by Sonia Shah
This lack of clear consensus, the open-ended time frame, and the repellent nature of the treatment began to shake our resolve. We started to wonder: Are they making it up? At the time, there’d been only one study on the effectiveness of bleach treatment, conducted in 2008. It showed that moderately concentrated bleach baths could “decolonize” material of MRSA. But how long-lasting the effect was, whether it would work on human skin as it did on the material used in the study, and, most important, whether it would make any difference in the frequency of MRSA infections one might get, nobody knew. Perhaps MRSA lived inside one’s body, or victims were somehow primed to pick it up or become infected by it from other sources, in which case the bleaching would make no difference at all. And maybe, as my husband pointed out, the same result, such as it was, could be had by regular swimming in the MRSA-neutralizing, highly chlorinated waters of our neighborhood swimming pool. Or by regularly exposing our skin to sunlight.
Medicine’s uncertainty about how to cope with this upstart offended my sensibilities. As the child of medical professionals (a psychiatrist and a pathologist), I’d grown up with the idea that medicine could solve all ills. How had the sureties of the past so quickly devolved into “perhaps” and “maybe”?
Adding to my sense of unease was the memory of an episode that had transpired the year before our initiation into life with MRSA. In 2009, a new kind of influenza virus, called H1N1, had arrived in the local elementary and middle schools. I had jostled at the clinic with scores of harried parents for a chance to get my kids vaccinated with the H1N1 shot. But H1N1 had come on too fast, too strong, and there wasn’t enough vaccine. By the time my kids got the shot, it was too late; influenza (presumably H1N1, since it was the dominant strain in circulation that winter) had already started to incubate in their bodies. For days, two unstoppable boys lay utterly still, as their bodies burned with 103° fevers to repel the virus. As with MRSA, there was nothing to do, nothing to offer them. Finally, they recovered, although more than half a million others around the world died of H1N1—including more than twelve thousand in the United States. The rest of that season my sons’ soccer car pools filled with the sound of a gaggle of boys emitting identical postflu hacking coughs.21
And then, within months of H1N1 and MRSA’s incursions into my household, cholera washed over Haiti, where it hadn’t been seen in more than a century.
* * *
This quick succession of events convinced me that the strange new infections we’d experienced were not isolated, circumstantial events but part of a larger, global phenomenon. Having spent several years reporting on one of humankind’s oldest pathogens, malaria, my interest was immediately piqued. Most of the time, the story of pandemic disease begins when pathogens are already entrenched in populations, exacting their pounds of flesh. The backstory of how they got there and where they came from has to be pieced together from disparate clues and signs, an especially challenging task when the subject is dynamic and constantly evolving. And yet it’s the backstory that is the most important one of all, for it gives us the knowledge we need to prevent pandemics from taking hold in the first place. The arrival of a spate of new pathogens provided an opportunity to capture that backstory in real time. The obscure mechanisms and pathways that turn microbes into pandemic-causing pathogens could be tracked firsthand.
But I struggled with the question of how to do it. One approach would have been to pick one emerging pathogen and track its development. For me, that seemed both risky and mercenary. Which one to choose? While the overall risk of a pandemic may be rising, there’s no telling which of our emerging and reemerging pathogens, if any, will cause one. I could make an educated guess—others have—but odds are that guess would be wrong. Most emerging pathogens won’t cause pandemics. That’s just a matter of math: very few pathogens do.
Another approach would have been to delve into the history of a pathogen that has already mastered the business of causing pandemics. That’s a safer strategy but still would provide only a partial glimpse into what’s happening now. As fascinating as the stories of cholera or smallpox or malaria are, each is necessarily rooted in its time and place. Plus, there’s an inherent paradox: the better, more detailed history one provides, the more likely it is that the conditions that led to a historical pandemic will come to seem unique and therefore tangential to the story of tomorrow’s pandemic.
