Spillover

by David Quammen

  They focused then on trying to culture it. This meant, first of all, giving the mystery creature an environment of living cells in which it was able to replicate, until it grew abundant enough in the culture, and caused enough damage to the cells, that its presence could be seen. The living cells of the culture had to be one or another “immortalized” lineage (such as the famous HeLa cells from an unfortunate woman named Henrietta Lacks), so that they would continue replicating indefinitely until something killed them. Peiris’s team began by offering the new bug five different cell lines that had variously proven hospitable to familiar respiratory pathogens: cells from a dog’s kidney, cells from a rat’s tumor, cells from the lung of an aborted human fetus, and others. No luck. There was no sign of cell damage and therefore no evidence of viral growth. Then they tried another line, derived from kidney cells of a fetal rhesus monkey. Yes luck. By the middle of March, they could see “cytopathic effect” in their monkey-cell culture, meaning that something had begun to replicate within those cells and destroy them, spilling from one cell to another and creating a visible zone of devastation. Within a few more days, the team had electron microscope images of round viral particles, each particle encircled by a corona of knobs. This was so unexpected that one microscopist on the team had recourse to what amounted to a field guide; he browsed through a book of viral micrographs, looking for a match, as you or I might do for a new bird or a wildflower. He found his match among a group known as the coronaviruses, characterized by a corona of knobby proteins rimming each viral particle.

  So the culturing work had established that an unknown coronavirus was present in SARS patients—some of them, anyway—but that didn’t necessarily mean it had caused the disease. To establish causality, Peiris’s team tested blood serum from SARS patients (because it would contain antibodies) against the newfound virus in culture. This was like splashing holy water at a witch. The antibodies recognized the virus and reacted strongly. Less than a month later, based on that evidence plus other confirming tests, Malik Peiris and his colleagues published a paper cautiously announcing this new coronavirus as “a possible cause” of SARS.

  They were right, and the virus became known as SARS coronavirus, inelegantly abbreviated as SARS-CoV. It was the first coronavirus ever found to inflict serious illness upon humans. (Several other coronaviruses are among the many viral strains responsible for common colds. Still others cause hepatitis in mice, gastroenteritis in pigs, and respiratory infection in turkeys.) SARS-CoV has no ominous ring. In older days, the new agent would have received a more vivid, geographical moniker such as Foshan virus or Guangzhou virus, and people would have run around saying: Watch out, he’s got Guangzhou! But by 2003 everyone recognized that such labeling would be invidious, unwelcome, and bad for tourism.

  Several other teams, working independently to isolate a SARS causal agent, had gotten the same answer at about the same time. In the United States, it was a group based at the CDC in Atlanta, with a long list of international partners. In Europe, it was a set of collaborators spread among research institutions in Germany, France, and the Netherlands. In China, it was a small squad of earnest, adept, and deferential researchers who had isolated a coronavirus and photographed it weeks before Peiris’s group did the same. These unfortunate Chinese scientists, based at the Academy of Military Medical Sciences, let themselves be cowed by the chlamydia theory and its august promoter in Beijing, passing up their opportunity to announce the real discovery first. “We were too cautious,” one of them said later. “We waited too long.”

  The next logical step for Malik Peiris and his gang, after having identified the virus, sequenced a portion of its genome, and placed it within a family tree of other coronaviruses, was to wonder about its origin. The thing hadn’t come out of nowhere. But what was its usual habitat, its life history, its natural host? One scientist involved in the work, a young biologist named Leo Poon, touched on that during a conversation with me in Hong Kong.

  “The data that we found in human samples,” said Poon, “suggested that this virus is novel to humans. What I mean is that humans had not been infected by this virus before. So it must have been coming from some kinds of animals.”

  But which animals, and how did they happen to transmit the infection to people? Those questions could only be answered by going into the forests, the streets, the markets, the restaurants of southern China to gather evidence. Nudging him toward that subject, I wondered: “Were you part of the fieldwork?”

