INTERMEDIATE ACTION THEORY 363 



within the cell and that one or more "events" have to occur within this 

 volume as a result of irradiation to produce a' lethal effect, a mutation, 

 or some other measurable change. A number of authors, particularly 

 Lea (18), have associated the "event" with the production of a single 

 ion pair. A recent review of the target theory has been published by 

 Atwood and others (19, 20, 21). Although recently doubts were raised 

 by some workers, for example Opatowski (22), as to the validity of the 

 single-event hypothesis in radiogenetics, others, for example Wijsman 

 (23), have strengthened the mathematical basis of the single-event 

 theory. Early success of the hit theory was due to finding survival 

 curves for various organisms which were exponentially decaying functions 

 of the dose (one ion pair in sensitive volume) and others which followed 

 the multihit curves (14). However, closer examination a number of 

 years ago revealed some discrepancies, not easily explainable in the 

 original form of the theory. For example, the theory predicted a sharp 

 decrease in biological effects of radiations when radiations of high specific 

 ionization were used. Many experiments were available, however (1, 24), 

 which showed opposite dependence on REL from the one expected. 



Some of the proponents of the target theory have identified the target 

 with the size of a gene (25, 18). Calculations based on dose-ef!"ect 

 relationships have come within a small factor of the size of objects which 

 resemble genes. How^ever, as early as 1936 Timofeeff-Ressovsky (26) 

 and Delbriick questioned this hypothesis. Sommermeyer (27) has 

 postulated that ionization within a gene may produce mutations with a 

 probability considerably less than unity. Lea and Catcheside (28) 

 assumed that an ionization outside a gene may also produce mutation. 

 Fano (29) reasoned that, if the dose-effect relationship is a single expo- 

 nential, the passage of a single ionizing particle must be sufficient to 

 cause mutation; therefore, a single ionization, or at most two, or a cluster 

 of ions, is sufficient to cause mutation. The question to be resolved, 

 then, remains the probability with which this process may occur. At 

 this symposium Fano gave a lucid presentation of the present status of 

 the theory of ion-cluster formation. 



Intermediate Action Theory 



Independent of the hit theory, certain biochemical effects on en- 

 zymes may be explained on the basis of the "intermediate action" 

 theory of Dale (30). He and others, notably Barron and his associates, 

 have conclusively shown that the biochemical action of radiations in 

 aqueous solutions depends greatly on the interaction of radiations with 

 water. Physical chemistry of the radiation effects on solutions has 



