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 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 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 amoebae, formerly but misleadingly known as protozoans), prions, and worms. Mad cow disease is caused by a prion, a weirdly folded protein molecule that triggers weird folding in other molecules, like Kurt Vonnegut’s infectious form of water, ice-nine, in his great early novel Cat’s Cradle. Sleeping sickness results from infection by a protist called Trypanosoma brucei, carried by tsetse flies among wild mammals, livestock, and people in sub-Saharan Africa. Anthrax is caused by a bacterium that can live dormant in soil for years and then, when scuffed out, infect humans by way of their grazing animals. Toxocariasis is a mild zoonosis caused by roundworms; you can get it from your dog. But fortunately, like your dog, you can be wormed.
Viruses are the most problematic. They evolve quickly, they are unaffected by antibiotics, they can be elusive, they can be versatile, they can inflict extremely high rates of fatality, and they are fiendishly simple, at least relative to other living or quasi-living creatures. Ebola, West Nile, Marburg, the SARS bug, monkeypox, rabies, Machupo, dengue, the yellow fever agent, Nipah, Hendra, Hantaan (the namesake of the hantaviruses, first identified in Korea), chikungunya, Junin, Borna, the influenzas, and the HIVs (HIV-1, which mainly accounts for the AIDS pandemic, and HIV-2, which is less widespread) are all viruses. The full list is much longer. There is a thing known by the vivid name “simian foamy virus” (SFV) that infects monkeys and humans in Asia, crossing between them by way of the venues (such as Buddhist and Hindu temples) where people and half-tame macaques come into close contact. Among the people visiting those temples, feeding handouts to those macaques, exposing themselves to SFV, are international tourists. Some carry away more than photos and memories. “Viruses have no locomotion,” according to the eminent virologist Stephen S. Morse, “yet many of them have traveled around the world.” They can’t run, they can’t walk, they can’t swim, they can’t crawl. They ride.
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Isolating the Hendra bug had been a task for virologists, working in their high-security labs down at AAHL. “Isolating,” in this sense of the word, means finding some of the virus and growing more. The isolate becomes a live, captive population of virus, potentially dangerous if any were to escape but useful for ongoing research. Virus particles are so tiny they can’t be seen, except by electron microscopy, which involves killing them, so their presence during isolation
must be detected indirectly. You start with a small bit of tissue, a drop of blood, or some other sample from an infected victim. Your hope is that it contains the virus. You add that inoculum, like a dash of yeast, to a culture of living cells in a nutrient medium. Then you incubate, you wait, you watch. Often, nothing happens. If you’re lucky, something does. You know you’ve succeeded when the virus replicates abundantly and asserts itself sufficiently to cause visible damage to the cultured cells. Ideally it forms plaques, large holes in the culture, each hole representing a locus of virus-caused devastation. The process demands patience, experience, expensively exact bench tools, plus meticulous precautions against contamination (which can falsify results) or accidental release (which can infect you, endanger your co-workers, and maybe panic a town). Laboratory virologists are not generally knockabout people. You don’t meet them in bars, waving their arms and bragging lustily about the perils of their métier. They tend to be focused, neat, and still, like nuclear engineers.
Discovering where a virus lives in the wild is work of a very different sort. It’s an outdoor job that entails a somewhat less controllable level of risk, like trapping grizzly bears for relocation. Now, the people who look for wild viruses aren’t rowdy and careless, no more so than the lab specialists; they can’t afford to be. But they labor in a noisier, more cluttered, more unpredictable environment: the world. If there is reason to suspect that a certain new virus infecting humans is zoonotic (as most such viruses are), the search may lead into forests, swamps, crop fields, old buildings, sewers, caves, or the occasional horse paddock. The virus hunter is a field biologist, possibly with advanced training in human medicine, veterinary medicine, ecology, or some combination of those three—a person who finds fascination in questions that must be answered by catching and handling animals. That profile fits a lanky, soft-spoken man named Hume Field, midthirtyish at the time he became involved with Hendra.
Field grew up in the provincial towns of coastal Queensland, from Cairns to Rockhampton, a nature-loving kid who climbed trees, hiked in the bush, and spent school holidays on his uncle’s dairy farm. His father was a police detective, which seems only too prefigurative of the son’s later role as a viral sleuth. Young Field earned an undergraduate degree in veterinary science at the University of Queensland, in greater Brisbane, and volunteered at an animal refuge on the side, helping to rehabilitate injured wildlife. After graduation in 1976, he worked in a mixed veterinary practice in Brisbane for some years and then as a temporary fill-in (the Australians call it “doing locums”) all over the state. During that time, he doctored a lot of horses. But he became increasingly aware that his deepest interest was wildlife, not livestock and pets, so in the early 1990s Field returned to the University of Queensland, this time for a doctorate in ecology.
He focused on wildlife conservation and, in due time, needed a dissertation project. Because feral cats (domestic cats gone wild on the landscape) cause considerable damage to native Australian wildlife, killing small marsupials and birds and acting as a source of disease, he undertook a study of feral cat populations and their impact. He was trapping cats, fitting them with radio collars to track how they lived, when the outbreak occurred at Vic Rail’s stable. One of Field’s doctoral mentors, a scientist who worked with the Department of Primary Industries, asked Field whether he would be interested in changing projects. The department needed someone to investigate the ecological side of this new disease. “So I forgot my feral cats,” Field told me, when I visited him long afterward at the Animal Research Institute, a DPI facility near Brisbane, “and started off looking for wildlife reservoirs of Hendra virus.”
