is that each gene controls the production, function and specificity of a particular 

 enzyme. Important experimental implications of these relations are that each 

 and every biochemical reaction in a cell of any organism, from a bacterium 

 to man, is theoretically alterable by gene mutation, and that each such mutant 

 cell strain differs in only one primary way from the non-mutant parental 

 strain. It is probably unnecessary to point out that these experimental ex- 

 pectations have been amply supported by the production and isolation, by 

 many investigators during the last 15 or more years, of biochemical mutant 

 strains of microorganisms in almost every species tried, bacteria, yeasts, algae, 

 and fungi. 



It is certainly unnecessary for me to do more than point out that mutant 

 strains such as those produced and isolated first in Neurospora and E. coli 

 have been of primary utility as genetic markers in detecting and elucidating 

 the details of the often exotic mechanisms of genetic recombination of micro- 

 organisms. 



Similarly, it seems superfluous even to mention the proven usefulness of 

 mutant strains of microorganisms in unraveling the detailed steps involved 

 in the biosynthesis of vital cellular constituents. I would like to list, however, 

 a few of the biosynthetic sequences and biochemical interrelationships which 

 owe their discovery and elucidation largely to the use of biochemical mutants. 

 These include: the synthesis of the aromatic amino acids via dehydroshikimic 

 and shikimic acids (14, 15), by way of prephenic acid to phenylalanine (16), 

 and by way of anthranilic acid, indole glycerol phosphate (17), and conden- 

 sation of indole with serine to give tryptophan (18); the conversion of trypto- 

 phan via kynurenine and 3-OH anthranilic acid to niacin (19, 20); the bio- 

 synthesis of histidine (21); of isoleucine and valine via the analogous di-OH 

 and keto acids (22); the biosynthesis of proline and ornithine from glutamic 

 acid (23); and the synthesis of pyrimidines via orotic acid (24). 



If the postulated relationship of gene to enzyme is correct, several conse- 

 quences can be predicted. First, mutation should result in the production of 

 a changed protein, which might either be enzymatically inactive, of inter- 

 mediate activity, or have otherwise detectably altered physical properties. 

 The production of such proteins changed in respect to heat stability, enzymatic 

 activity, or other properties such as activation energy, by mutant strains has 

 indeed been demonstrated in a number of instances (25 — 31). Recognition of 

 the molecular bases of these changes must await detailed comparison of their 

 structures with those of the normal enzyme, using techniques similar to the 

 elegant methods of Professor Sanger. That the primary effect of gene mutation 



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