Spillover

by David Quammen

  In the same month as Dugas’s death, March 1984, a team of epidemiologists from the CDC published a landmark study of the role of sexual contact in linking cases of what by then was called AIDS. The world had a label now but not an explanation. “Although the cause of AIDS is unknown,” wrote the CDC team, whose lead author was David M. Auerbach, “it may be caused by an infectious agent that is transmissible from person to person in a manner analogous to hepatitis B infection.” Hepatitis B is a blood-borne virus. It moves primarily by sexual contact, intravenous drug use with shared needles, or transfusion of blood products carrying the virus as a contaminant. It seemed like a template for understanding what otherwise was still a bewildering convergence of symptoms. “The existence of a cluster of AIDS cases linked by homosexual contact is consistent with an infectious-agent hypothesis,” the CDC group added. Not a toxic chemical, not an accident of genetics, but some kind of bug, is what they meant.

  Auerbach and his colleagues gathered information from nineteen AIDS cases in southern California, interviewing each patient or, if he was dead, his close companions. They spoke with another twenty-one patients in New York and other American cities, and from their forty case histories they created a graphic figure of forty interconnected disks, like a Tinkertoy structure, showing who had been linked sexually with whom. The patients’ identities were coded by location and number, such as “SF 1,” “LA 6,” and “NY 19.” At the center of the network, connected directly to eight disks and indirectly to all the rest, was a disk labeled “0.” Although the researchers didn’t name him, that patient was Gaëtan Dugas. Randy Shilts later transformed the somewhat bland “Patient 0,” as mentioned in this paper, to the more resonant “Patient Zero” of his book. But what the word “Zero” belies, what the number “0” ignores, and what the central position of that one disk within the figure fails to acknowledge, is that Gaëtan Dugas didn’t conceive the AIDS virus himself. Everything comes from somewhere, and he got it from someone else. Dugas himself was infected by some other human, presumably during a sexual encounter—and not in Africa, not in Haiti, somewhere closer to home. That was possible because, as evidence now shows, HIV-1 had already arrived in North America when Gaëtan Dugas was a virginal adolescent.

  It had also arrived in Europe, though on that continent it hadn’t yet gone far. A Danish doctor named Grethe Rask, who had been working in Africa, departed in 1977 from what was then Zaire and returned to Copenhagen for treatment of a condition that had been dragging her downward for several years. During her time in Zaire, Rask had first run a small hospital in a remote town in the north and then served as chief surgeon at a large Red Cross facility in the capital, Kinshasa. Somewhere along the way, possibly during a surgical procedure done without adequate protective supplies (such as latex gloves), she became infected with something for which no one at the time had a description or a name. She felt ill and fatigued. Drained by persistent diarrhea, she lost weight. Her lymph nodes swelled and stayed swollen. She told a friend: “I’d better go home to die.” Back in Denmark, tests revealed a shortage of T cells. Her breath came with such difficulty that she depended on bottled oxygen. She struggled against staph infections. Candida fungus glazed her mouth. By the time Grethe Rask died, on December 12, 1977, her lungs were clogged with Pneumocystis jirovecii, and that seems to have been what killed her.

  It shouldn’t have, according to standard medical wisdom. Pneumocystis pneumonia wasn’t normally a fatal condition. There had to be a broader explanation, and there was. Nine years later, a sample of Rask’s blood serum tested positive for HIV-1.

  All these unfortunate people—Grethe Rask, Gaëtan Dugas, the five men in Gottlieb’s report from Los Angeles, the Kaposi’s sarcoma patients known to Friedman-Kien, the Haitians in Miami, the cluster of thirty-nine (besides Dugas) identified in David Auerbach’s study—were among the earliest recognized cases of what has retrospectively been identified as AIDS. But they weren’t among the first victims. Not even close. Instead they represent midpoints in the course of the pandemic, marking the stage at which a slowly building, almost unnoticeable phenomenon suddenly rose to a crescendo. Again in the dry terms of the disease mathematicians, whose work is vitally applicable to the story of AIDS: R0 for the virus in question had exceeded 1.0, by some margin, and the plague was on. But the real beginning of AIDS lay elsewhere, and more decades passed while a few scientists worked to discover it.

