Virtual villagers origins mysterious vial

ALSO BY DAVID QUAMMEN NONFICTION The Reluctant Mr. Darwin Monster of God The Song of the Dodo ESSAYS Natural Acts The Boilerplate Rhino Wild Thoughts from Wild Places The Flight of the Iguana FICTION Blood Line The Soul of Viktor Tronko The Zolta Configuration To Walk the Line EDITED On the Origin of Species by Charles Darwin: The Illustrated Edition The Best American Science and Nature Writing 2000, with Burkhard Bilger

2

SPILLOVER Animal Infections and the

Next Human Pandemic DAVID QUAMMEN

W. W. NORTON & COMPANY NEW YORK • LONDON

3

again and ever,

to Betsy

4

And I looked, and behold a pale horse: and his name that sat on him was Death, and Hell followed with him. And power was given unto them over the fourth part of the earth, to kill with sword, and with hunger, and with death, and with the beasts of the earth.

—REVELATION 6:8

5

CONTENTS I. Pale Horse

II. Thirteen Gorillas III. Everything Comes from Somewhere

IV. Dinner at the Rat Farm V. The Deer, the Parrot, and the Kid Next Door

VI. Going Viral VII. Celestial Hosts

VIII. The Chimp and the River IX. It Depends

Notes Bibliography

Acknowledgments Index

6

I PALE HORSE

7

1

The virus now known as Hendra wasn’t the first of the scary new bugs. It wasn’t the worst. Compared to some others, it seems relatively minor. Its mortal impact, in numerical terms, was small at the start and has remained small; its geographical scope was narrowly local and later episodes haven’t carried it much more widely. It made its debut near Brisbane, Australia, in 1994. Initially there were two cases, only one of them fatal. No, wait, correction: There were two human cases, one human fatality. Other victims suffered and died too, more than a dozen—equine victims—and their story is part of this story. The subject of animal disease and the subject of human disease are, as we’ll see, strands of one braided cord.

The original emergence of Hendra virus didn’t seem very dire or newsworthy unless you happened to live in eastern Australia. It couldn’t match an earthquake, a war, a schoolboy gun massacre, a tsunami. But it was peculiar. It was spooky. Slightly better known now, at least among disease scientists and Australians, and therefore slightly less spooky, Hendra virus still seems peculiar. It’s a paradoxical thing: marginal, sporadic, but in some larger sense representative. For exactly that reason, it marks a good point from which to begin toward understanding the emergence of certain virulent new realities on this planet—realities that include the death of more than 30 million people since 1981. Those realities involve a phenomenon called zoonosis.

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. Pondering them as a group tends to reaffirm the old Darwinian truth (the darkest of his truths, well known and persistently forgotten) that humanity is a kind of animal, inextricably connected with other animals: in origin and in descent, in sickness and in health. Pondering them individually—for starters, this relatively obscure case from Australia—provides a salubrious reminder that everything, including pestilence, comes from somewhere.

8

2

In September 1994, a violent distress erupted among horses in a suburb at the north fringe of Brisbane. These were thoroughbred racehorses, pampered and sleek animals bred to run. The place itself was called Hendra. It was a quiet old neighborhood filled with racecourses, racing people, weatherboard houses whose backyards had been converted to stables, newsstands that sold tip sheets, corner cafes with names like The Feed Bin. The first victim was a bay mare named Drama Series, retired from racing and now heavily in foal—that is, pregnant and well along. Drama Series started showing signs of trouble in a spelling paddock, a ragged meadow several miles southeast of Hendra, where racehorses were sent to rest between outings. She had been placed there as a brood mare and would have stayed until late in her pregnancy, if she hadn’t gotten sick. There was nothing drastically wrong with her—so it seemed, at this point. She just didn’t look good, and her trainer thought she should come in. The trainer was a savvy little man named Vic Rail, with a forceful charm, swept-back brown hair, and a reputation for sharp practice in the local racing world. He was “tough as nails, but a lovable rogue,” Vickie was, by one judgment. Some people resented him but no one denied he knew horses.

