198 BACTERICIDAL SERA 



many problems connected with cytolytic action that are unsolved, 

 and there can be but little doubt that future research in this 

 direction will yield results of great pathological importance, both 

 in theory and in practice, and whether the therapeutical advance 

 will take the form of a potent serum or of a juster knowledge of 

 the inner processes of the body in disease the future will show. 



THERAPEUTIC APPLICATIONS OF BACTERICIDAL SERA. 



The discovery of the great therapeutic value of diphtheria anti- 

 toxin naturally led to attempts at antitoxin treatment of other 

 diseases, but it was soon found that it was impossible to prepare 

 a potent toxin, and therefore antitoxin, in the great majority of 

 cases. The discovery of Pfeiffer's phenomenon, and the sub- 

 sequent researches on bacteriolysis and haemolysis, with the 

 demonstration of the nature of substances at work, indicated that 

 the problem was to be solved, if at all, on other lines, and anti- 

 sera were made by injecting the bacteria themselves into suitable 

 animals. The process need not be described at length, and of 

 course slight modifications are necessary in different cases. In 

 general the early part of the treatment consists in the injection 

 of small doses of dead or avirulent bacteria, or in some cases 

 (e.g., anthrax) of a more virulent vaccine and of a protective serum 

 from an already immunized animal. The animal (horses, donkeys, 

 or goats, are usually employed) is thus immunized, and now large 

 doses of virulent bacteria are given in order to stimulate the 

 production of antibodies to as great an extent as possible. This 

 part of the treatment is often prolonged, and may last for a year 

 or more. At the end of this time the animal is bled in the 

 manner described above, and the serum used for protective or 

 curative purposes. In some cases it is standardized, the usual 

 method being to determine the amount which will just protect 

 a small animal from a lethal dose of living bacteria, or from some 

 multiple thereof. Thus Sclavo's serum is tested by injecting 

 i '6 c.c. into six rabbits, each of which receives shortly afterwards 

 a known dose of virulent bacilli ; if three of the animals survive, 

 and the rest have their lives greatly prolonged (as compared with 

 controls), the serum is considered to be efficacious. Antistrepto- 

 coccic serum may be standardized in a similar way : according to 

 Hewlett, 0-05 c.c. should suffice to preserve a rabbit from ten 

 lethal doses of living streptococci injected intravenously. In 

 other cases a somewhat more refined method is adopted, and the 



