment, somebody would want to find out if that might be the case here. The usual way that happens is somebody has a good case, publishes it and then it gets studied. I have reported our experience. The burden of proof is not on me. What if it was a serendipitous discovery for the wrong reasons? The reaction of the medical community to trying arv’s is irrational, as the reactions of the medical community often are, especially when it comes to anything to do with this disease. The reaction of the scientific community is a joke, with no basis for an opinion at all; practicing medicine without a license, understanding nothing of the disease about which they are so opinionated.
Take a look at this paper: Zidovudine in primary Sjögren’s syndrome. Steinfeld. Rheumatology (Oxford). 1999 Sep;38(9):814-7. Did everyone get up in arms about this small clinical trial? Were the authors discredited for trying it? It doesn’t look like anyone followed up on it.
I have shared many personal details here, both physical and emotional. I have been very forthcoming, approaching undressing in public at times, so it is strange to be accused of “hiding”. The problem is that my sharing a list of symptoms that are “better” than before isn’t terribly illuminating, since some things are better or gone and some things aren’t. I even have a couple of new things. Like most ME/CFS patients, my condition changes from day to day and tweeting my moment to moment condition would benefit no one. However, I will try to define the big things. 
The most tangible thing that happened to me, seemingly from arv’s, was the near resolution of my chronic malaise. I had it much of the time for 15 years. It went away shortly after starting AZT/Isentress and I almost never have it now. So 90% of the time before, 10% or less now. That alone was life changing for me. 
My down periods used to last for 5 days to a week at a time, and now, rarely more than part of a day. The worst moments happen less often.
When I started arv’s, I never slept more than two hours without awakening, and I didn’t dream at all. I now often sleep all night with one or two awakenings and I dream normally. My day to day wellness is linked to the quality of my sleep in a chicken or egg fashion, so this improvement is key. 
Painless migraines (scintillating scotoma without headache) and hypertensive crises are much reduced in frequency.
Another “big thing” that happened: I experienced a definite decrease in my peripheral neuropathy pain at one point early into arv’s. However, trying to explain one’s pain to anyone else is an exercise in futility. The pain I have now is worse than pain that almost drove me insane at the beginning of my illness, but my coping skills are very different. Still when the reduction happened, it seemed definite. I am not pain free, but my pain is quite tolerable and does not require pain medicine. Others have also reported less pain on arv’s. Again, I am reporting, not selling. For everyone who thinks they were helped, somebody else thinks they weren’t, but the risks of trying it are pretty minimal with proper monitoring.
I acknowledge that it is possible that all these things happened in spite of, and not because of, arv’s. 

A big disappointment for me has been that the abnormal response to big time stressors remains, though it may be attenuated. Impossible to tell.

As for my daily functioning? I am able to work long days, most days, electronically (phone, Skype, email). I don’t have brain fog, but do sometimes have more symptoms after mental exertion. I am limited physically, more so in Santa Fe than Hawaii. I can climb a couple of flights of stairs with some dyspnea, more if needed, if I go slowly. I can usually walk several blocks, but might have some mild PEM if I overdo it, though my exercise tolerance is very variable. I don’t need handicap parking. I have no difficulty lifting groceries, etc. Resistance exercise is easier than anything aerobic. Swimming is easier than walking. Standing still is the hardest. The most physically challenging thing I have to do is negotiating airports and I use the airport wheelchair service for that. Gentle yoga is helpful. Pretty much all of the above is better than before I started arv’s, though as a commenter said, and, as I have said all along, other things happened too, before, during and after. Also my illness historically follows my state of mind (knowing full well how unPC it is to say that out loud). I am also much more tolerant of symptoms than I used to be, and not a very compliant patient, more confounders. 

