Can We Predict Which Viruses Will Spread from Animals to Humans?

The natural world is a reservoir of plagues. At any moment, untold numbers of viruses circulate among animals. Inevitably, some will cross the species barrier, infecting people and making them sick. Scientists call such an event a “zoonotic spillover.” No one knows how often such spillovers happen—presumably, animal viruses are always establishing footholds that our immune systems destroy. We notice, though, when the viruses propagate. Today, countries around the world are seeing cases of monkeypox, a milder relative of smallpox. Just like COVID-19, the disease originated in other animals. It was seen first in monkeys, in 1958, before being detected in a boy, in 1970. Other recent spillovers have caused diseases including Ebola, flu, Lassa, Marburg, MERS, Nipah, SARS, and Zika.

Dawn Zimmerman, a fifty-one-year-old wildlife veterinarian formerly at the Smithsonian Global Health Program, has spent years studying zoonotic viruses in wildlife in Turkana county, Kenya. On one trip in 2017, she visited an area in the northwest called No Man’s Land. “It’s because no one owns it,” she told me. “People are always fighting over that land.” On a field day, her team might gather early in the morning to drive into the bush, sometimes accompanied by armed guards. They would check rodent traps set the night before, taking oral and rectal swabs from any animal they found, and follow troops of baboons, picking up droppings and sampling them. Occasionally, they would set a trap for a baboon—a cage that closes when a primate pulls on an ear of maize tied to a string—to facilitate sampling. In the evening, they’d use mist nets on riverbanks to catch the bats that emerged after dusk.

Sometimes the team took samples from camels—livestock animals that are known to be “viral reservoirs,” or sources of possible spillover. In one town, a woman named Ester was in charge of the livestock; after having tea in Ester’s house, Zimmerman’s team went out to meet the animals, bringing along medicine for them as a thank-you. They hadn’t brought enough, and an owner pointed what looked like an AK-47 at them. “She just put her finger up, and she’s, like, ‘No!’ ” Zimmerman recalled, of Ester. “And he put his gun away.” To access a different site, they had to cross a river. “The first thing I asked is, ‘Are there crocodiles in this river?’ And they said, ‘No, no, totally hunted out, no problem,’ ” Zimmerman told me. The researchers crossed as part of a large crowd, with Zimmerman immersed to her chest. That night, while they were setting up their bat nets, they saw two pairs of crocodile eyes shining in the water.

While sampling, researchers like Zimmerman wear N95 respirators, rubber boots, one or two pairs of gloves, and Tyvek suits—a getup that can become unbearable in the heat. They lug around a container of liquid nitrogen for storing their samples until they can be frozen and sent to a lab, where researchers will screen them for viruses, then sequence the viruses’ genes to determine if they’re known or novel. In another lab, further analyses might attempt to predict the risk that any novel viruses pose to people. For several years, Zimmerman’s data made its way to PREDICT, a program run by the United States Agency for International Development (U.S.A.I.D.) aimed at predicting, preventing, and containing emerging infectious diseases. From 2009 to 2020, PREDICT’s researchers collected samples from a hundred and sixty thousand animals and people in about thirty countries, and discovered almost a thousand new viruses. It’s since been replaced by DEEP-VZN (Discovery & Exploration of Emerging Pathogens—Viral Zoonoses), a five-year program, also funded by U.S.A.I.D., which will spend a hundred and twenty-five million dollars to find new viruses in animals around the world. DEEP-VZN will focus in particular on coronaviruses, filoviruses, and paramyxoviruses—the three viral families that include SARS-CoV-2, Ebola, and measles. (U.S.A.I.D. has also launched a hundred-million-dollar effort called STOP Spillover, aimed at preventing and catching spillovers, based on knowledge gained from viral surveillance.) “It will be a defining characteristic of this century, these zoonotic spillovers,” Dennis Carroll, the infectious-disease specialist who founded PREDICT, told me. Today, Carroll runs the Global Virome Project (G.V.P.), another successor to PREDICT.

