i6o 



NATURE 



[November 30, 191 1 



the application of chronic irritants to particular parts of the 

 body) provokes the disease in situations and or^^ans from 

 which it is absent when these customs do not obtain. It 

 is reasonable to suppose that the frequency of cancer would 

 be diminished if such practices as the use of the Kangri in 

 Kashmir, chewing betel-nut in India, and eating very hot 

 riCe in China were discontinued. It is also reasonable to 

 assume that the introduction into Hngland of these exotic 

 customs would greatly increase the frequency of cancer In 

 this country. 



So definite is the evidence of the meiiaXe causation of 

 certain forms of cancer by chronic irritants that the possi- 

 bility of variations in the cancer death-rate may be admitted 

 us regards particular organs and regions of the body. The 

 possibility of a variation of the main incidence of cancer in 

 conformity with changes in certain customs may also be 

 admitted. 



That irritation is really an important causative factor of 

 cancer is an assumption which at present is justifiable only 

 for certain forms of cancer occurring in particular parts of 

 the body. In view of these considerations, and also because 

 of the results of experiment as recorded in this report, it 

 appeared desirable to h»>/e data of the incidence of cancer 

 in persons pursuing various occupations and having different 

 habits of life. For the purposes of comparison it will be 

 necpssary to le^rn not only the incidence of cancer on par- 

 ticular sites liable to irritation, but also its incidence on all 

 other sites, as well as the frequency of the other causes of 

 death in the occupations considered. 



Breeding experiments with mice of known ancestry have 

 leen in progress for many years, and have been alluded to 

 on several previous occasions, but only now have the data 

 become sufficiently numerous to permit of conclusions being 

 drawn. All due precautions have been taken to avoid errors 

 in the interpretation of the figures. The data show that 

 heredity plays a part in affecting the liability of the mouse 

 mamma to develop cancer. At all age-periods the disease is 

 more frequent when the mother, or either grandmother, or 

 all three, have died from cancer of this organ than in the 

 group in which these ancestors were free from the disease. 



Apart from its bearing upon heredity, the obtaining of 

 such mice is most important for furthering the experimental 

 investigation of the genesis, nature, and, should it be neces- 

 sary, artificial production of cancer, and for attempting to 

 define the reasons for its apparently greater frequency in 

 some geographical areas than in others. It will be obvious 

 that a large field of investigation has been opened up by the 

 segregation of mice into two groups of different liability, 

 and it should be possible to obtain groups of animals of a 

 still higher and a still lower liability. While it is at pre- 

 sent impossible to explain how the liability is transmitted, 

 it can be aver>-ed with certainty that it does not consist in 

 the inheritance of a soil more suitable for the growth of 

 cancer in general. It can only be inferred with some 

 probability, that it is a local or circumscribed tissue pre- 

 disposition, in virtue of which the mammary tissue is prone 

 to pass from mere proliferative reaction into continuous 

 or cancerous proliferation. Further, hereditary predisposi- 

 tion is only one of the factors concerned, for it has been 

 found that chronic inflammatory changes are remarkably 

 frequent in the mammae of female mice of the laboratory ; 

 and other factors still unrecognised may exist. There is a 

 considerable body of evidence to show that the predisposi- 

 tion is not a general one affecting the whole body equally, 

 but that the tendency transmitted affects mainly one organ 

 system, so that groups of animals may ultimately be 

 obtained in which different organ-systems will present a 

 definite predisposition, the other organs of the body not 

 being unduly liable to the development of the disease. 



To guard against pessimistic conclusions, it is well to 

 point out that the influence of heredity has onlv been 

 demonstrated by studying stocks in which this factor has 

 been concentrated by careful mating, and that the influence 

 is mainly exerted in the immediate descendants. Such a 

 concentration as can be attained in experimental animals 

 can only occur in the human subject, by hazard, as a 

 coincidence of considerable rarity ; and it is probable that 

 the influence of heredity in the general population is 

 manifested as an average predisposition of low general 

 intensity. 



