Spillover

by David Quammen

  “The duck is the Trojan horse,” he repeated. It was a good line, vivid and clear, and I had seen it also in some of his published work. But today he was even more specific: mallards and pintails. The pathogenicity of this virus differs starkly for different kinds of birds. “It depends on the species,” Webster said. “Some duck species die. The bar-headed goose dies. The swans die. But the mallard, and the pintail in particular, carry. And spread.”

  Six years after its first outbreak in Hong Kong, H5N1 returned, infecting three members of a family and killing two. As I’ve described earlier, this occurred during the first alarms over what came to be known as SARS, complicating efforts to identify that very different bug. Around the same time, H5N1 started turning up among domestic poultry in South Korea, Vietnam, Japan, Indonesia, and elsewhere throughout the region, killing many chickens and at least a couple more people. It also traveled in wild birds—traveled pretty far. Qinghai Lake, in western China, thirteen hundred miles northwest of Hong Kong, became the site of one ominous event, to which Webster had alluded with his mention of bar-headed geese.

  Qinghai Lake is an important breeding site for migratory waterfowl, whose flyways lead variously from there to India, Siberia, and Southeast Asia. In April and May 2005, six thousand birds died at Qinghai of H5N1 influenza. The first animal affected was the bar-headed goose, but the disease also struck ruddy shelducks, great cormorants, and two kinds of gull. Bar-headed geese, with large wing areas relative to their weight, are well adapted to flying high and far. They nest on the Tibetan plateau. They migrate over the Himalayas. They shed H5N1.

  “And then presumably,” Webster told me, “the wild birds carried it westward to India, Africa, Europe, and so on.” It got to Egypt in 2006, for instance, and has been especially problematic for that country. “The virus is everywhere in Egypt. Through the commercial poultry, through the duck populations.” Egyptian health authorities tried vaccinating their poultry, with vaccine imported from Asia, but the vaccine efforts didn’t work. “It’s surprising there are not more human cases.” The toll in Egypt is high enough: 151 confirmed as of August 2011, of which 52 were fatal. Those numbers represent more than a quarter of all the world’s known human cases of bird flu, and more than a third of all fatalities, since H5N1 emerged in 1997. But here’s a critical fact: Few if any of the Egyptian cases resulted from human-to-human transmission. Those unfortunate Egyptian patients all seem to have acquired the virus directly from birds. This indicates that the virus hasn’t yet found an efficient way to pass from one person to another.

  Two aspects of the situation are dangerous, according to Robert Webster. The first is that Egypt, given its recent political upheavals and the uncertainty about where those will lead, may be unable to stanch an outbreak of transmissible avian flu, if one occurs. His second point of concern is shared by influenza researchers and public health officials around the globe: With all that mutating, with all that contact between people and their infected birds, the virus could hit upon a genetic configuration making it highly transmissible among people.

  “As long as H5N1 is out there in the world,” Webster said, “there is the possibility of disaster. That’s really the bottom line with H5N1. So long as it’s out there in the human population, there is the theoretical possibility that it can acquire the ability to transmit human-to-human.” He paused. “And then God help us.”

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  This whole subject, like an airborne virus, is at large on the breezes of discourse. 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.

  Yes, we are all gonna die. Yes. We are all gonna pay taxes and we are all gonna die. Most of us, though, will probably die of something more mundane than a new virus lately emerged from a duck or a chimpanzee or a bat.

  The dangers presented by zoonoses are real and severe but the degree of uncertainties is also high. There’s not a hope in hell, as Robert Webster pungently told me, of predicting the nature and timing of the next influenza pandemic. Too many factors vary randomly, or almost randomly, in that system. Prediction, in general, so far as all these diseases are concerned, is a tenuous proposition, more likely to yield false confidence than actionable intelligence. I have asked not just Webster but also many other eminent disease scientists, including some of the world’s experts on Ebola, on SARS, on bat-borne viruses generally, on the HIVs, and on viral evolution, the same two-part question: (1) Will a new disease emerge, in the near future, sufficiently virulent and transmissible to cause a pandemic on the scale of AIDS or the 1918 flu, killing tens of millions of people? and (2) If so, what does it look like and whence does it come? Their answers to the first part have ranged from Maybe to Probably. Their answers to the second have focused on RNA viruses, especially those for which the reservoir host is some kind of primate. None of them has disputed the premise, by the way, that if there is a Next Big One it will be zoonotic.

  In the scientific literature, you find roughly the same kind of cautious, informed speculation. A highly regarded infectious-disease epidemiologist named Donald S. Burke, presently dean of the Graduate School of Public Health at the University of Pittsburgh, gave a lecture (later published) back in 1997 in which he listed the criteria that might implicate certain kinds of viruses as likeliest candidates to cause a new pandemic. “The first criterion is the most obvious: recent pandemics in human history,” Burke told his audience. That would point to the orthomyxoviruses (including the influenzas) and the retroviruses (including the HIVs), among others. “The second criterion is proven ability to cause major epidemics in non-human animal populations.” This would again spotlight the orthomyxoviruses, but also the family of paramyxoviruses, such as Hendra and Nipah, and the coronaviruses, such as that virus later known as SARS-CoV. Burke’s third criterion was “intrinsic evolvability,” meaning readiness to mutate and to recombine (or reassort), which “confers on a virus the potential to emerge into and to cause pandemics in human populations.” 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.

