Primary Actions 281 



ideas. If we refer to the preceding discussion of the processes at the 

 chromosomal site, we are not quite sure whether Beadle assumes the 

 primary enzymatic activity of the direct gene products (the dupli- 

 cates) to take place in situ of the origin or in the nucleus or after 

 removal into the cytoplasm, or perhaps in all these places. The 

 question is not relevant for the one-one theory, but it is so for the 

 problem whether the primary gene products are actually the final 

 ones. This is a basic diJBBculty of the theory. 



A number of us have not felt happy with this original formulation 

 of Beadle's theory. The extrapolation from the mutant effect to the 

 normal one is not convincing, at least to me. If a mutant prevents an 

 enzyme from action, this does not mean necessarily that the normal 

 locus produces the enzyme. If the normal locus controls any of the 

 manifold physical and chemical conditions of an enzymatic synthesis, 

 a mutant might prevent the latter by many indirect means (e.g., the 

 control of pH). In time, Beadle's own group as well as others (e.g., 

 Caspari, 1949Zj; Wagner, 1949) showed that in such biochemical 

 mutants the specific enzyme may be present without acting for dif- 

 ferent reasons, for example, because of a temperature dependence or 

 because of a block to diflFusion (Garrod, 1909; Jucci, 1949, quoted 

 from Haldane, 1954). Such cases accumulated so that Beadle changed 

 the one gene — one enzyme idea into one gene — one function. This 

 means that the gene is not connected by means of a one-one relation 

 to an enzyme, which is a kind of repHca of the gene, but to any 

 function necessary for accomphshing one synthetic step. Thus the one- 

 one relation remains, though it is no longer a unique biochemical 

 effect producing one type of substance, an enzyme. It is rather the 

 production of some direct or indirect or even remote condition which 

 is necessary for a single synthetic step. 



It is clear that this formulation now takes away the great appeal 

 of the original theory, which made the primary gene product directly 

 the specific active substance and simultaneously a copy of the gene 

 structure. Furthermore, it no longer supports the classic theory of the 

 gene, since the present formulation can be applied to any concept of 

 the genie material. However, both formulations raise the question 

 whether a general law of genie action has been found or only a feature 

 of a hmited type of genie action, relating to the biochemical in- 

 gredients of metabolism. Specific pigments like the melanins, ommins, 

 anthocyanins, carotenes, and flavines may be described as metabolic 

 end products; amino acids are ingredients of protein synthesis; and 

 vitamins, those of coenzymes. Metabolism and the processes of growth 



