THE HISTORY OF PROTEIN THERAPY 5 



to use such an extract in patients. They were not able at the time 

 to account definitely for the therapeutic effect obtained but Zinsser 

 has since expressed the opinion that the results were probably to be 

 accounted for on the basis of a nonspecific reaction. 



Occasional clinical reports were made during the period between 

 1890 and 1910 which detailed success in infectious diseases through 

 a number of therapeutic measures purely nonspecific in character, 

 among them those of Paton, who used normal serum and diphtheria 

 antitoxin in the treatment of tuberculosis, arthritis, and cerebrospinal 

 meningitis. 



Paton's work was based on preceding observations made by De 

 Minicis, who had treated a small series of diphtheria cases with diph- 

 theria antitoxin per os, and on those of Lilienthal and of McCallum, 

 who had reported that diphtheria antitoxin possessed curative prop- 

 erties when given in a variety of infections such as sepsis, tuberculosis, 

 adnexal inflammatory conditions, lupus, etc. Paton published a small 

 volume detailing his clinical experience with the use of diphtheria 

 antitoxin given by mouth ; he found that not only normal horse serum 

 but sheep serum and ox serum possessed the stimulating qualities 

 to which he attributed the therapeutic effects. This paraspecific sero- 

 therapy has been used extensively in France. 



Darier has collected some of the clinical literature concerned with 

 the reaction and more recently Cumston has discussed it. That the 

 injection of diphtheria antitoxin might at times produce a transient 

 increase in the temperature of the patient had been observed very 

 early by Ewing, who also noted the leukocytic response after injections, 

 that is, a primary leukopenia lasting for about one-half hour, fol- 

 lowed by a leukocytosis. The use of normal horse serum in the treat- 

 ment of certain alterations of the coagulation balance of the blood has 

 also become quite common in recent years (Weil) and inoculation of 

 the patients serum, plasma or whole blood, either subcutaneously or 

 intravenously autoserotherapy as it is termed has been practiced 

 especially by the dermatologists. Within the past five years some 

 success has been reported in this limited field but the method was never 

 recognized as being part and parcel of a general reaction. 



In 1917 Deutschmann, seeking to find a method of treatment for 

 certain eye diseases against which remedial measures were unsat- 

 isfactory, began the immunization of horses with yeast cells and used 

 the serum for the treatment of a variety of infectious diseases. Yeast 

 has for many years been supposed to augment the resisting powers 

 of the body when given by mouth; yeast extract has also been given 

 subcutaneously for the same purposes and has also been applied in 

 the treatment of malignant diseases (especially by Italian clinicians 

 on the basis of the work of Sanfelice). When so injected the effect 

 is probably due to the nuclein content of the extract. 



In Deutschmann's work about 2 c.c. of the serum was injected 



