COVER STORY

Flu Fighters

A team of young Columbia scientists discovered the genetic origins of H1N1 swine flu this spring. Now they’re racing to determine its deadly potential.

by David J. Craig Published Fall 2009
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Columbia researchers, from left, Vladimir Trifonov, Benjamin Greenbaum, Alexander Solovyov, Raul Rabadan, Hossein Khiabanian, Oliver Elliott, and Joseph Chan. (Greenbaum is based primarily at the Institute for Advanced Study in Princeton, New Jersey.) / Photo: Beth PerkinsWhen a new form of influenza appeared in Mexico this past April, Columbia professor Raul Rabadan was in a unique position to identify its origins. Trained originally as a physicist, Rabadan, 35, had spent his early career describing black holes in outer space at the Institute for Advanced Study in Princeton, New Jersey. He had tired of that work about four years ago, though, so he studied biology in his free time and redirected his methods of mathematical analysis toward a poorly understood disease: swine flu.

Until this past spring, most scientists trying to anticipate the next flu pandemic were focused on H5N1 bird flu. That disease has killed nearly 70 percent of its human victims since appearing in Hong Kong in 1997. Fortunately, it doesn’t spread easily among people; virologists and epidemiologists have been monitoring bird flu closely to see if it becomes more contagious.

When Rabadan considered the threat of pandemic influenza, he asked different questions than other scientists. Flu experts, he says, tend to analyze the evolution of viruses on short timescales, in order to detect dangerous genetic changes where and when they occur. “If you’re worried about an outbreak of bird flu,” Rabadan says, “you go out and take samples from ducks to see how that virus is changing, one month to the next. Most people who study diseases work on that scale.” And they typically confine their analyses to small sample sets, he says, in accordance with a custom in the biological sciences that says you should only work on data that you collect.

Rabadan, like many scholars in the emerging field of biomedical informatics, wasn’t interested in obliging this protocol. “I left physics because I saw an enormous amount of biological data being studied only as part of small datasets,” he says. “I thought I could make a difference by looking at the big picture.”

A flu researcher capable of interpreting huge datasets would have a wealth of information at his fingertips, as most grant-giving institutions now require scientists to make public the genetic profiles of any flu viruses that they sequence. Rabadan believed that by sifting through the thousands of long, lettered chains that describe flu virus chromosomes, he could answer wide-screen questions: Does a virus’s propensity to kill a host impart any evolutionary advantage? In what circumstances are dangerous genetic changes most likely to occur? Is it possible to predict a virus’s evolution?

“This led me to focus not on birds,” he says, “but on pigs.”

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