BACTERIAL POISONS 43 



may explain the frequent failure of therapeutic success attending 

 the injection of tetanus antitoxin after the symptoms of the disease 

 have set in, since in such cases the poison is already distributed to 

 the nerves and is largely inaccessible to the antitoxin. They also 

 have pointed a way toward a more hopeful therapy, namely, the 

 method of injecting the antiserum directly into the nerves about the 

 point of injury. It is not surprising, however, in view of the stated 

 facts, that even this is unsuccessful when done at too late a time, 

 after a considerable amount of poison has already passed above the 

 point of injection to the spinal centers. 



Such selective action on the part of the bacterial poisons is en- ^- 

 tirely analogous to the similar specific action of alkaloids, narcotics, 

 and other drugs. In order that the poison may act upon a cell we 

 must, of course, assume that it has either chemical or physical affin- 

 ity for this cell. The problem, as many writers have pointed out, is 

 strongly analogous to that of tissue staining. A dye must be able to 

 form a chemical union with the cell or it must be soluble in the cell 

 substance in order to stain it. The chemical difference between cells 

 is a delicate one and not often definable by our present methods. We 

 can obtain an insight into the principles probably underlying selec- 

 tive action only by inference from the relation between the chemical 

 constitution of drugs or their physical properties, solubility, etc., and 

 their respective tissue affinities. These problems are difficult and, to a 

 large extent, obscure. They cannot be directly investigated upon 

 bacterial poisons since these are themselves of chemically unknown 

 nature. But the study of drugs of known constitution has revealed 

 certain definite relations of this kind which have furnished analogies 

 from which the general principles of selection in bacterial poisons 

 can be surmised. 



It is a well-known fact to pharmacologists that there is a definite 

 relation between chemical structure and toxicity. Fraenkel 44 ex- 

 presses it as follows : "By the addition of identical atom groups in 

 an identical manner, similarly acting substances are obtained." He 

 cites the well-known example of curare ; whichever the path by which 

 this poison is injected it leaves intact the tissues with which it comes 

 in contact, but after general distribution acts specifically upon the 

 nerve endings. It had been discovered by Brown and Fraser 45 that 

 by introducing methyl radicles (CH 3 ) into molecules of various alka- 

 loids, strychnin, morphin, atropin, and others, substances were ob- 

 tained which paralyzed nerve endings, and this irrespective of their 

 previous physiological action. It appears that the combination of 

 four methyl radicles attached to the nitrogen atom (quaternary bases) 



44 Sigmund Fraenkel. "Arzneimittel Synthese," 2d Ed., Springer, Ber- 

 lin, 1906. 



45 Brown and Fraser. Trans. Eoyal Soc. of Edinburgh, 25, 1868, cited 

 from Fraenkel. 



