THE HISTORY OF PROTEIN THERAPY 3 



Then Horbaczewski introduced nucleins and found that lupus vul- 

 garis reacted with a typical focal reaction to the nuclein, that is, 

 the nuclein injection caused a focal reaction about the lesion just 

 as well as the specific substance. Kiihne next analyzed the tuberculins 

 and noted the large amount of protein split products therein contained. 

 Koch was cognizant of the fact that the fever-producing element in 

 the tuberculins was not part of the specific effect which he was seek- 

 ing to accentuate; others (such as Hueppe and Scholl) insisted that it 

 was just this nonspecific bacterial protein that accounted for the 

 entire tuberculin reaction. As a result particularly of Kiihne's work, 

 Matthes and Krehl began their well-known experiments with protein 

 split products in tuberculous animals. In using various proteins to 

 bring about the tuberculin reaction in tuberculous guinea pigs they 

 found among others that milk injections would also activate the focus. 



In this work Matthes made several observations that have a di- 

 rect bearing on the problem under consideration. He noted for in- 

 stance that tuberculous guinea pigs reacted not only to tuberculin 

 with the well-known temperature rise, but to injections of deutero- 

 albumose as well. With small doses such animals responded with a 

 typical rise in temperature ; large doses caused a fall in body tempera- 

 ture and the death of the animal. Nontuberculous animals would at 

 times react with temperature to the deuteroalbumose injection, but 

 never to the same extent as infected animals. The dosage as compared 

 to tuberculin was large, nevertheless the results caused considerable 

 doubt in his own mind as to how far specificity entered into the tuber- 

 culin reaction and interested him in the role of protein split products 

 in the causation of fever. 



To the same period of time belongs the reintroduction of the arti- 

 ficial abscess (the fixation abscess of Fochier), a therapeutic pro- 

 cedure related to the seton and the fontanelle. Fochier used the sterile 

 abscess (produced by injecting turpentine) in puerperal infections with 

 some success. The method was in vogue for a number of years. From 

 Sahli's clinic Bauer published observations on a series of cases of 

 pneumonia treated with such sterile abscess formation (1 to 2 c.c. of 

 turpentine being injected to produce the abscess). The number of 

 cases so treated was too small to be of any particular value but it was 

 noted that a stimulation of leukocytes was always brought about as 

 a result of the injection. 



The introduction of nucleic acid by Horbaczewski has been men- 

 tioned. In the course of the next twenty years nucleic acid and its 

 salts and related chemical compounds that cause a leukocytic reaction 

 found their way into the treatment of infectious diseases. Their use 

 was advocated because it was assumed that their action consisted in a 

 general tissue stimulation. 



Colloidal metals, especially the silver preparations, had come into 

 use after their introduction by Crede. First it was assumed that the 