  “No, I’m a molecular scientist,” he said. It had been like asking Jackson Pollock if he painted houses, I suppose, but Leo Poon didn’t take my question amiss. He was happy to give credit where due. No, another of their colleagues, a wildcat fellow named Guan Yi, with the instincts of an epidemiologist and the balls of a brass macaque, had crossed into China and, with cooperation from some local officials, taken swabs from the throats, the anuses, and the cloacae of animals on sale in the biggest live market in Shenzhen. Those samples were what first led Leo Poon (who did the molecular analysis), Malik Peiris, Guan Yi himself—and, eventually, scientists and health officials all over the world—to cast their suspicious attentions upon a mammal called the civet cat.

  36

  In a crowded country with 1.3 billion hungry citizens, it should be no surprise that people eat snake. It should be no surprise that there are Cantonese recipes for dog. Stir-fried cat, in such a context, seems sadly inevitable rather than shocking. But the civet cat (Paguma larvata) is not really a cat. More accurately known as the masked palm civet, it’s a member of the viverrid family, which includes the mongooses. The culinary trade in such unusual wild animals, especially within the Pearl River Delta, has less to do with limited resources, dire necessity, and ancient traditions than with booming commerce and relatively recent fashions in conspicuous consumption. Close observers of Chinese culture call it the Era of Wild Flavor.

  One of those observers is Karl Taro Greenfeld, who served as editor of Time Asia in Hong Kong during 2003, oversaw the magazine’s coverage of SARS, and soon afterward wrote a book about it, China Syndrome. Before his editing role, Greenfeld had covered “the new Asia” as a journalist for some years, giving him opportunity to see what people were putting in their stomachs. According to him:

  Southern Chinese have always noshed more widely through the animal kingdom than virtually any other peoples on earth. During the Era of Wild Flavor, the range, scope, and amount of wild animal cuisine consumed would increase to include virtually every species on land, sea, or air.

  Wild Flavor (yewei in Mandarin) was considered a way of gaining “face,” prosperity, and good luck. Eating wild, Greenfeld explained, was only one aspect of these new ostentations in upscale consumption, which might also involve patronizing a brothel where a thousand women stood on offer behind a glass wall. But the food vogue arose easily from earlier traditions in fancy cuisine, natural pharmaceuticals, and exotic aphrodisiacs (such as tiger penis), and went beyond them. One official told Greenfeld that two thousand Wild Flavor restaurants were now operating within the city of Guangzhou alone. Four more received licenses during the hour Greenfeld spent in the man’s office.

  These eateries drew their supplies from the “wet markets” of Guangdong province, vast bazaars filled with row after row of stalls purveying live animals for food, such as the Chatou Wildlife Market in Guangzhou and the Dongmen Market in Shenzhen. Chatou began operating in 1998 and within five years had become one of the largest wild-animal markets in China, especially for mammals, birds, frogs, turtles, and snakes. Between late 2000 and early 2003, a team of researchers based in Hong Kong conducted an ongoing survey of wild animals on sale at Chatou, Dongmen, and two other big Guangdong markets. Compared to an earlier survey done in 1993–1994, the team found some changes and new trends.

  First, the sheer volume of the wild-animal trade seemed to have increased. Second, there was more cross-border commerce, legal or covert, drawing wildlife from other Southeast Asian countries into
southern China. Meaty but precious individuals of endangered species, such as the Bornean river turtle and the Burmese star tortoise, were turning up. Third, greater numbers of captive-bred animals had become available from commercial breeders. Certain kinds of frogs and turtles were being farmed. Snakes, according to rumor, were being farmed. Small-scale civet farms, operating in central Guangdong and southern Jiangxi (an adjacent province), helped supply the demand for that animal. In fact, much of the trade in three popular wild mammals—the Chinese ferret badger and the hog badger in addition to the masked palm civet—seemed to come from farm breeding and rearing. Evidence for this supposition, made by the survey team, was that the animals appeared relatively well fed, uninjured, and tame. Caught from the wild, they would more likely show trap wounds and other signs of desperation and abuse.

