The question. Did the conditions exist for the current epidemic of neuroimmune diseases to be the result of endogenous retroviruses present in animal tissues and used in the production of vaccines?
Epidemic neuromyasthenia; clinical syndrome?, by Henderson and Shelokov, published in the New Enland Journal of Medicine in 1959, describes what were probably the first cases of ME/CFS. This extraordinary paper lists 23 outbreaks of illness internationally, similar to the Lyndonville and Lake Tahoe outbreaks, between the years of 1934 and 1958.
Preceding the report of the outbreak in Iceland [of 1090 people] were 2 epidemics in the United States and 1 in England, all of which in retrospect, bear it a striking resemblance. Gilliam documents in detail an outbreak in 1934 of 198 cases among personnel at the Los Angeles County General Hospital during which 10 per cent of the 1531 physicians and nurses were afflicted. Occurring concomitantly in Los Angeles and in other areas of California were many cases that were considered typical of paralytic poliomyelitis and a great many others that were not. In addition to a number of hitherto unknown clinical manifestations particularly among adults, epidemiologic appraisal of reported cases revealed an unusually high attack rate, a low paralytic and case fatality rate and a relative age selection for adults, particularly females. Gilliam believed that the symptomatology among the hospital personnel was not characteristic and that the very high attack rate among the hosptial personnel was without parallel in the history of poliomyelitis. He concluded, however, that since classic poliomyelitis prevailed among a large number of the pateints with communcable disease in the hospital, the simpler explanation of the facts was that the atypical disease seen among the hospital staff was the same.
Edward Jenner, as an apprentice to a surgeon, observed that milkmaids who contracted cowpox were afterwards immune to smallpox. He first used cowpox material to produce cross-immmunity in a child in 1796 and, shortly after, reported a series of 23 cases, which included his son. The idea that a weak form of a disease can cause immunity was not new. As early as 1000 BC, it was known that an inoculation, or “variolation”, with material from smallpox lesions (Variola) produced a lighter form of the disease, though still with significant morbidity and mortality. Powdered material from smallpox scabs was blown up the noses of people in China in the 1500’s. It was observed in the early 1700’s that variolation had no effect on people who had had cowpox (Vaccinia).
Louis Pasteur, while working on chicken cholera, discovered that a faulty culture that didn’t kill as expected produced immunity in chickens. He used this concept to develop a post-exposure rabies vaccine. He grew the virus in rabbits, dessicated spinal cord to weaken the virus, and injected the dried product into the first human, an exposed child, in 1895. His treatment was quite successful as documented in this paper: Rabies And The Pasteur Treatment. Lackenbach. 1912. Pasteur’s work with anthrax and chicken cholera was different from Jenner’s in that the vaccine was artificially produced rather than using a naturally weak form of the disease. Pasteur coined the named vaccine from Jenner’s work with cowpox.
A couple of historically interesting papers with respect to the early use of animals to grow viruses for vaccinating humans:
Max Theiler, and his colleagues at Harvard, proved that Yellow Fever was not caused by a bacterium, but a filterable virus. He also proved that the virus could be transferred to monkeys and mice. In 1930, Theiler started working on a Yellow fever vaccine at the Rockefeller Institute, where much of the early vaccine work was done. He attenuated virus in mouse brain and chick embryo cell. Early vaccines were sometimes tested on volunteer doctors. Informative reference: The Yellow Fever Vaccine: A History. Frierson
From Theiler’s Nobel lecture in 1951:
The study of yellow fever may be divided into two periods. The first one occurred at the turn of the century when Walter Reed and his co-workers showed by the use of human volunteers that the causative agent of this disease was a filterable virus and that it was transmitted by the bite of the common urban mosquito, subsequently named Aedes aegypti. The second period began in 1928, when Stokes, Bauer, and Hudson found that the common Indian rhesus monkey was susceptible to yellow fever, thus making available an animal that could be used in the laboratory. The first strain of yellow fever established by these workers is known as the Asibi strain, named after the patient from whom it was isolated. It has been used extensively in yellow fever work and, as will be shown later, was the parent strain from which the 17D vaccine was eventually produced.
It was shortly after monkeys were found susceptible that, in searching for a less expensive and more readily available experimental animal, I found that the common white mouse was susceptible to the virus if inoculated by the intracerebral route. This method of inoculation was chosen as it was generally conceded that the common laboratory animals could not become infected if inoculated by the usual routes. The strain of virus with which this work was done was isolated by Mathis, Sellards, and Laigret in 1928 in Dakar, French West Africa, is known as the French strain, and, like the Asibi, is highly virulent for rhesus monkeys. The disease in mice was an encephalomyelitis with no involvement of the visceral organs, in contrast to that induced in man and monkey, in which the liver, kidney, and heart are involved. By serial passage in mice, the pathogenic action of the virus was altered in two respects. Firstly, the incubation period became progressively shortened until, after many passages, it became constant, or, to use the term introduced by Pasteur in his work on rabies, it became fixed. Now the incubation period in mice is used as a measure of the degree of neurotropism for these animals. Secondly, with the increase of virulence for the nervous system of mice, there was also evidence of a progressive loss of virulence for rhesus monkeys when inoculated parenterally. This loss of virulence for monkeys first suggested the possibility of the use of an attenuated active virus for the immunization of man. The finding that by mouse brain passage the virulence of yellow fever virus could be altered led me to undertake extensive studies on the variations induced in the virus by different laboratory procedures, which became my main scientific activity for several years. The results of only those experiments which are pertinent to the development of vaccines will be discussed here.