It was Rail’s girlfriend, Lisa Symons, who took a horse trailer out to collect Drama Series. The mare was reluctant to move. She seemed to have sore feet. There were swellings around her lips, her eyelids, her jaw. Back at Rail’s modest stable in Hendra, Drama Series sweated profusely and remained sluggish. Hoping to nourish her and save the foal, he tried to force feed her with grated carrot and molasses but she wouldn’t eat. After the attempt, Vic Rail washed his hands and his arms, though in hindsight perhaps not thoroughly enough.

That was September 7, 1994, a Wednesday. Rail called his veterinarian, a tall man named Peter Reid, sober and professional, who came and looked the mare over. She was now in her own box at the stable, a cinderblock stall with a floor of sand, close amid Rail’s other horses. Dr. Reid saw no discharges from her nose or eyes, and no signs of pain, but she seemed a pale image of her robust former self. “Depressed,” was his word, meaning (in veterinary parlance) a physical not a psychological condition. Her temperature and her heart rate were both high. Reid noticed the facial swelling. Opening her mouth to examine her gums, he noticed remnants of the carrot shreds that she hadn’t bothered or been able to swallow, and he gave her injections of antibiotic and analgesic. Then he went home. Sometime after four the next morning, he got a call. Drama Series had gotten out of her stall, collapsed in the yard, and was dying.

By the time Reid rushed back to the stables, she was dead. It had been quick and ugly. Growing agitated as her condition got worse, she had staggered out while the

9

stall door was open, fallen down several times, gouged her leg to the bone, stood up, fallen again in the front yard, and been pinned to the ground for her own protection by a stable hand. She freed herself desperately, crashed into a pile of bricks, and then was pinned again by joint effort of the stable hand and Rail, who wiped a frothy discharge away from her nostrils—trying to help her breathe—just before she died. Reid inspected the body, noticing a trace of clear froth still at the nostrils, but did not perform a necropsy because Vic Rail couldn’t afford to be so curious and, more generally, because no one foresaw a disease emergency in which every bit of such data would be crucial. Drama Series’s carcass was unceremoniously carted away, by the usual contract hauler, to the dump where dead Brisbane horses routinely go.

Her cause of death remained uncertain. Had she been bitten by a snake? Had she eaten some poisonous weeds out in that scrubby, derelict meadow? Those hypotheses crumbled abruptly, thirteen days later, when her stable mates began falling ill. They went down like dominoes. This wasn’t snakebite or toxic fodder. It was something contagious.

The other horses suffered fever, respiratory distress, bloodshot eyes, spasms, and clumsiness; in some, bloody froth surged from the nostrils and mouth; a few had facial swelling. Reid found one horse frantically rinsing its mouth in a water bucket. Another banged its head against the concrete wall as though maddened. Despite heroic efforts by Reid and others, twelve more animals died within the next several days, either expiring horrifically or euthanized. Reid later said that “the speed with which it went through those horses was unbelievable,” but in these early moments no one had identified “it.” Something went through those horses. At the height of the crisis, seven animals succumbed to their agonies or required euthanasia within just twelve hours. Seven dead horses in twelve hours—that’s carnage, even for a casehardened veterinarian. One of them, a mare named Celestial Charm, died thrashing and gasping so desperately that Reid couldn’t get close enough to give her the merciful needle. Another horse, a five-year-old gelding, had been sent from Rail’s place to another spelling paddock up north, where it was sick on arrival and soon had to be put down. A vet up there necropsied the gelding and found hemorrhages throughout its organs. And in a neighbor’s stable on the corner beside Rail’s place in Hendra, at the same time, still another gelding went afoul with similar clinical signs and also had to be euthanized.

