Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

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.

So was the so-called Spanish influenza of 1918–1919, which had its ultimate source in a wild aquatic bird and, after passing through some combination of domesticated animals (a duck in southern China, a sow in Iowa?) emerged to kill as many as 50 million people before receding into obscurity.

This form of interspecies leap is common, not rare; about 60 percent of all human infectious diseases currently known either cross routinely or have recently crossed between other animals and us.

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.

The eradication campaign for poliomyelitis, unlike other well-meant and expensive global health initiatives, may succeed. Why? Because vaccinating humans by the millions is inexpensive, easy, and permanently effective, and because apart from infecting humans, the poliovirus has nowhere to hide. It’s not zoonotic.

Screening for antibodies is distinct from isolating virus, just as a footprint is distinct from a shoe. Antibodies are molecules manufactured by the immune system of a host in response to the presence of a biological intruder. They are custom-shaped to merge with and disable that particular virus, or bacterium, or other bug. Their specificity, and the fact that they remain in the bloodstream even after the intruder has been conquered, make them valuable as evidence of present or past infection.

Meningitis is a term applicable to any inflammation of the membranes that cover the brain and the spinal cord; it might be caused by a bacterium, a virus, even a reaction to a drug, and it might go away as inexplicably as it appeared.

Similarity of one kind of host animal to another is a significant indicator of the likelihood that a pathogen can make the leap.

Pigs are special: They excrete far more of the virus than other livestock, and over a longer period of time, broadcasting it prodigiously in their respiratory exhalations. They sneeze it, they chuff it, they oink it, they wheeze it and burp it and cough it into the air. One experimental study found that pig breath carried thirty times as much FMD virus as the breath of an infected cow or sheep, and that once airborne it could spread for miles. That’s why pigs are considered an amplifier host of this virus. An amplifier host is a creature in which a virus or other pathogen replicates—and from which it spews—with extraordinary abundance.

Captain James Cook had already come and gone, “discovering” the place, but Phillip’s group would be the first European settlers. At a spot near what is now Sydney, within the fine natural harbor there, his penal arks put ashore 736 convicts, 74 pigs, 29 sheep, 19 goats, 5 rabbits, and 9 horses. The horses included two stallions, four mares, and three foals. Until that day there was no record, either fossil or historic, of members of the genus Equus in Australia. Nor were there any oral traditions (none shared with the world so far, anyway) of Hendra virus outbreaks among aboriginal Australians.

Make no mistake, they are connected, these disease outbreaks coming one after another. And they are not simply happening to us; they represent the unintended results of things we are doing. They reflect the convergence of two forms of crisis on our planet. The first crisis is ecological, the second is medical. As the two intersect, their joint consequences appear as a pattern of weird and terrible new diseases, emerging from unexpected sources and raising deep concern, deep foreboding, among the scientists who study them.

Mankind’s activities are causing the disintegration (a word chosen carefully) of natural ecosystems at a cataclysmic rate. We all know the rough outlines of that problem. By way of logging, road building, slash-and-burn agriculture, hunting and eating of wild animals (when Africans do that we call it “bushmeat” and impute a negative onus, though in America it’s merely “game”), clearing forest to create cattle pasture, mineral extraction, urban settlement, suburban sprawl, chemical pollution, nutrient runoff to the oceans, mining the oceans unsustainably for seafood, climate change, international marketing of the exported goods whose production requires any of the above, and other “civilizing” incursions upon natural landscape—by all such means, we are tearing ecosystems apart. This much isn’t new. Humans have been practicing most of those activities, using simple tools, for a very long time. But now, with 7 billion people alive and modern technology in their hands, the cumulative impacts are becoming critical.

But now the disruption of natural ecosystems seems more and more to be unloosing such microbes into a wider world. When the trees fall and the native animals are slaughtered, the native germs fly like dust from a demolished warehouse. A parasitic microbe, thus jostled, evicted, deprived of its habitual host, has two options—to find a new host, a new kind of host . . . or to go extinct. It’s not that they target us especially. It’s that we are so obtrusively, abundantly available.