I was idly browsing through papers about emerging diseases when I stumbled upon a 1996 Science paper by the microbiologist Rita Colwell. It was an adaptation of an address she’d given to the American Association for the Advancement of Science. In her talk, Colwell had posited what she called the Cholera Paradigm: the idea that inside the story of cholera, her longtime specialty, were all the clues required to understand the primary drivers behind other emerging diseases. It occurred to me then that what I needed to do was to essentially combine the two approaches I’d previously dismissed in isolation. By telling the stories of new pathogens through the lens of a historical pandemic, I could show both how new pathogens emerge and spread, and how a pathogen that had used the same pathways had already caused a pandemic. The path from microbe to pandemic would be illuminated in the overlap, where two dim beams intersected.
And so I set off for the slums of Port-au-Prince, the wet markets of south China, and the surgical wards of New Delhi, in search of the birthplaces of pathogens old and new. I delved into the history of pandemics, in the written record as well as the one etched into our genomes. I tapped fields that ranged from evolutionary theory and epidemiology to cognitive science and political history, as well as my own idiosyncratic story.
What I found is that as similar as today’s pace of economic, social, and political change is to that of the nineteenth century’s era of industrialization, there’s an important difference. In the past, the forces that drove pandemics were obscure to their victims. In the nineteenth century, people carried cholera across the seas on their ships and canals, allowed it to spread in their crowded slums and through their commercial transactions, and made its symptoms more deadly with their medicines without knowing how or why. Today, as we stand on the cusp of the next pandemic, the multistage journey from harmless microbe to pandemic-causing pathogen is no longer invisible. Each stage can be laid bare for all to see.
This book tracks that journey, from the wilds of colonial South Asia and the nineteenth-century slums of New York City to the jungles of Central Africa and the suburban backyards of the East Coast today. It begins, for cholera and its progeny, in the bodies of the wild animals around us.
ONE
THE JUMP
In search of the birthplace of new pathogens, I set out on a cool rainy day in early 2011 to find a wet market in Guangzhou, the capital of the southern Chinese province of Guangdong.
Wet markets are open-air street markets where vendors sell live animals captured from the wild to consumers to slaughter and consume. They service the Chinese taste for what’s called yewei, or “wild,” cuisine, in which exotic animals from snakes and turtles to bats are prepared into special dishes.1
It was in a wet market in Guangzhou that the virus that nearly caused a pandemic in 2003 was born. This particular virus normally lived inside horseshoe bats. It was a kind of coronavirus, a family of viruses that mostly cause mild respiratory illnesses. (In humans, they’re responsible for about 15 percent of all cases of the common cold.) But the virus that was hatched at the wet market in Guangzhou was different.2
From the horseshoe bats, it had spread into other wild animals caged nearby, including raccoon dogs, ferret badgers, snakes, and palm civets. As the virus spread, it mutated. And in November 2003, a mutant form of the horseshoe bat virus started infecting people.
Like other coronaviruses, the virus colonized the cells lining the respiratory tract. But unlike its more mild brethren, the new virus tinkered with the human immune system, disrupting infected cells’ ability to warn neighboring cells of the viral intruder in the body. As a resu
lt, in about a quarter of the infected, what started off seeming like flu rapidly escalated into life-threatening pneumonia as infected lungs filled with fluid and starved the body of oxygen. Over the following months, the virus sickened more than eight thousand with what came to be known as SARS, for severe acute respiratory syndrome. Seven hundred and seventy-four people perished.3
The SARS virus vanished after that. Like a brightly burning star, it used up all its available fuel, killing people too quickly to spread any farther. After scientific experts fingered wet markets as the hatcheries that birthed the strange new pathogen, Chinese authorities cracked down on the markets. Many closed. But then a few years passed and wet markets came back, albeit in smaller and more furtive form.
We’d been told there was a wet market somewhere around Zengcha Road, a traffic-clogged four-lane road that runs under a belching highway in Guangzhou. After walking around in circles for a bit, we stopped to ask a uniformed guard for directions. He laughed mirthlessly. The wet market was closed down six years ago, he said, after the SARS epidemic. But then, without pause, he grabbed the hem of a worker passing by and tugged on it, instructing us to reask our question, this time to the worker. We did, and the worker told a different story: go down around the other side of the building, he said, as the guard listened approvingly. We “may” find “some people” selling “some things.”
