In the mid-1930s, the advent of sulfa drugs offered the possibility of treating a wide range of infectious diseases and thus raised and renewed considerable hopes that medicine could be revolutionized through this newly proved power of chemotherapy. Apart from the empirical search for other effective products, many researchers attempted to understand the mechanism of action of sulphonamides in order to explain their anti-bacterial properties. In 1940 a young biochemist, Donald D. Woods, presented consistent proofs that sulfa drugs might act by interfering with an essential metabolite, that is some substance necessary for the growth of the cell. The hypothesis that anti-bacterials might act this way had been advanced by his boss and colleague, Paul Fildes. This explanation was rapidly and widely accepted, and came to be known later as the Woods-Fildes theory. A few months later, Fildes argued in an important article that this theory could be used as "a rational approach to research in chemotherapy". Effectively, the idea of designing drugs that could act by replacing essential metabolites quickly established a solid basis. Numerous studies were conducted at first towards finding new powerful anti-bacterials and anti-malarials, but they also went beyond the field of infectious disease since the search for potent anti-cancer drugs soon became another strong incentive. While the research into anti-metabolites as a new class of drugs encoutered a lot of disillusions and some lasting therapeutic successes, some of the newly synthesized compounds developed as useful tools in the study of cellular mechanisms.

This paper aims at tracing the origins of the Woods-Fildes theory, its reception and combination with other fields of research, and its consequent use in the 1940s and early 1950s. Stemming from fundamental studies in bacterial biochemistry, the knowledge produced was adapted to fit a programme of drug research that extended to cancerous disease once it had been enriched with the results of nutritional studies. Thus, the Woods-Fildes theory served as a point of departure for the production of anti-metabolites which navigated from Petri dishes to hospital wards and other biological research groups, and between countries, academia and the pharmaceutical industry.