PROPOSALS FOR FUTURE STUDIES 355 



large, and possibly variable, numbers of decisive processes, decisive 

 entities, and perhaps even decisive states. One of our greatest needs is 

 unremitting prospecting for cellular mechanisms of a favorable tj^pe. 

 By a favorable mechanism I mean one in which m/r and n/s are very 

 small integers and are constant from cell to cell, in which m/r, n/s, and 

 h can be modified by various factors, and in which the decisive state 

 either is identical with the end effect or is separated from it by relevant 

 processes none of which allows distortion of the dose-effect relations.* 

 Intensive study of a few such mechanisms might do for cellular radio- 

 biology what the exploitation of the simple line spectrum of hydrogen did 

 for spectroscopy. 



Between the beginning and the end of the mechanism we have the 

 great gap known as the latent period. Here we face the staggering prob- 

 lems of identifying the physical and chemical natures of the relevant and 

 competing processes, of determining their sequence and where they oc- 

 cur, and of working out the quantitative relations existing among them. 

 As pointed out earlier, it appears at present that our readiest weapons 

 for attack on these problems are radiation chemistry and exploitation of 

 the factors which modify dose-effect relations. 



In our present ignorance, it is impossible to state just what we need 

 in the way of radiation chemistry. However, it is clear that we need 

 much more information about the processes induced by radiation in 

 aqueous solutions of cellular constituents. For instance, it would be use- 

 ful to have reasonably good values for the lifetimes of H and OH in pure 

 water and in the presence of various solutes, and to know the diffusion 

 constants for these radicals. Moreover we need from biochemistry some 

 methods by which we can demonstrate and even measure abnormal proc- 

 esses occurring in the irradiated cell. This is, of course, an exceedingly 

 difficult requirement to meet. 



In the exploitation of the modifying factors, the two elementary pro- 

 cedures involved in every experiment are measurement of dose and meas- 

 urement of end effect. Both these measurements should be rapid and 

 reproducible, and each should be expressible in some one unit under all 

 experimental conditions. In both cases the present methods leave some- 

 thing to be desired. Dose measurements are usually fairly rapid and 

 reproducible, but at present we have no satisfactory, to say nothing of 

 standard, methods of measuring doses of all the high-energy radiations 



* The ease with which distortion might occur can be illustrated with Fig. 1. If, 

 despite irradiation, some of the cells should contain enough of the relevant enzyme 

 to permit cell division to occur, even though the relevant gene were inactivated, the 

 count of survivors would be too high and the dose-effect relations accordingly dis- 

 torted. 



