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DISCUSSION 



Alexander: I think we are extremely fortunate that in the days when 

 the indirect effect was not well understood Dr. Dale happened to choose 

 the particular enzyme systems which he has described, because this 

 enabled him to put the indirect effect on the sound basis which we now 

 take for granted. If he had used other proteins or, as criteria, changes 

 other than inactivation of enzymes, then the effect of concentration and 

 the relation with dose would have been much more complicated. When 

 solutions of protein — we have studied serum albumin and lysozyme — 

 are irradiated in dilute solutions, aggregation occurs and units of very 

 much larger molecular weight are formed. There is no simple relation- 

 ship between the dose or protein concentration and size of the aggregates 

 formed. This often exceeds several million and with higher doses the 

 whole material becomes quite insoluble. All these molecules which form 

 part of the very large aggregate have, in a sense, been removed from 

 the bulk solution, but are not necessarily enzymatically inactive. De- 

 pending on the method of test, very strange dose-relationships between 

 radiation effect and /or concentration may be observed. Changes in 

 ionic strength can alter critically the aggregation phenomena and thus 

 influence the radiation effect in a way which cannot be explained from 

 simple consideration of indirect action. 



The second point which I want to make is that for these aggregation 

 phenomena direct action is remarkably efficient, i.e. if we irradiate 

 serum albumin dry, and then dissolve it up and measure the amount of 

 change which has occurred, we find that direct action is remarkably 

 great. Six electron volts (or a G value of 18) is sufficient for the dis- 

 appearance of a protein molecule and its shift into an aggregate; if we 

 were choosing this as a criterion, we would find on Dr. Dale's histogram, 

 giving the proportion of direct and indirect effect at different concentra- 

 tions {see page 27), that the direct effect would be the most important 

 at the local concentrations of proteins encountered in cells. 



My last point concerns the attack on the tyrosine in proteins. Wlien 



