100 PROTEIN THERAPY 



bacterial cell and its metabolites or possibly from the pathologically 

 altered activity of cells of the invaded body, proteins and their 

 split products are the chief components with which we have to deal.* 

 Schittenhelm has emphasized the general conception that the splitting 

 of proteins (apart from the gastro-intestinal processes) is purely an 

 intracellular phenomenon and that whenever we have to do with 

 extracellular proteolysis we deal with a pathological condition with 

 tremendous inherent possibilities of intoxication. It is therefore our 

 chief concern to investigate and review our present knowledge of 

 protein intoxication, of enzymatic detoxication of the poisonous pro- 

 teins, of resistance to protein intoxication and of the bearing of this 

 knowledge to the problem of nonspecificity. 



Detoxication. It is apparent that the fundamental factor in over- 

 coming bacterial intoxication (not due to the soluble exotoxins) lies in 

 the ability of the cells or fluids of the invaded organism to digest the 

 toxic protein fragments (and the native protein to which the organism 

 may have become sensitized) to the lowest degradation product that 

 is, to the nontoxic stage, and in this way overcome the deleterious 

 effect. This detoxication may also be brought about by the formation 

 of addition products, by polymerization and by proteosynthesis in gen- 

 eral. Enzyme activity, then, no matter under what immunological 

 term we wish to classify the particular phase, must be considered 

 among the basic phenomena which have to do with overcoming bac- 

 terial invasion itself. The study of the proteolytic enzymes and 

 their relation to pathological conditions, of the factors that accelerate 

 and the factors that retard enzyme activity should lead us to some 

 final field wherein by controlling enzyme activity we may be able 

 to achieve therapeutic results. 



The role of the enzymes in pathological conditions has until very 

 recent years been a relatively neglected field of study. Enzymes, 

 whatever may be their nature or their composition, must have formed 

 the basis of the structure upon which the animal organism built up 

 it system of immunity. The unicellular organism must certainly 

 endeavor to overcome harmful extracellular forces by means of its 

 ability to excrete enzymes, and the intracellular enzymes, too, must 

 be called into play when some parasite invades the cell. The path- 

 finding work of Metchnikoff was based on this idea. Specific im- 

 munity must have been a much later development of this primitive 

 and nonspecific factor of resistance. A number of investigators have 

 at various times sought to identify the specific activity of anti- 

 bodies, more especially the activity of complement, with various 



* While this view of the subject is plausible and quite generally accepted 

 we must by no means ignore the fact that even here contradictory evidence has 

 accumulated, a discussion of which will be found in the recent papers of Zinsser 

 and of Tiele. These observers seek to find the source of the intoxication due to 

 the "endotoxin" producing bacteria, as well as the intoxication in anaphylaxis, 

 in certain physical alterations of the serum, as yet not clearly defined. 



