The 1904 pandemic of bacterial meningitis challenged scientists in Europe and North America to apply the methods of bacteriology and immunology to therapeutic research. This very public emergency was a chance for advocates of scientific medicine to demonstrate the value of laboratory-based experimental research. In only three years researchers in the United States and Germany began testing anti-meningitis sera on human subjects. It would take another decade to conclusively establish the efficacy of this treatment which reduced mortality from 80 to 20%.

In this paper, I evaluate the development of Simon Flexner’s anti-meningitis serum at the Rockefeller Institute for Medical Research. How Flexner produced his serum, determined its efficacy in animals, and then transferred this knowledge to human subjects, demonstrates the evolving standards of scientific medicine at the bench and in the clinic. The outlines of what was meant by scientific medicine were clear to the laboratory-oriented reformers of the period: medical research that sought to replace the perceived failings of clinical observation with rigorous experimental design. However, no precise definition of what was meant by scientific existed. The first part of Flexner’s meningitis research, based on animal models, illustrates the evolution of Flexner’s standards of practice at the bench and his early attempts to define the significance of his data. Flexner’s characterization of the German serum programs as empirical is revealing of how Flexner himself was coming to grips with these standards.

Part two of Flexner’s research, testing the serum’s efficacy in humans, sheds light on the history of clinical trials and Flexner’s struggles to adapt his methods and standards to the clinic. Flexner assembled dozens of physicians to conduct what was arguably one of the largest clinical trials before the influenza vaccine trials of 1918-19. Over six years, more than 1300 patients received the Flexner serum in ten countries. In the Progress of Experiment Harry Marks argued that similar cooperative trials from the 1920s seldom resulted in definitive changes to therapies due to the inherent difficulties of conducting large trials with multiple participants. However, the success of the anti-meningitis serum trial demonstrates that in at least this instance Flexner was able to overcome these obstacles due to the authority and resources of the Rockefeller Institute.