The Puzzling Origins of AIDS Although no one explanation has been universally accepted, four rival theories provide some important lessons Jim Moore hortly after the 1983 discovery of or to the mid-20th century, as well as its an experimental oral polio virus vaccine Sthe human immunodeficiency vi- absence previously in the New World took place from 1957 to 1960 in what are rus (HIV), the pathogen responsible for (which imported some 10 million Afri- now the Democratic Republic of the Con- AIDS, investigators became aware of can slaves during the 16th through 19th go, Burundi and Rwanda, seemingly the a strangely similar immune deficiency centuries), that transfer appears to have “hearth” of the global AIDS epidemic. disease afflicting Asian monkeys (ma- happened relatively recently—exactly When interviewed by Curtis, Hilary Ko- caques) held in captivity in various U.S. when is a point of considerable debate. prowski, the polio-vaccine pioneer who research labs. Soon, virologists identified And why did two distinct simian vi- mounted that massive campaign, could the culprit: a simian immunodeficiency ruses with which humans have appar- not recall or find documentary evidence virus (SIV) that is found naturally in a ently coexisted for centuries, or even as to whether his group had used kid- West African monkey species, the sooty millennia, suddenly pass into humans ney cells from green monkeys or Asian mangabey (Cercocebus atys), but is harm- multiple times within a few decades? macaques (which do not naturally carry less to that host. This virus, denoted The answers to these questions have an SIV). If culture media contained SIV SIVsm, is genetically similar to a weakly been slow in coming, despite the con- (a possibility, given that the techniques contagious form of the AIDS virus that is siderable efforts of molecular biologists available during that era were unable largely restricted to parts of West Africa, to understand the nature and evolution HIV-2, and thus is considered its likely of primate immunodeficiency viruses. Figure 1. Investigators puzzle over why the precursor. More recent work has shown I am not one of those molecular biolo- AIDS epidemic struck when it did. A simian that the closest relative of the primary hu- gists; rather, I became a player in the virus very similar to HIV-1 (the HIV type re- sponsible for the vast majority of AIDS cases) man immunodeficiency virus (HIV-1) is field of AIDS-origin research through is found in the chimpanzees of Central Africa, another simian immunodeficiency virus, my interest in chimpanzee socioecol- suggesting that these animals naturally harbor one carried by chimpanzees (SIVcpz). ogy. Although I am partial to a theo- the progenitor virus. The leading idea is that After comparing the SIVs in chimpan- ry I helped to fashion for why AIDS this virus first passed through cuts to someone zees and sooty mangabeys with HIV-1 emerged when it did, with time it might hunting or butchering a chimpanzee, but this and HIV-2 strains, investigators conclud- become clear that a competing idea bet- theory alone cannot explain why the AIDS ed that there must have been multiple ter accounts for genesis of the epidemic. epidemic did not arise before the 20th century, transmission “events” from simians to Or perhaps the answer will prove to lie because hunting chimpanzees for meat has humans—at least seven for HIV-2 (some with some complex combination of fac- presumably been going on for thousands of of which are known from only a single tors that no single explanation presently years. The author and two of his students sug- gested that the forced labor and population person who lives near mangabeys carry- encompasses. Whatever the case, the movements imposed on the natives of Central ing a uniquely similar SIV) and three for solution almost certainly will come from Africa during the colonial era—and the unster- HIV-1, the virus now infecting some 40 one or more of four competing theories. ilized needles used in health campaigns as- million people worldwide. sociated with those disruptions—might have How did SIVcpz and SIVsm cross Theory 1: Tainted Polio Vaccine created conditions favoring the transfer of the over into humans and become patho- The first theory is the most controversial. progenitor virus from chimpanzees to humans genic? Given the lack of historical refer- In a 1992 article in the magazine Rolling and its adaptation to become HIV. Vintage ences to AIDS-like disease in Africa pri- Stone, journalist Tom Curtis suggested postcards show some relevant scenes from the that HIV could have resulted from the region during the early part of the 20th century. use in Africa of an experimental oral po- Clockwise from top: vaccination in the Congo Free State (now Democratic Republic of the Jim Moore received his doctorate in biological an- lio vaccine (OPV), one contaminated by thropology from Harvard in 1985, where he studied Congo); Haute-Sangha (a province of what is a then-unknown