Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

(BSL-4) laboratory, a new sort of facility since Karl Johnson’s early work (and of which he was one of the pioneering designers), with multiple seals, negative air pressure, elaborate filters, and lab personnel working in space suits—a containment zone in which Ebola virus could be handled without risk (theoretically) of accidental release. No one knew whether any of these Zairian spleens contained the virus but each had to be treated as though it did. From the spleen material, minced finely and added to cell cultures, the lab people tried to grow the virus.

that infection of humans from the reservoir is a rare occurrence.

bleeding from the gums, bloody stools, bleeding from

and kills a bunch of people, and before you can get there and figure anything out, it’s gone.” It disappears back into the Congo forest, I said. “It disappears,” she agreed. “Yeah. Where did

was out

The

Ronald Ross’s eventual discovery of the mosquito-mediated life cycle of malarial parasites, for which he won his Nobel Prize in 1902, is famous in the annals of disease research

First, Ross delineated the life history of malarial parasites not as he found them infecting humans but as he found them infecting birds. Bird malaria is distinct from human malaria but it served as his great analogy.

Then, in 1906, after Louis Pasteur and Robert Koch and Joseph Lister and others had persuasively established the involvement of microbes in infectious disease, an English doctor named W. H. Hamer made some interesting points about “smouldering” epidemics in a series of lectures to the Royal College of Physicians in London. Hamer was especially interested in why diseases such as influenza, diphtheria, and measles seem to mount into major outbreaks in a cyclical pattern—rising to a high case count, fading away, rising again after a certain interval of time. What seemed curious was that the interval between outbreaks remained, for a given disease, so constant.

Reservoirs do not seek spillover; it happens accidentally and it gains them nothing. Therefore malaria is not zoonotic, because the four kinds of malarial parasite that infect humans infect only humans. Monkeys have their own various kinds of malaria. Birds have their own. Human malaria is exclusively human. So I was told, and it seemed to be true at the time.

The four kinds of malaria to which these statements applied are caused by protists of the species Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, and Plasmodium malariae, all of them belonging to the same diverse genus, Plasmodium, which encompasses about two hundred species. Most of the others infect birds, reptiles, or nonhuman mammals.

transmitted from person to person by Anophe...

MacDonald had identified a crucial index—fateful, determinative.

If the basic reproduction rate was less than 1, the disease fizzled away. If it was greater than 1 (greater than 1.0, to be more precise), the outbreak grew. And if it was considerably greater than 1.0, then kaboom: an epidemic.

If you read the recent scientific literature of disease ecology, which is highly mathematical, and which I do not recommend unless you are deeply interested or troubled with insomnia, you find the basic reproduction rate everywhere. It’s the alpha and omega of the field, the point where infectious disease analysis starts and ends. In the equations, this variable appears as R0, pronounced aloud by the cognoscenti as “R-naught.” (It’s a little confusing, I concede, that they use R0 as the symbol for basic reproduction rate and plain R as the symbol for recovered in an SIR model.

Outside of sub-Saharan Africa, most human cases are caused by Plasmodium vivax, the second-worst of the four kinds adapted particularly to infecting people.

He would allow them to cycle through three or four spikes of fever, delivering potent if not terminal setbacks to the Treponema, and then dose them with quinine, bringing the plasmodium under control. “The effect was remarkable; the downward progression of late-stage syphilis was stopped,” by one account, from the late Robert S. Desowitz, who was a prominent parasitologist himself as well as a lively writer.

PCR amplification of DNA fragments, followed by sequencing (reading out the genetic spelling) of those fragments, plumbs far deeper than microscopy. It allows a researcher to see below the level of cellular structure to the letter-by-letter genetic code.

scientists had made: that, unlike other malaria parasites, P. knowlesi is capable of reproducing in several kinds of primate. Its tastes in warm-blooded hosts are eclectic. It infects long-tailed macaques and pig-tailed macaques and banded leaf monkeys without distressing them much. It infects humans, sometimes, causing malaria that can be severe.

In late February 2003, SARS got on a plane in Hong Kong and went to Toronto.

officials at WHO headquarters in Geneva issued a global alert about these cases of unusual pulmonary illness in Vietnam and China. (Canada and the Philippines weren’t mentioned because this was just before their involvement was recognized.)

This seafood merchant was a man named Zhou Zuofeng. He holds the distinction of being the first “superspreader” of the SARS epidemic. A superspreader is a patient who, for one reason or another, directly infects far more people than does the typical infected patient. While R0 (that important variable introduced to disease mathematics by George MacDonald) represents the average number of secondary infections caused by each primary infection at the start of an outbreak, a superspreader is someone who dramatically exceeds the average. The presence of a superspreader in

In Geneva, at almost precisely the same time, WHO issued its global alert about a “severe, acute respiratory syndrome of unknown origin.” Officials at Singapore’s Ministry of Health were soon in the loop, made aware that three cases of atypical pneumonia (Esther Mok and her friend, plus another) had turned up at once, all traceable to Hong Kong’s Metropole Hotel.

As the first Intensive Care Unit filled up, two others were converted into SARS ICUs,

an unknown coronavirus was present in SARS patients—some of them, anyway—but that didn’t necessarily mean it had caused the disease. To establish causality, Peiris’s team tested blood serum from SARS patients (because it would contain antibodies)

SARS-CoV has no ominous ring. In older days, the new agent would have received a more vivid, geographical moniker such as Foshan virus or Guangzhou virus,

Watch out, he’s got Guangzhou! But by 2003 everyone recognized that such labeling would be invidious, unwelcome, and bad for tourism.

would more

Only three kinds of animal out of forty-four showed any sign of infection with a coronavirus. All three were microchiropterans. To you and me: little bats. Only one of those registered high prevalence as a group, with most of the sampled individuals testing positive, as measured by virus shed in their feces: a delicate thing called the small bent-winged bat.

