Penicillin-induced Penicillin Resistance 93 



change — either by mutation or by enzyme induction — in the 

 kind of protein produced. It is therefore perhaps permissible 

 to wonder how frequently truly qualitative changes at a 

 molecular level may in fact occur. Qualitative changes — 

 both from mutations and interactions of genes — have of course 

 often been described [e.g. hybrid antigens in red cells (a) of 

 pigeons (Irwin, 1947), (b) of rabbits (Cohen, 1956), atebrin 

 resistance in pneumococci, said to be due to alteration in a 

 flavo-protein (Sevag and Gots, 1948); two types of j9-nitro- 

 benzoic acid resistance in Esch. coli said to be due to altera- 

 tion in affinity of an enzyme for the drug (Davis, 1951)] but 

 only rarely have attempts been made to show that such 

 changes are due to intramolecular alteration of a protein 

 which can be properly isolated and characterized. 



The best instances of possibly qualitative, heritable 

 changes in proteins, due to single gene mutations or interac- 

 tions, are those involving alterations in the thermostability 

 of an enzyme [e.g. the pantothenate-synthesizing enzyme of 

 Esch. coli (Maas and Davis, 1952); and the tyrosinase of 

 Neurospora (Horowitz and Fling, 1953, 1956)]. Unfortunately, 

 thermostability is one of the properties of enzymes which is 

 known to vary considerably with variations in composition 

 of the medium and on association with other molecules 

 (Lawrence and Halvorson, 1954; Stewart and Halvorson, 

 1954). 



Other interesting instances are: (1) two types of glutamic 

 acid dehydrogenases (apparently differing in their extent of 

 reversible inactivation) isolated by Fincham (1957) from 

 strains of Neurosjjora differing by a single gene, and (2) the 

 aureomycin-resistant nitratase found by Saz and co-workers 

 (1956) and Saz and Martinez (1956) in an aureomycin-resistant 

 strain of Esch. coli (origin not studied genetically), and 

 reported to have a conjugated flavin moiety more firmly 

 bound than had the corresponding sensitive enzyme obtained 

 from the sensitive strain. In neither case have the enzymes 

 been isolated and compared after full purification. 



In cases where types of a well-characterized protein species 



