Life is full of misery, loneliness, and suffering – and it’s all over much too soon.
~ Woody Allen

Mood music for this post: Messages by Xavier Rudd

It was good to hear from “John” again in the comments this morning. My head has been so completely in the clinical world since I wrote that post, that it’s hard for me to come back to it. I’d rather step back and take a look at the big picture. I’m sorry if it’s too loose for you John. I’m a doctor again. I don’t have the time that I did to read the pure science in exquisite detail trying to divine the truth from little bits and pieces of incomplete information. Not my job. Thanks for the input though, and may you never need my services:). Fortunately, the patient community still has a few friends in the scientific world and we will continue to rely on them to help us. Dr. Mikovits and I continue to “translate” for one another.

I’ve been informed that the management at the WPI has decided that there will be no group in the clinic. The physicians will practice independently, rather than as the academic department I had envisioned. Thus there is no need for a clinical director and I have been given my pink slip, returning to volunteer status. I am disappointed by this decision, but remain completely supportive of the institute’s goals and the scientific effort. I still hope that further consideration will be given to my ideas in the future, when there are fewer obstacles than now, believing that a group would be a better way to manifest the translational research goals of the institute. I’ve launched the Physician Working Group and hope that the sharing of ideas in an ongoing way by this international group of medical practitioners will bear fruit.

I am relieved that there is no longer a question of who I am speaking for here. I write from my multiple perspectives as a doctor, a patient, the mother of a patient, the wife of a nearly recovered but symptomatic patient and the mother of a healthy son with subclinical signs of the illness. My practice is growing and my intention is to share my clinical impressions going forward. This is the 97th blog I’ve written in 15 months. I’ve never gone back and reread it, but from where I stand now, other than changing the URL to the plural, treatingxmrvs, I still believe pretty much what I’ve written. I am continually refining, but the basic concept hasn’t changed. Our illness is of retroviral origin, plus genetics, environment, injury. But a paradigm shift will be required to understand what has happened. That’s why the etiologic agent has been so hard to find. It isn’t one virus, one illness as required by the old paradigm. There’s too much sequence diversity, as Judy Mikovits and Frank Ruscetti have been reporting since the first negative studies. Too many viruses and parts of viruses. And people are working on it. A group in Wisconsin just uploaded sequences to GenBank that suggest more diversity than everybody has been looking for in all the negative PCR studies: Partial molecular cloning with novel consensus PCR primers of the murine JHK retrovirus of human origin, a variant of the Xenotropic murine leukemia virus-relatedvirus (XMRV): Xenotropic MuLV-related virus 5′ LTR, partial sequence; and gag protein (gag) gene, partial cps

The current technology is knocking at the door of solving it. Deep sequencing is beginning to be available, but still very expensive. XMRV has not yet been fully sequenced. VP62 was made in a lab from pieces of viruses taken from multiple tumors. Does it even occur naturally? It has been shown to be infectious in monkeys, but their antibodies don’t detect the strains present in humans, suggesting it’s different than whatever is infecting those humans. Zhang et al’s findings indicate that normal correct lab technique for retroviruses isn’t good enough for XMRV’s, which are not fastidious like HIV. Normal technique does not prevent spread throughout a clean lab in a matter of days. Therefore the contamination issues are serious and our best hope is that somebody develop a reliable serology test that picks up the whole group. A sensitive enough RT (reverse transcriptase) assay seems like it should work too.

Oddly, just as I was writing this, the following came through on Co-Cure:

The FDA is investigating vaccines for contamination by a variety of latent viruses, including XMRV.  They believe that cancer- and tumor-causing latent viruses may become active during the vaccine manufacturing process, and that some of these viruses are hard to detect with standard methods. 

“Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered human retrovirus that has been found in both chronic fatigue syndrome and prostate cancer patients. Although these findings need further confirmation, there is a potential safety concern regarding XMRV in cell substrates used in vaccines and in transmission by blood transfusion and blood products. We are developing sensitive detection assays for XMRV to evaluate cell substrates and investigate virus transmission by blood transfusion in a monkey model.”

Read the entire article at
http://www.fda.gov/biologicsbloodvaccines/scienceresearch/biologicsresearchareas/ucm127327.htm

This is truly wonderful news!

From Age of Autism and Kent Heckenlively:
FDA to Investigate Vaccines for XMRV Retrovirus

A consensus means that everyone agrees to say collectively what no one believes individually.
~ Abba Eban

At the end of the comments from the last blog, the conversation turned to the new International Consensus Criteria for ME: Myalgic Encephalomyelitis: International Consensus Criteria. Carruthers et al. I’m glad that this is becoming a place where we can consider the issues together. My personal reaction to the paper was mixed. While I found it immediately useful for sending to uninformed doctors who might recognize their patient in it, it excludes a lot of patients who will therefore be hurt by it, if anyone pays any attention to it, which they probably won’t. In particular, it excludes a large subset of patients who had gradual onset or recovered to a great extent following a first crash. I didn’t meet criteria for the first decade of my illness. I certainly do now, but if this had been the case definition, the same things would still have happened to me with respect to disability coverage, disbelief and misinformed treatment by physicians.

