TOXINS AND ANTITOXINS 49 



ence is believed to be due to the progressive formation of toxoid 

 from toxin and perhaps also from toxon. Ehrlich and also Madsen 

 found that the combination of one antitoxic unit with toxin in the 

 determination of the L dose was in multiples of 100 M.L.D.'s. 

 These multiples were rarely less than 100 and never more than 200. 

 This would indicate that the multiple is not less than 100, but even 

 though values of 200 are not obtainable, the failure may be ex- 

 plained by the fact that pure toxin is not procurable. By means of 

 the phenomenon of " partial absorption " Ehrlich established a 

 formula for the antitoxin-toxin combination which he expressed as 

 "toxin 200 antitoxin." This has been illustrated by means of a toxin- 

 antitoxin " spectrum " based on a total valency of 200, the total valency 

 including toxin, protoxoid, and toxon. In spite of the great academic 

 interest of this discussion, its immediate practical value is not apparent 

 and the reader is referred to larger works for complete discussion. 



Objections to the Ehrlich Theory. As indicated previously, the 

 Ehrlich hypothesis is based on the assumption that the toxin-anti- 

 toxin reaction follows in a fairly close manner the chemical reaction 

 between a strong acid and a strong base. Certain features of the 

 process of combination support the idea of chemical union, as, for 

 example, the fact that warmth accelerates the reaction, dilution 

 slows it. Furthermore, there is a liberation of heat in the reac- 

 tion, that is to say, about half as much heat per gram molecule as 

 would be liberated by the reaction between a strong acid and a 

 strong base. It is well known, however, that the union of toxin and 

 antitoxin is loose and within certain limits reversible. The Martin 

 and Cherry experiment referred to earlier in this chapter is of great 

 importance in this connection. They mixed snake venom and anti- 

 toxin to a point of neutralization and filtered through gelatin filters, 

 with the result that the toxin came through the filter first. This 

 they interpreted as being due to the smaller size of the toxin mole- 

 cule. It also shows the looseness of combination and the reversi- 

 bility of the reaction. They further showed that the longer the 

 mixture stands, the smaller the amount of toxin that comes 

 through the filter. Zinsser states that the " chief value of these 

 experiments lies in their proof of the element of time as an 

 important factor in the toxin-antitoxin union." Calmette had previ- 

 ously shown that venoms of certain snakes would remain virulent 

 after heating even to 100 degrees, and that the antitoxins were 

 thermolabile. He demonstrated that if the two were mixed so as to 

 be non-toxic, subsequent heating would liberate the toxin probably 

 through thermic destruction of the antitoxin. If the union were a 

 fixed one, this should not have been true. Martin and Cherry failed 

 to confirm this with the venom of an Australian snake, but this can- 

 not be regarded as a refutation of Calmette's work, especially as the 

 principle was found to apply to other toxins and antitoxins. 

 Morgenroth showed that acidulation with HC1 of a venom lysin- 

 antilysin mixture produced an acid-toxin molecule that resisted 

 4 



