So now the Emperor walked under his high canopy in the midst of the procession, through the streets of his capital; and all the people standing by, and those at the windows, cried out, “Oh! How beautiful are our Emperor’s new clothes! What a magnificent train there is to the mantle; and how gracefully the scarf hangs!” in short, no one would allow that he could not see these much-admired clothes; because, in doing so, he would have declared himself either a simpleton or unfit for his office.

~ Hans Christian Andersen

The moment of clarity has passed. Science isn’t going to save us. No cavalry coming over the hill any time soon. Back to business as usual. Even as the public display of insanity continues in Reno, the discussion of the WPI’s “bad patch” is dying down. New science into a possible viral etiology for ME/CFS has all but died down, awaiting the results of the Lipkin study. It’s hard to expect much when it seems likely they aren’t looking for the right thing, but nevertheless, I still hope against hope they will find something of significance. The backlash has already started, with recent papers about reward deficiency states and perception of pain. The most innovative scientific minds willing to think about us at all are applying their attention to the genetic piece, a factor for sure, but not the root cause, still a downstream effect.

In the midst of losing the interest of the scientific community, the run for Rituxan is on. As a bit of a stalker magnet for the more extreme elements of the ME/CFS community, I got slammed after my last blog by some who like this approach. It is ironic that my opinion about this particular choice is interpreted by some as my wanting to limit access to treatment, given that I was a guinea pig for the last round of uncontrolled human drug trials. And before that, antibiotics for chronic Lyme. This option seems like the most dangerous by far to me over the long haul: hurling bazookas at the immune system will cause increasing dysfunction over time. Though the risk from the infusion itself goes down with repeated administrations, the infectious disease doctors will continue to be busy mopping up the mess caused by this approach to the disease. We are not talking a round of chemo here, but treatment that will presumably be needed for life.

Even so, no one can judge the degree of suffering of another, or what may or may not be the best course of action for anyone else at a given moment. It seems just like Lyme Disease to me. Any disagreement with their doctors’ approach is unacceptable, because those doctors are at least validating the illness. Thank God someone is willing to prescribe the big guns for our disease, no matter how misguided. An approved major pharmaceutical intervention means we have a real disease, instead of an ill-defined syndrome. I agree, it’s better; I just don’t like the risks associated with this treatment.

Big Pharma, an Emperor with no clothes if there ever was one, has waged a war on human disease that is an obviously failed experiment. The newspapers are reporting that more people die of adverse reactions to drugs than automobile fatalities. Our government’s complicity with the devil has left the entire medical establishment in an unsustainable position. You can’t run a society where everyone expects to be maintained on expensive drugs for life. The whole concept is misguided anyway. Take statins for example, which come up in my practice, because even completely unsuitable patients are subjected to the statin knee jerk reflex, though it seems particularly inadvisable in a group of patients already suffering from chronic myalgias. How did the statin brainstorm happen?  Twenty five or so years back, somebody got the bright idea that since people who live to very old age sometimes have low cholesterol, we should give everyone who wants to live a long time these drugs to lower their cholesterol to some artificially predetermined number to prevent heart disease. A logical fallacy if there ever was one. It’s taken all this time for doctors to realize that maybe it wasn’t such a good idea after all. They knew it could cause Polymyalgia rheumatica way back when, so essentially healthy people wound up on steroids long term from this particular experiment. Now it turns out statins increase the risk of diabetes.  And they cause cognitive decline in the elderly. Brilliant. Would you hire these critical thinkers to make an important decision for you with respect to your long term health and well being? In the meantime, Lipitor has made more money than any drug in history. Over 12 billion dollars. No evidence that it prevents primary cardiovascular disease. No improvement in quality of life. Lots of maimed people. An aside: although red rice yeast lowers cholesterol with fewer side effects than statin drugs, it contains naturally occurring lovastatin and can cause the same side effects as the drugs, though it is less likely to do so.

Nobody hopes more than I do that somebody pulls some existing drug that didn’t make it to market for something else off the shelf for us, or fast tracks an orphan drug, in the next few years, but I don’t see it happening. No one cares. No one cared enough to test the already existing possibilities for us when it made sense to do so, at one particular point in time. The round of experiments in vivo that did happen, and the very few of us still taking antiretrovirals, should have been enough to raise the question of why they may be useful for neuroimmune illnesses, but apparently, it wasn’t to be. The question is dead as far as the scientific community is concerned. All conveniently chalked up to the failings of one scientist, per Dr. Racaniello’s final analysis, which he figured out with the assistance of his good buddies Trine Tsouderos and ERV (you’d think he’d be ashamed to admit that publicly, but I guess not).