For the first ten years of my illness, I had no PEM. I could bench press over a hundred pounds, rode on the back of a tandem for an hour or more a couple of times a week, played tennis, could scuba dive and ski. But if I worked a full, normally intense day, I’d get a headache and a hypertensive crisis (up to 220/140). So I was forced to circumscribe my life in ways that didn’t trigger it. I worked in a clinic attached to my home to keep the day short and reduce stress. Ken Wilber’s functional bubble: link to letter and check out his very cool website www.kenwilber.com. I had episodes of severe anxiety, autonomic dysfunction (cyclic vomiting, not OI or POTS) and bizarre sensory symptoms (dysgeusia, globus hystericus, hyperesthesia, hypoesthesia in a dermatomal distribution). Also flu-like malaise. I didn’t meet the new ICC criteria during any of that time. I now have or have had literally everything on the list, except, for some peculiar reason, I’m still sharp, never “foggy”, and my memory is pretty good, as good as it ever was anyway. I wonder why I’m different in that respect, when otherwise I’m classic, and the only thing I can come up with is lots and lots of exposure to high dose oxygen.

Careful history taking suggests  that HGRV’s can turn on and off, in a minor way, for a very long time without becoming a big problem. My history suggests this, with intermittent symptoms that went back to childhood, yet I considered myself healthy and had no medical record at all, except for pregnancies, until I became ill at 41. My husband has lots of symptoms, but doesn’t have ME or CFS by anyone’s criteria. I was intrigued by this paper about nail changes in CFS: Secondary structural changes of proteins in fingernails of chronic fatigue syndrome patients from Fourier-transform infrared spectra. Sakudo. I had nail changes that started maybe a decade before I knew I was sick, so over 25 years ago. I wore acrylic nails to hide it for a few years. I couldn’t find an explanation, except a little bit in Chinese medicine which is concerned with such things, but knew it meant that something wasn’t quite right. I have no lunulas now. Nail beds are short, not wide like clubbing. Nail plates curl at the end. I have Raynaud’s, subclinical for years, occasionally visible in the last few years. I think that the changes are probably due to cellular hypoxia at the periphery exacerbated by vascular instability.

There is one anecdotal report of a young patient who improved dramatically on AZT/raltegravir, stopped the drugs after 6 months and has maintained the improvement. Our assumption that the drugs would need to be taken forever, because that’s how we treat HIV, may be completely erroneous. After following a small group of patients informally for a year and a half, my impression remains that the drugs move the illness, but we don’t know how to use them. Dr. Snyderman’s data is certainly compelling, posted last April here in Another Perspective. HIV doses may be wrong for us. There is one report of someone who has improved on very low dose AZT alone. CFS doctors have long known, start low, go slow, but because that is a no no for HIV, there is no experience so far. AZT has been used for HTLV:

• Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL). Kchour
• Zidovudine and interferon-alpha treatment induces a high response rate and reduces HTLV-1 proviral load and VEGF plasma levels in patients with adult T-cell leukemia from North East Iran. Kchour.
• Efficacy of 3′-azido 3’deoxythymidine (AZT) in preventing HTLV-1 transmission to human cord blood mononuclear cells. Zhang
• HTLV-I and AZT: die another day. Mahieux 

The last two papers suggest that low dose AZT may be useful. AZT works for Adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy that develops in a subset of HTLV–infected individuals after a long period of latency. Mahieux suggests that in this setting, it works not through antiviral effect, but through an anti-proliferative effect, requiring long term treatment to activate tumor suppressor genes. An explanation is offered for why some patients with ATLL respond to AZT and some don’t, response to treatment being dependent upon an intact tumor suppressor gene. AZT shortens telomeres in fresh ATLL cells, eventually inducing senescence and death of infected cells. Patients with mutated tumor suppressor genes don’t respond. The relative contribution of proliferation versus viral replication likely varies between infected people, possibly determining in which direction the disease progresses, ATLL or HAM/TSP, cancer vs neurodegenerative outcome.

