The Bacongo girlfriend was vivacious and pretty and ambitious for wider horizons, so she crossed the pool to Léopoldville, where she had a successful career, though not a long one.
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If the virus reached Léopoldville in 1920 or so, that still leaves a gap of four decades to the time of ZR59 and DRC60, those earliest archival HIV sequences. What happened during the interim? We don’t know, but available evidence allows a rough sketch of the outlines of possibility.
The virus lurked in the city. It replicated within individuals. It passed from one person to another by sexual contact, and possibly also by the reuse of needles and syringes for treatment of well-known diseases such as trypanosomiasis. (More on that possibility, below.) Whatever its means of transmission, presumably HIV caused immunodeficiency, eventually death, among most or all people infected—except those who died early from other causes. But it didn’t yet assert itself conspicuously enough to be recognized as a distinct new phenomenon.
It may also have proliferated slowly in Brazzaville, across the pool, helped along there too by changing sexual mores and programs of therapeutic injection. It may have lingered in villages of southeastern Cameroon or elsewhere in the upper Sangha basin. And wherever it was, but definitely in Léopoldville, it continued to mutate. The wide divergence between ZR59 and DRC60 tells us that. It continued to evolve.
Studying the evolutionary history of HIV-1 is (notwithstanding that ill-advised comment by the WHO’s David Heymann to Tom Curtis) more than an idle exercise. The point is to understand how one strain of the virus, group M, has made itself so deadly and widespread among humans. Such understanding, in turn, may lead toward better measures to control the devastation of AIDS, possibly by way of a vaccine, more likely by way of improved treatments. That’s why scientists such as Beatrice Hahn, Michael Worobey, and their colleagues explore the molecular phylogenetics of HIV-1, HIV-2, and the various SIVs. One issue they address is whether the virus became virulent before, or only after, its spillover from Pan troglodytes. To state the question more plainly: Does SIVcpz kill chimps, or is it only an innocuous passenger? Answering that one could reveal something important about how human bodies respond to HIV-1.
For a while after the discovery of SIVcpz, the prevailing impression was that it’s harmless in chimpanzees, an ancient infection that may once have caused symptoms but no longer does. This impression was bolstered by the fact that, in the earlier years of AIDS research, more than a hundred captive chimpanzees had been experimentally infected with HIV-1 and none had shown immune system failure. When a single lab chimpanzee did progress to AIDS (ten years after experimental infection with three different strains of HIV-1), its case was remarkable enough to merit a six-page paper in the Journal of Virology. The researchers implied that this was good news, finally offering hope that chimpanzees do represent a relevant experimental model (that is, a sufficiently analogous test subject) for studying human AIDS. There was even a report, based on genetic analysis of captive animals in the Netherlands, suggesting that chimpanzees had “survived their own AIDS-like pandemic” more than 2 million years ago. They had emerged from the experience, according to this line of thought, with genetic adaptations that render them resistant to the effects of the virus. They still carry it but apparently don’t get sick. That notion, to repeat, was founded on captive chimpanzees. As for SIV-positive chimps in the wild: No one knew whether they suffer immunodeficiency. It was a difficult question to research.
These suppositions and guesses jibed with available information about other variants of the virus in other primates. SIV is highly diverse and broadly distributed, found as a naturally occurring infection in more than forty different species of African monkey and ape. (But it seems to be unique to that continent. Although some Asian primates have acquired the virus in captivity, it hasn’t shown up among wild monkeys in either Asia or South America.) Most of those SIV-carrying African simians are monkeys. Each kind of monkey harbors its own distinct type of SIV, such as SIVgsn in the greater spot-nosed monkey, SIVver in the vervet, SIVrcm in the red-capped mangabey, and so forth. Based on evidence presently available, none of those SIVs seems to cause immunodeficiency in its natural host. A close evolutionary kinship between two kinds of simian, such as L’Hoest’s monkey and the sun-tailed monkey, both classified in the genus Cercopithecus, is sometimes paralleled by a close similarity between their respective SIVs. Those deep taxonomic alignments, plus the absence of noticeable disease, led researchers to suspect that African monkeys have carried their SIV infections for a very long time—probably millions of years. That length of time would allow divergence among the viruses and mutual accommodation between each type of virus and its host.