Vast amounts of money are flowing to these initiatives, under the theory that understanding what’s out there, where it lies, and how it might jump to humans will help us stop spillovers and respond to them more effectively when they happen. Implicit in such efforts is an idea about how spillovers work. They are like ticking time bombs: spot them soon enough, and we might defuse them. But some scientists see money spent on spillover prediction as money misspent. Spillovers happen, they say, but predicting them is beyond our current or foreseeable abilities. Pandemics, in this view, are a bit like avalanches: we know that somewhere on a slope a small crack will open and spread, snowballing into something monstrous, and we know that this is more likely to happen in certain areas and under certain conditions—and yet we can’t forecast precisely when or where. Just as avalanches emerge from an accumulation of complex mechanical and meteorological processes, so pandemics happen when a knotted interplay of molecular, physiological, ecological, social, and economic conditions converge. They will always surprise us.

It could be that, instead of surveying wildlife, we are better off monitoring people and catching outbreaks early, after spillover has occurred. Richard Ebright, a microbiologist at Rutgers University who studies infectious disease, has emerged as a major critic of the prediction approach, and believes that wildlife monitoring could actually increase the risk of an outbreak. “The possibility that SARS-CoV-2 entered humans as a direct result of the activities of PREDICT—during field collection of bats and bat excreta, or during laboratory characterization of bats, bat excreta, or bat viruses—cannot be excluded,” he told me. As for whether the Global Virome Project will improve on PREDICT’s efforts, he said, “expanding a program that at best was an expensive failure would be frank insanity. One could not possibly invest research funding less wisely.”

James Bangura joined PREDICT after an Ebola outbreak in Sierra Leone, in 2014. “It was horrifying,” he said, of the virus’s toll. Bangura lost three friends and colleagues to Ebola. As a surveillance lead for the country’s Ministry of Health and Sanitation, he monitored the spread of the virus, winning a Presidential medal for his work. The next year, PREDICT started operations in Sierra Leone, and he signed on soon after.

Bangura’s team, like Zimmerman’s, looked for spillover-ready viruses in bats, rodents, and nonhuman primates, taking samples from forty to eighty animals during a typical two-week trip. In 2016, they discovered a new kind of Ebola virus that was hiding not in caves or forests but in people’s homes: four bats in three small villages within a dozen miles of one another, in the Bombali district of Sierra Leone, were found to be hosts for what would eventually be called Bombali ebolavirus. Whether it will sicken people, or travel between them, remains uncertain—there are no known cases of human infection. “Seeing a new kind of Ebola was a huge fulfillment for me in my career,” Bangura said. After the discovery, “the energy was there: ‘O.K., let’s look for more viruses.’ ” In 2020, Bangura’s team reported the first discovery of Marburg virus in bats in West Africa. Including the current outbreak, there have been fifteen recorded spillovers of Marburg; the largest, which occurred in Angola, in 2004-05, killed ninety per cent of the two hundred and fifty-two people known to have been infected. After both of Bangura’s discoveries, PREDICT mounted a public-information campaign on the dangers of interaction with bats, and increased animal-sampling for viruses—measures meant to prevent spillovers from occurring.

PREDICT has created a hot-spot map indicating where zoonoses, including coronavirus spillovers, are likely to occur. (Other groups, including researchers at Oxford and EcoHealth Alliance, an N.G.O. that studies emerging infectious diseases, have created similar maps for other viruses.) These maps extrapolate from past spillover events and ecological factors associated with them. One thing they look at is the distribution of animal species. Bats are a logical place to look if you want to predict spillovers. SARS-CoV-2 almost certainly came from bats—perhaps reaching humans through an intermediary animal, such as a pangolin—as did the coronaviruses that cause SARS and MERS. “Bats, for some reason, seem to be really good hosts for coronavirus,” Timothy Sheahan, a virologist at the University of North Carolina, told me. Some researchers have suggested that, in order to help their bodies cope with the stresses of flight, the animals have evolved to suppress inflammation, which makes it easier for them to tolerate viral infections without developing disease. Tracey Goldstein, a comparative pathologist at the University of California, Davis, School of Veterinary Medicine who served as PREDICT’s lab director, said that the project’s surveyors tended to find a few new coronaviruses inside each species of bat they surveyed.

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