Spillover: Animal Infections and the Next Human Pandemic

Most origins of AIDS do not mention zoonosis. Instead, the story often begins in 1980 when doctors noticed gay men suffering from pneumonia their immune systems should have been able to cope with, along with a reduced count of T-cells, which are “crucial in regulating immune responses” (385). The doctor who wrote up these cases, Michael Gottlieb, worked at UCLA Medical Center. He published his findings in a CDC newsletter, about a month after a dermatologist published in the same publication about an uptick in cases of a rare cancer called Kaposi’s sarcoma in gay men who also had reduced T-cell counts. Another cluster of cases occurred among heterosexual Haitian immigrants, though this episode was left out of the narrative for a long time due to its seeming inexplicability.

A flight attendant named Gaëtan Dugas was incorrectly identified as “patient zero” for many years in part because he had traveled to Africa for his work. Dugas had numerous sexual partners and appears to have infected others deliberately toward the end of his life (387). By 1984, CDC experts had named AIDS and speculated that it was “blood-borne,” like hepatitis B. Their original paper focused on Dugas as the origin—Quammen goes on to explain how this assumption was incorrect.

AIDS had in fact left Africa while Dugas was still very young—a Danish doctor named Grethe Rask picked up an infection when working in Zaire, and by the time she returned home, she was severely immunocompromised. She died of pneumocystis pneumonia. Quammen reports that the cause was eventually discovered, noting, “nine years later, a sample of Rask’s blood serum tested positive for HIV-1” (389). All these people were “midpoints” in the history of AIDS and its zoonotic status, but this would only be realized over decades of further research (389).

Causation took longer to determine, though a French scientist named Luc Montagnier was a specialist in retroviruses and began to speculate that AIDS might fall into this category. Retroviruses survive by a takeover process, which, as Quammen explains, guarantees “replication of the virus whenever the host cell reproduces itself” (391). That there were cases clearly passed through both sexual transmission and needle transmission proved AIDS was contagious; that hemophiliacs were infected proved that the virus was small and unaffected by standard filtering. These factors strengthened Montagnier’s case.

Robert Gallo of the National Cancer Institute suspected that AIDS belonged to a family of viruses he had studied that convert T-cells to cancer cells. Gallo analyzed his samples and labeled AIDS in the “human T-cell leukemia virus” (HTLV) family (392). Montagnier was working off a sample from a homosexual man with swollen lymph nodes and called his virus LAV (for lymphadenopathy virus), and the competition was fierce, likely because a Nobel Prize in medicine was at stake (393). It eventually went to Montagnier. A third team in San Francisco discovered a third but distinct virus. All were identified as “HIV” by the scientific community in 1986.

In what Quammen calls the “next phase” of research, a graduate student, Phyllis Kanki, was working on a public health degree after training as a veterinarian and had noticed an emerging disease among macaques in captivity in Southborough, Massachusetts. The macaques were all immunocompromised with reduced T-cell counts, which reminded Kanki of AIDS. After further study, the virus was named SIV, for “Simian Immunodeficiency Virus” (395). Kanki began to speculate that the monkeys caught the virus from other monkeys, possibly African ones, as human AIDS cases there were becoming noticeable around the same time. Kanki eventually found SIV in African green monkeys, with infection rates “between 30 and 70 percent” (396).

Kanki’s SIV was related to HIV, but it did not cause illness in green monkeys. Genetic study suggested it was also not an “immediate precursor” of the human illness (396). Kanki’s team began looking for an “intermediary”—a virus that connected SIV and HIV—and found it in Senegalese sex workers (397). This made some sense, given close human-monkey interaction and living environments, “but the new strain “more closely resembled SIV strains from African green monkeys than it did the Montagnier-Gallo version of HIV,” suggesting a second version of HIV might exist (397). Further research from Montagnier, based on a man in Guinea-Bissau, led this version to be called HIV-2.