  But even if they arrived healthy and robust from the farm, conditions in the markets weren’t salubrious. “The animals are packed in tiny spaces and often in close contact with other wild and/or domesticated animals such as dogs and cats,” the survey team wrote. “Many are either sick or with open wounds and without basic care. Animals are often slaughtered inside the markets in several stalls specialising in this.” Open wire cages, stacked vertically, allowed wastes from one animal to rain down onto another. It was zoological bedlam. “The markets also provide a conducive environment,” the team noted, almost passingly, “for animal diseases to jump hosts and spread to humans.”

  Guan Yi, the intrepid microbiologist from Hong Kong University, waded into these conditions at Dongmen Market, in Shenzhen, and persuaded sellers to let him take swab samples and blood from some of their animals. Exactly how he persuaded them is still mystifying—force of personality? eloquent arguments? clear explication of scientific urgency?—although holding a thick wad of Hong Kong dollars in his hand apparently helped. He anaesthetized twenty-five animals one by one, swabbed for mucus, swabbed for feces, drew blood, and then took the samples back to Hong Kong for analysis. The hog badgers were clean. The Chinese hares were clean. The Eurasian beavers were clean. The domestic cats were clean. Guan had also sampled six masked palm civets, which weren’t clean; all six carried signs of a coronavirus resembling SARS-CoV. In addition, the fecal sample from one raccoon dog (a kind of wild canid, which looks like an overfed fox with raccoon markings), tested positive for the virus. But the data overall pointed most damningly at the civet.

  This discovery, the first concrete indication that SARS is a zoonotic disease, was announced at a Hong Kong University press conference on May 23, 2003. One day later, the South China Morning Post, Hong Kong’s leading English-language newspaper, ran a front-page story (amid all its other SARS coverage) on the announcement, headlined: SCIENTISTS LINK CIVET CATS TO SARS OUTBREAK. Residents of the city were quite aware, by then, that the SARS contagion traveled on human respiratory emissions from person to person, not just in the juices and flesh of wild meat. Earlier editions of the Morning Post, as well as other Hong Kong newspapers, had carried articles accompanied by vivid photos of people in surgical masks—a masked couple kissing, a hospital official demonstrating a mask and visor, a comely model at an auto show wearing a mask decorated with car advertising—as well as hospital staff and soldiers doing infection control in full hazmat suits. Hong Kong’s governmental supplies department distributed 7.4 million masks to schools, medical personnel, and health officials on the front line of response, and demand was high too among the general public. Circle K, the convenience store chain, had sold almost a million masks; Sa Sa Cosmetics had moved 1.5 million. Prices per mask had quadrupled. Despite the widespread alarm over person-to-person transmission, though, there was still great interest in learning where this virus had its zoological source.

  Using a press conference to break the news about civets, rather than publishing first in a scientific journal, was unorthodox but not unprecedented. Journal publication would have taken longer, because of editorial work, peer review, backlogs of articles, and lead times. Circumventing that process reflected haste, driven by civic concern and the urgency of the outbreak but also possibly by scientific competition. The CDC in Atlanta had shown its own haste just two months earlier in announcing, also by way of a press conference, that scientists there had identified a new coronavirus as the likely cause of SARS. The CDC announcement didn’t mention that Malik Peiris and his team had found the same virus and confirmed its connection with SARS three days before. That act of claiming priority by the CDC, unnoticeable to the world at large, probably put the Hong Kong University scientists on edge against their competitors in Atlanta and elsewhere, and contributed to the decision to trumpet Guan Yi’s discovery at the earliest reasonable chance.

  One immediate consequence of Guan’s findings was that the Chinese government banned the sale of civets. In its uncertainty, the government also banned fifty-three other Wild Flavor animals from the markets. The ban inevitably caused economic losses, generating such foofaraw from animal farmers and traders that in late July, after an official review of the risks, it was rescinded. The rationale for reversal was that another group of researchers had screened masked palm civets and found no evidence whatsoever of a SARS-like virus. Under the revised policy, farm-raised civets could be legally traded again but the sale of wild-caught animals was prohibited.

