R. D. HOTCHKISS 



nism" in the table all in the theoretical stage, but we have little more 

 than a crude terminology with which to describe them. Some detail 

 could be given under the mechanism of respiratory and fermentative 

 catabolism, but almost none under any of the anabolic, energy- 

 utilizing mechanisms. The examples of agents given in the last 

 column are, at best, somewhat questionable. Nevertheless, it is hoped 

 that the table will serve to demonstrate that it is almost inexcusable 

 that, when considering the mode of action of new or proposed drugs, 

 we have all almost universally limited ourselves to a consideration of 

 possible eflfects of the drug upon some aspect of the respiratory or fer- 

 mentative degradation of foodstuffs. As heating engineers trying to see 

 why the house is cold, we have been shortsightedly preoccupied with 

 the flicker of the furnace fire and have never bothered even to feel 

 the pipes and radiators upstairs. 



Throughout the above, the viewpoint has been somewhat in- 

 sistently shifted back and forth from the planning of new chemo- 

 therapeutic agents to studying the action of the old ones. It is not 

 pretended that empirical ways of uncovering new agents have been 

 outmoded, but we do maintain that the most successful empiricism 

 will always use, consciously or unconsciously, what reasonable hy- 

 potheses are available. And the drugs are among our best cy to- 

 chemical reagents: they can give us information about the reactivities 

 of living cells, and this information will surely help us to foresee the 

 probable behavior of new drugs. Strictly speaking, there can be no 

 study of relation between pharmacological action and chemical struc- 

 ture and there can be no study of mechanisms of drug action — there 

 can only be the study of drug-protoplasm interaction. 



Selected References 



LOCALIZATION OF CELLULAR CONSTITUENTS 



Caspersson, T., "Studies on the protein metabolism of the cell," Naturwissen- 



schqften, 29, 33 (1941). 

 Claude, A., Hogeboom, G. H., and Hotclxkiss, R. D., "Distribution of enzymes 



in cytoplasmic constituents," to be published. 

 Bounce, A. L., "Further studies on isolated cell nuclei of normal rat liver," 



J. Biol. Chem., 151, 221 (1943). 

 Gomori, G., "The distribution of phosphatase in normal organs and tissues," 



J. Cellular Comp. Physiol., 17, 71 (1941). 



