Layer on Layer: The Bruce F. Cain Memorial Award Lecture

out of Fiske's laboratory where ATP was discovered some 10 to 12 years earlier. In 1942, there was a convergence of both factual and conceptual information that seemed to suggest that the time was right to begin to investigate nucleic acid biosyn thesis. The competitive antagonism between sulfanilamide and PAB was the first area of interest. Next, the secondary reversal of sulfanilamides by a purine plus thymine pointed to an associ ation between these substances and the active metabolite that PAB represented. Then there was an unknown vitamin with many aliases, the substance we call folie acid today; the variant we chose to work with was the Lactobacillus case/ factor, but there were others we could have chosen. There were microor ganisms that showed quite clearly that folie acid was connected with the biosynthesis of purines and pyrimidines because orga nisms like L case/ either would grow on thymine plus purine or would grow on L case/ factor. Thus, we used L. case/ as a "black box" of enzymes and metabolic pathways concerned with the biosynthesis of nucleic acids. I enlisted the help of Elvira Falco who was then in our Bacteriology Department, and to gether we worked out a screening test using L. case/ as the biological object. In the beginning, we proposed to make variants of the heterocyclic bases of the nucleic acids, mostly variants of the functional groups, to see whether these, as probes, could reveal anything about nucleic acid biosynthesis.