Discussion 351 



more of the corresponding amino acid by synthesis de novo. Dr. H. S. 

 Moyed has found evidence for this view (personal communication) in 

 experiments with analogues of histidine and of tryptophan. In both 

 cases the analogue inhibits the same early enzymicstep as the correspond- 

 ing amino acid. In a mutant which has been selected for resistance to 

 the histidine analogue, this early reaction, the condensation of AMP 

 (or ATP) with activated ribose phosphate, is no longer inhibited by 

 either histidine or by the analogue. It would appear, therefore, that 

 ability to interfere with the synthesis de novo of the corresponding 

 amino acid is the attribute which makes an amino acid analogue an 

 effective growth inhibitor. 



Pardee: That has been shown in several cases, where the analogue 

 prevents the formation of early intermediates in the biosynthesis of the 

 normal compound of which it is an analogue. 



Lehninger: Cytidine triphosphate inhibits the formation of ureido- 

 succinic acid ; can cytidine monophosphate be a repressor of the enzyme 

 which makes ureidosuccinic acid? 



Pardee: That is quite possible. We cannot tell whether the repressor 

 is cytidine triphosphate, cytidine monophosphate or uridine mono- 

 phosphate, etc. We added uracil and it made something which serves 

 to repress the formation of this enzyme. Incidentally, the uracil 

 analogue, azauracil, acts in the same way but less efficiently. 



Backer: The idea of the displacement of a repressor by an inducer 

 appeals to me ; they could both compete for a common site of the 

 template. 



Magasanik : There is no decisive evidence that the inducer is not part 

 of the template. The evidence is philosophical. If the gene already has 

 the information, why is the inducer needed? 



Pardee: Monod's argument is that, if an inducer is added, the bacteria 

 start forming enzyme with no appreciable lag, i.e. within a minute. 

 It is hard to see how bacteria can suddenly make a lot of new specific 

 templates within one minute ; one would expect an autocatalytic phase. 



Magasanik : I realize that it would be difficult to discuss here at this 

 time the brilliant experiment of Pardee, Jacob and Monod on the forma- 

 tion of p-galactosidase in zygotes. The results of this experiment provide 

 strong evidence that the primary event in the control of the formation 

 of p-galactosidase is repression, i.e. inhibition of a pre-existing enzyme- 

 forming system. 



Pardee: We have been working recently on bacterial recombination 

 (Pardee, Jacob and Monod, 1958, loc. cit.). The general principle, which 

 has been demonstrated by others, is that there are two kinds of bacteria, 

 male and female, in that the male bacterium can inject its genetical 

 material but not its cytoplasm into the female bacterium. One can 

 study a single gene, in our case the ^-galactosidase gene, in such a 

 system where the male bacterium has this gene in the active form and 

 the female is inactive in ability to form the enzyme. Originally the gene 

 is inside the male bacterium ; when it is mixed with the female bacter- 

 ium the gene is injected. Also, the female bacterium is constitutive : if 

 it were able to make [3-galactosidase it would make this enzyme all the 