NO. 2196, VOL. 88] 



In all previous reports guarded reference h- ^' 

 to the well-known association of chronic 

 certain forms of cancer, and it has been poiiv lat, 



common with all external conditions, they can only hfl 

 mediate relation to the occurrence of cancer, the esseol 

 preliminaries which lie between them and its incepd 

 being regarded, not as their specific reactions, but 

 manifestations of properties inherent in th' - " 1 

 employment of the term " mediate " when <■ At 



tion to the relationship is due to an effort to •._,._-.. tY 

 forms of cancer with which irritation is most constani 

 associated, without considering other forms in which 

 particular irritants concerned do not play a part, and 

 to the fact, already frequently emphasised, that ti 

 irritants have nothing in common beyond the capacity 

 excite extended proliferation of tissues (chronic inflamm 

 tion), and their association with cancer. 



The varied investigations of the past nine years ha' 

 added a knowledge of new forms of irritation. It has 

 come more and more evident that irritation, effective 

 one case, may be, and often is, quite ineffective in anot^ 

 species of animal, or even in other individuals of the 

 species. The experiments recorded in this report thrO 

 light both on the nature of predisposition to cancer, 

 alluded to above, and also on the long recognised, but 

 explicable, relation between chronic irritation i 

 cancer. 



A closer definition of the nature of cancer will invol 

 an analysis of the relation obtaining between the indivU 

 developing cancer and the tumour. This final analysis ' 

 be possible only on animals naturally afflicted with 

 disease, for, as pointed out consistently from the fii 

 annual report onwards, the genesis and the growth 

 cancer are distinct phenomena. The study of propagat 

 cancer supplements its observation under natural conditio 

 by investigation under varied artificial conditions, arid 

 only an indirect bearing upon the genesis of the dise 

 Hence breeding experiments acquire enhanced significaM 

 and are already being, and will continue to be, conduct 

 on a much more extensive scale. An adequate supply 

 animals of differing liability to the disease must be 

 available for the elucidation of problems, some of whi 

 are already adumbrated ; while past experience makes 

 likely that others, as yet unsuspected, will arise. 



Because of the hope that they may ultimately ha 

 therapeutical bearings, another reference may be made 

 the induction of resistance to the inoculation of cancer 

 the means which modify the growth of transpla 

 tumours. Experiments along these lines bear at pr 

 upon the nature, but not upon the prevention, treat 

 or cure of cancer ; notwithstanding this fact the applk 

 tion of the results to the human subject has been urged 

 some quarters. In 1906-7 it was pointed out that a lii| 

 degree of resistance to the transplantation of cancer did I 

 exempt an animal from the spontaneous development 

 the disease. The importance of the observation was grM 

 had immunity to the natural acquirement of cancer bl 

 also obtained, the control of the scourge would have bC 

 in sight. 



In the Third Scientific Report the previous warning ti 

 re-enforced, and it was pointed out that none of < 

 methods which had been found to influence transplanf 

 cancer should be applied to man until they had been teil 

 and found efficacious in the case of animals natur^ 

 affected. These warnings are borne out by further ei 

 ence and inability, as yet, to modify the growth of 

 in the animal naturally affected. Instead of ren 

 analogies with infective diseases, and placing sJ 

 remedial and preventive measures in the hands of 

 physician and surgeon, the study of resistance to 

 has, until now, but brought investigators to the ve 

 a region filled with problems previously undreamt ofT 

 the solution of these problems, or of more crucial on> 

 yet reached, lies the best hope of preventive and rem 

 measures ; but the preliminary facts are so new to ^|j||H 

 mental biology, and as yet so imperfectly comprehflHH 

 that observers throughout the world are still engag- "^^ 

 discussing what may be their true significance a? 

 posts indicating a road or roads by which th'^^ 

 advance is to be made. 



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