34 MOLECULES, VmUSES, AND BACTERLV 



We have indicated the existence of 23 proteins whose production 

 is controlled by the insertion of T-even phage DNA. Unquestionably a 

 number of other enzymes will be found to be increased: e.g., the 

 formation of deoxyribose, etc. On the other hand, other systems, such 

 as amino-acid activation, appear not to be increased, and these can be 

 conceived as rate-determining in the system as a whole. 



Since bacterial DNA is degraded very soon after infection, it is 

 reasonable to suppose that the code determining the amino-acid 

 sequence in each new protein is contained within the nucleotide 

 sequence of viral DNA. Although HMC and its glucosylated deriva- 

 tives can readily be conceived as equivalent to cytosine in this se- 

 quence, it is unlikely that all the elements for this sequence controlling 

 a single protein will be functionally identical for all amino acids, and 

 it is quite reasonable to imagine that bacterial and virus-induced 

 proteins will not be entirely identical in amino-acid sequence. Whether 

 this is true remains to be determined. The solution of this question is 

 only the first step pointing to one of the fundamental questions of 

 molecular biology: i.e., the correlation of the nucleotide sequence in 

 DNA with the amino-acid sequence in the protein whose structure is 

 controlled by the DNA. 



The problem of the intermediate steps in the control of protein 

 synthesis by viral DNA is also of the utmost importance. It can be in- 

 ferred, although proof can scarcely be considered adequate, that the 

 early RNA synthesis is functionally related to the synthesis of the new 

 enzymes and other proteins. It is a general phenomenon in these early 

 protein syntheses that they come to a halt about 15 minutes after in- 

 fection. Why do they stop? Is there a competition for amino acids 

 between enzymes and viral-coat proteins, or is there a destruction of 

 the specific RNA templates by conversion of component ribonucleo- 

 tides to the deoxyribonucleotides of viral DNA, or both? Is the turn- 

 over of RNA templates and competitive relation to protein and DNA a 

 general phenomenon which may account for the fact that differentiated 

 cells elaborating specific proteins do not normally produce DNA and 

 duplicate chromosomes? 



Although in a technical sense these systems are admirable for the 

 exploration of these questions, it is now evident that the T-even phages 

 contain too much DNA and too much information, that too many 

 proteins are produced, and that multiplication in cells infected by 

 these phages requires too many parallel events. This system is too com- 

 plicated to permit us to relate 1/20 of the genome in chemical terms to 

 one of the new proteins. Of course if we could insert a defined portion 

 of the genome at will, we would be in a much better position. How- 

 ever, E. coli has never been transformed, nor has the DNA of a T-even 

 phage ever been reproducibly fractionated. 



