l8 JOHN H. NORTHROP 



coupled reactions are known, but no autocatalytic coupled reactions have 

 been described, so far as the writer is aware. If every cell in every tissue 

 had such coupled reactions occurring for each protein, the chances of 

 the discovery of the reaction would be far greater than if it occurred 

 only in a special organ or organs. 



In the following sections an attempt is made to describe the formation 

 of normal proteins, viruses, adaptive enzymes, and antibodies in terms 

 of this working hypothesis. 



II. Formation of Normal Proteins 



It is becoming increasingly evident that some sort of equilibrium 

 exists between the various amino acids and the various proteins or both 

 (Madden and Whipple, 1940; Schoenheimer, 1942). Schoenheimer 

 demonstrated by means of isotopes that both the N and C atoms of an 

 ingested amino acid appear in nearly all the proteins and amino acids of 

 the body in the course of a few days. This result is totally unexpected 

 from the viewpoint of the classical theory of protein synthesis and 

 indicates the existence of a dynamic equilibrium (cf. Borsook and 

 Keighley, 1935), since such equilibria would result in a rapid distribu- 

 tion of the atoms. It is probable that, as Schoenheimer has suggested, 

 some unknown building stones take part in the equilibria, as otherwise 

 it is difficult to account for the transfer of the C atoms from one amino 

 acid to another. 



Whipple and Madden's results are extremely interesting in this 

 connection. These workers find that dogs may be kept in health when 

 the only source of nitrogen is plasma injected into the vein. The animal 

 must, therefore, be able to form any required protein from the protein 

 present in plasma without preliminary hydrolysis by the enzymes of the 

 digestive tract. Whipple and Madden consider the results to show that 

 an equilibrium exists between plasma protein and the cell proteins. They 

 suggest that large polypeptides may be the intermediate compounds in 

 the equilibrium. 



A similar equilibrium between the serum proteins themselves has 

 often been suggested, and there is considerable evidence to show that 

 these proteins can be transformed into each other. 



Pederson has found by ultracentrifugal studies that a lipoid-contain- 

 ing protein of enormous molecular weight, which he calls X-protein, 

 exists in serum. He assumes that this protein is in equilibrium with the 

 albumin and globulin fractions. It is true that albumin and globulin 



