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At least 40 million died of the 1918-19 "Spanish flu," the most deadly disease episode in history. Influenza cases were treated at places including this army ward in Kansas in 1918. (National Museum of Health and Medicine, Armed Forces Institute of Pathology)

The Flu Hunter

For years, Robert Webster has been warning of a global influenza outbreak. Now governments worldwide are finally listening to him

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(Continued from page 2)

How could that be? The answer is something now known as reassortment. The influenza virus, whether it’s carried by birds or humans, has ten genes, which are arranged on eight separate gene segments. When two different influenza viruses infect the same cell, their genes may become reassorted—shuffled, mixed up. The net effect is that a new strain of flu virus forms, one that people have never been exposed to before. Webster refers to the mixing process as “virus sex.” Perhaps Webster’s greatest contribution to science is the idea that pandemics begin when avian and human flu viruses combine to form a new strain, one that people lack the ability to fight off.

After he entered the Hong Kong poultry markets, Webster needed only a few days to turn up enough chicken droppings to show that the H5N1 strain was indeed circulating. Along with many of his colleagues, he recommended that all the chickens in the market area be killed, to prevent spread of the virus. About 1.5 million chickens in Hong Kong met their maker. And that seemed to do the trick. The virus was gone.

But Webster had a hunch it would be back. The reason was ducks. Webster thinks the most dangerous animal in the world is the duck. His research has shown that ducks can transmit flu viruses quite easily to chickens. But while chickens that come down with bird flu die at rates approaching 100 percent, many ducks don’t get sick at all. So they fly off to other parts of the world carrying the virus. “The duck is the Trojan horse,” Webster says.

After the chickens in Hong Kong were killed, wild ducks probably relocated the virus to other parts of Asia, where it continued to infect chickens and shuffle its genetic makeup. When the strain emerged from hiding again, in Thailand and Vietnam in late 2003, it was even stronger. The virus passed directly from birds to people, killing dozens in what the World Health Organization has described as the worst outbreak of purely avian influenza ever to strike human beings.

Webster says the world is teetering on the edge of a knife blade. He thinks that H5N1 poses the most serious public health threat since the Spanish flu pandemic of 1918, which killed an estimated 40 million to 100 million people worldwide. Though the H5N1 strain has so far shown no signs that it will acquire the ability to transmit easily from person to person—all evidence is that flu victims in Vietnam and Thailand acquired the virus from direct contact with infected poultry—that has provided Webster no comfort. It’s only a matter of time before this virus, as he puts it, “goes off.” He has been saying this for several years. The world is finally taking notice. Elaborate plans are now being created in dozens of countries to deal with a pandemic. In November, President Bush requested that $7.1 billion be set aside to prepare for one, with hundreds of millions of dollars to be spent on further developing a new vaccine that was recently hatched in Webster’s lab.

Webster has been advising federal health officials every step of the way. He does so out of fear of this virus and also because it is his job. When the H5N1 strain emerged in the late 1990s, the National Institute of Allergy and Infectious Diseases awarded Webster a major contract to establish a surveillance center in Hong Kong, to determine the molecular basis of transmission of avian flu viruses and isolate strains that would be suitable to develop vaccines. “He’s certainly one of those people in this field who have been way ahead of the curve in bringing attention to this issue,” Anthony Fauci, the institute’s director, told me. “He was out ahead of the pack. He’s one of the handful of people who have not only been sounding the alarm, but working to prevent this thing from turning into something that nobody wants to see happen.”

Webster’s job keeps him out of the country two to three weeks a month. Back in Memphis, his lab analyzes samples of influenza virus strains from around the world, to see how they are mutating. Recently, health officials have reported finding H5N1 avian flu in birds in Turkey, Romania, Croatia and Kuwait. It has not yet been found in birds in North America. If H5N1 makes its way here, Webster will likely be among the first to know.

This past June, I caught up with Webster at a meeting of the American Society for Microbiology, in Atlanta, where he was scheduled to deliver a speech about the threat of bird flu. There were more than 5,000 microbiologists in attendance, which, because I am a recovering hypochondriac, I found strangely comforting. Walking around with Webster at a meeting of scientists is an experience that must be similar to walking around with Yo-YoMa at a meeting of cellists. When Webster walked by, people suddenly stopped speaking, a fact to which he seemed oblivious.

He opened his talk by asking a series of intriguing questions: “Will the H5N1 currently circulating in Vietnam learn to transmit, reproduce, from human to human? Why hasn’t it done so already? It’s had three years to learn how, and so what’s it waiting for? Why can’t it finish the job? We hope it doesn’t.”

He paused. “Is it the pig that’s missing in the story?” Webster explained that the strain is still not capable of acquiring the final ingredient needed to fuel a pandemic: the ability to transmit from person to person. For that to happen, Webster and others believe that a version of the human flu virus, which is easily transmittable between people, and the H5N1 avian virus have to infect the same mammalian cell at the same time and have virus sex. If H5N1 picks up those genes from the human flu virus that enable it to spread from person to person, Webster says that virtually nobody will have immunity to it. If an effective vaccine based specifically on that newly emerged virus isn’t quickly available, and if antiviral drugs aren’t also, many deaths will ensue.

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