Spillover: Animal Infections and the Next Human Pandemic (24 page)

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

I
t 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.”

But disappointment, in science, is sometimes a gateway to insight. If not the civet, then what? “We hypothesized that, if this animal”—this unidentified creature—“is the natural reservoir for SARS, it must be quite widespread.” So they trapped, in several sylvan locations, whatever wild and feral animals they could find. The eventual list was richly various, ranging from rhesus macaques to porcupines, from rat snakes to turtle doves, from wild boars to black rats, and including at least one Chinese cobra. Again the PCR results were almost universally negative—almost. Only three kinds of animal out of forty-four showed any sign of infection with a coronavirus. All three were microchiropterans. To you and me: little bats.

Only one of those registered high prevalence as a group, with most of the sampled individuals testing positive, as measured by virus shed in their feces: a delicate thing called the small bent-winged bat.

Poon gave me a copy of the paper he published (sharing credit, again, with Guan and Peiris among its coauthors) in the
Journal of Virology
in 2005, about a year after the great civet slaughter. He wanted me to be clear about his findings. “This bat coronavirus is quite different from SARS,” Poon said. That is, he didn’t claim to have found the reservoir of SARS-CoV. “But this
is
the first coronavirus in a bat.” That is, he had turned up a strong clue.

Soon afterward, an international team of Chinese, American, and Australian researchers published an even more revealing study, based on sample collections they made in Guangdong and three other Chinese sites. This team, led by a Chinese virologist named Wendong Li, also included Hume Field, the laconic Australian who had found the reservoir of Hendra, and two scientists from the Consortium for Conservation Medicine, based in New York. Unlike the Hong Kong sampling study, Li’s focused specifically on bats. The team trapped animals from the wild, drew blood, took fecal and throat swabs, and then analyzed duplicate samples of the material independently at labs in China and Australia, creating a double-check on themselves that strengthened the certitude of their results. What they found was a coronavirus that, unlike Leo Poon’s, closely resembled SARS-CoV as seen in human patients. They called it SARS-like coronavirus. Their sampling showed that this SARS-like virus was especially prevalent in several bats belonging to the genus
Rhinolophus
, known commonly as horseshoe bats. Horseshoe bats are delicate little creatures with large ears and flanged, opened-out noses that, homely but practical, seem to play a role in directing their ultrasonic squeaks. They roost mainly in caves, of which southern China has an abundance; they emerge at night to feed on moths and other insects. The genus is diverse, encompassing about seventy species. Li’s study showed bats of three species in particular carrying SARS-like virus: the big-eared horseshoe bat, the least horseshoe bat, and Pearson’s horseshoe bat. If you ever notice these animals on the menu of a restaurant in southern China, you might want to choose the noodles instead.

High prevalence of antibodies to the virus among horseshoe bats, compared with zero prevalence among wild civets, was an important discovery. But there was more. Li’s team also sequenced fragments of viral genome extracted from fecal samples. Comparative analysis of those fragments showed that the SARS-like virus contained, from sample to sample, considerable genetic diversity—more diversity than among all the isolates of SARS-CoV as known from humans. This virus seemed to have been in the bat populations for some time, mutating, changing, diverging. In fact, the totality of diversity known in the human SARS virus nested
within
the diversity of the bat virus. That sort of nesting relationship can best be depicted as a family tree. Li and company drew one. It appeared as a figure in the paper they published in
Science.
Human SARS virus was a single branch, skinny and small, within a limb of branches representing what lives within horseshoe bats.