An unusual pattern of mutations explains the rapid spread of drug resistance in seasonal flu, according to a paper published yesterday in Science.

The drug oseltamivir, made by Roche and better known as Tamiflu, works by binding to a key flu virus protein called neuraminidase. A single amino acid change in the protein is enough to weaken the drug’s hold. But drug resistance comes at a price: viruses carrying the mutant neuraminidase also don’t grow well and so, in 2002, a team of researchers declared the mutation “unlikely to be of clinical consequence”.

And yet, somehow, it was. By the 2007-2008 flu season, mutated, Tamiflu-resistant viruses had cropped up around the globe. At the end of 2008, the US Centers for Disease Control and Prevention advised doctors to no longer treat flu patients with Tamiflu alone. By then, almost all of the seasonal H1N1 flu strains were resistant to the drug.

Now, David Baltimore and his colleagues at the California Institute of Technology in Pasadena, explain this unexpected turn of events. Two mutations — which occurred before the neuraminidase mutation showed up — happen to compensate for the negative effects of the mutated neuraminidase on growth. The flu got lucky.

The finding could help researchers keep an eye on resistance in other flu strains, including avian flu and swine flu.