The finding of the susceptibility of mice and its attenuation for monkeys was rapidly confirmed by others. It was shown that many, if not all, strains of yellow fever are pathogenic for mice, and this animal came into widespread use in all yellow fever work. The pathogenicity of unmodified strains for mice varied greatly – ranging from the highly neurotropic Asibi virus to the relatively avirulent French strain. Both of these, as noted before, are highly pathogenic for rhesus monkeys and almost invariably produce a fatal disease when inoculated parenterally. With most strains it was shown that the mouse could be used for the quantitative estimation of virus. This proved of great value, for as strains of virus avirulent for monkeys were developed, the mouse was the only animal by which the presence and amount could be readily determined.
In the development of vaccines for human beings, using my mouse-adapted virus, two paths were followed. In the first, used chiefly by French workers, virus alone was inoculated; and in the second, used by American and English workers, virus and human immune serum were inoculated simultaneously. The first immunizations of humans using mouse-adapted neurotropic virus alone were reported by Sellard and Laigret (1932)… Full lecture
The first attempts to vaccinate for polio were actually in the 1930’s. Live and killed virus was used, passaged in monkey brain and spinal cord. The vaccines were tested on children and it was a fiasco; some of the test subjects developed the disease. For historical interest:
In the late 1940’s Hillary Koprowski worked with rodent and mouse adapted viruses, including rabies, Colorado tick fever, various viral encephalitides, West Nile Virus and others, before turning his attention to polio. He made the earliest live polio vaccine using Swiss albino mouse brain cells. The first dose was administered to a child in 1950. He also used monkey kidney cells which were implicated in passing SV40 to humans. Albert Sabin’s live polio vaccine was produced from attenutated virus obtained from Koprowski. Here are the earliest papers:
So it was probably all a big accident, which occurred for the best of reasons, to remove the scourge of horrible viral diseases from the human race. The ethical problem started later, when there was enough information and technology at hand to understand what was happening and nobody studied it. Instead they decided that the patients were all crazy. Easier to marginalize them. The really sad part is that, certainly by the early ’90s, when De Freitas did her work at Wistar, there was enough information to question whether it was safe to inject endogenous animal retroviruses into humans, even though it was known that they could recombine and infect the cells of other species in tissue culture, including human. They knew the viruses were there, they knew there was risk, but chose to march ahead blindly anyway. Amazing arrogance.
And this paper whose senior author seems to ignore his own work:
J Virol. 2003 Jun;77(12):6709-19.
Mechanisms of avian retroviral host range extension.
Rainey GJ, Natonson A, Maxfield LF, Coffin JM.
Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
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:
The dangers of xenotransplantation.
There are lots of papers about the dangers of xenotransplantation:
More evidence that avian leukosis viruses can infect human cells under certain circumstances:
And the idea that it only happened once, in a particular cell line? It seems that the chances are not so vanishingly small after all. From an easy to understand review of retroviruses: C-type: As B-type, but with a central core and barely visible spikes – e.g. most mammalian and avian retroviruses (MLV, ALV, HTLV, HIV). All old work:
Cover-up or stupidity? I’m just a dumb ER doc and I’ve gotten this far with PubMed and a few scientist friends (who if asked will deny knowing me:). Though any detail of what I’ve written could be mistaken, and there is conflicting evidence, overall, it certainly seems to fit. People have written that they are concerned that I’m too invested in XMRV. This is not all about XMRV. If they prove tomorrow beyond a shadow of a doubt that XMRV is a lab contaminant and not present in humans, it doesn’t change a thing in terms of what needs to happen next. At the very least XMRV has brought attention to an international disgrace. If XMRV is buried under a mountain of negative studies, or if XMRV is truly not a human pathogen, millions of people still need treatment for neuroimmune illnesses that are consistent with simple retroviral infection.
Certain scientists have been particularly vocal against the use of antiretrovirals for XMRV. Scientists trying to tell doctors what to do. Why do they think that doctors or patients should care about their medical opinions? They need to do their work and stop trying to practice medicine. The real question is why do they care if patients try antiretrovirals for a retrovirus? Why wouldn’t they want to know if the drugs work?
The current epidemic of neuroimmune illnesses may be due to the introduction of simple retroviruses into the human population through the use of vaccines. This hypothesis needs to be studied. I am not some crazy conspiracy theorist. The pathogenesis of the illnesses needs to be further elucidated and specific treatment found. Now. Not after one specific etiologic agent has been deemed the real deal and there’s a foolproof test available at Quest. There may be many specific agents. It’s so unfortunate that it didn’t turn out to be one retrovirus with a serology test that picks up all cases. That would have been so easy compared to what we are facing – infections with one, or more than one, of a panoply of simple retroviruses, that remain latent for long periods of time, are activated by inflammation and steroid hormones, creating a vicious cycle of inflammation and viral replication. It could be that replication incompetent viruses are part of the picture as well. Co-pathogens, like Lyme, fuel inflammation and there may be helper viruses involved in various ways. And, most unfortunately, there is even a possibility that the new simple human retroviruses are or will be endogenized in subsequent generations. What a mess!