Largely uncontrolled influenza is a potentially devastating disease of humans and of a limited number of domestic and wild animals. Continued rapid evolution of the influenza A virus is responsible for the annual epidemics and occasional pandemics that have affected humans for centuries.1

Epidemics can be traced to genetic drift - the accumulation of mutations in the antigenic domains of the haemagglutinin and neuraminidase spike glycoproteins. These changes allow the virus to escape immunological surveillance and spread through human populations. More catastrophic are pandemics. These global outbreaks arise from genetic shift: the emergence of completely new haemagglutinin or neuraminidase molecules to which most people are not immune. The source of these new influenza virus gene segments is wild aquatic birds, which harbour all 14 haemagglutinin subtypes of influenza A viruses.

Five pandemics of influenza have occurred this century at irregular intervals, including the “Spanish” pandemic, which claimed over 20 million lives in 1918. In two of the three outbreaks for which viruses are available the pandemic strain arose by genetic reassortment between Eurasian avian …