The Fatal Strain Read online

  “If you put a burglar in front of a locked door with a sack of keys and give him enough time, he will get in,” she later warned at a summit of international health policy makers in Seattle. “Influenza viruses have a sack of keys and a bag full of tricks. They are constantly mutating, constantly delivering surprises.” She cautioned that a pandemic strain would be unstoppable once it became fully transmissible. No corner of the world would be spared. So no country could count on outside relief as with earthquakes or tsunamis. “This will almost certainly be the greatest health crisis experienced for almost a century,” she said.

  But back in the fall of 1997, as the mystery of Hoi-ka’s death had faded with Hong Kong’s steamy summer, flu had all but vanished from Margaret Chan’s mind. She was facing a new crisis. A public health clinic in Hong Kong had been mistakenly dispensing toxic mouthwash to sick babies instead of syrup for their fever. Many of the children had developed diarrhea and vomiting. The public was clamoring for an explanation. The scandal captured the city’s grim mood as an historic year approached its end. Months earlier, with the world watching on television, Britain had ended more than 150 years of colonial rule by relinquishing sovereignty over Hong Kong to China. But the sheen quickly came off the handover. The Asian financial crisis that autumn rocked Hong Kong. The stock market crashed. The property market tanked. Tourism dried up. Even the weather was rainier than usual.

  In late November, Wilina Lim’s lab received a sample from a two-year-old boy who had been briefly hospitalized in another building at Queen Mary with a fever, cough, and sore throat. The lab staff tested the specimen for seasonal flu. They drew a blank. But now they had the chemical reagents required to check for H5N1. When they ran this test, it came back positive.

  Lim called over to the health department headquarters. Dr. Thomas Tsang, a senior medical officer responsible for infectious diseases, got the news. “Not again,” he said to himself, thinking of all the work this would mean.

  Tsang led a team of Hong Kong investigators to the boy’s home. It was located in Kennedy Town, an older urban quarter of aging apartment buildings and street-level shops at the westernmost end of Hong Kong island, far from the site of the original case. The neighborhood is tucked between the island’s steep green slopes and the sea, the cranes of Kowloon’s port just visible across the channel. The boy was Vietnamese, the son of a migrant construction worker. Though the youngster suffered from a congenital heart condition, he had succeeded in recovering from the attack of flu and was back in the family’s cramped apartment when Tsang came calling.

  The interview was difficult because the parents spoke little other than Vietnamese. It took a lot of patience, and the investigators often resorted to hand gestures to convey the intent of their questions. Tsang asked about the boy’s recent history, in particular whether he’d had contact with ducks, chickens, or other birds. The parents insisted he hadn’t. But when the health officers produced a calendar and went over it day by day with the couple, they noted a Vietnamese festival about a week before the boy got sick. “What did you do for the holiday?” Tsang asked. The mother remembered she had bought a live duck or goose at the market. She had slaughtered it at home, littering the apartment with feathers and feces. To Tsang, the source of infection seemed clear.

  Lim had also e-mailed the CDC in Atlanta with the results of this most recent test. When Keiji Fukuda was notified of this second case, he had no doubts this time that the results were correct. “OK, are we off to the races?” he thought darkly. The initial case was no longer a freak occurrence. His mind sped through possibilities. “Is this the first of many cases? Are there more cases going on? Is this the tip of the iceberg?” Fukuda packed his bags again and on Friday, December 5, headed with a fellow CDC investigator for the airport. The probe would be under the auspices of WHO, but CDC staff would carry it out.

  The flight from Atlanta to Hong Kong takes about twenty-four hours. As Fukuda sat in his economy-class seat, he had a long time to reflect. He reviewed everything he would need to know. He thought about what his years on the trail of influenza had taught him and about the findings of the earlier investigation in Hong Kong. His mind groped for what was crucial, sorting and filtering the information. He sketched out the scientific surveys he’d want to conduct this time. He plotted out what he’d do as soon as he arrived. He didn’t want to waste a second. “Question one, two, and three,” he said to himself. “Are there other people infected? Are they passing it to each other? Is there an animal source?” So far, thankfully, the answer to the first question seemed to be no.

