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From The Chimp and the River: How AIDS Emerged from an African Forest, by David Quammen. Copyright © 2015, 2012 by David Quammen with permission of the publisher, W. W. Norton & Company, Inc. All rights reserved.
But what about HIV-1? Where did the great killer come from? That was a larger mystery that took somewhat longer to solve. The logical inference was that HIV-1 must be zoonotic in origin also. But what animal was its reservoir? When, where, and how had spillover occurred? Why had the consequences been so much more dire?
HIV-2 is both less transmissible and less virulent than HIV-1. The molecular bases for those fateful differences are still secrets embedded in the genomes, but the ecological and medical ramifications are clear and stark. HIV-2 is confined mostly to West African countries such as Senegal and Guinea-Bissau (the latter of which, during colonial times, was Portuguese Guinea), and to other areas connected socially and economically within the former Portuguese empire, including Portugal itself and southwestern India. People infected with HIV-2 tend to carry lower levels of virus in their blood, to infect fewer of their sexual contacts, and to suffer less severe or longer-delayed forms of immunodeficiency. Many of them don’t seem to progress to AIDS at all. And mothers who carry HIV-2 are less likely to pass it to their infants. The virus is bad, but not nearly so bad as it could be. HIV-1 provides the comparison. HIV-1 is the thing that afflicts tens of millions of people throughout the world. HIV-1 is the pandemic scourge. To understand how the AIDS catastrophe has happened to humanity, scientists had to trace HIV-1 to its source.
This takes us to the city of Franceville, in southeastern Gabon, Central Africa, and an institution called the Centre International de Recherches Médicales (CIRMF), the same place at which important work on Ebola virus has been done. It’s a nexus for the study of, and response to, emerging African diseases. At the end of the 1980s, a young Belgian woman named Martine Peeters worked as a research assistant at CIRMF for a year or so, during the period between getting her diploma in tropical medicine and going on for a doctorate. The CIRMF facility maintained a compound of captive primates, including three dozen chimpanzees, and Peeters along with several associates was tasked with testing the captive animals for antibodies to HIV-1 and HIV-2. Almost all of the chimps tested negative—all except two. Both exceptions were very young females, recently captured from the wild. Such baby chimps, like other orphan primates, are sometimes kept or sold off as pets after the killing and eating of their mothers. One of these animals, a two-year-old suffering from gunshot wounds, had been brought to CIRMF for medical treatment. She died of the wounds, but not before surrendering a blood sample. The other was an infant, maybe six months old, who survived. Blood serum from each of them reacted strongly when tested against HIV-1, less strongly when tested against HIV-2. That much was notable but slightly ambiguous. Antibody testing is an indirect gauge of infection, relatively convenient and quick, but imprecise. Greater precision comes with detecting fragments of viral RNA or, better still, isolating a virus—catching the thing in its wholeness and growing it in quantity—from which a confident identification can be made. Martine Peeters and her co-workers succeeded in isolating a virus from the baby chimp. Twenty years later, when I called on her at her office at an institute in southern France, Peeters remembered vividly how that virus showed up in a series of molecular tests.
“It was especially surprising,” she said, “ because it was so close to HIV-1.”
Had there been any previous hints?
“Yes. At that time we knew already that HIV-2 most likely came from primates in West Africa,” she said, alluding to the sooty mangabey work. “But there was no virus close to HIV-1 already detected in primates. And until now, it’s still the only virus close to HIV-1.” Her group published a paper, in 1989, announcing the new virus and calling it SIVcpz. They did not crow about having found the reservoir of HIV-1. Their conclusion from the data was more modest: “It has been suggested that human AIDS retroviruses originated from monkeys in Africa. However, this study and other previous studies on SIV do not support this suggestion.” Left implicit: Chimpanzees, not monkeys, might be the source of the pandemic bug.
By the time I met her, Martine Peeters was director of research at the Institut de Recherche pour le Développement (IRD), in Montpellier, a handsome old city just off the Mediterranean coast. She was a small, blonde woman in a black sweater and silver necklace, concise and judicious in conversation. What sort of response met this discovery? I asked.
“HIV-2, people accepted it readily.” They accepted, she meant, the notion of simian origins. “But HIV-1, people had more difficulties to accept it.”
Why the resistance? “I don’t know why,” she said. “Maybe because we were young scientists.”