  Guan Yi showed some annoyance at the doubts about his findings. But he forged ahead through scientific channels, presenting a detailed explication and supporting data (tables, figures, genome sequences) in a paper published in Science the following October. Leo Poon and Malik Peiris, his HKU colleagues, were included in the long list of coauthors. Guan and company worded their conclusions judiciously, noting that infection of civets didn’t necessarily mean that civets were the reservoir host of the virus. The civets might have become infected “from another, as yet unknown, animal source, which is in fact the true reservoir in nature.” They might have functioned as amplifier hosts (like those Hendra-infected horses in Australia). The real point, according to Guan and his colleagues, was that the wet markets such as Dongmen and Chatou provided a venue for SARS-like coronaviruses “to amplify and to be transmitted to new hosts, including humans, and this is critically important from the point of view of public health.”

  By the time that paper appeared, the SARS epidemic of 2003 had been stopped, with the final toll at 8,098 people infected, of whom 774 died. The last case was detected and isolated in Taiwan on June 15. Hong Kong had been declared “SARS-free.” Singapore and Canada had been declared “SARS-free.” The whole world was supposedly “SARS-free.” What those declarations meant, more precisely, was that no SARS infections were currently raging in humans. But the virus hadn’t been eradicated. This was a zoonosis, and no disease scientist could doubt that its causal agent still lurked within one or more reservoir hosts—the palm civet, the raccoon dog, or whatever—in Guangdong and maybe elsewhere too. People celebrated the end of the outbreak, but those best informed celebrated most guardedly. SARS-CoV wasn’t gone, it was only hiding. It could return.

  In late December, it did. Like an aftershock to a quake, a new case broke in Guangdong. Soon afterward, three more. One patient was a waitress who had been exposed to a civet. On January 5, 2004, the day the first case was confirmed, Guangdong authorities reversed policy again, ordering the death and disposal of every masked palm civet held at a farm or a market in the province. Wild civets were another question, left unanswered.

  Eradication teams from the Forestry Department (which regulates the wild animal trade) and the Health Department went out to civet farms. During the days that followed, more than a thousand captive civets were suffocated, burned, boiled, electrocuted, and drowned. It was like a medieval pogrom against satanic cats. This campaign of extermination seemed to settle the matter and made people more comfortable. That sense of comfort remained for, oh, a year or more—until other scientists showed that the doubts about reservoir identification were well-founded, that the judicious language of Guan Yi was percipient,
and that the story was just a little deeper and more complicated. Woops, civets aren’t the reservoir of SARS. Never mind.

  37

  It was Leo Poon who told me about the wild civets of Hong Kong. We were sitting in a small meeting room by the elevator on an upper floor of the Medical Faculty building at Hong Kong University, on its hillside above the towering banks and other sleek skyscrapers rising like spikes of obsidian above Central district. Below and beyond, across Victoria Harbor, were the funky streets, market stalls, alleys, shops, noodle parlors, housing projects, and tourist destinations of Kowloon, including the Metropole Hotel, now sterilized and renamed, where I was staying. I hadn’t imagined there was much of anything wild in such a hectic environment of people and vehicles and vertical concrete, but only because I’d been limited to a cityside view of Hong Kong. Wild civets, oh yes, out in the New Territories, Poon assured me. Those so-called New Territories (new to the colonial British when they leased them from China in 1898 for ninety-nine years) still encompass the less developed areas of the Hong Kong Special Administrative Region, from Boundary Street on the north edge of Kowloon to the Guangdong border, plus outlying islands, with forests and mountains and nature reserves that show green on a map. These are places where, even into the twenty-first century, masked palm civets might survive in the wild. “They’re all over the countryside!” Poon said.

  Just after the epidemic ended, his HKU team started trapping animals out there to look for evidence of coronavirus. They focused first on civets, capturing and sampling almost two dozen. From each animal they took a respiratory swab and a fecal swab—zip zap, thank you very much—and then released the civet back to the Hong Kong wilds. Each sample was screened by PCR methodology using what the technical lingo calls “consensus primers,” meaning generalized molecular jump-starters that would amplify RNA fragments shared commonly among coronaviruses, not just those unique to the SARS-like coronavirus that Guan Yi had found in his civets. So how much coronavirus did Poon find? I asked. “None at all,” he said. That absence suggested that the civet is not the reservoir for SARS coronavirus. “We were quite disappointed.”