Influenza is a crafty opponent. Just when researchers think they might know where it's headed next, it mutates. New strains form constantly, allowing the virus to evade detection by the human immune system, and these new strains can turn into pandemics with little to no warning. In 1918, the H1N1 subtype caused the most serious pandemic to date, killing 50 million people worldwide. That disaster was followed by the H2N2 pandemic in 1957, the H3N2 in 1968, and the resurgence last year of H1N1, now also known as swine flu.
To predict what the next dangerous strain will look like, researchers are trying to develop more sophisticated models of the biology and evolution of the virus. "If I was to make a prediction, I'd say that the H2 strain of the virus could cause the next pandemic," says Klaus Stohr, director of influenza vaccine franchises at Novartis and former head of the World Health Organization's global influenza program. But he admits that predictions like his are just educated guesses. Above all, he says, "we need better models that could genetically predict which subtype will cause the next pandemic—that would be a real breakthrough. That, in my view, could be a Nobel Prize-winning discovery."
In contrast to pandemic flu, seasonal flu occurs with predictable regularity and is largely controllable. Six months before the beginning of the flu season in each hemisphere, the World Health Organization examines circulating strains from the previous year and determines which six are mostly likely to be a problem. Those are the strains that appear in the flu vaccines distributed to physicians' offices each year, and they're usually spot on. But when the virus genome mutates in ways scientists don't anticipate—when it picks up a gene from one of the strains that infect birds or pigs, or when it manages to hop straight from livestock to humans—the result is a type of influenza against which humans have limited immunity. That has the potential to attack hard and spread fast.
A severe flu pandemic could result in as much as a 5.5 percent drop in the U.S. gross domestic product, amounting to a $683 billion loss to the country's economy, according to a report by the Trust for America's Health. And despite the unceasing work of labs around the world—the World Health Organization has more than 100 laboratories participating in its influenza network—there is not yet much that researchers or public health officials can do to predict a pandemic, let alone prevent one. "People are studying the virus and its genome all the time and want to get to those answers," says Martin Meltzer, a health economist with the Centers for Disease Control and Prevention. "We don't know enough about how the genome of the flu virus interacts with the human genome that it infects."