and fixed tissues of victims of the 1918 flu. Characterization of five of the eight RNA segments of the 1918 influenza virus indicates that it was the common ancestor of both subsequent human and swine H1N1 lineages, and experiments testing models of virulence using reverse genetics approaches with 1918 influenza genes have begun in hopes of identifying genetic features that confer virulence in humans.

In a parallel effort, subsequently described, epidemiologists are analyzing death records and serological data to better understand patterns of transmission, morbidity, and mortality in past influenza pandemics. Such findings could inform planning for public health interventions to reduce the incidence of severe outcomes in future pandemics. In particular, these studies reveal a signature change in excess mortality from the elderly to younger age groups, a “pandemic age shift,” that occurred with each of the three pandemics of the 20th century. If such a shift could be recognized in incipient pandemics, it might allow sufficient time for the production and distribution of vaccine and antiviral drugs before the worst pandemic impact occurs.

John M. Barry

Distinguished Visiting Scholar

Center for Bioenvironmental Research at Tulane and Xavier Universities

The 1918–1919 influenza pandemic killed more people in absolute numbers than any other disease outbreak in history. A contemporary estimate put the death toll at 21 million, a figure that persists in the media today, but understates the real number. Epidemiologists and scientists have revised that figure several times since then. Each and every revision has been upward. Frank Macfarlane Burnet, who won his Nobel Prize for immunology but who spent most of his life studying influenza, estimated the death toll as probably 50 million, and possibly as high as 100 million. A 2002 epidemiologic study also estimates the deaths at between 50 and 100 million (Johnson and Mueller, 2002).

The world population in 1918 was only 28 percent of today’s population. Adjusting for population, a comparable toll today would be 175 to 350 million. By comparison, at this writing AIDS has killed approximately 24 million, and an estimated 40 million more people are infected with the virus.

Front Matter (R1-R18)

Summary and Assessment (1-56)

1 The Story of Influenza (57-114)

2 Today (115-140)

3 Toward Preparedness: Opportunities and Obstacles (141-221)

4 Strategies for Controlling Avian Influenza Birds and Mammals (222-253)

5 Emerging Technical Tools (254-314)

6 Beyond Biomedical Response (315-372)

Appendix A: Pandemic Influenza: Assessing Capabilities for Prevention and Response (373-380)

Appendix B: Selected Bibliography (381-387)

Appendix C: The Critical Path to New Medical Products (388-389)

Appendix D: Forum Members, Speakers, and Staff Biographies (390-412)