n Neurospora, it was a simple matter to determine whether our newly induced 

 nutritional deficiencies were the result of mutations in single genes. If they 

 were, crosses with the original should yield four mutant and four non-mutant 

 spores in each spore sac. ["hey < 1 i<l (3, 21). 



In this long, roundabout way, first in Drosophila and then in Neurospora, 

 we had rediscovered what Gakkod had seen so clearly so many years before. 

 By now we knew of his work and were aware that we had added little if any- 

 thing new in principle. We were working with a more favorable organism and 

 were able to produce, almost at will, inborn errors of metabolism for almost 

 any chemical reaction whose product we could supply through the medium. 

 Thus we were able to demonstrate that what Garrod had shown for a few 

 genes and a few chemical reactions in man was true for many genes and many 

 reactions in Neurospora. 



In the fall of 1941 Francis J. Ryan came to Stanford as a National Research 

 Council Fellow and was soon deeply involved in the Neurospora work. A year 

 later David M. Bonner and Norman H. Horowitz joined the group. Shortly 

 thereafter Herschel K. Mitchell did likewise. With the collaboration of a 

 number of capable graduate students and a group of enthusiastic and able 

 research assistants the work moved along at a gratifying pace. 



A substantial part of the financial support that enabled us thus to expand 

 our efforts was generously made available by the Rockefeller Foundation and 

 the Nutrition Foundation. 



The directions of our subsequent investigations and their accomplishments I 

 shall leave to Professor Tatum to summarize. 



One Gene — One Enzyme. 



It is sometimes thought that the Neurospora work was responsible for the 

 one gene — one enzyme hypothesis — the concept that genes in general have 

 single primary functions, aside from serving an essential role in their own 

 replication, and that in many cases this function is to direct specificities of 

 enzvmatically active proteins. The fact is that it was the other way around 

 — the hypothesis was clearly responsible for the new approach. 



Although it may not have been stated explicitly, Ephrussi and I had some 

 such concept in mind. A more specific form of the hypothesis was suggested 

 by the fact that of all the 26 known eye-color mutants in Drosophila, there 

 was only one that blocked the first of our postulated reactions and one that 

 similarly interrupted the second. Thus it seemed reasonable to assume that 



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