334 SPECULATIONS ON CELLULAR ACTIONS 



stitiiting the beginning of the story. It accordingly would seem that 

 certain (possibly numerous) events must occur between the primary 

 energy transfer and the end effect. The time interval that comprises 

 these events is usually termed the "latent period" — something of a 

 misnomer because this period is obviously one of important activity. 

 So far as I have been able to learn, for no radiobiological action do we 

 have any direct and certain information about the nature of the events 

 of the latent period. However, for some actions we have considerable 

 suggestive and apparently pertinent information; and when we reflect 

 that, if we could discover and connect the main events of the latent 

 period, we would have substantially complete understanding of radio- 

 biological action, it seems worth while to attempt a systematic descrip- 

 tion of our ignorance, using the suggestive information as a guide for our 

 speculations. Such an attempt will be my chief concern in this paper. 

 First let us briefly review the currently available facts. 



Contributions of Radiation Physics and Chemistry 



Physics furnishes information about the amount of energy transferred. 

 Let us consider an x-ray dose of 10,000 r, which will produce many drastic 

 cellular effects. This corresponds to about 840,000 ergs (or 0.020 cal or 

 5.2 X 10^^ ev) per gram of ordinary soft cellular substance. Such a 

 small amount of energy per unit mass, if delivered in the form of heat, 

 would of course have no deleterious effects. If we assume that the 

 average amount of energy required to produce an ion pair in the cell is 

 the same as that in air (32.5 ev), we find that the dose of 10,000 r will 

 produce 1.6 X 10^^ ion pairs per gram. The number of excited but not 

 ionized molecules probably would be of the same order. Since average 

 cells contain about 3 X 10^^ molecules per gram, it is evident that 

 10,000 r activate only about one-millionth of the molecules in the cell. 

 Thus, although the ionizing particles have sufficient energy to activate 

 any species of molecule, a species represented by only a few individual 

 molecules per cell (for example, a specific type of gene) stands an ex- 

 cellent chance of escaping a direct activation. 



Physics also gives us information about the distribution of the acti- 

 vated molecules. These are not produced singly at random in the cell 

 but are localized along the tracks of the ionizing particles, the tracks 

 being located more or less at random, depending on the technique of ir- 

 radiation. In gases this is directly revealed by the Wilson cloud cham- 

 ber; and it would appear that what we se^ in the cloud chamber gives us 

 indirectly a good qualitative picture, magnified about 800 diameters, of 

 the distribution of activated molecules in tissue. The detailed distribu- 