I can only work part-time face to face, a couple of hours at a time, but I’m OK for many successive days. I could fake it for longer hours than that, but don’t want to do that. My patients travel a long way to see me, and I want it to be useful and special. I am seeing new patients for 4-5 hours on two different days, which is working out well for all concerned. It is a unique, collaborative endeavor. Sick doctor and sick patient. I am limited, but can function fairly reliably, though there are days when it’s tough; however, there are more days when it isn’t. 
When I started arv’s, I was unable to speak on the phone, because of auditory processing disturbance. I also had to lie down most of the day, only sitting or standing for a very short time, and I now sit up most of the day. Standing is more difficult some days than others, but there is never a time when I can’t if I need to; that was not always true. 
So huge functional change in the last 20 months on arv’s, but improvement started about 6 months before that, with cessation of Lyme and symptom-based treatment. From housebound to functional, but not at all “well”. I have written about the reasons why I abandoned the use of rating scales to evaluate our experiment and don’t want to rehash it again. It is sad that it’s all we have. I am collecting them on my patients, but don’t expect them to be as useful as patients’ subjective reports. Yes, I do believe what my patients tell me.
My illness certainly isn’t gone, though it has lifted, lessened, but it is a relapsing, remitting illness all on its own, making it extremely difficult to assess cause and effect. I have said this over and over again. I am fully aware that many ineffective or harmful treatments have been perpetuated because of this feature of the illness (see my prior blog entries about Lyme Disease treatment). Whenever anyone gets better, they think it’s because of whatever they were doing at the time. I received an email recently from a patient who was housebound for fourteen years and suddenly improved enough to get a life, having changed nothing. I was of course influenced by the fact that there were two of us sharing the same experience; Ali and I had similar experiences with respect to the timing of improvement, though she had no side effects and I did experience a flare of symptoms initially. And for the record, neither of us has a history of placebo responses. 
Ali went uphill during her first 6 months or so on arv’s, but had more therapeutic interventions concurrently than I did. The goal was always to get her better, not demonstrate something scientific to others. Her treatments did not prevent her crash when she tried to engage life again a year ago. She is doing well again now, but it is impossible to say if this level of wellness is the same, above or below her last remission. The “crash” didn’t become as serious as prior crashes have been for her. The important thing to her now, I think, is that she is better at this moment, and seems still to be slowly improving. Will it last? She is savoring it while it does.
My baseline was better prior to the events of early July than it is now, though I am not “crashed”. I have been under a great deal of stress, though I am hoping things will calm down a little now, so I can regain what I have lost. There is no way to know if I tolerated the crisis better than I would have without arv’s. I suffered the kinds of losses and persistent stress that have historically set me back in a major way. I stopped Isentress a while back, and am worse. Cause and effect? Who knows, but I don’t want to stay on monotherapy and am afraid to stop Viread, since a couple of patients who were forced to go off have lost gains. I may go back on Isentress. Also thinking about Lexiva (see Li on the sidebar).
I have received several demands for an apology from me to Dr. Peterson. As I said when I mentioned his name for the first time, I have never met him. Making enemies was never my intention, just the inevitable consequence of stating one’s opinions openly and publicly in such a contentious arena. My frustration feels overwhelming sometimes and it comes out in my writing. I hear from patients that love Dr. Peterson, and that does make a difference to me, but it still seems inconceivable that he abandoned the pursuit of a retroviral etiology when he jettisoned the WPI, knowing what he knows about the science and the disease. His teaming up with Konstance Knox to sink the WPI still seems really sleazy to me and his claim that it was to protect patients disingenuous. He could not have known there were problems with the VIP Dx test, or questions of contamination, at the time that he left, so how could he have been “right”. His agenda appears to go beyond figuring out how to treat the disease and help patients. I am not saying that I know precisely what that agenda is. It would seem that everyone who was involved with the WPI was hurt, likely including Dr. Peterson. I only wish that he hadn’t thrown the baby out with the bath water. 
I regret any pain that I have caused, but some truths are painful. For me, it is painful to acknowledge how few friends there are worth having in the medical or scientific communities. My referral list for mainland doctors is a very short list. When I think back over the people I have mentioned by name in an angry or personal way, it is a select few that had it coming. My lack of professional decorum, or whatever you want to call it, comes from outrage, and mostly justified. I challenge anyone who has been sick with this disease for any length of time to write their truth and not say some angry things. My writing is also full of hope for the future. It’s just that it is the hope of learning to live well with the disease, rather than to truly vanquish it any time soon.
I really think many have too much confidence in “science”, especially retrovirology, which seems to have an unusual number of landmines scattered across its landscape. Even if Dr. Lipkin were to say tomorrow that he agrees that there are gamma retroviruses infecting ME/CFS patients, it will be a long time before that translates into specific treatment. Compassionate use of existing drugs should be tried and available, especially for the sickest patients. There are possibilities besides arv’s. Lenolidamide? Pentoxyfyllin? Nexavir? Existing drugs. What others? I recently heard of a big time response to Copaxone. Is anyone looking in a systematic way? Really looking? Why does it feel almost subversive to talk about it? The idea that these patients should, or can, wait is indecent. Again, I am not trying to convince anyone to do anything other than consider my ideas. I continue to write because some find it helpful, and I have made many friends, but I have made enemies too, and that gives me pause. I do grow weary of the personal attacks, on top of everything else that has happened recently. I need to focus on my patients, but want to continue to reach out to readers; there is so little information with respect to how and what to consider for treatment in the here and now. Five or ten more years is too late for many of us. 
OK. Now I have some actual work to do:).
Aloha,
Jamie 
Today’s song: Can’t Find My Way Home 

