Two fateful things happened that night at the Metropole Hotel. The professor’s condition worsened; and at some point he seems to have sneezed, coughed, or (depending on which account you believe) vomited in the ninth-floor corridor. In any case, he shed a sizable dose of the pathogen that was making him sick—enough to infect at least sixteen other guests and a visitor to the hotel. Professor Liu thereby became the second known superspreader of the epidemic.
Among the hotel guests sharing floor nine was a seventy-eight-year-old grandmother from Canada. I mentioned her earlier. She had come to visit family and then spent several nights at the Metropole, along with her husband, as part of an airline-hotel package. Her room was 904, just across the corridor and a few steps down from Professor Liu’s. Her stay overlapped with his presence for only one night—the night of February 21, 2003. Maybe they shared a ride on the elevator. Maybe they passed in the hallway. Maybe they never laid eyes on each other. No one knows, not even the epidemiologists. What’s known is that, the next day, the professor awoke feeling too sick to attend any wedding and instead checked himself into the nearest hospital. He would die on March 4.
One day after Professor Liu left the Metropole, the Canadian grandmother left too, having finished her Hong Kong visit. Infected but not yet symptomatic, and presumably feeling fine, she boarded her flight home to Toronto, taking SARS global.
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Another route of international dispersal from the Metropole Hotel led to Singapore, when a young woman named Esther Mok returned from a shopping vacation in Hong Kong, feeling feverish. That was February 25. For the previous four nights, she and a female friend had shared room 938 at the Metropole, about twenty steps from Professor Liu’s room.
Back home in Singapore, Mok’s fever lingered and she developed a cough. On March 1 she consulted doctors at Tan Tock Seng Hospital, a large public facility housed in gleaming new buildings just north of the city center. After a chest X-ray showed white patches on her right lung, Mok was admitted under a diagnosis of atypical pneumonia. One of the doctors who saw her was Brenda Ang, a senior consultant for infectious diseases, who happened also to be in charge of infection control at Tan Tock Seng. There was no particular alarm about infection control, though, when Esther Mok brought her condition to the hospital. “At that time,” Brenda Ang told me later, “we didn’t know what it was.”
Ang agreed to take me through the story from memory, half a dozen years after the events, and though she warned that her recollections might be patchy, on many points they seemed rather precise. We met in a conference room within a small, detached structure on the landscaped grounds of Tan Tock Seng; it was a room that served intermittently for staff meetings and as a classroom for medical students on rounds, but we had it for an hour. Ang was a tiny, forthright woman in a lilac print dress. Observing medical discretion, she didn’t use Esther Mok’s name but spoke instead of “a young lady” who had been “the first index case.” In her role as infectious disease consultant, Dr. Ang had seen the first index case herself. She was assisted by her registrar (a younger doctor in specialty training), who took a mucus sample from Mok for culturing. The registrar wasn’t wearing a mask, Ang told me. No one at Tan Tock Seng was masked against this infection at the start, but unlike Ang herself, the registrar got sick.
His case, with some dramatic complications, unfolded later. In the meantime, Ang and her colleagues dealt with Esther Mok’s worsening pneumonia, unaware that the young woman was becoming another superspreader of this disease that had not yet been identified or named.
At first Mok was placed in an open ward, with closely spaced beds, in proximity to other patients and staff members coming and going. After a few days, now gasping for air, she was transferred to the Intensive Care Unit. It seemed unusual, Ang told me, for such a young person to be struck by pneumonia so severely—unusual enough that, on the Friday of that week, when doctors from the other Singapore hospitals visited Tan Tock Seng for weekly grand rounds, Ang and her colleagues presented the atypical pneumonia case for discussion. Having heard the symptoms and the history, one doctor from Singapore General Hospital spoke up, saying, That’s odd, we have an atypical pneumonia case too, another young woman, and she too has recently returned from Hong Kong. With a little checking, they learned that the Singapore General case was Esther Mok’s friend, who had shared room 938 at the Metropole. This brought a moment of chill recognition.
