"EMERGING VIRUSES: AIDS & EBOLA: Nature, Accident or Intentional"
by Leonard G. Horowitz
Tetrahedron Inc. Rockport, MA 1996.
Foreword written by
W. John Martin, M.D., Ph.D. http://www.ccid.org/safety.htm#
All at onces it seems, new viruses and virus-related diseases have threatened the health of humans and many animal species. How did this situation arise? Could it be that scientific studies and the emergence of new pathogens are not totally unrelated events? In writing this text, Dr. Horowitz has bravely questioned the extent to which scientific research and lax government oversight may have contributed to the present and coming plagues.
Open debate on this issue has been soundly discouraged. Opponents to open dialogue on the apparent relationship between early viral research and the latest germ discoveries argue that little good, and considerable harm, would come from a full disclosure of the facts. Exposing the truth, many believed, would likely: 1) tarnish the reputations of certain scientists, 2) make it more difficult to maintain science funding, 3) promote antigovernment sentiment, and 4) likely leave many issues unresolved. Others argued that it was simply too late to undo past mistakes. The fact that a better understanding of the new viruses' origins could lead to new treatment approaches, and, more importantly, to ways of preventing future outbreaks, was disregarded.
In considering the recent genesis of HIV and the Ebola viruses, Dr. Horowitz's book has explored three areas of great general and scientific interest: 1) the history of intensive research into the viral causes of cancer wherein readers can become familiar with the many, now questionable, virus transmission experiments, 2) the CIA and Department of Defense efforts to develop and defend against biological weapons of germ warfare. Here Dr. Horowitz should be especially congratulated for presenting well-researched little known facts that, though highly disturbing, are an important piece of history that may also bear heavily on the emergence of new viruses, and 3) vaccine production. Clearly, as anyone who reads this book will conclude, there is a great need for more open dialogue concerning the past and present risks inherent in the production of live viral vaccines. It is this topic that I am pleased to address here.
In 1798, Edward Jenner, an English physician advanced the use of cowpox (vaccinia)
virus for immunizing humans against smallpox. He recognized that pathogens can behave
differently while infecting different species. Indeed, he theorized that the vaccinia
infection, which caused mild problems for cows, caused more severe ailments in horses.
Only after adapting to cows, did vaccinia acquire limited infectivity for humans. The open
sores that humans developed were far less severe than those induced by smallpox (variola)
virus and essentially remained localized to the site of inoculation. Moreover, contact
with vaccinia virus caused individuals to become virtually immune to the widespread
disease caused by the smallpox virus. The success of vaccination is reflected in today's
total elimination of smallpox as a disease.
Jenner's vaccination approach was followed in the twentieth century by Pasteur's use of rabies virus grown in rabbit's brain, and by Theiler's finding that he could reduce the effect of yellow fever virus by growing it in chicken embryos.
These successes set the precedent for other scientists to attempt to reduce the pathogenicity of other human and animal viruses by inoculating them into foreign species. Although we now look back with some disdain at the crudeness of early immunization experimentssuch as the 1938 injections of polio virus, grown in mouse brains, into humans, most people, including scientists, are unaware that we still use primary monkey kidney cells to produce live polio virus vaccine. Likewise, dog and duck kidney cells were used to make licensed rubella vaccines. Experimental vaccines, grown in animal tissues and intended for human use, were commonly tested in African monkeys, and it is likely that many of these monkeys were released back into the wild. This practice may have led to the emergence of primate diseases, some of which could have been transmitted back to humans.
Large numbers of rural Africans were also chosen as test recipients of experimental human vaccines.
In veterinary medicine, live viral vaccines have been widely used in domestic pets and in animals destined to become part of the foodchain. Undoubtedly, many cross-species transfer of viruses have occurred in the process. Even today, more than ten foreign species are used to produce currently licensed vaccines for cats and dogs.
The general acceptance of the safety of cross-species produced vaccines was supported in part by the generalization that there are inherent restrictions to the interspecies spread of disease. Thus, like vaccinia, mostviruses are less harmful, but others can be far more dangerous after invading a foreign host. One dramatic example is that of the human infection caused by the herpes-type monkey B virus. This germ remains a rather harmless invader of monkeys, but place it in humans, and striking, severe, acute illness results which commonly ends in death. Likewise, a modified horse-measles-virus (morbillivirus) can be lethal to man. Other examples include the relatively mild dog distemper morbillivirus that was blamed for the death of some 3,000 lions in the Serengeti; the cat-adapted parvovirus that caused worldwide infection in dogs; and the mouse-derived lymphocytic choriomeningitis virus that caused severe hepatitis in monkeys.
It is the slow onset of disease that can be particularly baffling, especially when considering potential viral diseases transmitted through vaccines. Most acute diseases are relatively easy to recognize and amenable to further prevention. The delayed onset of chronic debilitating diseases that could be associated with animal viruses finding their way into a new species, e.g., man, are much more challenging. Here, the association between the germ and the symptoms it causes is obscured. Such an association would be especially hard to establish if the clinical features presented during the illness are poorly defined and mimic those of other known ailments. One example is the 1996 concern over the food-borne transmission of the prion disease scrapie. Initially carried by infected sheep, this protein caused bovine spongiform encepalopathy in "mad" cows. Then it was apparently passed on to humans resulting in juvenile Crutzfeldt-Jakob disease.
