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Authors: Laurie Garrett

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“In many ways an urban center may be considered an ecosystem that can amplify infectious diseases,” they concluded.
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“This appears to have happened with HIV in various African cities. The conclusion we draw from our study is that AIDS in Central Africa has spread not simply because the virus is present, since in one remote area that prevalence of HIV infection has remained low for over a period of 10 years. A change in the interaction between the agent, the host, and the environment is usually required for an epidemic to develop. In this context, we believe that social change, including the effects of urbanization and population movements, merits consideration in our attempt to understand the changing patterns of disease.”
Understanding how human activities were related to the presence and spread of HIV in Central Africa before 1981 still didn't answer questions about when and where the virus first emerged. The 1959 Manchester case argued for HIV's presence somewhere along the sailor's voyages around the planet, going back nearly three decades. But how long had it been in Africa?
Max Essex's group at Harvard, together with scientific teams from Emory University in Atlanta, Duke University in North Carolina, and the University of Washington in Seattle, tested 1,213 plasma samples collected between 1959 and 1982 in Zaire, Congo, South Africa, and Mozambique: one 1959 sample repeatedly tested positive for antibodies to HIV. It came from an individual (gender not known) who resided in colonial Leopoldville in 1959. Leopoldville was renamed Kinshasa when Patrice Lumumba took power; the 1959 sample was designated the “Leopoldville strain.”
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The debate about where and when the human immunodeficiency virus emerged was radically affected by two other discoveries: that Old World monkeys carried HIV-like viruses, but New World simians did not; and that there was a second species of AIDS virus, dubbed HIV-2, which seemed to exist only in Africa.
The discovery of monkey AIDS viruses dated back to the earliest days of the recognized human epidemic, when scientists with the California Primate Research Center in Davis noted similarities between disease symptoms experienced by gay men and those seen in four strange disease outbreaks among monkeys in their research facilities. The first outbreak occurred in 1969 and lasted six years. During that time, forty-two macaques suffered lymphomas and a host of opportunistic infections related to severe T-cell immune system depression. Two other outbreaks of macaques suffering immune deficiency and disease occurred in the California facility between 1976 and 1978.
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The disease, dubbed SAIDS, or simian AIDS, was produced experimentally by injecting the blood of two dying monkeys into four healthy rhesus that had been separately housed. All the injected animals became
sick, some developing Kaposi's-like skin patches.
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The California work indicated two things: the disease was transmissible, it could be experimentally created in susceptible animals, and it had existed—at least among captive macaques—since 1969.
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As described earlier in this chapter, in 1985 researchers at Harvard University and the New England Regional Primate Center discovered two simian AIDS viruses infecting their captive animals. The viruses were dubbed SIVmac (previously, STLV-IIImac) and SIVagm (STLV-IIIagm). While SIVmac seemed to be dangerous to macaques, Max Essex's group found that most African green monkeys carried SIVagm without any apparent ill effects.
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In March 1986 the Franco-American dispute over discovery of HIV was replayed, as Essex's Harvard group clashed with Montagnier's Pasteur lab over discovery of a second species of human AIDS virus. Dubbed HTLV-IV by Essex and LAV-II by Montagnier, the viruses were found exclusively in West Africa.
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For nearly six years the two laboratories would argue over who first discovered the second AIDS virus (eventually named HIV-2), how dangerous the virus was to human beings, and what its relationship was to the monkey viruses.
The Harvard group's virus was found in the blood of healthy Senegalese female prostitutes, and the individuals' immune responses to SIVagm and HTLV-IV were equally strong.
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Describing his new virus as “the missing link,” Essex asserted that it was very close to the monkey virus, and harmless to human beings. Between February 1985 and January 1987, Essex's group analyzed sera obtained from 4,248 West Africans, discovering HIV-2 infection rates that ranged from zero to a high of 19.8 percent among female prostitutes. Few, if any, of the infected individuals were sick, and Essex suggested that HIV-2 might be a “harmless progenitor of HIV-1” that conferred immunity against AIDS upon those carrying the West African virus.
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A battle ensued, with Montagnier's group warning that a new lethal virus was rapidly spreading across West Africa, and Essex's laboratory insisting that the microbe was basically harmless.
“We're saying that we're at the dawn of a new epidemic due to a virus that looks like HIV-1, the AIDS virus, but is different, and can induce AIDS,” said the Pasteur's François Clavel. “There is an epidemic that is rapidly spreading over West Africa of, if you like, HTLV-IV or HIV-2. And it is accompanied by AIDS.”
And Montagnier announced in 1987 that his group had treated thirty individuals who were infected with HIV-2, seventeen of whom had died of AIDS. “This virus is cytopathic for T4 cells,” Montagnier said.
It would eventually turn out that both groups were right and wrong. Essex's closest colleagues at Harvard and in Gallo's lab would do a detailed genetic analysis of HTLV-IV and SIVmac, eventually concluding that the
viruses were not just close cousins, but were
identical
viruses. Presumably, they argued, contamination occurred in Essex's laboratory, resulting in the mixing of monkey and human samples.
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Essex and Kanki would eventually publish a concession on the point, acknowledging that their HTLV-IV was essentially identical to a particular macaque strain of SIV found in an animal in the New England Regional Primate Center, samples of which had been in the Harvard lab. But years later Essex would remain personally unconvinced that a contamination error had actually occurred.
“There's no reason whatsoever to consider SIV and HIV-2 different viruses. You don't consider rabies a different virus if it's in bats or dogs or people. You don't consider eastern equine encephalitis a different virus if it's in mosquitoes or birds or horses. But for some reason this one people will forever think of as a totally different virus if it's called SIV in monkeys or HIV-2 in humans,” Essex would say.