In the meantime, Simon Wessley wonders why people are angry with him when he says that we’d rather have an incurable retrovirus than admit that we are mentally ill: BBC news (audio). Dr. Wessely, it’s because a psychiatrist without compassion is a terrifying thing indeed. Meaningful psychiatric care, safe rehab, disability coverage, the simplest supportive interventions have been denied us for decades, but we’re supposed to thank Dr. Wessely for taking an interest in us. Go push your worthless theories in some other arena, or suffer the reaction. We’ve had enough of your “help”. Enough of your blame. When I first became ill, any real doctor could tell that there was nothing wrong with me. And I was a real doctor… The nephrologist who fancied himself an astute diagnostician was sure I had a pheochromocytoma or carcinoid tumor, but after he did all his fancy tests and couldn’t find anything, he concluded, “You’ve lost your nerve.” My hypertensive crises were diagnosed as “white coat hypertension”. How right he was, though my fear of white coats certainly turned out to be justified.

In three words I can sum up everything I’ve learned about life. It goes on.  ~ Robert Frost

The week before I left to come to Hawaii was a difficult one for me. I took a series of emotional hits in quick succession, then had to leave home to take care of patients here, alone with no support. I arrived feeling sicker than I had in many months. My first patient was a well known advocate in our community, and I will always remember that she was there when I got off the plane, as well as her caring in the first difficult days. She knows who she is, a very special woman.

Childbirth was the initial trigger for my illness, and a concussion once, but sustained emotional stress was involved in my worst declines. So I was a little concerned, as was my family. I did dip a little, predictably, but I’ve been able to function throughout and am feeling better again. More resilient than expected. Able to weather some difficult stuff without going down, a degree of stability necessary for the patients who are choosing to put their trust in me. At least they can be sure they are sitting with a doctor who cherishes every encounter, whatever the future may hold. I know what it’s like to be unable to work. Actually, I know what it’s like to be unable to roll over. I get a little frustrated sometimes at having to pace myself pretty extremely when I’m at risk, like now, but if I stick to very restricted hours and activities, particularly when I don’t have help, I can do the things I need to get done in the physical world. The medicine is the easy part. A reflex. So far caring for my own patients is sustaining me. As always, I work diligently to stay focused on what I can do, rather than what I can’t, and I don’t allow myself to sweat the small stuff.

A few people wrote that they were disturbed that I said I didn’t expect a cure. I should have said in my lifetime or in the foreseeable future. In the same way that HIV patients are incurable, yet attain functional cures for long periods of time with treatment, I expect that a similar degree of successful management of the disease will be possible for ME/CFS patients. The politics and regulatory issues are a nightmare, as I’ve learned firsthand through my association with the WPI. Coming here to see patients one-on-one feels like respite compared to that. The hardest thing for me to absorb is that a giant hand came down and hit the pause button on the science, and therefore the search for appropriate specific treatments, until Lipkin opens the envelope and declares a winner. We have the technology! It’s just money and priorities. If everybody would wake up and recognize it for the public health disaster that it is, it would take a couple of years to get a handle on what’s there from an infectious disease standpoint, a couple more to figure out the basic pathophysiology and a couple more for compassionate use treatments to be available. But it doesn’t look like that is what is going to happen. The psychiatrists will have their way for a while longer. We will have a new diagnosis, CSSD, Complex Somatic Symptom Disorder. New name for Munchausen’s.

The best news is that my Munchausen’s by proxy is in remission:). Ali is doing very well again, with large amounts of supplemental oxygen. We put the concentrator in the middle of the house with a long hose allowing her to be wherever she wants to be. She has been using it at 10 L/min for about an hour a day, more if she has breakthrough symptoms. She has needed no prompting, but wants to do it, because it makes her feel better. She has also had a few Meyer’s Cocktail plus glutathione infusions that seemed helpful, supportive, but she hasn’t had any for 4 weeks now and continues to improve with oxygen being the only new treatment. Her MCS symptoms, or hyperosmia, have almost resolved. She was able to go to a party for a few hours at a neighbor’s house last week where she was exposed to perfumes without problems. She hasn’t tried the chamber yet, but I have asked her to figure out if pressure adds anything for her, since she is much more sensitive than I am. As for me, I do think I benefit from the effect of coming to sea level from altitude (my house in Santa Fe is at 7000 ft). It most likely would be short-lived if I stayed, but should happen each time I come here, planning to use oxygen when I return to elevation. The travel really doesn’t bother me much anymore. I use the wheel chair service and am grateful for it. Supplemental oxygen during flight would protect against adverse effects of hypobaria and hypoxemia, but it is very expensive and a hassle. If I just pretend I’m home on the sofa, play with my iPhone and let them transport my body, the travel doesn’t seem to be a problem for me.

