72 SENESCENCE AND REJUVENESCENCE 



is an exact measure of its total metabolism at that moment. If the 

 cyanides or other narcotics act directly on the oxidation processes, 

 a general relation between susceptibility and oxidation must exist, 

 but while the oxidations are fundamental metabolic reactions, and 

 serve in a general way as a measure of metabolic activity, a con- 

 siderable range of variation in the different reactions which go to 

 make up the the metabolic complex may undoubtedly exist. If, on 

 the other hand, these substances act on the substratum and affect 

 the metabolic reactions only or primarily through the substratal 

 changes, susceptibility must be related to the general average of 

 metabolic activity, but certain reactions may be more affected than 

 others in the early stages of action, though sooner or later the 

 metabolic process as a whole is retarded or inhibited. 



In concentrations of the cyanides or other narcotics, which not 

 only narcotize but gradually kill, a decrease in metabolism, as 

 measured by oxygen consumption, by carbon-dioxide production, 

 by functional activity, or by other means, occurs in all cases, and 

 metabolism finally ceases. In concentrations in which death 

 occurs at times varying from a few minutes to a few hours and when 

 complicating factors are absent, the susceptibility varies directly 

 with the general metabolic rate. Conditions which increase meta- 

 bolic activity increase susceptibility, and vice versa. This method 

 of determining susceptibility I have called the direct susceptibility 

 method (Child, '130). 



The capacity of organisms to acclimate themselves to, or acquire 

 a tolerance to, narcotics has long been recognized: this capacity is 

 well illustrated by the high degree of tolerance for alcohol, cocaine, 

 etc., developed in the human organism. In concentrations of nar- 

 cotics which are sufficiently low to permit partial, but not complete, 

 acclimation, we find that the relation between susceptibility and 

 metabolic rate undergoes reversal. In such concentrations the 

 individual or part with the higher metabolic rate becomes more 

 readily and more completely acclimated and therefore lives longer 

 than the individual or part with the lower metabolic rate which is 

 unable to acclimate itself and so dies earlier. This relation between 

 metabolic rate and capacity for acclimation is to be expected, for 

 the occurrence of acclimation evidently depends on conditions in 