When One Door Closes…

I believe this demonstrates a social ‘immune system’ in science which is remarkable for its ability to distinguish ‘self’ from ‘other’.  ~ From my email 

I feel like we are post-op. The patient got opened, the problem identified and resected, but the smallest movement produces a wince of pain. Still, it is becoming clear, there will in fact be a future. The dilettantes, fair weather friends, have all gone home, closed the shutters, locked their doors, and minds. Nothing more to think about. We have been easy to ignore for a long time. Now, it’s even worse than that. The scientific community is actually making fun of us in their ignorance, as is the CAA, our supposed representatives, who in 20 years have never managed to sound the alarm. If XMRV wasted some money, what about the CAA? If these scientists were truly objective, they wouldn’t all be so happy about the outcome. Mikovits, Ruscetti and Hanson, a very few others, are the only scientists in the world who know anything at all about the disease. And the fact that they care about us, doesn’t make them wrong. The rest of the scientists in this story are completely ignorant of the pathophysiology. Clueless, and not interested. Racaniello, ERV, commenter Jason, et al have not an iota of understanding about why simple retroviral disease is such a good fit. To them, it’s all about a test, not a disease. Money, glory, fame. Most certainly not about patients. They seem shocked to find out there are real people impacted.

The idea that it is better for the patient community if research into gamma retroviruses stops now, so that all the money can be spent on investigating the same old downstream effects and known pathogens, is a cruel joke.

From the limited anecdotal evidence we have, I’m pretty sure the response to antiretrovirals, even without specific drugs and without a PI, is better than placebo. The AIDS community doesn’t want to share their drugs, even though they are available to healthy partners and prostitutes for prophylaxis. Doctors who have already prescribed antiretrovirals are now, on the heels of the BWG results, refusing to refill prescriptions for their own patients who have improved on them! What could this be but politics and money? Why is the scientific community invested in creating a prohibition against these particular, not very dangerous, drugs? Why so much resistance to the idea of a retroviral etiology that they are gloating as the hypothesis takes a hit. Let’s have a party and burn Judy Mikovits at the stake. Glee. At our expense. Like psychopathic children who enjoy pulling the wings off insects. This, while babies are born with it, new cases are occurring every day and huge numbers of patients, already sick for decades, circle the drain.

