Spillover
Page 4
If you assembled a short list of the highlights and high anxieties of that saga within recent decades, it could include not just Machupo but also Marburg (1967), Lassa (1969), Ebola (1976, with Karl Johnson again prominently involved), HIV-1 (inferred in 1981, first isolated in 1983), HIV-2 (1986), Sin Nombre (1993), Hendra (1994), avian flu (1997), Nipah (1998), West Nile (1999), SARS (2003), and the much feared but anticlimactic swine flu of 2009. That’s a drama series more glutted and seething with virus than even Vic Rail’s poor mare.
A person might construe this list as a sequence of dire but unrelated events—independent misfortunes that have happened to us, to humans, for one unfathomable reason and another. Seen that way, Machupo and the HIVs and SARS and the others are “acts of God” in the figurative (or literal) sense, grievous mishaps of a kind with earthquakes and volcanic eruptions and meteor impacts, which can be lamented and ameliorated but not avoided. That’s a passive, almost stoical way of viewing them. It’s also the wrong way.
Make no mistake, they are connected, these disease outbreaks coming one after another. And they are not simply happening to us; they represent the unintended results of things we are doing. They reflect the convergence of two forms of crisis on our planet. The first crisis is ecological, the second is medical. As the two intersect, their joint consequences appear as a pattern of weird and terrible new diseases, emerging from unexpected sources and raising deep concern, deep foreboding, among the scientists who study them. How do such diseases leap from nonhuman animals into people, and why do they seem to be leaping more frequently in recent years? To put the matter in its starkest form: Human-caused ecological pressures and disruptions are bringing animal pathogens ever more into contact with human populations, while human technology and behavior are spreading those pathogens ever more widely and quickly. There are three elements to the situation.
One: Mankind’s activities are causing the disintegration (a word chosen carefully) of natural ecosystems at a cataclysmic rate. We all know the rough outlines of that problem. By way of logging, road building, slash-and-burn agriculture, hunting and eating of wild animals (when Africans do that we call it “bushmeat” and impute a negative onus, though in America it’s merely “game”), clearing forest to create cattle pasture, mineral extraction, urban settlement, suburban sprawl, chemical pollution, nutrient runoff to the oceans, mining the oceans unsustainably for seafood, climate change, international marketing of the exported goods whose production requires any of the above, and other “civilizing” incursions upon natural landscape—by all such means, we are tearing ecosystems apart. This much isn’t new. Humans have been practicing most of those activities, using simple tools, for a very long time. But now, with 7 billion people alive and modern technology in their hands, the cumulative impacts are becoming critical. Tropical forests aren’t the only jeopardized ecosystems, but they’re the richest and most intricately structured. Within such ecosystems live millions of kinds of creatures, most of them unknown to science, unclassified into a species, or else barely identified and poorly understood.
Two: Those millions of unknown creatures include viruses, bacteria, fungi, protists, and other organisms, many of which are parasitic. Students of virology now speak of the “virosphere,” a vast realm of organisms that probably dwarfs every other group. Many viruses, for instance, inhabit the forests of Central Africa, each parasitic upon a kind of bacterium or animal or fungus or protist or plant, all embedded within ecological relationships that limit their abundance and their geographical range. Ebola and Marburg and Lassa and monkeypox and the precursors of the human immunodeficiency viruses represent just a minuscule sample of what’s there, of the myriad other viruses as yet undiscovered, within hosts that in many cases are as yet undiscovered themselves. Viruses can only replicate inside the living cells of some other organism. Commonly they inhabit one kind of animal or plant, with whom their relations are intimate, ancient, and often (but not always) commensal. That is to say, dependent but benign. They don’t live independently. They don’t cause commotion. They might kill some monkeys or birds once in a while, but those carcasses are quickly absorbed by the forest. We humans seldom have occasion to notice.
