Primary Actions 271 



from the claim (Horowitz; see below) that most genes are involved 

 in only one metabolic reaction. This might make one expect that 

 genes with similar actions could be distributed in an orderly fashion 

 along the chromosome. Pontecorvo proposed a hypothesis which was 

 prompted by Mcllwain's evaluation of the rate at which certain reac- 

 tions involving vitamins take place in bacteria: rates of the order of a 

 few tens of molecules per cell per second. The idea was that chains of 

 reactions, the rate of which is very low, or chains of reactions involving 

 labile or non-diflFusible intermediates, must be localized; the reactions 

 must take place either on surfaces or in microvessels within the cell. ( A 

 long-forgotten idea of Hofmeister is that the alveolar structure provides 

 such microvessels; salivary gland, chromosomes may show alveolar 

 structure; Metz.) "We know that some genes are specifically involved 

 in individual steps of series of reactions. We assume that the action 

 of the genes is in some way mediated by corresponding enzymes, 

 either each gene playing a part in the synthesis of each enzyme, or on 

 the conditions for the enzyme to act, including structural organization. 

 The idea was that should the enzymes, acting on a series of reactions 

 of millimicromolar order, be arranged in proximity to one another, we 

 might find vestiges of this spatial organization reflected in the cor- 

 responding genes. The heuristic value of this working hypothesis Hes 

 in the fact that while the biochemical techniques for discovering 

 grouping or other kinds of spatial organization of enzymes are still in 

 their infancy, the genetical techniques for discovering fine details of 

 grouping of genes are already available" (Pontecorvo, 1952a). This 

 ingenious hypothesis, then, requires microchemical reactions of either 

 the genes or the primary gene products in situ on the chromosome, 

 as discussed above. Haldane (1954) considers this idea to be basic 

 for all future research on the biochemistry of genie action. 



We have already reported that a group of three loci, behaving 

 like pseudoalleles, all affecting biotin synthesis, were found when 

 looked for systematically by Roper. A similar case was reported for 

 nicotinic acid in Neurospora by Bonner (see 1951). Now these three 

 loci act like pseudoalleles. Pontecorvo expresses this in the following 

 manner: a normal action is possible only when all three normal alleles 

 are adjacent but not if they are in different chromosomes (i.e., 

 separated). Pontecorvo is very careful to say that we are still very far 

 from being entitled to say that one of the ways in which genes are 

 clustered along the chromosomes is that of small assembly lines of 

 genes which are involved in successive steps of the metabolism of a 

 scarce, ephemeral, or non-movable intermediate. We discussed before 



