While the days, weeks and months pass, the scientific community continues to work on what isn’t, instead of what is. The question of how a lab contaminant produces an immune response in patients hasn’t been addressed by any of the contamination theorists. And how do you manage to contaminate the patients’ samples at a higher rate than the controls when all samples were blinded and run at the same time? In fact, it is the patients that are contaminated with a family of MLV-related retroviruses, not Dr. Mikovits’ lab.

This abstract was presented at CROI a few days ago:
XMRV Probably Originated through Recombination between 2 Endogenous Murine Retroviruses during in vivo Passage of a Human Prostate Cancer Xenograft. Paprotka
Many questions arise without the full paper, but it seems that far from showing XMRV to be a lab contaminant, the study shows what may in fact have happened. Endogenous retroviruses recombined in or infected human tumor cells through subsequent passages in vivo (in mouse) to produce a fully replicative xenotropic exogenous retrovirus, that in fact may prove to be the most infectious human retrovirus yet. In animals, similar viruses are communicated casually. Lombardi et al demonstrated that this new human retrovirus is circulating in the blood of as many as 10 million Americans. A public relations nightmare. So what did the scientists who said this was impossible do? First they denied its existence, then tried to suggest results were the result of mouse parts in their reagents, but none of the arguments have in any way refuted the data of Lombardi et al or Lo et al, who rigorously ruled out contamination. What they have shown is that it is possible to produce XMRV in a lab. Like the murine retroviruses, recombination events produce new pathogenic variants. See my post from September 10 about Sandra Ruscetti’s work: Lessons from the murine retroviruses

As for the 22Rv1 cell line being the source of XMRV contamination responsible for the whole mistaken affair, none of the labs involved in the Science paper Lombardi et al, have ever used this cell line. They couldn’t have contaminated subjects’ blood with virus produced by a cell line which all three investigators at different institutions can prove beyond a shadow of a doubt never entered their laboratories (personal communication). Sillier still, is the idea that this supposedly singular event was the source of infection, since it has only been around since the late ’90s: A new human prostate carcinoma cell line, 22Rv1. Sramkoski

My guess is that passing lots of human tissue through mice and then culturing in the laboratory for now more than four decades produced the conditions to enable a very unlikely event- by giving it many chances to occur. A probable place for this to have happened was in the creation of live attenuated virus vaccines where virus is made less virulent with multiple passes through animal cells in tissue culture. The earliest live polio vaccine was made by Hilary Koprowski using Swiss albino mouse brain cells. The first dose was administered to a child in 1950. He also used monkey kidney cells which were implicated in passing SV40 to humans. Albert Sabin’s live polio vaccine was produced from attenutated virus obtained from Koprowski.

Mouse cells and the cells of other species have also been used over the years in the creation of other vaccines. Some vaccines, including attenuated Measles and Mumps in the MMR, are grown on duck and chick embryo cells. Domestic fowl have endogenous retroviruses, avian leukosis viruses (ALVs or ASLVs), that do very similar things to the gammaretroviruses. Recombination events are involved in pathogenicity and they can infect the cells of other species in tissue culture. XMRV requires the XPR1 receptor to infect cells. The XPR1 receptor is ubiquitous in mammalian cells. Lab mice are resistant by virtue of XPR1 polymorphisms. The alpha retroviruses use a receptor called TVB. TVB is a tumor necrosis factor receptor that is most likely the avian homolog of a TRAIL (TNF-related apoptosis-inducing ligands) receptor. Here is a paper about the receptor: A Fifteen-Amino-Acid TVB Peptide Serves as a Minimal Soluble Receptor for Subgroup B Avian Leukosis and Sarcoma Viruses. Knauss. The abstract contains the following sentence: “This peptide was sufficient not only for binding to ASLV-B but also for activating viral entry into mammalian cells that lacked the cognate viral receptor.”

Here are two recent papers that should be giving someone pause, but there is no evidence that anything is changing in the status quo at the CDC. Head in the sand or worse?

• Endogenous retroviruses as potential hazards for vaccines. Miyazawa
• Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets. Miyazawa

Beta retroviruses, e.g. mouse mammary tumor virus (MMTV), may also be present in tissue culture of murine cells. The first PubMed paper seems to have been published in 1948 when the “milk factor” was first identified on electron microscopy in tumor prone mice:
A particulate body associated with epithelial cells cultured from mammary carcinomas of mice of a milkfactor strain. Porter
MMTV is a vertically transmitted endogenous retrovirus that causes cancer when it inserts near an oncogene. Vertical transmission of murine breast cancer by adoptive nursing was demonstrated in 1936 by Dr. John Joseph Bittner. It was formerly classified as a simple retrovirus, but transcribes a regulatory protein similar to HIV, so is the first complex murine retrovirus identified. MMTV codes for a superantigen that stimulates T lymphocytes which in turn stimulate B cell proliferation. At puberty the virus enters the mammary glands with migrating lymphocytes and infects proliferating epithelial cells. MMTV can be transferred exogenously or endogenously through the germ cell line; the later infection produces virus present in every cell of the body. Mice that acquire the infection this way have a higher incidence of tumors. In lymphocytes, it may cause a T cell leukemia. MMTV has an enhancer region in its U3 long terminal repeat that activates the virus in mammary cells. It is activated by estrogen and other glucocorticoids, including progesterone. It is especially responsive to the synthetic steroid Dexamethasone which has been used to induce lactation in the dairy animals. And a few new MMTV papers.

• Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis. Ross
• Mouse mammary tumor like virus sequences in breast milk from healthy lactating women. Johal
• Mouse Mammary Tumor Virus in Anti-Mitochondrial Antibody Producing Mouse Models. Zhang
• Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer. Arendt

Gamma retroviruses are used as the backbone for gene vector therapy. It is known that retrovirus-mediated gene therapy of SCID-X1 can lead to leukemia and lymphoma because proto-oncogenes can be activated as a consequence of vector integration. Gammaretroviral vectors preferentially integrate near transcriptional start sites and CpG islands.

• Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. Hacein-Bey-Abina
• A novel model of SCID-X1 reconstitution reveals predisposition to retrovirus-induced lymphoma but no evidence of gammaC gene oncogenicity. Scobie
• Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy. Davé

Another place for it to have happened or to be happening, as demonstrated by the Paprotka CROI presentation, is in the creation of human to mouse xenografts. It turns out that by transplanting human tumors into mice and passing the tissue through subsequent generations, it becomes possible to establish tumor cell lines that couldn’t be established before. Also xenografts are used to study tumors, e.g. specific tumor immunogenicity and response to treatments. Why the presumption that the recombination that occurred in the Paprotka experiment was a unique event? They were fiddling with mouse viruses in the lab in the 1930s. The first outbreak of Epidemic Neuromyasthenia was in LA in 1934 and involved hospital staff. And suddenly the CDC is worried about lab workers and testing archived specimens. Will they find it? It would be funny if it weren’t so incredibly sad.

Take a look at this fascinating paper that covers a lot of material including the problems with xenotransplantation:
The discovery of endogenous retroviruses. Weiss

Are we to believe this recombination event occurred only once and that a pathogenic MLV-related human retrovirus is only produced by one particular cell line? Told to us by some of the very scientists that said it was impossible? Anyone smell a cover-up? Much easier to destroy a seminal work than admit that there may in fact be a family of XMRVs. Careful reading of the Science paper shows that the monoclonal antibody used to detect XMRV envelope in Lombardi et al detects all known xenotropic, polytropic and ecotropic MLVs. Antibodies made by patients recognized specific envelope and gag proteins. PCRs were optimized for sensitivity, not specificity. And quite possibly there are many other recombinant animal retroviruses infecting humans as well, created in laboratories and injected into almost everybody in the industrialized world, because of arrogance.

Putting it all together, it seems quite plausible that batches of vaccines containing retroviruses that are infectious to humans have been going out for over half a century. Much of what I’ve written here has been known but ignored for a long time. The assumption was made that endogenous animal retroviruses couldn’t harm people. It’s becoming clear that this was a very incorrect assumption.

So is there motivation for the cover-up and baseless attacks against Dr. Mikovits? They cannot attack the data because it is impeccable. Coffin and Stoye wrote the commentary in Science. Have they retracted it? Coffin said at the CFSAC in October 2009 that “This is as good as it gets…”. If this were HIV/AIDS, the year would be 1983. We have much still to learn about human MLV-related viruses. Is it even remotely possible that the findings reported in Lombardi et al were the result of contamination of their reagents? No more likely than that the retrovirus described by DeFrietas et al in 1991 was contamination. Had the CDC done something then, we could have prevented the autism epidemic and a second generation of infected people. Instead they buried DeFrietas’ work by withdrawing all funding. Deja vu?

The discussion generated by my implicit assumption that Dr. Vernon is guilty by association is defensible in my opinion when the said associate seems to be guilty of crimes against humanity. It sickens me that ME/CFS/X+ patients have to argue about whether their friends are really their friends or not. If we have to wonder, the response is inadequate for the emergency at hand. Pretty clearly our national representatives aren’t going to save us, especially if they are in bed with the people who have been running the concentration camp in which we are imprisoned. Moderate statements about how we are in fact sick shouldn’t placate us any longer, even if backed by a few papers, never designed to impact the treatment of the disease. I’m not really interested in being balanced at this point. I’m mad as hell and I’m not going to take it anymore. ACT UP (links to ACT UP NY and ACT UP civil disobedience manual) seems a better model to me than any moderate approach at this late date.

In response to the post in which I mentioned psychiatric care in the UK, I received this email from one of my penpals there. I am including it with permission:

I was sitting here thinking of all the bad times in the hospital.
…some things included pouring water on my face while I was asleep, tipping my bed up so I fell out. Using tape to tie me to a chair and laughing at me. I was so weak I couldn’t get out the chair.  Taking me for runs everyday. Not letting me rest.
Only allowed to see mum once a week for an hour.  I was only 15 and was allowed  only one phone call a week to anyone.
I also stopped eating and drinking. In the end, I kept managing to run away- climbed out of windows. But they found me. Self harmed because I wanted to die. so had to be watched 24 hours a day and put to sleep with medicine. One time my mum visited me at the hospital and said to me I’m calling the police we are getting you out of here. They are killing you. But the doctors said no.
I escaped and broke a window one time and got quite far. I was so weak and ill. I lay at the side of the road and cars stopped and people crowded round. I thought they would save me. But then someone from the hospital came along in their car and took me straight back. I was disbelieved about my illness and told I was making it up and pushed to breaking point.