While in some cases disease transmission has been traced to certain vaccine lots, other times, even widely distributed licensed vaccines have been found to be contaminated. Yellow fever vaccine was known to contain avian leukosis virus.* During World War II, batches of yellow fever vaccines were inadvertently also contaminated with hepatitis B virus. Current measles, mumps, rubella (MMR) vaccines contain low levels of reverse transcriptase, an enzyme associated with retroviruses. Both Salk and Sabin polio vaccines made from rhesus monkeys contained live monkey viruses called SV40, short for the fortieth monkey virus discovered. As Dr. Horowitz documents, polio vaccines may also have contained numerous other monkey viruses, some of which may have provided some building blocks for the emergence of HIV- 1 and human AIDS .
The finding of SV40 in rhesus monkey kidney cells, during the early 1960s, led to a rapid switch to African green monkeys for polio vaccine production. Kidney cells from African green monkeys, still being used to produce live polio vaccines today, may have been infected with monkey viruses that were not easily detectable. The monkeys used before 1980, for example, were likely to have been infected with simian immunodeficiency virus (SIV9a virus genetically related to HIV-1. The origin of this virus and whether it contaminated any experimental vaccines are issues that need addressing.
* Editor's note: This is the retrovirus that causes leukemia in chickens.
What makes vaccines so troublesome is that their production and administration allows viral contamination to breach the two natural barriers that often restrict cross-species infections:
First is the skin. Direct inoculation of vaccines breaches this natural barrier and has been shown to produce increased infections in animals and humans. Such was the case when SV40 was injected intramuscularly in contaminated Salk polio vaccine. Later it was learned that Sabin's orally administered polio vaccines were safer since the live simian viruses were digested in the stomach and thereby inactivated. Additionally risky, when it comes to breaking the skin barrier, is the chance of transmitting viruses from one person to another through the use of unsterilized needles.
Second is the unique and natural viral surface characteristics that reduce the chance that viruses might jump species. The mixing of vaccine viruses with others found in the cells and tissues used to develop the vaccine can potentially lead to the development of new recombinant mutants that are more adaptive and have wider host range than either of the original viruses. This can especially happen when a live viral vaccine produced in cells from one species is then given to another species.
Also of concern is the transmission of new genetic information along with the vaccine virus. For instance, early adenoviral vaccines, produced in rhesus monkeys' kidney cells, developed to protect people against respiratory infections, incorporated parts ofthe SV40 virus that remained as a vaccine contaminant even after production of the vaccine virus was switched to human cells. Numerous other vaccines, especially those that were used in early field trials in Africa, should be analyzed for those genetic components which characterize today's monkey and human pathogens.
Unfortunately, this new awareness of potential problems with live viral vaccines has had little impact on the viral vaccine approval process. Seemingly, U.S. government agencies, principally the FDA, have been reluctant to impose additional testing requirements on vaccines once they are approved for use. In effect, government officials are given a single opportunity to decide on a new vaccine's safety. Even then, government regulators themselves may be denied certain critical information belonging to the vaccine industry. Specifically, FDA regulations are written so as not to compel industry to reveal testing information not directly pertaining to the lots submitted for clinical use. The FDA is reluctant to admit its lack of knowledge about vaccines to the medical/scientific community. Yet, practicing physicians are expected to unquestionably endorse the safety of vaccines under all circumstances and to all individuals.
Aside from these bureaucratic barriers to viral vaccine safety assurance, there are additional major concerns. Since vaccine development information is considered proprietaryprotected by nondisclosure policies government officials and researchers must shield potential safety issues from public scrutiny. This censorship is rationalized by the all too persuasive argument that vaccines cannot be criticized lest the public become non-compliant in taking them. Finally, this silence is buttressed by the small number of people capable of critically evaluating vaccine manufacturing and safety testing procedures. In essence, health care professionals and the general public know little about the possible dangers of live viral vaccines.
As an illustration, the issue of possible simian cytomegalovirus (SCMV) contamination of live polio virus vaccines has been suppressed since 1972. On the eve of Nixon's war on cancer, a joint Lederle Corporation/FDA Bureau of Biologics study showed that eleven test monkeys, imported for polio vaccine production, tested positively for SCMV. The reluctance of the FDA to act on this matter was revealed in a corporate memo delivered the following year. Even in 1995, following a report to FDA officials concerning a patient infected with a SCMV-derived virus, no new in-house testing of polio vaccines for SCMV has occurred. Moreover, this author's specific requests for vaccine material to undertake specific testing, were denied on the basis of protecting "proprietary" interests.
This basic flaw in the regulatory process must be addressedthe FDA must be responsive to the medical-scientific community's need for accurate information regarding the potential hazards of products released for use in society. In the event that public health and safety concerns arise, industry should wave its right to maintain proprietary intelligence. This would enable the FDA to disclose more information concerning the safety of FDA regulated products to the medicalscientific community. Such a proposal should be included in the all pending and future FDA reforms.
It is against this background of possible risks of past viral vaccine studies, uncertain biological recombinants, bureaucratic censorship, a rising tide of medical consumerism in the information age, and an urgent need for legislative FDA reform, that Dr. Horowitz's work contributes. At minimum, what you are about to read exposes many important facts which, unfortunately, few people realize and all would be better off knowing. At best, this important text raises far greater hope that by knowing theirorigin, cures for the many complex emerging viruses, including AIDS, may be forthcoming.
-W. JOHN MARTIN, M.D. PH.D.*