10 PROTEIN THERAPY 



first brought into question. Bingel treated about 1,000 cases of diph- 

 theria, one-half of the group with the specific antitoxin, the other 

 half with "empty," i.e., normal horse serum. According to his report 

 the clinical results were equally satisfactory in both series. Subse- 

 quently a number of German clinicians went over his results but could 

 not confirm them to the extent that Bingel had claimed. One point 

 of value was, however, brought to our attention by this discussion 

 of the antitoxin question. Along with the specific antitoxin value 

 the serum contained a nonspecific stimulating element in the horse 

 serum protein. Our modern highly concentrated sera naturally have 

 lost this nonspecific factor to a considerable degree in the process of 

 concentration, thus justifying the criticism that has repeatedly found 

 expression in recent years, that the modern concentrated serum did 

 not seem so effective, all things considered, as the old serum which 

 was not so high in antitoxin units. Concentrated antitoxin contains 

 less of the nonspecific factor; whatever may have been the clinical 

 value of this element has been lost in the modern preparations. 

 (Meyer.) 



This recognition of dualism in the therapeutic effect, the specific 

 antitoxic factor and the nonspecific stimulating factor of the diph- 

 theria antitoxin merely illustrates the importance of the unbiased study 

 of all factors in therapy. 



We are fairly well grounded in our knowledge of the specific factors 

 of immunity. Our knowledge of the nonspecific elements is still de- 

 cidedly fragmentary. Enthusiasm in one direction should not for 

 an instant obscure our vision of all other possible factors in resistance. 



Here in America interest in this particular phase of resistance 

 was stimulated by the work of Vaughan and Wheeler, of Opie and 

 his associates and later by that of Jobling and his co-workers. 



During the course of these latter studies we had under observa- 

 tion a series of animals intoxicated with a variety of bacterial and 

 other protein substances and noted in these animals a marked mobili- 

 zation of serum enzymes. When we became familiar with the work 

 of Kraus and Ichikawa we studied the problem from the point of 

 view of its practical application and concluded that at least part of 

 the therapeutic effect must be due to enzyme action. Inasmuch as we 

 had previously found that other agents besides bacterial vaccines 

 would produce precisely the same enzyme mobilization we concluded to 

 try a series of protein split products in patients ill with typhoid fever. 

 While this work was under way an identical investigation carried out 

 by Liidke with albumoses came to our knowledge, delayed of course by 

 the exigencies of the war. Miller and Lusk had in the meantime also 

 become interested in this form of therapy and were the first in this 

 country to report a larger series of cases so treated. They used both 

 typhoid vaccine and secondary proteoses in their work. Smith in a 

 paper published at the same time reported on the therapeutic bene- 



