October 6, 1916] 



SCIENCE 



487 



Many other examples might be cited in 

 which organs which are apparently not 

 related, either morphologically or in func- 

 tion, react to poisons in quantities which 

 are indifferent to the tissues in general. 

 And this reaction in common can only be 

 interpreted to mean that there is some sub- 

 stance or group of related substances com- 

 mon to these organs. The reaction may 

 differ in character; thus a drug which ex- 

 cites one organ to greater activity may de- 

 press another, but the fact that it has any 

 effect whatever on these organs in prefer- 

 ence to the tissues in general indicates some 

 special bond between them, some quality 

 which is not shared by the unaffected parts 

 of the body. I have, therefore, not differ- 

 entiated between excitation and depression 

 in discussing this relation. One is tempted 

 to utilize the nomenclature introduced by 

 Bhrlich here and to state that the common 

 reaction is due to the presence of hapto- 

 phore groups while the nature of the re- 

 action (excitation or depression) depends 

 on the character of the toxophore groups. 

 But while these terms may be convenient 

 when applied to poisons whose chemical 

 composition is altogether unknown, they 

 merely lead to confusion when the question 

 concerns substances of ascertained struc- 

 ture. Thus, as Dale has pointed out, it is 

 impossible to suppose that such substances 

 as tetramethyl-ammonium and tetraethyl- 

 ammonium owe the difference in reactions 

 to specific haptophore groups in the one 

 which are absent in the other. It seems 

 more probable that in this instance and in 

 others the difference in the effect of these 

 bodies in the tissues arises from differences 

 in the behavior of the molecule as a whole 

 than in differences in the affinities of its 

 special parts; that is, that the action of 

 these poisons is due to their physical prop- 

 erties rather than to their chemical struc- 



ture, although this, of course, is the final 

 determining cause. 



In the same way the common reaction of 

 tissues, which I have so far ascribed to their 

 possessing some substance in common, may 

 arise from community of physical relation- 

 ship, and I wish to avoid the implication 

 borne by the word "substance," which I 

 have used in the widest sense, such as is 

 justified perhaps only by its historical em- 

 ployment in theological or philosophical 

 controversy. The reaction of living tissue 

 to chemical agents may arise from a specific 

 arrangement in its molecule, but may 

 equally be attributed to the arrangement of 

 the molecules themselves. And the curious 

 relationships in the reactions of different 

 tissues may indicate, not any common 

 chemical factor, but a common arrange- 

 ment of the aggregate molecules. "We are 

 far from being able to decide with even a 

 show of probability which of these alterna- 

 tives is the correct one, and my object to- 

 day has been to draw attention to these rela- 

 tionships rather than to attempt their elu- 

 cidation. Hitherto the speculative pharma- 

 cologist has been much engaged in com- 

 paring the chemical relationship of the 

 drugs which he applies to living tissues; 

 much useful knowledge has been inciden- 

 tally acquired, and the law has been formu- 

 lated that pharmacological action depends 

 directly on, and can be deduced from chem- 

 ical structure. This view, first elaborated 

 in this country, has in recent years shared 

 the fate of other English products in being 

 advertised from the housetops and prac- 

 tically claimed as the discovery of more 

 vociferous investigators. On examining the 

 evidence, old and new, one can not help 

 feeling that attention has been too much 

 directed to those instances which conform 

 to the creed, while the far more numerous 

 cases have been ignored in which this so- 

 called rule fails. The difficulties are very 