And lest anyone think that mouse retroviruses are not part of the picture whilst we are waiting for Dr. Lipkin, reminiscent of Waiting for Godot:), take a look at this important paper: Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts. Zhang/Gazdar. It’s reads like science fiction if one considers the consequences of this wee oversight, realizing that mouse xenografts have been used since at least the 40’s, though I still think the early yellow fever vaccine work was probably the beginning of human assistance in the natural process. Or it may have begun even further back, with the selective breeding of mice in the early 20th century, mice that were unable to survive in the wild, producing infectious viruses to which they are not susceptible due to receptor mutations. The use of animals, including mice, for the production of vaccines started in the early 30’s or before. Yellow fever was attenuated in mice and injected into monkeys and humans. See previous blogs here, here and here. Also there must have been lots of experiments at the time that didn’t make it into print. The records from the Rockefeller Institute would probably shed a lot of light. This paper was published in 1932 and the first documented outbreak of Epidemic Neuromyasthenia at LA County Hospital was in 1934: Vaccination Against Yellow Fever With Immune Serum And Virus Fixed For Mice. Sawyer/Lloyd. J Exp Med. 1932 May 31;55(6):945-69. Infectious mouse retroviruses probably infected humans before that, but at very low levels, since the sick mice died like they were supposed to. 

Hats off to Zhang et al for their vital work, and for calling a spade a spade. Finally someone stating the obvious. 22Rv1 doesn’t explain away all the ruckus, nor was it the incredibly rare event postulated by Paprotka et al. Like XMRV, it is a signpost to a much greater problem. It is the patients that are contaminated, and not by just one virus. Many infectious retroviruses. Just because way back when, Coffin, Stoye, Heneine and the gang all said it couldn’t happen, doesn’t mean that it didn’t. Some choice comments from the Zhang paper:

ERVs represent remnants of ancestral germline infection by exogenous retrovirues and after integration into the genome are transmitted vertically as proviruses. Murine leukemia viruses (MLV) as ERV provirus forms are present at about 60 copies per mouse genome from which up to 15 copies are related to infectious xenotropic murine leukemia viruses (XMLV)… Thus, active mouse ERV provirus present in common inbred mouse tissues can be the origin of XMLV or recombinant polytropic MLVs which are infectious to human tissues implanted in laboratory mice.

Earlier studies have documented that XMLV type-C retrovirus particles were indentified in human xenograft cultures derived after xenografting in immune-compromised mice… NCI-N417 SCLC cell line was established from a mouse xenograft by the Gazdar lab at the National Cancer Institute (NCI) in the early 1980s and this cell line was subse- quently found to contain XMLV a few years later.

Reports of XMLV strains being present in human xenograft cultures appeared in the 1970s…

Our results indicate that human tumor cells frequently become infected with MLV virus after xenografting and subsequent culture. We have observed that mouse stromal cells may persist in culture for lengthy periods. Mouse stromal cells, while they contain abundant provirus forms of MLV, including ecotropic, polytropic and xenotropic strains, seldom spontaneously release large amounts of infectious virus (authors’ unpublished findings). Virus infection of xenografted cells may require activation of XMLV virus by chemical or immunological induction in mouse and by prolonged mouse and human cell contact. Viral transfer may occur in the mouse host or during subsequent xenograft culture. Our findings of infectivity of XMLV-positive supernatant fluids demonstrated that XMLV can readily infect other human cultures without presence of mouse cells or other aiding factors, indicating that these viruses are highly infectious.

In conclusion, our studies demonstrated that several MLV strains were present in over one fourth of xenograft cell lines. Infected cell lines were identified in most laboratories working with or establishing xenograft cultures, indicating that such contamination was widespread. Infected cultures usually release large numbers of infectious virions, and intra-laboratory spread of MLV virus to other cell lines maintained in the same facilities may occur, confirming the highly infectious nature of MLV virus. Retroviruses have been associated with multiple diseases including solid and hematologic malignancies, AIDS as well as with non-malignant diseases. The high susceptibility of human cells to infection with XMLV, the high levels of reverse tran- scriptase activity present in culture supernatant fluids and the demonstrated infectivity of the shed virions suggest that such viruses may present potential biohazards to laboratory person- nel involved in cell culture facilities or to those handling human xenografts. In addition, the effects of the integrated provirus or the released virions on the biology of infected tumor cells are unknown. Provirus integration into the genome is not random, and occurs preferentially at transcription start sites, CpG islands, DNase-hypersensitive sites and gene-dense regions, suggesting that provirus integration may influence transcription in the host cell. Thus laboratories handling or culturing human xenografts should monitor for monitoring personnel for viral antigens or antibodies to them. 

I was in Reno last week. It was an honor to be there to meet Dr. Lipkin and hear about the study from the horse’s mouth. I also had the rare opportunity to listen to him brainstorm a little with Frank Ruscetti. It had a historically important feel to it. Dr. Lipkin is committed to being the perfect referee, “agnostic”, but I thought I saw the glint of desire to dive in to the discovery process. Dr. Ruscetti is a rare human being who sees his work in the context of the big picture. He is a realist, who never loses site of the patients that are the reason for the work in the first place.

The study, at a cost of $2.3 million, is designed to answer two questions:
1. Do XMRVs, and/or polytropic MLVs, exist in humans?
2. If so, do they occur at higher rates in CFS patients than healthy non-contact controls?

