2 AM

Awake, as I often am at this time of night, sick… nausea, pain. Lots of angry comments, as expected. Why did I put that out there? I’ve already pissed off scientists, doctors and now quite a few patients. Why would I want to do that? Am I trying to disidentify? I feel pretty identified as I write this. Why did I write something so critical? Because it’s my truth? That’s pretty presumptuous. Why should anyone care? The important part of the post is the medicine, which received very little comment. Interestingly, there were positive comments back channel from doctors about the same paragraph that made patients angry.

I’m not a writer. I’ve never written before. The blog was Ali’s idea. I felt that I was finally emerging from the medical darkness and that sharing my ideas as they were unfolding might have value. Blogging is interactive, so perfect for bidirectional running commentary. The anonymity of the internet makes it a bit tough for the blogger if you have controversial views of a complex issue, but so far it’s been worth it. I’m OK with the anger (within limits). I’ve written about anger here quite a bit. I’m angry too. And I have no interest in speaking with my “inside voice”, nor am I encouraging anyone else to do so. What I am trying to do is frame the discussion in a way that evokes compassion in people not living with the disease.

If you don’t like the comparison to a level of suffering outside of the industrialized world, then let’s talk about suffering in the world of cutting edge medicine. As a hospital based physician for many years, I learned that the myriad ways in which the human body can become deranged makes for a veritable chamber of horrors. ME/CFS patients don’t have any corner on suffering, though it’s a contender when the disease gets really severe. I saw unbelievable things as an ER doctor. There are lots and lots of horrible ways to get sick. What is different about our experience is the incredible degree of disbelief and misunderstanding we’ve had to endure. As a patient group, we’ve been stripped of our dignity. We’re not unique that way either, but there are an awful lot of us and it’s gone on for a really long time.

Where do we go from here? Medically it’s not that tough. The doctors need to treat the patients with very limited information, as usual. Their awareness needs to be raised so that they know how to approach the illness, but if it’s put on their radar, they can handle it. It seems clear from the animal retrovirology literature that the scientists can handle it too, if they stay engaged. That’s the big if right now. We need them to see the big picture, that it’s bigger than XMRV. Big enough for careers to be made and prizes claimed. We need to find a way to inspire the compassion that we deserve. We’ve all been wronged.

Personally, I find it helpful to remember that many people suffer more than I do. My illness has been my greatest teacher. I can’t control what happens, but my response to it is all mine. There are still amazing moments. I’ve had some wonderful moments reading comments on this blog – moments of connection. Now, from some of the comments, I guess I must be getting close to something that’s festering. I questioned a mindset that’s ineffective. What now?

Treatment

There’s been a shift in the quality of some of my mail. I am becoming very concerned about being misinterpreted. When I write, I assume that people have read what I’ve written before, but increasingly, that is not always the case. I’ve been writing for eleven months and have covered a good deal of ground. It is becoming clear that if I keep writing, I will have found a way to piss off almost everyone.

When I suggested that antiretrovirals may be useful to prevent transmission, activation or progression of the disease, I meant in the future. Please do not forget that treatment during pregnancy is very effective for preventing HIV from infecting the next generation. Likewise post-exposure prophyllaxis works for HIV. However I was NOT suggesting that prophyllactic use of antiretrovirals is reasonable for XMRV positive people at this time.

I am in favor of treatment. Repeat, I am in favor of treatment. I am against overly aggressive treatment that harms, e.g. indiscriminate prescribing of antibiotics a la ILADS guidelines. I do have the impression that folks who have avoided or not trusted doctors are generally better off, but there are treatments worth considering. I can’t forget that I was functioning as a doctor, and treatment brought me down completely, for six years; I started to improve when I stopped everything except my blood pressure medicine. Ali got four good years from antibiotics, but then was sick for three despite them. A word to the wise. Don’t beat a dead horse. We need to learn from the mistakes of the past.

Here are the current treatment options for consideration, as I see them:

  • Antiretovirals: Viread, Isentress, AZT
  • Antivirals for activated viruses EBV, CMV, HHV-6 and 7, genital herpes, shingles: Valtrex, Valcyte, Acyclovir, etc.
  • Antibiotics for Lyme Disease and other tick-borne diseases: orals, judicious use of IVs, treatment for Babesia
  • Anti-inflammatory drugs and supplements for NFkB inhibition (avoiding synthetic steroids when possible): Actos, aspirin, Celebrex, Meriva SR
  • Treatment for dysautonomia, POTS, OI: oral hydration, electrolytes, IV saline, Florinef, beta blockers (including Bystolic), midodrine, sublingual Zofran
  • Treatment for methylation blocks and glutathione depletion: Deplin, other folic acid derivatives, B12, parenteral glutathione, Meyer’s cocktail, NAC, undenatured whey protein
  • Supplements supported by the HIV literature (a work in progress)
  • Bioidentical hormone balancing and replacement
  • Vitamin D supplementation
  • Oxygen
  • Nootropics: selegilene, piracetam, vinpocetine, others
  • A few relatively harmless things that may be useful for some: Nexavir, LDN, Flexeril, isoprinosine
  • Eliminating stressors
  • Mind body therapies, especially biofeedback: EEG, heart rate variability and peripheral training
  • Dietary change: Specific Carbohydrate Diet, personally tailored elimination diets, probiotics
  • Detox and avoidance strategies, especially for MCS, toxic mold exposure, and specific dietary triggers, gluten, cassein, nightshades, sugar
  • Herbal treatments: hawthorne, stinging nettle, samento, ginseng, valerian, gingko, milk thistle, rhodiola, others
  • Medical marijuana (caution: can exacerbate POTS due to hypotensive effect)
  • Symptom based treatments: pain medicine, anti-anxiety medicine, anti-depressants, sleep medication, psychostimulants, etc, etc, etc.
  • IVIG?
  • GcMAF? 
  • Ampligen?

I won’t use the dreaded acronyms CBT and GET, but taking the politics out of it, very careful resistance exercise is important. If aerobic exercise is tolerated without PEM, it keeps the disease at bay (patient reports). It is possible to exercise even supine. And, though my own experience with psychiatrists has been dismal due to disbelief and misunderstanding, a good therapist can be a godsend.

Personally, I’m not interested in Rituxan, Vistide, Mitomycin C, or stem cells out of the country. Even stem cell proponents are now saying that repeated infusions are necessary. It seems to me that if placental stem cells are used, without control of the underlying retroviral infection, they will become infected, and if autologous cells are used, they are already infected. Also how are the donors screened, given that blood products are particularly unappealing at the moment? I have heard from a number of people who have pursued this with no impact on their illness.

The reactions to Ali’s post were all over the place. Please know, she is not without medical advice;). She is an extremely informed patient, familiar with conventional and alternative options. For now, she is trying dietary interventions, mind-body therapies, occasional alprazolam for rescue, and tincture of time. She tried atenolol, which helped the tachycardia, but made pretty much everything else worse. Ali is sharing her experiences, because of the philosophical questions raised, and to reach out, not because she is looking for a new treatment, though the concern expressed is of course appreciated. The symptoms she described, very common in CFS, GWI and ASD, represent the interface between the psychological and the physiological.

There’s a difference between sharing what has worked and telling someone else to “take the cure”. In the last couple of months, I’ve received so many protocol suggestions that there isn’t enough time left in this life to try them all, though quite a few probably have merit – at least seemed to work for someone. These suggestions underscore the many observations over the years that the best approach is to alter the internal and external environments in your favor whenever possible. With luck, you may hit something that makes enough of a difference to really impact the disease process. Treatments directed at reducing inflammation are useful. Strategies for silencing provirus need to be considered, now that we know what we’re thinking about. And an approach that makes us feel hopeful and peaceful is more likely to have a  positive outcome, because the disease is so stress related. The fact that the illness is exacerbated by stress is the reason why the assumption was made that it is a somatoform disorder. The connection with stress was always obvious to me. It was the thing that made me think my doctors and colleagues were right about me in the beginning, since what happened was so different from what I was taught to expect getting sick might be like.