When disbelief can do this, no wonder we put up with anyone who says we are sick. But when top CFS doctors (with HIV and GWI experience no less) are publishing papers telling me I need stress reduction lessons, I’ve had it. Not that therapy isn’t a good idea, if you like it, or exercise, if you can do it, but surely it is an abomination under the circumstances that 5 million pounds was spent to prove that badly. How polarized things have become that we have to waste time refuting or being outraged by such idiocy. The paradigm has changed. It’s the virus stupid. Even a doctor should be able to see it. It’s an AIDS-like illness. Infection, inflammation, immunodeficiency. Just because it doesn’t overwhelm the host like HIV doesn’t mean we should throw out everything that’s been learned in that disease. Now we even have a primate model. Not that we should have needed monkeys to prove it when we have millions of human beings freely sharing their by now many viruses. But the macaques show what the so-called Center For Disease Control should have figured out in 1991, when Elaine De Freitas published her paper:
Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. DeFreitas

Just because the disease has obvious psychiatric manifestations doesn’t mean that it is psychosocial in origin. The brain gets sick just like every other organ and when it does, there is content. In the case of X related disease it would appear that it can look like what psychiatrists call PTSD, OCD/PANDAS, bipolar disorder (in adults and children), various anxiety disorders and/or intractable depression. Nobody should understand better than a psychiatrist that inflammation in the brain, even if cortisol/catecholamine induced, doesn’t indicate a weakness or a need to be judged, but sadly psychiatrists seem pretty much universally useless when it comes to this disease, except as a conduit to drugs of limited efficacy or worse. I guess I shouldn’t single them out as all specialties have been equally bereft, but in their case, the perpetuation of their erroneous beliefs has played into the needs of evil elements and thus has been devastating to an enormous number of people. It’s not just that millions of sick people have been discounted, left to suffer in isolation, but an obviously infectious disease has been allowed to spread unchecked through the human population for decades.

With the publication of the Onlamoon/Villinger paper Infection, viral dissemination and antibody responses of Rhesus macaques exposed to the human gammaretrovirus XMRV, it becomes unconscionable to allow the detection difficulties to obscure what is obviously a threat to the health of the species. From the discussion section of this hugely important paper:

The discovery of XMRV raises important questions about its potential as a human pathogen in light of established links of the MLVs from which it is likely derived, to immunosuppression, neurological disorders, and cancers in mice, and established etiologic roles for similar diseases by the retroviruses HIV and HTLV in humans. We reasoned that nonhuman primates would constitute a model close to man with a comparable immune system, and this study is the first to report on the blood-borne infectivity, dissemination, and persistence of XMRV in animals known to express its natural functional receptor, XPR1. XMRV was not only infectious for rhesus macaques, but our results demonstrate that after intravenous injection, XMRV established a persistently replicative infection in select tissues and organs, even though circulation of free virus or infected cells outside of the acute infection period appeared minimal or below detection limits in these healthy animals. It remains possible though, that individuals with lowered immune functions such as RNASEL dysfunction may be more permissive for generalized infection and ongoing virus replication in tissues such as prostate, pancreas and blood. Of note, XMRV appeared to respond to immune activation, since low viremia (2040 vRNA/ml) was detected in the plasma of one of the 2 monkeys administered XMRV proteins adjuvanted with incomplete Freund’s adjuvant on the day of sacrifice. The rapid resolution of the acute viremia suggests that innate mechanisms may largely contribute in containing the virus in the circulation.

It is time for us to stop whining about the decades of neglect and abuse. We need to suck it up somehow and use what we are learning that finally provides some answers. Knowing is still everything for me, though it hasn’t resulted in wellness for myself or my daughter, at least not yet. If wisdom comes from suffering, as a group, we are wise indeed. Far from how we are portrayed, as defeated by lethargy, we have demonstrated a toughness of spirit just to be here still. We need to tap into that collective strength.

Doctors, healthcare workers and their families appear to be disproportionately represented in the patient group. I received a FaceBook message from Gisli in Iceland last night: 

I was reading your blog and the following did cross my mind: Since many doctors have CFS/ME . . I think a group called: –> Doctors with ME/CFS <– could give official international statements about the nature of the disease to other doctors and professionals. Designed as peer2peer (fx. official-statement-website advertised in academic publications ) and themed in a similar human-rights-watch manner as Amnesty International does (+ the peer2peer candid factor), I think it could do good things (perhaps on a bi-annual basis or similar). Some doctors, somewhere, might be interested. The situation is phenomenal and the gulf between doctors and patients is a human rights issue. 

I love this idea. Any doctors and nurses who want to work on this?

And enjoy:
Network – I’m As Mad As Hell!