The question of whether antiretrovirals are helpful or not and for whom, is a question that hasn’t even been asked, let alone answered. It is politics, not medicine, that prevents it from even being considered. The clinical piece still strongly suggests a retrovirus, or retroviruses. It is possible that it isn’t only gamma retroviruses. ALV’s, alpha retroviruses, do pretty much the same things as MLV’s. Although it is likely that ALV’s would be less infectious to human cells than MLV’s, because of phylogenetic distance from mammals, there is evidence in the literature, by none other than John Coffin, that suggests, under some circumstances, it is possible for ALV’s to infect human cells. But he didn’t think we should worry about it: Science Fiction? and Pure Speculation (I can see and hear the virologists, rolling their eyes and snorting, all the way from here). So what’s the motivation for making sure this hypothesis is found wrong? If it is right, it’s responsible for bringing down the health of the species, so some might be a little invested. But it’s so big, that saying it out loud makes you sound crazy. We have a possible source of infection: parenterally administered simple endogenous animal retroviruses. What else causes both neurological disease and cancer? Methylation issues, multiple gene activation in the same patient, persistent immune activation, multi-generational neuro endocrine immune disease. Think top down. What else does that? The fact that not everybody gets sick, that there are various opportunistic infections, that it goes in different directions in different people, that it is of variable onset shouldn’t be so bewildering. There is obviously a greatly increased risk of ME/CFS in the partners, children and parents of patients. Too much autism found in the same families. IT IS AN INFECTIOUS DISEASE. Where are the epidemiologists? 
There have been lots of questions, people asking for clarification of the last two blogs I wrote. For the most part, if it was ambiguous, it is ambiguous to me, at least I wouldn’t personally testify to it, especially anything about who did what for the BWG. I don’t think there are any villains in this story. Only people who lost their way, sailing into open ocean in a dense fog without a navigator. People are fallible, and we are where we are because they never had a chance. Much of what ensued was like middle school more than anything else. Nothing sinister. No malice and absolutely no aforethought. It still has a middle school flavor to it, all the way to bullying in order to cover-up.
What I meant by saying that the XMRV testing that was done at VIP Dx is now null and void is that there were likely many false negatives and false positives; therefore it had no clinical utility. It cannot be interpreted. However, everyone knew that it was experimental. At the time, we were grateful to have it. Dr. Mikovits stands by the testing done at the WPI research lab. My understanding of her position is that she was not responsible for quality control or precisely which assays were used at VIP Dx, after the initial release of the test, when Cooperative Diagnostics made their bid for the market. If contamination occurred, it sounds like it wasn’t necessarily with VP62, but with the cultures from hot patients (like us). Apparently, what has been learned through all this is that the labs need to be using precautions required for Mycoplasma. Retroviruses have not been thought to be aerosolized previously, but now it seems, some probably are. There are two papers that show rapid spread through a clean lab in a couple of days, Zhang and Sfanos, linked on the sidebar. The serology is picking up proteins that are, if not actually to HGRV’s, at least very similar to MLV proteins. It has nothing to do with XMRV per se, and cross reactivity has not been ruled out. At least this is how it’s been explained to me, though I know very little about the technicalities of lab testing; more than I used to, but still not much. Therein lies a key problem, little sharing between doctors and scientists.
The slide issue seems like a tempest in a teapot to me, part of the same insanity that requires Judy Mikovits to be a perfect human being or all is lost. There is now an investigation, so in the end, we will find out what the designated judge says. What I would like to know is, how did Dr. Mikovits’s firing go from ‘insolence’ to ‘fraud’ from Thursday to Monday? Dr. Mikovits was fired on September 29 and ERV blogged her over the top accusations on September 30, I’ve been told, though I still have not been to her blog (thousands have visited mine from her site). Who fed it to her? The editors at the Chicago Tribune should be ashamed that Tsouderos was taken in. Nothing more than tabloid journalism. For the record, I waited three days after Dr. Mikovits was fired, before I wrote anything. By then, it was clear to me that it had been decided that Dr. Mikovits’ reputation was the price of the WPI’s survival and my inbox was full of unanswerable letters. I said nothing for a very long time, hoping for a different outcome. Also for the record, I did not send any letters to the press. Trine Tsouderos wrote to me and asked me what I meant by lock-down. I told her “The personnel was locked out of the lab.” (proof of which is on my computer). Nothing else came from me. 
Obviously, something went very wrong. Most likely lots of things did. I know Dr. Mikovits would like to have the chance to figure out what. I think the probability that what went wrong was a ‘fraud’ committed by Judy Mikovits is at the very bottom of my list of possibilities. I know her personally and it seems beyond improbable. Inevitably mistakes were made and everyone on the planet has something to hide, so, poor Judy, and poor everyone else involved.
I hope to never be an insider again. Two people have asked me how I could have forgotten what the Whittemore’s did for me. I have not forgotten, but they seem to have forgotten what Dr. Mikovits did for them. I was videotaped for the WPI saying they had saved my life, and it was true. I said nothing, except that I had been fired; I said that because I wanted to distance myself from the decisions being made there. But then Dr. Mikovits was fired. If I hadn’t written anything, Trine and ERV would have had the only say. But I am not going to engage in any further mudslinging going forward. I am now supposed to apologize to this one and that one, who was right because the interloper has fallen; the WPI was wrong and I stood behind them. I was a starry eyed kid then, believing that the cavalry was actually coming over the hill. I am a battle weary soldier now, having taken a few arrows in the heart. I no longer think the cavalry is coming at all, any time soon. Also, I still think that all the people I mentioned at one time or another on this blog in a negative context have behaved very badly, even if everything the WPI ever did is wrong. It’s not black or white. It never was and it never will be. The patients are the ones that get screwed, over and over again. CAA, the most divisive force in our community, HHV-6 Foundation, WPI, it doesn’t matter. Loss and more loss.

