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
  • Comments (0)
  • Email
  • ShareThis
  • Print
  • Download
  • Text Size A A A

A sick mix

Pigs play an important role in the evolution of flu viruses and, at least until this spring, an underappreciated one. Among the handful of animals that influenza commonly infects — birds, pigs, dogs, horses, ferrets, whales, and humans — pigs are the most susceptible to catching flu strains from other species. When a pig, or any animal for that matter, becomes infected with two or more influenza strains simultaneously — say, when a farmer gives one of his pigs a human flu at the same time that the animal is fighting a porcine or avian variety — a dangerous new type of influenza can emerge. That’s because two flu viruses in the animal’s respiratory tract can mix genes, creating a new strain that contains enough genetic material from the human flu to infect people and to spread among us, and enough swine or avian flu genes, for instance, to confound our immune system. Such “genetic reassortments” involve much more dramatic alterations than do the routine mutations that occur when RNA strands make mistakes during the self-replication process. Mutations cause flu viruses to evolve constantly in subtle ways, forcing vaccine makers to tweak their drugs every year, while reassortments have spawned the vicious microbes behind all three flu pandemics of the 20th century — those in 1918, 1957, and 1968 — as well as the H5N1 bird flu of current concern. Each of these novel flu strains resulted from a joining of multiple viruses. The mixing vessel in the case of each of the past three pandemics, suspect a growing number of scientists, was the lung of a pig.

When Rabadan was recruited to Columbia from the Institute for Advanced Study last September, as an assistant professor of biomedical informatics, he immediately assembled a team of young number crunchers who could help him explain how flu viruses evolve to become killers. Among his postdoctoral hires are two other physicists, an astronomer, and a computer scientist. Not one of them could dissect a pig — not with a knife, anyway. “We’re all good at math,” says Rabadan, a boyish-looking native of Spain who dresses in designer jeans. “And we study biological phenomena by looking at how genomes change over long periods.”

Last year, Rabadan’s team began analyzing hundreds of swine flu gene sequences, dating back 90 years, held in public databases overseen by the NIH’s National Center for Biotechnology Information. His team looked at the unique genetic blueprints of these viruses against one another, examining how they had mutated and reassorted. Rabadan’s group quickly published some intriguing findings, demonstrating, for instance, that particular genes in swine flu are more likely than others to mutate or to nudge their way into a reassorted virus. Rabadan can’t explain this tendency, but the observation places him on the cutting edge of evolutionary biology. Most scientists in the field study how the physical environment favors some genetic traits over others; the Holy Grail of evolutionary biology has long been to observe — before natural selection obscures the data — the rate at which particular genetic changes occur in the first place. Rabadan is among a number of bioinformaticians who believe that, by analyzing vast quantities of genetic sequences, they can essentially slow down time, identifying patterns in how viruses mutate or reassort before these changes prove adaptable or deleterious, thereby untangling the twin phenomena of gene expression and natural selection.

  • Email
  • ShareThis
  • Print
  • Recommend (58)
Log in with your UNI to post a comment

The best stories wherever you go on the Columbia Magazine App

Maybe next time