1918 Spanish influenza: The secrets remain elusive

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Abstract
The worst pandemic of influenza ever recorded was caused by the 1918 Spanish influenza virus. Emotional reports of fit and healthy soldiers falling down on parade and dying the same or the next day are recorded (1). An initial mild wave of infection occurred in the spring of 1918 and the lethal wave appeared throughout the world, in the fall. At least 20 million persons died worldwide and probably 10 times that number were affected. The origin of this virus and the basis of high pathogenicity have remained elusive for the virus is not available for study. Interest in the causative agent of the 1918 pandemic is not new. Because no viruses from the period are available, serological epidemiology has been used to trace the virus. The first childhood infection with an influenza virus leaves an indelible immunological imprint, aptly termed “original antigen sin” (2). Subsequent exposure to an antigenically related variant induces an anamnestic response to the original virus and a primary response to the variant. Sero-archeological studies of samples from humans born in the time period from 1918 to 1920 have shown that the original sinner was a virus closely related to A/Swine/Iowa/30 (H1N1) (3–5). With the advent of reverse transcriptase–PCR technology, archivally stored tissues now can be examined for the footprints of the 1918 influenza virus. Archived material comes in two forms: formalin-fixed, paraffin-embedded tissue samples from infected humans, or tissues from infected persons who were buried in the permafrost. In this issue of the Proceedings, Reid et al. (6) report the complete sequence of the hemagglutinin (HA) gene of the 1918 influenza virus isolated from samples taken from three people who died of acute influenza in September and November 1918. Two samples were from paraffin blocks containing lung tissue from young soldiers, which had …