INTRODUCTION: CHOLERA’S CHILD
Cholera kills people fast. There’s no drawn-out sequence of progressive debility. The newly infected person feels fine at first. Then half a day passes, and cholera has drained his or her body of its fluids, leaving a withered blue corpse.
That’s why, even after being infected, you could, say, eat a decent breakfast at your hotel, of sunny-side-up eggs and tepid juice. You could drive over dusty, potholed roads to the airport. You’d feel perfectly well enough to withstand the long queues there. Even as the killer silently brewed in your gut, you’d push your bags through security, perhaps even pick up a croissant at the coffee shop and enjoy a brief respite in a cool molded-plastic chair at the gate before a crackly PA announced the boarding of your flight.
It would only be after you’d shuffled down the plane’s aisles and found your lightly tattered upholstered seat that the stranger within would make itself known, in a deadly, explosive onslaught of excretion, and your trip overseas would be suddenly and cruelly curtailed. Without the benefit of modern medicine rapidly administered, you’d be faced with a fifty–fifty chance of survival.
Such was the fate of a passenger ahead of me in line for Spirit Air Flight 952, from Port-au-Prince, Haiti, to Fort Lauderdale, Florida, in the summer of 2013. At the moment that cholera overcame the man, the rest of us were crammed inside a sweltering hall between the gate and the airplane, preparing to board. We waited there while the plane underwent an emergency disinfection. The airline didn’t tell us what had caused the sudden hour-long delay. When an airline worker sprinted out of the plane through the hall to gather more supplies, impatient passengers bombarded him with a chorus of questions. He yelled out over his shoulder, by way of explanation, “A man shit himself.” In Haiti, in the midst of a devastating cholera epidemic, there was little doubt as to what had happened.
If the stricken man had been infected an hour or two later, and sickened after we’d all taken our seats, with our arms jostling next to his on narrow strips of shared armrests, our knees grazing his, our hands brushing the overhead bins he’d touched, the pathogen might have been able to roost inside our bodies, too. I had spent my trip traipsing around to cholera treatment clinics and cholera-struck neighborhoods to see cholera firsthand. This formidable pathogen had nearly joined me on my flight home.
* * *
The disease-causing microbe, or pathogen, that will cause the world’s next pandemic lurks among us today. We don’t know its name or where it comes from. But for now call it “cholera’s child,” because what we do know is that it will likely follow the path that cholera blazed.
Cholera is one of only a handful of pathogens—including bubonic plague, influenza, smallpox, and HIV—that in modern times have been able to cause pandemics, contagions that spread widely among human populations. Among them, it stands alone. Unlike the plague, smallpox, and influenza, cholera’s emergence and spread were well documented from the beginning. Two centuries after it first emerged, it remains exceptionally potent, with an undiminished power to cause death and disruption, as its display on Flight 952 showed. And unlike relative newcomers like HIV, cholera’s an old hand at pandemics. So far, it’s caused seven, the latest hitting Haiti in 2010.
Today cholera is known primarily as a disease that affects impoverished countries, but that wasn’t always so. In the nineteenth century, cholera struck the most modern, prosperous cities in the world, killing rich and poor alike, from Paris and London to New York City and New Orleans. In 1836, it felled King Charles X in Italy; in 1849, President James Polk in New Orleans; in 1893, the composer Pyotr Ilyich Tchaikovsky in St. Petersburg. Over the course of the nineteenth century, cholera sickened hundreds of millions, killing more than half of its victims. It was one of the fastest-moving, most feared pathogens in the world.1
The microbe that causes the disease, Vibrio cholerae, was introduced into human populations during the era of British colonization of the South Asian hinterlands. But it was the rapid changes of the Industrial Revolution that provided the opportunities that turned the microbe into a pandemic-causing pathogen. New modes of travel—steamships, canals, and railways—ferried Vibrio cholerae deep into Europe and North America. The crowded and unsanitary conditions of rapidly growing cities allowed the bacteria to efficiently infect scores at a time.
Repeated epidemics of cholera posed a potent challenge to the political and social institutions of the societies it afflicted. Containing the disease called for a level of international cooperation, effective municipal governance, and social cohesion that had yet to be forged in newly industrialized cities and towns. Discovering its cure—clean water—required that doctors and scientists transcend long-held conventional wisdom about health and the spread of disease.
It took nearly a hundred years of deadly cholera pandemics for cities like New York, Paris, and London to rise to cholera’s provocations. To do it, they had to remake the way they housed themselves, managed their drinking water and their waste, governed the public’s health, conducted international relations, and understood the science of health and disease.
Such is the transformative power of pandemics.