25 patients and 25 controls are being selected by 6 doctors, Montoya, Kamaroff, Bateman, Klimas, Levine and Peterson. Inclusion criteria are very restrictive to a particular subset of CFS that includes sore throat and lymphadenopathy. Samples will be split in Dr. Lipkin’s lab and two from each patient will be sent to 3 labs, the WPI, Lo/Alter and Switzer, where each lab gets to do their own thing. The study will be concluded to be positive if any lab can find 2 positives from the same patient. Discordant results will be decided with a third specimen.

I think we are OK, that it’s a fair playing field. The most commonly asked question in the patient community right now is with respect to the possibility of specimen tampering at points of inception. Even if that did happen at one or two sites, it would skew the stats, but wouldn’t cause the study to be completely negative. It is wrong that so much rides on one study, that nothing else will go forward until it is completed, and that one man has been made judge, jury and executioner, though I came away with the impression that he was a good choice for a difficult task.

Drs. Mikovits and Lombardi, Max, Shanti and Svetlana, have their work cut out for them, 600 specimens, each needing multiple tests. The best possible outcome for the patient community is that the WPI finds XMRVs/HGRVs at a higher rate in patients than controls, that Lo/Alter find the Ps at a higher rate in patients than controls, and that Switzer finds nothing, as expected. Dr. Lipkin mentioned more than once that, when the study is over, there will be a valuable repository of specimens remaining to look for what is there, should the study be entirely negative. At the end of his public lecture, he said that if anyone in the audience wanted to write a check for a million dollars, he’d find out what’s going on; good news, though the comment caused me pain personally, confirming what we all know, that we have the technology, but it isn’t being applied. He lectured about past virus hunts that only took days, also rather painful for this audience to hear. Almost the best news for me was that he said that CFS “smells viral” to him. He is involved in autism research and said that he suspects thimerosal in vaccines may in fact be implicated, not a popular stance with the vaccine companies. Let us hope that when this exercise is over, “the virus hunter” will be inspired to hunt viruses for us.

I had an opportunity to discuss antiretrovirals with Dr. Lipkin and to share my personal experience. He stated his disapproval vehemently. I told him that we had significant anecdotal experience at this point and it appears to be better than placebo, though disappointing in speed and scope of response. I stated my opinion that prescribing arv’s constitutes the usual and customary off-label use of drugs, a decision to be reached between doctor and patient. We obviously disagree completely in terms of whether or not the prohibition against these particular drugs is justified, but, even though he had strong feelings on the subject in the present tense, he concluded it needs to be studied, though everybody agrees that, in the current economic climate, there’s no money for what will need to be a long, complicated study. I didn’t get the impression that he was in any way discounting the possibility of a family of retroviruses with too much sequence diversity to be found when looking with our current lenses.

It was my 5th trip to Reno in 10 months. It was short, but the most stressful for me so far, maybe because it felt so important, though it was good stress, not bad, while it was happening. I felt “on”, but not anxious or consciously uncomfortable. I returned home still feeling strong. The day after I got home to Santa Fe, the Las Conchas wildfire started, now the largest in the history of the state of NM, over 100,000 acres, threatening the town of Los Alamos and Los Alamos National Labs. The air quality has been extremely poor. Here is a picture taken from our house, the night the fire started. The smoke is pluming all over Santa Fe and environs, making the air quality unacceptable for people with pulmonary disease. Mitochondrial disease too, I’d bet.

Despite lots of oxygen, which helps everything during administration and for a while after, I’ve been in crash mode for six days now. First time I’ve gone down for more than a day since December, when I caught a cold after my second trip. No cold now; just CFS. I don’t like to report bad news if it takes away hope, but my commitment is to reporting the truth. Sleep, always a sentinel symptom for me, was the first to go. Then pain, nausea and orthostatic intolerance have put a serious damper on things. Cognition is the last to go for me, thanking God for the not small favor. Clearly, I am still at risk, despite dramatic improvement over the last year.

Ali has been doing better since starting Meyer’s cocktail with Leucovorin, plus glutathione, IV pushes and supplemental oxygen by high flow concentrator (10L/min delivered by non-rebreather mask). She does an hour or so of oxygen a day, and the effects are so immediate and positive that she doesn’t have any resistance to doing it. At this point, we both consider the concentrator a no-brainer. She hasn’t tried the chamber yet. I’ve been going in about twice per week and using normobaric oxygen by mask about twice a week as well, and I haven’t decided yet whether I think the chamber adds enough to justify the expense/trouble or not. Ali had a friend visit her for 10 days recently. She used supplemental oxygen ad lib the whole time, was much more active than she has been able to be since last fall, and didn’t crash afterwards. She remains more resilient, despite the fire. She is wanting to get out of the house and just ordered some protective masks that she hasn’t tried yet, which people are wearing in Santa Fe now anyway.

