The Flu Hunters: Racing to Outsmart a Pandemic

According to WHO figures, the H1N1 virus has so far proved to be mild, causing only 1,200 deaths among 160,000 confirmed cases. Hay says his team is watching for several changes in the virus' genome that could make the pandemic more severe. The first involves the H1N1 vaccine that is currently in production. The batch is based on a recipe that Hay's team helped put together in April. As it takes six months to produce a vaccine, virologists must be on the lookout for "antigenic drift" — changes in the virus that would let it escape the immune responses induced by the vaccine. (Because the flu virus can mutate so easily, antigenic drift is not unusual.)

Hay's team is also on the lookout for changes in the virus that might make it resistant to the antiviral drug Tamiflu, which has been shown to reduce the severity of the disease caused by many flu viruses. Tamiflu works by inhibiting the neuraminidase enzyme (that's the N in H1N1) and preventing it from doing its job of helping the virus replicate once inside a human cell. But certain amino-acid changes in the neuraminidase can render Tamiflu ineffective. This usually happens over time following extensive prescribing of the drug, but it can also occur spontaneously. In the winter of 2007-'08, a seasonal H1N1 variant circulating in Europe did just that, catching scientists by surprise. "We really didn't see that coming," says Daniels, who was one of the first scientists to identify the change. "Suddenly, an increasing number of H1N1 isolates were Tamiflu-resistant, and the resistant strains have persisted such that over 95% of H1N1 virus in America was [Tamiflu] resistant in the 2008-'09 season. And it doesn't appear to have had anything to do with overprescription of the drug. It was just a spontaneous mutation." (See pictures of soccer in the time of swine flu.)

Hay says the nightmare scenario would involve the pandemic appearance of the highly pathogenic H5N1 avian influenza. With a mortality rate of more than 60%, the virus is so dangerous to humans that his team can work with it only in biosecurity Level 4 laboratories, the highest level of biological containment available. So far, H5N1 is passed to humans only from birds and is not transmissible between humans. But if it were to swap genes with another influenza virus, possibly H1N1 (through, for example, a patient who contracts the two illnesses simultaneously), a new, more lethal pandemic strain could emerge with a high rate of contagion. "I would say that is an unlikely scenario," Hay says. "But the point is you don't know what's going to happen. You have to remain alert to all possibilities."

Hay and Daniels have spent the bulk of their working lives searching for a virus that could cause a pandemic. Now they are watching a pandemic unfold in front of their eyes. When he talks about influenza, Daniels tends to use his hand as a visual aid, cupping his palm to mimic the virus's spherical structure and pretending his curled fingers are the sphere's protein spikes. As he looks down at his hand, his face breaks into a wry smile. "Forget the pandemic strain for a second and consider seasonal flu," he says. "How this virus can continue to evolve, maintain its viability no matter what we throw at it and cause us problems on an annual basis — it's just mind-blowing. I'll say this about it — it's a worthy adversary."

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