DISCUSSION OF ZIRKLE'S AND TOBIAS' PAPERS 385 



three terms should be kept distinct for niaxium clarity in dealing with radio- 

 biological phenomena. The target concept assumes that, in a series of radiation 

 experiments, it is possible to calculate, from a knowledge of the amounts of 

 energy absorbed and the numbers of biological events of a particular kind which 

 result, the actual volume of the structures in which the molecular changes re- 

 sponsible for the given effects have taken place. The "multiplicity-of-hit" con- 

 cept presupposes that, because of the fundamentally discontinuous nature of 

 radiation absorption, it is possible to determine from the shape of the dose-effect 

 curve the number of such elementary processes which are necessary for a single 

 biological result of the given kind to be produced. Finally, the idea of direct vs. 

 indirect action implies that it is possible to determine whether the primary acts 

 of energy absorption take place within molecules of the medium which may then 

 interact with the cellular components in a secondary reaction. It is important 

 to note that these concepts are, to a considerable extent, independent, and that 

 in a particular experiment any or all of these conditions may be inoperative. For 

 example, the theoretical formulation given by Tobias for his extremely inter- 

 esting experiments actually depends only on the validity of his determination 

 of the difference in number of hits required to inactivate the haploid and poly- 

 phoid forms. 



Consider first the target theory. The data from a series of radiation experi- 

 ments enable one only to estimate the probability for a certain biological event 

 as a result of a given radiation experience. If this probability is uniform for all 

 the members of the biological population, it will be completely determined by 

 three factors : the average radius of migration of any disturbance which is created 

 by the energy absorption and which may produce the final biological action if 

 it reaches a susceptible site before its energy has been dissipated; the average 

 volume of all the sites in which the specified change can occur; and an efficiency 

 factor which tells how often success attends the absorption of energy within the 

 zone just defined. This efficiency factor may vary over very wide hmits, as- 

 suming values either greater or smaller than 1. As an extreme example, in the 

 reaction between Ho and C " induced by irradiation with alpha particles, this 

 factor has a value of more than 1000. Thus, the volume of a "target" calculated 

 in this very simple system would have no relationship whatever to the actual 

 space occupied by any of the atoms or molecules taking part in the reaction. 

 The conventional calculation of a sensitive volume in a radiobiological change 

 can be meaningful only if it can be known that the efficiency coefficient is close 

 to unity, and even in that case the value obtained will represent an average 

 volume equal to the sum of the actual "targets" plus the diffusion space of any 

 reactive intermediates. 



In this connection, too, it is necessary to consider that the same biological end 

 results may be achieved by several different mechanisms, particularly when the 

 action involved is something as complex as cell death or reproductive failure. 

 Whenever the biological effect which is observed can result from a number of 

 different atomic and molecular events, the overall probability is a composite 

 value of geometrical and chemical parameters of each pathway, and its expres- 

 sion in terms of a physical volume can be most misleading. 