So, “Cheshire Puss… Would you tell me, please, which way I ought to go from here?”, said Alice to the Cheshire Cat.

Since I am feeling like my change the world phase is over, as Kita said, what next? My job now is to interpret the events in terms of their clinical significance, one on one. Primum non nocere is my guiding principle, as it was for my first 25 years of practice. When possible, I include the pocket book in that. It is curious what insurance will and won’t pay for, having very little to do with what might produce results with the least risk of harm. In my practice, I am using only LabCorp and Quest for labs. I am no longer interested in results from labs that have a stake in the results.

My attention is on my daughter, as it has been all along. She was “Harvard material”, as my step-father, a Yale/Harvard educated surgeon, said before he died of the late effects of treatment of his Gleason 9 prostate cancer. Ali still might succeed at having a life with the right physical and social support. For a long time I have envisioned a collective with the goal of creating a supportive, assisted living environment for young people with CFS. It is clear to me that I will be dead before there is treatment that approaches a functional cure. Whether you think arv’s are a good or bad idea, we are both doing well on them. Ali is engaging her life again, dating, going out, shmoozing with her illness. Not suffering much at all. Last time she was at this point, she did too much too soon. She is wiser now.
She is very responsive to the right treatments, now that we know what we are treating (not a specific pathogen, but still a context and approach to the illness). Folinic acid is hot stuff for her, Leucovorin 10mg IV weekly for a while, and now she is playing with the oral form, finding some of the same side effects as with Deplin. It appears to build up over a period of time, days to weeks, and cause dose dependent sleep disruption. But some amount helps the overall picture. I am hearing similar things about Deplin from patients. Important initial response, then dose related insomnia, sometimes still with improvement in other things. For Ali, the amount of folic acid derivatives required for positive effect without sleep disruption seems to be decreasing with improved wellness. So she’s tinkering. Next stop, 5-MTHF. I’m starting to order MTHFR mutation testing on my patients (MTHFR Thermolabile Variant DNA Analysis at LapCorp and MTHFR DNA Mutation Analysis at Quest). 