Soon another debate arose, about whether HIV was a “recent spillover” or had evolved with humans for millennia and only recently become dangerous. The puzzle eventually led to another African primate called the sooty mangabey. Doctors at a primate research center in Louisiana noticed a chimp named Louise had an unusual skin infection that resembled leprosy. Cells from Louise were injected into another sooty mangabey and into Asian rhesus macaques. None of the sooty mangabeys developed symptoms, while three of the four macaques developed simian AIDS, which suggested that the Asian macaques were susceptible “presumably because it was new to them” (401). 

This demonstrated that there were multiple kinds of SIV specific to types of monkeys. Quammen goes on to explain the classification system that developed around this.

Simian immunodeficiency virus as found in sooty mangabeys became SIVsm. […] This little convention may seem esoteric, not to mention hard on the eyes, but it will be essential and luminous when I discuss the fateful significance of a variant that came to be known as SIVcpz (401). 

Further examination of viral genomes proved that “HIV-2 is a zoonosis” (402). This discovery meant that HIV-1 was also zoonotic, but researchers did not know how or when the spillover had occurred. A captured baby chimp was tested and found to contain live virus that was very similar to HIV-1. Later results confirmed this, but they were all from captured chimps—studies of wild chimps would take more time. SIV was not present in captive chimps. This fact, combined with the difficulty of taking samples and the possibility that these chimps had been infected by another primate, meant that the findings were treated as inconclusive. 

Additional research revealed multiple strains of HIV-1, with group “M […] for main” being far and away the most numerous and accounting for the majority of global deaths (405). HIV-2 had many strains also, but some only infected two or three people. Eventually researchers determined that all HIV-1 strains resembled the simian counterpart in chimpanzees, while HIV-2 resembled that in the sooty mangabey. This meant, additionally, that looking for a single spillover would find only one strain, because, “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” (406). These have occurred relatively often in evolutionary terms because of how often people interact with chimps.

For Quammen, this raises another set of questions—if the spillovers have been numerous, why did the pandemic take so long to arrive? When did it really begin? One case, in 1959, involved a man who had served in the British Royal Navy and became known to science as “the Manchester sailor” (407). Before the results were proven to be a laboratory error, it was thought he was the first person to die of AIDS. Soon after, 1959 blood plasma samples from a Bantu man in what was then Zaire (now Democratic Republic of the Congo) were proven to be a “genuinely old” form of HIV coded as “ZR 59.” A 1960 sample from the same country offered additional leads.

Quammen then takes up the trail himself, describing his journey to the University of Kinshasa to meet Professor Jean-Marie M. Kabongo, head of pathology in the university’s Department of Anatomic Pathology. He learns about biopsy tissue preservation technology and discovers that the sample that would become known as DRC 60 resided in “a specimen pantry, narrow and tight, lined with shelves and cabinets along one side” (412), an environment that offered no insights into its crucial role in the mystery of HIV’s origins.

The DRC 60 sample eventually found its way to an evolutionary biologist named Michael Worobey, who received an evolutionary biology PhD at Oxford and became an expert in dangerous diseases at the University of Arizona. He compared DRC 60 to ZR 59 and determined that HIV had likely been present in humans since 1908.

To explain the significance and reception of this discovery, Quammen returns to the scientific debates of the 1990s. One school of thought was the cut hunter hypothesis, positing that essentially, a hunter butchering an SIV-positive chimp was infected via some kind of cut or injury. Another, more “controversial” theory suggested that HIV had entered via a polio vaccine program in the 1950s. The program had been led by a Polish researcher named Hilary Koprowski, who worked in “parts of what would eventually be DRC, Rwanda, and Burundi” (414). Proponents of the theory asserted that Koprowski’s vaccine had been grown in chimpanzee organs and that these chimps had been SIV positive.

Journalists took up this question for years, resulting in a lawsuit against a Rolling Stone writer who was too definitive about the causal link between vaccines and HIV in 1992. Another journalist, Edward Hooper, wrote a long book in 1999 that insisted “the vaccine could have been made from chimp cells that might have been contaminated” (416). An evolutionary biologist named William Hamilton convened a meeting of the UK’s Royal Society to discuss the topic. In 2000, Hamilton died of malaria contracted in the field before the meeting convened, but much of the conversation still took place. Experts agreed that evidence of the virus prior to the vaccine program would be key to resolving the debate, which led to lab testing of DRC 60. A Congolese scientist got the sample out of the laboratory in Kinshasa and it wound up in Tucson via Belgium. This is where Michael Worobey’s lab comes back into the story.

