While the days, weeks and months pass, the scientific community continues to work on what isn’t, instead of what is. The question of how a lab contaminant produces an immune response in patients hasn’t been addressed by any of the contamination theorists. And how do you manage to contaminate the patients’ samples at a higher rate than the controls when all samples were blinded and run at the same time? In fact, it is the patients that are contaminated with a family of MLV-related retroviruses, not Dr. Mikovits’ lab.
This abstract was presented at CROI a few days ago:
XMRV Probably Originated through Recombination between 2 Endogenous Murine Retroviruses during in vivo Passage of a Human Prostate Cancer Xenograft. Paprotka
Many questions arise without the full paper, but it seems that far from showing XMRV to be a lab contaminant, the study shows what may in fact have happened. Endogenous retroviruses recombined in or infected human tumor cells through subsequent passages in vivo (in mouse) to produce a fully replicative xenotropic exogenous retrovirus, that in fact may prove to be the most infectious human retrovirus yet. In animals, similar viruses are communicated casually. Lombardi et al demonstrated that this new human retrovirus is circulating in the blood of as many as 10 million Americans. A public relations nightmare. So what did the scientists who said this was impossible do? First they denied its existence, then tried to suggest results were the result of mouse parts in their reagents, but none of the arguments have in any way refuted the data of Lombardi et al or Lo et al, who rigorously ruled out contamination. What they have shown is that it is possible to produce XMRV in a lab. Like the murine retroviruses, recombination events produce new pathogenic variants. See my post from September 10 about Sandra Ruscetti’s work: Lessons from the murine retroviruses
As for the 22Rv1 cell line being the source of XMRV contamination responsible for the whole mistaken affair, none of the labs involved in the Science paper Lombardi et al, have ever used this cell line. They couldn’t have contaminated subjects’ blood with virus produced by a cell line which all three investigators at different institutions can prove beyond a shadow of a doubt never entered their laboratories (personal communication). Sillier still, is the idea that this supposedly singular event was the source of infection, since it has only been around since the late ’90s: A new human prostate carcinoma cell line, 22Rv1. Sramkoski
My guess is that passing lots of human tissue through mice and then culturing in the laboratory for now more than four decades produced the conditions to enable a very unlikely event- by giving it many chances to occur. A probable place for this to have happened was in the creation of live attenuated virus vaccines where virus is made less virulent with multiple passes through animal cells in tissue culture. The earliest live polio vaccine was made by Hilary Koprowski using Swiss albino mouse brain cells. The first dose was administered to a child in 1950. He also used monkey kidney cells which were implicated in passing SV40 to humans. Albert Sabin’s live polio vaccine was produced from attenutated virus obtained from Koprowski.
Mouse cells and the cells of other species have also been used over the years in the creation of other vaccines. Some vaccines, including attenuated Measles and Mumps in the MMR, are grown on duck and chick embryo cells. Domestic fowl have endogenous retroviruses, avian leukosis viruses (ALVs or ASLVs), that do very similar things to the gammaretroviruses. Recombination events are involved in pathogenicity and they can infect the cells of other species in tissue culture. XMRV requires the XPR1 receptor to infect cells. The XPR1 receptor is ubiquitous in mammalian cells. Lab mice are resistant by virtue of XPR1 polymorphisms. The alpha retroviruses use a receptor called TVB. TVB is a tumor necrosis factor receptor that is most likely the avian homolog of a TRAIL (TNF-related apoptosis-inducing ligands) receptor. Here is a paper about the receptor: A Fifteen-Amino-Acid TVB Peptide Serves as a Minimal Soluble Receptor for Subgroup B Avian Leukosis and Sarcoma Viruses. Knauss. The abstract contains the following sentence: “This peptide was sufficient not only for binding to ASLV-B but also for activating viral entry into mammalian cells that lacked the cognate viral receptor.”
Here are two recent papers that should be giving someone pause, but there is no evidence that anything is changing in the status quo at the CDC. Head in the sand or worse?