There is a divisiveness, an ugliness, that has developed within the patient community, and it comes out in some of the reactions when people disagree. There is often an angry edge expressing even mildly dissenting opinions. It’s defensive and a reaction to past disputes and slights. Ali mentioned the new young adult people’s forum and I read very negative, gossipy things about its creator. That young man is using all of his limited energy to provide a much needed forum for very isolated young people to come together. Why would anyone attack him? Many of the recent comments sound like people don’t feel heard and aren’t hearing each other. Due to variable response, different factions have developed. Accept that whether something did or didn’t work for you may have little predictive value for others. We should be coming together as a patient group and listening to each other, not fighting. Often past experiences of being doubted or judged color the reaction to current developments. We have all made mistakes. Let’s let it go.

I can’t believe the heat around my being “too easy” on Tsouderos. Even my last post was thought to be a sell out. I’ve received more negative mail about her than anything else I’ve written. I wasn’t around for her autism/vaccine articles, but there was once a photoshopped picture posted on the Age of Autism of her and others eating a baby for dinner. What’s that about? You may think she’s a bad reporter, or even a bad person, but she’s not exactly a baby murderer. It’s all too emotional. When you scream at people, it’s hard for them to hear you. It hurts the cause. There is a sense of entitlement that comes across and makes us an unsympathetic patient group. Everyone being healthy isn’t an inviolable right. People suffer worse every day all over the world. I imagine starvation is worse. Or being tortured. I treated a Cambodian woman in the ER once whose eleven children had been shot in front of her by the Khmer Rouge. When I think “why me?”, I remember her. There’s something wrong with this modern expectation that we’ll all be taken care of. The world is a really messed up place. Life isn’t neat. We don’t all get to be comfortable. It is a peculiarly modern phenomenon, this disease where so many people get sick and don’t die, living their lives with all modern comforts, but unable to get comfortable, no matter the luxuries.

Reentry Phenomena: Part 8

 By Ali Deckoff-Jones

     The first months of the New Year have presented me with new challenges. Many of my symptoms like fatigue, pain, and brain fog are drastically reduced. I have the energy to write on a regular basis, something I could never do before ARVs. However, I have spent these last three months housebound because of a brand new symptom.

     Every time I try to leave the house, I am struck with horrible episodes of dysautonomia. My pulse races and my blood pressure drops. I get dizzy, pale, nauseated, and my hands turn to ice. But the worst part of the episodes is the element of panic, an anxiety so intense I feel as if I am going to die. This anxiety seems to be secondary, a result of the physiological imbalance rather than its cause. I seem to be suffering from too much sympathetic tone – an overdose of the flight or fight response.

     In my experience, certain symptoms like fatigue and PEM are a constant presence; it is simply a question of severity. Other symptoms seem to come in clusters, making life difficult for a few months and then fading away. I am hoping this will be the case with these new episodes. In the mean time I am experimenting with natural ways to deal with them like biofeedback, neurofeedback, and EFT. It seems unlikely that any of these things will be a cure on their own, but hopefully a combined effort will help to reduce the episodes to something manageable.

     The reason I bring this up is because the episodes have brought a new question to my mind. While it is true that the episodes are largely physiological, there is an obvious psychological component. A fear component. I am afraid of the episodes, and that very fear makes the episodes worse. It is a vicious cycle.

     What am I afraid of? Many answers come to mind, some logical, some less so. I am afraid of being sick, and I am even more afraid of being sick in public. I am afraid of being helpless and losing control of my body. I am afraid of going out and getting sick, disappointing the people I am with by ruining their plans and messing up their day.

     Fear has invaded other parts of my life as well. The episodes have made me terrified of being alone lest I should have an attack with no one around to help me. They have also made me afraid to travel. As my mom continues to broaden her horizons and rebuild her career, she is going to be traveling a lot. It is becoming inevitable that I will have to spend a lot of time alone or gather the courage to travel with her. Both options are terrifying.

     More than anything, I am afraid of change. My life has become so static, so stagnant, and I am afraid of the unknown. Logically, this is ridiculous. Why would a CFS patient, whose life is so full of suffering, be afraid to change things up? It seems like anything new and different should be an improvement. Any progress or evolution should be a good thing. Still, the fear remains.

     But the more that I confront my fear, the clearer my mind becomes. I am unwilling to let this fear rule my life. I am unwilling to let it tear down all of the progress that I have made. Yes, the episodes are a significant problem, and they make me feel horrible, but they are not life threatening. I know that they make me feel deathly ill, but I am not going to die. If I can learn to control the fear, then maybe I can learn to work past these episodes and regain the steps I have made towards a normal life.

     I am determined to start going out, and I will face these episodes head on. They are the only thing holding me back, and being locked away in my house is becoming unbearable. I am going to fight my fear every way that I can.

     Will I succeed? Of that I am not sure. But one thing is certain: if I succumb to my fear, if I give up without trying, failure is inevitable. And the result of that, a life forever caged, would be the most terrifying thing of all.

Hospitals

     Removed from the stress and pressure of eleventh grade, my health slowly improved, but I never reached another full remission. The biweekly Bicillin shots alleviated the worst of my symptoms, but fatigue lurked over my shoulder, constantly taunting me with its presence.

     That summer my cousin and my brother’s best friend from Sedona came to visit. Spending time with other kids was a nice distraction from the disappointment of the last year. Unfortunately, the joy of that summer was marred by health tragedy. My mother had an accident while horseback riding that landed her in the ER with a concussion. The head trauma precipitated a full blown crash and a cluster of severe abdominal migraines that sent her to the ER multiple times that summer. I did my best to remain oblivious to what was unfolding around me, trying to enjoy what remained of my vacation, but the stress of my mother’s illness was weighing me down.

     A few weeks after my cousin went home, I woke up one morning with my left arm paralyzed and numb. I couldn’t move it at all, and I couldn’t feel anything above my elbow. My father and grandfather rushed me to the ER because my mother was too ill to accompany me. My grandfather was a vascular surgeon and the rock of our family. As I was waiting to be seen, he examined me. He tried to hide his worry, but I could tell that he was truly concerned. I had never seen him scared before, and I knew at that moment that whatever was happening to me was serious.

     I tried to remain stoic, but I was terrified. The nurses poked and prodded me, sticking me four times before succeeding at getting an IV in place. A harried ID doctor rushed in from her private practice, clearly irritated at the interruption, to do a neurological exam. She was harsh and blunt and doubted my diagnosis of Chronic Lyme Disease.

     I tried to fight back tears and terror while my grandfather made inappropriate jokes to try and keep me distracted. I distinctly remember being horrified at his politically incorrect comment about a Sikh in a turban and hospital gown. Still, I appreciated his company and constant presence.

     A few minutes later they wheeled me away to get an MRI and CAT scan. Much to my relief, I was already beginning to regain feeling in my arm, but there was no way I was going to avoid a complete battery of tests. The testing passed by in a blur; thank goodness I was not claustrophobic. But more anxiety was in store when we heard the results of the MRI. The doctor had found a small spot in my brain; it was in the right location to cause my paralyzed arm. I remember more terror as the word ‘stroke’ passed though my mind.

     St. Vincent’s Hospital in Santa Fe did not have a pediatric ward, and my ER doctor decided that I needed to be sent to the pediatric ward at the University of New Mexico Hospital in Albuquerque. They loaded me in an ambulance, and my dad rushed home to pick up a few of our belongings before driving down to meet me. The EMTs in the ambulance were the nicest people I had met all day. They distracted me with stories, including one about seeing Jessica Simpson on the site of her newest movie. The frivolous, non-medical chat was a soothing relief.