Worobey had accompanied Hamilton on his last trip into the field to continue HIV research by collecting chimp samples. Their time in the DRC was both personally and politically hazardous, as the country was in a civil war and Hamilton contracted malaria. They returned to London with their samples, relieved. These were not ultimately conclusive—Worobey’s work with DRC 60 would prove to have more lasting implications for science.

After proving that DRC 60 contained HIV-1, Worobey then compared DRC 60 to ZR 59 to see how much HIV had evolved between those two strains. Worobey found that the divergence point was around 1908, putting the date of an initial spillover into humans much earlier than previously supposed. This “directly refuted” the theory that vaccine trials had had anything to do with the emergence of HIV (421).

Another scientist, Beatrice Hahn, continued studying HIV on a different track—where it emerged, rather than when. Hahn, like Worobey, is invested in a subfield known as “molecular phylogenetics […] to learn the shape of lineages and evolutionary descent” (422). Hahn is both a doctor and a scientist, so her studies are invested in what this history suggests about treatments and “maybe even a cure” (422).

Two of Hahn’s students worked on chimp SIV. One, working with captive chimps, established the close genetic and evolutionary relationship between SIVcpz and HIV-1. Another study based on wild chimps proved conclusively that chimp SIV existed there and established urine collection as a valid evidence-gathering technique. This team worked at Gombe National Park, where Jane Goodall had done her initial work, so the chimps were especially comfortable with humans. Another of Hahn’s students, Brandon Keele, developed a method for reliably testing fecal samples while they were still viable. He used a “liquid stabilizer called RNAlater” (424). Scientists could use this tool to safely screen for viral RNA quickly and then study the samples after taking them to a better equipped laboratory. This also allowed for testing of wild chimps in places where comfort with humans was not established, which expanded the geographic reach into Cameroon.

At this point, Quammen introduces his own fieldwork—his meeting with Brandon Keele, now studying HIV at the National Cancer Institute in Bethesda, Maryland. Keele was based at the same military base where Kelly Warfield carried out her work with Ebola. Keele described his previous work in Cameroon, noting that they found much higher prevalence of chimp SIV than expected. This occurred in a “hotspot” near where two rivers meet, close to Cameroon’s border with the Republic of the Congo. Samples from there led to the “closest thing to a match” with HIV-1 that had yet been found (426).

Hahn, Keele, and their coauthors only turned briefly to the question of how the spillover occurred, but their speculations centered around the “cut-hunter” hypothesis and the idea that the virus had spread from there to the larger city of Kinshasa. Hahn argued that while apes had caused the initial spillover, infected people traveling along the river had perpetuated the rest of the spread. Quammen notes that this was partly a gradual process because of gender disparity and population size: while some women engaged in sexual and domestic arrangements with colonial officials, their numbers were too few to give HIV much opportunity. Between 1940 and Congolese independence, in 1959, Kinshasa became a major urban center, which likely explains the origins of the ZR 59 and DRC 60 samples. Quammen had a more personal epiphany when studying these discoveries: He realized he had been to that exact area previously, when looking for Ebola and explanations of chimp deaths with Mike Fay. He decided to make the journey again.

This time, Quammen had his own support team:

Moïse Tchuialeu was my driver, Neville Mbah my Cameroonian fixer, and Max Mviri, from the Republic of the Congo, was along to handle things when we reentered his country in the course of the crazy loop I had planned (431).

In Cameroon, he met an Israeli expat named Ofrir Drori, working to prevent poaching and preserve gorilla populations. In a situation reminiscent of conditions in China, most of the butchered gorillas were eaten in restaurants in urban centers, not for basic subsistence. They also visited the offices of the World Wildlife Fund in a small Congolese city called Yokadouma. The workers there emphasized that personal networks and smuggling on logging trucks were key to getting animal contraband into cities. Quammen learned that one local tribe, the Bakwele, use chimp and gorilla meat in their adolescent initiation ceremonies. This might explain the spillover, as might “sheer hunger.” 

