later brought this to the attention of Essex, her thesis adviser, and together with colleagues from Southborough, they started to look for what was killing those monkeys. Based on their knowledge of FeLV and other factors, they wondered whether it might be a retrovirus infection.
Taking blood samples from macaques, they did find a new retrovirus, and saw that it was closely related to the AIDS virus. Because this was 1985, they used Gallo’s slightly misleading label (HTLV-III) for what would soon be renamed HIV. Their monkey virus would be renamed too and become, by analogy, simian immunodeficiency virus: SIV. The group published a pair of papers in Science, which had grown hungry for AIDS breakthroughs. This discovery, they wrote, could help illuminate the pathology of the disease, maybe even advance efforts to develop a vaccine, by providing an animal model for research. Only a single sentence at the end of one of the papers, a modest but pertinent comment dropped in like an afterthought, noted that SIV might also be a clue toward the origin of HIV.
It was. Phyllis Kanki performed the lab analysis of samples from the captive macaques and then made it her business to wonder whether the same virus might exist in the wild. Kanki and Essex looked at Asian macaques, testing blood samples from wild-caught animals. They found no trace of SIV. They tested other kinds of wild Asian monkey. Again, no SIV. This led them to surmise that the macaques at Southborough had picked up their SIV in captivity by exposure to animals of another species. It was a reasonable guess, given that the primate center at one point had a monkey playpen in its lobby, where Asian and African infant monkeys were sometimes allowed to mingle. But then which kind of African monkey was the reservoir? Where exactly had the virus come from? And how might it be related to the emergence of HIV?
“In 1985, the highest rates of HIV were reported in the U.S. and Europe,” Essex and Kanki wrote later, “but disturbing reports from central Africa indicated that high rates of HIV infection and of AIDS prevailed there, at least in some urban centers.” The focus of suspicion was shifting: not Asia, not Europe, not the United States, but Africa might be the point of origin. Central Africa also harbored a rich fauna of nonhuman primates. So the Harvard group got hold of blood from some wild-caught African simians, including chimpanzees, baboons, and African green monkeys. None of the chimps or the baboons showed any sign of SIV infection. Some of the African green monkeys did. It was an epiphany. More than two dozen of the monkeys carried antibodies to SIV, and Kanki grew isolates of live virus from seven. That finding too went straight into Science, and the search continued. Kanki and Essex eventually screened thousands of African green monkeys, caught in various regions of sub-Saharan Africa or held captive in research centers around the world. Depending on the population, between 30 and 70 percent of those animals tested SIV-positive.
But the monkeys weren’t sick. They didn’t seem to be suffering from immune deficiency. Unlike the Asian macaques, the African green monkeys “must have evolved mechanisms that kept a potentially lethal pathogen from causing disease,” Essex and Kanki wrote. Maybe the virus had changed too. “Indeed, some SIV strains might also have evolved toward coexistence with their monkey hosts.” The monkeys evolving toward greater resistance, the virus evolving toward lesser virulence—this sort of mutual adaptation would suggest that SIV had been in them a long time.
The new virus, SIV as found in African green monkeys, became the closest known relative of HIV. But it wasn’t that close; many differences distinguished the two at the level of genetic coding. The resemblance, according to Essex and Kanki, was “not close enough to make it likely that SIV was an immediate precursor of HIV in people.” More likely, those two viruses represented neighboring twigs on a single phylogenetic branch, separated by lots of evolutionary time and probably some extant intermediate forms. Where might the missing cousins be? “Perhaps, we thought, one could find such a virus—an intermediate between SIV and HIV—in human beings.” They decided to look in West Africa.
With help from an international team of collaborators, Kanki and Essex gathered blood samples from Senegal and elsewhere. The samples arrived with coded labeling, for blind testing in the laboratory, so that Kanki herself didn’t know their country of origin, nor even whether they derived from