Three: But now the disruption of natural ecosystems seems more and more to be unloosing such microbes into a wider world. When the trees fall and the native animals are slaughtered, the native germs fly like dust from a demolished warehouse. A parasitic microbe, thus jostled, evicted, deprived of its habitual host, has two options—to find a new host, a new kind of host . . . or to go extinct. It’s not that they target us especially. It’s that we are so obtrusively, abundantly available. “If you look at the world from the point of view of a hungry virus,” the historian William H. McNeill has noted, “or even a bacterium—we offer a magnificent feeding ground with all our billions of human bodies, where, in the very recent past, there were only half as many people. In some 25 or 27 years, we have doubled in number. A marvelous target for any organism that can adapt itself to invading us.” Viruses, especially those of a certain sort—those whose genomes consist of RNA rather than DNA, leaving them more prone to mutation—are highly and rapidly adaptive.
All these factors have yielded not just novel infections and dramatic little outbreaks but also new epidemics and pandemics, of which the most gruesome, catastrophic, and infamous is the one caused by a lineage of virus known to scientists as HIV-1 group M. That’s the lineage of HIV (among twelve different sorts) that accounts for most of the worldwide AIDS pandemic. It has already killed 30 million humans since the disease was noticed three decades ago; roughly 34 million other humans are presently infected. Despite the breadth of its impact, most people are unaware of the fateful combination of circumstances that brought HIV-1 group M out of one remote region of African forest, where its precursor lurked as a seemingly harmless infection of chimpanzees, into human history. Most people don’t know that the real, full story of AIDS doesn’t begin among American homosexuals in 1981, or in a few big African cities during the early 1960s, but at the headwaters of a jungle river called the Sangha, in southeastern Cameroon, half a century earlier. Even fewer people have caught wind of the startling discoveries that, just within the past several years, have added detail and transformative insight to that story. Those discoveries will get their place later (“The Chimp and the River”) in this account. For now I’ll just note that, even if the subject of zoonotic spillover addressed nothing but the happenstance of AIDS, it would obviously command serious attention. But as mentioned already, the subject addresses much more—other pandemics and catastrophic diseases of the past (plague, influenza), of the present (malaria, influenza), and of the future.
Diseases of the future, needless to say, are a matter of high concern to public health officials and scientists. There’s no reason to assume that AIDS will stand unique, in our time, as the only such global disaster caused by a strange microbe emerging from some other animal. Some knowledgeable and gloomy prognosticators even speak of the Next Big One as an inevitability. (If you’re a seismologist in California, the Next Big One is an earthquake that drops San Francisco into the sea, but in this realm of discourse it’s a vastly lethal pandemic.) Will the Next Big One be caused by a virus? Will the Next Big One come out of a rainforest or a market in southern China? Will the Next Big One kill 30 or 40 million people? The concept by now is so codified, in fact, that we could think of it as the NBO. The chief difference between HIV-1 and the NBO may turn out to be that HIV-1 does its killing so slowly. Most other new viruses work fast.
I’ve been using the words “emergence” and “emerging” as though they are everyday language, and maybe they are. Among the experts, they’re certainly common parlance. There’s even a journal dedicated to the subject, Emerging Infectious Diseases, published monthly by the CDC. But a precise definition of “emergence” might be useful here. Several have been offered in the scientific literature. The one I prefer simply says that an emerging disease is “an infectious diseas
e whose incidence is increasing following its first introduction into a new host population.” The key words, of course, are “infectious,” “increasing,” and “new host.” A re-emerging disease is one “whose incidence is increasing in an existing host population as a result of long-term changes in its underlying epidemiology.” Tuberculosis is re-emerging as a severe problem, especially in Africa, as the TB bacterium exploits a new opportunity: infecting AIDS patients whose immune systems are disabled. Yellow fever re-emerges among humans wherever Aedes aegypti mosquitoes are allowed to resume carrying the virus between infected monkeys and uninfected people. Dengue, also dependent on mosquito bites for transmission and native monkeys as reservoirs, re-emerged in Southeast Asia after World War II due at least partly to increased urbanization, wider travel, lax wastewater management, inefficient mosquito control, and other factors.