There’s no reason to assume that AIDS will stand unique, in our time, as the only such global disaster caused by a strange microbe emerging from some other animal. Some knowledgeable and gloomy prognosticators even speak of the Next Big One as an inevitability. (If you’re a seismologist in California, the Next Big One is an earthquake that drops San Francisco into the sea, but in this realm of discourse it’s a vastly lethal pandemic.) Will the Next Big One be caused by a virus? Will the Next Big One come out of a rainforest or a market in southern China?

Any such spillover in the reverse direction—from humans to a nonhuman species—is known as an anthroponosis.

This is a pointed example of why solving the reservoir mystery is important: If you know which animal harbors a certain virus and where that animal lives—and conversely, where it doesn’t live—you know where the virus may next spill over, and where it probably won’t.

Four different ebolaviruses are scattered variously across Central Africa and have emerged from their reservoir hosts to cause human disease (as well as gorilla and chimpanzee deaths) in six different countries: South Sudan, Gabon, Uganda, Côte d’Ivoire, the Republic of the Congo, and the Democratic Republic of the Congo. A fifth ebolavirus seems to be endemic to the Philippines, and to have traveled from there several times to the United States in infected macaques.

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.

They found evidence suggesting that the medical outcome for an individual patient—to survive and recover, or to die—might be related not to the size of the infectious dose of Ebola virus but to whether the patient’s blood cells produced antibodies promptly in response to infection.

But epidemiologists have recognized that, with measles virus, as with other pathogens, there’s a critical minimum size of the host population, below which it can’t persist indefinitely as an endemic, circulating infection. This is known as the critical community size (CCS), an important parameter in disease dynamics.

Another crucial aspect of measles is that the virus is not zoonotic. If it were—if it circulated also in animals living near or among human communities—then the question of critical community size would be moot. There wouldn’t be any necessary minimum size of the human population, because the virus could always remain present, nearby, in that other source.

Continuation of the outbreak depended on the likelihood of encounters between people who were infectious and people who could be infected. This idea became known as the “mass action principle.”

By a strict definition, zoonotic pathogens (accounting for about 60 percent of our infectious diseases, as I’ve mentioned) are those that presently and repeatedly pass between humans and other animals, whereas the other group of infections (40 percent, including smallpox, measles, and polio) are caused by pathogens descended from forms that must have made the leap to human ancestors sometime in the past.

So you have density, infectivity, mortality, and recovery—four factors interrelated as fundamentally as heat, tinder, spark, and fuel. Brought together in the critical measure of each, the critical balance, they produce fire: epidemic.

Political communications are filtered through the national government in Beijing. That constraint applies also, and unfortunately, to the scientific and medical institutions in both places—such as Hong Kong University, with its excellent medical school, and the Guangzhou Institute of Respiratory Diseases. Lack of basic communication, let alone resistance to collaborative work and sharing of clinical samples, caused problems and delays in responding to SARS.

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.

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

More accurately known as the masked palm civet, it’s a member of the viverrid family, which includes the mongooses. 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.

The whole world was supposedly “SARS-free.” What those declarations meant, more precisely, was that no SARS infections were currently raging in humans. But the virus hadn’t been eradicated. This was a zoonosis, and no disease scientist could doubt that its causal agent still lurked within one or more reservoir hosts—the palm civet, the raccoon dog, or whatever—in Guangdong and maybe elsewhere too. People celebrated the end of the outbreak, but those best informed celebrated most guardedly. SARS-CoV wasn’t gone, it was only hiding. It could return.

This was an enormously consequential factor in the SARS episode—not just lucky but salvational. 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.

If SARS had conformed to the perverse pattern of presymptomatic infectivity, its 2003 emergence wouldn’t be a case history in good luck and effective outbreak response. It would be a much darker story.

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.

First of all, it’s an intracellular bacterium, meaning that it 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.

“Deer ticks” of the species Ixodes scapularis do not draw their crucial sustenance from deer.

