Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

the death of more than 30 million people since 1981. Those realities involve a phenomenon called zoonosis. A zoonosis is an animal infection transmissible to humans. There are more such diseases than you might expect. AIDS is one. Influenza is a whole category of others.

Infectious disease is all around us. Infectious disease is a kind of natural mortar binding one creature to another, one species to another, within the elaborate biophysical edifices we call ecosystems. It’s one of the basic processes that ecologists study, including also predation, competition, decomposition, and photosynthesis. Predators are relatively big beasts that eat their prey from outside. Pathogens (disease-causing agents, such as viruses) are relatively small beasts that eat their prey from within. Although infectious disease can seem grisly and dreadful, under ordinary conditions it’s every bit as natural as what lions do to wildebeests and zebras, or what owls do to mice.

Smallpox, to take one counterexample, is not a zoonosis. It’s caused by variola virus, which under natural conditions infects only humans.

That helps explain why a global campaign mounted by the World Health Organization (WHO) to eradicate smallpox was, as of 1980, successful. Smallpox could be eradicated because that virus, lacking ability to reside and reproduce anywhere but in a human body (or a carefully watched lab animal), couldn’t hide.

Virus particles are so tiny they can’t be seen, except by electron microscopy, which involves killing them, so their presence during isolation must be detected indirectly. You start with a small bit of tissue, a drop of blood, or some other sample from an infected victim. Your hope is that it contains the virus. You add that inoculum, like a dash of yeast, to a culture of living cells in a nutrient medium. Then you incubate, you wait, you watch. Often, nothing happens. If you’re lucky, something does. You know you’ve succeeded when the virus replicates abundantly and asserts itself sufficiently to cause visible damage to the cultured cells. Ideally it forms plaques, large holes in the culture, each hole representing a locus of virus-caused devastation. The process demands patience, experience, expensively exact bench tools, plus meticulous precautions against contamination (which can falsify results) or accidental release (which can infect you, endanger your co-workers, and maybe panic a town).

Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly. There are three elements to the situation. One: Mankind’s activities are causing the disintegration (a word chosen carefully) of natural ecosystems at a cataclysmic rate.

Two: Those millions of unknown creatures include viruses, bacteria, fungi, protists, and other organisms, many of which are parasitic.

Three: But now the disruption of natural ecosystems seems more and more to be unloosing such microbes into a wider world.

A bai in Francophone Africa is a marshy meadow, often featuring a salt lick, and surrounded by forest like a secret garden.

infectious diseases that threaten gorilla health, of which Ebola is only the most exotic. The others were largely human diseases of more conventional flavor, to which gorillas are susceptible because of their close genetic similarity to us: TB, poliomyelitis, measles, pneumonia, chickenpox, et cetera. Gorillas can be exposed to such infections wherever unhealthy people are walking, coughing, sneezing, and crapping in the forest. Any such spillover in the reverse direction—from humans to a nonhuman species—is known as an anthroponosis. The famous mountain gorillas, for instance, have been threatened by anthroponotic infections such as measles, carried by ecotourists who come to dote upon them.

You know about this if you’ve read The Hot Zone, Richard Preston’s account of a 1989 outbreak of an Ebola-like virus among captive Asian monkeys at a lab-animal quarantine facility in suburban Reston, just across the Potomac from Washington, DC. Filovirus experts express mixed opinions about Preston’s book, but there’s no question that it did more than any journal article or newspaper story to make ebolaviruses infamous and terrifying to the general public. It also led to “a shower of funding,”

One animal died and, after it tested positive for Reston virus, forty-nine others housed in the same room were euthanized as a precaution. (Most of those, tested posthumously, were negative.) Ten employees who had helped unload and handle the monkeys were also screened for infection, and they also tested negative, but none of them were euthanized.

Advisory: If your husband catches an ebolavirus, give him food and water and love and maybe prayers but keep your distance, wait patiently, hope for the best—and, if he dies, don’t clean out his bowels by hand. Better to step back, blow a kiss, and burn the hut.

“We have a lot to learn from these people,” Barry Hewlett told me, one day in Gabon, “as to how they’ve responded to these epidemics over time.” Modern society has lost that sort of ancient, painfully acquired accumulation of cultural knowledge, he said. Instead we depend on the disease scientists. Molecular biology and epidemiology are useful, but other traditions of knowledge are useful too. “Let’s listen to what people are saying here. Let’s find out what’s going on. They’ve been living with epidemics for a long time.”

If you devoured The Hot Zone when it was published, as I did, or if you have been secondarily exposed to its far-reaching influence on public impressions about ebolaviruses, you may carry some wildly gruesome notions. Richard Preston is a vivid writer, a skillful writer, an industrious researcher, and it was his purpose to make a truly horrible disease seem almost preternaturally horrific.