     By the time I reached UNM, my arm was functioning normally again, but I had a lingering headache. I spent four long days in the UNM hospital attached to heart rate monitors and constant IV fluids. I was examined by countless people – nurses, neurologists, attending pediatricians, psychiatrists. Some of them were polite; some of them were crass; all of them seemed doubtful about Chronic Lyme Disease. The questioning, sometimes accusatory looks grew wearing.

     The nights were worse than a bad dream, filled with blaring lights, wires attached to my chest, and the scuffling noise of the hospital. There was one premature baby in the ward whose heart rate kept dropping, setting off a blaring alarm every half hour or so. The days were filled with bland hospital food, the distant cries of children, and more invasive examinations, including multiple psychiatric evaluations.

     On the final day of my stay, they gave me a spinal tap. The test itself was terrifying and painful; the headache and nausea that followed were worse. Finally, they told me the test had come back negative, and I was discharged with a diagnosis of atypical migraine. 

     Meanwhile, my mother was undergoing trials of her own. The physicians were blatantly clueless to what was wrong with her, labeling her with various incorrect diagnoses. Their continual mistreatment that summer brought her to the brink of death. She spent months in and out of the hospital unable to eat. She was finally rushed into emergency surgery at midnight, and after a transfusion, they had to remove a foot of her small intestine.

     It wasn’t until a few months later that my mom received the records of my stay and discovered that my spinal tap had in fact not been clear, but contained some white cells. We now recognize their mistake as a blessing in disguise; had they treated my abnormal spinal tap, it would have been with steroids, and my mom was too sick to intervene at the time.

     The hospital’s complete incompetence in both of our cases was and still is astounding. They judged and doubted our diagnoses simply because they were unfamiliar with them. The current medical system is unable to think outside of the box in any way. If a diagnosis isn’t on their radar, they will not only miss the true problem, they will make the problem worse. As I reflect on this experience, all I can do is shake my head and think that it is no wonder so many people are terrified of hospitals. They should be.

* * *
      I’d like to take this opportunity to announce the creation of a forum specifically for young adults with ME/CFS/Lyme/MCS/Mold Illness etc. etc. etc. ;) The group was created by an online acquaintance of mine who is planning on upgrading the site to a social networking platform. It is a wonderful opportunity for young patients to meet and interact with others who suffer from the same illness. There is a nice mixture of medical and non-medical discussions taking place on the forums. Currently, the group is limited to patients under the age of forty. The forum can be found at: 

Reflections about right and wrong

It was much easier to write this blog at the beginning when I was so hopeful of having found a solution. I still believe that antiretrovirals may be a piece of a solution, and I continue to take them. Their use needs to be explored, probably in conjunction with other things, but they are not the slam dunk we needed. However, we need not wonder for years, waiting for somebody to approve an IRB that says we are allowed to find out. We already “know” part of the answer. It should be noted that, for the most part, the people who have tried antiretrovirals have been sick for a long time. The best response I’ve heard of was in a patient who is young and had not been sick for long. It may be that the drugs are useful for the newly crashed, the unborn, or even harder to study, the not yet crashed. A good percentage of people who try them experience cause and effect improvement in the first months of therapy. Like the detection and testing issues, it’s not so simple. Nor is it as simple as, don’t use them, since the drugs move the illness. Nothing with this disease is ever simple.

My impressions of available treatment options in my last post weren’t meant to be in any way dismissive. Believe me, it is all personally relevant. As I’ve said before, I could be wrong about anything. I’ve certainly been wrong before. I’m not writing because I think I’m right about everything, but because I have perspective, for various reasons, and want to shed any light I can. There is so much darkness. The comments sharing experiences are very valuable to all of us. I heard from a penpal in Belgium yesterday who is seeing Dr. De Meirleir, started GcMAF and is doing very well. She also mentioned that she needs to sell her house as she has a mold problem. I do think that mold and other chemical exposures are an important piece for many. The comments about moderate avoidance seemed particularly useful to me. We are always looking for a cure, but improvement counts.

When I was in practice in the Berkshires, I helped people a lot just by stopping things they were taking. I prescribed very little in that practice, other than hormones and weaning schedules for drugs that other doctors had started, often many years before. Sometimes huge gains can be made by stopping things. All drugs have side effects. Patients are often taking drugs prescribed by multiple doctors who don’t communicate with one another. Like an elimination diet, it can be best to stop things, find out what the baseline is and then add things back judiciously. NOTE: some medications are dangerous to stop suddenly. Benzodiazepines and opiates are particularly problematic long term, even if they were lifesaving when started. The memory of how much they helped at the beginning and the fear of how much worse it will be without them, coupled with physical dependence, makes them very difficult to stop. Often tolerance has become a problem and patients don’t believe that going down won’t be terrible, but not even noticing a slow reduction is a common reaction. Going from something to nothing can be a little difficult, but the rewards may be considerable. Klonopin is very commonly in use, because benzo’s help so much with the symptoms of increased sympathetic tone and Klonopin is more socially acceptable than Valium or Xanax, even though the later drugs are actually more effective in the short term. In practice I used to see epileptics desperate to get off Klonopin because of cognitive decline and depression. I’ve posted the references before (CFS treatment myths). This is not a value judgment, having been on both sides of this problem.

I don’t want to turn this into a discussion of Trine Tsouderos, but mentioning her generated so much heat that it can’t possibly be about her. Her stuff is accurate, if a little slanted, not that bad, even with respect to us. I speak to other reporters who think she’s competent. “She makes the calls, asks the questions and writes down the answers”, one said. None of them profess to understand the science deeply, though some do more than others, but that really isn’t the point. They ask somebody what they think and quote them. Then they ask somebody else who disagrees and quote them. They’re not supposed to write what they think. Their personal bias shows despite their best efforts, because they choose who to quote and which quotes to lift at random, but nobody really thinks their opinion is important. The anger that Tsouderos generates seems important though. She is parroting scientists and doctors whose interests don’t extend to helping us, like Offit, who has made lots of money on his vaccine and been hailed a hero, but can’t or won’t face the possibility that the vaccine program may have hurt millions of people, even while saving others. I don’t think it’s about Trine. She’s the messenger. Lois Lane, who can’t figure out that Clark Kent is really Superman, even though she’s standing right outside the phone booth. It’s the people who tell her what to think that are the problem, because she truly doesn’t think for herself, and isn’t being paid to. Some of the people she talks to are evil and, even if they’re not, they are without compassion. That’s what hurts. There is something cold about the way she approaches the problem, hiding behind “the evidence”, largely absence of proof, while ignoring the evidence of millions of suffering people. Clearly her editors are more concerned with pleasing scientists and doctors than patients, who they see as powerless.

I am struck by the occasional angry outbursts from scientists, who have been reading and feel the need to say I’m wrong about everything. I feel like an Aikido student deflecting energy, because I really do want their input. Why all the anger? Because you disagree with me? Because my medical mind skipped a few steps in your deductive reasoning process? You couldn’t possibly think I’m wrong about everything. The most important thing that is happening here is the discussion about the clinical problems. Why not contribute to that in a constructive way? Because I’ve painted a picture that makes the ivory tower look like the Leaning Tower of Pisa? Why should you be protected from the patients who are the reason for the work? If the science is a nay, then everybody can go home and forget about all these difficult patients again, just like before? We can’t let that happen this time. If the first attempt to find the causative retrovirus has revealed the tip of a very large iceberg, burying XMRV doesn’t get anybody off the hook. Give it up, get to work and find the truth for us. We need your help. I know that there are very good scientists out there who really wanted to find XMRV and haven’t been able to. Neither were Drs. Alter and Lo. They found something else of significance. Please don’t give up.

