386 ENERGY LOSS AND BIOLOGICAL EFFECTS 



The hit theory or multiplicity concept is a method for estimating the minimum 

 number of energy-absorption acts which are required, on the average, to effect 

 the biological change under study. Its physical significance is analogous to that 

 attached to the determination of the order of a chemical reaction. Such a deter- 

 mination is used to obtain information about the number of molecules, or, in 

 radiochemical reactions, the number of separate acts of energy exchange which 

 are involved in the given process. However, caution must be exercised in draw- 

 ing conclusions from such kinetic data about actual reaction mechanisms. The 

 order of a chemical reaction can definitely determine the number of molecules of 

 each species involved, or the number of energy quanta which are required, only 

 when a single, definite reaction occurs. If several consecutive steps take place, or 

 if chains are set up, deductions concerning the actual reaction mechanism may 

 prove difficult. A complex reaction may have several radiochemical and thermal 

 steps. In this case, the observed dose dependence may only reflect the efifect of 

 the slowest step of the process. If the given end product can be achieved by more 

 than one path, the slope of the dose-dependence curve will be a complex function 

 of the various mechanisms involved. If chain reactions are initiated, a single 

 act of energy absorption may eventually produce multiple biological effects. 



Finally, the differentiation between direct and indirect action is often a very 

 difficult matter. Ionizing radiations can transfer energy to any molecule they 

 encounter. The extent to which a given effect proceeds more extensively through 

 a direct rather than an indirect mechanism will depend on the relative concen- 

 trations of the various molecular species, the probability of energy absorption 

 in each type, and the probability that such absorption will produce the specific 

 end results under study. Reactive intermediates doubtless appear in both kinds 

 of energy absorption. The separation of direct and indirect components of 

 complex reactions can be accomplished with certainty only when the inter- 

 mediates of the indirect action have fairly long half lives, so that unequivocal 

 demonstration of their action is possible. Dilution studies, demonstration of 

 protective action by various substances, and similar procedures afford only 

 inferential evidence whose interpretation may be open to question. 



These remarks should emphazise the great care which must attend an attempt 

 to interpret radiobiological phenomena in terms of atomic and molecular trans- 

 formations. Careful and detailed analysis of radiochemical kinetics in the 

 simpler biological systems is urgently needed. Such studies doubtless will 

 furnish useful models which should clarify the nature of the interactions of high- 

 energy radiations with more complex biological structures. 



Tobias: 



I agree with Puck's discussion. When a single action occurs in these calcula- 

 tions, it cannot be assumed that the receiving molecule cannot receive from 

 more than one source. 



Latarjet : 



I was very much interested in Tobias' analysis of his experimental results and 

 by the attempt to interpret them through a single genetic hypothesis. In Paris, 