  Much more recently, Burke told me: “I made a lucky guess.” He laughed a self-deprecating hoot and then added that “prediction is too strong a word” for what he had been doing.

  Donald Burke can be trusted on this as much as anyone alive. But the difficulty of predicting precisely doesn’t oblige us to remain blind, unprepared, and fatalistic about emerging and re-emerging zoonotic diseases. No. The practical alternative to soothsaying, as Burke put it, is “improving the scientific basis to improve readiness.” By “the scientific basis” he meant the understanding of which virus groups to watch, the field capabilities to detect spillovers in remote places before they become regional outbreaks, the organizational capacities to control outbreaks before they become pandemics, plus the laboratory tools and skills to recognize known viruses speedily, to characterize new viruses almost as fast, and to create vaccines and therapies without much delay. 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.

  To a considerable degree, such things are already being done on our behalf by some foresighted institutions and individuals in the realm of disease science and public health. Ambitious networks and programs have been created, by the World Health Organization, the Centers for Disease Control and Prevention, the United States Agency for International Development, the European Center for Disease Prevention and Control, the World Organization for Animal Health, and other national and international agencies, to address the danger of emerging zoonotic diseases. Because of concern over the potential of “bioterrorism,” even the US Department of Homeland Security and the Defense Advanced Research Projects Agency (aka Darkest DARPA, whose motto is “Creating & Preventing Strategic Surprise”) of the US Department of Defense have their hands in the mix. (Since the United States foreswore offensive bioweapons research back in 1969, presumably DARPA’s disease program is now aimed at preventing, not creating, strategic surprise of the epidemiological sort.) These efforts carry names and acronyms such as the Global Outbreak Alert and Response Network (GOARN, of WHO), Prophecy (of DARPA), the Emerging Pandemic Threats program (EPT, of USAID), and the Special Pathogens Branch (SPB, of the CDC), all of which sound like programmatic boilerplate but which harbor some dedicated people working in field sites where spillovers happen and secure labs where new pathogens can be quickly studied. Private organizations, such as EcoHealth Alliance (led by a former parasitologist named Peter Daszak and now employing Jon Epstein for his Nipah work in Bangladesh and elsewhere, Aleksei Chmura for his bat research in China, Billy Karesh for his continuing wildlife-health studies around the world, and others), have also tackled the problem. There is an intriguing effort called the Global Viral Forecasting Initiative (GVFI), financed in part by Google and created by a bright, enterprising scientist named Nathan Wolfe, one of whose mentors was Don Burke. GVFI gathers blood samples on small patches of filter paper from bushmeat hunters and other people across tropical Africa and Asia, and screens those samples for new viruses, in a systematic effort to detect spillovers and stop the next pandemic before it begins to spread. Wolfe learned the filter-paper technique from Balbir Singh and Janet Cox-Singh (the malaria researchers who study Plasmodium knowlesi in humans, remember?), during field time he spent with them as a graduate student in the 1990s. At the Mailman School of Public Health, part of Columbia University, Ian Lipkin’s laboratory is a whiz-bang center of efforts to develop new molecular diagnostic tools. Lipkin, trained as a physician as well as a molecular biologist, calls his métier “pathogen discovery” and uses techniques such as high-throughput sequencing (which can sequence thousands of DNA samples quickly and cheaply), MassTag PCR (identifying amplified genome segments by mass spectrometry), and the GreeneChip diagnostic system, which can simultaneously screen for thousands of different pathogens. When Jon Epstein takes serum from flying foxes in Bangladesh, when Aleksei Chmura bleeds bats in southern China, some of those samples go straight to Ian Lipkin.

  These scientists are on alert. They are our sentries. They watch the boundaries across which pathogens spill. And they are productively interconnected with one another. When the next novel virus makes its way from a chimpanzee, a bat, a mouse, a duck, or a macaque into a human, and maybe from that human into another human, and thereupon begins causing a small cluster of lethal illnesses, they will see it—we hope they will, anyway—and raise the alarm.

  Whatever happens after that will depend on science, politics, social mores, public opinion, public will, and other forms of human behavior. It will depend on how we citizens respond.

  So before we respond, either calmly or hysterically, either intelligently or doltishly, we should understand in some measure the basic outlines and dynamics of the situation. We should appreciate that these recent outbreaks of new zoonotic diseases, as well as the recurrence and spread of old ones, are part of a larger pattern, and that humanity is responsible for generating that pattern. We should recognize that they reflect things that we’re doing, not just things that are happening to us. We should understand that, although some of the human-caused factors may seem virtually inexorable, others are within our control.

