worked out and the homogentisic acid isolated and identified many years 

 before. 



Our idea — to reverse the procedure and look for gene mutations that in- 

 fluence known chemical reactions — was an obvious one. It followed logically 

 from the concept that, in general, enzymatically catalyzed reactions are gene- 

 dependent, presumably through genie control of enzyme specificity. Although 

 we were without doubt influenced in arriving at this approach by the antho- 

 cyanin investigations, by Lwoff's demonstrations that parasites tend to 

 become specialized nutritionally through loss of ability to synthesize sub- 

 stances that they can obtain readily from their hosts (i8), and by the specula- 

 tions of others as to how genes might act, the concepts on which it was based 

 developed in our minds fairly directly from the eye-color work Ephrussi and 

 I had started five years earlier. 



The idea was simple: Select an organism like a fungus that has simple nutri- 

 tional requirements. This will mean it can carry out many reactions by which 

 amino acids and vitamins are made. Induce mutations by radiation or other 

 mutagenic agents. Allow meiosis to take place so as to produce spores that 

 are genetically homogeneous. Grow these on a medium supplemented with 

 an array of vitamins and amino acids. Test them by vegetative transfer to 

 a medium with no supplement. Those that have lost the ability to grow on 

 the minimal medium will have lost the ability to synthesize one or more of the 

 substances present in the supplemented medium. The growth requirements 

 of the deficient strain would then be readily ascertained by a systematic series 

 of tests on partially supplemented media. 



In addition to the above specifications, we wanted an organism well suited 

 to genetic studies, preferably one on which the basic genetic work had already 

 been done. 



Neurospora. 



As a graduate student at Cornell, I had heard Dr. B. 0. Dodge of the 

 New York Botanical Garden give a seminar on inheritance in the bread mold 

 Neurospora. So-called second division segregation of mating types and of 

 albinism were a puzzle to him. Several of us who had just been reviewing the 

 evidence for 4-strand crossing over in Drosophila suggested that crossing over 

 between the centromere and the segregating gene could well explain the result. 



Dodge was an enthusiastic supporter of Neurospora as an organism for 

 genetic work. "It's even better than Drosophila", he insisted to Thomas Hunt 

 Morgan, whose laboratory he often visited. He finally {)ersuaded Morgan 



s-34 