Random thoughts

It is difficult to imagine how XMRV is being dismissed as a lab contaminant by some supposedly intelligent people despite the publication of the following three papers in The Journal of Urology:

The recent paper Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. Schutzer/Natelson contributes to the literature supporting a biological basis for both CFS and chronic Lyme Disease. The authors believe that treatment resistant Lyme Disease is a distinct entity from CFS, and in my opinion, that is not likely. The Lyme group probably met inclusion criteria for the CFS group, but it isn’t clear from the paper. There was much overlap of “proteomes” between the groups, which makes sense, as there are probably some CFS patients without Lyme and possibly some treatment resistant Lyme patients without CFS, whatever “CFS” is. A better explanation than two distinct diseases is that the immune deficit from the underlying retroviral infection causes Lyme to be a bigger problem than it otherwise would be. As I’ve said before, the very few clinicians who care for both groups of patients find them clinically indistinguishable. My impression is that the patients who wind up in the Lyme group are sicker and have more pain, either from neuroborreliosis or excessive treatment, very hard to say.

I love the meeting place feeling that is developing here. There are now well over a thousand comments on this blog. I haven’t moderated it at all. There has been no spam (knock on wood). The comments have been insightful, compassionate, funny, sad. They often stimulate me to write more. They demonstrate that the patients get it, even if most of the scientists and doctors don’t. I’ve removed only two comments, directed at someone else, that were over the top. The invisible counter shows it’ll hit 150,000 pageviews, at a year next month, from six continents. Parts of it have been translated into German and Spanish. It has been discussed and linked to in many languages, some of which I don’t recognize. Every post is read by thousands of people in a few days. It doesn’t cost a dime. The internet is an amazing thing. We would all be alone and powerless and we’re not. Personally I think FaceBook and Twitter are really creepy, but they are powerful enough to bring down dictators, so should be used to our advantage.

I continue to communicate with many patients by email and phone. My impression is firmer than ever that the people who have done very little are doing better than the people who have pursued aggressive or experimental treatments. Radical avoidance has worked to control symptoms for some and the stories of our mold warriors are intriguing. It’s not hard to figure into the model I’ve proposed how biotoxins causing inflammation would activate virus and keep it activated while the exposure continues. My impression is that men are more likely to recover an adequate level of function and more likely to be able to exercise. My husband is an extreme mountain biker at almost 50, seven years after onset of cardiac symptoms and severe dysautonomia; he has thrived with the disease and he mostly refused treatment. Although PEM is probably pathognomonic, there are people who can exercise. I had a year of episodic neurological and vascular symptoms, followed by a full crash and period of disability, then near recovery, without treatment, for most of ten years during which I could exercise, but had symptoms. In addition to the common viral onset and immediate PEM which never goes away, histories like mine are not uncommon. A crash with a very slow recovery over a period of many years is a variation, and lots of others. My general impression is that the second generation is sicker. I have even heard from families with three generations of clinically apparent illness. There is lots and lots of subclinical disease in family members.

It is a relapsing, remitting illness. Whatever someone was taking (or prescribing) at the time the improvement happened is thought to be causative. Lately I’ve had particular difficulty with people who believe they know how to cure me with their favorite therapy. Some people who have recovered have a lot of ego about having gotten well and that makes it even more difficult for those who haven’t. IV hydrogen peroxide comes up a fair bit. Please folks, if you want to try some oxygen, use oxygen. If you want to try a higher dose of oxygen, try HBOT. Don’t let anyone inject peroxide into your veins. Or endanger you in other ways. There is no cure, though some people get better spontaneously. If anybody had the answer, so many people wouldn’t still be sick.

What do I think about Ampligen? I have no personal experience with it. From my mail and the impressions of friends in practice, like everything that has been tried over the years, there seem to be a very few successes, some modest results and some harm. It’s been around forever, so it’s hard for me to believe that it works that well, or we’d know by now. It’s IV, is needed indefinitely, so requires permanent access, and is financially out of reach for most. It’s making some doctors wealthy though. The patients are even paying for their own clinical trials.

IVIG has helped quite a few people, incompletely and the improvement doesn’t always last. It’s intravenous, you have to take it forever, it’s expensive and difficult to get covered. Also it’s a pooled blood product. 

Rituximab? It sounds really scary to me. To take or prescribe. The initial infusion can kill you. Complications include life threatening infections. From the drug monograph:

Serious adverse effects, sometimes fatal, have occurred in patients receiving rituximab. Severe or fatal infusion-related reactions; tumor lysis syndrome associated with fatal renal failure; severe or fatal mucocutaneous reactions; progressive multifocal leukoencephalopathy causing death; hepatitis B reactivation with fulminant hepatitis, hepatic failure, and death; other severe or fatal, bacterial, fungal, and viral infections; serious or life-threatening cardiac arrhythmias; severe or fatal renal toxicity; and fatal bowel obstruction and perforation have occurred in patients receiving rituximab.

Adverse effects, including serious adverse effects, commonly occur with rituximab therapy. In clinical studies of rituximab in patients with relapsed or refractory low-grade or follicular non-Hodgkin’s lymphoma (NHL), adverse effects were reported in 99% of patients, and grade 3 or 4 adverse effects were reported in 57% of patients. The most common adverse effects reported in 25% or more of patients in clinical studies are infusion-related reactions, fever, lymphopenia, chills, infection, and asthenia.

GcMAF? I’ve heard from a few people in Europe who are trying it and so far, the reports I’ve heard haven’t been exciting. Let’s hope it’s better than that. I haven’t heard any first, or even second hand, reports of dramatic response, but nothing negative either. Early days.

I’ve gotten a lot of mail about how awful Trine Tsouderos is, since last week’s Chicago Tribune article. Trine Tsouderos is not my enemy. We actually have a cordial relationship, having agreed to disagree about some things. I thought her chronic Lyme story was pretty good. I do not believe that she is part of a conspiracy. Nor, apparently, is she Paul Offit’s sister-in-law or connected to the CDC in some way. It’s all silliness. She is trying to do her job, which is to report the news. She has always dealt with me in a professional manner. I think it’s great that she’s keeping our plight in the public’s face. She is reporting that ME/CFS is a real disease, even if she thinks that XMRV is a contaminant or that the vaccination program is flawless. It’s a good thing that it’s news. She is raising awareness, even if we disagree on the details.

For the record, I am not “anti-vax”. I vaccinated my kids selectively (no Hep B or chicken pox), other shots a little late and not all at once. Seemed common sense at the time. It had nothing to do with being part of any kind of movement. My concern about vaccinations now is two fold. It seems obvious to me that vaccination injured people are over-represented in the ME/CFS patient group. And the hypothesis outlined in my last few posts explains too much of the mystery to be dismissed. I am completely comfortable urging caution until we know more. Not such a radical concept. We routinely withhold vaccines from other immune compromised people.

Here is the question that I submitted to the chat with Paul Offit hosted by Trine Tsouderos on the Chicago Tribune website a couple of days ago:

Are you concerned that the current epidemics of ME/CFS, ASD and GWI are related to vaccines? These neuroimmune disease cohorts are all of mysterious etiology and share many clinical similarities: sensory and cognitive processing deficits, susceptibility to and inability to clear certain infections, an unusual susceptibility to stress, increased  oxidative stress, glutathione depletion, methylation blocks, mitochondrial defects, high levels of heavy metals, inflammatory bowel issues, hormone abnormalities and a suspicion that vaccines are implicated in pathogenesis. The pathology in humans is extremely similar to what is known of simple retroviral infections in animals. We have evidence that xenotropic and polytropic MuLVs are infecting humans (Lombardi et al Science Oct 2009, Lo et al PNAS Sept 2010). Given the history of the use of mouse and chick embryo cells for vaccine production coinciding with the history of Epidemic Neuromyasthenia (as documented by Henderson and Shelokov, NEJM 1959), the known presence of animal retroviruses in those cells, and the documented ability of these viruses to infect human cells, aren’t you the least bit concerned?

