138 S. S. COHEN 



with this subject that we ahnost bridge the gap between biology and en- 

 zymology in the field of jDoIymer sjmthesis. Studies in this area have provided 

 httle information concerning the maimer in which the genetic apparatus 

 estabhshes a potentiahty for protein synthesis or the nature of the link 

 between the gene and tlie protein-synthesizing apparatus; however, given 

 the existence of the gene and the potentiality which is in some way conferred 

 upon the cell, it has been possible to analyze many of the steps in 

 bringing the protein-synthesizing apparatus into play to produce a given 

 enzyme. 



The modern liistory of work in this area is only 15 years old and is mainly 

 confined to the study of microorganisms. It begins with the dissertation of 

 Monod (1942) on the growth of E. coli in various carbon sources and the 

 studies of Spiegelman and his collaborators on enzyme production m yeast. 

 Although the earhest work described the elaboration of poorly defined 

 catalytic systems for the metabolism of one or another carbon source, the 

 discovery of an inducible sucrose phosphorylase in Pseudomonas saccharopJnla 

 (Doudoroif, 1940) pointed to the possibility of studying the production 

 of a single specific protein. This lead has been pursued in most serious 

 investigations. 



Karstrom (1937) made the distinction between "constitutive" and 

 "adaptive" or inducible enzymes,^ i.e., constitutive enzymes are present in 



^ The terminology to be used in this discussion is one whicli was adopted relatively 

 recently by a number of groups working in this field (Cohn et al., 1953b). Until this time, 

 it had been customary to use the term "enzjrmatic adaptation" to describe the elabora- 

 tion of an enzyme by a cell in response to the presence of a specific exogenous substance. 

 These workers preferred to avoid the usual biological connotations of "adaptation," 

 i.e. structural or functional changes of an organism to increase fitness by a process which 

 is usually associated with genetic variation and selection, particularly since the induced 

 biosynthesis of enzymes was being studied under conditions of constant genetic back- 

 ground. Stanier (1953) has discussed the varieties of evolutionary and physiological 

 adaptations in microorganisms and their relation to the more limited phenomena of the 

 inducible production of enzymes. 



It is relatively simple to distinguish the two classes of adaptation which appear in a 

 culture in response to a new carbon source. If in a culture the development of the ability 

 to metabolize a substrate as carbon source is of genetic origm, the acquisition of poten- 

 tiality is found originally in only a few cells of the entire culture, i.e., in mutants, and 

 these may be detected by plating large numbers of cells on the substrate as sole carbon 

 source. Only a small percentage of the total number of plated cells Avill form colonies. 

 These mutants, of course, have a selective advantage in the presence of the new sub- 

 strate and their progeny will soon replace the original cells in this medium. On the 

 other hand, if all the cells do possess the potentiality but lack the enzyme because 

 the culture has been grown under conditions in which inducer is absent, plating on 

 the substrate, nevertheless, will reveal as many inducible colonies as cells plated. 



When a culture of bacteria possessing the potentiality for induced biosynthesis is 

 exposed to a high concentration of a new inducer, e.g., a j8-galactoside, such as lactose. 