The same two-part hypothesis applied also to chimps: that their virus, SIVcpz, is (1) an ancient infection that now (2) causes no harm. But for chimps those were just tenuous assumptions. Then new evidence and analyses addressed them, and both parts turned out to be wrong.
The first premise, that SIVcpz has lurked within chimpanzees for a very long time, began to look doubtful in 2003. That’s when another team of researchers (led by Paul Sharp and Elizabeth Bailes of the University of Nottingham, and including again both Beatrice Hahn and Martine Peeters) noticed that SIVcpz seems to be a hybrid virus. The Nottingham group reached that conclusion by comparing the genome of SIVcpz with the genomes of several monkey SIVs. They found that one major section of the chimp virus’s genome matches closely to a section of SIVrcm. Another major section closely resembles a section in SIVgsn. In plain words: The chimp virus contains genetic material from the virus of red-capped mangabeys and also genetic material from the virus of greater spot-nosed monkeys. How did it happen? By recombination—that is, genetic mixing. A chimpanzee infected with both monkey viruses must have served as the mixing bowl in which two viruses traded genes. And when did it happen? Possibly just hundreds of years ago, rather than thousands or tens of thousands.
How did a single chimpanzee become infected with two monkey viruses? Presumably that occurred through predation, or through the combined circumstances of predation (bringing aboard one virus) plus sexual transmission (bringing aboard a second), followed by a chance rearrangement of genes between one virus and the other during viral replication. Chimpanzees are omnivores who love an occasional taste of meat. They kill monkeys, rip them apart, fight over the pieces or share out gobbets and joints; then they eat the flesh, red and raw. It doesn’t happen often, just whenever the opportunity and the hankering arise. Such gore fests must sometimes involve blood-to-blood contact. Chimpanzees, even without the use of machetes, suffer wounds on their hands and in their mouths. Bloody meat plus an open sore equals exposure. What the Nottingham group suggested was another chimpanzee version of the cut-hunter hypothesis—except in this case the cut hunter was the chimp.
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So the very existence of SIVcpz is relatively recent. It has no ancient association with chimpanzees. And now, based on a study published in 2009, part two of the two-part hypothesis has also been cast into doubt. The virus is not harmless in its chimpanzee host. Evidence from the chimps of Gombe—Jane Goodall’s study population, known and beloved around the world—suggests that SIVcpz causes simian AIDS.
I’ve mentioned already that the first wild chimp to test SIV-positive was at Gombe. What I didn’t say, but will here, is that SIV-positive status among Gombe’s chimpanzees correlates strongly with failing health and early death. Again it was Beatrice Hahn and her group who made the discovery.
Having found SIVcpz in captive chimps, Hahn wanted to look for it in the wild. But she and her team of young molecular biologists knew little about sampling chimpanzees in an African forest. What do you do—go out and dart one? Knock the ape out with ketamine, take blood, wake him up, and send him on his way? Egads, no! said field primatologists, horrified at the prospect of any such invasive violation of their sensitive, trusting subjects. It was a new realm for Hahn, with a new set of concerns and methods, to which she
quickly became attuned. At a scientific meeting that brought primate researchers together with virologists, she met Richard Wrangham, of Harvard, highly respected for his work on the behavioral ecology and evolution of apes. Wrangham has for many years led a study of chimpanzees at Kibale National Park, in western Uganda; before that, four decades ago, he did his own PhD fieldwork at Gombe. He responded enthusiastically to Hahn’s idea of screening wild chimps, and ultimately it was Wrangham, she recalled, “who convinced Jane that we were okay to work with.” But before any such work began at Gombe, they looked at the chimps of Kibale, Wrangham’s own research site. Crucial help came from a Wrangham grad student named Martin Muller, who in 1998 had collected urine samples for a study of testosterone, aggression, and stress. Mario Santiago, of Hahn’s lab, cooked up the requisite tools for detecting SIVcpz antibodies in a few milliliters of piss, and Martin Muller supplied some frozen samples from his collections at Kibale. For this part of the story, I went to Albuquerque and talked with Muller, now an associate professor of anthropology at the University of New Mexico.