When does it stop being the human genome and become a rescuable virus that can make other people sick? How many deletions do you have to put back to call it retrovirology instead of genomics? Take the next step. What are the most likely sources of animal viruses and pieces of viruses (not just murine) that could be rescuing defective remnants of past infections long quelled by the sands of time, causing some people to spit out enough viral product to cause disease, and others, exogenous virus that can infect other people? Because it isn’t simple, in the sense that it doesn’t fit the one virus, one disease paradigm, it, or much more likely they, have been missed for decades. Also it was assumed that exogenous retroviruses known to be present in tissue culture, and known to be able to infect human cells in the lab, weren’t a problem for people, even parenterally introduced, since most human cells have retroviral restriction factors. I am not a virologist, but I can read, and retrovirology is an extension of genomics, and visa versa, meeting in the middle of each field.

Here is a paper from 1987. The Four Classes of Endogenous Murine Leukemia Virus: Structural Relationships and Potential for Recombination. The authors, John Coffin and Jonathan Stoye, went after Dr. Mikovits very publicly on multiple occasions. Coffin said publicly that she would be “burned at the stake”. I’m sure that’s what he wanted. After all, when this all comes clear, he will have to admit that almost the entire human race is infected with retroviruses that he chose not to worry about. Not surprisingly, he doesn’t want to think about that possibility now. Max Planck said science changes one funeral at a time. Highlights from this paper:

The modified polytropic proviruses can serve as env donors in some recombinants. Two viruses derived by recombination with the Friend strain of MLV have been sequenced and appear to have acquired env genes from different proviral classes.

It thus appears that  different ecotropic viruses can recombine with different endogenous sequences. It is possible that viral sequences themselves directly determine whether recombination can take place… Endogenous sequences expressed in a differentiation specific fashion would thus provide distinct opportunities for recombination to occur.

In light of this relationship it seems reasonable to speculate that evolution of the ecotropic virus endogenous to inbred strains of mice might have involved a recombination between a nonecotropic virus of the type present in the mouse genome with another virus which has not been fixed in laboratory strains of mice. Thus, the recombinations which occur in highly leukemic strains of mice might in fact be reciprocal to an event that occurred many years ago.

Dr. Michael Snyderman, who has CLL (chronic lymphocytic leukemia) and CFS, and for whom we have the only hard data showing a response to antiretrovirals, was culture negative for XMRV, but had positive serology. Here is a link to Dr. Snyderman’s last guest post. We don’t know if MMTV-like virus infection can cross react with a serology test that picks up MLVs. Andrew Mason believes he has isolated a beta retrovirus associated with primary biliary cirrhosis and an anti-mitochondrial antibody. I have presented his work and lots of other evidence on this blog in the past that supports a retroviral etiology for certain neuroimmune diseases, as well as case reports of responses to antiretrovirals.

Since gamma retroviruses (and other simple animal retroviruses) replicate mostly by mitosis, unlike HIV, in hindsight, we shouldn’t have expected anything other than slow improvement, since stopping viral replication doesn’t fix the problem (n.b. there was one rapid complete response, anecdotally, in a young patient who hadn’t been sick for long). Infected cells need to be replaced by apoptosis, which the virus tries to prevent, hence the clonality that Dr. Snyderman is studying.

We have no marker of disease. When I started antiretrovirals, I naively expected to have viral load measures in a year or so, to benefit from all the work that had already been done for HIV disease. But now there is nothing to follow but patient report. Instead of going back to the drawing board to figure out what it is, everybody went home, since XMRV was created in a lab. However, that lab contaminant spreads through a clean lab in a few days, infecting human cells. It also establishes a persistent infection in macaques. Dr. Snyderman has real trackable numbers. His CFS symptoms have waxed and waned with his remissions and relapses. He will try to publish as a clinical case study in a medical journal, but no one will notice. Just like the occasional case reports that have shown antiretrovirals to be effective for MS and Sjogren’s Syndrome (both of which show up frequently in the families of CFS patients).

In what follows, any time you read “XMRV”, think instead, “similar simple animal retrovirus”…

Silverman abstract, XMRV infection induces 30 host genes that regulate inflammation and cellular physiology, published only as a supplement: XMRV Infection Induces Host Genes that Regulate Inflammation and Cellular Physiology – Source: The Journal of Urology, Apr 2011 Supplement (#280) and Integration Site Preference of Xenotropic Murine Leukemia Virus-Related Virus, a New Human Retrovirus Associated with Prostate Cancer

There are other known instances where virus is necessary, but not sufficient without the genetic piece. I have a Crohn’s diagnosis, along with many others that are almost right (most autoimmune diagnoses in ME/CFS patients are not full blown, symptoms and antibodies, but not the full picture). Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine

Simple animal retroviruses have glucocorticoid (and hormone) response elements and anyone who knows anything about the disease knows how well this fits. It is one of the reasons why the patients look so crazy. The disease is definitely exacerbated by persistent stress in many people, in much too direct a way. Hormonal shifts, puberty, childbirth and menopause were also obvious triggers historically for many. Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity in Prostate Carcinoma Cells and Androgen Stimulates Transcription and Replication of Xenotropic Murine Leukemia Virus-Related Virus

Here is a paper from 1978 showing that murine and primate sequences can mix it up with each other and rescue defective endogenous sequences. Rescue of endogenous 30S retroviral sequences from mouse cells by baboon type C virus.