- Endogenous retroviruses as potential hazards for vaccines. Miyazawa
- Isolation of an Infectious Endogenous Retrovirus in a Proportion of Live Attenuated Vaccines for Pets. Miyazawa
Beta retroviruses, e.g. mouse mammary tumor virus (MMTV), may also be present in tissue culture of murine cells. The first PubMed paper seems to have been published in 1948 when the “milk factor” was first identified on electron microscopy in tumor prone mice:
A particulate body associated with epithelial cells cultured from mammary carcinomas of mice of a milkfactor strain. Porter
MMTV is a vertically transmitted endogenous retrovirus that causes cancer when it inserts near an oncogene. Vertical transmission of murine breast cancer by adoptive nursing was demonstrated in 1936 by Dr. John Joseph Bittner. It was formerly classified as a simple retrovirus, but transcribes a regulatory protein similar to HIV, so is the first complex murine retrovirus identified. MMTV codes for a superantigen that stimulates T lymphocytes which in turn stimulate B cell proliferation. At puberty the virus enters the mammary glands with migrating lymphocytes and infects proliferating epithelial cells. MMTV can be transferred exogenously or endogenously through the germ cell line; the later infection produces virus present in every cell of the body. Mice that acquire the infection this way have a higher incidence of tumors. In lymphocytes, it may cause a T cell leukemia. MMTV has an enhancer region in its U3 long terminal repeat that activates the virus in mammary cells. It is activated by estrogen and other glucocorticoids, including progesterone. It is especially responsive to the synthetic steroid Dexamethasone which has been used to induce lactation in the dairy animals. And a few new MMTV papers.
- Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis. Ross
- Mouse mammary tumor like virus sequences in breast milk from healthy lactating women. Johal
- Mouse Mammary Tumor Virus in Anti-Mitochondrial Antibody Producing Mouse Models. Zhang
- Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer. Arendt
Gamma retroviruses are used as the backbone for gene vector therapy. It is known that retrovirus-mediated gene therapy of SCID-X1 can lead to leukemia and lymphoma because proto-oncogenes can be activated as a consequence of vector integration. Gammaretroviral vectors preferentially integrate near transcriptional start sites and CpG islands.
- Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. Hacein-Bey-Abina
- A novel model of SCID-X1 reconstitution reveals predisposition to retrovirus-induced lymphoma but no evidence of gammaC gene oncogenicity. Scobie
- Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy. Davé
Another place for it to have happened or to be happening, as demonstrated by the Paprotka CROI presentation, is in the creation of human to mouse xenografts. It turns out that by transplanting human tumors into mice and passing the tissue through subsequent generations, it becomes possible to establish tumor cell lines that couldn’t be established before. Also xenografts are used to study tumors, e.g. specific tumor immunogenicity and response to treatments. Why the presumption that the recombination that occurred in the Paprotka experiment was a unique event? They were fiddling with mouse viruses in the lab in the 1930s. The first outbreak of Epidemic Neuromyasthenia was in LA in 1934 and involved hospital staff. And suddenly the CDC is worried about lab workers and testing archived specimens. Will they find it? It would be funny if it weren’t so incredibly sad.
Take a look at this fascinating paper that covers a lot of material including the problems with xenotransplantation:
The discovery of endogenous retroviruses. Weiss
Are we to believe this recombination event occurred only once and that a pathogenic MLV-related human retrovirus is only produced by one particular cell line? Told to us by some of the very scientists that said it was impossible? Anyone smell a cover-up? Much easier to destroy a seminal work than admit that there may in fact be a family of XMRVs. Careful reading of the Science paper shows that the monoclonal antibody used to detect XMRV envelope in Lombardi et al detects all known xenotropic, polytropic and ecotropic MLVs. Antibodies made by patients recognized specific envelope and gag proteins. PCRs were optimized for sensitivity, not specificity. And quite possibly there are many other recombinant animal retroviruses infecting humans as well, created in laboratories and injected into almost everybody in the industrialized world, because of arrogance.
Putting it all together, it seems quite plausible that batches of vaccines containing retroviruses that are infectious to humans have been going out for over half a century. Much of what I’ve written here has been known but ignored for a long time. The assumption was made that endogenous animal retroviruses couldn’t harm people. It’s becoming clear that this was a very incorrect assumption.
So is there motivation for the cover-up and baseless attacks against Dr. Mikovits? They cannot attack the data because it is impeccable. Coffin and Stoye wrote the commentary in Science. Have they retracted it? Coffin said at the CFSAC in October 2009 that “This is as good as it gets…”. If this were HIV/AIDS, the year would be 1983. We have much still to learn about human MLV-related viruses. Is it even remotely possible that the findings reported in Lombardi et al were the result of contamination of their reagents? No more likely than that the retrovirus described by DeFrietas et al in 1991 was contamination. Had the CDC done something then, we could have prevented the autism epidemic and a second generation of infected people. Instead they buried DeFrietas’ work by withdrawing all funding. Deja vu?