136 Discussion 



Sacher: If mutations are considered to be molecular events, then 

 one has to ask why the molecules in the mouse mutate some thirty 

 times faster per unit time than they do in man. I have shown that 

 two physical characteristics of mammals, namely the metabolic 

 rate and the goodness of physiological regulation, account for most 

 of the lifespan variance. Some fraction of the remaining variance is 

 undoubtedly under specific genotypic control, but this is a small 

 part of the total. Thus it would appear to be true that species tend 

 to have the maximum attainable lifetimes permitted by their body 

 size and complexity of organization. 



Danielli : You suggested that there might be a standard amount of 

 metabolism which was permissible per gram of tissue before it 

 deteriorated beyond hope. Could any information about this be 

 obtained, perhaps in fish, by using a poison such as dinitrophenol, 

 which causes a good deal of useless metabolism to go on ? This might 

 enable one either to discover that the life expectancy was a function 

 of the amount of oxygen utilized in respiratory processes, or else to 

 distinguish between one type of metabolism which has an ageing 

 effect, and other types of metabolism which have not. It is probably 

 easier to keep up a constant concentration of dinitrophenol in fish 

 than it is in many other animals. 



Sacher: I have not yet had the opportunity to do such experi- 

 ments ; it would certainly be extremely productive to use metabolic 

 poisons. In warm-blooded mammals one also could replace part of 

 the basal energy production by producing heat internally with 

 radiofrequency heating. Anything that would produce a dissocia- 

 tion between the amount of metabolism and the other physical 

 characteristics of the organism would be extremely valuable. 



I would also like to determine whether one could systematically 

 yet diffusely decrease the general regulatory ability, perhaps by 

 destroying the brain to a certain degree, with sonic radiation or 

 diathermy. Can anyone suggest how a uniform controllable deterior- 

 ation could be produced which could be followed in terms of its 

 effect on survival ? 



Lindop : Could one use colchicine as a mitotic inhibitor in different 

 doses ? 



Danielli: It might have some effect, but I should have thought it 

 might be better if you could use something of the nature of a 

 cholinesterase inhibitor, or strychnine. 



Comfort: An experiment with dinitrophenol was done upon mice 

 by M. L. Tainter (1936. Proc. Soc. exp. Biol. (N.Y.), 31, 1161). Mice 

 treated over a period of time did not seem to have their lifespan very 

 much affected — certainly not in proportion to their metabolic rate. 



