Spillover: Animal Infections and the Next Human Pandemic

by David Quammen

What I can tell you is that Bangladesh, wondrous in so many ways, engaging and fascinating as well as horrifying to an affluent visitor, is an especially difficult country in which to be a poor citizen, either urban or rural, because if you’re poor it’s a difficult country in which to remain healthy.

Blood tests, done on several of the patients, showed dramatic depletions of certain lymphocytes (white blood cells) that are crucial in regulating immune responses. Specifically, it was thymus-dependent lymphocytes (T cells, for short) that were “profoundly depressed” in number.

Another perceived starting point was Gaëtan Dugas, the young Canadian flight attendant who became notorious as “Patient Zero.” You’ve heard of him, probably, if you’ve heard much of anything about the dawning of AIDS. Dugas has been written about as the man who “carried the virus out of Africa and introduced it into the Western gay community.” He wasn’t. But he seems to have played an oversized and culpably heedless role as a transmitter during the 1970s and early 1980s. As a flight steward, with almost cost-free privileges of personal travel, he flew often between major cities in North America, joining in sybaritic play where he landed, notching up conquests, living the high life of a sexually voracious gay man at the height of the bathhouse era. He was handsome, sandy-haired, vain but charming, even “gorgeous” in some eyes. According to Randy Shilts, author of And the Band Played On (which includes much heroic research and a fair bit of presumptuous reimagining), Dugas himself reckoned that in the decade since becoming actively gay he had had at least twenty-five hundred sexual partners.

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.

“In 1985, the highest rates of HIV were reported in the U.S. and Europe,” Essex and Kanki wrote later, “but disturbing reports from central Africa indicated that high rates of HIV infection and of AIDS prevailed there, at least in some urban centers.” The focus of suspicion was shifting: not Asia, not Europe, not the United States, but Africa might be the point of origin.

The straights were just banging away in 1985, no idea of the risks they were exposing themselves to

might: a virus intermediate between HIV and SIV. With the code unblinded, Kanki learned that the positive results came from Senegalese prostitutes. In retrospect it made sense. Prostitutes are at high risk for any sexually transmitted virus, including a new one recently spilled into humans. And the density of the rural human population in Senegal, where African green monkeys are native, makes monkey-human interactions (crop-raiding by monkeys, hunting by humans) relatively frequent.

The paths of discovery may be sinuous, the labels may seem many, and maybe you can’t tell the players without a scorecard; but these details aren’t trivial. The difference between HIV-2 and HIV-1 is the difference between a nasty little West African disease and a global pandemic.

Recent spillover seemed more likely. Still, the case against that idea got a boost in 1988, when a group of Japanese researchers sequenced the complete genome of SIV from an African green monkey. The animal came from Kenya. The nucleotide sequence of its retrovirus proved to be substantially different from the sequence for HIV-1, and different in roughly the same degree from HIV-2.

Back in September 1979, scientists at a primate research center in New Iberia, Louisiana, south of Lafayette, noticed a leprosy-like infection in one of their captive monkeys. This seemed odd, because leprosy is a human disease caused by a bacterium (Mycobacterium leprae) not known to be transmissible from people to other primates. But here was a leprous monkey.

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.

the awesome decrepitude of a postcolonial metropolis shaped by eight decades of Belgian opportunism, three decades of dictatorial misrule and egregious theft, and then a decade of war, but filled with 10 million striving people, some of whom are dangerous thugs (as in all cities) and most of whom are amiable, hopeful, and friendly.

All that mattered was blood-to-blood contact. The cut-hunter hypothesis was speculative but plausible. It was parsimonious, requiring few complications and no unlikelihoods.

from animals infected with SIVcpz. The result of that flawed vaccinating, certain people have argued, was iatrogenic infection (disease caused by medical treatment) of an unknown number of Central Africans with what later became recognized as HIV-1. By this notion, known for short as the OPV (oral polio vaccine) theory, a single reckless researcher had seeded the continent—and the world—with AIDS.

This is how molecular biologists calculate an important parameter they call TMRCA: time to most recent common ancestor. Okay so far? You’re doing great. Take a breath.

much for where as well as when. 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. That leaves our third question: how?