His reply:

The xenotropic murine retrovirus story as a cause of neurologic disease, including chronic fatigue syndrome has clearly fallen apart. And for those of us old enough to remember, many careers have fallen off a cliff claiming retroviruses as a cause of a variety of illnesses: most noteworthy, MS and Kawasaki’s disease. Retroviruses are so ubiquitous and such a frequent lab contaminant that they’re the Sirens of the lab.

Completely non-responsive. How can he sleep at night?

Science fiction or fact?

The question. Did the conditions exist for the current epidemic of neuroimmune diseases to be the result of endogenous retroviruses present in animal tissues and used in the production of vaccines?

Epidemic neuromyasthenia; clinical syndrome?, by Henderson and Shelokov, published in the New Enland Journal of Medicine in 1959, describes what were probably the first cases of ME/CFS. This extraordinary paper lists 23 outbreaks of illness internationally, similar to the Lyndonville and Lake Tahoe outbreaks, between the years of 1934 and 1958.

Preceding the report of the outbreak in Iceland [of 1090 people] were 2 epidemics in the United States and 1 in England, all of which in retrospect, bear it a striking resemblance. Gilliam documents in detail an outbreak in 1934 of 198 cases among personnel at the Los Angeles County General Hospital during which 10 per cent of the 1531 physicians and nurses were afflicted. Occurring concomitantly in Los Angeles and in other areas of California were many cases that were considered typical of paralytic poliomyelitis and a great many others that were not. In addition to a number of hitherto unknown clinical manifestations particularly among adults, epidemiologic appraisal of reported cases revealed an unusually high attack rate, a low paralytic and case fatality rate and a relative age selection for adults, particularly females. Gilliam believed that the symptomatology among the hospital personnel was not characteristic and that the very high attack rate among the hosptial personnel was without parallel in the history of poliomyelitis. He concluded, however, that since classic poliomyelitis prevailed among a large number of the pateints with communcable disease in the hospital, the simpler explanation of the facts was that the atypical disease seen among the hospital staff was the same.

Edward Jenner, as an apprentice to a surgeon, observed that milkmaids who contracted cowpox were afterwards immune to smallpox. He first used cowpox material to produce cross-immmunity in a child in 1796 and, shortly after, reported a series of 23 cases, which included his son. The idea that a weak form of a disease can cause immunity was not new. As early as 1000 BC, it was known that an inoculation, or “variolation”, with material from smallpox lesions (Variola) produced a lighter form of the disease, though still with significant morbidity and mortality. Powdered material from smallpox scabs was blown up the noses of people in China in the 1500’s. It was observed in the early 1700’s that variolation had no effect on people who had had cowpox (Vaccinia).

Louis Pasteur, while working on chicken cholera, discovered that a faulty culture that didn’t kill as expected produced immunity in chickens. He used this concept to develop a post-exposure rabies vaccine. He grew the virus in rabbits, dessicated spinal cord to weaken the virus, and injected the dried product into the first human, an exposed child, in 1895. His treatment was quite successful as documented in this paper: Rabies And The Pasteur Treatment. Lackenbach. 1912. Pasteur’s work with anthrax and chicken cholera was different from Jenner’s in that the vaccine was artificially produced rather than using a naturally weak form of the disease. Pasteur coined the named vaccine from Jenner’s work with cowpox.

A couple of historically interesting papers with respect to the early use of animals to grow viruses for vaccinating humans:

Max Theiler, and his colleagues at Harvard, proved that Yellow Fever was not caused by a bacterium, but a filterable virus. He also proved that the virus could be transferred to monkeys and mice. In 1930, Theiler started working on a Yellow fever vaccine at the Rockefeller Institute, where much of the early vaccine work was done. He attenuated virus in mouse brain and chick embryo cell. Early vaccines were sometimes tested on volunteer doctors. Informative reference: The Yellow Fever Vaccine: A History. Frierson

From Theiler’s Nobel lecture in 1951:

The study of yellow fever may be divided into two periods. The first one occurred at the turn of the century when Walter Reed and his co-workers showed by the use of human volunteers that the causative agent of this disease was a filterable virus and that it was transmitted by the bite of the common urban mosquito, subsequently named Aedes aegypti. The second period began in 1928, when Stokes, Bauer, and Hudson found that the common Indian rhesus monkey was susceptible to yellow fever, thus making available an animal that could be used in the laboratory. The first strain of yellow fever established by these workers is known as the Asibi strain, named after the patient from whom it was isolated. It has been used extensively in yellow fever work and, as will be shown later, was the parent strain from which the 17D vaccine was eventually produced.

It was shortly after monkeys were found susceptible that, in searching for a less expensive and more readily available experimental animal, I found that the common white mouse was susceptible to the virus if inoculated by the intracerebral route. This method of inoculation was chosen as it was generally conceded that the common laboratory animals could not become infected if inoculated by the usual routes. The strain of virus with which this work was done was isolated by Mathis, Sellards, and Laigret in 1928 in Dakar, French West Africa, is known as the French strain, and, like the Asibi, is highly virulent for rhesus monkeys. The disease in mice was an encephalomyelitis with no involvement of the visceral organs, in contrast to that induced in man and monkey, in which the liver, kidney, and heart are involved. By serial passage in mice, the pathogenic action of the virus was altered in two respects. Firstly, the incubation period became progressively shortened until, after many passages, it became constant, or, to use the term introduced by Pasteur in his work on rabies, it became fixed. Now the incubation period in mice is used as a measure of the degree of neurotropism for these animals. Secondly, with the increase of virulence for the nervous system of mice, there was also evidence of a progressive loss of virulence for rhesus monkeys when inoculated parenterally. This loss of virulence for monkeys first suggested the possibility of the use of an attenuated active virus for the immunization of man. The finding that by mouse brain passage the virulence of yellow fever virus could be altered led me to undertake extensive studies on the variations induced in the virus by different laboratory procedures, which became my main scientific activity for several years. The results of only those experiments which are pertinent to the development of vaccines will be discussed here.

The finding of the susceptibility of mice and its attenuation for monkeys was rapidly confirmed by others. It was shown that many, if not all, strains of yellow fever are pathogenic for mice, and this animal came into widespread use in all yellow fever work. The pathogenicity of unmodified strains for mice varied greatly – ranging from the highly neurotropic Asibi virus to the relatively avirulent French strain. Both of these, as noted before, are highly pathogenic for rhesus monkeys and almost invariably produce a fatal disease when inoculated parenterally. With most strains it was shown that the mouse could be used for the quantitative estimation of virus. This proved of great value, for as strains of virus avirulent for monkeys were developed, the mouse was the only animal by which the presence and amount could be readily determined.

