IV 



THE CLONAL SELECTION THEORY OF 

 ANTIBODY PRODUCTION 



In the last chapter I gave a short account of what I regarded 

 as the important experimental and observational facts of the 

 immune responses. In this, I want to discuss the possible 

 ways in which a general theoretical account of the findings 

 can be constructed. It would be difficult, presumptuous, and 

 inappropriate to this series of lectures to attempt to deduce 

 directly from the facts the most likely theory of antibody 

 production. Instead, I shall consider only points of view that 

 have already been expressed, beginning with Ehrlich's 

 side-chain theory. 



I . The side-chain theory of Ehrlich 



This is, of course, based on an old-fashioned picture of cell 

 metabolism, but its essence can be expressed in terms that 

 would be intelligible today. Ehrlich assumed that all foreign 

 antigens, and especially the bacterial toxins with which he 

 was primarily concerned, damaged body cells by combining 

 with pre-existent chemical patterns (side chains) normally 

 concerned with some metabolic function. The union was 

 specific and irreversible and the damage to the cell could 

 only be overcome by casting off the blocked side chain and 

 replacing it with a new one. Such regeneration was 

 regarded as conforming to the general law of over-compensa- 

 tion that had been formulated by Weigert, and would there- 

 fore tend to produce an excess of side chains which were 

 liberated into the body fluids. 



The side-chain theory implies the existence of cellular 

 patterns complementary to all possible antigenic deter- 

 minants. With Landsteiner's studies of serological specificity 



4 49 Bc 