And from 1985: Maturation of murine leukemia virus env proteins in the absence of other viral proteins. “Cell surface gp70 was found alike in the mutant and wild type. However, cleavage of Pr15E to p15E did not occur in the mutant. This final cleavage step of AK 71 Prp15E could be made to occur by superinfecting cells containing the mutant with baboon endogenous virus.”

Here are three blogs I wrote when I was figuring out the vaccine/biotechnology piece. My understanding is deeper now, but I still think the basic thesis is correct. I’ve made some scientists angry (preferable to being ignored), but nobody has yet told me why my hypothesis is wrong, or offered a better explanation for the clinical observations; what else explains all of the observed phenomena? If you haven’t read them, there’s some interesting stuff  in these posts about the history of vaccinations that you may not know.

• Cover-up and Contamination Theories
• Vaccinations and Frankencells
• Science fiction or fact?

Now in the 21rst century we have “humanized” monoclonal antibodies produced from hybridomas, derived from antigenically stimulated B cells from sick mice that are known to be producing infectious virus; these B cells are then “fused” with immortalized human myeloma cells. We inject the antibodies produced, and the sludge?, into people, e.g. high risk babies to prevent RSV. Then there is xenotransplantation. And on and on. And what about the lab workers, since they are working with exogenous adventitious retroviruses that easily spread throughout the lab uncontrolled by the usual precautions?

• The Human Lung Adenocarcinoma Cell Line EKVX Produces an Infectious Xenotropic Murine Leukemia Virus
• Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines

There are still readers coming to this blog from public and private institutions of higher learning. Not as many as when Dr. Mikovits was fired, sued and arrested, but quite a few still visit and new ones are finding it. There is no “translation” happening between the clinic and the lab. Sadly, the internet is all we’ve got. Anyone who knows something about the science in question, please tell me why I’m wrong. I want to be wrong. It’s difficult to find the energy to continue to think about the science in a vacuum, with little hope now that understanding the frontiers of the science will have clinical utility any time soon.

Questions:

1. Does the “normal” human genome contain murine sequences? Avian sequences?
2. What processes other than retroviral replication might be impacted by a reverse transcriptase inhibitor?
3. Do retroviral RTI’s have activity against other reverse transcriptase enzymes?  Do RTI’s inhibit telomerase reverse transcriptase? Here’s a paper that suggests the answer is yes: Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence.
4. Do retroviral RTI’s inhibit transpositional behavior? Please read this very important paper: Inhibition of endogenous reverse transcriptase antagonizes human tumor growth

Meanwhile, Ali and I continue to do amazingly well. Not every minute, but we are having many wonderful minutes. Ali just finished her first semester at U Mass Lowell online and her first college grade was an A. She is planning to increase to a full program for the summer. She has friends and is currently in a relationship. She is starting to go out, just for fun, without any major MCS set backs. She has been making and going to her own health care appointments and dealing with the other odious tasks of life. She has been regularly cooking inspired meals for the family. She has begun to do calisthenics, without weights and walk a little, without significant PEM.

I was in Hawaii for two months, so Ali didn’t have any infusions during that time. She had an adverse reaction to a glutathione push early in the year that had soured me a bit on IV’s, and I didn’t use any for K (guest blog by her mom a few back), since we were getting good improvement without it, but Ali wanted one when I got home and she responded to her usual modified Meyer’s, no glut, with a burst of energy that has so far lasted a week.

I had a huge push to get home. I went to a big local party in North Kohala, spent the next day packing up the house so it would be together when I return, then took the red eye home. I hit the ground running and left four days later for a six day RV trip in Arizona, where my husband was entered in a mountain bike race. We went to some amazing places, Prescott, Sedona, Petrified Forest National Park. I hiked every day of the trip, including the hard part of a hike, described as “strenuous” by the park service.

Petrified Forest National Park May Day, 2012

I have been able to throw myself off the proverbial cliff and fly for a day or two for quite some time; all the while payback has been reducing in severity and duration, but this is the first time I’ve been able to keep it up. I’ve had a little PEM here and there, to let me know I was up against my limit, but at a hard half mile hike, with rock clambering, I am much beyond where I was six months ago when we went to New Orleans and I wasn’t up to walking around the Tulane campus, even though I really wanted to. The only things I’m doing consistently is taking Viread, using a little oxygen here and there, Cozaar, aspirin, hormones. I need to take my own advice and be more consistent with oxygen and do some neurofeedback. I’m on minimal supplements, D3, B12, Deplin, ubiquinone, others sporadically.