In coming days, more atypical pneumonias arrived at Tan Tock Seng, most or all of them with connections to Esther Mok. First was her mother. Three days later, the pastor of her church, who had visited Esther at the hospital to pray, came back as a patient. Then her father showed up, suffering a cough with blood-streaked sputum. Then her maternal grandmother, then her uncle. By midmonth they were all patients at Tan Tock Seng. And as the Mok family cluster began to generate alarm, another bit of ominous news reached Brenda Ang. It was Thursday, March 13, when an administrative assistant informed her that four nurses from Mok’s original ward had called in sick. Four nurses out sick on one day—that wasn’t anywhere near within the boundaries of normal. “Defining moment for me,” Ang said dryly, as I sat before her scribbling notes. “Everything was accelerating.”
And related events were accelerating worldwide, not just at Tan Tock Seng—though Ang and her colleagues didn’t yet know it. In Geneva, at almost precisely the same time, WHO issued its global alert about a “severe, acute respiratory syndrome of unknown origin.” Officials at Singapore’s Ministry of Health were soon in the loop, made aware that three cases of atypical pneumonia (Esther Mok and her friend, plus another) had turned up at once, all traceable to Hong Kong’s Metropole Hotel. That put Mok’s case into a much larger picture. Someone from the ministry seems to have called the CEO of Tan Tock Seng, whereupon a meeting of senior hospital staff was convened. The CEO, the chairman of the medical board, the nursing director, Ang herself as head of infection control, and others—they all came to this room, Ang said, to discuss what was happening.
“Came to this room?” I asked.
“This room,” she said. “Same room.” That’s when the CEO told them: “I think we’ve got an outbreak on our hands. And we need to organize.”
A doctor named Leo Yee Sin, with previous experience of handling a Nipah outbreak, was charged with mobilizing special measures of response. The Ministry of Health advised Tan Tock Seng’s leadership: Get ready to accept cases, because we’re starting to see more—friends and relatives of the first group, now showing symptoms. Leo Yee Sin got people moving. They set up a tent outside one ward, for screening patients, and brought down an X-ray machine to check possible cases for lung involvement. Most of the patients were admitted to general wards, but the sicker ones went to Intensive Care. As the first Intensive Care Unit filled up, two others were converted into SARS ICUs, exclusively for handling additional cases. Isolation and barrier nursing were important control measures, though Ang and her colleagues still didn’t know what they were isolating. “Remember,” she told me, “all this time there are no diagnostic tests.” No tests, she meant, that detected presence or absence of the culpable infectious agent—because no one had yet identified that agent. “We are going purely based on epidemiology—whether there is contact with some of the source patients.” It was blind man’s bluff.
On Friday of that week, March 14, the hospital’s annual dinner and dance, long planned and anticipated, would occur at the Westin Hotel. It went ahead as scheduled, more or less, although Brenda Ang and some colleagues sat at half-empty tables wondering, Where’s Leo Yee Sin, where’s this colleague, where’s that one? Well, they were absent in extremis—back at the hospital, shifting beds and other furniture to put the place on an emergency footing. Ang herself rejoined the scramble on Saturday morning.
In her capacity as head of infection control, Ang started getting all staff members into gowns, gloves, and high-filtration N95 masks, the kind that fit more snugly than mere surgical masks. But she faced a shortage
of those supplies, and then also black-market inflation; N95 masks in Singapore went from $2 to $8 apiece. Still, they were doing the best that could be done. On March 23, by which point the disease had an internationally recognized name, Tan Tock Seng became the designated SARS hospital for Singapore, with all patients to be transferred there from other hospitals. Visitation was restricted. Staff members were masked, gloved, and gowned.