SIV carried most prob- demography and sociality in primates. Since then now Central African Republic), doctor vacci- he has been on the faculty of the University of Cali- ably (Curtis supposed) by African green nates natives in the field; French Congo (now fornia, San Diego, where his research focuses on monkeys. Green-monkey kidney cells Republic of the Congo), missionaries vaccinate primate behavioral ecology. Address: Anthropology were widely used as a substrate to grow in the field in the vicinity of Brazzaville; Bel- Department, University of California, San Diego, viruses for research and vaccine produc- gian Congo (now Democratic Republic of the La Jolla, CA 92093. Internet: [email protected] tion. And one of the first major trials of Congo), construction of a bridge over a ravine. © 2004 Sigma Xi, The Scientific Research Society. Reproduction 540 American Scientist, Volume 92 with permission only. Contact [email protected]. © 2004 Sigma Xi, The Scientific Research Society. Reproduction www.americanscientist.org © 2004 Sigma Xi, The Scientific Research Society. Reproduction 2004 November–December 541 with permissionwith permission only. Contact only. [email protected]. Contact [email protected]. to guard against unknown viruses that Multiple localized strains of HIV have delphia) were tested and found nega- did not cause overt symptoms in their now been discovered, and mass vac- tive for both chimpanzee DNA and SIV. monkey hosts), more than 900,000 peo- cination appears unlikely to account for However, this result did not rule out ple might have received it with their all of them. But the early distribution of the possibility, previously suggested by medicine, laying the basis for the current the major pandemic strain, HIV-1 group Hooper, that local amplification of the epidemic. M (for “main”), seems to fit reasonably live-virus vaccine in Africa (to create Curtis credited this theory to Blaine well with the location of Koprowski’s more doses) could have introduced the Elswood, a Californian AIDS activist. campaigns, and the OPV theory now is SIV. The key issue is thus whether chim- Interestingly, the idea that the admin- applied primarily to this strain. panzee kidneys were used as a culture istration of a contaminated oral polio Contamination of OPV is the only one medium at any stage of Koprowski’s vaccine might have been involved in of the four current theories that is read- vaccine program. There is eyewitness the genesis of AIDS was suggested ily falsifiable: Finding the HIV-1 group testimony on both sides of this question, independently by two others at about M virus in a tissue sample that predated and failure to find SIVcpz in a handful the same time. The first to do so was the suspect vaccine would eliminate this of samples of the live vaccine strain of Louis Pascal, who like Elswood is not possibility. So far that has not happened. the type used in Africa does not prove a scientist. After years of rejections, Still, many investigators give the theory the virus was absent in (putative) locally Pascal, a New Yorker, finally man- little weight for other reasons, which produced batches. aged in 1991 to get the University of has led to the widespread belief that the A second reason to question the OPV Wollongong in Australia to publish a theory has been definitively disproved. theory also came to light in 2000, with a paper describing his ideas. Not sur- In 2001, for example, Science magazine report in Science by Bette T. Korber (of prisingly, few noticed it. Attorney published a piece titled “Disputed AIDS Los Alamos National Laboratory) and Walter Kyle also published a broadly Theory Dies its Final Death,” and Na- colleagues. They used molecular differ- similar theory in The Lancet, a British ture ran one under the heading “Polio ences among HIV-1 group M subtypes medical journal, in 1992. Since then, Vaccines Exonerated.” Earlier this year to estimate the date of their last com- writer Edward Hooper, author of the Nature also published “Origin of AIDS: mon ancestor. The conclusion: 1931 controversial 1999 book The River, has Contaminated Polio Vaccine Theory Re- (with 95 percent confidence limits giv- become the contaminated-vaccine the- futed”—a surprising title given that this ing the range 1915 to 1941), preceding ory’s most ardent supporter. Hooper, theory ostensibly died three years ago. OPV administration by decades. How- noting a passing mention by Curtis of The recent findings of various mo- ever, the calculation of such common- a chimpanzee colony run by Koprow- lecular biologists have indeed failed to ancestor dates can be thrown off by ge- ski’s team, suggested that kidneys provide support for the OPV theory. For netic recombination among subtypes from these chimpanzees—not from example, in 2000 a few existing samples (“viral sex”), which can make such dates green monkeys—may have been the of the vaccine from Koprowski’s home come out too early, and there is increas- original source of the virus.