The Kibale samples all tested negative for SIV. “We were slightly disappointed,” Muller recalled. “That was because, at the time, the conventional wisdom was that this didn’t have any negative impacts on chimps.” Disappointment at negative results was allowable, he meant, because positive results would not have spelled doom for those Kibale chimps—or so it was thought. Meanwhile, though, he was getting some interesting results in his hormone study and wanted to broaden his data. He and Wrangham agreed that it might be instructive to sample a few other chimp populations for comparison. That led Muller down to Gombe, in August 2000, with his urine-collecting bottles and all the cumbersome equipment necessary to keep samples frozen. He stayed only a couple weeks, training Tanzanian field assistants to continue the collecting, and brought away just a few samples himself. Back home in the United States, he e-mailed Hahn to ask whether she would like six tubes of frozen Gombe urine, to which she replied: “YES, YES, YES.” He sent them with coded labels, standard procedure, so Hahn had no way of knowing whose was whose. Two of the six tested positive for SIV antibodies. Breaking the code, Muller informed her that both samples came from a chimp named Gimble, a twenty-three-year-old male.
Gimble was a well-known member of one of the famed Gombe families; his mother had been Melissa, a successful matriarch, and his brothers included Goblin, who rose to be the community’s alpha male and lived to age forty. Gimble’s life and career would be different—and shorter.
Soon after getting the results on Gimble, Beatrice Hahn wrote a long e-mail to Jane Goodall, explaining the context and the implications. Goodall herself had trained as an ethologist (she took a PhD at Cambridge), not as a molecular biologist, and the realm of Western blot analysis for antibodies was as alien to her as field sampling had been to Hahn. Her work on chimpanzees began back in July 1960, at what was then the Gombe Stream Game Reserve, on the east shore of Lake Tanganyika, and which later became Gombe National Park. She established the Gombe Stream Research Center in 1965, based in a small concrete building near the lake, and continued her study of chimps in the hilly forest for another twenty-one years. In 1986 Goodall published an imposing scientific opus, The Chimpanzees of Gombe, and then ended her own career as a field scientist because, appalled by the treatment of chimpanzees in medical labs and other captive situations around the world, she felt obliged to become an activist. The study of Gombe’s chimps went ahead in her absence, thanks to well-trained Tanzanian field assistants and later generations of scientists, adding decades of data and precious continuity to what Goodall had started. She remained closely connected to Gombe and its chimps, both personally and through the programs of her Jane Goodall Institute, but she wasn’t often present at the old research camp, apart from stolen interludes of rest and reinvigoration. Instead she traveled the world, roughly three hundred days a year, lecturing, lobbying, meeting with media people and schoolchildren, delivering her inspirational message. Hahn understood the intensity of Goodall’s protectiveness toward chimps in general, toward Gombe’s chimps in particular, and of her wariness toward anything that might put them in more jeopardy of exploitation, especially in the name of medical science. At the end of the long e-mail, Hahn wrote:
Let me finish by saying that finding SIVcpz in the Gombe community is a virologist’s DREAM-COME-TRUE. Given the wealth of behavioural and observational data that you and your colleagues have collected over decades, it is the IDEAL setting to study the natural history, transmission patterns and pathogenicity (or lack thereof) of natural SIVcpz infection in wild chimpanzees. Moreover, all this can be done entirely non-invasively. AND there certainly are funding opportunities for such a unique study. So, the virologist’s dream-come-true does not have to be the primatologist’s nightmare, although I am sure it will take some time before I can convince you of that.
