l6 JOHN H. NORTHROP 



may be able to direct the synthesis so that the proper protein is formed, 

 but the energy must come from some other reaction, so that at least two 

 reactions, and not a single autocatalytic reaction, are necessary. 



The working hypothesis outlined in the rest of this discussion is an 

 attempt to formulate the simplest assumption that is adequate to account 

 for the known facts. It is quite probable that future experiments will 

 force modification to be made and may render the entire mechanism un- 

 tenable. If the hypothesis leads to the discovery of new facts it will 

 have served its purpose even though the new facts destroy the assump- 

 tions which led to their discovery. 



In general the hypothesis may be stated as follows : 



The formation of proteins occurs in two steps. The first step consists 

 in the synthesis of one or more "type" proteins ("proteinogens") ("ur- 

 protein" of Alcock) which are specific for the species and perhaps for 

 the organ. This step requires energy which may be obtained from a 

 coupled reaction or from preliminary formation of high energy building 

 stones (not amino acids). It is "autocatalytic" in that the structure of 

 this proteinogen is determined by itself. No experimental evidence for 

 this step exists at present. It probably takes place in the cell, since respira- 

 tion and similar reactions that liberate energy occur usually in the cell. 



Since even the existence of such a protein is purely hypothetical, dis- 

 cussion of its properties is hardly warranted. The only essential proper- 

 ties are that stable proteins may be formed from it without the addition 

 of energy and that its own formation is autocatalytic. There may be 

 several such proteinogen structures, one for each general group of 

 proteins. They probably contain nucleic acids. The virus proteins may 

 be special examples of these proteinogens. 



Spiegelman and Kamen (1946) have suggested that nucleoproteins 

 are the controlling factor in protein synthesis, and present evidence 

 indicates that the energy may be supplied by the phosphoric acid of the 

 nucleoprotein. Muller (1945) has made a similar suggestion.* 



The possibility that the proteinogen has the characteristics of a de- 

 natured, rather than a native protein, was suggested by M. Kunitz. 

 This assumption would account for the observed immunological reac- 

 tions as well as the energy requirements (cf . pp. 10, 27) , since denatured 

 proteins do not cross-react with the native proteins, nor do they show 



♦Recent experiments by Reiner and Spiegelman (1948) and by Price (1948) bear 

 out this hypothesis and also indicate a relationship between virus and adaptive enzyme 

 formation. Spiegelman and Reiner found that a desoxyribonucleic acid fraction from 

 yeast cells stimulates the formation of adaptive enzyme in yeast. Price finds that the 

 same fraction greatly increases the yield of virus particles per cell, formed by S. muscac. 