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  In the early years after its detection, the new illness was a shifting shape that carried several different names and acronyms. GRID was one, standing for Gay-Related Immune Deficiency. That proved too restricted as heterosexual patients began to turn up: needle-sharing addicts, hemophiliacs, other unlucky straights. Some doctors preferred ACIDS, for Acquired Community Immune Deficiency Syndrome. The word “community” was meant to signal that people acquired it out there, not in hospitals. A more precise if clumsier formulation, favored briefly by the CDC’s Morbidity and Mortality Weekly Report, was “Kaposi’s sarcoma and opportunistic infections in previously healthy persons,” which didn’t abbreviate neatly. KSOIPHP lacked punch. By September 1982, MMWR had switched its terminology to Acquired Immune Deficiency Syndrome (AIDS), and the rest of the world followed.

  Naming the syndrome was the least of the early challenges. More urgent was to identify its cause. I just alluded to “the virus in question,” but remember: No one knew, back when those reports from Gottlieb and Friedman-Kien began capturing attention, what sort of pathogen caused this combination of puzzling, lethal symptoms—nor even if there was a single pathogen. The virus idea arose as a plausible guess.

  One scientist who made the guess was Luc Montagnier, then a little-known molecular biologist at the Institut Pasteur in Paris. Montagnier’s research had focused mainly on cancer-causing viruses, especially the group known as retroviruses, some of which cause tumors in birds and mammals. Retroviruses are fiendish beasts, even more devious and persistent than the average virus. They take their name from the capacity to move backward (retro) against the usual expectations of how a creature translates its genes into working proteins. Instead of using RNA as a template for translating DNA into proteins, the retrovirus converts its RNA into DNA within a host cell; its viral DNA then penetrates the cell nucleus and gets itself integrated into the genome of the host cell, thereby guaranteeing replication of the virus whenever the host cell reproduces itself. Luc Montagnier had studied these things in animals—chickens, mice, primates—and wondered about the possibility of finding them in human tumors too. Another disquieting possibility about retroviruses was that the new disease showing up in America and Europe, AIDS, might be caused by one.

  There was still no solid proof that AIDS was caused by a virus at all. But three kinds of evidence pointed that way, and Montagnier recalls them in his memoir, a book titled Virus. First, the incidence of AIDS among homosexuals linked by sexual interactions suggested that it was an infectious disease. Second, the incidence among intravenous drug users suggested a blood-borne infectious agent. Third, the cases among hemophiliacs implied a blood-borne agent that escaped detection in processed blood products such as clotting factor. So: It was infinitesimal, contagious, blood-borne. “AIDS could not be caused by a conventional bacterium, a fungus, or protozoan,” Montagnier wrote, “since these kinds of germs are blocked by the filters through which the blood products necessary to the survival of hemophiliacs are passed. That left only a smaller organism: the agent responsible for AIDS thus could only be a virus.”

  Other evidence hinted that it might be a retrovirus. This was new ground, but then so was AIDS. The only known human retrovirus as of early 1981 was something called human T-cell leukemia virus (HTLV), recently discovered under the leadership of a smart, outgoing, highly regarded, and highly ambitious researcher named Robert Gallo, whose Laboratory of Tumor Cell Biology was part of the National Cancer Institute in Bethesda, Maryland. HTLV, as its name implies, attacks T cells and can turn them cancerous. T cells are one
of the three major types of lymphocyte of the immune system. (Later the acronym HTLV was recast to mean human T-lymphotropic virus, which is slightly more accurate.) A related retrovirus, feline leukemia virus, causes immune deficiency in cats. So a suspicion arose among cancer-virus researchers that the AIDS agent, destroying human immune systems by attacking their lymphocytes (in particular, a subcategory of T cells known as T-helper cells), might likewise be a retrovirus. Montagnier’s group began looking for it.

  Gallo’s lab did too. And those two weren’t alone. Other scientists at other laboratories around the world recognized that finding the cause of AIDS was the hottest, the most urgent, and potentially the most rewarding quest in medical research. By late spring of 1983, three teams working independently had each isolated a candidate virus, and in the May 20 issue of Science, two of those teams published announcements. Montagnier’s group in Paris, screening cells from a thirty-three-year-old homosexual man who’d been suffering from lymphadenopathy (swollen lymph nodes), had found a new retrovirus, which they called LAV (for lymphadenopathy virus). Gallo’s group came up with a new virus also, one that Gallo took for a close relative of the human T-cell leukemia viruses (by now there was a second, called HTLV-II, and the first had become HTLV-I) that he and his people had discovered. He called this newest bug HTLV-III, nesting it proprietarily into his menagerie. The French LAV and the Gallo HTLVs had at least one thing in common: They were indeed retroviruses. But within that family exists some rich and important diversity. An editorial in the same issue of Science trumpeted the Gallo and Montagnier papers with a misleading headline: HUMAN T-CELL LEUKEMIA VIRUS LINKED TO AIDS, despite the fact that Montagnier’s LAV was not a human T-cell leukemia virus. Woops, mistaken identity. Montagnier knew better, but his Science paper seemed to blur the distinction, and the editorial occluded it entirely.

