CHAPTER LXXXI 



A CRITIQUE OF THE EHRLICH THEORY, WITH AN 



OUTLINE OF THE ENZYME THEORY OF 



ANTIBODY FORMATION 



W. H. MANWARING 



Stanford University 



The Ehrlich theory of the origin and nature of specific antibodies beautifully ex- 

 plains and co-ordinates all known immunological facts. For three decades this theory 

 has been the accepted basis for immunological deduction and clinical interpretation 

 by the majority of medical workers. Nevertheless, I am convinced there is hardly an 

 element of truth in most of the hypotheses incorporated in the Ehrlich theory, and 

 that for two decades the wide acceptance of the theory has been a serious handicap 

 to medical progress. 



THE EHRLICH HYPOTHESES 



Analysis shows that the four major hypotheses formally incorporated or implied 

 in the Ehrlich theory are the assumptions: (a) that specific antibodies are hereditary, 

 preformed, highly specialized, chemical substances, normally present in the animal 

 body; (b) that these substances originate in the fixed and wandering cells of the body, 

 and are by them given ofif into the body fluids; (c) that the humoral elements thus 

 formed and liberated are purposeful, defensive chemical substances for the body as 

 a whole; and (d) that the formation and liberation of these specific chemical defenses 

 with their subsequent transmission and absorption by other cells are the only specific 

 adaptive mechanisms in the body. 



The Ehrlich theory is usually characterized by its minor hypotheses, dealing with 

 the exact method of formation and liberation of these specific defensive internal se- 

 cretions by the body cells. These hypotheses are based on the specific receptor theory 

 of cell nutrition. This theory pictures each cell of the body as provided with numerous 

 highly specialized superficial atomic groups or side-chains, each side-chain having a 

 highly specialized chemical affinity for a certain food material. By means of these 

 highly specialized side-chains or "receptors" foods are assumed to be selected from 

 the blood stream and brought into chemical union with the living cytoplasm. Ehr- 

 lich's minor h^'po theses assume: (e) that some of these highly specialized food re- 

 ceptors have accidental affinities for certain antigens; (/) that a receptor having this 

 accidental affinity is permanently injured or denatured by its chemical union with 

 this antigen; (g) that the resulting denatured receptor is eventually cast off by the 

 living cell; and (//) that the cell now regenerates a new receptor of identical chemical 

 structure. 



In response to a sufficiently large single dose, or to repeated doses of the same 

 antigen, Ehrlich assumes: (/) that this regeneration is overslimulated, more than one 

 receptor being formed to replace the one denatured and lost; (J ) that the superfluous 



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