Eventually she did convince Goodall, but not before another nightmarish discovery emerged from the work.
Earlier in her e-mail, Hahn had written: “With respect to the chimpanzees, it is probably safe to say that SIV infection will NOT cause them to develop immunodeficiency or AIDS.” On that point, she would prove herself wrong.
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Jane Goodall described her own concerns when I caught up with her during one of her stopovers. We knew each other from previous adventures—among chimps in the Congo basin, among black-footed ferrets in South Dakota, over single-malt scotch in Montana—but this was a chance to sit down quietly at a hotel in Arlington, Virginia, during a paralyzing snowstorm, and talk about Gombe. The fiftieth anniversary of her own chimp study was approaching, and I was assigned by National Geographic to write about it. After we discussed her childhood influences, her dream of becoming a naturalist in Africa, her mentor Louis Leakey, her early days in the field, and her time as a PhD student at Cambridge, she herself mentioned genetics and virology. At that point I turned the conversation to SIV.
“I was really, really apprehensive about Beatrice Hahn’s research,” Jane volunteered. “We were, a lot of us, really nervous about the result of what might happen if she found HIV/AIDS.” She had met Hahn, talked with her, and was reassured by the force of Hahn’s concern for the chimps’ welfare. “But still. I still have this unease because, even though she cares, once these results are out, as they are now, other people can use them in different ways.” For instance? What sort of dangers, I asked, did Jane have in mind? “That this would start a whole new flurry of research on captive chimps in medical labs.” The news of chimps with AIDS, she feared, would sound like a promising opportunity to learn more about AIDS in humans, never mind the chimps.
What about the impact of the virus at Gombe itself? We both knew that Hahn had found something resembling AIDS, and by now Gimble was dead. What about the prospect that other members of the Gombe community might die of immune failure? “Yeah, exactly,” Jane said. “That’s a very scary thought.”
As scary as it was, though, she had realized from the start of her conversations with Hahn that such a finding could be taken two ways. On the one hand, she said, there was a possible consolation: If people heard that wild chimps carry an AIDS-causing virus, they might stop hunting and butchering and eating them. “Because they’ll be afraid. That was one side of it. Then the other side of it was, well, people will say, ‘All these creatures are really dangerous for us, so let’s kill them all.’ It could have gone either way.” Jane is a perspicacious woman. She has the aura of a secular saint but is actually quite human, grounded, savvy, and capable of ambivalence. As things have transpired so far, she noted, neither of the extreme outcomes has occurred.
Briefly we discussed Hahn’s noninvasive sampling methodology: Urine might contain antibodies, and feces could yield viral RNA. Jane allowed that it had been reassuring, that part about no necessity of knocking chimps out and jabbing them with needles. “Don’t need blood,” she said. “Just need a bit of poo.” Amazing what they can do from a bit of poo, I agreed.<
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So she had given her consent for Hahn’s study, and the work proceeded. At the end of November 2000, Hahn’s lab in Alabama received the first batch of material, which included three fecal samples from poor Gimble. Hahn’s grad student Mario Santiago did the screening, and again all three of Gimble’s samples tested positive. Santiago then amplified a viral RNA fragment and sequenced it, confirming that Gimble’s virus was indeed SIVcpz. It seemed to be a new strain, distinct enough from other known strains that it might be unique to East Africa. This was significant on several counts. Yes, the chimps of Gombe were infected. No, they couldn’t be source animals for the human pandemic. The variants of SIV found by Martine Peeters in western Africa (this was before Hahn’s own findings from Cameroon) more closely matched HIV-1 group M than the Gombe virus did.
The Chimp and the River: How AIDS Emerged from an African Forest Page 10