Second, the thermal inactivation constants for these materials are 

 completely different from those that are obtained in the wet state. If you heat- 

 inactivate, under the condition that we usually use for work on a virus or an 

 enzyme, you will find that the inactivation is characterized by a low entropy of 

 activation, zero or negative. This seems to be characteristic of inactivation in 

 the dry state, and you can show a very striking contrast between how the mate- 

 rial behaves as far as heat is concerned. This we look on as an auxiliary sort 

 of evidence. Whether any biological material can be considered as absolutely 

 dry is doubtful; but that radiation can migrate via the medium of water under 

 these conditions I would strenuously deny. I don't see how it can. 



Now I should like to say a little about what I call a theoretical approach 

 to radiobiology . Looking back, the strongest needle I put into the conference 

 last year was in the form of a somewhat impassioned plea for recording of all 

 the effects that radiation produces. I felt that we were relieved when we learned 

 that radiation can produce an effect on water and that this in turn can produce 

 an effect on the cell, and I tried to indicate that that relief was perhaps a little 

 excessive, that there had to be a consideration of all the effects that radiation 

 can bring about, and that among these effects, the direct action on the biological 

 components of the system was most important. 



I should like now to suggest that it is altogether possible to formulate 

 a theoretical approach to radiobiology in the following terms. We can say what 

 the parts of the cell are and list them, not just talk about them in absolute gen- 

 eralities but list them. Then we can inquire as to what the radiation action is 

 on these parts separately. Having done that, we can inquire as to what function 

 these parts have in the work of the cell and then we can synthesize a probable 

 explanation for radiation action. 



I am amazed, to tell the truth, that this is being done so little. We 

 have tried it in what I thought was an amateurish way, and in the progress re- 

 ports of our work we have, each year, written a sort of statement as to what 

 we think this sort of theoretical radiobiology should be like. Among the things 

 that we have discussed has been the relative proportion of direct and indirect 

 action based solely on this theoretical approach. 



The fact is that when you get into this theoretical approach you become 

 acutely aware that a lot of data that you need are not only unknown, but are not 

 even being sought. In the first place, it is urgently necessary to know the life- 

 times of all the products of radiation action everywhere: not only lifetimes in 

 water, but lifetimes in the solid state, and lifetimes of things such as HO^ and, 

 in fact, any agent that can be thought of as being involved in the response to ra- 

 diation. The study of these lifetimes is at least not clearly visible in the litera- 

 ture. 



In this connection. Dr. Smith, working at Yale during a leave of ab- 

 sence from the Department of Radiotherapeutics at Cambridge, conducted, I 

 thought, a very nice experiment along the line of the one first used by Dr. 

 Mazia. He made a measurement of the lifetime of radicals in water (3), and 

 came out in two cases with a magnitude of about 3 microseconds. Just this one 

 value alone completely modifies Lea's own speculations as to the relation be- 

 tween direct and indirect action. Lea adopted, without measurement, a figure 

 of 0. 3 microsecond. Clearly, when you have a lifetime as low as 0. 3 micro- 

 second, a radical formed far away from the important biological molecule 

 would not be effective. It will hit something unimportant before it gets there, 

 and the unimportant thing may even be the thing that causes it to recombine as 

 measured in these experiments. A figure 10 times greater modifies this. 



