The Fatal Strain

by Alan Sipress

  More people are traveling more places than ever before. Though Hong Kong remains an exceptional crossroads, Yi Guan rightly suggests that the world increasingly resembles the ninth floor of the Metropole.

  “Today you are in England, tomorrow in New York, and the third day you might be in Hong Kong,” Guan noted. Imagine how many people an infected traveler encounters along the way. “The case lands in London or New York or Hong Kong. Maybe ten thousand people have connecting flights in that airport within two hours. It spreads to the whole world. Globalization accelerates the transmission speed, maybe by a hundred times.”

  A century ago, he continued, a novel flu strain could take more than a year to circle the world. “Now, currently, does it take one year? I don’t think so. Maybe one month,” he said.

  Over history, each advance in transport and trade has sped disease on its way. The Black Death of the Middle Ages spread faster by merchant ship on the Mediterranean than by horseback on the Asian steppe. The last of three cholera epidemics in nineteenth-century America was the swiftest, exploiting the country’s new railroads. Even since 1968, the date of the last flu pandemic, change has been dramatic. Air traffic has increased about tenfold since then. Using data on the volume of travelers at fifty-two major cities around the world, a team of American researchers projected how long it would take a flu pandemic to spread and compared it to the Hong Kong flu of 1968. They found that the same virus, if it had erupted in 2000, would have struck cities in the Northern Hemisphere nearly four months earlier. And while the Hong Kong flu required almost a year to sweep the globe, in 2000 the virus would have peaked in every one of the cities in half that time. A separate team of researchers in Britain, using a different statistical approach and more recent data, from 2002, concluded that in some cities in the Southern Hemisphere, the epidemic actually would have peaked a full year faster than it had in 1968.

  An accelerating epidemic leaves public health officials little chance to top off their stockpile of antiviral drugs or distribute them. There’s less lead time to prepare measures meant to slow the inexorable advance of epidemic—for instance, isolation policies and school closings—or to make sure that strategic infrastructure and crisis manpower plans are in place. Most crucially, scientists expect it will take at least six months to develop a pandemic vaccine and far longer to make sure everyone gets it.

  “All of technology cannot keep up,” Guan warned. “To manufacture a vaccine takes months. The transmission of disease is by the hour now.”

  No matter how many ways Guan and his colleague Malik Peiris tried to find a flu virus in the specimens smuggled back from Guangzhou, they couldn’t. For that matter, they couldn’t isolate a virus of any sort at all. In the lab, they tried to grow the puzzling pathogen using chicken embryos, dog cells, monkey cells, and even human larynx and lung cells. Nothing. But each disappointment refined the search. Each time they failed to corner their quarry in the Guangzhou samples—for weeks, the only ones outside the hands of the Chinese government—the Hong Kong University team weeded out false pretenders, bringing the researchers that much closer to the golden moment of discovery.

  When it came, it was Peiris who made it. His lab isolated a pathogen called Coronavirus in a new specimen taken at a Hong Kong hospital from the dying brother-in-law of Liu Jianlun. Precisely one month after Dr. Liu had checked into the Metropole, Peiris sent an e-mail to a global network of laboratory scientists announcing that he had found the cause of the disease now named SARS.

  The discovery was an unprecedented coup for WHO. Peiris was part of a virtual laboratory network that Klaus Stohr had assembled in mid-March 2003 for the SARS hunt. He had recruited eleven premier labs from nine countries for a rare collaborative effort, appealing to many of virology’s brightest and most competitive researchers to set aside their egos and their lust for scholarly publication. Instead they compared notes, speaking daily by teleconference to review their progress. Crucial findings were shared through a secure Web site. WHO also established parallel networks, so epidemiologists could analyze how SARS was spreading and clinicians could consult about how to treat it.