It has now been over 500 days since Lombardi et al was published in Science. Yet we are being subjected to the publication of a five million pound study that was designed by people with conflicts of interest to prove that the treatment for ME/CFS patients is exercise and therapy. Isn’t it disgusting? Even though they excluded patients who were really sick or had neurological problems, and included some depressed people, they still couldn’t show more than small improvement in a little more than half the participants with a significant number of adverse events! For a disease that waxes and wanes a little if you do nothing. Lots of people can exercise in the early stages of the illness, until they can’t. Not a single lab test. It’s unbelievable that anyone would be willing to put their name on it. While new people are being infected, new babies being born with it every day, the British Medical Research Council spends a pile of money to try to prove that therapy and exercise are helpful, if you are well enough to attend regularly. What a joke! Except that it isn’t a joke. It’s barbaric.

Professor Malcolm Hooper’s formal complaint:
Magical Medicine: How To Make A Disease Disappear

This morning I got an email from an HIV specialist in the UK who would like to prescribe antiretrovirals for a patient with CFS who is XMRV positive and well informed. He is of course extremely experienced with the drugs. He consulted the necessary powers that be and was told that he couldn’t do it without collaborating with an ME/CFS specialist. An ME/CFS specialist in the UK seems to be a doctor who believes that the best treatment is to talk your patients into exercising. The mail I get from the UK is beyond heartbreaking. It seems to be acceptable to lock teenagers up in psychiatric hospitals, tell them they’re not sick and force them to exercise until they want to die. Why not just euthanize them? Save everybody a lot of trouble and money.

I’ve had a lot of mail lately about the CAA. The recent comments, and absence of meaningful commentary, by Kim McCleary, the president of the CAA, on CNN, are a disgrace: link. And the fact that Suzanne Vernon, the Director of research, has 30 papers on PubMed coauthored by William Reeves, most recently in 2009, pretty much puts the nail in the coffin for me. Is this really the best they can do with the 3.5 million dollars of public contributions in their last three annual reports?

I’ve been asked by several people to call the illness ME instead of CFS. Personally, I don’t think ME is much better. It hasn’t done much for patients in the UK. For now, X related disease works for me, X being not just XMRV, but what looks like in the end will turn out to be several or even many simple retroviruses.

I don’t see how anyone can read the following paper and still be in doubt. It is a public health emergency. To spend years arguing about what isn’t, instead of coming together to discover what is, no matter how devastating, compounds the crime against humanity that has already occurred:
Infection, viral dissemination and antibody responses of Rhesus macaques exposed to the human gammaretrovirus XMRV. Onlamoon

I got home last night from another successful trip to Reno to interview doctors. So far this morning, I’m doing well. I’m planning another short visit next week. Things are coming together very nicely. We have the pieces needed to move forward. I’ve stood beside Judy in the lab and looked at cells. I still don’t know enough to be able to second guess her work. I can’t evaluate the technical piece. But I can tell you that there’s not a mouse anywhere:) and that Dr. Judy knows her stuff. There is a fusion of knowledge and skills happening. We’re not going to wait for the scientific community to prove what should be obvious to anyone studying the pathogenesis in animals of similar retroviral infections. It took Barry Marshall seventeen years to prove to the world that H. pylori causes peptic ulcers, and he had to infect himself to make his point. We won’t ask our scientists to do that this time. Lots of the doctors I’m hearing from already have the illness.

My reasons for disclosing personal information have nothing to do with feeling pressured. I started this blog, because I was emerging from incredible isolation and confusion into a place where I could put all of these awful experiences into context. Sharing has an important place in all this because isolation is so often a result of the disease. Never have a group of patients needed community more. I often think that there should be a way for CFS patients to live together communally, for company and to share services and economies of scale.

One of the reasons that people become doctors is because they believe that it will give them some kind of immunity when illness hits home. Most doctors have little awareness of this, are in denial, and it causes a separation between doctor and sick patients. When the patient is a doctor it is even worse, because the doctor doesn’t want to identify in any way. My colleagues to whom I went for help were the first to abandon ship, in order to disidentify. It was much easier for them to think that I was weak or overreacting to little things. The LLMD’s to whom I eventually turned validated the experience, but were engaging in voodoo for the most part. The fear and isolation I was experiencing made that validation and any hope of improvement, especially for my daughter, too compelling to listen to my own doubts. Their treatment required a suspension of disbelief on my part in order to participate, but I did anyway.

I got mail last night concerned about my dignity. I don’t feel undignified for sharing experiences that others may be able to use to help themselves or their loved ones. There is redemption in helping. What is undignified is the harm that is done to the individuals of this community on a daily basis because of the disbelief that comes from the complete misunderstanding of the disease. I want to make it clear that there is no immunity. I had a privileged upbringing and life. I was a doctor. I’ve heard from lots of doctors who’ve had experiences like mine. The doctors and lawyers, scientists, rich people are just as isolated and without help as everyone else. The disease is a great leveler.

I am so far past caring what anyone knows about me. I have nothing to hide. I’ve been wronged over and over and so have many of you reading this. I get contacted regularly by people who want to die because they have no hope. I wrote what I did yesterday, and other personal things at other times, in hope that it will help someone out there to realize what I have come to realize. It can all change in an instant and you are not alone.

