The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine (review)

The history of the therapeutic revolution that took place during the twentieth century often begins with the discovery of penicillin. A key episode in development of this miracle drug was the decision made by Howard Florey and his colleagues at Oxford University in the summer of 1941. Giving up hopes of having the British drug companies engage in the production of large amounts of the antibiotic, they crossed the Atlantic to approach American pharmaceutical companies. The pharmaceutical companies did not show strong interest, but thanks to the commitment and mediation of the U.S. Office for Scientific Research and Development, a U.S. penicillin program was nonetheless launched. This episode has been told and retold, although the reasons why most pharmaceutical firms were so reluctant to jump into what was not yet an antibiotic bandwagon have usually been described as ignorance and bureaucratic entrenchment. The negative evaluation of penicillin was not only the product of uncertainties regarding its efficacy and production costs. It was also rooted in fact that there was an alternative. Sulfa drugs were then at the top of the research and development agendas of most drug entrepreneurs.

It all the more surprising that the history of the "first miracle drug," sulfa, has remained uncharted territory for such a long time. Filling this gap, John Lesch's recent book is a most welcome addition to the history of twentieth-century medicine. The book explores pharmaceutical research practices in the 1930s and 1940s. As expected, Lesch describes the work of G. Dogmak, F. Mietsch, and their colleagues completed at I. G. Farben to synthesize the dye Prontosil, identify its antibacterial properties, and produce many analogs. Recapitulating his own work on I. G. Farben's system of invention, in The First Miracle Drugs, Lesch retrieves the origins of the screening model of drug research. Combining organic chemistry with microbiological (or physiological) testing to achieve the selection of therapeutic leads among thousands of chemicals, screening was invented in Germany and became the norm for pharmaceutical research after 1945.

The book's novel insights, however, originate in a different inquiry, namely, the exploration of research in firms other than I. G. Farben. Leaving the birthplace of sulfonamides, Lesch follows their development in France and in Great Britain, thus pointing to other ways of inventing drugs. The first alternative to screening is the approach that dominated the work of Rhône-Poulenc and of its main scientific associates, the microbiologists and chemists at the Pasteur Institute in Paris. It is well known that the latter identified the active component of Prontosil as the sulfonamide core of the molecule and not its dye component. Lesch manages to insert this famous story in his detailing of the system of invention that guided Rhône-Poulenc, a system that focused on the habit of copying and diversifying existing (and promising) molecules. A second alternative less known to historians of medicine was the diversification of therapeutic indications and uses through clinical research. Discussing the collaboration among the British Medical Research Council, the chemists of the firm May and Baker (a subsidy of Rhône-Poulenc), and the physicians of London Middlesex Hospital, Lesch recounts how sulfa derivatives effective against pneumonia and gonorrhea were identified. The most telling case is that of sulfapyridine (MB-693), a compound that May and Baker put on trial in 1938 with local clinicians slowly building the case for such use on the basis of case-by-case assessment and historical control.

Finally, Lesch's interest in what happened outside the factory provides us with a detailed exploration of the role sulfa drugs played during the war. He brings back the comparison with penicillin in both chapters on U.S. wartime medicine. The figures are in this respect quite impressive. By 1942–43, when their production peaked, 4,800 tons of sulfa derivatives were elaborated. The book...