“This bat coronavirus is quite different from SARS,”

Li’s study showed bats of three species in particular carrying SARS-like virus: the big-eared horseshoe bat, the least horseshoe bat, and Pearson’s horseshoe bat. If you ever notice these animals on the menu of a restaurant in southern China, you might want to choose the noodles instead.

High prevalence of antibodies to the virus among horseshoe bats, compared with zero prevalence among wild civets, was an important discovery.

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

It meant that you could kill every civet in China and SARS would still be among you. It meant that this virus existed—facing its ecological limits and opportunities—within a culture where “an infectious consignment of bats” might arrive at a meat market as a matter of course. It meant, Let the diner beware. And it meant that further research was needed.

Aleksei took me out to a food market for a glimpse of what’s presently available in Guilin’s aboveground economy. Strolling the narrow corridors between stalls, I saw vegetables laid out in neat bundles. The fruits were carefully piled. The mushrooms were gnomic. The red meat was sold mainly in slabs, joints, and pieces by women at large plywood tables, wielding sharp cleavers. The catfish, the crabs, and the eels churned slowly in aerated tanks. The bullfrogs huddled darkly in scrums. It was grim to be reminded how we doom animals with our appetite for flesh, but this place seemed no more odd or morbid than a meat market anywhere. That was the point. This was the “after” condition in a “before/after” contrast revealing how SARS had put a damper on yewei. What had changed here in recent years, Aleksei told me, was the disappearance of the trade in wildlife.

At the Chatou market in Guangzhou, for instance, he had seen storks, seagulls, herons, cranes, deer,

alligators, crocodiles, wild pigs, raccoon dogs, flying squirrels, many snakes and turtles, many frogs, as well as domestic dogs and cats, all on sale as food. There were no civets, not when he saw the place; they had already been demonized and purged.

You could also buy leopard cat, Chinese muntjac, Siberian weasel, Eurasian badger, Chinese bamboo rat, butterfly lizard, and Chinese toad, plus a long list of other reptiles, amphibians, and mammals, including two kinds of fruit bat. Quite an epicure’s menu. And of course birds: cattle egrets, spoonbills, cormorants, magpies, a vast selection of ducks and geese and pheasants and doves, plovers, crakes, rails, moorhens, coots, sandpipers, jays, several flavors of crow.

“People in south China will eat everything that flies in the sky, except an airplane.” He was a northerner himself.

After the SARS outbreak and the civet publicity, local governments (presumably with some pressure from Beijing) had tightened down, enacting new restrictions against wildlife in the markets. The Era of Wild Flavor hadn’t ended but it had been driven underground.

Likewise in a Chinese bat cave. If you were absolutely concerned to shield yourself against the virus, you’d need not just a mask but a full Tyvek coverall, and gloves, and goggles—or maybe even a bubble hood and visor, your whole suit positive-pressurized with filtered air drawn in by a battery-powered fan.

What is it that makes this virus unusual? and 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.

COVID-19 is infectious before symptoms appear.

Symptoms tend to appear in a person before, rather than after, that person becomes highly infectious. The headache, the fever, and the chills—maybe even the cough—precede the major discharge of virus toward other people.

The much darker story remains to be told, probably not about this virus but about another. When the Next Big One comes, we can guess, it will likely conform to the same perverse pattern, high infectivity preceding notable symptoms. That will help it to move through cities and airports like an angel of death.

Q fever. Never mind, for the moment, the origin of that name. The most notable thing about Q fever is that, even now in the age of antibiotics, for reasons related to its anomalous biology, it’s still capable of causing serious devilment. Psittacosis. Around the same time as Q fever emerged, in the 1930s, another peculiar bacterial zoonosis hit the news. This one also had links to Australia, but its scope was global, and it seems to have first reached the United States by way of a shipment of diseased parrots from South America. That was in late 1929, just in time for the Christmas season of parrot-giving. One unlucky recipient was Lillian Martin, of Annapolis, Maryland, whose husband bought her a parrot from a pet store in Baltimore. The bird keeled over dead on Christmas Day, a bad omen, and Mrs. Martin started feeling ill about five days later.

Lyme disease. This seems to be a more recent version of the spooky-new-bacteria phenomenon. In the mid-1970s, two alert mothers in Lyme, Connecticut, near Long Island Sound, noticed that not only their children but a high incidence of other youngsters nearby had been diagnosed with juvenile rheumatoid arthritis.

Ticks of the genus Ixodes, commonly called “deer ticks,” were abundant in the forests of eastern Connecticut and surrounding areas. In the early 1980s, a microbiologist named Willy Burgdorfer found a new bacterium in the guts of some Ixodes ticks, a likely suspect as the causative agent. It was a spirochete, a long spiral form, closely resembling other spirochetes of the genus Borrelia. After further research confirmed its role in the arthritis-like syndrome, that bacterium was named Borrelia burgdorferi in honor of its principal discoverer. Lyme disease is now the most common tick-borne disease in North America and one of the fastest-increasing infectious diseases of any sort,

In this building, Roest told me, we work also on West Nile virus, Rift Valley fever, and foot-and-mouth disease, among other things. Rift Valley fever, I said, you have that in the Netherlands? Not yet, he said.