Next Quammen visited Mambele National Park, where Brandon Keele had collected his fateful samples, and Lobele, an ape preserve. The director described struggles with poachers leading to declining populations. Most of the poachers traded their wares in the next closest city, Ouesso. Quammen noticed that there, unlike in the West, public health warnings about AIDS focused on the dangers of ape consumption. They observed logging operations and traveled down the river to the Congo so Quammen could better imagine the origins of the cut-hunter hypothesis.

Here, Quammen turns to an imaginary narrative, temporarily taking on the role of a speculative fiction writer. He imagines a Bantu man, a hunter, who kills a chimp after catching it in a trap. An injury occurs during butchering, perhaps one the man barely notices. The virus goes to work, and this man becomes “Patient zero” (443). Quammen goes on to imagine the chimp being eaten, or perhaps sold for food in a market, but anyone who ate the chimp would likely remain unaffected because they lack the hunter’s open wound.

The hunter infects his wife and other sexual partners and dies in the course of attempting to hunt an elephant. No one who tends to him gets sick because they do not have an open wound. The virus persists after the hunter’s wife remarries but does not spread widely. In some cases, people die of other causes, or their deaths are attributed to malaria or tuberculosis. HIV remains localized—until Quammen’s other hypothetical protagonist, whom he dubs “The Voyager” (446).

A young man whose father died early is shunned by the village community after his mother was suspected of sorcery. A fisherman, he knows the Ngoko river well and trades on it. He has sex with a woman, a trader, with an open wound on his penis, which leads to his HIV infection. He travels to Ouesso, by means of a random find of elephant tusks taken from a dead animal left abandoned by a hunting party. He buries the tusks and ponders what to do with his sudden, dangerous good fortune. Selling the ivory might attract attention from French officials, so he waits six months and consults with a Portuguese trader about where he might sell the ivory. This results in his camp being ransacked, but the trader does not find the tusks. The voyager hides the tusks in his canoe and sets out for Ouesso.

The man hides his canoe in a riverbank and visits the market; then, finding what he assumes is a man rummaging in his hidden canoe, he kills him with a machete. Turning the body, he discovers he killed a youth and quickly dumps the body in the river. He begins a journey away from Ouesso, searching for a place to sell the ivory.

He kills a crocodile and is warned by passersby to avoid the Bobangi tribe, but he is not lucky enough. One day a Bobangi man raids his canoe, and the voyager convinces him to take one tusk and go. The man, somewhat emboldened, takes both the tusk and a fish. He arrives at the Congo river, sells fish, and aims for Brazzaville. He sells his tusk in Brazzaville, and with it becomes a resident of the city. He also brings HIV. He infects his wife and a sex worker he visits occasionally. Quammen imagines that this woman later travels to Leopoldville.

Quammen turns from his hypothetical biography to the virus, imagining it lurking in what would become Kinshasa, and perhaps in Brazzaville. Another, more scientific exercise, takes Quammen back to SIV in chimps. Does it kill these hosts, or not? Answering this is key to understanding humanity’s future with HIV-1. Initial research suggested that captive chimps suffered few ill-effects, with only one infected chimp progressing to AIDS 10 years after infection. SIV occurs in about 40 species of African primate and none seems to suffer much from it, suggesting the virus had evolved over time to “mutual accommodation.”

Further study by Beatrice Hahn and Martine Peeters revealed that chimp SIV had a more complicated genetic history. It was a “hybrid virus,” resulting from a monkey in the past becoming infected with red capped mangabey SIV and spot-nosed monkey SIV. This likely occurred recently in evolutionary terms, “possibly just hundreds of years ago, rather than thousands or tens of thousands” (465). There is no conclusive proof as to how, but it is entirely likely that both predation and sexual contact contributed. As Quammen sums it up, this suggests “another chimpanzee version of the cut-hunter hypothesis—except in this case the cut hunter was the chimp” (465).