In the development of vaccines for human beings, using my mouse-adapted virus, two paths were followed. In the first, used chiefly by French workers, virus alone was inoculated; and in the second, used by American and English workers, virus and human immune serum were inoculated simultaneously. The first immunizations of humans using mouse-adapted neurotropic virus alone were reported by Sellard and Laigret (1932)…   Full lecture

The first attempts to vaccinate for polio were actually in the 1930’s. Live and killed virus was used, passaged in monkey brain and spinal cord. The vaccines were tested on children and it was a fiasco; some of the test subjects developed the disease. For historical interest:

In the late 1940’s Hillary Koprowski worked with rodent and mouse adapted viruses, including rabies, Colorado tick fever, various viral encephalitides, West Nile Virus and others, before turning his attention to polio. He made the earliest live polio vaccine 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. Here are the earliest papers:

So it was probably all a big accident, which occurred for the best of reasons, to remove the scourge of horrible viral diseases from the human race. The ethical problem started later, when there was enough information and technology at hand to understand what was happening and nobody studied it. Instead they decided that the patients were all crazy. Easier to marginalize them. The really sad part is that, certainly by the early ’90s, when De Freitas did her work at Wistar, there was enough information to question whether it was safe to inject endogenous animal retroviruses into humans, even though it was known that they could recombine and infect the cells of other species in tissue culture, including human. They knew the viruses were there, they knew there was risk, but chose to march ahead blindly anyway. Amazing arrogance.

And this paper whose senior author seems to ignore his own work:

J Virol. 2003 Jun;77(12):6709-19.
Mechanisms of avian retroviral host range extension.
Rainey GJ, Natonson A, Maxfield LF, Coffin JM.
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Abstract
Alpharetroviruses provide a useful system for the study of the molecular mechanisms of host range and receptor interaction. These viruses can be divided into subgroups based on diverse receptor usage due to variability within the two host range determining regions, hr1 and hr2, in their envelope glycoprotein SU (gp85). In previous work, our laboratory described  selection from a subgroup B avian sarcoma-leukosis virus of an extended-host-range variant (LT/SI) with two adjacent amino acid substitutions in hr1. This virus retains its ability to use the subgroup BD receptor but can also infect QT6/BD cells, which bear a related subgroup E receptor (R. A. Taplitz and J. M. Coffin, J. Virol 71:7814-7819, 1997). Here, we report further analysis of this unusual variant. First, one (L154S) of the two substitutions is sufficient for host range extension, while the other (T155I) does not alter host range. Second, these mutations extend host range to non-avian cell types, including human, dog, cat, mouse, rat, and hamster. Third, interference experiments imply that the mutants interact efficiently with the subgroup BD receptor and possibly the related subgroup E receptor, but they have another means of entry that is not dependent on these interactions. Fourth, binding studies indicate that the mutant SU proteins retain the ability to interact as monomers with subgroup BD and BDE receptors but only bind the subgroup E receptor in the context of an Env trimer. Further, the mutant SU proteins bind well to chicken cells but do not bind any better than wild-type subgroup B to QT6 or human cells, even though the corresponding viruses are capable of infecting these cells. Full paper

This paper exists only in print and there is no abstract, but it must be interesting:

Nat Med. 1995 Nov;1(11):1100.
The dangers of xenotransplantation.

There are lots of papers about the dangers of xenotransplantation:

More evidence that avian leukosis viruses can infect human cells under certain circumstances:

And the idea that it only happened once, in a particular cell line? It seems that the chances are not so vanishingly small after all. From an easy to understand review of retroviruses: C-type: As B-type, but with a central core and barely visible spikes – e.g. most mammalian and avian retroviruses (MLV, ALV, HTLV, HIV). All old work:

Cover-up or stupidity? I’m just a dumb ER doc and I’ve gotten this far with PubMed and a few scientist friends (who if asked will deny knowing me:). Though any detail of what I’ve written could be mistaken, and there is conflicting evidence, overall, it certainly seems to fit. People have written that they are concerned that I’m too invested in XMRV. This is not all about XMRV. If they prove tomorrow beyond a shadow of a doubt that XMRV is a lab contaminant and not present in humans, it doesn’t change a thing in terms of what needs to happen next. At the very least XMRV has brought attention to an international disgrace. If XMRV is buried under a mountain of negative studies, or if XMRV is truly not a human pathogen, millions of people still need treatment for neuroimmune illnesses that are consistent with simple retroviral infection.

Certain scientists have been particularly vocal against the use of antiretrovirals for XMRV. Scientists trying to tell doctors what to do. Why do they think that doctors or patients should care about their medical opinions? They need to do their work and stop trying to practice medicine. The real question is why do they care if patients try antiretrovirals for a retrovirus? Why wouldn’t they want to know if the drugs work?

The current epidemic of neuroimmune illnesses may be due to the introduction of simple retroviruses into the human population through the use of vaccines. This hypothesis needs to be studied. I am not some crazy conspiracy theorist. The pathogenesis of the illnesses needs to be further elucidated and specific treatment found. Now. Not after one specific etiologic agent has been deemed the real deal and there’s a foolproof test available at Quest. There may be many specific agents. It’s so unfortunate that it didn’t turn out to be one retrovirus with a serology test that picks up all cases. That would have been so easy compared to what we are facing – infections with one, or more than one, of a panoply of simple retroviruses, that remain latent for long periods of time, are activated by inflammation and steroid hormones, creating a vicious cycle of inflammation and viral replication. It could be that replication incompetent viruses are part of the picture as well. Co-pathogens, like Lyme, fuel inflammation and there may be helper viruses involved in various ways. And, most unfortunately, there is even a possibility that the new simple human retroviruses are or will be endogenized in subsequent generations. What a mess!

Vaccinations and Frankencells

When I started writing this blog, I was a very sick patient and the mother of a very sick patient, who had been neglected and abused by the medical profession. I made our experiences about trying to treat the disease public, because it was the only way I could be of service. Helping helps, and I was very much in need of help. Now I work for a non-profit dedicated to finding a cure for patients. I certainly don’t want the WPI to be hurt because I am controversial. I’m not really sure what to do about it, but keep restating that the WPI does not endorse my opinions and in my capacity as an administrator for them, I will not be telling other doctors how to treat their patients. But so many have written that it helps them for me to share my thoughts, that I will muddle through. There are an unbelievable number of people, isolated and without help. I’ve been there. I believe that my current understanding of the illness has and will result in finding ways to ameliorate the suffering, sooner rather than later. The scientific effort is desperately needed, because meaningful treatment options are so limited at this time.I would like to state publicly that I am personally grateful to any scientist working on XMRV. I really am sorry if my blog seems inflammatory, but I wish I could share my mail with the scientific community. In fact, scientists working on an illness should meet patients with that illness on a regular basis. Nobody is objective when you get right down to it. Everybody has an ax to grind. It is very sad that the issue is so politicized that the scientists and patients would feel at odds.I would like to restate that the words “cover up” used a couple of posts ago, referred to individuals who have been wrong, for example, people who encouraged psychiatric explanations for the disease, epidemiologists who didn’t study the right things, perhaps people who said that endogenous animal retroviruses in tissue culture couldn’t harm humans. Lots of reasons for individuals to be upset about how things are turning out and humans are, well human. They don’t like to be wrong. Cover up, consciously or unconsciously, is a normal human response to having been seriously wrong with unimaginably horrible consequences.Non-scientists discussing the science resembles two English speakers trying to communicate in Chinese. But there seems to be so little dialog about why the patients are sick, that it has become necessary for lay people to try to second guess the science, even without fluency in the language. The scientists are as isolated as the patients. They don’t share, because of fear of having work stolen, intellectual property issues and who is going to get the Nobel Prize.

For me, as a doctor, the proof is in the pudding. A simple retroviral etiology explains the pathology perfectly. Antiretrovirals move the illness. Case closed. It’s a retrovirus stupid. On to treatment, while the scientists figure out the details, so we have a test, and then the drug companies will get interested. Where the infectious agents came from is not important anymore, unless it is still happening; hence my willingness to put a target on my back to open up the discussion about X related disease and vaccines.