It’s my duty to advise that you need not take these descriptions quite literally—at least, not as the typical course of a fatal case of Ebola virus disease. Expert testimony, some published and some spoken, tempers Preston on several of these more lurid points, without minimizing the terribleness of Ebola in terms of real suffering and death.

about the public perception that this disease is extraordinarily bloody, Rollin interrupted me genially to say: “—which is bullshit.” When I mentioned the descriptions in Preston’s book, Rollin mockingly said, “They melt, splash on the wall,” and gave a frustrated shrug. Mr. Preston could write what he pleased, Rollin added, so long as the product was labeled fiction. “But if you say it’s a true story, you have to speak to the true story, and he didn’t. Because it was much more exciting to have blood everywhere and scaring everywhere.” A few patients do bleed to death, Rollin said, but “they don’t explode, and they don’t melt.” In fact, he said, the often-used term “Ebola hemorrhagic fever” is itself a misnomer for Ebola virus disease, because more than half the patients don’t bleed at all. They die of other causes, such as respiratory distress and shutdown

I got him to sit for an interview, and The Hot Zone inescapably came up. Waxing serious, Karl said: “Bloody tears is bullshit. Nobody has ever had bloody tears.” Furthermore, Karl noted, “People who die are not formless bags of slime.” Johnson also concurred with Pierre Rollin that the bloodiness angle has been oversold.

During the Kikwit outbreak, 59 percent of all patients didn’t bleed noticeably at all, and bleeding in general was no indicator of who would or wouldn’t survive. Rapid breathing, urine retention, and hiccups, on the other hand, were ominous signals that death would probably come soon. Among those patients who did bleed, blood loss never seemed massive, except among pregnant women who spontaneously aborted their fetuses. Most of the nonsurvivors died stuporous and in shock. Which is to say: Ebola virus generally killed with a whimper, not with a bang or a splash.

One notable implication of their work was stated near the end: “Small increases of the infectivity rate may lead to large epidemics.” This quiet warning has echoed loudly ever since. It’s a cardinal truth, over which public health officials obsess each year during influenza season. Another implication was that epidemics don’t end because all the susceptible individuals are either dead or recovered. They end because susceptible individuals are no longer sufficiently dense within the population.

The culinary trade in such unusual wild animals, especially within the Pearl River Delta, has less to do with limited resources, dire necessity, and ancient traditions than with booming commerce and relatively recent fashions in conspicuous consumption. Close observers of Chinese culture call it the Era of Wild Flavor.

It meant that horseshoe bats are a reservoir, if not the reservoir, of SARS-CoV. It meant that civets must have been an amplifier host, not a reservoir host, during the 2003 outbreak. It meant that no one knew just what had happened in Guangdong that winter to trigger the outbreak, although Li and his colleagues could speculate. (“An infectious consignment of bats serendipitously juxtaposed with a susceptible amplifying species,” they wrote, “could result in spillover and establishment of a market cycle while susceptible animals are available to maintain infection.” Infection by association. Susceptible animals might include not just masked palm civets but also raccoon dogs, ferret badgers, who knows what. So many different candidates pass through the wildlife supply chain.) It meant that you could kill every civet in China and SARS would still be among you.

One fellow, a Chinese colleague of Aleksei’s, told me that the bird-and-bat trade was covered by an adage: “People in south China will eat everything that flies in the sky, except an airplane.”

What have we learned from the SARS experience? One thought that turns up in the latter sort is that “humankind has had a lucky escape.” The scenario could have been very much worse. SARS in 2003 was an outbreak, not a global pandemic. Eight thousand cases are relatively few, for such an explosive infection; 774 people died, not 7 million. Several factors contributed to limiting the scope and the impact of the outbreak, of which humanity’s good luck was only one. Another was the speed and excellence of the laboratory diagnostics—finding the virus and identifying it—

Do you put flea-and-tick collars on your kids’ ankles before they go out to play? No, none of those. “I would feel a lot more comfortable,” Ostfeld answered, “if I knew that the landscape would support healthy populations of owls, foxes, hawks, weasels, squirrels of various kinds—the components of the community that could regulate mouse populations.” In other words, biological diversity. This was his offhand way of expressing the most notable conclusion that has emerged from twenty years of research: Risk of Lyme disease seems to go up as the roster of native animals, in a given area, goes down.

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, captured public attention like headlights freezing a deer, and brought drastic changes to the way large-scale medical research is financed and conducted. 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.

From where do these viruses jump? They jump from animals in which they have long abided, found safety, and occasionally gotten stuck. They jump, that is, from their reservoir hosts. And which animals are those? Some kinds are more deeply implicated than others as reservoirs of the zoonotic viruses that jump into humans. 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.

But a large fraction of all the scary new viruses I’ve mentioned so far, as well as others I haven’t mentioned, come jumping at us from bats. 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.

How did the virus go from bats to pigs? All it required was a mango or water apple tree, laden with ripe fruit, overhanging a pigsty. An infected bat feeds on a water apple, discarding the pulp (as bats do), which is besmeared with virus; the pulp drops down among the pigs; one pig snarfs it up and gets a good dose of virus; the virus replicates in that pig and passes to others; soon the whole herd is infected and human handlers begin to fall sick. It wasn’t a far-fetched scenario.

