528 IMMUNITY 



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 result ; that is, 

 L t L 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 neces- 

 sary 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 estimated 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 dis- 

 tinct 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-, deutero-, 

 and trito-toxins (with corresponding toxoids). It will thus be 

 seen that Ehrlich regards the combination toxin-antitoxin to be 

 a firm one, and that the neutralisation 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 con- 

 tention 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 ammonia were removed a certain amount of 

 the combined ammonia would become dissociated to take its 

 place ; further, if to the mixture, in a state of equilibrium, 

 more ammonia or more boracic acid were added, part would 

 remain free while part would combine. Accordingly, if toxin 

 and antitoxin behaved in a similar manner an explanation of the 

 Ehrlich phenomenon 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 



