Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

Hong Kong wasn’t the origin of SARS, merely the gateway for its international dispersal . . . and very close to its origin. The whole phenomenon had begun quietly, several months earlier, in the southernmost province of mainland China, Guangdong,

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.

They were right, and the virus became known as SARS coronavirus, inelegantly abbreviated as SARS-CoV. It was the first coronavirus ever found to inflict serious illness upon humans.

Human SARS virus was a single branch, skinny and small, within a limb of branches representing what lives within horseshoe bats. What did this mean? 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.

A pair of porcupines was worth $1,000, Mr. Wei said. He did not lift one and poke its scrotum.

Many questions remain unanswered. Are bats the sole reservoir hosts of SARS-like coronavirus? If so, which kinds of bats? Is the coronavirus that was detected in least horseshoe bats the direct ancestor of SARS-CoV as found in humans? If so, how did the original spillover occur? Was it just a single transmission—from one bat into one civet—or several such happenings? And from civet into human—how many occurrences, how many independent spillovers?

One further factor, possibly the most crucial, was inherent to the way SARS-CoV affects the human body: 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. Even among some of the superspreaders, in 2003, this seems to have been true. That order of events allowed many SARS cases to be recognized, hospitalized, and placed in isolation before they hit their peak of infectivity. The downside was that hospital staff took the first big blasts of secondary infection; the upside was that those blasts generally weren’t emitted by people still feeling healthy enough to ride a bus or a subway to work.

With influenza and many other diseases the order is reversed, high infectivity preceding symptoms by a matter of days. A perverse pattern: the danger, then the warning. That probably helped account for the scale of worldwide misery and death during the 1918–1919 influenza: high infectivity among cases before they experienced the most obvious and debilitating stages of illness. The bug traveled ahead of the sense of alarm.

(An ordinary bacterium differs from a virus in several obvious ways: It’s a cellular organism, not a subcellular particle; it’s much larger than a virus; it reproduces by fission, not by invading a cell and commandeering the cell’s machinery of genetic copying; and it can usually be killed by antibiotics.)

The bird keeled over dead on Christmas Day, a bad omen, and Mrs. Martin started feeling ill about five days later. Psittacosis is the medical name for the ailment she contracted; it passes from birds (especially those of the order Psittaciformes, meaning parrots and their kin) to humans, causing fever, aches, chills, pneumonia, and sometimes death. “Parrot fever” was the label under which it raised alarm in the United States during early 1930, when people exposed to those unhealthy imported birds started getting sick, especially in Maryland.

“Sooner or later, all these episodes were established as Q fever.” After the war, research showed “the extraordinary versatility of C. burnetii as a parasite,” infecting dairy cows in California, sheep in Greece, rodents in North Africa, and bandicoots back home in Queensland. It passed from one species to another in the form of minuscule airborne particles, often dispersed from the placenta or the dried milk of an infected female animal, inhaled, and then activated through the lungs, or taken directly into the bloodstream from the bite of a tick. As he said, it was versatile.

The most revealing result from this analysis was that direct contact with animals was not a significant risk factor for infection. Nor was drinking raw milk. Some of the cases—but only a minority, less than 40 percent—involved contact with agricultural products such as hay, straw, and manure. From these data, the team narrowed it down to “windborne transmission” as the most likely source of Q fever in the area. The high incidence of infection among goats, the cascade of abortions, the practice of fertilizing fields with manure from the kidding sheds, the nature of the bacterium itself (more on this below), the dry April weather, and the easterly winds had combined to becloud the village of Herpen with Coxiella burnetii.

reproduces within cells of its host—as does a virus, though by dissimilar mechanisms—not out in the bloodstream or the gut, where it could be more easily targeted by immune response.

High-density dairy-goat husbandry, Dutch style—that’s one factor among several to account for the recent outbreaks, Roest said. Factor two was concomitant to factor one: proximity of humans.

Factor three was the weather: Yes, very dry springtime conditions, during each year since 2007, had doubtless exacerbated the airborne spread of the bacterium. And Roest suspected a fourth factor: It might be, he said, that the nature of the bug itself had changed. An evolutionary twitch could have enabled an ecological

Fieldwork along the lower Connecticut River revealed that Ixodes scapularis ticks were far more numerous in small woodlands and brush on the east bank of the river—the bank on which sat the village of Lyme—than on the west bank. That finding, combined with the fact that human cases also were far more common on the east bank, pointed further suspicion at the “deer tick” as a vector of what even Steere and his rheumatologist colleagues, having dropped the term “Lyme arthritis,” were now calling “Lyme disease.”

The one-word answer seemed to point toward a pragmatic solution to the problem of Lyme disease: Reduce the number of infected ticks by reducing the number of white-tailed deer.

So forget about deer abundance. White-tailed deer are involved in the Lyme disease system, yes, but involved like a trace element, a catalyst. Their presence is important but their numerousness is not. The littler mammals are far more critical in determining the scale of disease risk to people.

White-footed mice love acorns and, because the mice reproduce quickly and mature quickly, responding to food abundance with bursts of heightened fecundity, big masting events are often followed (after a two-year lag) by big increases in the mouse population. One pair of mice, given circumstances of plentiful food, could produce a net gain of fifty to seventy-five mice within a year. More acorns, more mice, more infected ticks, more Lyme.

Bear in mind that any patch of forest, surrounded by pavement and buildings and other forms of human impact, is to some degree an ecological island. Its community of land animals is insularized because, when individuals try to leave or to enter, they get squashed.

Be aware too that big islands generally support more diversity than small islands do. Madagascar is more richly diverse than Fiji, which in turn is more richly diverse than Pohnpei. Why? The simple answer is that greater land area and greater habitat diversity allow the survival of more kinds of creatures.