  The overriding fear was that this killer could become endemic, like HIV-AIDS, before the world had time to diagnose the threat, contain its spread, and eradicate it. WHO rallied scores of disease specialists from inside the agency and out, dispatching them to East Asia. Keiji Fukuda, for one, spent eight weeks in mainland China and Hong Kong. It was what Fukuda saw in the wards of Prince of Wales Hospital that prompted WHO to sound its first global alert about this severe, unidentified pneumonia in mid-March 2003 and urge that patients be isolated. A second, stronger alert followed three days later after Mike Ryan, WHO’s global alert coordinator, was awakened with news that an infected physician had boarded an airplane in New York bound for Singapore. The man was bundled off the airplane during a stop in Frankfurt by German emergency medical staff in orange hazmat suits. Within hours, WHO had begun taking measures to curtail the international spread of SARS.

  This was the agency at its best. “The quality, speed and effectiveness of the public health response to SARS brilliantly outshone past responses to international outbreaks of infectious disease, validating a decade’s worth of progress in global public health networking,” according to an assessment by the U.S. Institute of Medicine. “The World Health Organization (WHO) deserves credit for initiating and coordinating much of this response.”

  Yet even after the Coronavirus had been isolated and containment efforts put in place, the source of the disease remained a mystery. WHO investigators suspected a link to wild animals. Some of the earliest cases in Guangdong had been in restaurant employees who prepared exotic fare, often from small imported mammals, to sate southern China’s appetite for what locals called “wild flavor.” To choke off the epidemic, researchers would have to determine which creature was the culprit. Someone would have to literally stick a needle into the heart of an animal and a swab up its anus. Once again, the mission would fall to Guan.

  In early May 2003, he crossed to the Chinese city of Shenzhen, just beyond the narrow river that serves as Hong Kong’s border with the mainland. Once a fishing village, Shenzhen had been designated a special economic zone in 1979 to attract foreign investment. The gold rush had transformed it into an audacious boomtown with a population rivaling New York’s and skyscrapers to rival Hong Kong’s. It had become China’s wealthiest and fastest-growing city and the quintessence of excess. In the city’s storied restaurants, the new rich spent hundreds, even thousands of dollars to dine on nearly any form of life they hankered after. At Dongmen Market, the hungry and the adventurous perused wire cages stacked high with writhing snakes, barking raccoon dogs, growling ferret badgers, turtles, hares, palm civets, hog badgers, house cats, scaled pangolins, rabbits, beavers, and the miniature Asian deer called muntjac.

  By the time Guan set foot on the slick, bloody floors of the covered market, he had lost count of how many thousands of birds he’d sampled over the years, looking for flu. But he’d never collected specimens from the kind of grim menagerie that now confronted him. Many of these animals were carnivores with claws and fangs. The merchants, engaged in a shadowy yet highly lucrative trade, could be equally vicious. Guan had won prior permission from Shenzhen health officials for this expedition. At least that would keep the police off his back.

  Dongmen Market was huge. It sprawled across an entire city block, consuming the ground floor of a mammoth clothing-and-textile center. Stalls disappeared into the twilight of scattered fluorescent bulbs dangling from the metal ceiling. The odor was oppressive. “Where do I start?” Guan asked himself. He had applied his full deductive powers to the question even before he arrived. Whatever creature was the source of the virus, it had to be a mammal, he reasoned. That would explain why the microbe was so quick to become transmissible among humans, which of course are also mammals. So no turtles, snakes, or, for once, birds. The creature would also have to be fairly common. If it was too ra
re, the virus might have burned itself out before it had a chance to cross to people. Guan narrowed the list to eight species. He was especially interested in Himalayan palm civets, also known as masked civets because of the black and white stripes that run from forehead to nose and white circles around their eyes. About two feet long and ten pounds in weight, these catlike creatures have long been a popular Chinese delicacy.

  He approached the traders. He explained that he and his team were looking to take a few samples from the animals: a throat swab, a rectal swab, and some blood. To get the blood, he would have to jab a needle into the heart of each beast. It would be too hard to find a vein through all the fur.

  The dealers wanted no part of it. They were afraid Guan might kill or otherwise harm their lucrative creatures, perhaps somehow rob them of that raw bestial energy that made them so coveted by customers. But if Guan was willing to buy the animals, well, then they could do a deal.