In any scenario there will be individuals who are dishonest or simply assholes. There are others who are being true to their beliefs and intentions, but get caught in the cross-fire because of honest disagreement. The bigger issue I see expressed in my letters and what I’ve seen on the forums is a disaffection with the CAA. I haven’t spent any time in their sphere, but a quick look at their annual reports show that in 2009 they took in $1.7 million and spent $700,000 on research. In 2008, it was $1.5 million in and $350,000 out for research. In 2007, $3.3 million in and $265,000 for research! Here is their mission: Mission: For CFS to be widely understood, diagnosable, curable and preventable. Strategy:To stimulate research aimed at the early detection, objective diagnosis and effective treatment of CFS through expanded public, private and commercial investment. I think it’s safe to say they’ve failed rather miserably, even without being privy to all the sordid political details. In the world of political organizations, everybody gets to vote with their feet and checkbooks.

My trip to Reno was very productive. Energizing even. No crash this time (knock on wood). The nuts and bolts of the practice are getting worked out, but the exciting part to me is the synergy of like-minded people with complementary talents and skills. Never have I been exposed to a work environment where everyone is so passionate about what they are doing and why. All for one and one for all.

I am tolerating the stress pretty well. I bounced back from my crash/viral infection following my last trip fairly quickly. I regularly have waves of symptoms, but at a level where I can ride above it most of the time. The work is actually providing some escape from the physical reality of the illness. It’s a bit like carrying around a ball and chain all the time, but it reminds me to keep looking for the key to unlock it. For me, the illness is like living with a very strict Zen master. If I engage in any serious hand wringing, I get a rap across the knuckles. Emotional PEM (post exertional malaise) is almost instantaneous for me. Tough teacher.

Ali is not doing as well as she was a few months ago. I can’t even tell you if she is better or worse than when she started antiretrovirals, because some symptoms are still better, but she has new ones (inflammatory). It is not at all clear why she has taken this downturn. She is considering holding AZT to see if things are better, worse or no different without it. We don’t have clinical evidence that both RT inhibitors are better than one and AZT toxicity could be contributing to the energy deficit. Anecdotally, tenofovir has a clearer positive clinical effect than AZT. There are a few people who are improved on tenofovir alone and AZT alone seems to have little clinical impact. We experienced the most obvious improvement from antiretrovirals when we added tenofovir as a third drug. Ali’s gut feeling, and mine, is that AZT is not what is making her worse, but the drug has a short half life and it shouldn’t take long to see if she gets a lift when it clears her system. There are a few people that I know of who have stopped AZT for suspected side effects or mild anemia, but they are back on it or considering being back on it. I have heard of only one patient that stopped it for profound anemia requiring epo. At eleven months, we have no signs and have heard no reports from others of changes consistent with lipodystrophy or muscle atrophy. The only clear sign we have of toxicity is the expected macrocytosis and compensatory decrease in red cell number. However, there are a couple of patients who report improvement on tenofovir and raltegravir without AZT, probably an easier regimen to tolerate for the long haul if effective.

One of the things I’ve learned about the lay of the land is that scientific research happens in individual labs that generally don’t share with one another. The credit and intellectual property issues preclude much cooperation. I have a great deal of trouble with it, because real collaboration between scientists that wanted to help each other might illuminate rather than obscure the truth. Physicians are similarly isolated, but the reasons are different; it’s more about being over-worked, unsupported and disengaged. For most, the reasons why they became doctors are no longer anywhere in sight.

People write and ask me if I agree with this or that piece of the politics, but the medicine and science is all I can handle. As an observer, I am struck by the divisiveness in the ME/CFS community, when so many worthy common enemies abound. I am a newbie to the politics. I diagnosed myself when I read the Science paper, fifteen years into my illness and six years into my daughter’s. I am not typical of ME/CFS, by history or current clinical picture. I could still exercise for the first ten years of my illness and my symptoms were primarily neurological and vascular. Ali had a history of acute Lyme and subsequent crashes which responded to antibiotics. Neither of us had a viral onset. Childbirth and puberty were our triggers. The revelation was not about having a diagnosis of CFS. It was about having a retrovirus. That realization cleared up much of the mystery for me. With everything I’ve learned since, I still believe we are suffering from the effects of one or more retroviruses. A sad reality, but also our best hope. In the end, it will be about having an infectious disease, not a syndrome with a terrible stigma. Personally, I’d rather be a leper, than a psychotic malingerer. And with that happy thought, is there some way for us to put aside the internal strife and turn our attention to our common goals?

Bench-to-bedside is a translational research term used to describe the process by which the results of research done in the laboratory are used directly to develop new treatments for patients. The close relationship between the research lab and the clinic should take it still farther – the clinical findings will drive the direction of the research. Dr.’s Mikovits and Lombardi are committed to this kind of collaboration. In fact, an interdisciplinary blending of ideas has already begun. We are learning to speak each others’ languages. The camaraderie engendered by being down the hall from one another will nourish all aspects of the real work, which is to heal the patients.

Interview by Cort Johnson with more information about the clinic.

Every CFS patient with federally sponsored health insurance has experienced firsthand that it is very poor coverage for anything but the most mainstream care. However, now all of a sudden, some expect the WPI to provide boutique care for what Medicaid will pay. And cure everybody of an incurable disease. On the first visit.