Before the isolation and protection measures were fully implemented, though, another superspreader event occurred, this one in the hospital’s Coronary Care Unit. A middle-aged woman with multiple health problems, including diabetes and heart disease, had been admitted to one of the open wards; she was infected there by a health-care worker, who had in turn been infected by Esther Mok. Then the older woman suffered a heart attack and was moved to the CCU. Her atypical pneumonia symptoms hadn’t yet manifested—not enough, anyway, to be weighed against her coronary crisis. In the CCU she was intubated by the attendant cardiologist, with assistance from a cardiology resident. Again, as with the Poison King in Guangzhou, intubation seems to have been an occasion for transmission. Eventually twenty-seven people became infected in the CCU, including five doctors, thirteen nurses, one ultrasound technician, two cardiac technicians, one attendant, and five visitors. I found that tally in a later report. Brenda Ang’s account was more personal. She recollected that the cardiologist, a pregnant woman, had worn a mask while performing the intubation, and though that doctor got ill afterward, she recovered. The resident, standing nearby, had worn no mask. “It was a guy. He was sick for a while and brought it home. His mother,” Ang said. “His own mother nursed him and she became sick.”
“Did they survive?”
“No.”
“Neither one of them,” I said.
“It was one of the most painful things. Because he was a young, twenty-seven-year-old doctor. And his mother also died.”
Another young doctor who faced similar exposure was Brenda Ang’s registrar—remember him?—who had taken a throat swab from Esther Mok. His story reflects the dawning awareness that this syndrome was caused by some highly infectious bug, maybe a bacterium, maybe a virus, which spread readily through face-to-face contact, especially in crowded or intimate circumstances. Days after assisting Ang with her examination of Mok, the registrar boarded a plane. He flew to an infectious-disease conference in New York, twenty hours’ worth of air travel from Singapore, and was there when he began feeling sick. Before embarking to come home, via Frankfurt, he phoned a colleague in Singapore and mentioned that he was ill. The colleague alerted Singaporean authorities, who alerted WHO, who alerted German officials, who met the plane when it landed in Frankfurt and took the doctor away into quarantine. He spent almost three weeks in a Frankfurt hospital, along with his wife and his mother-in-law, who by then were sick too. One crewmember from the plane, but only one, had also been infected. Unlike the cardiology resident who assisted the intubation, though, these patients in Frankfurt all survived.
Back in Singapore, health officials and government authorities cooperated to stanch further transmission. They enacted firm measures that reached far beyond the hospitals—such as enforced quarantine of possible cases, jail time and fines for quarantine breakers, closure of a large public market, school closures, daily temperature checks for cab drivers—and the outbreak was brought to an end. Singapore is an atypical city, firmly governed and orderly (that’s putting it politely), therefore especially capable of dealing with an atypical pneumonia, even one so menacing as this. On May 20, 2003, eleven people were taken to court and fined $300 each for spitting.
By the middle of July, when the last SARS patient left Tan Tock Seng Hospital, more than two hundred cases had been recognized. Thirty-three of those people died, among whom were Esther Mok’s father, her pastor, her mother, and her uncle, in that order of demise. Esther herself survived.
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Dead or recovered, they had all been infected—but infected with what?
As the disease spread internationally, scientists on three continents worked in their laboratories with samples of tissue, blood, mucus, feces, and other vital, unsavory materials taken from one patient or another, trying to isolate and identify a causal agent. The very name coined during that early period, SARS, reflects the fact that this thing was known only by its effects, its impacts, like the footprints of a large, invisible beast. Ebola is a virus. Hendra is a virus. Nipah is a virus. SARS is a syndrome.
