THE ORIGIN OF ANTITOXIN THE SIDE-CHAIN THEORY III 



in others this is extremely slight, or not more than that due to 

 the injection of any so-called " inert " fluid into that situation. 

 Consider in this connection the reactions of certain animals to 

 tetanus toxins. When this substance is injected into guinea-pigs, 

 the effect is practically the same whether the injection is sub- 

 cutaneous or intracerebral. In rabbits, on the other hand, 

 a very much smaller dose suffices to kill if injected into the brain 

 than is necessary if the injection is subcutaneous. Now rabbits 

 are less susceptible to tetanus toxin than are guinea-pigs, requiring 

 relatively larger doses to bring about a fatal issue. On the other 

 hand, it is easier to prepare tetanus antitoxin from rabbits than 

 from guinea-pigs by the injection of tetanus toxin, though difficult 

 in both cases. Compare these results with those obtained from 

 fowls. These animals are resistant against tetanus toxin (except 

 in absolutely enormous doses) when injected subcutaneously, but 

 are easily affected when the injection is made into the brain 

 or subarachnoid space. The probable explanation turns on the 

 varying affinity of the toxin for different parts of the body. We 

 may assume in all cases that the tetanus toxin acts as a poison 

 only on the brain and spinal cord, and that in the guinea-pigs it 

 has practically no affinity for the subcutaneous tissues, and 

 that when injected into this situation it passes ultimately to the 

 brain almost without loss. In rabbits some of the toxin is united 

 to the tissues, and only a part reaches the central nervous system, 

 whilst in fowls the affinity of the tissues for the toxin is so great 

 that the whole of the latter is absorbed and the brain escapes 

 injury. Now it is practically impossible to obtain antitoxin by 

 injecting toxin into the guinea-pig, difficult to obtain it from the 

 rabbit, but easy to obtain it from the fowl, so that it would appear 

 that it is the tissues which are not especially vulnerable to the 

 toxin which yield it. If this is true, it is no argument against the 

 validity of the side-chain theory. It simply indicates that the 

 cells which are profoundly affected with toxin are thereby 

 rendered unable to produce antitoxin in virtue of the toxic action 

 of the poison, the other conditions being suitable. We know this 

 to be the case from the fact that we can produce tetanus 

 antitoxin from guinea-pigs as a result of the injection of toxoid, 

 which we must assume to unite entirely with the cells of the 

 central nervous system, just as the toxin does, though without 

 injuring them. We may assume, therefore, that antitoxin is 

 produced from cells which unite with toxin or toxoid, but which 



