The 1918 influenza pandemic: Lessons from the past raise questions for the future

The 'Spanish' influenza pandemic of 1918-1919 was the most severe in recorded history, affecting approximately 25% of the world's population and killing in the order of 50 million people. Subsequent influenza pandemics of the 20th century have been less severe. An understanding of the mechanisms underlying the severity of the 1918 pandemic could potentially help to reduce the extent of future pandemics. To this end, the entire 1918 virus and viruses bearing combinations of 1918 genes have been reconstructed through reverse genetics techniques. The availability of a viable 1918 strain has enabled researchers to investigate the viral and host factors underlying the extreme pathogenicity of the 1918 virus. These studies and others have revealed many features regarding the unusual epidemiology, pathogenicity, replication and transmission of the 1918 virus, and aid us in predicting the severity of future pandemic outbreaks.