What was causing this mayhem? How was it spreading from one horse to another, or anyway getting into so many of them simultaneously? One possibility was a toxic contaminant in the feed supply. Or maybe poison, maliciously introduced. Alternatively, Reid began wondering whether there might be an exotic virus at work, such as the one responsible for African horse sickness (AHS), a disease carried by biting midges in sub-Saharan Africa. AHS virus affects mules, donkeys, and zebras as well as horses, but it hasn’t been reported in Australia, and it isn’t directly contagious from horse to horse. Furthermore, Queensland’s pestiferous midges don’t generally

10

come biting in September, when the weather is cool. So AHS was not quite a fit. Then maybe another strange germ? “I’d never seen a virus do anything like that before,” Reid said. A man of understatement, he recalled it as “a pretty traumatic time.” He had continued to treat the suffering animals with what means and options he had, given the inconclusive diagnosis—antibiotics, fluids, antishock medicine.

Meanwhile, Vic Rail himself had taken sick. So had the stable hand. It seemed at first that they each had a touch of flu—a bad flu. Rail went into the hospital, worsened there, and, after a week of intensive care, died. His organs had failed and he couldn’t breathe. Autopsy showed that his lungs were full of blood, other fluid, and (upon examination by electron microscopy) some sort of virus. The stable hand, a big- hearted man named Ray Unwin, who merely went home to endure his fever in private, survived. Peter Reid, though he had been working on the same suffering horses amid the same bloody froth, stayed healthy. He and Unwin told me their stories when I found them, years later, by asking around Hendra and making a few calls.

At The Feed Bin, for instance, someone said: Ray Unwin, yeah, most likely he’ll be at Bob Bradshaw’s. I followed directions to Bradshaw’s stable and there on the driveway was a man who turned out to be Unwin, carrying grain in a bucket. At that point he was a middle-aged working bloke with a sandy red ponytail and a weary sadness in his eyes. He was a little shy about attention from a stranger; he’d had enough of that already from doctors, public health officials, and local reporters. Once we sat down to chat, he professed that he wasn’t a “whinger” (complainer) but that his health had been “crook” (not right) since it happened.

As the horse deaths came to crescendo, the government of Queensland had intervened, in the form of veterinarians and other personnel from the Department of Primary Industries (responsible for livestock, wildlife, and agriculture throughout the state) and field officers from Queensland Health. The DPI veterinarians began doing necropsies—that is, cutting up horses, looking for clues—right in Vic Rail’s little yard. Before long there were horse heads lying around, severed limbs, blood and other fluids flowing down the gutter, suspect organs and tissues going into bags. Another neighbor of Rail’s, a fellow horse man named Peter Hulbert, recollected the gruesome pageant that had transpired next door, while serving me instant coffee in his kitchen. As the kettle came to a boil, Hulbert recalled the garbage containers used by DPI. “These street wheelie bins here, there was horses’ legs and heads . . . —do you have sugar?”

No thanks, I said, black. “. . . horses’ legs and heads and guts and everything, going into these wheelie bins.

It—was—horrendous.” By midafternoon that day, he added, word had spread and the TV stations showed up with their news cameras. “Agh. It was bloody terrible, mate.” Then the police arrived too and threw a tape cordon around Rail’s place, treating it as a crime scene. Had one of his enemies done this? The racing world had its underbelly, like any business, and probably more so than most. Peter Hulbert even faced pointed

11

questioning about whether Vic might have poisoned his own horses and then himself. While the police wondered about sabotage or insurance scam, the health officials

had other hypotheses to concern them. One was hantavirus—which is actually a group of viruses, long known to virologists following outbreaks in Russia, Scandinavia, and elsewhere but newly conspicuous since a year earlier, 1993, when a new hantavirus emerged dramatically and killed ten people around the Four Corners area of the American Southwest. Australia is justifiably wary of exotic diseases invading its borders, and hantavirus in the country would be even worse news (except for horses) than African horse sickness. So the DPI vets packed up samples of blood and tissue from the dead horses and sent them on ice to the Australian Animal Health Laboratory, a high-security institution known by its acronym, AAHL, pronounced “aahl,” in a town called Geelong, south of Melbourne. A team of microbiologists and veterinarians there put the sample material through a series of tests, attempting to culture and identify a microbe, and to confirm that the microbe made horses sick.

