Watching Harvey Alter, Judy Mikovits and John Coffin on YouTube struck me as life immitating myth. Spock, Kirk and the Klingon. Yoda, Skywalker and Darth Vader. God, Moses and Pharaoh.

Here is the tape of Dr. Alter as King Solomon, one of our dragon slayer, Dr. Mikovits, and another of Dr. Coffin trying helplessly to close Pandora’s box with this unbelievable statement: “I see the next step as leaving the virus that we know as XMRV behind.”

Dr. Coffin’s conclusions don’t make any sense to me. Let’s for a moment say he is correct and XMRV was created in the lab in the early 90’s. It is still a xenotropic MuLV related virus, capable of infecting human cells. Why does he think it couldn’t have infected humans in the lab and gotten out that way? Because there were sick patients before the event? A more likely explanation would be that there was already something else out there before this one. It’s not clean and neat, so let’s all close up shop and go home for another couple of decades. Even he said there could be another retrovirus. And why pray tell isn’t he looking for it? The patients have something consistent with retroviral infection. You won’t find it unless you look.

The discussion of the name is a sad one. I don’t have much of a stake in the name. I don’t mind CFS that much and I don’t think it’s going to go away. I think of the word fatigue the way materials, like metal, can become fatigued. I don’t like ME much either because I think it’s stigmatizing in another way. It implies we’re all brain damaged, encephalopathic, and I believe the damage is mostly reversible. I like non-HIV AIDS.

The case definition discussion also seems besides the point to me. My belief is that the presence of infectious retroviruses is the only true biomarker for the disease and we don’t know what is there yet. There are clearly XMRV negative people who are clinically indistinguishable from the positives. Those people shouldn’t be excluded from a diagnosis. Like Hep C used to be non A non B hepatitis, I think our disease should be called non-HIV AIDS. Personally I think that the people excluded by this or that set of criteria mostly do in fact have the disease. Another problem with definitions is that it is a relapsing remitting process. People who meet a set of criteria today, may not tomorrow (thank God).

Case definitions and new names aren’t going to save us. The only biomarker for the disease is the detection of the responsible retroviruses. For now, that is XMRV, but there will be more. Until then, we can only measure downstream effects, cytokines and NK cell profiles, inflammatory markers, a few other things that demonstrate how sick we really are.

Our down and dirty survey is producing fascinating unanalyzed data. We’ve already refined the questions slightly based upon what’s coming back to produce a more complete picture and thank you to everyone who has responded to requests for further clarification. We will report. For now, the impression from reading the surveys is that many CFS patients have family members with CFS and associated diseases. Please spread the word and encourage everyone with the disease to reply, whether you have an affected family member or not. If any statisticians or epidemiologists are interested in participating, please get in touch.

I thought this article about Google’s founder inspiring and relevant to our predicament: Sergey Brin’s Search for a Parkinson’s Cure.

The blog’s readership has been growing recently, currently averaging well over 1000 pageviews/day. Not a big number in internet terms, but still an awful lot of people. Knowledgeable people, because it isn’t exactly easy reading.

Dr. Snyderman and I have been discussing how we might use the blog as an investigative tool. Polls with self-selection are not statistically valid but may provide clues about what to look at in a more formal study. In this case, we are hoping to demonstrate patterns of transmission. As an initial exploration, we’d like to get a sense of how many ME/CFS patients reading have family members, by marriage and blood, with ME/CFS or other neuroimmune diseases. Include ASD, GWI, MCS, atypical MS, fibromyalgia, chronic Lyme Disease, other. Include neurodegenerative diseases, MS, ATLS, Alzheimer’s, Parkinson’s Disease, other. Note inflammatory bowel diseases, IBS, Crohn’s and UC. Note any prostate cancer, leukemia, lymphoma, other cancers. Also please include neuropsychiatric diseases, PTSD, OCD, bipolar disorder, other. Do include subclinical disease. Please err on the side of inclusion. If you are familiar with the Canadian Criteria for CFS, note if you meet criteria or not.

We are asking ALL readers with ME/CFS to send an email, even if you have no other affected family members, in an attempt to have a denominator. If your spouse/partner is ill, report as a family member. Please present the information with yourself first and family members listed below, in the following format.

