Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

The genomes packed within such small containers are correspondingly limited, ranging from 2,000 nucleotides up to about 1.2 million. The genome of a mouse, by contrast, is about 3 billion nucleotides. It takes three nucleotide bases to specify an amino acid and on average about 250 amino acids to make a protein (though some proteins are much larger). Making proteins is what genes do; everything else in a cell or a virus results from secondary reactions. So a genome of just two thousand code letters, or even thirteen thousand (as for the influenzas) or thirty thousand (the SARS virus), is a very sketchy set of engineering specs.

Three days later, Brebner noticed “pain, redness, and slight swelling” around the bite. Another three days passed and he was admitted to Bellevue Hospital. His symptoms developed slowly—tender lymph nodes, abdominal cramps, paralysis of his legs, inability to urinate, tingling numbness in his arms, and then a high fever and hiccupping—until, after two weeks, he was very sick indeed. His breathing became labored and he turned blue. Put into a respirator, he convulsed and lost consciousness. Frothy liquid came wheezing out of his mouth and nostrils. Five hours later, William Brebner was dead at the age of twenty-nine.

Herpes B is a very rare infection in humans but a nasty one, with a case fatality rate of almost 70 percent

The most recent big one is AIDS, of which the eventual total bigness (the scope of its harm, the breadth of its reach) cannot even be predicted. About 30 million deaths, 34 million living people now infected, with no end in sight.

Polio was a big one, at least in America, where it achieved special notoriety by crippling a man who would become president despite it. Polio also, during its worst years, struck hundreds of thousands of children and paralyzed or killed many,

The biggest of the big ones during the twentieth century was the 1918–1919 influenza. Before that, on the North American continent, the big one for native peoples was smallpox, arriving from Spain about 1520 with the expedition that helped Cortez conquer Mexico. Back in Europe, two centuries earlier, it was the Black Death, probably attributable to bubonic plague.

Between the years 1347 and 1352, this epidemic seems to have killed at least 30 percent of the people in Europe.

Can the virions concentrate themselves in a host’s throat or nasal passages, cause irritation there, and come blasting out on the force of a cough or a sneeze? Once launched into the environment, can they resist desiccation and ultraviolet light for at least a few minutes? Can they invade a new individual by settling onto other mucous membranes—in the nostrils, in the throat, in the eyes—and gaining attachment, cell entry, another round of replication? If so, that virus is highly transmissible.

Rubella (loosely known as German measles) is caused by a virus capable of vertical as well as airborne transmission, and it can kill a fetus or inflict severe damage, including heart disorders, blindness, and deafness. That’s why young girls were counseled, in the era before rubella vaccine, to get themselves infected with the virus—suffer a mild bout and be done with it, permanently immune—before they reached childbearing age.

virulence is such an iridescent, relativistic concept that some experts refuse to use the word. They prefer “pathogenicity,” which is nearly a synonym but not quite. Pathogenicity is the capacity of a microbe to cause disease. Virulence is the measurable degree of such disease, especially as gauged against other strains of similar pathogen.

The first rule of a successful parasite? Myxoma’s success in Australia suggests something different from that nugget of conventional wisdom I mentioned above. It’s not Don’t kill your host. It’s Don’t burn your bridges until after you’ve crossed them.

Hendra and Nipah, Ebola and Marburg, West Nile, Machupo, Junin, the influenzas, the hantas, dengue and yellow fever, rabies and its cousins, chikungunya, SARS-CoV, and Lassa, not to mention HIV-1 and HIV-2. All of them carry their genomes as RNA.

things like varicella zoster virus, a classic DNA virus that begins its infection of humans as chickenpox and can recrudesce, decades later, as shingles. The downside for DNA viruses, Eddie said, is that they can’t adapt so readily to a new species of host. They’re just too stable.

Hantaviruses jump from rodents. Lassa too jumps from rodents. Yellow fever virus jumps from monkeys. Monkeypox, despite its name, seems to jump mainly from squirrels. Herpes B jumps from macaques. The influenzas jump from wild birds into domestic poultry and then into people, sometimes after a transformative stopover in pigs. Measles may originally have jumped into us from domesticated sheep and goats. HIV-1 has jumped our way from chimpanzees.

Hendra: from bats. Marburg: from bats. SARS-CoV: from bats. Rabies, when it jumps into people, comes usually from domestic dogs—because mad dogs get more opportunities than mad wildlife to sink their teeth into humans—but bats are among its chief reservoirs. Duvenhage, a rabies cousin, jumps to humans from bats. Kyasanur Forest virus is vectored by ticks, which carry it to people from several kinds of wildlife, including bats. Ebola, very possibly: from bats. Menangle: from bats. Tioman: from bats. Melaka: from bats. Australian bat lyssavirus, it may not surprise you to learn, has its reservoir in Australian bats.

Nipah, one of the more dramatic RNA viruses to emerge within recent decades, which leaps into pigs and via them into humans: from bats.

former philosophy major who turned to medicine and epidemiology, and then chose to focus on infectious diseases in low-income countries.

He hears a steady tolling of preventable deaths and tries hard to prevent as many as possible.

the more opportunity viruses have to jump hosts, the more opportunity they have to mutate when they encounter new immune systems.”

Antibodies and RNA fragments, though significant, were just the same sorts of secondary evidence that had provisionally linked the Ebola virus to bats.

They’d found live virus. Working in one of the CDC’s BSL-4 units, Towner and his co-workers had isolated viable, replicating Marburg virus from five different bats. Furthermore, the five strains of virus were genetically diverse, suggesting an extended history of viral presence and evolution within Egyptian fruit bats.

