B. F. Elswood (1) and R. B. Stricker (2)(*)
(1) University of California, San Francisco, CA 94143, and
(2) California Pacific Medical Center, San Francisco, CA 94120
(*) Corresponding author
Submitted January 3, 1992, accepted February 2, 1993.
Reprinted from Research in Virology, vol. 144, 1993, pp. 175-177.
LETTER TO THE EDITOR
More than ten years after the acquired immunodeficiency syndrome (AIDS) burst upon the scene, the origin of this devastating pandemic remains a mystery. Only two facts about human immunodeficiency virus (HIV) type 1, the causative agent of most cases of AIDS, are generally accepted: first, the virus was derived from a precursor simian retrovirus (Myers et al., 1992; Seale, 1989); second, the pandemic unleashed by the virus originated in Africa (Grmek, 1990). However, questions about how and when the virus entered the human population remain unresolved.
Many theories have been proposed to explain the origin of AIDS. The most popular is the so-called “cut-hunter” hypothesis, in which an African hunter was parenterally exposed to monkey blood contaminated with a virus closely related to HIV (Karpas, 1990; Hrdy, 1987). The infected individual then spread the virus throughout Africa via war, prostitution, unbanization and tribal rituals. The problem with this theory is that it would take hundreds of years for HIV to spread in this manner, and AIDS is a relatively recent disease (Krause, 1992; Huminer et al., 1987). A more likely explanation for the AIDS pandemic is a massive population exposure to an HIV-like virus contained in a vaccine.
Such an exposure may have taken place in the Belgian Congo (now Zaire, Rwanda and Burundi) from 1957 to 1959. An oral polio vaccine manufactured at the Wistar Institute in Philadelphia was administered to hundreds of thousands of inhabitants of this area, including 320,000 infants and children (Koprowski, 1960). The vaccine was made in fresh monkey kidney cells that were known to be contaminated with at least 18 different simian viruses (Hayflick et al., 1962). The vaccine itself was found to be contaminated with an “unidentified nonpoliomyelitis virus” that was never characterized (Sabin, 1959).
Several facts lend support to the polio vaccine hypothesis of the origin of AIDS. The vaccine was probably developed in fresh monkey explants from macaque monkeys, although African green monkeys may also have been used, and the exact monkey species remains uncertain (Smith, 1990). It is now known that HIV can infect at least one species of macaque (Agy et al., 1992), and HIV antibodies have been detected in African green monkeys (Lecatsas and Alexander, 1992). Thus HIV or a precursor virus could have contaminated the kidney cell cultures. The area where the vaccination program took place had the highest incidence of AIDS-related diseases in the “pre-AIDS” 1960s and 1970s (Williams, 1992). This observation is consistent with exposure of the population to HIV during childhood prior to dissemination of the virus to other areas during adulthood. In the Congo vaccine trial, the vaccine was administered by nebulizer into the pharynx of each infant and child. This method of administration would expose mucosal cells to the virus and increase the likelihood of latent infection (Lehner et al., 1991). Other infectious diseases in the vaccinated population might also have contributed to an increased susceptibility to an HIV-like virus contained in the Congo vaccine.
Can this hypothesis be tested, and why should it be tested? The answer to the first question lies in the freezers at the Wistar Institute, where samples of the Congo vaccine may still be stored (Curtis, 1992a). The answer to the second question is more esoteric. Understanding the evolution of HIV would help in defining the pathogenesis of AIDS, and it would also yield clues for successful treatment of the disease (Stricker and Elswood, 1992). In addition, by learning from the dark side of vaccine history, we might avoid repeating it.
It has been more than a year since we proposed our polio vaccine/AIDS hypothesis (in September 1991). During that time, there have been numerous articles written on the subject, from Science to the lay press (Curtis, 1992b,c; Cribb, 1992; Cohen, 1992; Fox, 1992). In addition, previous versions of our hypothesis have come to light as a result of this discussion (Ratner, 1988; Gillon, 1992). Reactions to the hypothesis have ranged from excitement and concern to outrage and ridicule. We can only hope that careful consideration of our hypothesis will give AIDS researchers further insight into this deadly disease.
Agy, M. B., Frumkin, L. R., Corey, L. et al. (1992), Infection of Macaca nemestrina by human immunodeficiency virus type 1. Science, 257, 103-106.
Cohen, J. (1992), Debate on AIDS origin: Rolling Stone Weighs in. Science, 255, 1505.
Cribb, J. (1992), Was this science’s biggest blunder? Weekend Australian, April 25-26.