“The notion that Lyme disease risk is closely tied to the abundance of deer arose from field studies that began shortly after the discoveries of the bacterial agent of Lyme disease and the involvement of ticks as vectors of these bacteria,” he wrote. Those studies were thorough and energetic, he noted, but perhaps driven too much by desire for a simple answer from which public health actions could be taken. Their context was “the hunt for the culprits—the critical species.”

Nineteen deer (sixteen does and three bucks) were killed, after which a Dover newspaper explained confidently: “The higher the number of deer in an area, the higher the chances are of spreading Lyme disease to humans.” Well, actually, no. That simple formula is as false as the notion that swamp vapors bring malaria.

Generally what seems to happen is that a larval tick acquires the spirochete by taking its blood meal from an infected host—a mouse, a shrew, a whatever. It molts to become a nymph and then, if it gets its next meal from an uninfected host, the nymph passes the infection to that animal, by drooling spirochetes into the wound along with its anticoagulant saliva. “If mammals didn’t make ticks sick,” Ostfeld said, “ticks wouldn’t make mammals sick later on.” Such reciprocal infectivity helps keep the prevalence of B. burgdorferi high in both tick populations and hosts.

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.

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.

The mouse is a good colonizer, a good survivor, a fecund breeder, an opportunist; it is there to stay. Restrained by few predators and few competitors, its population fluctuates around a relatively high average level and, in summers following a big acorn crop, goes much higher still. A plague of mice will infest the little woodland, like rats on the road out of Hamelin. There will also be plenty of ticks. The ticks drink heartily of mouse blood and have a high rate of survival, because white-footed mice (unlike possums, catbirds, or even chipmunks) are not very good at grooming themselves clear of larvae. And because the mouse is such a competent reservoir of Borrelia burgdorferi—so efficient at harboring and transmitting it—most ticks carry the infection.

Some people take “All life is connected” to be the central truth of ecology, Ostfeld added. It’s not. It’s just a vague truism. The real point of the science is understanding which creatures are more intimately connected than others, and how, and to what result when change or disturbance occurs.

Mutation supplies new genetic variation. Variation is the raw material upon which natural selection operates. Most mutations are harmful, causing crucial dysfunctions and bringing the mutant forms to an evolutionary dead end. But occasionally a mutation happens to be useful and adaptive. And the more mutations occurring, the greater chance that good ones will turn up.

Poliomyelitis is not a zoonosis; it doesn’t naturally affect any animals other than humans; but with the help of a hypodermic needle, it could be made to grow in monkeys.

Herpes B is a very rare infection in humans but a nasty one, with a case fatality rate of almost 70 percent among those few dozen people infected during the twentieth century (before recent breakthroughs in antiviral pharmaceutics) and almost 50 percent even since then. When it doesn’t kill, it often leaves survivors with neurological damage.

However dangerous herpes B might be when infecting a person, the chances of monkey-human transmission seem to be extremely small. That’s what those research results from the Sangeh Monkey Forest in Bali suggest. Lisa and Gregory found a high prevalence of the virus among the macaques there, and a high incidence of macaque bites and scratches among the people, but no evidence of herpes B transfer. If cases do sometimes occur in Bali, they must escape medical notice, or else get taken for some other dreadful disease, such as polio, or rabies, which is a serious problem in Bali because of its prevalence among the island’s dogs. Nobody knows whether any undetected herpes B infections have come out of Sangeh. Possibly, none have.

To understand why some outbreaks of viral disease go big, others go really big, and still others sputter intermittently or pass away without causing devastation, consider two aspects of a virus in action: transmissibility and virulence. These are crucial parameters, defining and fateful, like speed and mass. Along with a few other factors, they largely determine the gross impact of any outbreak. Neither of the two is an absolute constant; they vary, they’re relative. They reflect the connectedness of a virus to its host and its wider world. They measure situations, not just microbes. Transmissibility and virulence: the yin and yang of viral ecology.

Transmission is travel from one host to another, and transmissibility is the packet of attributes for achieving it. 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. It goes airborne from one host to another.

Bacterial pneumonia, for instance, accounts for about ninety thousand deaths annually just among Bangladeshi children under age five. Bacterial diarrhea kills about twenty thousand newborn infants every year.

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.

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.