Ali’s MCS symptoms are subsiding somewhat and, if not triggered, she is doing really well. She can wear clothes from the dryer again, though choice of laundry products is crucial. She and I both believe that her symptoms are not triggered by chemicals per se, but certain strong odors, so hyperosmia, much the way some patients have hyperacusis and photophobia, which are also cranial nerve dysfunctions. I believe these sensory symptoms to be related to dysregulation of the cranial nerve afferants, which are relayed through nuclei in the dorsal brain stem, and then to the thalamus, which integrates sensory information to the cortex, regulates arousal/sleep and organizes/controls the timing of the brain’s circuitry. The heightened signal triggers what can be thought of for practical purposes as a subclinical seizure. For some, the instabilities in the brain stem can progress to observable atypical seizures or even full blown tonic-clonic seizures. Here is a study by Frank Duffy at Harvard showing coherence abnormalities on QEEG (measured on the cortex), in patients with CFS, not seen in depressed patients: EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients. Duffy/Kamaroff. Inability to detox properly is likely a piece too, but in Ali’s case, I think that the reactive dysautonomia is triggered by input from the first cranial nerve, rather than a reaction to a toxic substance.

I leave for Hawaii later this week to see patients, looking forward to sea level and clean air. My patients all know I’m sick. When I hear their histories, I often remember exactly how that symptom felt to me, even though my illness has changed a great deal as it has progressed. They know that I don’t have the answer and that I don’t believe there will be a cure. Healing and curing are not the same thing. What we do have to fight with is a coherent model from which to plan a strategy for each person from where they are now. It will be two years soon since Lombardi et al was published; it has been nearly shot down by politics, not science, and  nothing has changed from a treatment point of view, other than antiretrovirals haven’t turned out to be the slam dunk for anyone, including me, that we needed. Of course there are hundreds or thousands of drugs sitting on pharmaceutical company shelves right now that might work, but so far, nobody is looking.

Despite my disappointment (not surprise) that the science is not keeping up with the medical need, I remain hopeful and determined. It won’t be fast enough, but I do believe they will get it right this time, even if the route is circuitous. The scope of the discovery is spectacular in terms of the impact it will have on our understanding of chronic disease. It will transform many fields of medicine, but especially psychiatry, which still views our symptoms as arising from a defect of character. We are the ultimate mind body experiment, and it’s not about character, or lack thereof, that our psyches are too closely linked to soma, the body. There is a biological basis. Heightened senses come with the territory. The misunderstanding, even derision, from our supposed caregivers has caused great harm. It is one of the most painful truths in my life that should I be forced to seek help from my colleagues in the conventional medical world, they will likely laugh at me, not to mention do the wrong thing. But there is redemption in turning suffering into meaning, in using painful experience to become wiser. The disbelief has caused terrible isolation. Healing, separate from curing, is possible, in connection with the truth, and in connection with other people who understand and care.

We must never forget that we may also find meaning in life even when confronted with a hopeless situation, when facing a fate that cannot be changed.  For what then matters is to bear witness to the uniquely human potential at its best, which is to transform a personal tragedy into triumph, to turn one’s predicament into a human achievement.  When we are no longer able to change a situation- we are challenged to change ourselves…
~ Viktor Frankl in Man’s Search for Meaning

1. How can I be seen at the WPI?
There is already a long wait list. Patients will be contacted on a first come, first serve basis to be scheduled for the doctor of their choice. If you would like to be added to the wait list, please email, rather than call, your request to the WPI office: info@wpinstitute.org

2. Do I have to be XMRV positive to be seen?
No. Our physicians will treat ME/CFS and related neuroimmune illnesses, without respect to the results of any particular test.

3. What treatments will be offered? Will antiretrovirals be prescribed?
Each physician will treat their own patients. There will be no set protocol. Our physicians will be practicing in an environment that supports openness to all options. All decisions will be made within the context of a physician patient relationship at a particular moment, as always. Antiretrovirals are not promised, nor will they be forbidden. Off-label use of drugs is the usual and customary practice of medicine. We see ourselves as working within the context of a public health crisis. We believe that ME/CFS patients with severe disease should have the right to compassionate use of unproven drugs.

4. What will be different than the care I’ve had in the past?
The group nature will encourage a deeper insight into the illnesses at hand, and provide each physician with exposure to the treatment approaches most likely to be effective. Daily interaction between physicians and scientists will cross-fertilize the thinking of both, impacting patient care directly. Our doctors will be part of an international consortium of practitioners sharing experiences in our Physician Working Group. Records will become part of our database, which, with time, will grow to include a very large number of patients treated by a group of doctors, enabling us to look at outcomes in a broader way than is possible for a single doctor. Adverse outcomes will be reviewed and discussed within the group.

