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THE CANCER-SMOKING CONTROVERSY SIR RONALD A. FISHER, F.RS.- I ;;a.135 1 CTR rltq 003375

THE CANCER-SMOKING CONTROVERSY SOME ATTEMPTS TO ASSESS THE EVIDENCE SIR RONALD A. FISHER, Sc.D., F.R..S. i OLIVER AND BOYD FAINBURGH : T1ti'F_F.DDALE COURT LONDON: 34A WE.L.BECg Sl"RLET, W.1. I --4' •1- 1352 CTR NN 0O ,K37t;

Scientists in many fi inference, and tbcsc zre, PropalY, czpcri of intemt and teac} Unfortunately, it departments, with r cations, have plunc discipline, in spite c the logic of scientific u iadeea., the sta teaclLing, Were perr6 and confirming, in within their ia8uenc( obsesvrntioaal data, timple auoaation, abc have been made thc For this reason I attacked at both o.` uaentist, and as a z ?he ha.'zor of Procc:: on the general a,ucsc andnotespociallN•cc cancrr. As the subject rtz.5 has soemed impor~- mictly in order of L~. O 1959, sa ROK~ A. F,m3m .:""= PC owTS&ff,.MI .,. ~ r.,m j. o.A., =OOPU&Q. ~Cr~; 1353 r ~fa • 'Y { • { ~~ ` ~ RF ~F

PREFACE Sdentists in many Selds have felt the need for canons of valid infcrcnce, and these have beca becoming available in what are, properly, experimental sciences, by the rapid development of interest and teaching in "T'he Design of E.xperimesnts". Unfortunately, it has become obvious that many teaching departments, with mathematical but without s,dmti5c qus.li5- cations, have plunged into the task of teaching this new disripline, in spite of harbouring gravely confused notions of the logic of scientific rescarch. Ii; indeed, the statistical departments engaged in tiniverrity tC chinv, were perfermin8 thdr appmprizte task, of clarifying and confrrming, in the future research workers who come within their influence, an understandi.ng of the art of tra.mining observational data, the fallacious conclusions dnwn, , front a simplr srwdatiaa, about the danger of cigzretta, could scarcely have been made the basis of a teaifying propaganda. For this reasou I have thought that the fillaaes mtm be attacked at both of two distinct levels; as an ezperimmtal scientist, and as a mathemadcal statisdeian. I'he lecture on 77u Xator of Probabili) was to a non-mathematical audicacc, on the general question of the validity of infesences from facts, and not especially eoncerned with the fazt3 available on lung eance*. As the subject has developed during the last year or so, it hzs seemed important to rrprint these lette=s and addresses strictly in order of their date. Rotcar..D A. Fasu ® C7R• 13S4 C`9 R ~"I~`q 0~'~ ~ ~ ~;~"~"

GENERAL ACKNOWLEDGMENTS Grateful u.]mowledgment is made to the Edit.ors of the BritirA M,A~ 30wwL, xauffi, and Tie Qrxtm~ xnww (Michigan State Uaivcrrity) for pcrmis6on to republiib material from their pages. / I Allegc< Lcm vol. ~ Cigarc Lcc: PP. Cen- tiiic ~ ThcN Ltc: no. b\. - La:_ Lunc Lcrs jui~ Cancr Le-. Auc lnha_. CTR HN 003,3'79

CONTENTS ~iriJh :3iigin from Alleged Dangers of Cigarette-Smoking. Letter to the Editor of T1u British Mdicad j7osanal, vol.u,p•43. 6JWy 1957 .. . .. 7 Alleged Dangers of Cigarette-Smoking. Letter to the Editor of The Brirish Mcdica! ,jJOvaal, volL a, pp. ?97-298. 3 August 1957 .. . . 8 Cigarettes, Cancer, and Stitistics. Lecture published by Tlu Cmtemial Rsaism, vol. a, no. 2, pp. z5t-t66 (Spring t958). Copyright t958 by The Centennial Review of Arts and Science, East L.aasing, Mchigan, U.S.A. . . . . . . t t 'I'he Nature of Probability. Lecture published by The Csntwrial Rsoiao, vol. u, no. 3, PP. 261-274 (Summer t958). Copyright 1958 by The Ccncennial Review of Arts and Saence, East L.aasing, Michigan, USA .. .. 26 Lung Cancer and Cigarettes? Lcttcr to the Editor of Xatm, vol. 182, p. zo8, 12 July 1958 39 Cancer and Smoking. Letter to the Editor of Xador, vol. 182, p. 596, 30 August 1958 Inhaling 5 41 45 C ~WF~ ~~~~ ~ ~6 ~~