Montagnier's laboratory would be credited with discovery of HIV-2, but would prove wrong about the lethality of the virus. With time it would become clear that HIV-2 was, as Essex and Kanki claimed, far less virulent and perhaps less infectious than HIV-1.
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In Senegal, M'Boup would track HIV-2 for nine years, concluding that it was an older, less dangerous virus, found primarily in middle-aged female prostitutes.
As the technology for analyzing genetic material improved during the 1980s,
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it became possible to compare all the various monkey and human AIDS viruses nucleotide by nucleotide, noting where similarities and differences existed. Using such techniques, scientists would begin to construct family trees for the viruses: lineages of evolution. At the heart of the technique, which was called molecular epidemiology or archeoepidemiology, were a few key assumptions: the more alike two viral genetic sequences were—the higher their degree of homology, as scientists phrased it—the greater was the likelihood that they shared a recent common ancestor, or that one virus was descendant from the other; because genetic divergence required time, degrees of viral variation could be correlated with a timetable of years or centuries; there were certain genetic features that were so essential to the survival of HIVs and SIVs that they would be conserved over generations of viruses; and it was unlikely that evolution progressed from humanly infectious virus to monkey virus, therefore the family tree began with SIV.
Each of these assumptions would be challenged with time, but the basic approach would survive criticism, remaining in use well into the 1990s.
Gallo's lab used such techniques to determine the genetic DNA sequences of SIVagm, HIV-1, and the Pasteur group's strain of HIV-2, discovering that the two human viruses (HIV-1 and HIV-2) shared about 43 percent genetic homology. In other words, they were more different than they were alike. The SIVagm and HIV-1 were also about 43 percent homologous. But SIVagm and HIV-2 shared 72 percent of their genetic sequences.
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Vanessa Hirsch's group at Georgetown University in Washington, D.C., found 91.4 percent homology for the envelope genes of SIVagm and SIVmac.
A joint Pasteur Institute/New England Regional Primate Center study of HIV-2, SIVagm, SIVmac, and HIV-1 confirmed the Georgetown findings, showing that SIV and HIV-2 were close, sharing over 75 percent homology. In contrast, HIV-1 had only 40 percent homology with either virus.
As for HTLV-IV, Essex's virus, the Paris/Boston team concluded that it was “a laboratory acquired contaminant”: SIVmac.
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And Beatrice Hahn, then working with Robert Gallo, announced that STLV-III and HTLV-IV were “99
%
identical and we conclude they are the same virus.”
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The scientific community recognized that they had a problem on their hands as long as emphasis remained on analysis of monkeys raised or studied in captivity, because the animals were in unnaturally close contact with species of simians they would never see in the wild. Under such conditions disease and contamination were commonplace.
The key lay with the very difficult task of capturing and testing reasonable samplings of wild primates. A Japanese team of scientists did just that, testing enough wild African green monkeys to be able to say definitively that SIVagm was a bona fide wild virus found in about half of all wild African greens on the African continent, but not found in Asian monkeys.
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The same team sequenced their wild monkey virus, and showed that it was equally similar/dissimilar to both HIV-1 and HIV-2. That meant that neither human virus came recently from SIVagm: rather, they both evolved at some equally distant time from the monkey virus, probably through some intermediaries.
The discovery of other simian AIDS viruses helped clarify the picture. The Japanese team found that wild mandrills carried another virus, SIVmnd. And that virus shared the same percentages of genetic homology with SIVagm, HIV-1, and HIV-2. That put another distant point somewhere on the AIDS family tree.
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Eventually, viruses were found in sooty mangabeys (SIVsm1 and SIVsm2), stump-tailed macaques (SIVstm), cynomolgus monkeys (SIVcyn), and chimpanzees (SIVcpz). And careful examination of the genetic sequences of these and various HIV viruses would reveal that some particular strains of HIV-2 and SIVs were so similar that scientists concluded cross-species transmission
had
occurred within the post-World War II period; some were convinced that monkey/human transmission was still occurring, albeit rarely, in the 1990s.
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Tragic proof that SIV infection of humans could occur would be found in a July 2, 1992, memo from the office of NIH director Bernardine Healy. Two U.S. lab workers had become infected as a result of bites, needle sticks, and scratches while handling macaques or their tissue. One technician had early symptoms of HIV-2 disease. Genetic analysis of the SIV-2 strain found in one of the workers would show a near-perfect match with
a strain found in a sooty mangabey. The scientists who did the genetic analysis would conclude: “Our findings support both the idea that this lentivirus can cause zoonotic infections and the hypothesis that HIV-2 originated from SIV.”
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Eventually some consensus was reached. The macaque virus (SIVmac) and HIV-2 were so similar that some scientists took to using a new notation system for the two: HIV-2/SIVmac.
In Liberia in 1989, a team of researchers led by Beatrice Hahn of the University of Alabama in Birmingham tested 372 villagers living in the country's remote northern region and 944 employees of the huge Firestone rubber plantation. Three individuals were HIV-1 positive, five carried HIV-2. Detailed genetic analysis of two of the HIV-2 strains found in the Liberian men revealed remarkable homogeneity between the local human virus and two monkey viruses: SIVsm and SIVmac. Capture and testing of wild sooty mangabeys found in Côte d'Ivoire and Liberia revealed that 10 percent of the animals carried SIVsm. And the SIVsm virus had pieces of genetic information otherwise found exclusively in HIV-2.
The researchers concluded that SIVsm, found in wild mangabeys, SIVmac—only seen in
captive
macaques—and HIV-2 were all members of “a single, albeit genetically diverse, group of viruses. Although the evolutionary origins and transmission patterns of this virus group remain to be defined, there is mounting evidence that the sooty mangabey is a natural reservoir and that the human infection probably represents a zoonosis (a disease communicable from animals to man under natural conditions).”
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