Although this was Saturday night, the lights of Mambele Junction didn’t amount to much and despite their dim glow we could see not just the Big Dipper, Orion’s Belt, and the Southern Cross but even the Milky Way, arcing overhead like a great smear of glitter. You know you’re in the boonies when the galaxy itself is visible downtown.

lingered long enough for the oddness to strike me. Throughout the rest of the world you see AIDS-education materials crying out: Practice safe sex! Wear a condom! Don’t reuse needles! Here the message was: Don’t eat apes!

This study by Gilbert and Worobey and their colleagues delivered one other piquant finding. Their data and analysis indicated that just a single migration of the virus—one infected person or one container of plasma—accounted for bringing AIDS to America. That sorry advent occurred in 1969, give or take about three years.

An entomologist named Alan A. Berryman addressed it some years ago in a paper titled “The Theory and Classification of Outbreaks.” He began with basics: “From the ecological point of view an outbreak can be defined as an explosive increase in the abundance of a particular species that occurs over a relatively short period of time.” Then, in the same bland tone, he noted: “From this perspective, the most serious outbreak on the planet earth is that of the species Homo sapiens.” Berryman was alluding, of course, to the rate and the magnitude of human population growth, especially within the last couple centuries. He knew he was being provocative.

Another way to comprehend it is this: From the time of our beginning as a species (about 200,000 years ago) until the year 1804, human population rose to a billion; between 1804 and 1927, it rose by another billion; we reached 3 billion in 1960; and each net addition of a billion people, since then, has taken only about thirteen years. In October 2011, we came to the 7-billion mark and flashed past like it was a “Welcome to Kansas” sign on the highway. That amounts to a lot of people, and certainly qualifies as an “explosive” increase within Berryman’s “relatively short period of time.” The rate of growth has declined within recent decades, true, but it’s still above 1 percent, meaning that we’re adding about 70 million people yearly.

the abundance of humans on Earth right now. Our total weight amounts to about 750 billion pounds. Ants of all species add up to a greater total mass, krill do too, but not many other groups of organisms.

A trillion pounds of cows, fattening in feedlots and grazing on landscapes that formerly supported wild herbivores, are just another form of human impact. They’re a proxy measure of our appetites, and we are hungry. We are prodigious, we are unprecedented. We are phenomenal. No other primate has ever weighed upon the planet to anything like this degree. In ecological terms, we are almost paradoxical: large-bodied and long-lived but grotesquely abundant. We are an outbreak.

And here’s the thing about outbreaks: They end. In some cases they end after many years, in other cases they end rather soon. In some cases they end gradually, in other cases they end with a crash. In certain cases, even, they end and recur and end again, as though following a regular schedule.

that such death and misery don’t occur again. Even during an average year, seasonal flu causes at least 3 million cases and more than 250,000 fatalities worldwide. So influenza is hugely dangerous, at best. At worst, it would be apocalyptic.

First, the basics. Influenza is caused by three types of viruses, of which the most worrisome and widespread is influenza A. Viruses of that type all share certain genetic traits: a single-stranded RNA genome, which is partitioned into eight segments, which serve as templates for eleven different proteins. In other words, they have eight discrete stretches of RNA coding, linked together like eight railroad cars, with eleven different deliverable cargoes. The eleven deliverables are the molecules that comprise the structure and functional machinery of the virus. They are what the genes make. 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.

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 peopl...

Robert Webster today is arguably the most eminent influenza scientist in the world. He grew up on a New Zealand farm, studied microbiology, did his doctorate at Canberra, worked and cavorted with Laver, then moved to the United States in 1969, taking a post at St. Jude Children’s Research Hospital in Memphis, and has been there (apart from his frequent travels) ever since.

One of the things that makes influenza so problematic, Webster said, is its propensity to change.

First of all there’s the high rate of mutation, as in any RNA virus. No quality control as it replicates, he said, echoing what I’d heard from Eddie Holmes. Continual copying errors at the level of individual letters of code. But that’s not the half of it. Even more important is the reassortment. (“Reassortment” means the accidental swapping of entire genomic segments between virions of two different subtypes.

