What influenza virologist wouldn't be interested in understanding the molecular mechanisms underlying the extreme pathogenesis of the virus responsible for the 1918 influenza pandemic? Studies related to this virus, which killed and estimated 50 to 100 million people worldwide [30] , have been (and remain) a prominent fixture of the laboratory, and genomic analyses are providing important new insights into what made this virus so lethal. In our first experiments associated with the 1918 virus, we evaluated global gene expression patterns in cells infected with wild-type influenza, engineered viruses lacking all or part of the NS1 gene, or with a virus containing the NS1 gene of the 1918 pandemic virus [31] . Deletion of the NS1 gene increased the magnitude of expression of cellular genes implicated in the interferon, NF-κB, and other antiviral pathways, and a virus with a C-terminal deletion in its NS1 gene induced a cellular gene expression pattern intermediate between the patterns induced by wild-type and NS1 knockout viruses. In contrast, a virus containing the NS1 gene from the 1918 pandemic virus was more efficient at blocking the expression of interferon-regulated genes than its parental virus. Together, these results suggested that the cellular response to influenza virus is significantly influenced by the NS1 gene and that the 1918 NS1 is a particularly effective interferon antagonist. Of course, we have since learned that the story is much more complicated.