As we turned the corner, the smell hit first, pungent, musky, and damp. The wet market consisted of a series of garage-like stalls lining a cement walkway. Some had been fashioned into office-cum-bedroom-cum-kitchens, in which the animal traders, bundled up for the weather, were passing the time waiting for customers. In one stall, three middle-aged men and a woman played cards on a folding table; in another, a bored-looking teenage girl watched a television bolted to the wall. As we walked in, a man flung the dregs of his soup bowl into the shallow gutter between the stalls and the walkway, a family of eight huddled around steaming bowls of hot pot behind him. A few minutes later, he reappeared to vigorously blow his nose into it.
Ignored entirely were the goods that we’d come to see: the caged wild animals that had been captured and acquired from other traders, in a long supply chain extending deep into China’s interior and as far afield as Myanmar and Thailand. A thirty-pound turtle in a white plastic bucket sat desultorily in a puddle of gray water next to cages of wild ducks, ferrets, snakes, and feral cats. Row after row of animals who’d rarely if ever encounter each other in the wild were here, breathing, urinating, defecating, and eating next to each other.
The scene was remarkable in several ways that might explain why SARS had begun there. One was the unusual, ecologically unprecedented conglomeration of wild animals. In a natural setting, horseshoe bats, which live in caves, never rub shoulders with palm civets, a kind of cat that lives in trees. Neither would normally come within spitting distance of people, either. But all three came together in the wet market. The fact that the virus had spread from bats into civet cats had been especially critical to SARS’s emergence. The civet cats were, for some reason, especially vulnerable to the virus. This gave the virus the opportunity to amplify its numbers, like a whistle in a tunnel. With increased replication came increased opportunities to mutate and evolve, to the extent that it evolved from a microbe that inhabited horseshoe bats to one that could infect humans. Without that amplification, it’s hard to say whether the SARS virus would have ever emerged.
We approached one vendor in a stall lit by a single bare bulb. Behind him, on a sagging shelf, was a smudged, gallon-size glass jar packed with snakes floating in some kind of brine. As my translator Su engaged in small talk with the vendor, two women appeared and flung white cloth sacks on the floor at my feet. Inside one, a tangle of thin brown snakes slithered over each other. In the other, a single, much larger, violently jerking snake hissed. Clearly, this snake was perturbed. Through the sheer fabric I could see that the snake’s head had a wide hood, which meant it was a cobra.
While those two facts sank in, the man and the two women, who had thus far not acknowledged my presence, turned to face me with some urgency in their expressions. Su translated their question: Exactly how many people do I plan to feed with this snake?
I stammered “ten” and turned away, flustered. A few minutes later, a woman approached us with another question. She gestured at me and, politely hiding a smirk behind her hand, asked Su whether it was true that foreigners like me ate turkeys. For her, I was the one with the strange eating habits.
