I094 NON-SPECIFIC PROTEIN THERAPY 



that should be kept in mind. In the first place, all effects on cells result, in 

 their ultimate analysis, either in an acceleration and augmentation or in a diminution 

 or retardation of their function, and in these alterations the changes of the cell surface 

 are of greatest importance (Straub,' Heubner,^ Schade'), an increase in activity being 

 associated with an increase in permeability and a decrease in permeability with re- 

 tardation of function. Ordinary pharmacological agents — the indifferent narcotics, 

 the alkali salts, the alkaloids — produce changes that are readily reversible because 

 they produce only physical changes in the cell membrane (Beutner).^ But the non- 

 speciiic agents, largely colloidal, and including such agents as sulphur, salvarsan, 

 novasurol, produce changes that are less readily reversible, and the effects may be 

 apparent for a long period of time.s They seem to alter the cell membrane in a much 

 more profound manner. I have pointed out these relations in some detail elsewhere.^ 



In general, the pharmacologist has had difficulty in approaching the problems of 

 non-specific therapy. Apart from typhoid fever, the method is most useful in the 

 more chronic types of infection which occur commonly in man and which can be 

 reproduced with difficulty, if at all, in the lower animals. 



There must be considered, too, the fact that most of the agents are practically 

 indifferent when tested by the ordinary experimental methods (muscle and nerve 

 preparations) used in pharmacological technique. Nor are the agents selective poisons 

 in the usual sense of pharmacological activity, i.e., agents which possess affinity for 

 certain cells and for certain organs. Freund^ groups the agents into three classes: (i) 

 those which obviously affect certain organs in the living animals, but in which the 

 action differs in the isolated, surviving tissue; (2) those that are inactive when given 

 by mouth, but which seem active when given parenterally; (3) those of the type 

 wherein no direct chemical agent enters the body (irradiation, cautery, venesection, 

 etc.). Without doubt, a basic factor lies in the change of the entire organism after 

 the reaction to the non-specific agent. The Germans use the term Umstimmung to 

 denote that the body reacts differently to a stimulus after the reaction than before 

 the injection. It is a "non-specific desensitization," a state very closely related to 

 specific desensitization or the anti-anaphylactic period that follows in the wake of an 

 anaphylactic shock. Pharmacologically this is novel in that with ordinary drugs an 

 effect is manifest when the drug makes contact with the specific tissue and the effect 

 ceases with the excretion or the neutralization of the agent. Not so with protein 

 therapy. It is the continued effect which becomes manifest that is the basis of the 

 therapeutic effectiveness. I am by no means certain that the pharmacologist is cor- 

 rect in assuming that the original status of the cell is always regained after the ordi- 

 nary pharmacological effect has apparently subsided; that, however, is a subordinate 



' Straub; see Schade, H.: Physikalische Cfiemie in der inneren Medizin (3d ed.)- Dresden and 

 Leipzig: Steinkopff. 1923. 

 ^ Heubner, W.: ibid. 



i Schade, H., Giesche, T., and Kielholz, S.: Zeil.f. d. ges. Med., 49, 334. 1926. 

 ^ Beutner, R., and Monetoff, A.: Proc. Soc. Exp. Biol, and Med., 24, 462. 1927. 

 5 Berger, VV.: loc. cit. 



"Petersen, W. F.: Jour. Amer. Med. Assoc, 76, 312. 1921. 

 ' Freund, H.: loc. cit. 



