PRODUCTION OF ANTIPNEUMOCOCCIC SERUM 529 



jecting progressively increasing doses of dead organisms until the 

 animals were able to tolerate the sedimented residue from one liter 

 of living, virulent culture. Cole and Moore (1917) 268 also favored 

 this method. Their experiments indicated that, for the most rapid 

 production of primary immunity, several series of small doses of 

 dead cultures should be given, but in order to produce the highest 

 degree of immunity, living organisms were required. 



In the Rockefeller Monograph, Avery, Chickering, Cole, and 

 Dochez 36 outlined their methods for the immunization of horses. 

 After the administration of two series of injections of heat-killed 

 organisms, a sample of blood was obtained for agglutination and 

 protection tests. Serum taken at this time was never found to be of 

 satisfactory titer and, consequently, injections of living organ- 

 isms were given in increasing amounts until tests on the serum 

 samples indicated the desired potency. Cole (1917) 257 obtained po- 

 tent serum from horses injected over a period of six to seven weeks 

 with gradually increasing doses of dead organisms. Wadsworth 

 and Kirkbride (1917) 1470 reported the development of protective 

 serums in horses immunized first by injections of heated organisms 

 followed by increasing doses of living pneumococci. In 1918, Alex- 

 ander 7 described the use of mixtures of pneumococci and leuco- 

 cytes, and of serum-sensitized organisms and leucocytes, in immu- 

 nizing rabbits, and found that protective antibodies were devel- 

 oped within eight to eleven days. 



Despite the observations and beliefs that living cultures of pneu- 

 mococci induce the production of more effective therapeutic serum 

 than do killed organisms, there has been an increasing tendency to 

 use dead cultures. It is doubtful if any of the larger manufactur- 

 ing laboratories employ living cultures for the routine immuniza- 

 tion of horses. The writers of the present volume question whether 

 the alleged superiority of living antigens over devitalized prepara- 

 tions in stimulating antibody production outweighs the hazards 

 associated with the use of living, virulent cultures. Granting the 

 opinion to be sound, the problem arises of choosing a method by 