For yourself:
Diagnosis
Gender
Age
Date of birth
Place of birth
Breastfed?
Date of onset of illness
Location where became ill
Trigger if known
Number of children, note if adopted
Are Canadian criteria met?

For your family members:
Relationship to you
Diagnosis
Gender
Age
Date of birth
Place of birth
Breastfed?
Date of onset of illness
Location where became ill 
If ME/CFS diagnosis, trigger if known
If ME/CFS diagnosis, are Canadian criteria met?

For ALL respondents, including those with no affected family members, please answer the following questions:

How many unaffected children do you have?
Were unaffected children breastfed or not?
How many unaffected siblings do you have?
Do you think that a vaccination was implicated in yours or a family member’s illness? If yes, provide any details remembered.
Have you or any family members been tested for XMRV? If so, please report results.

All information will be kept confidential and used for statistical purposes only. The surveys will only be shared with involved physicians and biostatisticians. Results will be shared publicly.

Please share the link to this page, but it would be helpful if the survey were NOT posted elsewhere in full (except for translations, thank you!), as we’d like to track responses as a percentage of pageviews.

Send with subject line: Family Survey
If you have no affected family members, please put NEG in the subject line.
Cc both of us:
mcs@buffalo.edu
jdeckoffjones@gmail.com

Thank you,
Michael Snyderman MD and Jamie Deckoff-Jones MD

Can we give it a rest for now? I don’t want to moderate or censor, so I’ve let the mold war go on, but it was a little like being kidnapped, since the rest of the discussion died. I felt unheard; it’s annoying to be told again and again that your observations of your own triggers are incorrect. As I believe I made clear, I support the mold warriors theory in part, just not to the extent they would like, but that makes me a dissenter. On the other hand, I got mail blaming me for giving them a forum. And mail holding me responsible for other peoples comments! Maybe I’m dreaming, but I’d like to think it’s possible for us to come together and further the discussion without overwhelming it. I did ask them back channel to have their say and let it go for now. It will come up again, no doubt. It seems a good time to ask everybody, please, could we try to show a little sensitivity to the rest of the group? We are a sensitive bunch.

There is lots of disagreement. Contradictory ideas abound. Rumor has it that when I started AZT, a well know CFS doctor predicted it would kill me:). We’ve lived in the dark for a long time, but it should be different now. We have a framework from which to further the discussion. We are in a place to finally figure it out. Mold fits as a trigger. Anything that turns on an inflammatory cascade favors the virus, maybe even “ick”.

I appreciate Dr. Enlander’s considered comment. I like you too Derek, and I appreciate that the financial realities of studying Ampligen are not of your choosing. Personally, it would take a lot to get me to undertake long term intravenous treatment again, without a very good statistical chance of success, and I just don’t see it here. The data presented looks like 16 of 100 people will do better than placebo. Presumably a few of them will do really well, but a few will do worse. Not very good odds. Maybe a little better if you’re XMRV positive. I haven’t seen anything about adverse events. People are writing to me that they are desperate to access it, despite its being financially out of reach. It involves paying out of pocket for the drug, the doctor and, in many cases, relocating for a long period of time, enduring two infusions per week, and the effects are temporary. I think I’ll wait this round out, thanks.

I am feeling a little worn out by all the contentiousness. We need to lift each other up, not bring each other down. There must be a way of sharing without clobbering one another. Our goals are aligned, even if we are not all on the same page at a given moment. We all have enough troubles without fighting amongst ourselves.

The Lancet Infectious Diseases just published this letter:
 Mouse viruses and human disease. Magiorkinis 

Once a virus is endogenised, it is forced to follow the evolutionary rate of the host. Since XMRV is integrated in cell-lines the virus evolution is restricted to the host’s pace of evolution, and viral descendants have none or minimum sequence diversity. Thus, if a contaminated product, previously cultured in cell-lines, is administered to people then the infections would provide the evolutionary patterns reported by Hue and colleagues. If the immunological data reported by Lombardi and colleagues are correct, then we need to trace the common source for these infections to prevent possible public health concerns. Products from cell-lines should be the first candidates. 

Good news, though I think his conclusion about person to person transmission is incorrect, based on the epidemiology. At least it says that a few people in the scientific community, including the editors at The Lancet, are thinking about what we need them to think about: Where did it come from? How did we get it? A big step up from: Is it there?