The steady incidence of mutations yields incremental change in how the virus looks and behaves. Ergo you need another flu shot every autumn: This year’s version of flu is different enough from last year’s. Reassortment yields big changes. Such major innovations by reassortment, introducing new subtypes, which may be infectious but unfamiliar to the human population, are what generally lead to pandemics.

Only subtypes bearing H1, H2, or H3 as their hemagglutinin cause human flu epidemics, because only those spread readily from person to person. Pigs offer conditions intermediate between what a flu virus finds in people and what it finds in birds; therefore pigs get infected with both human subtypes and bird subtypes. When an individual pig is infected simultaneously with two viruses—one adapted to humans, one adapted to birds—the opportunity exists for reassortment between those two.

Other subtypes, featuring H7 and H5, have occasionally “tried on” the prospect of targeting people, Webster said. And in all cases so far, the fit has been bad. “They infect humans,” he said, “but they haven’t acquired transmissibility.”

But some things bear watching. Case in point: H5N1, more familiar to you and me as bird flu.

Webster himself played a crucial role in responding to that scary subtype when it first emerged. A three-year-old boy died in Hong Kong of influenza, in May 1997, and a swab sample from his windpipe yielded virus. The lab scientists in Hong Kong didn’t recognize that virus. Some of the boy’s sample went to the CDC, but no one there got around to characterizing it. Then a Dutch scientist on a visit to Hong Kong was given a bit of the virus, and he went home and worked on it immediately. Hmm, mijn God. The Dutchman informed his international colleagues that it looked like an H5. A bird flu. “And we all said, ‘no, impossible,’ ” Webster recalled. “Since H5 doesn’t affect humans. We thought it was a mistake.” It wasn’t. What seemed so alarming is that this was the first documented case of a purely avian influenza virus—containing no human-flu genes brought in by reassortment—to cause killer respiratory illness in a person. Three more cases turned up in November, at which point Webster himself jumped on a plane for Hong Kong.

The virus was hard to trace in such circumstances, harder still to eliminate, because infected ducks showed no symptoms. “The duck is the Trojan horse,” Webster told me. That’s where the danger lurked secretly, he meant. Wild ducks might land on your flooded paddy, carrying the virus, fouling the water, and infecting your domestic ducks. Your ducks would appear fine, but when your son brought them home to their coop for the night, they could infect your chickens. Before long your chickens—and your son too—might be dead of bird flu.

Most people aren’t familiar with the word “zoonotic,” but they have heard of SARS, they have heard of West Nile virus, they have heard of bird flu. They know someone who has suffered through Lyme disease and someone else who has died of AIDS. They have heard of Ebola, and they know that it’s a terrifying thing (though they may confuse it with E. coli, the bacterium that can kill you if you eat the wrong spinach). They are concerned. They are vaguely aware. But they don’t have the time or the interest to consider a lot of scientific detail. I can say from experience that some people, if they hear you’re writing a book about such things—about scary emerging diseases, about killer viruses, about pandemics—want you to cut to the chase. So they ask: “Are we all gonna die?” I have made it my little policy to say yes.

As examples he returned to retroviruses, orthomyxoviruses, and coronaviruses. “Some of these viruses,” he warned, citing coronaviruses in particular, “should be considered as serious threats to human health. These are viruses with high evolvability and proven ability to cause epidemics in animal populations.” It’s interesting in retrospect to note that he had augured the SARS epidemic six years before it occurred.

If we can’t predict a forthcoming influenza pandemic or any other newly emergent virus, we can at least be vigilant; we can be well-prepared and quick to respond; we can be ingenious and scientifically sophisticated in the forms of our response.

That’s the salubrious thing about zoonotic diseases: They remind us, as St. Francis did, that we humans are inseparable from the natural world. In fact, there is no “natural world,” it’s a bad and artificial phrase. There is only the world. Humankind is part of that world, as are the ebolaviruses, as are the influenzas and the HIVs, as are Nipah and Hendra and SARS, as are chimpanzees and bats and palm civets and bar-headed geese, as is the next murderous virus—the one we haven’t yet detected.

I don’t say these things about the ineradicability of zoonoses to render you hopeless and depressed. Nor am I trying to be scary for the sake of scariness. The purpose of this book is not to make you more worried. The purpose of this book is to make you more smart.