  Then again, neither was Gallo’s “HTLV-III” an HTLV, once it had been clearly seen and correctly classified. It turned out to be something nearly identical to Montagnier’s LAV, of which Montagnier had given him a frozen sample. Montagnier had personally delivered that sample, carrying it on dry ice during a visit to Bethesda.

  Confusion was thus sown early—confusion about what exactly had been discovered, who had discovered it, and when. That confusion, irrigated with competitive zeal, fertilized with accusation and denial, would grow rife for decades. There would be lawsuits. There would be fights over royalties from the patent on an AIDS blood-screening test that derived from virus grown in Gallo’s lab but traceable to Montagnier’s original isolate. (Contamination from one experiment to another, or from one batch of samples to another, is a familiar problem in lab work with viruses.) It wasn’t a petty squabble. It was a big squabble, in which pettiness played no small part. What was ultimately at stake, besides money and ego and national pride, was not just advancing or retarding research toward an AIDS cure or vaccine but also the Nobel Prize in medicine, which eventually went to Luc Montagnier and his chief collaborator, Françoise Barré-Sinoussi.

  Meanwhile the third team of researchers, led quietly by a man named Jay A. Levy in his lab at the University of California School of Medicine, in San Francisco, also found a candidate virus in 1983 but didn’t publish until more than a year afterward. By summer of 1984, Levy noted, AIDS had affected “more than 4000 individuals in the world; in San Francisco, over 600 cases have been reported.” Those numbers sounded alarmingly high at the time, though in retrospect, compared with 30 million deaths, they seem poignantly low. Levy’s discovery was also a retrovirus. His group detected it in twenty-two AIDS patients and grew more than a half dozen isolates. Because the bug was an AIDS-associated retrovirus, Levy called it ARV. He suspected, correctly, that his ARV and Montagnier’s LAV were simply variant samples of the same evolving virus. They were very similar but not too similar. “Our data cannot reflect a contamination of our cultures with LAV,” he wrote, “since the original French isolate was never received in our laboratory.” Harmless as that may sound, it was an implicit jab at Robert Gallo.

  The details of this story, the near-simultaneous triple discovery and its aftermath, are intricate and contentious and seamy and technical, like a ratatouille of molecular biology and personal politics left out in the sun to ferment. They lead far afield from the subject of zoonotic disease. For our purposes here, the essential point is that a virus discovered in the early 1980s, in three different places under three different names, became persuasively implicated as the causal agent of AIDS. A distinguished committee of retrovirologists settled the naming issue in 1986. They decreed that the thing would be called HIV.

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  The next phase began, appropriately, with a veterinarian. Max Essex studied retroviruses in monkeys and cats.

  Dr. Myron (Max) Essex, DVM, PhD, is not your ordinary small-animal vet. (Then again, this book is filled with extraordinary veterinarians who are keen scientists as well as caring animal doctors.) Essex is a professor in the Department of Cancer Biology at the Harvard School of Public Health. He worked on feline leukemia virus (FeLV), among other things, and cancer-causing viruses formed the broad frame of his interests. Having seen the effects of FeLV in wrecking the immune systems of cats, he suspected as early as 1982, along with Gallo and Montagnier, that the new human immune deficiency syndrome might be caused by a retrovirus.

  Then something strange came to his notice, by way of a grad student named Phyllis Kanki. She was a veterinarian like him, but now working on a doctorate at the School of Public Health. Kanki grew up in Chicago, spent her adolescent summers doing zoo work, and then studied biology and chemistry on the way toward veterinary medicine and comparative pathology. During the summer of 1980, while still amid her DVM studies, she worked at the New England Regional Primate Research Center, which was part of Harvard but located out in Southborough, Massachusetts. There she saw a weird problem among the center’s captive Asian macaques—some of them were dying of a mysterious immune dysfunction. Their T-helper lymphocyte counts were way down. They wasted away from diarrhea or succumbed to opportunistic infections, including Pneumocystis jirovecii. It sounded too much like AIDS. Kanki 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 Afri
ca 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.