The conclusion we come to from the sort of broad theoretical approach 

 in which we consider the effects of radiation on proteins, nucleic acid, and the 

 microscopic cytoplasmic components is that direct and indirect actions are split 

 about 50:50 but that they are both variable. You can, on occasion, get a cell in 

 which only 25 percent of the action is direct, or the other way around. One 

 must not consider either of these to be the functions of radiation that are con- 

 stant. They depend on the condition of the cells and on the molecules that are 

 in them, and we have to recognize that both of these can be variable. There is 

 no question whatever about the variability of indirect action with respect to the 

 nature of the cytoplasm. 



I should like to suggest that this can also be said of direct action, and 

 this is a somewhat bolder statement than I think anybody has made in the past. 



One tremendous and absolutely vital datum is sitting, waiting to be 

 found by somebody. No one knows the ionic yield for indirect action on large 

 nucleic acid molecules. Large nucleic acid molecules obviously play a most 

 dramatic role in cellular function, particularly in any function that takes time 

 and requires the cell to develop. Yet I do not know of any work in which the 

 ionic yield for indirect action on nucleic acid molecules is given. By a nucleic 

 acid molecule, I mean one that has a biological function. I discount measure- 

 ments in which the nucleic acid is either polymerized or depolymerized without 

 a guarantee that at the same time biological function goes along with it. 



CARTER: Do you mean transforming principle? 



POLLARD: Transforming principle, for example, would be beautiful, 

 but at the moment I don't think it is pure enough to measure. 



CARTER: I think transforming principle is pure enough to measure 

 and I am surprised that Dr. Chargaff does not have the data. 



CHARGAFF: It is very difficult to say really what proportion of the 

 transforming principle you have in any nucleic acid preparation. That is one of 

 the great difficulties. We are now fractionating preparations. Maybe we will 

 know soon a little more about that. 



POLLARD: We know the yield for direct action. This has already 

 been measured in three places and the agreement is good. But we do not know 

 the efficiency for indirect action. It is not known, for example, whether it takes 

 10 ion pairs to inactivate one transforming principle molecule or, say, 1, 000. 

 Empirically, we would expect a figure of 1 , 000 but it might be as low as 1 . If, 

 indeed, it is 1 , it would be well worthwhile to concentrate on that one subject as 

 the probable single basic radiobiological action. But until we know that, the 

 basis for this theoretical radiobiology is missing. It does not seem to be an 

 impossible experiment. 



CARTER: Actually the obstacle is that Dr. Chargaff has not purified 

 the transforming principle. 



CHARGAFF: You are faced with an almost philosophical dilemma. 

 You may have between 1 , 000 and 10, 000 different species of nucleic acid per 

 nucleus, and if you equate the nucleic acids with the genes obviously you really 

 don't know what you are nneasuring. If you are measuring one transformation 

 feature, e.g. , Hotchkiss' sulfonamide factor, you don't know what proportion of 

 the total nucleic acid really corresponds to this particular activity. I think it 

 will be a long time before we will be able to answer that question. 



