S. SPIEGELMAN AND A. M. CAMPBELL 



examination of the enzymatic consequences of individual modi- 

 fications in the genome with the hope that the interrelations re- 

 vealed by their careful analysis would ultimately yield a clue to 

 the underlying mechanisms of genetic control. The other, 

 starting from the enzyme, adopted the premise that fruitful 

 speculation on the role of the gene was unlikely in the absence of 

 a relatively detailed understanding of the mechanism of enzyme 

 formation. Those who felt inclined toward the second ap- 

 proach were necessarily forced to look for a system in which the 

 process of enzyme synthesis could be experimentally analyzed. 

 It is not surprising that the attention of these workers was im- 

 mediately turned to the phenomenon known as "enzymatic 

 adaptation." There had existed in the microbiological litera- 

 ture since 1888 a number of instances subsumed under this desig- 

 nation in which the presence of a particular compound ap- 

 parently resulted in a well-defined change in the enzymatic 

 activities. However, before these or similar examples could be 

 accepted as systems suitable for the study of enzyme synthesis, 

 the following criteria had to be rigorously satisfied. 



7. The changed enzymatic activity observed must not be 

 due to the selection of preexistent mutant types but rather to an 

 induced enzymatic modification against a constant genetic back- 

 ground. 



2. The observed change in enzymatic activity must be a 

 reflection of the appearance of an active apoenzyme, rather than 

 due to the accumulation of cofactors or intermediates unique to 

 the metabolism of the inducing substrate. 



The use of recently evolved genetic methodology adapted 

 to the analysis of microbial populations, and of modern en- 

 zymological procedures, made it possible to demonstrate in 

 certain instances that both criteria could be met. These re- 

 searches have been thoroughly summarized and discussed in 

 recent reviews (55,75,90) and need not be detailed again here. 

 Certain consequences (71,72) may, however, be noted. The- 

 oretically these findings possess obvious implications for the 

 problem of gene function. They establish that possession by a 



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