My choice for the scariest reading of the year was recently published in the journal Cancer Biology and Therapy and has the unwieldly title of Frequent Detection of Infectious Xenotropic Leukemia Virus (XMLV) in Human Cultures Established from Mouse Xenografts.
For those of you who may be confused by the idea of a "xenograft" I'll provide you with the definition given by the U. S. Public Health Service. "Any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (a) live cells, tissues, or organs from a non-human animal source or (b) human body fluids, cells, tissues or organs that have had ex vivio contact with live non-human animal cells, tissues, or organs." This covers vaccines as well as other surgical procedures in which human tissue is manipulated prior to transplantation.
In the scientific community mouse xenografting is often used to manipulate cancer cells for research purposes, among other things. With research that has linked XMRV (which is a xenotropic murine leukemia virus) to prostate cancer, chronic fatigue syndrome/ME, and to a lesser extent autism, scientists from Johns Hopkins University and the University of Texas Southwestern Medical Center as well as a few other institutions thought it made sense to investigate the frequency of XMLVs in human cell lines "established from mouse xenografts and to search for the evidence of horizontal spread to other cell lines."
In layman's terms the question they were asking was, "when we do xenografting with mouse biological products how often do we get XMLVs popping up in our samples?"
The answer they found is that six out of twenty three (26%) mouse DNA free xenografts "were strongly positive for MLV and their sequences had greater than 99% homology to known MLV strains." These samples were obtained from seven independent laboratories.
Further on the authors wrote, "Of the 78 non-xenograft derived cell lines maintained in the xenograft culture containing facilities, 13 (17%) were positive for MLV, including XMRV, a virus strain first identified in human tissues." (My daughter with autism has tested positive for XMRV.) In scientific terms this is an absolute train wreck.
This means that every surgical patient receiving any biological product which used mouse tissue in any way has a one in four chance of being exposed to an XMLV. And that also means that any biological sample which is maintained in a facility containing xenograft cultures has a 17% chance of becoming infected.
On the question of vaccines, let's just say that only 10% of the nearly 40 vaccines children are expected to receive prior to the age of five contain mouse biological products. This translates into roughly a 100% chance that our current generation of children will be exposed to an XMLV through a vaccination.
Are you scared yet?
It gets worse.
From the article is the following passage. "In one case XMRV virus infection to a non-xenograft colorectal carcinoma cell line RKO was demonstrated from an XMRV containing prostate xenograft derived cell line 221 Rv1 even though the two cell lines had been maintained in the same culture facility for only a few days."
The translation for a non-medical person is this: XMRV is highly infectious and spreads easily.
How about this for scary? "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."
For those of you keeping score at home, the CpG islands are responsible for methylation. Is any of this starting to sound familiar? And the transcription start sites of genes? Pretty damned important.
I know there are those who question the role of viruses in conditions like autism and state correctly that a well-functioning immune system will deal with any such pathogens. I agree. The problem is that we don't know the immune status of people in the population. For example, the discovery of XMRV itself was preceded by the finding that men with the most aggressive forms of prostate cancer had a deficiency in their RNasel gene, lowering the amount of an anti-viral defense enzyme their body produced. How widely is that RNasel mutation spread throughout the population? Do you know the RNasel status of your genes? Of your children? And that's just what we know about.
And can toxic chemicals and heavy metals interfere with your body's immune system response to pathogens, regardless of your genetic make-up? You betcha.
The closest example I can make is that of what happened to the native population in the Americas when Europeans crossed the ocean. A natural barrier was breached and the native population had no immunity to our pathogens. Some experts speculate that the diesases Europeans brough to the New World killed 90% of the native population.
While we have shared the Earth with mice and other creatures from the dawn of history, we haven't been culturing their cells, then injecting those cells into our bloodstream. We have breached a natural barrier and we need to ask the question of what consequences have been wrought from this decision.
In the conclusion the authors write, "Thus laboratories handling or culturing human xenografts should monitor for the presence of MLV, and should consider monitoring personnel for viral antigens or antibodies to them. Laboratories working with xenograft cultures should have full knowledge and understanding of the potential biological and biohazardous risks and should not distribute or publish their findings without full disclosure of the virus status of their xenograft-derived materials."
Translation for the ordinary person: Hey, we might be infecting our lab workers! Let's find out what diseases these viruses might cause! And maybe much of our research has been compromised!
I've heard some commentators lament what it will take for the medical authorities to deal with this issue seriously. They've noted with the despair the finding of XMRV in men with prostate cancer, those with chronic fatigue syndrome/ME and children with autism and how it has failed to provoke action. They've said to me, "These people have no problem screwing over the old men, those with CFS/ME, and even the children."