  When the plane landed, Tsang met him at the airport. While officers were clearing Fukuda’s passport through immigration and customs, Tsang whisked him into a side room to begin briefing him on the outbreak.

  “I’ve got good news and bad news,” Tsang quipped.

  Fukuda waited for the rest.

  The good news, Tsang said, is that he’d be taking Fukuda to a nice dinner. The bad news was that while Fukuda had been in the air, Hong Kong had confirmed two more cases.

  Tsang brought Fukuda to his hotel in the downtown Wan Chai neighborhood, the former red-light district of The World of Suzie Wong, which in recent years had gone through a commercial renaissance. Then they went to work. They reviewed the lab data and the findings from the preliminary investigation, mapping out the next steps. It would be the first of many late nights spent together.

  Fukuda and a growing CDC team was set up with an office in Wu Chung House, the imposing thirty-eight-story tower on Queen’s Road East that was home to the health department and assorted other government agencies and private enterprises. From the windows of their corner room on the seventeenth floor, the Americans looked out at one of Asia’s great skylines and each night watched the lights in the opposing buildings go dark. The team consistently worked past midnight, recapping the progress of their probe and debating its mystifying results. Cases continued to surface all over the city with no apparent geographic pattern. The ultimate source of infection remained elusive. “I’ve never been in an investigation where the stakes were both so high and information was so little about what was going on,” Fukuda said. “I don’t think I have ever slept less over a sustained period of time.”

  Early each morning, the questions would rouse him, at five o’clock, four o’clock, even three thirty, and he would resume his self-interrogation. “What are we missing?” he pondered. “What are we not asking? Is there anything obvious going on?”

  He and his growing team of CDC investigators would meet for breakfast and compare notes on the day. By eight o’clock, they were back at the health department. They had dragged the desks to the center of the room to form a single large rectangular table and covered it with computer printers and laptops they had brought from home. At the far end of this command center was a whiteboard, where they recorded each suspected case, jotting down the age, gender, location, and crucial dates of the illness. The ultimate outcome was marked at the end of each listing. A downward arrow meant death.

  The scrutiny from politicians, foreign officials, and particularly the press grew intense. The earlier investigation in August had received little media attention. But when Fukuda returned to the health department in December, the hallways were already crammed with reporters. Walking to the bathroom, he recounted, was an “exercise in photography.” Press conferences became high-pressure events where the subtleties of epidemiology were often lost in the journalistic scrum, buried beneath shouted questions and the forest of microphones. One day after he arrived, Fukuda faced the media. “There’s a possibility these cases are the only cases that appear and the virus completely vanishes. Another possibility,” he added with foreboding, “is that these viruses may increase.” By the middle of December, the number of cases had in fact reached double digits.

  Hong Kong residents with little more than sniffles streamed to hospitals and clinics, fearing the worst. In normal times, these health centers took only a few samples each day
from suspected flu cases. But now the samples were being wheeled into Wilina Lim’s lab by the trolleyful, at least five hundred specimens every day. And health officials were demanding that the lab analyze them immediately for H5N1, rather than screening them first to see if they were flu at all. The workload overwhelmed the small influenza lab and its staff of two technicians. Lim yanked staff from the hepatitis and HIV labs and put them to work on flu, more than twelve hours a day, seven days a week.

  Most samples came back negative. But the few that were positive made a terrifying impression. To Lim, this virus behaved like an alien. Her lab, adhering to international norms, normally tested for flu by culturing the virus in special cells harvested from the kidney tissue of cocker spaniels. Scientists consider these canine cells to be especially good for growing flu viruses, far better than most other types of cells. So it was little surprise when Lim’s technicians placed the virus into the canine cells and it grew. But when they inserted it into a variety of other cells to see what would happen, they were stunned by what they saw under the microscope. “This one, it grows well in all kinds of cells,” Lim recalled. “You can see the cell change very quickly. It seems that whatever cell you put it in, it just grows.”

