This research program is aimed at using structural, biochemical, computational, genetic, virologic, genomic, and epidemiologic techniques to understand the unusual high lethality of the 1918 influenza virus, also known as "Spanish flu." Although the 1918 influenza pandemic remains the most devastating infectious disease known to mankind (as measured by the number of deaths in a single year) little is known about the reasons for the high lethality of this virus. Until recently, a major reason for this lack of knowledge was the absence of influenza virus isolates from 1918, which made it impossible to analyze the genotypic and phenotypic characteristics of this highly virulent virus.

Two major technological breakthroughs have changed this scenario. The first one, led by Dr. Jeffery Taubenberger, is the molecular amplification and sequencing of RNA pieces from the 1918 virus. This was accomplished using human material from 1918-1919 samples derived from archived pathology slides and from preserved human tissue under the permafrost line in Alaska. This outstanding achievement has led to the complete sequencing of the coding regions of all 8 genes from the 1918 virus.

The second technological breakthrough came from collaborative studies between the groups of Drs. Adolfo Garcia-Sastre and Peter Palese. A novel technique was developed allowing for the generation of infectious influenza viruses entirely from plasmids.

These two technological breakthroughs now permit the investigation of the role of individual genes of the 1918 virus in its high virulence phenotype. These studies are generating critical information that is needed to tackle highly lethal influenza viruses in the event of a new pandemic.