352 GENERAL DISCUSSION 



berenbltjm: Mr Chairman, you say that I have been very cautious. I am afraid, on the 

 contrary, that I have gone much further than I should have done with results which were 

 from experiments not completed. If these results are confirmed and extended; if it is 

 established that by radiation you can produce witliin 24 horn's something wliich is 

 transmissible; and if the transmissible entity proves to be not a living cell not a complete 

 virus, yet somethmg which becomes leukaemogenic when urethane is given subsequently, 

 then we wUl certainly have a new system m leukaemogenesis. We have the feeling that the 

 earh'er, exciting work of Kaplan and his colleagues seems to have come to an end. We 

 hope that the two-stage system might serve as a new technique, to permit us to explore the 

 problem further. 



BACQ: Can you tell us if there is some pecuhar property of urethane which can be linked 

 with that promoting effect? 



berenblum: We have also been following up the problem from the urethane angle and 

 whereas from the biological angle it seems to be straightforward, from the metabolic 

 angle is the very opposite. Whatever you ihid out about how urethane acts, the results 

 are always negative. We have, for instance, failed to confirm Rogers' claim of an inter- 

 mediate metabolite of urethane, and were able to account for his results as being due to 

 residual unchanged urethane. His further claim that urethane might act by mterfering 

 with the biosynthesis of pyrimidine also led to negative results in our hands. My colleague. 

 Dr. Kaye, went to the trouble of testing urethane on each of the individual metabolic 

 steps in the biosynthesis of pyrimidine and found that not a single one was hindered by 

 urethane. 



BACQ: Is it true that urethane increases the tolerance to a homograft if applied to the host? 

 cottier: I should like to mention just one point, very Uttle has been said about immuno- 

 logical processes in connection with carcinogenesis and leukaemogensis. It would be 

 worthwlule to check the action of urethane on immune response. 



mole: Tliis is a biological footnote to what Berenblum has said. There have been some 

 recent experiments which suggest that there is another sort of breaktlu-ough in the Kaplan 

 system. In Kaplan's experiments the thymectomized irradiated animal had the leukae- 

 mogenic potentiality restored by a subcutaneous graft of thymus. It has been recently 

 reported that putting the thymic graft mto the spleen or into the capsule of the kidney 

 does not restore the leukaemogenic capacity of the animal. (O'Gara, R. W., and Ards, J. 

 (1961). J. nat. Cancer Inst. 27, 299.) 



lajnierton: Perhaps, ]\Ii- Chahman, the action of urethane may be non-specific, in which 

 case to look for specific biochemical pathways will get nowhere and m fact what you 

 have to do is look for its damagmg action on the thymus or on the marrow and recognize 

 that the effect may be via some essential cell damage or cell destruction. 

 berenblum: It means really widerdng our scope of search for substances that have the 

 same properties. It is interesting to note that other anaesthetics, or other analogues of 

 iirethane, do not act in the same way. So, from the chemical-structure point of view, 

 there appears to be no correlation. 



BACQ: I know that our colleague. Professor Mayneord, has a beautiful quotation about 

 life-span with which to conclude tliis Symposium and, if no-one has any further con- 

 tribution to make, I wiU ask liim to give it. 



MAYNEORD: One of the most distmguished workers in tliis subject was no less a person 

 than the great Lord Chancellor, Francis Bacon, who WTote a book ''Historia Vitae et 

 Mortis" pubhshed in 1623. There is one sentence I would like .to quote: "Toucliing the 

 length or shortness of life in beasts, the Knowledge which may be had is slender, the 

 Observation neghgent, the Tradition fabulous." 