The news of Astrid Joosten’s death carried far. She was the first person known to have left Africa with an active filovirus infection and died. The Swiss graduate student from Côte d’Ivoire, back in 1994, had recovered.

one of four new viruses that emerged around the same time from this single group of bats, the pteropids. Soon after Hendra virus made its debut north of Brisbane, in 1994, there was Australian bat lyssavirus, appearing at two other sites along the Queensland coast, in 1996; then Menangle virus, emerging near Sydney, in 1997; and then Nipah virus, up in Malaysia, in September 1998. “For four viruses to emerge from one host genus within a short period of time is unprecedented,” she said. “So we feel there’s been some change in the ecology of Pteropus species that could precipitate disease emergence.”

those large aggregations—comprising bats that are more sedentary, more urban, less needful of flying long distances in search of wild food—tend to reinfect one another less frequently? And in the interim they accumulate more susceptible individuals? So when the virus does arrive, the spread of new infections is more sudden and intense? The virus is more prevalent and abundant? “Exactly. That’s it,” she said. “And then a great likelihood of spillover into another species?”

The context was an outbreak of Ebola virus that occurred in and around a village called Luebo, along the Lulua River, in a southern province of the Democratic Republic of the Congo. Between late May and November 2007, more than 260 people sickened with what seemed to be or (in some confirmed cases) definitely was Ebola virus. Most of them died. The lethality was 70 percent.

Human-to-human transmission is the crux. That capacity is what separates a bizarre, awful, localized, intermittent, and mysterious disease (such as Ebola) from a global pandemic.

But if H5N1 mutates or reassembles itself in just the right way, if it adapts for human-to-human transmission, then H5N1 could become the biggest and fastest killer disease since 1918.

Some swabs, both from the wall and the bed frame, tested positive for Nipah RNA. I’ll repeat that: Fragments (at least) of Nipah virus, left from what the patient had spewed out, were still present after five weeks, invisibly decorating the room.

Bangladesh, wondrous in so many ways, engaging and fascinating as well as horrifying to an affluent visitor, is an especially difficult country in which to be a poor citizen, either urban or rural, because if you’re poor it’s a difficult country in which to remain healthy. Thousands of people, young and old, die of cholera and other diarrheal diseases and pneumonia and tuberculosis and measles.

Given the global scorecard of morbidity and mortality caused by old-fashioned infectious diseases—such as cholera, typhoid, TB, rotavirus diarrhea, malaria (excepting Plasmodium knowlesi), not to mention chronic illnesses such as cancer and heart disease—why divert attention to these boutique infections, these anomalies, that spill out of bats or monkeys or who knows where to claim a few dozen or a few hundred people now and then?

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.

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.

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.

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.

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.

a virus intermediate between HIV and SIV. With the code unblinded, Kanki learned that the positive results came from Senegalese prostitutes. In retrospect it made sense. Prostitutes are at high risk for any sexually transmitted virus, including a new one recently spilled into humans. And the density of the rural human population in Senegal, where African green monkeys are native, makes monkey-human interactions (crop-raiding by monkeys, hunting by humans) relatively frequent.

the new bug from Senegalese prostitutes wasn’t just halfway between HIV and SIV. It more closely resembled SIV strains from African green monkeys than it did the Montagnier-Gallo version of HIV. That was important but puzzling. Were there two distinct kinds of HIV?

in the past 30–40 years SIV from a West African sooty mangabey (or closely related species) successfully infected a human and evolved as HIV-2.” It was official: HIV-2 is a zoonosis.

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 immune deficiency. 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.

HIV-1 is the thing that afflicts tens of millions of people throughout the world. HIV-1 is the pandemic scourge.

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.

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

ZR59 was a glimpse back in time, a genuinely old form of HIV-1, not a recent contamination. ZR59 proved that HIV-1 had been present—simmering, evolving, diversifying—in the population of Léopoldville by 1959.

in 1992 a contrary theory arose. This one was heterodox and highly controversial: that HIV-1 first got into humans by way of a contaminated polio vaccine tested on a million unsuspecting Africans. The vaccine itself, by this theory, had been an unintended delivery system for AIDS.

roughly seventy-five thousand kids were vaccinated just in Léopoldville. The heterodox theory argued two additional points about this enterprise: First, that Koprowski’s vaccine was produced by growing the virus in chimpanzee kidney cells (rather than in monkey kidney cells, the standard technique); second, that at least some batches of that vaccine were produced from chimpanzee kidneys drawn from animals infected with SIVcpz

molecular phylogeneticist scrutinizes the nucleotide sequences in the DNA or RNA of different organisms, comparing and contrasting, for the same reason a paleontologist scrutinizes fragments of petrified bone from extinct giant saurians—to learn the shape of lineages and the story of evolutionary descent.

When his computer delivered its latest tree, LB7’s isolate of SIVcpz showed up as a twig amid the same little branch that held all known human strains of HIV-1 group M. (In scientific lingo, it fell within the same clade.)

AIDS began with a spillover from one chimp to one human, in southeastern Cameroon, no later than 1908 (give or take a margin of error), and grew slowly but inexorably from there.

We show here that the SIVcpzPtt strain that gave rise to HIV-1 group M belonged to a viral lineage that persists today in P. t. troglodytes apes in southeastern Cameroon. That virus was probably transmitted locally. From there it appears to have made its way via the Sangha River (or other tributaries) south to the Congo River and on to Kinshasa where the group M pandemic was probably spawned.

“What brings the money are the protected species,” he said. “Things that are rare.” It sounded like the Era of Wild Flavor back in southern China.