In three words I can sum up everything I’ve learned about life. It goes on. ~ Robert Frost
The week before I left to come to Hawaii was a difficult one for me. I took a series of emotional hits in quick succession, then had to leave home to take care of patients here, alone with no support. I arrived feeling sicker than I had in many months. My first patient was a well known advocate in our community, and I will always remember that she was there when I got off the plane, as well as her caring in the first difficult days. She knows who she is, a very special woman.
Childbirth was the initial trigger for my illness, and a concussion once, but sustained emotional stress was involved in my worst declines. So I was a little concerned, as was my family. I did dip a little, predictably, but I’ve been able to function throughout and am feeling better again. More resilient than expected. Able to weather some difficult stuff without going down, a degree of stability necessary for the patients who are choosing to put their trust in me. At least they can be sure they are sitting with a doctor who cherishes every encounter, whatever the future may hold. I know what it’s like to be unable to work. Actually, I know what it’s like to be unable to roll over. I get a little frustrated sometimes at having to pace myself pretty extremely when I’m at risk, like now, but if I stick to very restricted hours and activities, particularly when I don’t have help, I can do the things I need to get done in the physical world. The medicine is the easy part. A reflex. So far caring for my own patients is sustaining me. As always, I work diligently to stay focused on what I can do, rather than what I can’t, and I don’t allow myself to sweat the small stuff.
A few people wrote that they were disturbed that I said I didn’t expect a cure. I should have said in my lifetime or in the foreseeable future. In the same way that HIV patients are incurable, yet attain functional cures for long periods of time with treatment, I expect that a similar degree of successful management of the disease will be possible for ME/CFS patients. The politics and regulatory issues are a nightmare, as I’ve learned firsthand through my association with the WPI. Coming here to see patients one-on-one feels like respite compared to that. The hardest thing for me to absorb is that a giant hand came down and hit the pause button on the science, and therefore the search for appropriate specific treatments, until Lipkin opens the envelope and declares a winner. We have the technology! It’s just money and priorities. If everybody would wake up and recognize it for the public health disaster that it is, it would take a couple of years to get a handle on what’s there from an infectious disease standpoint, a couple more to figure out the basic pathophysiology and a couple more for compassionate use treatments to be available. But it doesn’t look like that is what is going to happen. The psychiatrists will have their way for a while longer. We will have a new diagnosis, CSSD, Complex Somatic Symptom Disorder. New name for Munchausen’s.
The best news is that my Munchausen’s by proxy is in remission:). Ali is doing very well again, with large amounts of supplemental oxygen. We put the concentrator in the middle of the house with a long hose allowing her to be wherever she wants to be. She has been using it at 10 L/min for about an hour a day, more if she has breakthrough symptoms. She has needed no prompting, but wants to do it, because it makes her feel better. She has also had a few Meyer’s Cocktail plus glutathione infusions that seemed helpful, supportive, but she hasn’t had any for 4 weeks now and continues to improve with oxygen being the only new treatment. Her MCS symptoms, or hyperosmia, have almost resolved. She was able to go to a party for a few hours at a neighbor’s house last week where she was exposed to perfumes without problems. She hasn’t tried the chamber yet, but I have asked her to figure out if pressure adds anything for her, since she is much more sensitive than I am. As for me, I do think I benefit from the effect of coming to sea level from altitude (my house in Santa Fe is at 7000 ft). It most likely would be short-lived if I stayed, but should happen each time I come here, planning to use oxygen when I return to elevation. The travel really doesn’t bother me much anymore. I use the wheel chair service and am grateful for it. Supplemental oxygen during flight would protect against adverse effects of hypobaria and hypoxemia, but it is very expensive and a hassle. If I just pretend I’m home on the sofa, play with my iPhone and let them transport my body, the travel doesn’t seem to be a problem for me.