It is an old discussion, one in which the autism community has been embroiled for a long time. But the scientific community has chosen to believe that all those mothers of autistic kids are deluded, and don’t really know how or when their kids got sick. That they had normal kids and, within a few days of a vaccination were never the same, is just coincidence. The literature about CFS and vaccines seems to consist of one negative paper; here is the sum total of literature I could find:

There are, however, some very interesting papers in the Gulf War Illness literature:

Inflammation activates latent virus, as does the stress hormone cortisol. For me, the fact that the disease is activated by physical and emotional stress was obvious from the beginning, as it has been for many people. It is the reason why the assumption was made that the illness is psychogenic. The fact that animal retroviruses have GREs and HREs (glucocorticoid and hormone responsive elements) in their LTRs was one of the facts that clinched it for me. Huge clinical correlation. The findings on PTSD and sustained cortisol levels with brain damage to the amygdala and hippocampus come into play here for GWI and ME/CFS.

Take a look at the vaccination schedule for military recruits, which includes Anthrax and Small Pox, if deployed to a place where there is a “biological threat”: Military vaccination schedule

The press has been calling me recently. Why are vaccines such a hot potato? The big response to the subject exposes it as a sacred cow. What’s so controversial about a doctor saying that there is a chance that an unnecessary intervention may be harming patients and that, until we know more, the intervention should be held for people at risk? The automaticity with which doctors have come to prescribe vaccines is medically incorrect. We need to look at where we are now, not where we were when we started vaccinating Polio, Small Pox or Diphtheria. At this juncture, in my opinion, each vaccination should be thought about by a physician, in the same way prescribing a drug is. You don’t give drugs in batches to everyone. You consider each prescription carefully, for that patient, at that moment. That’s what is expected for every other prescription. Why should physicians suspend disbelief for this one therapeutic modality? A doctor is not supposed to hurt anybody, except that if he hurts somebody with a vaccination, that’s OK? Even if he already knows that this person has an immune dysfunction that hasn’t been studied with respect to vaccines? The patient has to live with the damage forever. Something is really wrong here. Doctors should think about that individual patient before ordering the shot. It shouldn’t be automatic if the patient has a history of CFS. What is the risk of worsening the disease from the shot? Or causing it in a family member? Risk to the individual, not the society.

There is of course a long literature on vaccine safety. The argument mostly goes that vaccines are safe in terms of unanticipated infection, because a study of the vaccine in question failed to show transmission of anything unexpected in a small number of people. But absence of proof is not proof of absence.

The literature is also filled with failure to identify adventitious virus.

Some of the failure to figure out what’s true with respect to XMRV is about one trick ponies having an over-reliance on PCR. It’s pretty clear as an observer that a negative PCR study means nothing. I don’t understand how somebody can say that there is no association between a virus and a particular condition if they can’t find the virus at all. There have even been PCR tests brought to market with no validation in humans. Just because you can detect a clone in a lab doesn’t mean you can detect a virus in human blood, especially when it has become clear that blood is a difficult place to detect it without amplification. The macaques cleared it quickly from the blood. It reminds me of doctors who no longer know how to do a physical exam because of an over-reliance on tests.

As I said before, we need to see the full Paprotka paper, but couldn’t the same detection problems be at work here that scientists are having with respect to sorting out whether XMRV is there or not? Did they really show more than that the virus was amplified in the xenograft? It doesn’t prove where it originated. Even if they did correctly prove that this is where XMRV came from, it doesn’t disprove that it is loose in the population now. And it doesn’t say anything about whether or not there are other retroviruses infectious to humans, originally derived from endogenous animal retroviruses, possibly created in the lab by accident, and  around for a lot longer than 15 or 20 years. Here’s the paper about the creation of the CWR22 cell line from which 22Rv1 was derived. Note the use of testosterone which would amplify XMRV.
Xenografts of Primary Human Prostatic Carcinoma. Pretlow

The argument about whether the recombination event of 2 pre-XMRV sequences was unique or not seems to center around the improbability of throwing clones when DNA mixes. But we are talking about short sequences that may have preferences as to how they fit together, and many, many chances to succeed. Simple retroviruses recombine. The pre-sequences are in the soup, even contained within human endogenous retroviruses. The first of the following references seems very important to the discussion, so I’m including the abstract here in its entirety:

  • J Biomed Sci. 2000 Mar-Apr;7(2):77-99.

    Genetic reassortment and patch repair by recombination in retroviruses.

    Mikkelsen JG, Pedersen FS.
    Department of Molecular and Structural Biology, University of Aarhus, Denmark.

    Abstract

    Retroviral particles contain a diploid RNA genome which serves as template for the synthesis of double-stranded DNA in a complex process guided by virus-encoded reverse transcriptase. The dimeric nature of the genome allows the proceeding polymerase to switch templates during copying of the copackaged RNA molecules, leading to the generation of recombinant proviruses that harbor genetic information derived from both parental RNAs. Template switching abilities of reverse transcriptase facilitate the development of mosaic retroviruses with altered functional properties and thereby contribute to the restoration and evolution of retroviruses facing altering selective forces of their environment. This review focuses on the genetic patchwork of retroviruses and how mixing of sequence patches by recombination may lead to repair in terms of re-established replication and facilitate increased viral fitness, enhanced pathogenic potential, and altered virus tropisms. Endogenous retroelements represent an affluent source of functional viral sequences which may hitchhike with virions and serve as sequence donors in patch repair. We describe here the involvement of endogenous viruses in genetic reassortment and patch repair and review important examples derived from cell culture and animal studies. Moreover, we discuss how the patch repair phenomenon may challenge both safe usage of retrovirus-based gene vehicles in human gene therapy and the use of animal organs as xenografts in humans. Finally, the ongoing mixing of distinct human immunodeficiency virus strains and its implications for antiviral treatment is discussed.

  • Generation of diversity in retroviruses. Katz
  • High prevalence of an IgG response against murine leukemia virus (MLV) in patients with psoriasis. Molès
  • Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. Christensen 

Here is an excellent review article about HERVs, written in 1996, by Urnovitz, an author of the GWI paper above about RNA in the sera of GWI subjects:
Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease. Urnovitz
I thought this passage particularly fascinating in light of what we observe with respect to viral triggers leading to long standing morbidity and the presence of activated viruses, such as EBV, HHV-6 and CMV:

With the development of primary cell culture techniques it became possible to analyze virus-cell genome interactions. For example, when low doses of the Bryan high-titer strain of Rous sarcoma virus (RSV) were used to transform primary chicken embryo cells, such transformed cells failed to produce detectable quantities of virus unless exposed to super- infection by an unrelated avian virus. When this was done, the cells produced significant amounts of RSV-like particles. Ultimately, it was shown that the original RSV nonproducer (NP) cells carried a defective endogenous virus that required superinfection by ‘‘helper’’ virus to permit a full cycle of endogenous virus replication. Endogenously produced virus (RSV-0), defective in replication, was detected in NP cells by DNA hybridization techniques. In some cases, infectious virus was inducible from NP cells by chemical or physical inducing agents.

The described results are relevant in attempts to detect HERVs: they document that a defective endogenous retrovirus genome can be expressed if missing gene functions are provided by a suitable superinfecting helper virus, i.e., a phenomenon known as complementation; that a defective endogenous virus can be induced by a physical agent such as X-irradiation or chemical agents such as the halogenated pyrimidines; that the induced endogenous virus may form pseudotypes with the helper virus to yield progeny with a new, albeit temporary, host range; and that the events described may be only temporary or spasmodic. However, if such events occur in vivo, they may suffice to elicit antibodies to viral agents that otherwise might go undetected.

