Alan Sipress - The Fatal Strain

So what distinguishes avian and human flu strains? Research suggests there may be several factors explaining why some viruses circulate primarily or exclusively in birds while others spread easily among people. Much of the suspicion centers on the receptors in the human respiratory tract. The hemagglutinin of human flu viruses fit better into one type of receptor common in the nose, sinuses, and upper reaches of the airway. Avian viruses, including H5N1, prefer a different type of receptor that is characteristic of birds but relatively rare in the upper airway of humans. Instead, this avian-type receptor is found deep in our lower respiratory system. Scientists surmise this is why H5N1 primarily strikes the lungs, as opposed to the throat and nasal cavity. This could also explain why the virus remains hard to catch, since these avian-type receptors are buried and relatively inaccessible. And when the deep lung does get infected, the virus has a long trip back up the windpipe before being coughed or sneezed into the air, making it hard to spread.

Yet all that separates the world today from an unprecedented calamity could be a slight retooling of the virus, some evolutionary tinkering with the hemagglutinin to make it a better fit for the receptors in the nose and throat, a change in another protein allowing the virus to better replicate in the temperatures of the upper airway, a few other genetic tweaks. Some researchers estimate it would take at most a dozen minor adjustments.

Scientists were aware of H5N1 even before it killed Hoi-ka in 1997. A version of the strain had initially been detected four decades earlier in chickens in Scotland. But no one thought it could jump the species barrier to people. It was strictly avian. That’s why its sudden appearance in the lab sample from Hong Kong was so startling. By making the leap, the virus had satisfied two of three conditions for a pandemic. It was novel—no one had been exposed, so no one had immunity—and it had proven it could infect people. Now it just had to show it could get around.

One day before Hoi-ka died in May 1997, Hong Kong’s public-health laboratory at Queen Mary Hospital had received a specimen of fluid from his windpipe. The sample was one of more than eighty collected every day from patients at the city’s hospitals and clinics. They were all sent to the lab, a small but hectic facility on the seventh floor of the clinical pathology building, erected on a hillside overlooking the western approaches to Victoria Harbor. The waters below were crowded with freighters emerging out of the mists of the South China Sea. Inside, the staff busily tested the samples, sorting them for flu, hepatitis, HIV, and other viruses, categorizing them by subtype when appropriate.

The technicians suspected that Hoi-ka was suffering from influenza and placed his specimen in a cell culture designed to grow the virus. When they looked at it a little later under a microscope, sure enough, it was flu. But what sort? Using an antibody test, they determined it was a kind of influenza A. They assumed it was one of two run-of-the-mill subtypes, either H3N2 or H1N1. The lab had chemical reagents to identify each of these seasonal strains. Yet every time they ran the test, they came up empty. They were stumped.

Dr. Wilina Lim was the adept yet unassuming chief of the virology lab. She spoke in quick, clipped sentences and had a no-nonsense manner that won her the respect of colleagues. Lim was sure the boy’s sample had to be seasonal flu. Since she never expected it to be something utterly new, she wasn’t particularly worried. Lim concluded that one of the ordinary strains must have evolved ever so slightly, which would explain why her lab’s reagents no longer picked it up. Still unaware that the boy had died, Lim decided to divvy up the specimen and ship these samples out for further analysis in specialized flu labs overseas, including the CDC in Atlanta and Mill Hill in London. She also sent a sample to a veteran Dutch virologist named Jan de Jong, who worked at an institute outside Utrecht in the Netherlands. Though they had never met, Lim and de Jong shared a fascination with odd and offbeat viruses and over the years had compared notes from time to time.

More than two months passed. Lim never heard back. Then, on a Friday in early August, she got a call from de Jong. He was coming to Hong Kong, arriving in two days, and would like to see her. He didn’t say why. Lim assumed he was just passing through. She said she’d be pleased to finally meet him. She reserved him a room at the Ramada Hotel in Tsim Sha Tsui, a teeming quarter of narrow streets jammed with shops hawking clothes, shoes, and electronics, where the air was pungent with the smells of tropical cooking and the night skies blazed with neon.

First thing Monday morning, she picked him up. They set off for Queen Mary Hospital. De Jong wanted to see her lab. Lim was behind the wheel of her Nissan, seated on the right like all drivers in Hong Kong, de Jong to her left.

After five minutes, as they approached the harbor tunnel, de Jong looked over and asked, “Do you have any idea what virus you sent me?”

“No, I don’t know,” she responded. She was betting it was some idiosyncratic version of the common H3 strain.

“It’s an H5.”

“What?” she asked. “H5?”

Lim was bewildered. She had never come across an H5 strain. She wondered to herself, “Where did this H5 come from?”

De Jong didn’t say much more about the test results during the ride, but privately he had a suspicion. It could be contamination or some confusion in classifying samples. That was why he wanted to inspect her lab, why he had come all the way to Hong Kong. But once they arrived at the hospital, he quickly saw her operation was well run.

A few hours later, Lim called Margaret Chan, the health department director. The scientists at the CDC in Atlanta, which had independently reached the same results, had yet to inform Hong Kong of their findings. So Lim’s news came as a shock.

“Are you sure?” Chan pressed. “H5N1? I have never heard of H5N1 infecting people.”

“That’s why I’m calling you,” Lim explained.

“Please educate me,” Chan told her.

Chan’s expertise was not infectious diseases. Her early medical interest had been pediatrics, followed later by women’s and family health issues. In reality, she had never intended to be a doctor at all. Growing up in Hong Kong, Chan had trained to be a teacher and for a year taught English, math, and home economics to elementary school students. But when her sweetheart, David, left for Canada to attend college in 1969, she followed him to the far side of the world and enrolled in a Catholic women’s college in Ontario. Before long, they were married. When David then decided to brave the rigors of medical school, she concluded the only way to assure his continuing attention was to become a doctor, too. Chan had little background in college science. But she did have the late-night tutoring of her new husband. After receiving their medical degrees from the University of Western Ontario, she and David returned to Hong Kong. Chan joined the government in 1978, rising quickly through the ranks of the health department. Sixteen years later, she was running it.

Chan has a charm that makes her seem taller than her modest height. Her manner is eminently self-assured yet empathetic. Her black hair is coiffed and her preferred lipstick bright red. Her brown eyes radiate warmth from behind large, round lenses. She speaks with authority, whether lecturing on health-care politics or the therapeutic qualities of her mother’s recipe for pork tenderloin soup. (Chan swears it’s good for stamina. Years later, after leaving Hong Kong and rising to the top post at WHO, she would get the Chinese herbal ingredients shipped to her in Geneva.) But in a realm of outsize egos, she is quick to admit what she doesn’t know.