Let’s see what mainstream medicine has to offer. Here are the Mayo Clinic guidelines for CFS: link. That’s what Medicare will pay for, and they say right there that they think IVIG and antivirals don’t work, so that finishes the discussion of expensive treatments. There were comments yesterday that there are a few CFS doctors that accept Medicare. If that’s true, then what’s the problem? My mail indicates that the best known CFS/Lyme doctors do not accept Medicare, let alone Medicaid, or they have other ways of generating income. But if they do take it, then there’s less of a problem if we can’t. And we can’t for now – not won’t or don’t want to.

It is impossible to budget without knowing in advance the percentage of federally insured patients that will want to be seen, but it is likely to be high. Medicare will pay if you need a million dollars worth of ICU care, but they won’t pay a few hundred dollars for you to be seen by a doctor that has the time to listen and think about a complex history. I have no interest in discussing the state of the health care system. We all know up close and personal how bad it’s gotten. It would be better if doctors worked for love instead of money like Mother Theresa, but apparently there aren’t many that do, or the clinic would already be up and running.

I’m certainly not going to touch whether doctors are worth what they expect to be paid or not. I do think everybody needs to remember that whatever a doctor’s fees, he or she doesn’t take it all home. There are many expenses involved in running a medical practice, including but not limited to malpractice and other insurance, rent or maintenance on the space, salaries, supplies, accounting and legal fees.

As for whether the WPI should have a clinic that treats a volume of patients, or just be doing a few clinical trials, that decision has already been made. Annette Whittemore’s vision of translational medicine included treating patients from the beginning. Bench to bedside to bench. The clinic exists. It is a very large space, capable of seeing a large volume of patients. There are many patients asking to be seen. In an amazing display of synchronicity, all of my professional and many personal experiences are a piece of what’s needed to organize it. Although there are many ways in which I am the right man for the job, I’m also sick and that is far from ideal, but no CFS/neuro-immune disease knowledgeable doctors have stepped up to the plate. So it seems to be my fate. I appreciate all the support from the community that I am receiving. I will do my best not to disappoint.

What are we going to offer that’s different? Medical decision making will be influenced by continuous interaction with the research lab and physicians around the world. We’re going to keep track of a large number of patients, so there is an opportunity to contribute to the greater good of the community. We are going to have doctors who are not wedded to their particular black box protocol and who are willing to consider all therapeutic options for each individual they care for, whichever neuro-immune disease cohort you fall into. We can’t offer a magic bullet that doesn’t exist, but we will be looking for one, and if we find it, you won’t have to come to Reno to hear about it. We’re going to offer quality care; that’s not unique, but there’s precious little of it to go around. We’re going to treat some patients for free as soon as we can. That unfortunately is pretty much unheard of.

There will be no solicitation of any kind. There will be no products pushed or sold. Nobody who has any questions about our motives need come. This is a unique endeavor. No one has helped us before, so we are going to help ourselves. Of course I hope that the ME/CFS community is behind us. I have no illusions about being able to be all things to all people. The harsh realities of practicing medicine preclude that, but we will do our best to serve our patients and the larger community as well.

“I can make more generals, but horses cost money.“
Abraham Lincoln

As expected, there are many comments and letters this morning about money. Many ask that reconsideration be given to accepting insurance assignment. I have promised transparency and money is always one of the hardest things to talk about openly, but here goes.

For a number of excellent legal reasons, the institute and the medical practice are separate entities. There is NO money to float the expenses of the clinic while waiting for collections. So if there is no cash coming in immediately, we can’t open. It’s that simple. We have no subsidy. We may be able to revisit accepting insurance later, but for now, if it isn’t fee for service, there will be no clinic. I wanted to accept insurance. Everyone at the WPI wanted to accept insurance. It isn’t possible at this time.

The idea that the institute should fund large scale clinical trials is not realistic, since the government has no interest in funding XMRV research and the drug companies won’t go to work until the detection/causation issues are worked out. The funds actually need to flow the other way, from the clinic to the institute. The reality is that the patients are going to need to fund the research. Not fair, but true. So yes, once again, the patients get screwed. Money has a way of highlighting difficult reality.

People have asked if we could charge a higher copay for Medicare/Medicaid patients. It is illegal to balance bill federal insurance. Also accepting Medicare/Medicaid is an all or nothing proposition. You have to play completely by their rules or opt out all together. They don’t allow a middle ground. The government thinks a 20 minute visit is adequate, particularly since there is no treatment. We are not going to fix the system; it is broken and cannot be fixed in it’s current form.

I am assuming that everyone realizes that paying the provider is only part of paying the bills. Even if I could figure out how to fund the startup, and even if we used PAs instead of doctors on the frontline, the numbers don’t come close to working out. Personally I prefer PAs, because in general I don’t like doctors and, as a group, PAs tend to be more compassionate and detail oriented than doctors. However a physician is still necessary to supervise and bill for PA services. Also insurance won’t pay for anything telephonic and that will likely be a significant part of follow-up care. Mid-level practitioners would make it possible for ongoing care at a distance to be less expensive.