With this recent finding regarding the dangers of XMLV and XMRV transmission in labs, the question becomes, "Will these same medical authorities screw the very people who work for them?"
Addition to original article - I understand a Dr. Dusty Miller from the Fred Hutchison Cancer Center has raised some questions as to my suggestion that mouse tissue which harbors XMRV may possibly end up in a vaccine. For Dr. Miller I submit the following article:
Biologicals. 2010 May;38(3):371-6. Epub 2010 Apr 8.
Endogenous retroviruses as potential hazards for vaccines.
Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan. email@example.com
Retroviruses are classified as exogenous or endogenous according to their mode of transmission. Generally, endogenous retroviruses (ERVs) are not pathogenic in their original hosts; however, some ERVs induce diseases. In humans, a novel gammaretrovirus was discovered in patients with prostate cancer or chronic fatigue syndrome. This virus was closely related to xenotropic murine leukemia virus (X-MLV) and designated as xenotropic murine leukemia virus-related virus (XMRV). The origin and transmission route of XMRV are still unknown at present; however, XMRV may be derived from ERVs of rodents because X-MLVs are ERVs of inbred and wild mice. Many live attenuated vaccines for animals are manufactured by using cell lines from animals, which are known to produce infectious ERVs; however, the risks of infection by ERVs from xenospecies through vaccination have been ignored. This brief review gives an overview of ERVs in cats, the potential risks of ERV infection by vaccination, the biological characteristics of RD-114 virus (a feline ERV), which possibly contaminates vaccines for companion animals, and the methods for detection of infectious RD-114 virus. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.
PMID: 20378372 [PubMed - in process]
Dr. Miller also might want to read this section of the article "Of Mice and Men: On the Origin of XMRV" from the journal Frontiers in Virology and published in January of 2011: You can read the complete text http://www.frontiersin.org/virology/10.3389/fmicb.2010.00147/full
Vaccines, Viruses, and Contamination
One of the most widely distributed biological products that frequently involved mice or mouse tissue, at least up to recent years, are vaccines, especially vaccines against viruses. Some, for instance vaccines against rabies virus (Plotkin and Wiktor, 1978), yellow fever (YF) virus (Frierson, 2010), and Japanese encephalitis (JE) virus (Inactivated Japanese Encephalitis Virus Vaccine, 1993), consisted of viruses that were cultured on mouse brains. Such vaccines were in use from 1931 (YF vaccine) until now (JE vaccine, licensed in Japan since 1954). For rabies virus, early vaccines were mainly of goat or sheep nerve tissue origin. In addition, suckling mouse brain-derived rabies virus vaccines were used in South America and France (Plotkin and Wiktor, 1978). No mouse-derived rabies vaccine was ever licensed in the USA (Dennehy, 2001). Live-attenuated YF vaccines were originally also grown on mouse brain, but an YF vaccine grown on chicken eggs (named 17D) became available in 1937, and was since the vaccine of choice in the America’s. In 1962, contamination of the 17D vaccine with oncogenic avian leukosis virus was detected both in England and in the USA, but fortunately no excess of cancer incidence among vaccines was reported (Frierson, 2010). In France, the mouse brain-derived YF vaccine was discontinued as late as 1982.
Although being the most effective means to prevent infectious diseases and to safe lives, serious contamination problems involving vaccines have occurred (Pastoret, 2010). Contamination with unrelated viruses such as the presence of hepatitis B virus (HBV) in YF vaccine preparations stemming from the use of human serum for stabilization, and simian virus 40 (SV40) and foamy viruses through the use of monkey cell cultures (Pastoret, 2010). Some vaccine viruses are inactivated before use, hopefully also inactivating any contaminating virus particles, but the contaminating virus may be more stable than the vaccine virus. For instance, SV40 is highly resistant to inactivation (Murray, 1964). Endogenous retroviruses constitute a distinct class of contaminating viruses, as these viruses are encoded by all cells of a certain species, and therefore cannot be avoided even through rigorous screening (Miyazawa, 2010). Contamination with endogenous avian leukosis viruses is a major problem for vaccine viruses grown in chicken embryos or chicken embryonic fibroblasts (Hussain et al., 2003). Infectious cat endogenous RD-114 virus has been found in several veterinary vaccines produced in cat cell cultures (Miyazawa et al., 2010; Yoshikawa et al., 2010).
Dr. Miller, I await your reply.
Kent Heckenlively is a Contributing Editor to Age of Autism