tion of both humans and swine. Interestingly, swine influenza was first recognized as a clinical entity in that species in the fall of 1918 (Koen, 1919) concurrently with the spread of the second wave of the pandemic in humans (Dorset et al., 1922–1923). Investigators were impressed by clinical and pathological similarities of human and swine influenza in 1918 (Koen, 1919; Murray and Biester, 1930). An extensive review by the veterinarian W.W. Dimoch of the diseases of swine published in August 1918 makes no mention of any swine disease resembling influenza (Dimoch, 1918–1919). Thus, contemporary investigators were convinced that influenza virus had not circulated as an epizootic disease in swine before 1918 and that the virus spread from humans to pigs because of the appearance of illness in pigs after the first wave of the 1918 influenza in humans (Shope and Lewis, 1931).
Thereafter the disease became widespread among swine herds in the U.S. midwest. The epizootic of 1919–1920 was as extensive as in 1918–1919. The disease then appeared among swine in the midwest every year, leading to Shope’s isolation of the first influenza virus in 1930, A/swine/ Iowa/30 (Shope and Lewis, 1931), 3 years before the isolation of the first human influenza virus, A/WS/33 by Smith, Andrewes, and Laidlaw (Smith et al., 1933). Classical swine viruses have continued to circulate not only in North American pigs, but also in swine populations in Europe and Asia (Brown et al., 1995; Kupradinun et al., 1991; Nerome et al., 1982).
During the fall and winter of 1918–1919, severe influenza-like outbreaks were noted not only in swine in the United States, but also in Europe and China (Beveridge, 1977; Chun, 1919; Koen, 1919). Since 1918 there have been many examples of both H1N1 and H3N2 human influenza A virus strains becoming established in swine (Brown et al., 1998; Castrucci et al., 1993; Zhou et al., 2000), while swine influenza A virus strains have been isolated only sporadically from humans (Gaydos et al., 1977; Woods et al., 1981).
The unusual severity of the 1918 pandemic and the exceptionally high mortality it caused among young adults have stimulated great interest in the influenza virus strain responsible for the 1918 outbreak (Crosby, 1989; Kolata, 1999; Monto et al., 1997). Because the first human and swine influenza A viruses were not isolated until the early 1930s (Shope and Lewis, 1931; Smith et al., 1933), characterization of the 1918 virus strain previously has had to rely on indirect evidence (Kanegae et al., 1994; Shope, 1958).
Analyses of antibody titers of 1918 influenza survivors from the late 1930s suggested correctly that the 1918 virus strain was an H1N1-subtype