They found a virus. It wasn’t a hantavirus. It wasn’t AHS virus. It was something new, something the AAHL microscopist hadn’t seen before but which, from its size and its shape, resembled members of a particular virus group, the paramyxoviruses. This new virus differed from known paramyxoviruses in that each particle carried a double fringe of spikes. Other AAHL researchers sequenced a stretch of the viral genome and, submitting that sequence into a vast viral database, found a weak match to one subgroup of these viruses. That seemed to confirm the visual judgment of the microscopist. The matching subgroup was the morbilliviruses, which include rinderpest virus and canine distemper virus (infecting nonhuman animals) and measles (in humans). So the creature from Hendra was classified and given a name, based on those provisional identifications: equine morbillivirus (EMV). Roughly, horse measles.

About the same time, the AAHL researchers tested a sample of tissue that had been taken from Vic Rail’s kidney during his autopsy. That sample also yielded a virus, identical to the virus from the horses, confirming that this equine morbillivirus didn’t afflict only equines. Later, when the degree of its uniqueness became better appreciated, the label “EMV” was dropped and the virus was renamed after its place of emergence: Hendra.

Identifying the new virus was only step one in solving the immediate mystery of Hendra, let alone understanding the disease in a wider context. Step two would involve tracking that virus to its hiding place. Where did it exist when it wasn’t killing horses and people? Step three would entail asking a further cluster of questions: How did the virus emerge from its secret refuge, and why here, and why now?

After our first conversation, at a café in Hendra, Peter Reid drove me several miles southeast, across the Brisbane River, to the site where Drama Series took sick. It was in an area called Cannon Hill, formerly pastoral land surrounded by city, now a booming suburb just off the M1 motorway. Tract houses on prim lanes had been built

12

over the original paddock. Not much of the old landscape remained. But toward the end of one street was a circle, called Calliope Circuit, in the middle of which stood a single mature tree, a Moreton Bay fig, beneath which the mare would have found shelter from eastern Australia’s fierce subtropical sun.

“That’s it,” Reid said. “That’s the bloody tree.” That’s where the bats gathered, he meant.

13

3

Infectious disease is all around us. Infectious disease is a kind of natural mortar binding one creature to another, one species to another, within the elaborate biophysical edifices we call ecosystems. It’s one of the basic processes that ecologists study, including also predation, competition, decomposition, and photosynthesis. Predators are relatively big beasts that eat their prey from outside. Pathogens (disease- causing agents, such as viruses) are relatively small beasts that eat their prey from within. Although infectious disease can seem grisly and dreadful, under ordinary conditions it’s every bit as natural as what lions do to wildebeests and zebras, or what owls do to mice.

But conditions aren’t always ordinary. Just as predators have their accustomed prey, their favored targets, so do pathogens.

And just as a lion might occasionally depart from its normal behavior—to kill a cow instead of a wildebeest, a human instead of a zebra—so can a pathogen shift to a new target. Accidents happen. Aberrations occur. Circumstances change and, with them, exigencies and opportunities change too. When a pathogen leaps from some nonhuman animal into a person, and succeeds there in establishing itself as an infectious presence, sometimes causing illness or death, the result is a zoonosis.

It’s a mildly technical term, zoonosis, unfamiliar to most people, but it helps clarify the biological complexities behind the ominous headlines about swine flu, bird flu, SARS, emerging diseases in general, and the threat of a global pandemic. It helps us comprehend why medical science and public health campaigns have been able to conquer some horrific diseases, such as smallpox and polio, but unable to conquer other horrific diseases, such as dengue and yellow fever. It says something essential about the origins of AIDS. It’s a word of the future, destined for heavy use in the twenty-first century.

