Spillover: Animal Infections and the Next Human Pandemic (64 page)

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.

But it’s not all about human disease. Different subtypes, Webster noted, have their affinities for different species of host. H7N7 does well among horses. The dead terns in South Africa, back in 1961, had been infected with H5N3. 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. Although wild aquatic birds are now known to be the ultimate origin of all influenzas, the viruses reassort themselves in pigs and elsewhere (quail also serve as mixing bowls), and by the time they get into humans, they have generally been assembled from H1, H2, or H3 plus the ten other necessary proteins, some of those in forms borrowed from this or that bird flu or pig flu virus. 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.” They don’t pass from person to person. They may kill a lot of poultry, spreading through entire flocks, but they don’t travel on human sneezes. (Influenza among birds is primarily an infection of the gastrointestinal tract, with transmission occurring by the fecal-oral route; a sick bird shits the virus onto the floor of its coop, or onto the ground of a barnyard, or into the water of a lake or an estuary, and another bird picks it up while pecking or dabbling for food. That’s presumably how those South African terns and Australian shearwaters encountered the virus.) So you’ve got to handle a hen, or butcher a duck, to get infected. Still, with such a variable group of viruses, always mutating, continually reassorting, the next “try on” could be different. Consequently there’s “not a hope in hell, at this time,” Webster said, of predicting just what the next pandemic will be.

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.

It was bad timing for a medical emergency, 1997, that being the year of Hong Kong’s big political transition from a British colony into a special administrative region of China. Public institutions were unsettled, management and staffing were in flux, and Robert Webster found the University of Hong Kong depleted of influenza experts. Then still more human cases appeared, for a total of eighteen by the end of the year, with a case fatality rate of 33 percent. The bird subtype was highly virulent. But how transmissible? No one had traced its origin, let alone learned whether it might spread quickly among humans. “So I whistled up all the postdocs that I had trained around the Pacific,” Webster said, “and told them to get to Hong Kong. And within three days, we located the virus in the live poultry markets.”

It was a crucial start. Hong Kong officials ordered the culling of all domestic poultry (1.5 million birds) and closed the bird markets, which solved the immediate problem. For a while there were no further cases, not in Hong Kong, not anywhere. But the nasty new virus hadn’t been eradicated. It continued to circulate quietly among domestic ducks in the coastal provinces of China, where many rural people kept small flocks of quackers and led them out daily to feed in the rice paddies. 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.

“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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T
his 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.