304 O. C. A. SCOTT 



right direction for protection and from this we infer, as Dr. Scott emphasized, that the 

 data were at best suggestive; we certainly didn't see anything like a two-fold reduction of 

 radiation dose under the conditions of this experiment that we would have expected if 

 AET had protected against leukaemia induction to the same extent as it protected against 

 acute lethahty. As regards the way in which you try to correct the incidence of leukaemia 

 or any other disease to adjust for intercurrent mortaUty from other causes, I have very 

 serious doubts as to whether this kind of statistical juggling really gets us anywhere. 

 There is a substantial latent period, or induction period, and then the disease occurs, the 

 cumulative incidence increases as the population ages. Obviously, if you start kiUing 

 animals before the disease appears not as many animals are at risk and so not as many 

 would have developed the disease, even though the radiation were in fact acting on that 

 tissue in a carcinogenic maimer. What we have done, Dr. Alan Kimball and I, is to try 

 trunking the probability by sub-dividing the population and adding at the different 

 periods under consideration, animals to compensate for those that were lost from other 

 diseases and to calculate the probability of the incidence of the disease assuming the 

 population at risk had not been decimated. This presupposes independent probabilities 

 apart from the interaction of various lesions within the animal. We must not assume that 

 all tissues are independent of one another and that if we simply had larger numbers of 

 animals we would see a larger number of tumours irrespective of effects on other organs. 

 So I don't really know how much one could trust this sort of thing. I was interested to 

 see that Prof. Rotblat and Dr. Lindop used a similar kind of statistical correction and 

 perhaps he would like to comment on this point too. In regard to effects on leukaemia 

 induction and life-shortening, we have had under observation now, a large number of Fl 

 hybrids of this strain derivation. These preliminary observations have been presented 

 before. I show them again to emphasize that when one compares the extent of life- 

 shortening calculated as the percentage of survivors per roentgen, then it would seem 

 that animals exposed to LD5Q (30 days) when irradiated in the presence of MEG do show 

 substantially less life-shortening per roentgen than animals given radiation alone at the 

 LD50 (30 day) level without any protective treatment. 



Now the complication here is that you can't really give this kind of a dose without 

 protection and have any animals alive at the end of 30 days to follow, so unless you are 

 willing to assume that there is in fact this kind of a life-shortening effectiveness of irradia- 

 tion over the entire dose-response curve then you really don't know that this is, in fact, 

 protection. What I am saying is that if one were to plot median survival time against 

 dose and do an experiment and show that curve was in fact linear after 1,400 r, then 

 this would be mdicative of protection, but it could well turn out that the curve flattens 

 out anyway so that there is less life-shortening per roentgen at a dose-level of this order 

 of magnitude without any protection. So we have extended the experiment to include 

 animals at 700 r with and without AET, bone-marrow, or both and 500 r with, and 

 without the treatments, and then another group of unprotected animals at about 350 r, 

 and before I came away from Oak Ridge, Dr. Carlsgrove told me that there was in fact 

 an appreciable dose reduction at the 700 r level but that, for the animals at 500 r, the 

 dose reduction was not significant. This would suggest, perhaps, that in tliis strain- 

 combination under this kind of experimental condition, dose-reduction may be dose- 

 dependent; the amount of protection one gets may vary with the radiation dose-level. I 

 think this simply points to the need to do experiments of this sort to compare curves 

 and not single points on a curve; unless you have a dose-response curve you really don't 

 know whether your treatment is moving it one way or another. 



ALEXANDER: It seems to me that in your data you had one indication which suggests 

 that this way of handling the data isn't fully justified m that bone-marrow also gave you 



