482 COLLECTED STUDIES IN IMMUNITY 



an authority as Arrhenius recognizes my method as correct in prin- 

 ciple and proceeds along the same lines. 



The study of Arrhenius and Madsen deals principally with tetano- 

 lysin, the hsemolytic poison discovered by me in tetanus toxin. Tetano- 

 lysin and tetanospasmin differ from each other in their haptophore 

 groups, as a result of which each possesses a particular antibody 

 in the tetanus serum of the market. Madsen studied this tetano- 

 lysin in my Institute, and found that when it is gradually neutralized 

 with increasing amounts of antitoxin, the same definite amounts of 

 antitoxin first added neutralize far more poison than subsequent 

 additions. Because of this and also because of other reasons (atten- 

 uation, phenomena during neutralization) Madsen concluded that 

 several poisons of different affinities were present. 



On taking up these studies in tetanolysin Arrhenius and Madsen 

 obtained practically the same results, and these authors succeeded 

 in constructing a formula for the action of antitetanolysin on tetano- 

 lysin which conforms to the law of Guldberg-Waage. Based on 

 this they next attempted to determine similar relations in the case 

 of very simple blood poisons. This had already been done by Danysz, 

 but the method was open to criticism. Arrhenius and Madsen chose 

 a weak base and an acid (ammonia and boric acid) as hsemolysin 

 and antihaemolysin. It was found that in these the neutralization 

 phenomenon is very similar to that of tetanolysin and antilysin, 

 from which they concluded that in the neutralization of toxins and 

 antitoxins we are dealing with reactions between simple substances 

 of weak affinities. 



In this connection they express themselves as follows: "The 

 last-mentioned curve gives a fairly accurate picture of the neutraliza- 

 tion of ammonia with boric acid. In the investigation of ammonia 

 as hsemolysin a spectrum analogous to that of toxin or tetanolysin 

 (Fig. 3) could have been constructed ; the following conclusion could 

 also perhaps have been drawn: One part of boric acid (antitoxin) 

 added to ammonia neutralizes 50% of this base; if two parts are 

 added it neutralizes 66.7%; if three parts, 75%; and four parts, 

 80%. From this it follows that since the respective amounts 50, 

 16.7, 8.3, and 5% are each time neutralized by the same amount 

 of boric acid, the amount first neutralized is three times as toxic as 

 the amount next neutralized, this again twice as toxic as the next 

 after it, which in its turn is one and one-half times as toxic as the 

 following, etc. In other words, ammonia is not a simple substance, 



