Copyright, Dr. John Martin

Vaccine Safety

Dr. John Martin

One of society's highest obligations is the protection of its children. Vaccine programs provide a proven method for childhood disease prevention. The safety of such programs has been entrusted to vaccine manufacturers and to government. regulatory agencies. Although widely touted as the major medical triumph of the 20th century, the development of viral vaccines has elements of less than stellar performance. The discovery in 1960 of live SV-40 virus contamination in formalin-treated poliovirus vaccine, produced in kidney cells cultures from rhesus monkeys, did not lead to an immediate recall of the contaminated vaccines. Rather the production method was switched to the use of kidney cells from the much less well characterized African green monkeys. This switch in monkey species was soon followed by the decision to forgo formalin inactivation by using a weakened (attenuated) live strain of poliovirus. Persisting concerns regarding contaminating viruses in the live poliovaccine led in 1972 to a joint study between the vaccine manufacturer and the United States Food and Drug Administration (FDA). Kidney cultures from all 12 monkeys tested grew African green monkey simian cytomegalovirus (SCMV). Only 4 of the SCMV isolates were detectable using the regular methods for virus detection. No changes in testing methodology were imposed, nor was the scientific community alerted to the findings. An excuse that was subsequently offered was that all such information about the study was deemed to be proprietary. The results of this earlier study were, however, not conveyed to me in 1977 when, as an FDA scientist, I notified the Director of the FDA's Bureau of Biologics that certain poliovaccine lots contained unexplained non-cellular DNA; and were therefore potentially viral contaminated.

The issue of SCMV contamination of poliovirus vaccines was again raised with the FDA in May 1995. I was then working as a virologist at the University of Southern California. I had developed tissue culture methods which indicated the presence of atypical viruses in patients with complex neurological diseases. The viruses were striking in that they failed to evoke an inflammatory reaction in the patients from whom they were isolated. They were termed stealth viruses on this basis and seemingly they lacked target antigens for recognition by the body's cellular immune system. Sequencing studies on a stealth virus indicated it had originated from SCMV. Several meetings with FDA and Center for Disease Control and Prevention (CDC) officials clearly pointed to their unwillingness to allow any outside review of vaccine safety procedures. For example, a simple request to review histological slides of neurological tissue of monkeys inoculated with poliovaccine was refused, again on the basis that it was proprietary information. Noteworthy was the admission that the vaccines were routinely tested in rhesus monkeys because African green monkeys commonly show evidence of neurological disease. Moreover, even in rhesus monkeys, the vaccine was said to induce considerable damage, although less than that induced by non-attenuated poliovirus.

The actual sequence data were published in a respected virology journal in July 1995. The article aroused the interest of anti-vaccine consumer groups. Through the efforts of one of these groups, I was invited to attend a vaccine safety meeting of the Institute of Medicine, National Academy of Sciences. The open meeting held on November 6, 1995 was followed the next day by an "executive session." I was informed that several individuals at this meeting were "furious" that I was allowed to speak. A very much watered down account of what I said subsequently appeared in the official report of the meeting.

Some insight into the lack luster nature of the existing system was provided by several brief interchanges with Government and other officials during the last several years. For example, I was asked whether formalin treatment would inactivate stealth viruses. My response was that I did not know. The chairman of the National Immunization Advisory Committee suggested his advocacy of a split protocol in which both formalin inactivated and live attenuated poliovaccine would provide the necessary time window for the manufacturer of the inactivated vaccine to develop the stocks required for a complete switch. True to his suggestion, the official switch to inactivated vaccine is scheduled for January 2000. Of course, those "in the know" would have already switched to the inactivated vaccine. An FDA reform bill was being considered by Congress in 1997. I suggested that the bill include the provision that "If a safety issue is identified in the regulation of a biological product, then Industry will waive its proprietary protection so that the information could be made available to the scientific community." The suggestion was well received by the counsel for the House Commerce Committee. It was soon dropped, however, when support was not forthcoming from Industry, FDA or the American Medical Association (AMA). In speaking with an AMA lobbyist, I understood they "would not want the public to know that their doctors were not in the knowledge loop." I once asked industry personnel involved in poliovaccine production whether they were still encountering SCMV in poliovaccine production lots. After some hesitation that disappeared as we all identified ourselves as parents, the straightforward answer was "not infrequently." Armed with this information I again requested of an FDA official to please use modern techniques such as the polymerase chain reaction (PCR) to screen poliovaccine lots for SCMV. "We would not know what to do with a positive result" was his answer.

Continued sequencing of the prototype SCMV-derived stealth virus have helped substantiate the original suggestion that stealth adapted viruses simply lack the critical target antigens for cellular immune recognition. More impressively, the virus has the capacity to assimilate genes from infected cells and from bacteria. The cellular genes identified within the stealth virus include a gene with potential oncogenic (cancer causing) activity. The bacterial genes serve a wide range of metabolic functions that could enhance bacterial growth. Human and animal viruses with bacterial sequences represent a novel life form that has been christened viteria. The recombination of viral, bacterial and cellular genes within broadly infectious viteria is clearly of major medical and Public Health significance. For instance, it could provide a viral explanation for positive findings in clinical assays designed to detect various bacteria including the Borrelia burgdorferi (the agent for Lyme disease), mycoplasma, and chlamydia. FDA and CDC were informed of the publication of the results. It was disheartening, yet challenging, that neither organization responded. NIH was also notified but merely acknowledged that research is supportable by grants.

During the last decade, I have written several clinical articles describing stealth virus infected patients with complex illnesses. The patients have included children with autism, adults with psychotic disease and several individuals with chronic fatigue/fibromyalgia syndrome. An additional recent publication described a stealth virus infected child whose illness began in 1997 as a behavioral problem. It took over seven months before the illness was attributed to brain damage, as confirmed by magnetic resonance imaging (MRI). Even then the neurologist was unable to detect impaired motor or sensory functions. A brain biopsy performed shortly after the essentially normal clinical examination showed marked vacuolating/spongiform change. The child's clinical condition progressively deteriorated. He was examined at several major medical centers where it was wrongly concluded that he had a genetic disease from which he would soon die. He was shown to be stealth virus infected by tissue culture and significantly improved with anti-viral therapy, although he still has major residual deficits.

Where is the Public Health concern that a childhood viral infection was not recognized at major medical centers. Where is the interest in the many other children who have tested positive for stealth viruses. Why the lack of discussion about possible brain damage causing national tragedies such as school shootings, and the increasing prevalence of autism, attention deficit, asthma and sudden infant death syndrome. Are stealth virus infected patients populating our psychiatric institutions, allergy clinics and even our cancer wards.

The world and, in particular, its children appear to be at risk for stealth adapted viruses. The contribution of vaccines to the formation and dissemination of these viruses should be an open topic for scientific discussion. This is not occurring with those presently in charge of overseeing the safety of the Nation's immunization program.

W. John Martin, M.D., Ph.D.
Center for Complex Infectious Diseases
Rosemead CA 91770