* * *
The medical and public-health advances developed to contain nineteenth-century pathogens like cholera were so effective that for most of the twentieth century, the conventional wisdom among epidemiologists, medical historians, and other experts was that developed societies had vanquished infectious diseases for good. Western society had achieved “the virtual elimination of infectious diseases as a significant factor in social life,” the virologist Sir Macfarlane Burnet wrote in 1951.2 “To write about infectious disease,” he added in 1962, “is almost to write of something that has passed into history.”3 The average American who survived for around five decades at the beginning of the twentieth century lived for nearly eight by century’s end.4
According to the popular theory of “epidemiological transitions,” first articulated by the Egyptian scholar Abdel Omran, the demise of infectious diseases in wealthy societies was an inevitable result of economic development. As societies prospered, their disease profile shifted. Instead of being plagued by contagion, they suffered primarily from slow-moving, chronic, noncommunicable conditions, like heart disease and cancer.
I confess to once being a true believer in this theory. I knew from visiting places like the south Mumbai ghetto where my father had grown up that societies that suffered significant burdens of infectious diseases were indeed crowded, unsanitary, and impoverished. We stayed in south Mumbai every summer, crammed with relatives into two-room flats in a dilapidated tenement building. Like the hundreds of other residents, we flung our waste into the courtyard, carried our own water in aging plastic buckets to shared latrines, and fitted two-foot boards over the thresholds to keep out the rats. There—as in other crowded, waste-ridden, poorly plumbed societies—infection was a constant reality.
But at the end of every summer, we boarded planes back home, and it seemed like we’d left behind that contagion-ridden way of life for good, tracing the path my parents had blazed when they’d first left India for New York, plastic-framed medical degrees in their bags. In the American towns where we lived, where drinking-water supplies had been cleaned up; sewage contained, treated, and distantly disposed of; and a public-health infrastructure built, infectious diseases were a problem that had been solved.
But then, thanks to the same conditions that brought cholera to the shores of New York City, Paris, and London in the nineteenth century, writ large, the microbes staged their comeback. Development in once remote habitats introduced new pathogens into human populations. A rapidly changing global economy resulted in faster modes of international travel, offering these pathogens new opportunities to spread. Urbanization and the growth of slums and factory farms sparked epidemics. Like cholera, which benefited from the Industrial Revolution, cholera’s children started to benefit from its hangover: a changing climate, thanks to the excess carbon in the atmosphere unleashed by centuries of burning fossil fuels.
The first new infectious disease that struck the prosperous West and disrupted the notion of a “postinfection” era, the human immunodeficiency virus (HIV), appeared in the early 1980s. Although no one knew where it came from or how to treat it, many commentators exuded certainty that it was only a matter of time before medicine would vanquish the upstart virus. Drugs would cure it, vaccines would banish it. Public debate revolved around how to get the medical establishment to move quickly, not about the dire biological threat that HIV posed. In fact, early nomenclature seemed to negate the idea that HIV was an infectious disease at all. Some commentators, unwilling to accept the contagious nature of the virus (and willing to indulge in homophobic scapegoating) declared it a “gay cancer” instead.5
And then other infectious pathogens arrived, similarly impervious to the prevention strategies and containment measures we’d long taken for granted. Besides HIV, there was West Nile virus, SARS, Ebola, and new kinds of avian influenzas that could infect humans. Newly rejuvenated microbes learned to circumvent the medications we’d used to hold them in check: drug-resistant tuberculosis, resurgent malaria, and cholera itself. All told, between 1940 and 2004, more than three hundred infectious diseases either newly emerged or reemerged in places and in populations that had never seen them before.6 The barrage was such that the Columbia University virologist Stephen Morse admits to having considered the possibility that these strange new creatures hailed from outer space: veritable Andromeda strains, raining down upon us from the heavens.7
By 2008, a leading medical journal acknowledged what had become obvious to many: the demise of infectious diseases in developed societies had been “greatly exaggerated.”8 Infectious pathogens had returned, and not only in the neglected, impoverished corners of the world but also in the most advanced cities and their prosperous suburbs. In 2008, disease experts marked the spot where each new pathogen emerged on a world map, using red points. Crimson splashed across a band from 30–60° north of the equator to 30–40° south. The entire heart of the global economy was swathed in red: northeastern United States, western Europe, Japan, and southeastern Australia. Economic development provided no panacea against contagion: Omran was wrong.9
As this realization ripples through the medical establishment, the power of microbes—that is, the army of minute organisms too small to see with the naked eye, such as bacteria, viruses, fungi, protozoa, and microscopic algae—looms large. Instead of conquest, today infectious-disease experts speak of their diminishing odds, of the possibility that perhaps even the cancers and the mental illnesses that we’d once chalked up to lifestyle and genetics were actually the work of other untamed microbes.10 The old talk of mastery has vanished. “You hear this analogy that we have to win this war against microbes,” said the UCLA infectious-disease expert Brad Spellberg to a room full of colleagues in 2012. “Really? They are so numerous that they collectively outweigh us by one-hundred-thousand-fold. I don’t think so.”11
