APPLICATION OF THE PHENOMENON 403 



are of special interest since progress of the treatment of cerel)ro- 

 spinal fever inidoubtedly depends on the thorough understanding 

 of these substances. The extensive literattire on this subject is 

 reviewed by Murray (1929) . It is generally believed that these 

 substances appear as a result of massive cell autolysis (endo- 

 toxins) . Some investigators were able to obtain highly toxic sub- 

 stances in culture filtrates (Ohlmacher, 1927; Flexner) . Animals 

 vary considerably in their susceptibility to the toxic substances 

 oljtained in various ^vays so that sometimes small doses kill the 

 animals and larger doses produce no effect. It is, therefore, ex- 

 tremely difficidt to make a quantitative determination of their 

 potency by the "lethal dose" method. In addition, these siU)- 

 stances appear to be quite unstable. The strains of meningococcus 

 also vary in their toxigenicity. The effect of sera on the menin- 

 gococcus toxic substances ^vas studied by Kratis and Doerr, W'as- 

 sermann and Leuchs, Kratis and Baecher, Flexner, Dopter, 

 Boechncke and Kriunbein and more recently by Ciordon (quoted 

 by Murray) . These studies l3rought oiu the fact that the lethal 

 effect of the toxic substances can be netUralized by imminie sera. 

 Normal sera appear to ha\e some neturalizing potency as ^vell. 

 It seems from Gordon's studies that those therapeutic sera ^vhich 

 ^vere most effective in the treatment of military cases of menin- 

 gitis ^vere distinguished by their being able to neutralize one 

 minimal lethal dose of meningococctis toxin prepared by his 

 methods, whereas sera of less therapetuic value failed in this re- 

 spect. Unfortiuiately, however, because of the variable factors 

 already pointed otit (instability of toxic substances, varying stis- 

 ceptibility of animals, etc.) , the qtiantitative measurement of 

 the neutralizing potency of therapeutic sera based on these factors 

 is rendered impracticable and tmreliable. For this reason it is 

 impossible to prepare consistently poAverful antitoxic sera for 

 therapetuic tise. The agglutination tests ^vere, therefore, adopted 

 as a standard procedure for laboratory evaluation of the curative 

 effect of the sera. It is hardly doubted by any investigators that 

 sera of nearly the same agglutinin content may be qtiite different 

 therapeutically. This may, in part, be due to the presence or 

 absence of more or less hitherto luirecognized antibodies, as 

 already pointed out. 



The discrepancy bet^veen the agglutinating potencies of thera- 

 petuic sera and their clinical \alue has been recognized by nti- 

 merous investigators. Neal, Jackson, Apj)lebaum and Banzhaf 



