THE TOXICITY OF ENZYMES 71 



that the rate of enzyme action is modified, and perhaps it is a 

 means of defense of the body against its own enzymes ; as the 

 prozymes are more resistant to harmful agencies than the 

 enzymes, it also may be a method of storage. 



THE TOXICITY OF ENZYMES 



Although present normally in greater or less amounts in all 

 the cells in the body, when artificially isolated and injected 

 directly into animals nearly all enzymes seem to be extremely 

 toxic. The first thorough study of the toxicity of enzymes was 

 made by Hildebrandt, 1 who found that pepsin, invertase, dias- 

 tase, emulsin, myrosin, and rennin were all toxic. Emulsin 

 and myrosin were most toxic, 0.05 gram being the lethal 

 dose for a rabbit (average size) ; for pepsin, invertase, and dias- 

 tase the lethal dose was 0.1 gram, while rennin required 2 

 grams. The symptoms produced in dogs were trembling, 

 uneasiness, difficulty in walking, and finally coma. The ana- 

 tomical changes observed were : numerous hemorrhages through- 

 out the body, fatty degeneration of the liver and myocar- 

 dium, renal congestion, and numerous thromboses. Consid- 

 erable fever results, and Mayer considers this responsible for 

 the relative harmlessness of rennin, the action of which is 

 impaired above 40. That these effects are due to the enzymes 

 themselves rather than to contaminating bacteria is shown by 

 Kionka and by Achalme 2 who obtained similar results with 

 enzymes made sterile by filtration through porcelain. Achalme 

 found that such sterile preparations of pancreatic juice injected 

 subcutaneously into guinea-pigs produce a marked local pink 

 gelatinous edema, followed by gangrene ; if the animal dies, the 

 blood is non-coagulable. Intraperitoneal injection is better 

 withstood than subcutaneous. Fiquet 3 also observed that tryp- 

 sin and pepsin rendered the blood incoagulable, but after some 

 time the coagulability of the blood is increased and thrombosis 

 is frequent. Wells 4 found that pancreatic extracts containing 

 very active trypsin and lipase injected intraperitoneally pro- 

 duced an acute inflammatory reaction, but no fat necrosis. 

 Extracts containing active lipase and inactive trypsin were less 

 toxic, but produced fat necrosis. Extracts of liver and blood- 

 serum, rich in lipase, were almost without effect on dogs and cats. 

 Papain was found to be much more toxic than any animal 



1 Virchow's Archiv, 1890 (121), 1. 



2 Ann. d. 1 'Inst. Pasteur, 1901 (15), 737. 



3 Arch. d. Md. Exper., 1899 (11), 145. 



4 Jour. Med. Eesearch, 1903 (9), 92. 