The search for the SARS pathogen proceeded urgently in those laboratories, but it was hampered by some confusing signals and false leads. For starters, the symptoms looked a little bit too much like influenza—or, more precisely, like influenza at its worst. One form of influenza at its worst is the so-called bird flu, caused by a virus designated as H5N1, with which Hong Kong in particular had had fearful experience just half a dozen years earlier, when eighteen people became infected by spillovers from domestic poultry. Eighteen doesn’t sound like a large number of patients; the fearful aspect was that six of those eighteen died. Health authorities had responded quickly, ordering the closure of live poultry markets and the destruction of every chicken in Hong Kong—amounting to 1.5 million doomed, squawking birds—followed by a seven-week hiatus for decontamination. This draconian response, combined with the fact that H5N1 didn’t transmit well from human to human, only from bird to human, had succeeded in ending the 1997 Hong Kong outbreak. But in February 2003, just when alarming rumors about “a strange contagious disease” began to emerge by email and text message from Guangdong, avian flu struck again in Hong Kong. It was entirely distinct from the SARS outbreak, but that couldn’t easily be seen at the time.
The flu killed a thirty-three-year-old man and sickened (but didn’t kill) his eight-year-old son. It probably also killed the man’s seven-year-old daughter, who had died two weeks earlier of a pneumonia-like illness during a family visit to Fujian, the Chinese province just northeast of Guangdong. Possibly the little girl had consorted too closely with Chinese chickens; her brother had definitely done that, according to his own later testimony. Samples of nasal mucus from both the father and the son showed positive for H5N1, which seemed to suggest that the wider flurry of case reports from Guangdong might likewise pertain to avian flu. So the scientists tested their SARS samples for H5N1. But that was a false lead.
Another wrong notion was that SARS might be caused by some form of chlamydia, a diverse group of bacteria that includes two kinds associated with respiratory disease in humans (as well as another, more famous among teenagers, that’s sexually transmitted). One of the respiratory chlamydias is zoonotic, leaping from birds (notably, pet parrots) into humans. During late February, a very senior Chinese microbiologist found what looked like chlamydia in some SARS specimens and, based on his tenuous evidence—also, his august standing in the respectful milieu of Chinese science—the chlamydia hypothesis was embraced overconfidently by high health officials in Beijing. At least one other eminent Chinese researcher dissented, arguing that, if a chlamydia was the cause, SARS cases should have responded to treatment with antibiotics—which they did not. But that fellow was down in Guangdong, at the Institute for Respiratory Diseases, and Beijing didn’t want to hear him.
The laboratory scientists meanwhile explored other possibilities too, quite a list: plague, spotted fever, Legionnaires’ disease, typhus, several kinds of bacterial pneumonia, seasonal influenza, E. coli in the blood, Old and New World hantaviruses, and more. Part of what made the task difficult was that, in pursuing the SARS agent, they didn’t know whether they were looking for something familiar, something newish but closely resembling something familiar, or something entirely new.
And there was one other possible category: something familiar to veterinarians but entirely new as an infection of humans. In other words, an emerging zoonosis.
The sorts of lab methodology I’ve described earlier, involving PCR to screen for recognizable fragments of DNA or RNA, combined with molecular assays to
detect antibodies or antigens, are useful only in searching for what’s familiar—or, at least, for what closely resembles something familiar. Such tests essentially give you a positive, negative, or approximated answer in response to a specific question: Is it this? Finding an entirely new pathogen is more difficult. You can’t detect a microbe by its molecular signature until you know roughly what that signature is. So the lab scientist must resort to a slightly older, less automated approach: growing the microbe in a cell culture and then looking at it through a microscope.
At the University of Hong Kong, high on the side of a peak overlooking the downtown neighborhoods, a team led by Malik Peiris took this approach to its fruitful conclusion. Peiris is an Oxford-educated microbiologist, born and raised in Sri Lanka, soft-spoken and judicious, with fine dark hair that hugs his skull roundly. He is known primarily as an influenza researcher and, having come to Hong Kong in 1995, just before the big bird-flu scare, he had reason to consider avian influenza as a leading hypothesis for what was now coming out of Guangdong. “The first thing going through our minds was that the H5N1 virus had possibly acquired the ability to transmit from human to human,” he told a reporter in 2003. But after testing their SARS samples for H5N1, as well as for a roster of the usual suspects, and finding no evidence of any, his team moved toward the idea that they were dealing with a new virus.
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