  Guan pulled a thick wad of Chinese banknotes from his pocket. He had thousands of dollars worth. Yes, he’d pay, he told them. But not full price. Here’s how it was going to be: He would give them one hundred yuan to sample an animal, about twelve dollars each. If the animal died within a day, the trader could notify Shenzhen’s disease-control officers and be compensated in full. The traders agreed and crowded around, eager for easy money.

  There wasn’t enough space at each stall to take specimens, and it was too dark to see. In any case, Guan didn’t want to scare off anyone’s business. So once he made his selection, he had the merchants lug the cages to the muddy alley outside. There, amid all the hustle, among the army of porters hauling crates of poultry and produce, exotic roots, mushrooms, and broad bushy vegetables, in between the handcarts, trolleys, and bicycles stacked with boxes, Guan spread a plastic tarp, put down his gear, and prepared to operate. He slipped on a white lab coat and mask. He donned thick protective gloves. The curious quickly crowded around. Guan and his colleagues asked the security guards to push them back. “There’s virus,” he warned.

  Before they could begin, Guan’s team had to anesthetize each animal, pump it full of ketamine. That meant coaxing an often hostile creature out of its cage and plunging a needle into its flesh. “It’s very, very dangerous,” Guan advised. “They can bite you. The civet, his head can spin around 360 degrees and you never expect it. To catch it by its back, it’s too hard to do that.” Some beasts cowered, some lunged. So to restrain them, the researchers used a special tool fashioned from a long tube with a Y-shaped attachment that fit around the animal’s neck. With its head thus pinned down, Guan and his colleagues wrestled the critter to the ground and injected the anesthesia.

  The subject soon went limp. Guan stuck a needle into its heart, filling a vial with blood. “My medical training helped me a lot,” he recalled. Next he inserted a swab into the animal’s throat and finally into its anus. Over the course of two days, he jabbed and swabbed twenty-five animals, including a half-dozen civets and assorted beavers, hog and ferret badgers, muntjacs, raccoon dogs, and domestic cats.

  Back at the university lab, he quickly found the evidence he was looking for. He isolated the SARS Coronavirus in samples from the civets and one raccoon dog. These animals plus a ferret badger had antibodies that indicated they had been infected. There was no way to know whether these species were the ultimate origin of the pathogen or had caught it somewhere else. But it was now clear how the virus was spreading to people. The wild-game markets had to be shuttered.

  Based on Guan’s research, WHO urged China to close them down. This time, at least for a while, China listened. New infections ceased.

  On July 5, 2003, the world officially defeated what Shigeru Omi, WHO’s regional director for East Asia, later called “the first emerging disease of the age of globalization.” The agency reported that the SARS epidemic was over. The last chain of transmission had been severed in Taiwan, with no new cases detected there since mid-June. The global death toll had been kept below eight hundred.

  This epidemic had been contained, first and foremost, through the successful isolation of those infected. Some countries, like Vietnam and Singapore, had tackled it more aggressively than others, adopting measures like temperature screening for airplane passengers and hospital visitors, isolation rooms at airports, designated wards for suspected cases, and rapid tracing of those who’d been exposed. But in the end, the key everywhere was preempting the virus before it could infect again.

  Had the pathogen been a novel strain of flu, the strategy would have failed.

  Pandemic would have followed, potentially with millions of deaths, and not because of any human miscue. The difference is wired into the biology of these two viruses.

  On many scores, there is an uncanny resemblance between influenza and SARS. They are both cruel respiratory afflictions that originate in animals and cross to the humans who prey on them. Like SARS, flu has often if not always emerged out of southern China, where live markets have proven central in amplifying and spreading the disease. Yet flu is far more sinister.

  Flu, for starters, is a more nimble virus that spreads with an ease unmatched by other respiratory diseases. “Flu replicates far more efficiently in humans than SARS,” Guan reminded me. “After adapting to humans, SARS can spread quite quickly. But if compared to flu, it is still quite slow.”

  In analyzing outbreaks, researchers focus on what they call the basic reproductive number. That figure represents how many other people are typically infected by each sick person. Obviously, the higher the number, the more infectious the disease. An early study of SARS concluded that its reproductive number was lower than that for other respiratory viruses. Researchers said this accounted for why SARS could be contained. Later research compared SARS and flu and found that the transmissibility of flu, as represented by its reproductive number, might be three times greater or more.