There is clearly a huge need for a consultation service for patients who can’t leave home. It is illegal to prescribe for a patient that has not been physically seen within a period of time, as it should be, but we will interface with local doctors to help encourage appropriate care. Eventually, we would like to partner in some way with like-minded local physicians to become satellites of sorts. Care needs to be available everywhere. All suggestions will be considered.

Lots of mail about how to get cheaper doctors from overseas or other kinds of discounted help. People have made suggestions such as using PAs for poor people and doctors for rich people. I can tell you clearly now, nothing like that is going to happen. The providers will be of the highest caliber or we will not open. There will not be two tiered care. I am unwilling to deal with the administrative difficulties of a sliding scale. But there will be a wait list for free care. The physician group will donate a percentage of time to patients who cannot afford to be seen – percentage to be determined when we have some real numbers to look at. We will ask that patients who can afford it donate for patients who cannot pay. Any ideas about how to fund for this group of patients is appreciated.

Rest assured that I too have lived the downwardly mobile life of a CFS patient. When I left practice, we had substantial savings that is now gone, having spent an unbelievable amount of money on $500/hr doctors and uncovered IV antibiotics for two people. I am determined not to do that to others. I hereby promise that nobody is going to get rich on the budget I’m putting together. Salaries will be fair, but we are looking for people for whom it is more than a job. The purpose of the clinic is to treat individual patients, but because of the translational medical approach that will be engendered by existing in concert with the research lab, there is a bigger purpose as well.

There will be no attempt made to “entice” patients to travel to Reno in order to make money, as someone put it in an email. Success would mean no need for patients to travel. Time will tell whether we offer anything new and different or not. I share the dismay of many as to how ineffective prior attempts at improving outcomes have been. One of the most upsetting things to absorb from the epidemiological study that is my mail is that the patients who have avoided doctors and expensive treatments have generally done better than many who have pursued endless aggressive experimental treatments. My impression is that the chronic Lyme patients are sicker and have more pain than the CFS group. That may have something to do with Borrelia burgdorferi infection, or it may have more to do with all the antibiotics these patients have been exposed to. Which doesn’t mean that antibiotics aren’t an essential part of treatment for some. As I’ve said before, I am not against the use of antibiotics, any more than I am for the use of antiretrovirals. I am for what works that doesn’t harm. I am in favor of making all treatment options available and tracking response in collaboration with the research lab. The goal is to develop a coherent approach to treatment that is finally informed by research and understanding the nature of the disease.

I’ve accepted the position of Director of Clinical Services for the WPI, or the Center for Neuro-Immune Disease as the clinic will be called. I am currently recruiting in earnest. Physicians, nurses, PAs, practice manager. We are planning to open in May, but that is of course completely dependent upon finding the right doctors. A few good men or women. If you are out there reading this, please get in touch. It’s a phenomenal opportunity to be part of something unique from inception. The space is amazing and Judy’s lab is down the hall. I’m still too sick to rely upon this body to see patients scheduled a long way in advance, but I have a background in Emergency Department administration, physician recruiting and management. And I know the enemy intimately. In fact, all of my experience, as a doctor, a patient and the mother of a patient, seems a part.

I see it as a primary care emergency. There are already a huge number of patients on an interest list, even though a trip to Reno is a daunting proposition for most. My mail is full of tales of unbelievable neglect by the medical profession and the care that has been rendered has often been more harmful than helpful in hindsight. Most are lacking a local physician with even a basic understanding of their illness. Whatever care they have had has been idiosyncratic, hit or miss. Whole families need to be hooked in to appropriate care. CFS parents with autistic kids. There’s never been a systematic approach to either illness.

Since many patients will be traveling to be seen, and many have never had a chance to tell their story to a doctor who wasn’t trying to escape from the room, first visits will be two hours, revisits an hour. For those needing long distance follow-up by Skype or phone, it will be available with your physician or physician extender. Continuity of provider will be a goal, but there will be continuity of care that will allow transitioning easily to a new doctor if there is no chemistry or if there is staff turnover. We are forming a Physician Working Group to help us think about a decision tree. Consensus is too much to expect, but I’m sure we will learn a lot and it will shape the thinking of our doctors. Patients should be able to expect a uniformity of approach, but not a cookie cutter protocol.

I’ve looked hard at accepting insurance and unfortunately have concluded that it isn’t possible to offer quality care to this group of patients at current reimbursement rates. Medicare/Medicaid simply won’t pay the bills. Private insurance generally doesn’t cover out of state care anyway and patients are going to come from overseas. Any way we structure it will be unfair to somebody. Whatever fair physician fee we will need to charge, the travel costs will be the biggest chunk anyway. I have read rumors on the internet that range from the WPI is going to see patients for free to it’s going to cost some crazy amount. It looks like it will have to be a cash practice, hourly fee to be set, but I can say for sure it will be at the lower end of the CFS/Lyme/alternative doctor fee scale. We will provide a superbill and documentation to support a claim. Fully operational, the clinic should generate income that will be donated back to the WPI and the research, percentage of gross to be announced at year end. We intend to have a fund for patients who otherwise cannot access care as soon as we are in the black.

