276 R. H. MOLE 



MOLE: This is partly a question of the meaiung of words. "SimUar" must mean to some 

 extent additive mustn't it? Dissimilar, anjnvay, means non-additive. 

 CASAEETT: I think Dr. Mole has pomted out very well many of the vagaries and the 

 difficulties of using LDgg and Ufe-shortening in judging ageing processes, points which I 

 emphasized myself. In regard to the differences in life-shortening when one irradiates 

 animals at different ages, I would like to take up the suggestion of long development time. 

 I think that when you irradiate older animals there is not enough time to get the full 

 development of the Ufe-shortening potential of the dose. This is something to consider 

 besides those pomts you brought up. I would also like to ask whether Dr. Mole thinks that 

 all of the causes of death of the irradiated animals are entirely induced by the radiation 

 and aU of the causes of death m the non-irradiated animals are entirely brought about by 

 agemg processes, if he says there is nothing additive. If I may clarify this, one can take 

 the point of view that m irradiated animals each of the lesions which kiU are induced 

 separately bj^ the radiation given, but it seems much more sensible to regard the uni- 

 formities of the response, taking fuU account of the non-uniformities that exist, as 

 evidence of some generalized additive non-specific process that aifects the diseases and 

 causes of death in both populations. 



MOLE: I don't see how one can possibly say that everything in the irradiated animal is due 

 to the irradiation, ever^-thhig in control animals to sometliing different. Also, is death ever 

 due to a non-specific cause? If pathology and post-mortems are taken seriously a lot of 

 lesions wiU be found. Now a really competent human pathologist can put his finger on 

 the cause of death m between one-quarter and one-third of a non-specific collection of 

 human post-mortems. In the remainder there will be many lesions but it would be hard to 

 say which is the cause of death. (It's perhaps much easier to say that post-mortem exam- 

 inations show you what it's possible to Uve with.) I tliink that to equate ageing just with 

 death-time is the basic mistake. We know that ageing of anything is a progressive process 

 and death can only happen once. It often happens m radiobiology, since survival time 

 can be scored so easily, that a teclmician can do it for you. Then you can sit at your desk 

 and do some calculations, but I don't think that reaUy has any bearing on the subject. 

 You've got to try and do the best you can to decide what did kill the animals. Now 

 suppose you confine your attention to those tilings which quite clearly do kill, like 

 leukaemias, or tumours which lead to haemorrhage or to gross mfection and thmgs like 

 this. When you find regularly a higher incidence of such kinds of lesion in irradiated 

 animals than in control animals, I don't see how you can avoid concluding that irradiation 

 has specifically produced particular forms of disease. The fact that the same disease 

 occvu's in control animals is exactly what you would expect because the cells of any one 

 organ of the body can react only in particular kinds of way. It doesn't matter what the 

 agent is wliich starts a process off, the reaction must depend on the nature of the cells 

 and the organs. 



CASABETT: I think you are putting emphasis on life-termmating diseases, on tliis one 

 event rather than on the pathogenesis of the disease. 



cottier: I would stress Dr. ]\Iole's view that tliis Hfe-shortenmg is not necessarily 

 identical with ageing. If you compare the histopathological picture of spontaneously 

 dying mice or mice killed at several mtervals after irradiation throughout life-span there 

 is a discrepancy insofar as a specific change hes in the vascular and other changes wliich 

 progress very mcely durmg Ufe, Uke calcification of rib cartilage or calcification of 

 tendons or of mtra vertebral discs. They foUow the same course hi irradiated as m non- 

 irradiated animals. Tliis is just one example of a discrepancy between these two and I 

 think one really has to consider carefully what the causes of death are in these irradiated 

 animals. 



