"The 1918 pandemic occurred in an era when viruses, as we know them today, were largely theoretical conceptualizations. Back in 1918, the extraordinarily high pandemic mortality, especially in young adults, frustrated physicians and scientists, who were unable to identify an etiological agent and thus were unable to diagnose and successfully treat the disease it caused. As virology matured as a scientific discipline, influenza A viruses were eventually isolated from pigs (1930) and from humans (1933). Serological data from the 1930s first suggested that the 1930s “classical” swine virus and the 1918 pandemic virus were closely related antigenically (23). This was later verified by viral genetic sequence analysis and by antigenic and pathogenesis studies. The subsequent pandemics, beginning with the 1957 H2N2 pandemic, revealed that new pandemic viruses could arise from previous pandemic viruses through genetic reassortment (Fig. 1). But where the 1918 virus had come from and what the basis of its severity had been remained among the most discussed medical mysteries throughout most of the 20th century. Solving that mystery was often referred to as a scientific “Holy Grail,” and few believed that it would ever be found. In 1976, historian Alfred Crosby (1931–2018) wrote that “It has been the dream of scientists working on influenza for over a half century to somehow obtain specimens of the virus of Spanish influenza, but only something as unlikely as a time capsule could provide them”."