As the number of new pathogens rises, so does the death toll. Between 1980 and 2000, the number of deaths pathogens caused in the United States alone rose nearly 60 percent. HIV was responsible for a large proportion of those deaths, but not all. Excluding HIV, the number of people felled by pathogens rose by 22 percent.12
Many experts believe that a cholera-like pandemic looms. In a survey by the epidemiologist Larry Brilliant, 90 percent of epidemiologists said that a pandemic that will sicken 1 billion, kill up to 165 million, and trigger a global recession that could cost up to $3 trillion would occur sometime in the next two generations.13 So far, neither of the two pandemics caused by our newly emerged pathogens—HIV and H1N1—has been as fast and deadly as cholera. HIV is deadly, to be sure, but it spreads slowly; in 2009, H1N1 flu had spread quickly and widely but caused death in less than 0.005 percent of its victims.14 But new pathogens have caused species-destroying pandemics among our fellow animals. Chytrid fungus, first spotted in 1998, now threatens the collapse of many species of amphibians. In 2004, pollinating insects began disappearing, victims of the still-mysterious colony collapse disorder. In 2006, white-nose syndrome, caused by the fungal pathogenPseudogymnoascus destructans, started to decimate North American bats.15
Partly, this sense of an impending pandemic derives from the increasing number of candidate pathogens with the biological capacity to cause one. But it’s also a reflection of the shortcomings in our public-health infrastructure, modes of international cooperation, and ability to maintain social cohesion in the face of contagion. The way modern societies have handled outbreaks of new diseases so far does not bode well. The Ebola virus broke out in a remote forest village in Guinea in early 2014. It would have been easy to contain using only the simplest, cheapest measures had it been squelched early on at its source. Instead, the virus, which had previously infected no more than a few hundred people at a time, in a single year spread into five neighboring countries, infected more than twenty-six thousand people, and would cost billions to contain.16Well-understood diseases that can be easily contained with drugs and vaccines escaped control even in the wealthy countries best situated to stanch them. An outbreak of vaccine-preventable measles that began in Disneyland over winter holidays in 2014 spread into seven states, exposing thousands to the contagion. Between 1996 and 2011, the United States experienced fifteen such outbreaks.17
Which, if any, of the new pathogens will cause the next pandemic in humans remains to be seen. By the time I boarded that plane in Haiti, I’d encountered a few of the contenders myself.
* * *
In 2010, my two sons, age ten and thirteen, were like walking scabs. With legs bare beneath flimsy athletic shorts, they kicked torn-up soccer balls on the tarmac, leapt off bridges into the rocky streambed behind the house, scuffled on the rough slate floor.
I hadn’t registered the Band-Aid that my older son had affixed to his knee that spring. By the time he began complaining about it, the bandage’s edges had started to fray and the exposed adhesive had captured a few days of grit. He said his knee hurt, but that was easy to explain away. The purported scab was located over his kneecap, after all, and it wasn’t likely that he’d remained still long enough for it to ossify. A quick glance at the maroon blotch in the middle of the bandage provided sufficient evidence: this particular scab was being continually reopened. “Sure,” I thought to myself, “that would hurt.”
A few days later, he was wincing whenever he stood up. “Drama queen,” I thought. The next morning, he came down to the kitchen limping.
We removed the Band-Aid. There was no scab. Instead, we found a mountain range of angry pus-filled boils. One peak summited at over an inch—an inch!—and had wept a sickly stream of liquid into the gummed-up bandage.
The pathogen that had created these abscesses, we soon learned, is called methicillin-resistant Staphylococcus aureus, aka MRSA (“mursa” as experts pronounce it). It’s an antibiotic-resistant bacterium that first emerged in the 1960s and by 2010 was killing more Americans than AIDS.18 The pediatrician, usually so jovial, turned sternly businesslike after one look at my son’s knee. She whipped off a barrage of prescriptions even before the lab results came in: the heavy-duty antibiotic clindamycin and the old standby Bactrim, plus a brutal regime in which we’d have to force the pus out of the boils using hot compresses and viselike squeezing. This would be both excruciatingly painful, since the layer of pus extended deep under the tissue (tears ran down my son’s face at the thought of it), and fraught, as scores of MRSA bacilli teemed inside the pus. Each drop would have to be meticulously captured and disposed of, lest it find its way into a microscopic fissure in our skin or, worse, embed itself in our rugs, sheets, couches, or counters, where it could lie in wait for up to a year.19
After weeks of squeezing and drugs, the infection seemed tamed. “He was lucky,” a leading microbiologist said to me. “He could have lost his leg.”20 But summoned back to the pediatrician’s office for a follow-up, we were told we hadn’t seen the last of this unpredictable, hard-to-control new pathogen.
Whole families come down with MRSA, continually reinfecting each other for years, the pediatrician told us. I knew, having done some research by then, that this bug could kill, too. But none of the various physicians we visited knew how to prevent the infection from reoccurring or from spreading from my son to the rest of the family. One doctor recommended twice-weekly twenty-minute baths in bleach solution. “It’s not a beauty treatment,” he added, as if any clarification were needed. This, he said, we should continue until we were certain that there would be no more episodes—that is to say, for months, or even years. Another recommended the same treatment but with different specifics, namely, that the bath should have ½ cup of bleach in it. The doctor provided no details on duration or frequency, and in my shell-shocked state, I neglected to ask.
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.
Copyright © 2016 by Sonia Shah