TOXINS AND ANTITOXINS 251 



111 regard to the antigens and antibodies involved in the floc- 

 culation reaction, there has been much controversy as to whether 

 it is a bacterial precipitation or a toxin-antitoxin flocculation 

 phenomenon. Bayne- Jones (1928) states that he has reviewed 

 and confirmed the conclusion of H. Schmidt (1926) that toxin- 

 antitoxin flocculation occurs independently of bacterial precipitins. 

 Some of the reasons upon which he bases his conclusion may be 

 summarized as follows : 



1. The flocculating and agglutinating titers of an antitoxic 

 serum bear no relationship to each other. 



2. Bacterial agglutinins may be demonstrated in the super- 

 natant fluid of the indicator tube after flocculation is complete. 



3. According to Moloney and Weld (1925) diphtheria bacilli 

 are separable into groups by means of agglutinating sei-um but 

 all produce a toxin that is flocculated by one antitoxin. 



4. When bacterial precipitin is mixed with toxin, the latter is 

 not removed and furthermore the presence of the precipitin does 

 not interfere with the subsequent flocculation of toxin by anti- 

 toxin. 



5. Various controls also offer further evidence pointing to the 

 specificity of the toxin-antitoxin reaction. 



Theories of Toxin-Antitoxin Mechanism. — In regard to the 

 mechanism of diphtheria toxin-antitoxin neutralization, there have 

 been three theories that have received extensive consideration. 

 They were formulated by Ehrlich (1898, 1903, 1910), ArrheniiLS 

 and Madsen (1907) and Bordet (1909), respectively. 



Ehrlich. — Ehrlich (1910) says that when he began the study 

 of diphtheria toxin-antitoxin neutralization he regarded the toxin 

 as a simple chemical substance but that his experimental results 

 led him to think of it as a very complex compound of toxic and 

 nontoxic antigenic substances. He concluded that the diphtheria 

 bacillus secretes two antigenic toxic substances : one he called toxin 

 and the second, which possesses less affinity for antitoxin, he called 

 toxone. To toxin he ascribes the acute symptoms and death, while 

 toxone produces slowly developing emaciation, paralysis and death 

 of the experimental animal. In detei*mining an L^. dose of toxin, 

 which theoretically would be 101 M.L.D.'s, he found that it is 

 always larger than the theoretical figure, being very frequently 

 120, 130 or more M.L.D.'s. This led him to believe that in every 