She continues to use oxygen with great regularity. We both find it useful for rescue, as well as believing that it supports our recovery, which seems steady and real, but slow. There was a single comment a while back that oxygen had been bad for someone, but without specifics. I want to hear about any problems, since I’ve been advocating its use. I have a lot of experience prescribing oxygen as a hyperbaricist and the risks, without adding pressure, are so minimal as to be almost non-existant. You can always turn it off, after all. Long term, there may be a risk of accelerating aging. That’s all I can think of. I can’t really come up with another reason not to try it, but I certainly want to hear it, if someone has something to add to the discussion. So far, practically speaking, my patients are liking oxygen. It is representative of the insanity in all this that patients can have Fentanyl patches for years and years, but can’t try an oxygen concentrator.
My illness is pretty much refractory to everything, except being positively engaged. For me, helping helps the most. I do best when I don’t mess with it much. I was the sickest when I was taking the most drugs. Antiretrovirals are one of the few things that actually seemed to move me. I sent specimens to the WPI regularly during first year of our experiment. Dr. Mikovits had evidence of our positive response to antiretrovirals, at least initially. I wonder where those specimens are now? I’ve tolerated 5 trips to Reno and 3 to Hawaii in the last 13 months. Pretty good for an ME/CFS patient who had been desperately ill twice in the previous few years. It is becoming clearer and clearer that I do feel better in Hawaii than Santa Fe. I think for me it is the elevation, because Santa Fe is one of the cleanest cities in the country, Los Alamos aside. However I’m hearing from lots of people that say they felt better in Hawaii but who live at sea level (and others who didn’t get better there of course). Some of those people live in really polluted places, like LA and NYC, so that may be the greater factor for them.
I am in complete and total agreement with the mold warriors that environment is critical to success, defining success as the patient’s maximum possible wellness within the context of an incurable, but remittable disease, though my idea of environment is much broader, not just avoidance, but feeding the positive, including strengthening the spirit. Stress makes us sick. My fantasy kibbutz would be organic, as chemical free as possible, MCS friendly, and of course as mold free as achievable. But as important, would be an opportunity to be alone, with necessary help, or to be able to with others who understand and support. To be able to go out, but not fear ruining it for everyone else, if assistance is needed. To not have to apologize for existing. I see the mold warriors insistence that I am the enemy as a microcosm of what anybody with this disease who finds a way out feels. Huge frustration that they aren’t being heard in the face of immense unnecessary suffering. It’s just that from my perspective, hearing from people from the full spectrum of the ME/CFS community, it’s one of many factors, most important for some, but not so much for others. 
Almost the most important thing that didn’t happen at the WPI clinic was the use of an electronic EMR by multiple clinicians, so that a large database would be created, which would ultimately be searchable by any parameter chosen. I am using Practice Fusion, free cloud based EMR. It is brilliant. It can only improve patient care for doctors using it. Converting from another method of documentation is difficult, but it’s not insurmountable. It’s possible that physicians might be able to contribute to the creation of a large patient database anyway, even though they are not physically in the same place. I mentioned a particular test above; it is beyond time that clinical research (pardon the oxymoron) was happening in a broader context than one physician’s practice. Thinking about this, and what might be still be possible…
Tonight’s song: Closer To Fine