Ebola is a zoonosis. So is bubonic plague. 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. All of the human influenzas are zoonoses. So are monkeypox, bovine tuberculosis, Lyme disease, West Nile fever, Marburg virus disease, rabies, hantavirus pulmonary syndrome, anthrax, Lassa fever, Rift Valley fever, ocular larva migrans, scrub typhus, Bolivian hemorrhagic fever, Kyasanur forest disease, and a strange new affliction called Nipah encephalitis, which has killed pigs and pig farmers in Malaysia. Each of them reflects the action of a pathogen that can cross into people from other animals. AIDS is a disease of zoonotic origin caused by a virus that, having reached humans

14

through just a few accidental events in western and central Africa, now passes human- to-human by the millions. 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. Some of those—notably rabies— are familiar, widespread, and still horrendously lethal, killing humans by the thousands despite centuries of efforts at coping with their effects, concerted international attempts to eradicate or control them, and a pretty clear scientific understanding of how they work. Others are new and inexplicably sporadic, claiming a few victims (as Hendra does) or a few hundred (Ebola) in this place or that, and then disappearing for years.

Smallpox, to take one counterexample, is not a zoonosis. It’s caused by variola virus, which under natural conditions infects only humans. (Laboratory conditions are another matter; the virus has sometimes been inflicted experimentally on nonhuman primates or other animals, usually for vaccine research.) 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. Likewise poliomyelitis, a viral disease that has afflicted humans for millennia but that (for counterintuitive reasons involving improved hygiene and delayed exposure of children to the virus) became a fearsome epidemic threat during the first half of the twentieth century, especially in Europe and North America. In the United States, the polio problem peaked in 1952 with an outbreak that killed more than three thousand victims, many of them children, and left twenty-one thousand at least partially paralyzed. Soon afterward, vaccines developed by Jonas Salk, Albert Sabin, and a virologist named Hilary Koprowski (about whose controversial career, more later) came into wide use, eventually eliminating poliomyelitis throughout most of the world. In 1988, WHO and several partner institutions launched an international effort toward eradication, which has succeeded so far in reducing polio case numbers by 99 percent. The Americas have been declared polio-free, as have Europe and Australia. Only five countries, as of latest reports in 2011, still seemed to have a minor, sputtering presence of polio: Nigeria, India, Pakistan, Afghanistan, and China. 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.

Zoonotic pathogens can hide. That’s what makes them so interesting, so complicated, and so problematic.

Monkeypox is a disease similar to smallpox, caused by a virus closely related to variola. It’s a continuing threat to people in central and western Africa. Monkeypox differs from smallpox in one crucial way: the ability of its virus to infect nonhuman

15

primates (hence the name) and some mammals of other sorts, including rats, mice, squirrels, rabbits, and American prairie dogs. Yellow fever, also infectious to both monkeys and humans, results from a virus that passes from victim to victim, and sometimes from monkey to human, in the bite of certain mosquitoes. This is a more complex situation. One result of the complexity is that yellow fever will probably continue to occur in humans—unless WHO kills every mosquito vector or every susceptible monkey in tropical Africa and South America. The Lyme disease agent, a type of bacterium, hides effectively in white-footed mice and other small mammals. These pathogens aren’t consciously hiding, of course. They reside where they do and transmit as they do because those happenstance options have worked for them in the past, yielding opportunities for survival and reproduction. By the cold Darwinian logic of natural selection, evolution codifies happenstance into strategy.

The least conspicuous strategy of all is to lurk within what’s called a reservoir host. A reservoir host (some scientists prefer “natural host”) is a living organism that carries the pathogen, harbors it chronically, while suffering little or no illness. When a disease seems to disappear between outbreaks (again, as Hendra did after 1994), its causative agent has got to be somewhere, yes? Well, maybe it vanished entirely from planet Earth—but probably not. Maybe it died off throughout the region and will only reappear when the winds and the fates bring it back from elsewhere. Or maybe it’s still lingering nearby, all around, within some reservoir host. A rodent? A bird? A butterfly? A bat? To reside undetected within a reservoir host is probably easiest wherever biological diversity is high and the ecosystem is relatively undisturbed. The converse is also true: Ecological disturbance causes diseases to emerge. Shake a tree, and things fall out.

Nearly all zoonotic diseases result from infection by one of six kinds of pathogen: viruses, bacteria, fungi, protists (a group of small, complex creatures such as a