Among the most important things to remember about evolution—and about its primary mechanism, natural selection, as limned by Darwin and his successors—is that it doesn’t have purposes. It only has results. To believe otherwise is to embrace a teleological fallacy that carries emotive appeal (“the revenge of the rain forest”) but misleads. This is what Jon Epstein was getting at. Don’t imagine that these viruses have a deliberate strategy, he said. Don’t think that they bear some malign onus against humans. “It’s all about opportunity.” They don’t come after us. In one way or another, we go to them.

In some zoonotic pathogens, efficient transmissibility among humans seems to be inherent from the start, a sort of accidental preadaptedness for spreading through the human population, despite a long history of residence within some other host. SARS-CoV had it, from the earliest days of its 2002–2003 emergence in Guangdong and Hong Kong. SARS-CoV has it, no matter where or why SARS-CoV may be hiding since then.

It worries the flu scientists because they know that H5N1 influenza is (1) extremely virulent in people, with a high lethality though a relatively low number of cases, and yet (2) poorly transmissible, so far, from human to human. It’ll kill you if you catch it, very likely, but you’re unlikely to catch it except by butchering an infected chicken. Most of us don’t butcher our own chickens, and health officials all over the world have been working hard to assure that the chickens we handle—dead, disarticulated, wrapped in plastic or otherwise—have not been infected. 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.

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? Why? Isn’t it misguided to summon concern over a few scientifically intriguing diseases, some of them new but of relatively small impact, while boring old diseases continue to punish humanity?

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.

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.

he warned me against the myth that ape hunting is a problem because local people are hungry. The reality, he said, is that local people eat duikers or rats or squirrels or monkeys—if they eat meat at all—whereas the fancy stuff, the illicit delicacies, the chimpanzee body parts, the gobs of elephant flesh, the hippopotamus steaks, get siphoned away by upscale demand from the cities, where premium prices justify the risks of poaching and illegal transport.

Plasmapheresis entails drawing blood from a donor, separating the cells from the plasma by means of filtering or centrifuging, putting the cells back into the donor, and keeping the plasma as a harvested product. One advantage of this process is that it allows donors (who are usually in fact sellers, paid for their trouble and needing the money) to be tapped often rather than just a couple times per year. Giving up your plasma, for the good of others or for profit, doesn’t leave you anemic. You can go back and give again the following week. One disadvantage of the procedure—and it’s a huge one, but wasn’t recognized in the early days—is that a plasmapheresis machine, gargling your blood and the blood of many other donors over the course of days, can infect you with a blood-borne virus. This happened to hundreds of paid plasma donors in Mexico during the mid-1980s. It happened to a quarter million luckless donors in China.

Two of those molecules become spiky protuberances from the outer surface of the viral envelope: hemagglutinin and neuraminidase. Those two, recognizable by an immune system, and crucial for penetrating and exiting cells of a host, give the various subtypes of influenza A their definitive labels: H5N1, H1N1, and so on. The term “H5N1” indicates a virus featuring subtype 5 of the hemagglutinin protein combined with subtype 1 of the neuraminidase protein. Sixteen different kinds of hemagglutinin, plus nine kinds of neuraminidase, have been detected in the natural world. Hemagglutinin is the key that unlocks a cell membrane so that the virus can get in, and neuraminidase is the key for getting back out. Okay so far? Having absorbed this simple paragraph, you understand more about influenza than 99.9 percent of the people on Earth. Pat yourself on the back and get a flu shot in November.

These scientists are on alert. They are our sentries. They watch the boundaries across which pathogens spill. And they are productively interconnected with one another. When the next novel virus makes its way from a chimpanzee, a bat, a mouse, a duck, or a macaque into a human, and maybe from that human into another human, and thereupon begins causing a small cluster of lethal illnesses, they will see it—we hope they will, anyway—and raise the alarm. Whatever happens after that will depend on science, politics, social mores, public opinion, public will, and other forms of human behavior. It will depend on how we citizens respond.

the ambitious goal of eradicating some infectious diseases entirely. They tried hard with yellow fever, spending millions of dollars and many years of effort, and failed. They tried with malaria, and failed. They tried later with smallpox, and succeeded. Why? The differences among those three diseases are many and complex, but probably the most crucial one is that smallpox resided neither in a reservoir host nor in a vector. Its ecology was simple. It existed in humans—in humans only—and was therefore much easier to eradicate. The campaign to eradicate polio, begun in 1988 by WHO and other institutions, is a realistic effort for the same reason: Polio isn’t zoonotic. And malaria is now targeted again. The Bill and Melinda Gates Foundation announced, in 2007, a new long-term initiative to eradicate that disease. It’s an admirable goal, a generously imaginative dream,