i 11t * ~ In the Journal of July 20 (p. t58) Dr. Robert N. C. McCurdy writes: "Fisher's criticism (joinnal, July 6, P• 43) ••• would not be so unfair if he had specified what alternative explanations of the facts still await cxc]usion". I had hoped to be brief A few days hter the B.B.C. gave me the opportunity of putung forward e:amples of the two clarses of alternative theories which any statistical assodation, observed without the precautions of a definite experiment, always allows-namely, (z) that the supposed effect is reall,v the cause, or in this case that incipient cancer, or a pre-cancerous condition with chronic inflamaution, is a factor in inducing the smoking of cigarettes, or (2) that cigarette smoking and lung cancer, though not mutually csusative, are both influenced by a common cause, in this case the individual genotype. The latter tsncxduded possibility was known to Dr. McCurdy but he bzushes it asidc with abundant irony. Is he really persuaded that this is the way to arrive at scientific truth? Dr. McCurdy points out correctly that difference in the geno- typic composition of the smoking cla.ucs-~on-tuwkers, dgarette smokers, pipe smokers, etc., would not explain the secular change in lung canccr incideace. I had never thought it would be charged with this task. Is it axiomatic that the differences between smoking classes should have the satne cause as the secular change in incidence? Is there the faintest cvidcnce to support this view? Indeed, Dr. McCurdy's belief that cigarette smoking causes htng cancer would be more secure if he did not enambcr it with the .on ssauiAo that incrcase of smoking is the cause of increasing ca.nccr of the lung. For at this point there appears one of those massive and recalcitrant facts which have been emerging through the smoke-surcn of propaganda. Wben the sexes are compared it is found that lung cancer has been increasing more rapidly in men rriatively to women. The absolute rate of incrux is, of course, obscured by improved methods of diagnosis, and by the incrcascd attention paid to this diseuc, but the relativc proportionate changes in men and women should be free from these disturbances, and the change has gone decidedly against 8 i C rR ; 135S thc of: an P° is cal

:urdy ~ative iopcd e the zes of tsvcd 11WA r v the YrOu3 -Ig the i lung enced c. ~urdy really 7u:hu geno- okers, -n the ought at the sarnc untest belicf tnore r that of the :assi ve ,h the Lred it dly in is, of nd by clative Erom gainst the men. But it is notorious, and conspicuous in the memoryf of most of us that over the last fifty years the increase of smoking among women has been great, and that among men (even if positive) certainly small. The theory that increased smoking is "the cause" of the change in apparent incidence of lung cancer, is not even tenable in face of this contrast. For the secular change, therefore, neither the smoking causation theory nor the theory of differentiated genotype will afford an explanation. For the contrast between cigarette smokers and non-smokers both are available; for the contrast between cigarette smokers and pipe smoken the first theory requires some special pleading, but this has never been lacking. Ile two circumstances (i) thit heavy smokers show a greater effect than light smokers, and (2) that prnons who have voluntarily abandoned smoking react like non-smokers or light staokers, are not independent experimental eonfirmations of the smoking theory. They are only rriterations of the main association to be explained. Any theory which explains this association may be expected to explain these facts also. Differcntiation of genotype is not in itxlf an unreasonable possibility. Inbred stzai,m of mice if genotypically different almost invariably show differences in the frequency, age- incidence and type of the various kinds of cancer. In Man cancer of the stomach has been shown to be favoured by the gene for the blood group A. My claim, however, is not that the various alternative possibilities which have not bcen excluded all command instant assent, or are going to be demonstrated. It is rather that excessive con5dencc that the solution has already been found is the main obstacle in the way of such more penetrating rrsearch as might eliminate some of them. I am sure it is useless to treat the question as though it were a matter of loyalty to a political ideology or of forensic disputation. Statistics has gained a place of modest usefutncss in medical research. It can deserve and retain this only by complete impartialiry, which is not unattainable by rational minds. We should not be content to be "not so unfair", for without fairness the statistician is in danger of scientific 9 i C ~~L~~~ ~t~~ ~~~'.~ ~ °.~~°~~

errors through his moral fault. I do not relish the pnoapect of this science bcing now discredited by a cztastrophic and conspicuous bowler. For it will be au clear in rrnrospcct, as it is now in logic, that the data so far do not warrant the conclusions based upon them. (Sgd.) Roxwm A. FzsHxx 10 1 QT .4% 13C0 ~' 7(- R"" N N 0 +~"0 13 123"e-3'

CIGARETTES, CANCER, AND STATISTICS Lecture published by ?7u Csnlential Rsviata, Spring, 1958 Srvur oR tlos-r years ago, those of us interested in sueh things in Engia.nd heard of a rather remarkable piece of research carried out by Dr. Bradford Hill and his eolleagtles of the London School of Hygiene. We heard, indeed, that it was thought that he had made a remarkable discovery to the effect that smoking was an important cause of lung euncer. Dr. Bradford Ii~ill was a weU-laown Fellow of the Royal Statistical Society, a member of Cot, and a past president-a man of great modesty and transparent honesty. Most of us thought at that time, on hearing the nature of the evidence, which I hope to make clear a little later, that a good prima facie case had been made for further investigation. But time has passed, and although further investigation, in a sense, has taken place, it has eonrisud very laxgely of the repetition of observrations of the same kind as those which H'iU and his colleagues ealled attendon to several years ago. I read a recent article to the e$ect that nineteen different investigations in different parts of the world had all concurred in confirming Dr. Fi~ill's findings. I think they Aad concurred, but I think they were mere rcperiti.oas of evidence of the same kind, and it is ncccssary to try to ex1r*+ine whether that kind is sufficient for any scientific conclusion. Tle need for such scrutiny was brought home to me very forcibly about a year ago in an annotation published by the British Medical Association's Journsl, leading up to the almost shrill conclusion that it was neccaary that every drvicz of modern publicity should be employed to bring home to the world at large this terrible danger. When I read that, I wasn't sure that I liked "all the deviees of modem publicity", and it seemed to me that a moral distinction ought to be I I CTR• 1361 M-; HN 00336-4