The state of science, microbiology, and vaccines circa 1918.

The influenza pandemic of 1918-1919 dramatically altered biomedical knowledge of the disease. At its onset, the foundation of scientific knowledge was information collected during the previous major pandemic of 1889-1890. The work of Otto Leichtenstern, first published in 1896, described the major epidemiological and pathological features of pandemic influenza and was cited extensively over the next two decades. Richard Pfeiffer announced in 1892 and 1893 that he had discovered influenza's cause. Pfeiffer's bacillus (Bacillus influenzae) was a major focus of attention and some controversy between 1892 and 1920. The role this organism or these organisms played in influenza dominated medical discussion during the great pandemic. Many vaccines were developed and used during the 1918-1919 pandemic. The medical literature was full of contradictory claims of their success; there was apparently no consensus on how to judge the reported results of these vaccine trials. The result of the vaccine controversy was both a further waning of confidence in Pfeiffer's bacillus as the agent of influenza and the emergence of an early set of criteria for valid vaccine trials.

The fog of research: influenza vaccine trials during the 1918-19 pandemic.

Bacterial vaccines of various sorts were widely used for both preventive and therapeutic purposes during the great influenza pandemic of 1918-19. Some were derived exclusively from the Pfeiffer's bacillus, the presumed cause of influenza, while others contained one or more other organisms found in the lungs of victims. Although initially most reports of the use of these vaccines claimed that they prevented influenza or pneumonia, the results were inconsistent and sometimes contradictory. During the course of the debates over the efficacy of these vaccines, it became clear that the medical profession had no consensus on what constituted a proper vaccine trial. Even among those who asserted that clinical impression was not enough, there was no agreement on how a trial ought to be conducted. The American Public Health Association, through its Working Program on Influenza, sought to establish standards for the profession. The standards the APHA set in December 1918 guided American vaccine trials for a quarter century.

De Kruif's boast: vaccine trials and the construction of a virus.

This article describes the sustained effort by American researchers between the mid-1930s and the mid-1950s to develop an effective influenza vaccine. From almost the beginning of this project, researchers succeeded in protecting laboratory animals from lethal influenza infection, and they believed that success with humans would follow quickly. Yet although they succeeded in producing a vaccine that proved effective in field trials in 1943 and 1945, that same vaccine failed to offer any protection in 1947. This vaccine failure forced researchers to reconsider the growing evidence of antigenic variation and challenged the model of the virus that had been taken for granted.

Constructing vital statistics: Thomas Rowe Edmonds and William Farr, 1835-1845.

This paper describes the role of these two English statisticians in establishing mortality measurements as means of assessing the health of human populations. Key to their innovations was the uses for the law of mortality Edmonds claimed to have discovered in 1832. In reality he had merely rediscovered a relationship between aging and mortality first described mathematically by Benjamin Gompertz a decade earlier. During the 1830s Edmonds attempted to interest the medical profession in his discovery and to suggest how his discovery could be used to assess health of large communities and to study case fatality and therapy. Using the rich data of the General Register Office William Farr would develop Edmonds's suggestions to produce some of the most sophisticated uses of vital statistics in the 19th century. In understanding the motivation of these two statisticians, it is essential to recognise their reform sympathies in an age deeply troubled by the human costs of rapid industrialisation and urbanisation. The two set out to reform both their professions and society.