PRODUCTION OF ANTIPNEUMOCOCCIC SERUM 577 



termining the curative properties of serum in pneumococcal infec- 

 tions. 



Washbourn 1487 administered a single dose of serum to rabbits 

 five to six hours following inoculation of a test dose of culture and 

 observed protection, but when the serum was given eight to twelve 

 hours after the culture he observed only retardation of death. 

 Wadsworth 1458 utilized rabbits in testing the curative action of 

 immune rabbit serum, but used the method for experimental com- 

 parison rather than for actual standardization. In a series of pub- 

 lications beginning in 1928, Goodner 625 reported experiments deal- 

 ing with the therapeutic effect of antipneumococcic serum in 

 rabbits following intradermal infection. By inoculating rabbits in- 

 tradermally with small amounts of living, virulent pneumococci it 

 was found that a local lesion developed and symptoms appeared 

 somewhat analogous to lobar pneumonia. The results of intrave- 

 nous treatment of animals so infected with antipneumococcic serum 

 administered twenty-four hours after inoculation were advanced as 

 a means of estimating therapeutic efficacy. The curative value 

 of serum as determined by the Goodner technique did not corre- 

 spond with the results of the mouse-protective test. The intrader- 

 mal method was suggested (1929) 527 for the routine standardiza- 

 tion of serum since it was based on the ability of a serum to combat 

 a preexistent infection. Later (1933), 631 however, it was admitted 

 that the method was too elaborate for routine use, and it was 

 found (1934), 532 " 4 furthermore, that variable factors, such as the 

 severity of the infection, the number of white cells, and the breed 

 and weight of the test animals complicated the results. In the ob- 

 servations of Francis and Terrell (1934) 476 on experimental Type 

 III intratracheal infection in monkeys, it was found that the mor- 

 tality was dependent upon the presence and severity of the septi- 

 cemia following inoculation. Thus, there were no deaths in animals 

 without bacteriemia ; with a low degree of blood invasion the mor- 

 tality-rate was 45 per cent ; with a moderate degree of septicemia 

 75 per cent died ; and with massive septicemia all animals died. 