And lest anyone think that mouse retroviruses are not part of the picture whilst we are waiting for Dr. Lipkin, reminiscent of Waiting for Godot:), take a look at this important paper: Frequent detection of infectious xenotropic murine leukemia virus (XMLV) in human cultures established from mouse xenografts. Zhang/Gazdar. It’s reads like science fiction if one considers the consequences of this wee oversight, realizing that mouse xenografts have been used since at least the 40’s, though I still think the early yellow fever vaccine work was probably the beginning of human assistance in the natural process. Or it may have begun even further back, with the selective breeding of mice in the early 20th century, mice that were unable to survive in the wild, producing infectious viruses to which they are not susceptible due to receptor mutations. The use of animals, including mice, for the production of vaccines started in the early 30’s or before. Yellow fever was attenuated in mice and injected into monkeys and humans. See previous blogs here, here and here. Also there must have been lots of experiments at the time that didn’t make it into print. The records from the Rockefeller Institute would probably shed a lot of light. This paper was published in 1932 and the first documented outbreak of Epidemic Neuromyasthenia at LA County Hospital was in 1934: Vaccination Against Yellow Fever With Immune Serum And Virus Fixed For Mice. Sawyer/Lloyd. J Exp Med. 1932 May 31;55(6):945-69. Infectious mouse retroviruses probably infected humans before that, but at very low levels, since the sick mice died like they were supposed to.
Hats off to Zhang et al for their vital work, and for calling a spade a spade. Finally someone stating the obvious. 22Rv1 doesn’t explain away all the ruckus, nor was it the incredibly rare event postulated by Paprotka et al. Like XMRV, it is a signpost to a much greater problem. It is the patients that are contaminated, and not by just one virus. Many infectious retroviruses. Just because way back when, Coffin, Stoye, Heneine and the gang all said it couldn’t happen, doesn’t mean that it didn’t. Some choice comments from the Zhang paper:
ERVs represent remnants of ancestral germline infection by exogenous retrovirues and after integration into the genome are transmitted vertically as proviruses. Murine leukemia viruses (MLV) as ERV provirus forms are present at about 60 copies per mouse genome from which up to 15 copies are related to infectious xenotropic murine leukemia viruses (XMLV)… Thus, active mouse ERV provirus present in common inbred mouse tissues can be the origin of XMLV or recombinant polytropic MLVs which are infectious to human tissues implanted in laboratory mice.
Earlier studies have documented that XMLV type-C retrovirus particles were indentified in human xenograft cultures derived after xenografting in immune-compromised mice… NCI-N417 SCLC cell line was established from a mouse xenograft by the Gazdar lab at the National Cancer Institute (NCI) in the early 1980s and this cell line was subse- quently found to contain XMLV a few years later.
Reports of XMLV strains being present in human xenograft cultures appeared in the 1970s…
Our results indicate that human tumor cells frequently become infected with MLV virus after xenografting and subsequent culture. We have observed that mouse stromal cells may persist in culture for lengthy periods. Mouse stromal cells, while they contain abundant provirus forms of MLV, including ecotropic, polytropic and xenotropic strains, seldom spontaneously release large amounts of infectious virus (authors’ unpublished findings). Virus infection of xenografted cells may require activation of XMLV virus by chemical or immunological induction in mouse and by prolonged mouse and human cell contact. Viral transfer may occur in the mouse host or during subsequent xenograft culture. Our findings of infectivity of XMLV-positive supernatant fluids demonstrated that XMLV can readily infect other human cultures without presence of mouse cells or other aiding factors, indicating that these viruses are highly infectious.
In conclusion, our studies demonstrated that several MLV strains were present in over one fourth of xenograft cell lines. Infected cell lines were identified in most laboratories working with or establishing xenograft cultures, indicating that such contamination was widespread. Infected cultures usually release large numbers of infectious virions, and intra-laboratory spread of MLV virus to other cell lines maintained in the same facilities may occur, confirming the highly infectious nature of MLV virus. Retroviruses have been associated with multiple diseases including solid and hematologic malignancies, AIDS as well as with non-malignant diseases. The high susceptibility of human cells to infection with XMLV, the high levels of reverse tran- scriptase activity present in culture supernatant fluids and the demonstrated infectivity of the shed virions suggest that such viruses may present potential biohazards to laboratory person- nel involved in cell culture facilities or to those handling human xenografts. In addition, the effects of the integrated provirus or the released virions on the biology of infected tumor cells are unknown. Provirus integration into the genome is not random, and occurs preferentially at transcription start sites, CpG islands, DNase-hypersensitive sites and gene-dense regions, suggesting that provirus integration may influence transcription in the host cell. Thus laboratories handling or culturing human xenografts should monitor for monitoring personnel for viral antigens or antibodies to them.