5. Will there be clinical trials?
As all of us know too well, there is no slam dunk, quick and easy trial to do. Tenofovir is probably worthy of study, but until we have a way to monitor, the clinical response is too incomplete and too slow for a short, simple study, given that any study we do now must be possible with extremely limited funds. Dr. Snyderman is interested in studying lenalidomide and we are looking at that. We are open to all options, but unfortunately, pharmaceutical options for study are limited at this time.

6. Is it going to be an alternative medicine clinic?
It will be a “conventional” medical facility, located on a medical school campus, with physicians who are CAM, complementary and alternative medicine, aware.

7. Will insurance be accepted?
No. A superbill will be provided for submission to insurance. Current Medicare and Medicaid reimbursement rates make it impossible for us to accept insurance and provide patients with the time consuming care necessary to impact the illness.

8. Can I see you or be supervised by you in Reno?
No. I’m not licensed in Nevada and getting a new license there with a “practice gap” will take some time. My duties in Reno are administrative. I have started a private practice on the Big Island, where I am licensed. Each physician in Reno will be responsible for seeing and following their own patients.

The enormity of the need feels a lot like charging hell with a bucket of water, considering our limited resources, but we’re going to do it anyway, as we start seeing patients one case at a time.

As the battle is waged on the scientific front, it is with great joy that I am able to announce that we will begin to see patients at the WPI on August 1. It will close the circle necessary to be a true translational research center with synergy between disciplines.

Dr. Chitra Bhakta is a Family Practitioner with a private practice in Orange County where she treats ME/CFS and autism. She brings medical insight, scientific literacy and compassion for the patients. Dr. Bhakta will continue to be available to her Orange County patients during this transition.

Dr. Robert Fredericks is an Endocrinologist in private practice in Reno. His special interests include the endocrinology of neuroimmune illnesses and he is an expert in bone metabolism. He has decided to join us and is in the process of moving his practice into the clinic, thus providing us with our first specialist.

There are a very large number of patients asking to be seen. We will only be able to accommodate a few in the beginning. We have other interested doctors, but Nevada’s licensure process for new physicians coming into the state is long and can be convoluted. Dr. Bhakta has had a Nevada license since her residency at the University of Nevada, allowing her to begin without a delay. Our goal is to create a group of like-minded physicians. I tried active recruiting hoping to accommodate the volume of patients at the outset, but it will have to happen more organically, as we find the right doctors with passion for the project.

It’s a start.  The need is enormous. We will get our systems in place, fill in the gaps with respect to pathophysiology, and approach treatment with the benefit of the perspective of our scientists. The seeds are sown. We will water and care for this unique garden, growing our knowledge for the day when we can harvest in the form of clinical results.

A journey of a thousand miles begins with a single step.
~ Lao-tzu

Where large sums of money are concerned, it is advisable to trust nobody. ~ Agatha Christie

Thank you to Kristin Loomis, for contributing her comment and for the additional information she provided privately. I have a better understanding of the HHV-6 Foundation’s policies and interests. I understand that retroviruses really aren’t on the foundation’s radar these days. I apologize for any inaccuracies, this time, and anytime; I do my best to fact check before publishing, and to limit any criticism that is directed at an individual to what can be verified on the internet, not gossip. I write each blog with the information at hand at that moment, intending to stimulate discussion. It is personal opinion, reaction to the events, public and private, not investigative journalism, though I wish a good investigative journalist would take it on. I’m getting mail suggesting that I interview people before posting blogs, but I have a day job again:). In any case, the information circulating that HHV-6 Foundation funded Knox et al is apparently incorrect. I invite anyone who feels they have been criticized unfairly to join us. Everyone needs to know the truth.

In your comment, Kristin, you said that you believe that Abbott funded Knox et al. I guess it’s logical to conclude that if Abbott appears on a paper, there is money involved, either because they funded the study and/or there is a patent and potential lucrative test involved. This raises a number of questions. I hope that anyone with information to answer these questions will contribute to the discussion as you did. I have never thought that there is a conspiracy in the sense that Peterson, Knox, Coffin, Stoye, Vernon, McCleary, the editors at Science, et al are having conference calls plotting our destruction. Each individual has their own reasons for doing and saying the things they have.

In my opinion, whoever funded their study, Knox et al have some pretty unsavory stuff to explain to the patient community. If I put the best spin on it possible, then the patients have been harmed by misguided acts. The publication of their shoddy work was unethical and immoral, in my opinion. The collection of the specimens in the first place for this purpose is inexplicable to me. Even if Peterson woke up one morning and said OMG, XMRV is all a big mistake, it is inconceivable to me that he no longer believes it is a retrovirus. So his desire to bury XMRV has to be about being right, ego and revenge, or money. Roche funding Valcyte? Hemispherx funding Ampligen? As I’ve said, he is welcome to respond. I will be happy to post anything he’d care to share. I would like to point out here that although I’ve had a lot of questions about Dr. Peterson for a long time, and have heard many stories, from protagonists and patients (always my most important source), I didn’t mention his name on this blog until the publication of Knox et al, which I took as a declaration of war on the patient community.