I am still responding to the firestorm brought on by my use of the words “entitlement” and “unsympathetic”. I am not a professional writer and the printed word lacks affect, though I’m pretty blunt in person too. Words can be taken out of context as sound bytes, as happens when one talks to reporters. I notice that there is a tendency for some people to fixate on a particular sentence or phrase. It’s scary, but all I can do is ask that everyone please take it all in the spirit it’s offered.

Two important clarifications. I did not in any way mean to imply that the government should not be on the hook for figuring it all out, or that there may not have been criminal events that took place at the CDC. I actually think it likely that crimes against humanity have been committed. Also I was not trying to minimize the neglect and abuse to which we have been subjected. Everybody knows how I feel about most doctors. All covered in many previous blogs. I was talking about how we behave and how we appear to caregivers, doctors, scientists, the media. A separate issue.

I say “we” because it happened to me. It is the interface between the physical and mental, physiological and psychological. The disease brings out the worst at times and that is a piece of what leaves us alone, whether there’s still family around or not. I’m writing about it because I found a way out, at least for the time being, and it is helping me to minimize my own suffering. A spiritual perspective and positive attitude help. Helping helps, if there’s anything at all that you can do. Now we can even explain the physiology of why that might be true with respect to a stress activated retroviral infection. I am not religious, so that isn’t where it’s coming from. Toni Bernhard wrote about it in her wonderful book How To Be Sick, and in this clear interview about suffering, and our resistance to it. Lots of people have figured it out. The Buddha said life is suffering (not exactly, but close enough). Then he outlined the way out. I’m not a Buddhist. Not even a Jewish Buddhist. I’m talking about what may work for alleviating suffering, even practically speaking, like all the things on my list of things to consider.

Many people have expressed concern for my health and I am profoundly grateful for your good wishes. I am holding up well, maintaining my usual state of poor health. It is wonderful to be useful again.

I’m feeling like a lightening rod, but I guess I asked for it. I thought about making people sign in and tell us who they are, but that would keep some people away whose thoughts we would like to hear, so I’m going to leave it alone. Dissenting opinions are welcome, and no need to be apologetic, but I ask that everyone be civil and I do encourage leaving real names. You know who I am; I’d like to know who you are. Please don’t take your frustrations out on me. I don’t want to moderate, and I want everyone to have a chance to have their say, in a considered way. The few who have needed to lash out have been more than offset by the statements of personal triumph by people finding meaning in their lives despite the losses and injustices they have suffered.

The list of treatment options that I posted a few days ago is a work in progress and I hope it will be viewed as such. One of my concerns is that things will be lifted from the blog as my prescription for everybody. The downside of this blog for me is that I may get quoted incorrectly. Also my opinion may change. So I ask everyone to respect that I am sharing my thoughts openly in real time, and not put the list out there as Dr. Deckoff-Jones’ treatment protocol, written in stone and never to be changed. It’s for discussion. I have added a few things to it since I posted, from your suggestions. Keep it coming.

Like everything I write, I am putting it out there in the hope that it helps someone. I AM NOT TELLING ANYONE WHAT TO DO. I am sharing my ideas. There may be inconsistencies that I’m working on. Please contribute your experiences. If you disagree with something, don’t attack me or be defensive yourself. Just tell us why you disagree. Maybe we can figure out how to have the discussion without people becoming hot and bothered. But if not, we’ll forge ahead anyway.

Lots of questions about Ampligen. I don’t know very much about Ampligen. My bias in all this is to believe the patients, because that’s where the best information comes from. Just about everyone else has a dog in the fight. The things I have heard about Ampligen are mostly negative, or positive and then negative, but it’s a small number. There are very few advocates for it after more than 20 years. Hemispherx reports that 900 people have been treated with 90,000 doses to date. The available evidence with respect to XMRV is mixed. From Dr. Lapp’s newsletter of March 2011:

Dr. David Strayer, Medical Director at Hemipsherx Biopharma, described a retrospective study… 208 subjects from a previous double blind placebo controlled Ampligen study were analyzed for XMRV. About one third were positive for the virus and two-thirds were not. Activity monitoring demonstrated less activity in XMRV+ subjects. That is, they were less active and presumably more ill. Specifically, the improvement in exercise ability was monitored in these subjects. More improvement was measured inXMRV+ subjects than in XMRV-subjects. The table below describes the percentage of subjects who obtained at least 25% improvement in treadmill exercise duration at week 40 of treatment, as related to XMRV serology:

XMRV Status	Improved on Ampligen	Improved with placebo	Difference (AMP-PBO)
Pos (n=81)	44.7%	17.6%	27.1%`
Neg (n=127)	34.0%	25.7%	8.3%
Overall	39%	23%	15.9%

Dr. Strayer concluded that there was a 70% greater than average exercise response in XMRV+ subjects, and a 40% lower response in those who were XMRV-. Medication use was monitored in all of these subjects as well. 53% of XMRV+ subjects were able to reduce their use of symptomatic medications, while only 32% of XMRV- subjects were able to reduce medication use.

These aren’t exactly stellar results given all the wear and tear, unless of course you are one of the lucky ones. Dr. Mikovits reported in her Santa Rosa talk that about a third of the patients she has looked at had evidence of viral activation when treated with Ampligen (unpublished). So her observation, in addition to the less than exciting anecdotal evidence, gives me serious pause, but apparently a multi-site study is forthcoming, so we will have more information to consider. At least someone is studying something with respect to treatment, though it is the first clinical trial I have ever heard of where the patients are paying for the drug. While waiting for the results, I guess it is up for consideration, so I added it to the list with a question mark, but it’s a big question mark. Personally, I am not interested at this time.

The most interesting thing I’ve heard about recently is Dr. Urnovitz’s new rapid deep sequencer. From the press releases linked here for the Chronix/Hemispherx joint patent application announcement for a CFS blood test:

The Chronix experimental approach analyzes fragments of DNA often released into the bloodstream during the process of apoptosis or programmed cell death. Chronix is using its proprietary technology and advanced DNA sequencing platforms to measure alterations in specific regions of the chromosome, which can be detected as distinctive “signatures” in cell-free blood-borne DNA. By focusing on these signatures, Chronix’s technology can detect the presence of disease-damaged cells in simple blood samples without needing to biopsy diseased cells or tissues.

“Our technology—based on DNA released into the bloodstream by dying and damaged cells—taps into the dynamic information provided by the genomic alterations unique to each diseased cell. We capture what is happening to the DNA very early in and throughout the disease process, in real time, and patient by patient. That’s how our approach differs from other tests that focus on static genomic data or protein biomarkers,” said Dr. Urnovitz. The patient-unique signatures captured by the Chronix technology may prove useful as a companion diagnostic – a test that is used to help guide treatment decisions – and to provide information about the disease process to help pharmaceutical companies select the most efficacious drug candidates.

The Chronix approach has been validated in a number of peer-reviewed settings. At the ASCO meeting in June, Chronix researchers presented data showing that its assay detected breast cancer and invasive prostate cancer with 92% sensitivity and 100% specificity. Additional published studies have demonstrated that the Chronix technology can identify the presence or absence of active disease in multiple sclerosis patients, and that it can accurately detect early stage breast cancer with high diagnostic sensitivity and specificity.

A number of people have asked me what supplements I take. I have swallowing and appetite problems. If I take all the things I would like to, it’s a small meal that doesn’t go down well. When I take supplements, I take Meriva SR, B12 (in addition to Deplin), NAC, glutamine, L carnitine, CoQ 10, Vitamin C and undenatured whey protein. I also take Hawthorne tincture sometimes. I have never noticed a difference from a supplement, except transient effects from high doses of single amino acids. I have responded to herbs at times, especially teas. I miss Deplin if I stop it. There are other supplements that make sense with respect to what is known about how supplements impact HIV. I’ll discuss those ideas more in the future.

The active form of Vitamin D, D3, is a hormone with effects all over the body, including regulation of the immune system. Vitamin D ligands enhance NK cell and macrophage function. Supplementation for inadequate levels is very important. I left it off my list initially and one penpal reminded me that Vitamin D3 supplementation is the only thing that ever helped her noticeably. Levels should be followed. The literature is vast. Here, for the flavor, are a few abstracts from the last couple of months.