  The long hours were also taking their toll on Margaret Chan, who was often up until the middle of the night speaking with anxious WHO officials in Geneva. But as the face of the health department, she tried to remain cool and upbeat. Once she went too far. Accosted by reporters after delivering a luncheon speech, she was asked whether she still ate chicken despite the flu scare. “Yes, I eat chicken every day. Don’t worry,” Chan told them reassuringly. Her response was scientifically sound, since the virus cannot spread in cooked meat. But to many in panicky Hong Kong, her answer seemed frivolous and out of touch. It sparked a brief furor in the local media, and she later admitted she’d fumbled the public relations.

  In the privacy of her office, by contrast, Chan and her senior lieutenants were growing extremely worried. “Has the situation got out of hand?” Tsang recalled them wondering at one meeting. The disease seemed to be spreading exponentially. They suspected it might now be jumping from one person to another. They feared that hundreds of thousands in the city could soon fall sick. They still didn’t understand where the virus was coming from, so they didn’t know how to stop it.

  Hong Kong’s senior health officials looked to Fukuda for reassurance. But now he, too, was frightened, and his anxiety showed. Unlike in August, he was in the middle of a storm with no end in sight. Moreover, time was running out. In just a few more weeks, Hong Kong would enter its regular winter flu season, and Fukuda feared that the convergence of prosaic and novel infections would overwhelm the city’s hospitals since there was no easy way to tell them apart. Even worse, if both strains were circulating at the same time, the opportunity for them to swap genes and spawn an epidemic strain would be tremendous. “All of that was very pressing,” he said. “We were racing against time.”

  “It was striking that this was not regular influenza we were looking at, whatever it was,” Fukuda later told me. Ordinary flu preyed on the weak: infants, the elderly, and the infirm. But this strain had demonstrated that even the young and healthy—especially the young and healthy—were its targets. “What does it look like?” he asked. “It looks like young people dying from something new. So it really brought us back to 1918.”

  The parallels were eerie. Ordinary flu has what scholars describe as a U-shaped mortality curve, with deaths concentrated among the very young and very old and a far lower proportion among those in between. The milder pandemics of 1957 and 1968 adhered to the same pattern. But during the Spanish flu of 1918, more than half the deaths were among those between eighteen and forty. This gave the disease a W-shaped mortality curve, reflecting the heavy toll in the middle of life as well as at the beginning and end. The avian flu outbreak in Hong Kong was much the same. And after the virus resurfaced in 2003, spreading its reach across much of East Asia, the deaths continued to follow this disquieting pattern. The largest toll was among those between ages ten and nineteen, followed by those in their twenties. The overall case-fatality rate was highest among those between ages ten and thirty-nine.

  “Most of the time in public health and in medicine,” Fukuda continued, “there’s a fair amount of uncertainty, but you rarely come across issues where there’s a really high degree of uncertainty and what you’re sitting on may be something like a 1918. You feel like, ‘I don’t know what is going to happen. I don’t know what is going on. But what is going on is not good, and what it reminds me of is the worst not-good of the century.’ ”

  Researchers have yet to account fully for why the Spanish flu and avian flu, alone among contemporary flu outbreaks, manifest this W-shaped curve. “Explaining the extraordinary excess mortality in persons 20-40 years of age in 1918 is perhaps the most important unsolved mystery of the pandemic,” wrote researchers at the U.S. National Institutes of Health. The answer could lie with another uncanny similarity between the two viruses. Historical accounts from 1918 and experiments on a version of the Spanish flu strain resurrected in the lab reveal that it also provoked tremendous cytokine storms, those withering counterattacks by the body’s immune system. Scientists speculate that the young and healthy may be most vulnerable because, ironically, they have the most robust immune systems, thus the ones that launch the most vicious and ultimately suicidal responses. These victims may be undone by their own strength.