The 1989 paper got little attention, which seems peculiar in retrospect, given the novelty and gravity of what it implied. In 1992 Peeters published another, describing a third case of SIVcpz, this one in a captive chimpanzee that had been shipped to Brussels from Zaire. All three of her SIV-positive results were from “wild-born” chimpanzees taken captive (as distinct from animals bred in captivity) but that still left a gap in the chain of evidence. What about chimps still in the wild?
With only such tools of molecular biology as available in the early 1990s, the screening of wild chimps was difficult (and unacceptable to most chimp researchers), because the diagnostic tests required blood sampling. Lack of evidence from wild populations, in turn, contributed to skepticism in the AIDS-research community about the link between HIV-1 and chimps. After all, if Asian macaques had become infected with HIV-2 in their cages, from contact with African monkeys, might not SIV-positive chimpanzees simply reflect cage-contact infections too? Another reason for skepticism was the fact that, by the end of the 1990s, roughly a thousand captive chimpanzees had been tested but, apart from Peeters’s three, not a single one had yielded traces of SIVcpz. These two factors—the absence of evidence from wild populations and the extreme rarity of SIV in captive chimps—left open the possibility that both HIV-1 and SIVcpz derived directly from a common ancestral virus in some other primate. In other words, maybe those three lonely chimps had gotten their infections from some still-unidentified monkey, and maybe the same unidentified monkey had given HIV-1 to humans. With that possibility dangling, the origin of HIV-1 remained uncertain for much of the decade.
In the meantime, researchers investigated not just the source of HIV but also its diversity in humans, discovering three major lineages of HIV-1. “Groups” became the preferred term for these lineages. Each group was a cluster of strains that was genetically discrete from the other clusters; there was variation within each group, since HIV is always evolving, but the differences between groups were far larger. This pattern of groups had some dark implications that dawned on scientists only gradually and still haven’t been absorbed in the popular understanding of AIDS. I’ll get to them shortly, but first let’s consider the pattern itself.
Group M was the most widespread and nefarious. The letter M stood for “main,” because that group accounted for most of the HIV infections worldwide. Without HIV-1 group M, there was no global pandemic, no millions of deaths. Group O was the second to be delineated, its initial standing for “outlier,” because it encompassed only a small number of viral isolates, mostly traceable to what seemed an outlier area relative to the hotspots of the pandemic: Gabon, Equatorial Guinea, and Cameroon, all in western Central Africa. By the time a third major group was discovered, in 1998, it seemed logical to label that one N, supposedly indicating “non-M/non-O” but also filling in the alphabetical sequence. (Years later, a fourth group would be identified and labeled P.) Group N was extremely rare; it had been found in just two people from Cameroon. The rarity of N and O put group M dramatically in relief. M was everywhere. Why had that particular lineage of virus, and not the other two (or three), spread so broadly and lethally around the planet?
Parallel research on HIV-2, the less virulent virus, also found distinct groups but even more of them. Their labeling came from the beginning of the alphabet rather than the middle, and by the year 2000 seven groups of HIV-2 were known: A, B, C, D, E, F, and G. (An eighth group, turning up later, became H.) Again, most of them were extremely rare—represented, in fact, by viral samples taken from only one person. Groups A and B weren’t rare; they accounted for the majority of HIV-2 cases. Group A was more common than group B, especially in Guinea-Bissau and Europe. Group B was traceable mainly to countries on the eastern end of West Africa, such as Ghana and Côte d’Ivoire. Groups C through H, although tiny in total numbers, were significant in showing a range of diversity.
As the new century began, AIDS researchers pondered this roster of different viral lineages: seven groups of HIV-2 and three groups of HIV-1. The seven groups of HIV-2, distinct as they were from one another, all resembled SIVsm, the virus endemic in sooty mangabeys. (So did the later addition, group H.) The three kinds of HIV-1 all resembled SIVcpz, from chimps. (The eventual fourth kind, group P, is most closely related to SIV from gorillas.) Now here’s the part that, as it percolates into your brain, should cause a shudder: Scientists think that each of those twelve groups (eight of HIV-2, four of HIV-1) reflects an independent instance of cross-species transmission. Twelve spillovers.
In other words, HIV hasn’t happened to humanity just once. It has happened at least a dozen times—a dozen that we know of, and probably many more times in earlier history. Therefore it wasn’t a highly improbable event. It wasn’t a singular piece of vastly unlikely bad luck, striking humankind with devastating results—like a comet come knuckleballing across the infinitude of space to smack planet Earth and extinguish the dinosaurs. No. The arrival of HIV in human bloodstreams was, on the contrary, part of a small trend. Due to the nature of our interactions with African primates, it seems to occur pretty often.