  SARS was also a soft target because its victims became contagious only after developing a fever and other symptoms. An analysis of SARS patients in Hong Kong found the amount of virus in their nose and throat remained low for the first five days after they started feeling sick, only peaking on the tenth day. When researchers looked at the actual pattern of cases, they reached a similar conclusion that people were rarely contagious in the first few days after they came down with symptoms. Typically it took almost a week or more. For public health authorities, this pattern was a blessing. It gave them ample chance to identify and isolate victims before they disseminated the virus further.

  “It is difficult to escape the conclusion that the world was very lucky this time,” wrote a team of researchers from Britain and Hong Kong, adding that an anticipated flu pandemic by contrast could have a “devastating impact.”

  With flu, people may be contagious even before they develop symptoms. One analysis estimated that between 30 and 50 percent of those infected with a novel flu strain would catch it from someone who wasn’t yet ostensibly sick. The true figures will depend on the specifics of the strain. But still, in a brewing flu epidemic, there may be no sure-fire way to determine who is contagious and isolate them. Even those infected might be ignorant of their fateful role in spreading the plague until it’s too late.

  “Once adapted to human-to-human transmission, influenza is highly transmissible, both in the late incubation period as well as early in the disease. Therefore, its spread may not be amenable to interruption with the same public health measures used to contain SARS,” wrote Peiris and Guan in the cautious language of scholarly publication.

  In person, Guan was more succinct: “From a single spark, you can burn up the world.”

  I visited Guan several times in the years after SARS. When I last met him at his university office, he was agitated as usual. It was flu, not SARS, that was keeping him up late at night.

  “I can see what many people cannot see,” he told me. He had always been a bit of a Jeremiah. “For me as a scientist, my record and reputation are fully acceptable to the scientific community.
So why do I keep working so hard?”

  He paused and reached across the table to pour me a cup of traditional Oolong tea from a white ceramic pot.

  He resumed. “The flu virus is not easy to track down. I am building up information so I can know where and how a pandemic might happen. I want to tell the world we can create a different future.” He was on his pulpit, urging humanity to prepare for the inevitable mutation of the virus and adopt economic and political reforms that would stem its spread. These should include restructuring farms, markets, and trade and improving how disease is monitored. Most important, he preached, was candor in disclosing outbreaks when they occur. “If not, who will be the losers? The whole globe.”

  Guan shifted on the edge of his chair and told me he envied Al Gore. As a former U.S. vice president, Gore could find the financing to make his film An Inconvenient Truth about the threat of global warming. Guan had been finding it hard to make his own exhortation heard.

  “We are all sitting at the same table,” he continued. “We share the same benefits, share the tea. Globalization is good for promoting civilization. But if you’re part of globalization, you need to take responsibility. If not, it will damage not only one country but many, many countries.”

  Guan himself had come to epitomize the age of globalization. From Jiangxi, where he grew up reading in the courtyard with chickens for companions, this country boy had worked his way to Tennessee to study with the dean of all influenza researchers and then found a perch at Hong Kong’s most exclusive university. There, he was quickly promoted to professor, awarded his own laboratory, and installed in a corner office on the fifth floor of the Faculty of Medicine with a spectacular hillside view of the western approaches to Victoria Harbor and Lantau Island beyond. When he breaks for a cigarette, he stares out the floor-to-ceiling picture windows, watching the procession of freighters and the setting sun burning into the mist. He travels the world, lecturing and consulting. Shortly before my last visit to see him, he had flown to my home city of Washington for a meeting with U.S. health officials, sending me a message by BlackBerry when his airplane landed but departing again before we could meet. Just three days after he’d set out from Hong Kong, he was home again. “Fifty hours in transit,” he told me afterward, somewhat bemused. The pace had left him little time for Jiangxi. Though he sent money home to support his brothers and sisters, he could only spare five days a year for his aging, melancholy mother. “I’m so sorry, mother,” he told her. “For 360 days a year I belong to the world.”