And this about HERVs containing murine sequences: 

HERV 4.1 (HERV-E): Multicopy Type C
Martin and coworkers used as a probe a 2.75-kb seg- ment of African green monkey DNA that hybridized to murine leukemia virus (MuLV; AKR mouse ecotropic leukemia virus) and endogenous baboon virus (BaEV). The described probe detected related sequences in human brain fragments and in a human DNA library. Clone 4.1 made up a full-length provirus. The related clone 51.1 approximated a retroposon. The complete nucleotide sequence of HERV 4.1 was determined. The 3ï¿¿ LTR is 449 bp and the 5ï¿¿ LTR is 495 bp, with 95% homology between them. Genomic DNA consisted of 8,806 bp organized into gag, pol, and env sequences interspersed between the two LTRs. On the basis of deduced amino acid sequences, HERV 4.1 gag-pol sequences exhibited approximately 40% homology to Moloney MuLV. Termination codons and point deletions in the genome indicated that HERV 4.1 was replication defective. However, long ORFs in the pol and env regions suggest that they might be expressed. The fact that the 18-bp primer binding site for tRNA does not match tRNAPro (found in most mammalian type C retroviruses), but is homologous to tRNA glutamine, is unusual and has suggested a primordial origin of HERV 4.1.

The diversity of the RTVL-H family is further illustrated by the report of Hirose et al. cDNA libraries were prepared from poly(Aï¿¿) RNA obtained from various tissues and cell lines by using oligo(dT)- or tRNAHis-derived oligonucleotide primers. PCR was used for amplification with appropriate primers. Several RTVL-H clones containing env-related se- quences were isolated. One clone (RGH 2) approximated a provirus in size (8.7 kb in length), with both 3ï¿¿ and 5ï¿¿ LTRs. The env gene had an ORF capable of encoding 570 amino acid residues. Comparison of the deduced amino acid sequence of the env region of clone SA49 with the immunosuppressive peptide regions (p15E) of various conventional retroviruses revealed homologies of 75 and 71.2% for Mason-Pfizer monkey virus (type D) and reticuloendotheliosis-associated virus (type C), respectively, and ca. 58% homology to both feline leukemia virus and Moloney MuLV. Thus, HERV SA49 is a mosaic of sequences related to both type C and D retroviruses.

Scientists have been playing with mixing animal and human cells in the lab for many decades now. Animal-Human Hybrids Spark Controversy.
Chimeric cells and whole animals have been and are being created. This is a new subject for me, but first blush reads like science fiction:

Again, it seems plausible, not in any way conspiracy theory or even wild conjecture, but a worthwhile hypothesis, that animal retroviruses have been finding their way into humans from the lab for a very long time. Questions supported by references. My concerns need to be addressed, not dismissed. After introduction, horizontal and vertical spread would have obscured the epidemiology, especially given the extremely long time period that can pass before activation of the infection. I have the impression from the only epidemiology I have available to me at this time, my mail, that there are peaks, both in patients’ current age and in the year when they became ill, that suggest something or somethings went out horizontally in a batch related fashion. This combined with the obvious family involvement, as documented repeatedly in the comments of this blog. To me, it is an epidemiologist’s dream. We need it studied.

A year of antiretroviral therapy

Ali and I started antiretroviral therapy a year ago. We both improved noticeably for the first nine months, though the treatment didn’t prevent our crashing when we started to engage life again. My setback was brief and I seem to be able to push the envelope a little now without crashing in a prolonged way. Ali has had a tougher time of it. In the last few months tachycardia became a serious problem, not new, but worse, and she started atenolol. It helped with the tachycardia, but some new symptoms started. She ended up stopping atenolol and AZT at close to the same time a month ago, to see if they were making things worse. Stopping the atenolol clearly helped, stopping AZT less clearly so, but the tachycardia does seem to be subsiding and in the last week or so, she seems to be on an upswing. Although she has been homebound for a couple of months, she is feeling like she can go out again. She has been writing productively throughout. I also stopped AZT a couple of weeks ago. I was wondering if maybe I’m a little weaker than a year ago though my CPK is fine and who can tell? But AZT is the most problematic of the drugs long term and there is no way at this point to evaluate whether it is worth it or not. I didn’t notice anything coming off it. We continue on Viread and Isentress. When I think about stopping them, I remember the fifteen years of malaise I endured, now mostly gone, and the intense neuropathy pain that is now little more than background noise.

Under the best of circumstances, the drugs available to us based on in vitro studies (reverse transcriptase inhibitors and an integrase inhibitor), are an incomplete solution, as they can only control early stage replication events. Patients who have been sick for a long time most likely have a large amount of integrated virus cranking out viral product and fueling persistent immune activation. The drugs we have will not affect this, only preventing infection of new cells. Also we do not have a protease inhibitor to prevent assembly of new viral particles. The HIV protease inhibitors were ineffective against XMRV in vitro in the Singh study. XMRV protease is not the same as HIV’s. Crystal structure of XMRV protease differs from the structures of other retropepsins. Dimaio

I would like to restate that this blog is personal and not endorsed by the WPI. It precedes the association. The opinions expressed here are mine alone. I am working for the WPI in an administrative capacity, recruiting, planning the clinic to meet the needs of patients, fielding questions. My job is to create an environment where the best possible care can be provided and implement the clinical database. Organizing, creating a framework, but no one need be concerned that I will be setting medical policy based on my own opinions. Medical decision making will of course occur within the context of individual physician patient relationships. We are gathering a network of physicians to work at a distance with the clinic doctors and over time we will work towards consensus.

“Cover-up” in my last post refers to people who have been wrong and now don’t want that to come to light. I was not trying to suggest that there was or is a conspiracy in the sense that people are planning with each other to do dastardly deeds. My interest in the dangers of vaccines has nothing to do with conspiracy theories. It has to do with the very strong anecdotal evidence that vaccines have harmed a lot of people in the various neuroimmune disease cohorts, ME/CFS, ASD, GWI. If you listen to many histories, there is a clear suggestion that vaccination is one of the major triggers for X related disease. Whether the reason for that is the immune challenge or the introduction of a retrovirus, it seems prudent for the moment to refrain from administering vaccines which are not immediately necessary until we know more. We need to be sure that we aren’t putting patients at more risk from vaccinations than they are from the diseases for which they are being vaccinated. There has always been an element of the vaccination program that sacrifices a few individuals for the greater good, but this seems higher than a small statistical risk for this group of patients. It’s strange that this is such a controversial thing to say. Seems like a no brainer to me. Primum non nocere.

Like everybody, I’ve wondered a lot about where XMRVs came from. I’ve been thinking about the ideas in my last post, reading widely for some time, but my thoughts coalesced when I read the Paprotka CROI abstract. Frankly, I was expecting that people far more knowledgeable than I would punch holes in what I’d written. But it has now been read by thousands of people including a bunch of virologists and although some found it inflammatory, nobody has yet taken exception with the science. Pretty scary. If my hypothesis turns out to be correct, we’ve given retroviral evolution a leg up by a couple of hundred thousand years or so in less than a century. And seriously weakened the health of the species. So let’s hope I’m wrong.

Good doctors must engage in inductive reasoning. Educated guess. There may be much unknown, but there is still a real patient sitting there in need of treatment. Scientists argue that they must go through all the necessary deductive steps to get to the solution. That leaves a lot of patients with no meaningful treatment. In an emergency, it’s a good idea to skip to the answer if you can, figure out what you can do and fill in the blanks later. It’s pretty clear we have a public health emergency. Whether the etiology of the illness is X, Y or Z, it is retroviral in origin. It fits like a glove, better than anything else ever has. Making that leap allows one to think about the illness in a way that doesn’t yet offer a cure, or even a functional cure, but it does help in the choices of useful or palliative therapies. Most importantly, it should help us not to hurt the patients. Huge damage has been done because of ignorance. At least we can put an end to that.

Cover-up and contamination theories

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?

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.

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.

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?