In the PNAS Early Edition this week, an international research collaboration led by Chengjun Li at the University of Wisconsin-Madison describes their finding that genetic reassortment between the avian H5N1 and human H3N2 flu viruses causes hybrid strains with substantial virulence. To evaluate the pathogenic potential of these reassortant viruses, Li et al. created all 254 possible hybrids of H5N1 and H3N2 by using reverse genetics.