Vitamin d as a T-cell modulator in multiple sclerosis. Smolders
Vitamin d and inflammatory bowel disease. Ardizzone
Vitamin d deficiency and connective tissue disease. Zold
Vitamin d and innate and adaptive immunity. Hewison
Antibacterial effects of vitamin D. Hewison 

Antibiotics again. I am in support of using antibiotics if they work. I think the ILADS guidelines are dangerous with respect to their recommending long term intravenous drugs in combinations for years, even if it’s not clear they’re working. I did it. It didn’t work. It hasn’t worked for many people. It appears to work for a few people, like anything. There is no way to know if those people got better because of their treatment or despite it, because some people get better slowly anyway without treatment. Putting it all together, some people need a long term oral antibiotic to maintain a level of poor health, maybe because Borrelia burgdorferi is being suppressed, or maybe not, but it’s obvious that those people should continue their antibiotic. It is also rational, if you think Bb is the problem and it’s been there for a long time untreated or the patient is immunocompromised to try and clean them up with IV antibiotics. If they respond partially, you might want to continue for a while, duration to be determined within the confines of the doctor patient relationship. If a patient responds to IVs they should be offered orals after. Babesia, if present, should be treated in a symptomatic or deteriorating patient, but treatment doesn’t always get rid of it.

I am aware of the apparent inconsistency, mentioned by several people, that I am “for” antiretrovirals and “against” antibiotics. I hope that what I’ve written above clears up part of it. I listed anitretrovirals, not because I think everyone should take them, but because I think they should be considered, like everything else on the list. The option should not be buried because it’s not a cure. There is no cure. The list is in no particular order. I suppose I listed antiretrovirals first, because it’s the thing on the list that is hardest to access, but should be up for discussion, in my opinion. When I started taking them, I expected there would be a viral load measure available by now, and there isn’t. That makes it a tough call with respect to where to go from here, needing to make a decision in the dark. I can say without qualification that for me, antiretrovirals are much easier to take than antibiotics, but it is not an either or.

The responses I get from the Lyme community are sometimes irrational. They feel I am attacking the only help they have, their LLMDs. But I am attacking the extremely faulty guidelines that ILADS continues to put out there to influence unsuspecting physicians. I know quite a few doctors who treat Lyme and are most definitely “Lyme literate” that don’t belong to ILADS, or did and have quit. They resent that they are being painted with the same brush. If you have a good Lyme doctor, I hope he or she will consider my ideas. I am most certainly not attacking any doctor who wants to figure out how to help patients. ILADS was a good try. I was a member for six years. Time to move on. My opinion. Everybody gets to do what they want.

As for privilege. I grew up with advantages. My husband grew up poor. We’ve had money and not had money. It’s better to have money, but money and privilege are in no way protection from the disease. The real privilege I have, is the privilege of perspective, and that perspective is growing from your contributions.

I am all for angry advocacy, as I’ve said. I think we should do something dramatic, like camp out in front of the CDC this summer and throw fake blood on the steps in a proper demonstration, demanding big time funding for a change. CFS, ASD, GWI all together. A lot of people. In the Lyme community anger problems are called “Lyme Rage”. Like anxiety and depression, anger problems are common in neurodegenerative diseases, but blind striking out works against us. It turns off people that we need, reasonable people with normal lives who would like to help. We want what people with other diseases get, compassion, so we can stop saying we’d rather have cancer or AIDS. We are in need of help. When asking for help, one should remember the costs and rewards to the helper. The feeling of compassion for another is it’s own reward, but it’s hard to be compassionate when under attack, too busy turning the other cheek or striking back.

This discussion of who suffers the worst seems to me to be at the heart of the problem at hand. How do you come to terms with the anger and loss, while maintaining or growing compassion for others? There is a small subset of CFS patients that are unbelievably sick and stay that way for a very long time. A living hell. A contender for one of the worst things that can happen to someone. Yet, even they sometimes have some spontaneous recovery. In that way, we are lucky. And it’s important for those that are not so sick to know that this is not where the disease always goes. It doesn’t usually get so severe and there are ways to move it in your favor. We don’t know why some people get so sick and others don’t. But getting sick isn’t a given, nor is progression. Though there are clearly stages to the disease, there may be ways to slow progression.

There was a very sad comment by a woman who said she hadn’t been touched since her doctor shook her hand in January. Touch is a basic human need. I often think there needs to be communal living with assistance for CFS patients. To the woman who wrote that comment. I know many of us wish we could hug you. The energy I get from friends in the ether helps me. Not the same as a hug, but something.

