74 



actual machinery could be simple, but if it is a 1-step process, than it must be 

 complex. There are only 3 candidates that one can propose, which could serve 

 this purpose. They are: Protein, DNA and RNA. 



CHARGAFF: They are all that you have found ? 



SPIEGELMAN: They are the only 3 candidates that I can name. 



CARTER: What about polysaccharides? 



SPIEGELMAN: They are large but they don't have the informational 

 content necessary. 



CARTER: Well, you have not postulated them yet. 



SPIEGELMAN: There are no polysaccharides that I know that are 

 sufficiently complex to serve such a purpose. 



CARTER: The antigenic polypeptides are complex. 



SPIEGELMAN: Antigenisis per se does not necessarily mean com- 

 plexity. The addition of one simple group can convert an antigenically inactive 

 substance to an antigenically active one. 



CARTER: I don't want to deny that you probably are correct. 



SPIEGELMAN: In any case, the candidates that we can perform ex- 

 periments with are those that we can name, and those which we actually seek to 

 test experimentally are those we think are the most likely. 



In principle, one can perform elimination experiments to seek to de- 

 termine whether the interference with the synthesis of a particular component, 

 has as a consequence the cessation of the ability to form enzyme. These are, 

 in part, the kinds of experiments that we carried out. We have interfered se- 

 lectively with the synthesis of DNA using a variety of procedures including the 

 use of X-rays, low dosages of UV, sulphur mustard, and analogues of thymine. 

 In none of the cases could we show any parallelism between the extent and the 

 severity of the inhibition, and the effect on enzyme forming capacity. Indeed, 

 in certain cases there was virtually no interference. Cohen has recently added 

 another interesting example in the form of a thymineless mutant that will con- 

 tinue to synthesis enzyme after it has exhausted the thymine in the medium We 

 have repeated and confirmed these results with another enzyme system. It 

 should be noted in this connection that this behavior is not observed, for exam- 

 ple with the uracil-like mutant or with an amino acid deficient mutant In these 

 cases, the elimination of the required metabolite from the medium leads to the 

 complete cessation of the ability to form new enzyme molecules. 



These experiments taken together certainly do not encourage one to 

 .-^postulate the personal involvement of DNA in the act of fabricating new enzyme 

 liiolecules. 



The situation is quite different if one turns to RNA synthesis. In the 

 first place, relatively slight impairment (50 percent) of RNA synthesis by UV 

 leads to complete abolishment of the ability of yeast cells to synthesize a-gluco- 

 sidase. Further, unlike thymine analogues, analogues of uracil and adenine can 

 cause immediate cessation of p-galactosidase formation inE.coli. I have al- 

 ready noted that uracilless mutants of E.coli are unable to synthesis enzyme in 



