566 IMMUNITY 



base, Lt- Lo ought to be the equivalent of a minimum lethal dose of the 

 toxin alone. This, however, was never found to be the case, the differ- 

 ence being always considerably more than one M.L.D. For example, in 

 the case of one toxin, M.L.D. = '0165 c.c, Li. = l'26 c.c., L = - 9 c.c. ; 

 difference = '36 c.c, i.e., 21 '9 M.L.D. This, in brief, is what is known 

 as the " Ehrlich phenomenon," and it has been explained by him as the 

 result of the presence of toxoids {vide p. 195), i.e., toxin molecules in 

 which the toxophorous group has become degenerated. He distinguishes 

 three possible varieties of such bodies according to the affinity of the 

 haptophorous group, namely, prototoxaid with more powerful affinity than 

 the toxin molecule, epitoxoid with less powerful affinity, and syntoxoid 

 with equal affinity. The presence of epitoxoids would manifestly explain 

 the above phenomenon. The L dose would represent toxin + epitoxoid 

 molecules all united to antitoxin molecules, and the addition of another 

 M.L.D. of toxin would not result in there being a free fatal dose, but in 

 the added toxin taking the place of epitoxoid. Several lethal doses would 

 need to be added before the mixture was sufficient to produce a fatal re- 

 sult — that is, Lt-Lo would equal several M.L.D.'s. 



Ehrlich observed another fact strongly in favour of the existence of 

 toxoids, namely, that in the course of time the toxin might become much 

 weakened, so that in one case observed the M.L.D. came to be three times 

 the original fatal dose, and still the amount of antitoxin necessary to 

 neutralise it completely was the same as before. Ehrlich also investigated 

 the effects of partial neutralisation of the L amount of toxin — that is, he 

 added to this amount different fractions of an immunity unit and esti- 

 mated the toxicity of the mixture. He found by this method that the 

 neutralisation of the toxin did not take place gradually, but as if there 

 were distinct bodies present with different combining affinities— the 

 graphic representation of the effects of the mixture not being a curve but 

 a step-stair line. Thus he distinguished proto-, dentero-, and trito-toxins 

 (with corresponding toxoids). It will thus be seen that Ehrlich regarded 

 the combination toxin-antitoxin to be a firm one, and that the neutralisa- 

 tion phenomena are to be explained by the complicated constitution of 

 the crude toxin. 



The chief criticism of Ehrlich's views has come from the important 

 work of Madsen and Arrhenius. Their main contention is that the toxin- 

 antitoxin combination is not a firm one but a reversible one, and is 

 governed by the laws of physical chemistry. For example, in the case of 

 a mixture of ammonia and boracic acid [i.e., of a weak base and a weak 

 acid) in solution, there is a constant relation between the amounts of each 

 of the substances in the free condition and the amounts in combination, 

 — the combination is reversible, so that if some of the free anlmonia were 

 removed a certain amount of the combined ammonia would become dis- 

 sociated to take its place ; further, if to the mixture, in a state of equili- 

 brium, more ammonia or more boracic acid were added, part would 

 remain free while part would combine. Accordingly, if toxin and anti- 

 toxin behaved in a similar manner, an explanation of the Ehrlich pheno- 

 menon would be afforded. Madsen and Arrhenius have worked out the 

 question in the case of a great many toxins, and find that the graphic 

 representation of neutralisation is in every case a curve which can be 

 represented by a formula. 



It should be noted in connection with this controversy that 

 there are two questions which may be independent of each other, 