The chimps at Gombe, the preserve associated with Jane Goodall, proved that the relatively recent arrival of chimp SIV did have negative health effects. Beatrice Hahn wanted to study chimp SIV among relatively trusting primates and began at a wildlife preserve in Uganda due to a professional association with a primatologist named Richard Wrangham. A graduate student working with Wrangham sent Hahn some urine samples from his past studies of chimp aggression and included samples when he expanded his work to Gombe. Two of the six Gombe samples tested positive for SIV.

Hahn immediately emailed Jane Goodall about her results, hoping to study SIV there and emphasizing that her methods were non-invasive. In a meeting with Quammen, Goodall described how giving Hahn access frightened her: It might lead to increased pressure to study chimps in captive labs, along with the threat of HIV in Gombe’s chimp population. Goodall imagined additional extreme cases: people ending all hunting of chimps out of fear, or people butchering all chimps from the same motive. As of Quammen’s writing, neither outcome transpired.

In late 2000, Goodall gave her consent for Hahn’s study, including fecal sampling. The samples from a chimp named Gimble remained positive but distinct enough from human HIV-1 that they could not be the origin point of the virus. Brandon Keele reenters the story at this point, as he was in Hahn’s lab analyzing the chimp data over time. He noticed an increasing number of SIV positive chimps and considered writing a paper on its harmless effects. When he called Gombe to follow up, however, he was told all of those chimps had died.

In spring 2008, Keele received some “unusual pathology results” from a Gombe chimp named Yolanda (473). Necropsy by a Tanzanian veterinarian was followed by closer examination in the US by a veterinarian and pathologist who specialized in diseases spreading between animals and humans. Closer study of samples from Yolanda revealed that she had died of SIV, which had attacked her immune system. Keele, Hahn, and many other collaborators published their findings in what became known as “The Gombe Paper.” The paper established that contrary to previous thought, SIV had negative health outcomes for chimps, including reducing their birthrates (476).

Returning to the problem of HIV’s origins, Quammen recaps that HIV group M entered humans from chimps, diverged from HIV-2 after evolving there, and wound up in Leopoldville (later Kinshasa). What happened next was taken up by a microbiologist named Jacques Pepin. He noted the near-constant use of syringes in medical campaigns against sleeping sickness. Syringes were glass, and expensive, so they were frequently re-used. Sterilization was infrequent. This likely played some role in spreading the virus more widely, though some researchers think person-to-person transmission was sufficient.

While injection campaigns for sleeping sickness were limited to the countryside, Pepin found similar injection programs dedicated to fighting venereal disease and screening sex workers for infection. While some early treatments were ineffective, the clinic in Leopoldville was providing antibiotics in the 1950s and 1960s. This, too, could account for both ZR 59 and DRC 60. The injection campaigns may have accelerated mutations.

After 1960, the various subgroups of HIV spread throughout Africa and the world, which brings Quammen back to a mystery first discovered in the 1980s: the explanation for Kaposi’s sarcoma among Haitians. In the early period of Congolese independence, the country lacked doctors and professionals, as most educated individuals were Belgian. The WHO responded to this crisis by sending Haitians, who spoke French and were eager for professional growth. By the 1970s, when the Mobutu government became hostile to foreigners, they returned home. At least one returnee brought back HIV-1.

Pepin unearthed the mechanism of HIV’s fairly rapid spread in Haiti: plasma harvesting, which could pass on bloodborne viruses. There was a major plasma harvesting center in Port au Prince owned by an American that operated in 1971 and 1972. It was closed after “Baby Doc” Duvalier disliked its publicity in foreign newspapers, the Catholic church condemned it, and its likely role in HIV was known to very few.

Eventually, a man who had worked in an airport called Michael Worobey with his memories of planes full of blood arriving in Miami from Port-au-Prince. In the 1980s, a Miami tuberculosis expert named Arthur Pitchenik had documented increases in pneumocystis pneumonia in Haitian patients and alerted the CDC, while freezing some samples for later research. One of Worobey’s postdocs used these samples for his study on when HIV-1 arrived in the US. From there, researchers traced how this subtype of HIV had gone global: “just a single migration of the virus—one infected person or one container of plasma—accounted for bringing AIDS to America” (488). From there it spread into known individuals—taking the narrative back to the story of Los Angeles men with pneumocystis pneumonia in 1981.