  The experts have alerted us to these factors and it’s easy enough to make a list. We have increased our population to the level of 7 billion and beyond. We are well on our way toward 9 billion before our growth trend is likely to flatten. We live at high densities in many cities. We have penetrated, and we continue to penetrate, the last great forests and other wild ecosystems of the planet, disrupting the physical structures and the ecological communities of such places. We cut our way through the Congo. We cut our way through the Amazon. We cut our way through Borneo. We cut our way through Madagascar. We cut our way through New Guinea and northeastern Australia. We shake the trees, figuratively and literally, and things fall out. We kill and butcher and eat many of the wild animals found there. We settle in those places, creating villages,

  work camps, towns, extractive industries, new cities. We bring in our domesticated animals, replacing the wild herbivores with livestock. We multiply our livestock as we’ve multiplied ourselves, operating huge factory-scale operations involving thousands of cattle, pigs, chickens, ducks, sheep, and goats, not to mention hundreds of bamboo rats and palm civets, all confined en masse within pens and corrals, under conditions that allow those domestics and semidomestics to acquire infectious pathogens from external sources (such as bats roosting over the pig pens), to share those infections with one another, and to provide abundant opportunities for the pathogens to evolve new forms, some of which are capable of infecting a human as well as a cow or a duck. We treat many of those stock animals with prophylactic doses of antibiotics and other drugs, intended not to cure them but to foster their weight gain and maintain their health just sufficiently for profitable sale and slaughter, and in doing that we encourage the evolution of resistant bacteria. We export and import livestock across great distances and at high speeds. We export and import other live animals, especially primates, for medical research. We export and import wild animals as exotic pets. We export and import animal skins, contraband bushmeat, and plants, some of which carry secret microbial passengers. We travel, moving between cities and continents even more quickly than our transported livestock. We stay in hotels where strangers sneeze and vomit. We eat in restaurants where the cook may have butchered a porcupine before working on our scallops. We visit monkey temples in Asia, live markets in India, picturesque villages in South America, dusty archeological sites in New Mexico, dairy towns in the Netherlands, bat caves in East Africa, racetracks in Australia—breathing the air, feeding the animals, touching things, shaking hands with the friendly locals—and then we jump on our planes and fly home. We get bitten by mosquitoes and ticks. We alter the global climate with our carbon emissions, which may in turn alter the latitudinal ranges within which those mosquitoes and ticks live. We provide an irresistible opportunity for enterprising microbes by the ubiquity and abundance of our human bodies.

  Everything I’ve just mentioned is encompassed within this rubric: the ecology and evolutionary biology of zoonotic diseases. Ecological circumstance provides opportunity for spillover. Evolution seizes opportunity, explores possibilities, and helps convert spillovers to pandemics.

  It’s a neat but sterile historical coincidence that the germ theories of disease came to scientific prominence at about the same time, in the late nineteenth century, as the Darwinian theory of evolution—neat because these were two great bodies of insight with much to offer each other, and sterile because their synergy was long delayed, as germ theories remained for another sixty years largely uninformed by evolutionary thinking. Ecological thinking, in its modern form, arose even later and was equally slow to be absorbed by disease science. The other absent science, until the second half of the twentieth century, was molecular biology. Medical pe
ople of the earlier eras might guess that bubonic plague was somehow related to rodents, yes, but they didn’t know how or why until Alexandre Yersin, during an 1894 epidemic in Hong Kong, found the plague bacterium in rats. Even that didn’t illuminate the path to human infection until Paul-Louis Simond, several years later, showed that the bacterium is transmitted by rat fleas. Anthrax, caused by another bacterium, was known to kill cows and people but seemed to arise by spontaneous generation until Koch proved otherwise in 1876. Rabies was even more obviously associated with transmission to humans from animals—notably, mad dogs—and Pasteur introduced a rabies vaccine in 1885, injecting a bitten boy, who survived. But rabies virus itself, so much smaller than a bacterium, couldn’t be directly detected nor traced to wild carnivores until much later. During the early twentieth century, disease scientists from the Rockefeller Foundation and other institutions conceived the ambitious goal of eradicating some infectious diseases entirely. They tried hard with yellow fever, spending millions of dollars and many years of effort, and failed. They tried with malaria, and failed. They tried later with smallpox, and succeeded. Why? The differences among those three diseases are many and complex, but probably the most crucial one is that smallpox resided neither in a reservoir host nor in a vector. Its ecology was simple. It existed in humans—in humans only—and was therefore much easier to eradicate. The campaign to eradicate polio, begun in 1988 by WHO and other institutions, is a realistic effort for the same reason: Polio isn’t zoonotic. And malaria is now targeted again. The Bill and Melinda Gates Foundation announced, in 2007, a new long-term initiative to eradicate that disease. It’s an admirable goal, a generously imaginative dream, but a person is left to wonder how Mr. and Mrs. Gates and their scientific advisers propose to deal with Plasmodium knowlesi. Do you exterminate the parasite by killing off its reservoir hosts, or do you somehow apply your therapeutics to those hosts, curing every macaque in the forests of Borneo?