PRODUCTION OF ANTIPNEUMOCOCCIC SERUM 567 



Tests of protective effect: the mouse 'protection test. In 1909, 

 Neufeld and Haendel 989 described a method of testing antipneumo- 

 coccic serum that was more or less generally adopted and used 

 until comparatively recent times. Mice were injected intraperi- 

 toneally with 0.2 cubic centimeter of serum and three hours later 

 different groups of the animals were given increasing amounts of 

 culture by the same route. It appeared that the action of anti- 

 pneumococcic serum follows the law of multiple proportions only 

 within certain limits and under certain conditions and, further- 

 more, that there is a limit to the effectiveness of the serum. To 

 this latter character was applied the term Schwellenwert. Unger- 

 mann and Kandiba (1912) 1436 found that when 0.2 cubic centi- 

 meter of serum protected mice against 0.1 cubic centimeter of cul- 

 ture, one-tenth of that amount of serum did not protect against 

 0.01 cubic centimeter of culture, thus substantiating Neufeld and 

 Haendel's observations regarding multiple proportions. Neufeld 

 and Haendel 992 reported additional technical details of their 

 method in which varying amounts of both serum and culture were 

 employed and recommended duplicate series of tests and the inclu- 

 sion of a standard serum of known potency. Wadsworth and Kirk- 

 bride 1470 reported that more consistent results were obtained when 

 one-half the amount of serum recommended by Ungermann and 

 Kandiba was used, but Avery, Chickering, Cole, and Dochez 36 were 

 in favor of adhering to the more commonly used quantity. 



In 1918, as a result of a regulation requiring that control tests 

 on antipneumococcic serums in this country be done at the United 

 States Hygienic Laboratory (now the National Institute of 

 Health), Way son and McCoy 1493 reported the adoption of the 

 Neufeld method as modified by Cole, with a serum supplied by Cole 

 as the standard for purposes of comparison. Official control was 

 confined to Type I serum. Because of the importance of this ac- 

 tion in developing methods of standardization, a brief citation of 

 the essentials of the technique is given. The test consisted in inocu- 

 lating a series of mice with a fixed dose of serum and varying doses 