Curtis, T. (1992a), Officials continue to ignore signs of AIDS-vaccine link. Houston Post, August 19.
Curtis, T. (1992b), The origin of AIDS. Rolling Stone, March, 19.
Curtis, T. (1992c), Did a polio vaccine experiment unleash AIDS in Africa? Washington Post, April 5.
Fox, C. H. (1992), Possible origins of AIDS. Science, 256, 1259-1260.
Gillon, R. (1992), A startling 19,000 word thesis on the origin of AIDS: should the JME have published it? J. Med. Ethics, 18, 3-4.
Grmek, M. D. (1990). History of AIDS: emergence and origin of a modern pandemic. Princeton University Press, Princeton.
Hayflick, L., Plotkin, S. A., Norton, T. W. & Koprowski, H. (1962), Preparation of poliovirus vaccines in a human fetal diploid cell strain. Amer. J. Hyg., 75, 240-258.
Hrdy, D. B. (1987), Cultural practices contributing to the transmission of human immunodeficiency virus in Africa. Rev. Infect. Dis., 9, 1109-1119.
Huminer, D., Rosenfeld, J. B. & Pitlik, S. D. (1987), AIDS in the pre-AIDS era. Rev. Infect. Dis., 9, 1102-1108.
Karpas, A. (1990), Origin and spread of AIDS. Nature (Lond.), 348, 578.
Koprowski, H. (1960), Historical aspects of the development of live virus vaccine in poliomyelitis. Brit. Med. J., II, 85-91.
Krause, R. M. (1992), The origin of plagues: old and new. Science, 257, 1073-1078.
Lecatsas, G. & Alexander, J. J. (1992), Origins of AIDS. Lancet, 339, 1427.
Lehner, T., Hussain, L., Wilson, J. et al. (1991), Mucosal transmission of HIV. Nature (Lond.), 353, 709.
Myers, G., MacInnes, K. & Korber, B. (1992), The emergence of simian/human immunodeficiency viruses. AIDS Res. Human Retroviruses, 8, 373-386.
Ratner, A. (1988), Monkey viruses, AIDS and the Salk vaccine. Child & Family, 20, 134-138.
Sabin, A. B. (1959), Present position of immunization against poliomyelitis with live virus vaccines. Brit. Med. J., I, 663-680.
Seale, J. (1989), Crossing the species barrier — viruses and the origins of AIDS in perspective. J. Royal Soc. Med., 82, 519-523.
Smith, J. S. (1990), Patenting the sun. William Morrow Co., New York.
Stricker, R. B. & Elswood, B. F. (1992), Origin of AIDS, Lancet, 339, 867.
Williams, A. O. (1992), AIDS: An African perspective. CRC Press, Boca Raton, FL.
Note from the Editorial Board
Dr. Koprowski, whose name and role have been mentioned in the above letter, is of course encouraged to reply if he wishes to do so.
However, the Editorial Board of Research in Virology felt it appropriate to give its own opinion concerning the possibility raised by Drs. Stricker and Elswood that the origin of the AIDS epidemic may have been the anti-polio vaccination campaigns carried out in Africa in the fifties.
It is legitimate to raise questions about the still mysterious origin of the AIDS epidemic and not to exclude the role of medical actions.
However, available data indicate that HIV1 is not present, nor is any related virus (SIV), in wild rhesus macaques and in cynomolgus monkeys, which were the sources of kidney cultures used to produce the poliovirus for vaccines up until 1961. Only two macaque colonies were infected in US Primate Centers in the seventies, with the so-called SIVmac, probably originating from experimental inoculation of SIVmm, a virus which infected a colony of African soot mangabeys, and which seemingly infected some animals of that same species in Africa.
From 1961 onwards, polio vaccines were prepared from cells derived from African green monkeys and baboons (this was because of SV40 contamination of rhesus macaques).
Both of these monkey species can be infected by a retrovirus of the SIV type, but which is different from SIVmac and SIVmm.
Nucleotide sequence analysis of the genomes of these various primate retroviruses indicates that all of them are very distant from HIV1 and therefore could not be at the recent origin of the latter virus.
Moreover, retrospective PCR studies of tissues from a British sailor who died of AIDS in 1959 indicate the presence of HIV1 in a European adult already at that time.
The primate virus which is closest to HIV1 is the CPZ virus isolated from lymphocytes of a chimpanzee captured in Gabon. Since chimpanzee tissues have never been used for poliovirus production, it is difficult to imagine how massive contamination of polio vaccines by a virus rarely detectable in chimpanzees could have occurred.