DISEASES OF BLOOD AND STEEL

What about the chronic disease that sparked the cur-rent concern over emerging diseases? The conventional wisdom is that AIDS arose from a secluded area in Africa where a virus was transmitted to humans from another primate, spread locally, and then spread globally within a decade or so. If this interpretation is correct, the AIDS pandemic, together with the lack of similar novel pandemics throughout the past two centuries, gives some perspective on the threat of new pandemics over the next few centuries. The threat would be real over the long run but probably not imminent over the short run. Yet according to a different hypothesis for the origin of AIDS, most thoroughly presented by Edward Hooper in his book The River, the pandemic may have been more controllable than is generally believed. The control in this case would not have been generated from a surveillance system or an ability to combat the pathogen after it was globally embedded. Rather, the control could have been generated by better safeguards of medical procedures.
Resolving the question of the origin of AIDS bears on the broader theme of where the future threats to human health will come from. AIDS is a chronic malady. The arrival of the AIDS pandemic therefore accords with the idea that the stealth infections are the modern threats for the most prosperous countries; but the various explanations for the origin of AIDS implicate different social, geographic, and biological sources of the AIDS pandemic. AIDS is the only twentieth-century example of a new kind of pandemic plague; its emergence therefore provides the only hard evidence of how a pathogen has emerged—and therefore can emerge—in modern times from a local source to cause a fundamentally new kind of pandemic plague. If we ignore this bit of hard evidence, we risk our future.
Hooper argues that the contamination of polio vaccines used during the late 1950s in sub-Saharan Africa is the source of the AIDS pandemic. This idea has surfaced in several places since the early 1990s. It has been dismissed by many experts, often with ridicule. But ridicule from experts is not necessarily a good reason for rejecting an idea. To move toward the truth, we need to assess the evidence.
Viruses need to grow in host cells. So to generate polioviruses in sufficient abundance for use in polio vaccines, virologists grew the viruses in cells taken from other primates, such as green monkeys. The cells and viruses were grown together in flasks containing media suitable for cell growth. After the viruses had replicated to high densities, they were separated from the monkey cells, media, and cellular debris left in the media by the viral feast. The viruses were then used in the next phase of vaccine preparation, and everything else was discarded. Ideally only the poliovirus would be isolated during this step, but the laboratory procedures that separate polioviruses at this stage often fail to exclude other viruses that might have been living in the cells that were taken from the monkeys and that reproduced in the cell culture right along with the poliovirus. Without adequate safeguards, these viruses could inadvertently be harvested with the polioviruses and included in the vaccine as contaminants.
Just this kind of contamination of polio vaccines occurred during the 1950s and early 1960s. A particularly worrisome contaminant, a virus called SV40 (for simian virus number 40), was inoculated into children along with the killed polio vaccine virus. The procedure used for killing the poliovirus during the preparation of the Salk vaccine did not kill all of the SV40s. The concerns over contamination of oral polio vaccines have generally been even greater because oral polio vaccines introduce live viruses and so were not subjected to treatments that inactivate poliovirus and might similarly inactivate other stowaway viruses. Indeed, some viruses have been found in live polio vaccines, including at least one retrovirus, the family of viruses to which HIV belongs.
The transmission of SV40 in polio vaccines lends some credibility to the possibility that a precursor of HIV could have similarly contaminated cells used for the production of polioviruses. This “contaminated vaccine” hypothesis offers a mechanism for what looks like a simultaneous transfer of different immunodeficiency viruses to humans from simians (nonhuman primates such as monkeys and chimpanzees). The names used for these viruses can be confusing. When one of them is isolated from humans it is called HIV (human immunodeficiency virus). When one is isolated from a simian (a monkey or chimpanzee) it is called SIV (Simian Immunodeficiency Virus). HIV experts believe that different HIVs have arisen from the transfer of different SIVs from simians to humans. The pandemic HIVs belong to one half of the HIV evolutionary tree and are referred to as HIV-Is. The pandemic HIVs make up the main cluster of viruses in the HIV-1 tree and are referred to as group M, M being short for “main.” Most of the other HIV-Is are found in West Central Africa, particularly Cameroon and Gabon; they are collected into a group called O, for “outgroup.” The other half of the HIVs arose in West Africa and are referred to as HIV-2s. The HIV-Is are most similar to a group of SIVs found in chimpanzees; the HIV-2s are most similar to a group of SIVs found in sooty mangabeys.
Evolutionary relationships among the different HIVs and SIVs can be deduced by comparing the sequences of building blocks that make up the genes of the different viruses. All else being equal, the more similar the genetic sequences of the viruses, the more recent is the last common ancestor shared by the two viruses. These evolutionary trees allow researchers to visualize branching points between different genealogical lineages of viruses. When these family lineages are combined with information about the species from which the viruses were isolated, researchers can speculate about when viruses may have moved from one species to another. The more complete the evolutionary tree, the more reliable the interpretation. Some researchers using this method suggest that several viruses recently entered humans from simians over a short period of time, perhaps a decade or even less.
If this interpretation is true, it raises a perplexing question. Why would immunodeficiency viruses stay put in simians for thousands of years and then suddenly, within a decade, be transferred several times into humans? The contaminated-vaccine hypothesis offers an explanation: cells used for oral polio vaccines were contaminated with several different SIVs that were transmitted to humans during the first decade of the oral polio vaccination program, thus generating several different lineages of HIVs.
Some incarnations of the contaminated-vaccine hypothesis can be dismissed on the basis of available information. Because monkey kidney cells were the standard for growing polioviruses, and SIVs were present in green monkeys, early attention, prompted by New Hampshire attorney Walter Kyle, focused on this possible source of HIV. Critics rightly pointed out that the SIVs found in green monkeys were not the viruses implicated in the origin of HIV. The genealogical trees instead implicated SIVs found in sooty mangabeys for the origin of HIV-2, and SIVs found in chimpanzees for HIV-1. Hooper and other defenders of the contaminated-vaccine hypothesis pointed out that many different primates may have been used as sources for cells, perhaps even chimpanzees and sooty mangabeys. Vaccine researchers in sub-Saharan Africa may have used locally available primates—chimpanzees in one area, green monkeys in another, and mangabeys in still another. This potential for local use confounds explanations of natural origin, which often assume that the presence of similar viruses in humans and nonhuman primates of a given area implies transmission from the primates to the humans by natural means. The contaminated-vaccine hypothesis suggests that the same pattern may arise from artificial transmission because cells from indigenous animals were used to prepare the vaccines of a particular region.
Critics also pointed out that kidney cells were not the right kind of cells for primate immunodeficiency viruses, but defenders responded that the right kind of cells—white blood cells—are often present in cultures of kidney cells that are used in vaccine preparation. White blood cells containing the SIVs could therefore contaminate vaccine stocks made from kidney cells.
The contaminated-vaccine hypothesis was given added weight when the great evolutionary biologist William D. Hamilton emphasized the need to evaluate it more rigorously in the foreword to Hooper’s book. The mild-mannered Hamilton had a long track record of putting forward groundbreaking ideas without fanfare, being overlooked, and then, over the ensuing decade or so, being borne out by the evidence. Evolutionary biologists have learned to listen carefully to his soft-spoken assertions. Hamilton did not claim that contaminated vaccine lots introduced a simian virus into humans to create HIV. Rather, in keeping with principled guidelines of scientific inquiry, he suggested that this idea was being too eagerly dismissed without adequate evidence.
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