What Next? by Kita Rael

Time to stop feeding the beast that is intent on eating us. I believe that until some sort of money making model is invented to reap CFS/ME, our community will be the target of and subject to parties and people whose job it is to keep us divided, traumatized and so focused on that trauma that we are rendered as politically disabled as many of us are physically disabled.
Can you see how this takes us off the playing field? The one we just really stepped on with so much hope not too long ago? We finally found our voices. The thing to remember is that these are OUR voices and they weren’t given to us by research, they were inspired by research. And research/government/science/(whatever) cannot take them away unless we give them away.
Yes, there is howling pain when there is a setback. What looks like a huge crash right now may well prove to be a really big speed bump, on the order of what I once encountered while driving around in Mexico. The dreaded “tope” (pronounced toe-pay). It’s about three times the size of our American speed bumps with sharp corners. If you’re not paying attention they can be lethal to your tires. So one person was appointed to watch and would sing out “TOPE!” in order to avoid more problems than were required on this particular trip.
I vote to call these latest events a pretty big tope. Everyone had their eyes on the horizon and were speeding up. Then bang. Now we are on the other side of it, maybe sitting on the side of the road. Damage is being assessed. There are some of us in fistfights in the back seat and it’s taking all of the attention off of the road. Yes, we’re still on the road, it was just a tope.
Pay no attention to the onlookers who are trying to tell you that the damage is so terrible that they will have to help tow your car off to the repair shop, (there to “try” to repair it and possibly even causing more problems than you arrived with in order to make that tope into such a disaster that you can’t continue on your way) even though, with careful inspection, you can see that you’ll probably be okay. It’s worth getting back in the car, quelling the uproar in the back seat, turning the key and easing back onto the road and heading further towards your destination.
We still have our voices. We’re still moving forward, even if we took a bigger hit than we thought possible to sustain. There will always be outbreaks of fighting in the back seat even after periods of relative quiet and harmony. An elbow will be thrown, someone will feel crowded, someone else really enjoys a tussle. The car keeps moving. Now and then it’s time to switch drivers. Either a driver got tired or their stop came along, a different destination than the majority in the car. We just saw a designated driver pitched out, but who says there can’t be a way to circle around and pick her back up, dust her off and cheer her amazing driving skills once again?
But guess what? We patients OWN the car and we actually do have a say in where it goes and how it gets there. Every time research/government/science/(whatever) throws a wall in front of us we can go around! What will we do when it’s actually a wall and not a tope? I say this was a terrific exercise in preparedness and courage and fortitude. Our community is diverse and filled with inventive and capable people, sick or not. A great example of that was the write-in campaign that morphed into such creative forms that it was stunning. Who knew? Who knew what we could be and do until it got started? We have deep resources in the people around us who DO care. That’s a proven thing.
I don’t know about you, but I still feel excitement in the air and movement with our community and also with investigations on the part of researchers. This is so different from the 25 years of stagnation that preceded the Science paper. Like it or not, the dam was breached and here comes a flood. I do not believe it can be stopped because there is the weight of aware and passionate people pushing ahead.
Again I say that I hold with this: he of the highest light wins.

No Good Deed Goes Unpunished

Yesterday made clear that it is going to be a circus. All that’s needed is cotton candy and clowns. Annette Whittemore is still selling fairy dust and the fate of humanity depends on whether Judy Mikovits was perfect or not. It’s more exciting than a high wire act. The CAA, the folks at the CDC, most of the scientific community are all gleeful. They wanted to turn the iconoclast into Joan of Arc. Since she isn’t a saint, the Salem Witch Trials is a better metaphor. If the scientific community had actually been impartial, they wouldn’t be so happy. They say it needs to be about the science, not the scientist, but in fact, it was, and is, very personal, not about the science at all.

I am not a lab scientist and cannot evaluate the slides written about in yesterday’s Chicago Tribune. I refuse to read ERV’s blog on general principles. Trine Tsouderos seems to be slumming for sources. And Annette Whittemore, who has no viable option but to blame Dr. Mikovits for everything that ever happened at the WPI, has turned to the journalist with an agenda. The debunker. Necessity makes strange bedfellows. Even discounting my own experience of Dr. Mikovits, which makes fraud as an explanation for an error extremely unlikely, it makes no sense that she would intentionally subject herself to the possibility of that fraud being detected by using the same slide again on purpose. The only person who has a reason right now to characterize a mistake, if one was made, as fraud, is the person trying to save the WPI. And maybe ERV and her ilk. Now all that money that was just raised at Vivant and the WPI annual fund raiser can be spent on lawyers to go after Dr. Mikovits, as they try to continue to lure patients down the yellow brick road. The baby in this divorce? The grants. An institute without a chief scientist and a scientist without a lab.

What’s left? A lab running a bunch of tests that I can order from Quest and LabCorp, for which insurance will pay. A CEO who, when I was there, had six people working for her, including a personal assistant, while Dr. Mikovits had two, and then one. A doctor working for himself. An awful lot of empty space. Less than no respect at the medical school. A post doc. A paper which looks like, one way or another, it will be completely discredited soon with everybody calling everybody a liar. Some GenBank sequences and related patents, which I know very little about, but which I imagine are enough to muddy the waters for everyone else, and therefore prevent work from seeing the light of day. Why would anyone want to get into this mess now? My fear is that the WPI will try to exist without substance to preserve their intellectual property. At this point, the counter on the top of the side bar is counting more lost time.

All this in the context of: I still think a gamma retroviral hypothesis is the best one we have.

Today’s song: Stuck In The Middle With You

Square One

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