based on metabolic disturbances or not. To be narrow here would be like 

 discussing only the beneficial effects of drugs and omitting the toxic actions. 

 Of course, space limitations make it impossible to treat all these actions 

 equally, and I have tried to emphasize those actions in which a disturbance 

 of metabolism is the most likely mechanism. But we must never ignore the 

 possibilities of other mechanisms with any inhibitor, particularly those 

 reacting with groups on proteins and other cell components. The mercurials 

 offer an especially clear example of enzyme inhibitors producing character- 

 istic effects on many tissues (e.g. kidney, heart, central nervous system, 

 liver, muscle, etc.) and where not a single action can be definitely corre- 

 lated with a mechanism involving enzyme inhibition. Nevertheless, with 

 further improvements in techniques and more knowledge, it is quite pos- 

 sible that in the future at least some of these actions will be related to 

 effects on enzymes. To be perfectly honest, at the present time we cannot 

 say in the majority of cases just how substances called enzyme inhibitors 

 act to produce their interesting and often clinically or industrially important 

 effects on microorganisms or tissues, and it is necessary to realize our igno- 

 rance so that progress in understanding may take place. Inhibitors do 

 produce some very intriguing effects on tissue function or in whole animals, 

 and many of these effects are unknown to those who look upon inhibitors 

 merely as biochemical tools; so by reading of these effects some may be 

 activated to study the ultimate causes in greater detail. Incidentally, 

 since inhibitors will be used more and more frequently in animals, infor- 

 mation on dosage ranges to produce various effects may serve a very prac- 

 tical purpose. 



I would like to express my gratitude to those who have written to me 

 saying they have found the first volume of interest or of some value to 

 them, who have sent me unpublished manuscripts or difficultly obtainable 

 material, and who have given me encouragement during those periods 

 when I sincerely wished I were in a monastery in Kyoto. 



J. Leyden Webb 

 November, 1965 