One of the signal lessons of Lyme disease, as Rick Ostfeld and his colleagues have shown, is that a zoonosis may spill over more readily within a disrupted, fragmented ecosystem than within an intact, diverse ecosystem.

A virus won’t grow in a medium of chemical nutrients because it can only replicate inside a living cell. In the technical parlance, it’s an “obligate intracellular parasite.” Its size is small and so is its genome, simplified down to the bare necessities for an opportunistic, dependent existence. It doesn’t contain its own reproductive machinery. It mooches. It steals.

Viruses face four basic challenges: how to get from one host to another, how to penetrate a cell within that host, how to commandeer the cell’s equipment and resources for producing multiple copies of itself, and how to get back out—out of the cell, out of the host, on to the next. A virus’s structure and genetic capabilities are shaped parsimoniously to those tasks.

That’s reflected in the fact that viruses are impervious to antibiotics—chemicals valued for their ability to kill bacteria (which are cells) or at least impede their growth. Penicillin works by preventing bacteria from building their cell walls. So do its synthetic alternatives, such as amoxicillin. Tetracycline works by interfering with the internal metabolic processes by which bacteria manufacture new proteins for cell growth and replication. Viruses, lacking cell walls, lacking internal metabolic processes, are oblivious to the effects of such killer drugs.

So the rate of mutation in most DNA viruses is relatively low. RNA viruses, coded by a single-strand molecule with no such corrective arrangement, no such buddy-buddy system, no such proofreading polymerase, sustain rates of mutation that may be thousands of times higher.

A virus doesn’t necessarily achieve anything by making its host sick. Its self-interest requires just replication and transmission. The virus enters cells, yes, and subverts their physiological machinery to make copies of itself, yes, and often destroys those cells as it exits, yes; but maybe not so many cells as to cause real harm.

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.

RNA viruses replicate speedily, generating their big populations (high titers) of virions within each host. Stated another way, they often produce acute infections, severe for a short time and then gone. Either they soon disappear or they kill you.

Culturing those samples sedulously, Chua’s group grew three isolates of Nipah virus, two from urine and one from a gobbet of water apple. The virus closely matched strains found in Nipah-sickened humans. This proved that flying foxes are reservoirs of Nipah virus, capable of spilling it into pigs that spill it into people.

Bangladesh is at special risk from infectious disease outbreaks for several reasons, most obvious of which is the density of its population. Within its fifty-seven thousand square miles of territory it contains almost 150 million people, making it the most densely populated country in the world (apart from tiny city-states such as Singapore and Malta). Its generally low elevation (barely thirty feet above sea level in most areas) and its regular cycles of flooding (because of monsoonal rains and high rivers) exacerbate the problem of waterborne diseases such as cholera and bacterial diarrhea, which kill tens of thousands of Bangladeshis (especially children) each year.

See how tricky it is to do epidemiology in a Bangladesh village? None of those innocent childhood pastimes I’ve mentioned, from duck burial to cricket, was significantly more associated with the infected boys (whether recovered or dead) than with their healthy peers. But one was: climbing trees.

The order Chiroptera (the “hand-wing” creatures) encompasses 1,116 species, which amounts to 25 percent of all the recognized species of mammals. To say again: One in every four species of mammal is a bat. Such diversity might suggest that bats don’t harbor more than their share of viruses; it could be, instead, that their viral burden is proportional to their share of all mammal diversity, and thus just seems surprisingly large.

Besides being diverse, bats are very abundant and very social. Many kinds roost in huge aggregations that can include millions of individuals at close quarters. They are also a very old lineage, having evolved to roughly their present form about 50 million years ago. Their ancientness provides scope for a long history of associations between viruses and bats, and those intimate associations may have contributed to viral diversity. When a bat lineage split into two new species, their passenger viruses may have split with them, yielding more kinds of virus as well as more kinds of bat.

Bats probably meet the critical community size standard more consistently than most other mammals. Their communities are often huge and usually large, offering a steady supply of susceptible newborns to become infected and maintain the viral presence.

Speaking of airborne: It’s not insignificant that bats fly. An individual fruit bat may travel dozens of miles each night, searching for food, and hundreds of miles in a season as it moves among roosting sites. Some insectivorous bats migrate as much as eight hundred miles between their summer and winter roosts. Rodents don’t make such journeys, and not many larger mammals do.

There was still no solid proof that AIDS was caused by a virus at all. But three kinds of evidence pointed that way, and Montagnier recalls them in his memoir, a book titled Virus. First, the incidence of AIDS among homosexuals linked by sexual interactions suggested that it was an infectious disease. Second, the incidence among intravenous drug users suggested a blood-borne infectious agent. Third, the cases among hemophiliacs implied a blood-borne agent that escaped detection in processed blood products such as clotting factor. So: It was infinitesimal, contagious, blood-borne.

HIV-2 is both less transmissible and less virulent than HIV-1. The molecular bases for those fateful differences are still secrets embedded in the genomes, but the ecological and medical ramifications are clear and stark. 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.

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

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.

A chimpanzee nest is simply a small platform of interwoven branches, often in the fork of a smallish tree, which provides just enough support for the ape to sleep comfortably. Each individual makes one each night, though a mother will share hers with an infant.

It did what a retrovirus does: penetrated cells, converted its RNA genome into double-stranded DNA, then penetrated further, into the cells’ nuclei, and inserted itself as DNA in the DNA genome of those host cells.

In ecological terms, we are almost paradoxical: large-bodied and long-lived but grotesquely abundant. We are an outbreak.