He began his search by going back to the index case—the first equine victim, its history and locale. That was Drama Series, the pregnant mare, fallen ill in the paddock at Cannon Hill. The only clues he had were that this virus was a paramyxovirus and that another Queensland researcher had found a novel paramyxovirus in a rodent some years earlier. So Field established a trapping regime at the paddock, catching every small and medium-sized vertebrate he could—rodents, possums, bandicoots, reptiles, amphibians, birds, the odd feral cat—and drawing blood from each, with a particularly suspicious eye to the rodents. He sent the blood samples to the DPI lab to be screened for antibodies against Hendra.
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. That’s the evidence Hume Field was hoping to find. But the rodents from Cannon Hill had no antibodies to Hendra virus. Neither did anything else, leaving him to wonder why. Either he was looking in the wrong place, or in the right place in the wrong way, or at the wrong time. Bad timing might indeed be the problem, he thought. Drama Series had sickened in September, half a year had passed, and here he was searching in March, April, May. He suspected that “there could be some sort of seasonal presence of either the virus or the host” at the Cannon Hill paddock, and that maybe now it was out of season. Screening the cats, dogs, and rats around Rail’s stable yielded no positives either.
Seasonal presence of the virus was one possibility. Coming and going on a shorter time scale was another. Bats, for instance, fed in large numbers at the Cannon Hill paddock by night but returned to their roosts, elsewhere, to sleep out the day. Peter Reid heard a Cannon Hill resident say that, during hours of darkness in the neighborhood, “flying foxes were as thick as the stars in the sky.” Reid had therefore suggested to AAHL that the bats should be looked at, but his suggestion evidently wasn’t passed along. Hume Field and his co-workers on the reservoir hunt remained stumped until the following October, 1995, when an unfortunate event gave them a helpful new lead.
A young cane farmer named Mark Preston, who lived near the town of Mackay, about six hundred miles north of Brisbane, suffered a spate of seizures. His wife got him to a hospital. Preston’s symptoms were especially alarming because they signaled a second health crisis for him in barely more than a year. Back in August 1994, he had endured a mysterious illness—headache, vomiting, stiff neck, then a provisional diagnosis of meningitis, cause unspecified—from which he had recovered. Or had seemingly recovered. 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. Preston continued to live a robust life on the farm with his wife Margaret, a veterinarian who based her practice there amid the sugar cane and the stud horses.
Did Mark Preston’s seizures now indicate a recurrence of his indeterminate meningitis? Admitted to the hospital, he sunk into severe encephalitis—that is, brain inflammation, cause still unknown. Medication controlled his seizures but the doctors could watch storms of distress flickering on the electroencephalograph. “He remained deeply unconscious with persisting fever,” according to a later medical report, “and died 25 days after admission.”
Blood serum taken during Preston’s final illness tested positive for antibodies to Hendra virus. So did his serum from a year earlier, which had been taken during the first episode, stored, and was now tested in retrospect. His immune system had been fighting the thing back then. Postmortem examination of his brain tissue, as well as other tests, confirmed the presence of Hendra. Evidently it had attacked once, subsided, lingered in latent form for a year, and then reared up and killed him. That was scary in a whole new way.
Where had he gotten it? Investigators, working backward to assemble the story, learned that in August 1994 two horses had died on the Preston farm. Mark Preston helped his wife care for them during their sudden, fatal illnesses and assisted her, at least marginally
, when she performed the necropsies. Preserved tissue that Margaret Preston had drawn from both horses now also tested positive for Hendra. Despite her own exposure, though, Margaret Preston remained healthy—just as Peter Reid would remain healthy despite his exposure weeks later at Vic Rail’s place. The good health of the two veterinarians raised the question of just how infectious this new virus might be. And the Preston case, at such distance from the first outbreak, caused the experts to wonder—to worry—about how far it might already have spread. Take the mileage from Hendra to Mackay as a radius of potential distribution, draw circles with that radius around the site of each outbreak, and you would circumscribe about 10 million people, nearly half the population of Australia.
How big was the problem? How widely was the virus dispersed? One group of researchers, led by an infectious diseases man named Joseph McCormack, based at the Brisbane hospital where Vic Rail had died, took a broad look. They screened serum from five thousand Queensland horses—every horse they could put a needle in, evidently—and from 298 humans, each of whom had had some level of contact with a Hendra case. None of the horses contained Hendra antibodies, nor did any of the humans. Those negatives, we can assume, brought sighs of relief from the health authorities and deepened the puzzled scowls on the faces of the scientists. “It seems,” McCormack’s group concluded, “that very close contact is required for transmission of infection to occur from horses to humans.” But they were whistling in the dark. To say that “very close contact is required” didn’t explain why Margaret Preston had outlived her husband. The reality was this: that very close contact, plus bad luck, plus maybe one or two other factors were necessary for a person to become infected, and nobody knew what the other factors were.
But the Mark Preston case gave Hume Field valuable clues—a second point on the map, a second point in time. Hendra virus in Mackay, August 1994; Hendra virus at the Cannon Hill paddock and in Rail’s stable, September 1994. So Field went up to Mackay and repeated his method, trapping animals, drawing blood, sending serum to be tested for antibodies. And again he found nothing. He also drew samples from injured or otherwise debilitated wildlife of various types, creatures being nurtured in captivity until they could be released (if possible) back to the wild. The people who do such nurturing, a loose network of good-hearted amateurs, are known in Australian parlance as wildlife “carers.” They tend to specialize by zoological category. There are kangaroo carers, bird carers, possum carers, and bat carers. Hume Field knew of them from his years of veterinary practice; he had virtually been one of them, during his student days at the animal refuge. Now he sampled some of the animals in their care.
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