  Scientists’ understanding of this novel bird flu strain is still evolving, and the more they learn, the more they worry. Some now suspect that bird flu is moving down the same path as the virus responsible for the deadliest epidemic in human history. “This is a kissing cousin of the 1918 virus,” warns Michael Osterholm, director of the Center for Infectious Disease Research and Policy and a frequent commentator on the pandemic threat.

  Spanish flu, like bird flu, is thought by scientists to have been a wholly avian virus that developed solely through a series of internal mutations, as opposed to the genetic reassortment that spawned the 1957 and 1968 strains in addition to the swine flu of 2009. Some of the mutations discovered in the 1918 virus look familiar. “Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic,” wrote a team of researchers led by Jeffrey Taubenberger, the American scientist who first fully analyzed the genes of the 1918 virus. Just since 1997, bird flu has become more like the Spanish flu strain. A series of studies shows bird flu has grown more virulent and less susceptible to antiviral drugs. “The H5N1 avian flu viruses are in a process of rapid evolution,” said researcher Elena A. Govorkova in 2005. “We were surprised at the tenacity of this new variant.” A later lab study suggested that bird flu may have already become more ferocious than the 1918 virus, laying even greater waste to the respiratory system and, fiendishly, targeting those lung cells specifically involved with repairing damaged tissue. In September 2006, WHO brought the world’s premier flu specialists to Geneva to scrub the evidence. Malik Peiris, the renowned microbiologist from Hong Kong, told the three dozen participants at this private session something that took their breath away. If the virus continued to develop along the same path, ultimately emerging as a pandemic strain through internal mutation rather than genetic reassortment, its high lethality could persist. He concluded there was no scientific reason for expecting a decrease in the fatality rate, currently at 60 percent of recorded cases. His comments, though later reported by WHO, were largely overlooked by the media. Their import was horrifying. Once the virus evolved into a form easily passed among people, it would be expected to infect a quarter of humanity. So even if the actual fatality rate was only 50 percent after accounting for overlooked mild cases, this could mean the deaths of nearly a billion people.

  That figure is so big as to be incomprehensible. Researchers would rather dwell on sc
enarios more akin to 1918. That strain claimed fewer than five percent of those it infected. If the coming pandemic follows suit, the global death toll would only be 62 million, according to one extrapolation.

  The World Bank originally projected that a severe pandemic could cost the world economy $800 billion in the initial twelve months. By late 2008, the World Bank had nearly quadrupled this estimate, concluding that an epidemic would cost about $3.13 trillion during the first year. Even a mild pandemic, like the 1968 Hong Kong flu, would cost $450 billion, and a moderate one like the 1957 Asian flu would reach $1.3 trillion.

  The gloom was suffocating in those final weeks of 1997, like the cold, foul mist wrapping Hong Kong’s steep slopes and settling on its myriad islands. A small, tongue-shaped islet called Ap Lei Chau had become the latest focus of the city’s collective anxiety.

  Five-year-old Chan Man-kei had been playing with friends at her kindergarten, a brightly decorated school on the ground floor of a public housing project in Ap Lei Chau, when she started throwing up. Her parents had been called. A doctor had referred her to nearby Queen Mary Hospital, where her lab samples tested positive for bird flu. About a week later, on Tuesday, December 16, Hong Kong health officials announced that two of her younger cousins had also been hospitalized in Queen Mary’s isolation ward. They, too, might have the virus.

  Hours after that disclosure, Fukuda and Chan addressed the press about the heightened prospect of human transmission. “It’s a possibility in this case and one of the things we are concerned about,” Fukuda acknowledged at the evening news conference. Chan agreed that Man-kei might have infected her cousins. “They live together at Grandma’s and play together,” she said. The health department was trying to crack the case, she told reporters, assuring them, “We are working at breakneck pace.”