Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past

ABSTRACT The influenza pandemic of 1918–1919 killed approximately 50 million people. The unusually severe morbidity and mortality associated with the pandemic spurred physicians and scientists to isolate the etiologic agent, but the virus was not iso-lated in 1918. In 1996, it became possible to recover and sequence highly degraded fragments of influenza viral RNA retained in preserved tissues from several 1918 victims. These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics. The “Spanish ” influenza pandemic of 1918 –1919 stands as thedeadliest single event in recorded human history, killing ap-proximately 50 million people worldwide (1, 2). The unprece-dented burden of morbidity and mortality frustrated physicians and scientists, who were unable to identify the etiologic agent, but also spurred advances in microbiology, clinical infectious diseases, and public health practice (3). Influenza viruses were finally iso-lated about 15 years after the pandemic, but scientists of the early 20th century were not then capable of studying the biological basis of pandemic viral emergence, pathogenicity, or disappearance, le