* * *
Cholera also started out in the bodies of animals. The creatures that harbored cholera live in the sea. They’re a kind of tiny crustacean called copepods. They’re about a millimeter long, with teardrop-shaped bodies and a single bright-red eye. Since they can’t swim, they’re considered a kind of zooplankton, drifting in the water and delaying gravity’s pull to the depths with long antennae splayed outward like wings on a glider plane.4 Though they’re not talked about much, they’re actually the most abundant multicellular creatures on Earth. A single sea cucumber might be covered with over two thousand copepods, a single hand-size starfish with hundreds. In some places, the copepods are so thick that the water turns opaque, and in a single season each one may produce nearly 4.5 billion offspring.5
Vibrio cholerae are their microbial partners. V. cholerae is a microscopic, comma-shaped species of bacteria from the genus Vibrio. Although V. cholerae can live on its own, free-floating in the water, it collects most lushly in and on copepods, sticking to copepods’ egg sacs and lining the interior of their guts. Vibrio bacteria performed a valuable ecological function there. Like other crustaceans, copepods encase themselves in crusty exteriors made of a polymer called chitin (pronounced “kite-in”). Several times during their lifetimes, they shed their outgrown skins like snakes, discarding 100 billion tons of carapaces annually. Vibrio bacteria feed on this abundance of chitin, collectively recycling 90 percent of the ocean’s excess chitin. Were it not for them, copepods’ mountain of exoskeletons would starve the ocean of carbon and nitrogen.6
Vibrio bacteria and copepods proliferated in warm, brackish coastal waters, where fresh and salty waters met, such as in the Sundarbans, an expansive wetlands at the mouth of the world’s largest bay, the Bay of Bengal. This was a netherworld of land and sea long hostile to human penetration. Every day, the Bay of Bengal’s salty tides rushed over the Sundarbans’ low-lying mangrove forests and mudflats, pushing seawater as far as five hundred miles inland, creating temporary islands of high ground, called chars, that daily rose and vanished with the tides. Cyclones, poisonous snakes, crocodiles, Javan rhinoceros, wild buffalo, and even Bengal tigers stalked the swamps.7 The Mughal emperors who ruled the Indian subcontinent up until the seventeenth century prudently left the Sundarbans alone. Nineteenth-century commentators called it “a sort of drowned land, covered with jungle, smitten by malaria, and infested by wild beasts,” and possessed of an “evil fertility.”8
But then, in the 1760s, the East India Company took over Bengal and with it the Sundarbans. English settlers, tiger hunters, and colonists streamed into the wetlands. They recruited thousands of locals to chop down the mangroves, build embankments, and plant rice. Within fifty years, nearly eight hundred square miles of Sundarbans forests had been razed. Over the course of the 1800s, human habitations would sprawl over 90 percent of the once untouched, impenetrable, and copepod-rich Sundarbans.9
Contact between human and vibrio-infested copepod had probably never been quite so intense as in these newly conquered tropical wetlands. Sundarbans farmers and fishermen lived in a world semisubmerged in the half-salty water in which vibrio bacteria thrived. It wouldn’t have been particularly difficult for the vibrio to penetrate the human body. A fisherman who splashed his face with water by the side of a boat, say, or a villager drinking from a well corroded with a few ounces of floodwaters, could easily ingest a few invisible copepods. Each one might be infested with as many as seven thousand vibrios.10
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sp; This intimate contact allowed Vibrio cholerae to “spill over” or “jump” into our bodies. The bacteria wouldn’t have found a particularly welcoming reception there, at first. Human defenses are designed to repel such intrusions, from the acid environs of our stomachs, which neutralize most bacteria, and the competitive wrath of the microbes that inhabit our gut to the constantly patrolling cells of the immune system. But in time, V. cholerae adapted to the human bodies to which it was repeatedly exposed. It acquired, for example, a long, hairlike filament at its tail that improved its ability to bond to other vibrio cells. Endowed with the filament, the vibrio could form tough microcolonies that could stick to the lining of the human gut like scum on a shower curtain.11
Vibrio cholerae became what’s known as a zoonosis, from the Greek zoon for “animal” and nosos for “disease.” It was an animal microbe that could infect humans. But V. cholerae wasn’t a pandemic killer yet.
* * *
As a zoonosis, Vibrio cholerae could infect only people who exposed themselves to their “reservoir” animals, the copepods. It was a pathogen on a leash, unable to infect anyone outside its limited purview. It had no way of infecting anyone who wasn’t exposed to copepod-rich waters. While it could cause outbreaks, when multiple people exposed themselves to copepods simultaneously, for example, those outbreaks would always be self-limited. They’d collapse on their own.
For a pathogen to cause a wave of sequential infections—an epidemic or a pandemic, depending on how far the wave traveled—it must be able to spread directly from one human to another. That is to say, its “basic reproductive number” has to be greater than 1. The basic reproductive number (also known as R0, or “R-naught,” as the Anglophiles pronounce it) describes the average number of susceptible people who are infected by a single infected person (in the absence of outside interventions). Say you have a cold, and you infect your son and his friend with it. If this hypothetical scenario were typical of the entire population, your cold’s basic reproductive number would be 2. If you infect your daughter as well, your cold’s basic reproductive number would be 3.