Abbott turns up all over the place, e.g. link; see Industry Relationships at the bottom of the page. They are clearly interested in XMRV. Their employees appeared as co-authors on negative and positive papers in Belgium, the positive paper being about a test for XMRV in prostate cancer tissue, not blood. When someone does a study, they know what they want to find; then they blind it to make it convincing, keep it honest. It makes no sense to do a study knowing at the outset that your test detects nothing, unless that is what you were trying to show in the first place.

From where I sit, there are many unanswered questions. It would be lovely to have no need of considering anything but the unfolding science, answering all of our questions in logical sequence, so everyone could take the high road; but that isn’t what happened. Thus my questions of the moment. Why and when did Abbott approach Konstance Knox to do a study on XMRV, when she had never published on anything but HHV-6 and owns a commercial lab dedicated to it’s detection? Why is Abbott’s funding of Knox et al not disclosed? Why would Abbott want to publish a negative detection study? Who is Graham Simmons and what is his stake, as he appears on negative, equivocal and positive papers? He works for a business entity involved in transfusion science and has a teaching appointment at UCSF, as does Jay Levy. Where do Roche, manufacturer of Valcyte, and Hemispherx, manufacturer of Ampligen, fit in to all this, since it seems likely they are a piece of the puzzle as well? What else do these people/companies have waiting in the wings? Intellectual property laws support a unique patent. Who put pressure on Science to rush Knox and their EEC to press when they did? When did Dr. Peterson collect the specimens for Knox, and what was his relationship to the WPI at the time? Did he inform everyone of what he was doing? You can’t get into anyone’s head. In the end, only the Shadow knows. But facts, actions, dates can be verified.

Nobody wants to have anything to do with CFS, except the WPI (and the CAA, with their peculiar spin). It’s common to hear that this or that researcher is sorry they got involved in CFS, because the advocacy community is becoming so strident. I’m not sure what the answer is. Polite hasn’t gotten us anywhere, as witnessed by the useless money that’s been spent on the CAA over the years in their pitiful attempt to validate the illness scientifically. If that had worked we wouldn’t be confronted with the psychiatric community wanting to label us with “CSSD”. The CAA too is free to respond in any way they like; the comments on this blog aren’t moderated.

ME/CFS is of retroviral origin, as is ASD, in my opinion. Read the HIV and animal retrovirology literature, much of which is referenced in previous blogs. It’s all there, plus the methylation defect and mitochondrial issues, covered to a large degree in the HIV literature, that were making up the bulk of my reading until the recent salvo was fired. The parallels are obvious. Nothing we’ve ever had to work with as physicians comes even close as a workable model to provide us with an approach to treatment, with a chance of healing the patients, forgetting about whether XMRV is the major player or not. For an individual to take any action at this time which has the effect of shutting down research into the retroviral origin of the disease is a crime against humanity.

Nobody is saying that the associated, opportunistic infections seen in ME/CFS aren’t important, anymore than Pneumocystis is unimportant in AIDS. It is exactly analogous. In this case, there may be interaction between viruses. Activation of latent viruses may benefit the underlying retroviral process, turn it on if you will. Another possibility is that any persistent infection causes downstream inflammatory changes that favor activation of provirus. The research into how retroviral etiology explains CFS pathophysiology needs to proceed, even before everything is sequenced and proven, even while XMRV’s defendants are being raked over the coals. Everyone involved knows it’s much bigger than whether individuals get discredited or laughed at. Scientists and doctors are much the same when it comes to fear of ridicule restricting their abilities to fulfill their prime directives.

In the end, science will tell us who is right, irrespective of personalities, unless the work isn’t done at all. Although I look forward to the results of Dr. Lipkin’s study, and from what I have read and heard, he is worthy of the respect he has been proferred by being put in charge of such crucial work, it seems wrong to me that it all rests on one man’s conclusions, or the ability of a couple of scientists to flawlessly reproduce their work, though they will certainly try. Maldarelli, Lipkin, XMRV Blood Working Group. That’s not much for a million sick people. When John Coffin declared XMRV dead, he said it could be another retrovirus. Is he looking for it? Why is the federal government going to let this go another year, waiting for a ruling on one virus, before considering the bigger questions? It needs to be studied as an enormous health crisis, whatever the outcome of the work on XMRV. If it were anything other than a kangaroo court in session on a federal level, the work would be a priority, with our Center for Disease Control finally trying to do some controlling of our disease.