It is important to know who you are mad at. It’s not us against the world. We won’t get anywhere that way. We need to differentiate between our friends, the misguided who should be forgiven and a few evil people who don’t deserve our forgiveness. We will grow if we can have compassion for others who suffer too. Nelson Mandela spent 27 years in prison, came out and worked with his jailers. He helped his countrymen much more by working for reconciliation than if he had needed to spit on his captors.

Does anyone remember the old movie “On The Beach”? Gregory Peck, Ava Gardner, Fred Astaire? For some reason, it’s been in my thoughts recently, maybe because of the nuclear disaster in Japan. The world is ending after a nuclear holocaust and a few people in Australia are still alive, waiting for the fallout to come, gathering together in a park. Waltzing Matilda is playing in the background. The Salvation Army has hung up a giant banner that says, “There Is Still Time Brother.”

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?

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.

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.

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:

• XMRV Infection Induces Host Genes That Regulate Inflammation And Cellular Physiology. Lee/Silverman
• Xenotropic Murine Leukemia Virus Related Virus (XMRV) Is Present In Malignant Prostate Tissue But Does Not Affect Pathological Or Clinical Outcome. Ritch/Cordon-Cardo
• A Preliminary Screening Of Xenotropic Murine Leukemia Virus-Related Virus In Japanese Prostate Cancer Patients. Igawa/Sakai

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?

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:

• Pure Cultivation In Vivo Of Vaccine Virus Free From Bacteria. Noguchi. 1915
• Vaccination Against Yellow Fever With Immune Serum And Virus Fixed For Mice. Sawyer. 1932
• The Use Of Yellow Fever Virus Modified By In Vitro Cultivation For Human Immunization. Theiler. 1937

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:

• Active Immunization Against Poliomyelitis. Brodie1932
• Active Immunization Against Poliomyelitis. Brodie 1935
• Vaccination Against Acute Anterior Poliomyelitis. Kolmer 1036

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:

• Isolation of poliomyelitis virus from human serum by direct inoculation into a laboratory mouse. Koprowski. 1947
• Immune responses in human volunteers upon oral administration of a rodent-adapted strain of poliomyelitis virus. Koprowski. 1952

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.

• Replication of Mouse Sarcoma Virus (Moloney) and its helper in a human heteroploid cell line of malignant origin. Saal
• Presence of circulating antibodies against gag-gene MuLV proteins in patients with autoimmune connective tissue disorders. Rucheton
• High prevalence of circulating antibodies to MuLV p30 antigen in human sera. An autoimmune response? Kovarík
• High prevalence of an IgG response against murine leukemia virus (MLV) in patients with psoriasis. Molès
• Lack of evidence of endogenous avian leukosis virus and endogenous avian retrovirus transmission to measles, mumps, and rubella vaccine recipients. Hussain
• Identification and Characterization of Avian Retroviruses in Chicken Embryo-Derived Yellow Fever Vaccines: Investigation of Transmission to Vaccine Recipients. Hussain

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.

Stoye JP, Coffin JM.

There are lots of papers about the dangers of xenotransplantation:

• Endogenous retroviruses: a potential problem for xenotransplantation? Stoye
• Clinical xenotransplantation: pigs might fly? Dorling
• Strategies to enhance the safety profile of xenotransplantation: minimizing the risk of viral zoonoses. Mattiuzzo

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

• Spontaneous mutations affecting the host range of the B77 strain of avian sarcoma virus involve type-specific changes in the virion envelope antigen. Zarling
• Oncogenic retroviruses of cattle, chickens and turkeys: potential infectivity and oncogenicity for humans. Johnson
• Detection of antibodies to avian leukosis/sarcoma viruses and reticuloendotheliosis viruses in humans by western blot assay. Johnson
• Poultry oncogenic retroviruses and humans. Johnson

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:

• Search for C-type particles in human neoplasia. Szakacs
• Infectious murine type-C viruses released from human cancer cells transplated into nude mice. Suzuki
• C-type virus particles in human urogenital tumours after heterotransplantation into nude mice. Wunderli
• Murine type C retroviruses and intracisternal A-particles in human tumors serially passaged in nude mice. Tralka

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?

• Of mice and men: on the origin of XMRV. van der Kuyl

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!

• Retroviral invasion of the koala genome. Tarlinton
• Biology and evolution of the endogenous koala retrovirus. Tarlinton