BACTERIAL POISONS 43 



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 

 selective action only by inference from the relation between the chem- 

 ical 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 un- 

 known 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 

 Eraser 45 that by introducing methyl radicles (CH 3 -) into molecules 

 of various alkaloids, strychnin, morphin, atropin, and others, sub- 

 stances were obtained which paralyzed nerve endings, and this irre- 

 spective of their previous physiological action. It appears that the 

 combination of four methyl radicles attached to the nitrogen atom 

 (quaternary bases) universally possesses this paralyzing action. 

 Tertiary bases on the other hand lack this property. 



CH 



L 3 

 t< 



Ammonium lose" "Tertiary lose 



Y *i<? TnUnd FraenkeL "Arzneimittel Synthese," 2d Ed., Springer, Ber- 

 lin, lyOo. 



from Fraenk T* FraSer * Trans ' Eoyal Soc ' ? Edinb ^gh, 25, 1868, cited 