Emergence and spillover are distinct concepts but interconnected. “Spillover” is the term used by disease ecologists (it has a different use for economists) to denote the moment when a pathogen passes from members of one species, as host, into members of another. It’s a focused event. Hendra virus spilled over into Drama Series (from bats) and then into Vic Rail (from horses) in September 1994. Emergence is a process, a trend. AIDS emerged during the late twentieth century. (Or was it the early twentieth century? I’ll return to that question.) Spillover leads to emergence when an alien bug, having infected some members of a new host species, thrives in that species and spreads among it. In this sense, the strict sense, Hendra hasn’t emerged into the human population, not yet, not quite. It is merely a candidate.
Not all emerging diseases are zoonotic, but most are. From where else might a pathogen emerge, if not from another organism? Well, granted, some novel pathogens do seem to emerge from the environment itself, without need for shelter in a reservoir host. Case in point: The bacterium now called Legionella pneumophila emerged from the cooling tower of an air-conditioning system at a hotel in Philadelphia, in 1976, to create the first-known outbreak of Legionnaires’ disease and kill thirty-four people. But that scenario is far less typical than the zoonotic one. Microbes that infect living creatures of one kind are the most likely candidates to infect living creatures of another kind. This has been borne out statistically by several review studies in recent years. One of them, published by two scientists at the University of Edinburgh in 2005, looked at 1,407 recognized species of human pathogen and found that zoonotic bugs account for 58 percent. Of the full total, 1,407, just 177 can be considered emerging or re-emerging. Three-fourths of those emergent pathogens are zoonotic. In plain words: Show me a strange new disease and, most likely, I can show you a zoonosis.
A parallel survey, from a team led by Kate E. Jones of the Zoological Society of London, appeared in the journal Nature in 2008. This group considered more than three hundred “events” of emerging infectious disease (EIDs, in their shorthand) that occurred between 1940 and 2004. They wondered about changing trends as well as discernible patterns. Although their list of events was independent of the Edinburgh researchers’ list of pathogens, Jones and her colleagues found almost the same portion (60.3 percent) to be zoonotic. “Furthermore, 71.8% of these zoonotic EID events were caused by pathogens with a wildlife origin,” as distinct from domestic animals. They cited Nipah in Malaysia and SARS in southern China. Further still, the increment of disease events associated with wildlife, as opposed to livestock, seems to be increasing over time. “Zoonoses from wildlife represent the most significant, growing threat to global health of all EIDs,” these authors concluded. “Our findings highlight the critical need for health monitoring and identification of new, potentially zoonotic pathogens in wildlife populations, as a forecast measure for EIDs.” That sounds reasonable: Let’s keep an eye on wild creatures. As we besiege them, as we corner them, as we exterminate them and eat them, we’re getting their diseases. It even sounds reassuringly doable. But to highlight the need for monitoring and forecasting is also to highlight the urgency of the problem and the discomfiting reality of how much remains unknown.
For instance: Why did Drama Series, the original mare, fall sick in that paddock when she did? Was it because she shaded herself beneath a fig tree and munched some grass besmeared with bat urine containing the virus? How did Drama Series pass her infection to the other horses at Vic Rail’s stable? Why did Rail and Ray Unwin get infected but not the devoted veterinarian, Peter Reid? Why did Mark Preston get sick but not Margaret Preston? Why did the outbreaks at Hendra and Mackay occur in August and September 1994, close in time though distant geographically? Why did all those bat carers remain uninfected, despite their months and years of fondling flying foxes?
These local riddles about Hendra are just small forms of big questions that scientists such as Kate Jones and her team, and the Edinburgh researchers, and Hume Field, and many others around the world are asking. Why do strange new diseases emerge when they do, where they do, as they do, and not elsewhere, other ways, at other times? Is it happening more now than in the past? If so, how are we bringing these afflictions upon ourselves? Can we reverse or mitigate the trends before we’re hit with another devastating pandemic? Can we do that without inflicting fearful punishment on all those other kinds of infected animals with which we share the planet? The dynamics are complicated, the possibilities are many, and while science does its work slowly, we all want a fast response to the biggest question: What sort of nasty bug, with what unforeseen origins and what inexorable impacts, will emerge next?
