THE HISTORY OF PROTEIN THERAPY 9 



therapeutic effect on a number of inflammatory conditions of non- 

 typhoidal origin. 



Clinical results such as those reported by Renaud, by Kraus and 

 by Ichikawa were not to be explained away as due to accident. The 

 conception of strict specificity in therapeusis that had been built up 

 in the laboratory had to give way before a clinical demonstration that 

 could no longer be ignored. Our recognition of nonspecific therapy 

 really had its inception with these three papers. Nor was it long 

 before a series of corroborative observations appeared in the European 

 literature from a number of clinics and in a number of diseases. Many 

 clinical phenomena heretofore obscure and never satisfactorily ac- 

 counted for on our older conception of immunity began to appear 

 relatively simple and understandable when studied from the new 

 point of view. 



From heterobacteriotherapy it was but a logical step to attempt 

 the intravenous injection of bacterial components and bacterial split 

 products, then to protein split products of nonbacterial origin and 

 finally to the realization that any substance which was capable of 

 inducing the shock reaction on the part of the patient would result 

 in general in the same therapeutic change. We were dealing with an 

 ergotropie as von Groer termed the reaction "eine Umstimmung" 

 of the whole organism (analogous to our term desensitization) which 

 made it resistant to intoxication. Soon a number of agents were so 

 used. Schmidt and Saxl introduced milk injections, Liidke the in- 

 jection of proteoses or albumoses, Mittlander the use of hypertonic 

 salt solution. Distilled water and foreign sera were next added 

 and recently the ancient method of producing sterile abscesses by 

 injecting minute doses of turpentine and hypertonic salt solution has 

 been revived. 



It was recognized, too, that some of the older substances, such 

 as nucleic acid, colloidal metals, enzymes, lipoids and a long list of 

 substances, the therapeutic effect of which had been variously ex- 

 plained, all belonged in the same category. When reviewed from 

 this point of view it became evident that they all brought about a 

 general reaction which manifested itself as a rule in the chill, the 

 fever and the leukocytosis, and those which were most successful 

 clinically were the ones following the use of which the reaction was 

 greatest. It had also been the common experience with the entire 

 group that in order to be effective they had to be given early in the 

 disease ; when used late the effect was much less certain. 



In view of the undeniably striking therapeutic results at times 

 achieved with nonspecific therapy certain enthusiastic workers im- 

 mediately went to the extreme view that specificity was valueless 

 in therapeusis and were ready to throw overboard the accumulated 

 results of the past thirty years. And the best known and most widely 

 used of our specific agents, diphtheria antitoxin, was the one that was 