When I started this blog, it was pretty much of a personal rant from the perspective of a disabled doctor. I have a bigger responsibility now, but I want to continue to share my experience openly. One of the many unusual things about the people running the show at the WPI is the clarity of their intention to help. A major intention of mine is to end any feelings that there is something worth knowing that is secret. Secrecy in the face of a public health emergency is a travesty. Anything but collaboration to ameliorate the unbelievable suffering is intolerable. Going forward, what we learn will be incorporated into the thinking of mainstream physicians everywhere so that care will be available locally. At this point the treatment options worth considering are limited. With a large patient volume and a group of physicians sharing with each other and with the scientific team, it should be possible to look at these options systematically.

Down the road, I’d like to be able to offer comprehensive care, including an extended stay to begin rehab, though it’s just a twinkle in my eye at this point. We will offer the opportunity to be seen on more than one day during a trip. We’ve traveled for care to be seen for an hour and it’s a miserable experience. There’s a wonderful opportunity in Reno for someone to take on a Ronald McDonald type house, if you are out there reading this.

We are in the special position of being a startup, so we’re going paperless. I’m looking at Electronic Medical Record systems now. We will be able to search charts horizontally, by medication or other intervention, symptom, particular abnormal lab result, pretty much anything we want. Many who write want to help in some way and there will be collective value in contributing to our database. The doctors on the frontline will be sharing with the best and most experienced clinicians and scientific minds from around the world; they will know what the current options are and how to think about them for a given individual. My vision is to create what I needed fifteen years ago when I first became ill, and again seven years ago when it happened to Ali and my husband. We were never even diagnosed properly due to the incredible ignorance surrounding this disease. We are going to change all that.

Leaving for Reno again on Monday night. I’ll do the wheelchair thing and use oxygen in the plane this time. Pace myself while I’m there. Grumble. Grumble.

I was pretty sick when I wrote my end of the year post. Right after I wrote it, I came down with an upper respiratory infection that I am still recovering from. The rest of my family now have it too. I’m not back to where I was a month ago, but I am approaching function again. This episode has reminded me of how grateful I am not to feel like that all the time anymore.

My Hard Truths post hit some readers like a wet blanket. In particular, there are some patients who are noticeably improved after a couple of months of treatment and already feel that antiretrovirals are worth it for them. Ali, who was the skeptic when we began, has been reminding me of how much better we are than when we started. I was most definitely writing from a place of personal disappointment, having gotten so close to where I need to be for productivity. Perhaps I was feeling the need to say something to moderate the enthusiasm I expressed months ago, since it clearly is not a slam dunk, at least for patients who have been sick for a long time. Perhaps I was expressing my frustration that this far into it, the science has not progressed enough to enable adequate assessment of what the drugs are doing, but neither Ali nor I have any thought of stopping them.

We do unfortunately find ourselves back in that place of “fiddling around the edges” as a friend put it in an email. My New Year’s resolution was to get serious about supplements again (I have difficulty swallowing pills), in the hopes that it will be more productive now that we are healthier. In the early years of my illness supplements and botanicals were more noticeably effective than they have been in recent years; maybe they will be again. I have been struck by the fact that any intervention mentioned, no matter how benign, seems to have made somebody worse, including supplements. Personally, I have never found a supplement to be anything worse than useless.

It still seems intuitively obvious to me that preventing infection of new cells is a good idea. The drugs we are taking, that have tested against XMRV in vitro, interfere with early stage replication events only. They do nothing to prevent provirus from producing viral product and fueling persistent immune activation. The HIV model continues to fit very well, complemented by what we know about simple animal retroviruses. Here are a couple of good papers about HIV that also shed light on the downstream effects of XMRV/HMRV’s:
Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity. Walsh
HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Price
Another MLV paper that fits our evolving model:
Activation of Transcription Factor Nrf-2 and Its Downstream Targets in Response to Moloney Murine Leukemia Virus ts1-Induced Thiol Depletion and Oxidative Stress in Astrocytes. Qiang
Here is an interesting, well referenced paper (unpublished):
HIV infection in children – neurodevelopmental (autistic) outcomes and clinical pathologies – and their correlations to idiopathic autism. Lozac

My opinion is still that patients have the right to consider antiretrovirals as one of their treatment options. My goal here is certainly not to aid the considerable forces that want to shut down that option in any way, but to have it be an informed decision in light of the anecdotal evidence that we do have. It bears repeating here that doctors do this every day with less evidence and much more dangerous drugs than the drugs under consideration here. What must be said is that the response to antiretrovirals has been mixed, though there has been some success. It does not appear that anyone has been harmed. I still believe that there are compelling reasons to consider antiretrovirals for certain, but certainly not all, X+ CFS patients.

There continues to be tangible progress towards making the WPI’s vision of collaborative science and medicine a reality. There were lots of curve balls in 2010, but it’s a new year, if not a whole new ballgame. We are gaining momentum. A team is assembling. We finally know how to think about the disease. A coherent approach to treatment is within reach at last. There is a rapidly evolving framework for considering the needs and best options for an individual patient. We have an unprecedented opportunity for scientists and doctors to work together to move our understanding ahead as quickly as possible: understanding to translate into clinical successes. The obstacles are considerable, but failure is unthinkable. Breaking new trail is never easy, but was there ever a group of patients who needed new trail more desperately?