7
During one trip to Australia I stopped in Cairns, a balmy resort city about a thousand miles north of Brisbane, for a conversation with a young veterinarian there. I can’t recall how I located her, because she was wary of publicity and didn’t want her name used in print. But she agreed to talk to me about her experience with Hendra. Although her experience had been brief, it included two roles: as doctor, as patient. At that time she was the only known Hendra survivor in Australia, besides the stable hand Ray Unwin, who had also suffered infection with the virus and lived. We spoke in the office of a small veterinary clinic where she worked.
She was an ebullient woman, twenty-six years old, with pale blue eyes and hennaed brunette hair pulled back in a tight bun. She wore silver earrings, shorts, and a red short-sleeve shirt with a clinic logo. While an earnest border collie kept us company, nudging my hands for affection as I tried to write notes, the vet described a night in October 2004 when she had gone out to attend to a suffering horse. The owners were concerned because this particular animal, a ten-year-old gelding, seemed “off color.”
The horse was named Brownie, she remembered that. He lived on a family farm down at Little Mulgrave, about twenty miles south of Cairns. She remembered it all, in fact, a night full of vivid impressions. Brownie was a quarterhorse-thoroughbred cross. Not a racer, no, a pet. The family included a teenage daughter; Brownie was her special favorite. At eight o’clock that evening the horse seemed normal, but then something went suddenly wrong. The family suspected colic, bad stomach—maybe he had eaten some toxic greens. Around eleven o’clock they phoned for help and got the young vet, who was on call that night. She jumped in her car, and when she arrived Brownie was in desperate condition, panting heavily, feverish, down on the ground. “I found the horse had a heart rate through the roof, temperature through the roof,” she told me, “and there was bloody red froth coming out the nose.” Giving him a quick look, taking his vitals, she came close to the horse and, when he snorted, “I got quite a degree of bloody sort of red mucousy froth on my arms.” The teenage girl and her mother were already smeared with blood from having tried to comfort Brownie. Now he could barely lift his head. The vet, a fiercely caring professional, told them the horse was dying. Knowing her duty, she said: “I want to euthanize it.” She ran back to her car, got the euthanasia solution and tools, but by the time she returned Brownie was dead. In his last agonal gasps, he had brought up more bubbly red froth through his nostrils and mo
uth.
Were you wearing gloves? I asked.
No. The protocol was to use gloves for a postmortem, but not for live animals. Then the one situation led so swiftly to the other. “I was wearing exactly what I’m wearing now. A pair of shoes, short socks, blue shorts, and short sleeves.”
A surgical mask?
No, no mask. “You know, in the laboratory all those precautions are easy to take. When it’s twelve at night and it’s pouring down rain and you’re out in the middle of the dark and you’re operating via the car headlights with a hysterical family in the background, it’s not always easy to take the proper precautions. And the other thing was, that I just didn’t know.” Didn’t know what she was confronting in Brownie’s case, she meant. “I wasn’t really thinking infectious disease.” She was defensive on these points because there had been second-guessing of her procedures, an investigation, questions about negligence. She had been exonerated—in fact, she made her own complaint about having not been properly warned—but it couldn’t have been helpful to her career, and that’s presumably why she wanted anonymity. She had a story to tell, yet she also wished to put it behind her.
In the minutes after Brownie’s death, she had changed into boots, long pants, and shoulder-length gloves and begun the postmortem exam. The owners were keen to know whether Brownie had eaten some sort of poisonous grass that might threaten their other horses too. The vet sliced opened Brownie’s abdomen and found his guts looking normal. No sign of twisted bowel or other blockage that might cause colic. In the process, “I got a couple of splashes of abdominal fluid on my leg.” You can’t do a postmortem on a horse without getting smeared, she explained. Next she looked into the chest, by way of a modest incision between the fourth and fifth ribs. If it wasn’t colic it was probably cardiac trouble, she suspected, and saw that hunch immediately confirmed. “The heart was massively enlarged. The lungs were wet and full of bloody fluid and there was just fluid right through the chest cavity. So he died of congestive heart failure. That was all I could conclude. I couldn’t conclude whether it was infectious or not.” She offered to take samples for lab testing, but the owners declined. Enough information, enough expense, too bad about Brownie, and they would simply bury the carcass with a bulldozer.