Document nmZdXYNON6DRobnZBx4QZJ3om

>'~ `l'fc!urt Vtfi. 284 27 March 1980 in ---- r v - ' ''.VU-A'.-i.-j . . . *( - * . gas.*. s *r * * ^T-r siqrdag(&y>\ the epMemioIog cancer: like need for a more |H' ;: - overview . .i.i-iV-h tThe politics of cancer are becoming increasingly polarised with fl>.o-ninivnirrnonn':inc'ntrafllliksts rtaaktiinneg ones extreme view and industrialists thhe frVfler. Richard Peto argues that a more dispassionate and consultants are inevitably distrusted. Over the past quarter century, the "environmentalist" camp in Noun American society has pressed for (and *;? disinterested approach is required for a realistic assessment both achieved) stricter control of particular I- oi the risks from environmental carcinogens and of the ft-^preventative regulations needed - , carcinogens in the work-place, the general ' environment, and the diet. Usually, their efforts have been directly resisted by the relevant financial interests. Inevitably, in view of the scantiness of reliable :Thexe exist, bom in the general the consumers of their products, their quantitative knowledge about the cancer;f> ravircnment and ::i certain occupations, immediate response has usually been to risks to man of nearly all carcinogens, the :icmical or physical agents which increase delay acceptance of the findings, to argument has polarised. In the politics of rae likelihood of human cancer. Our minimise their relevance to current cancer, each side takes a very extreme r political response to this would, in an ideal practice, and in general to delay or obstruct position. Industry usually argues for the &-t>or:d \.iv"e sufficient knowledge was any hygienic measures which will cost irrelevance to man of animal or in vitro k *iilat It; i rpairt on the direct and indirect money. Even when human danger has been cancer tests, or minimisies the quantitative Ky tjsts of varisu* possible measures of unequivocally demonstrated, industrial hazards and exaggerates the costs of $vtozuci. sac on now many cancers each : consortia may actively lobby for controls control. The environmentalists usually ' '' iFr'f&h R^runr would prevent. In the real so weak that (as with the new UK exaggerate the likely hazards and are cnimates of the direct financial government regulations limiting inhaled largely indifferent to the costs of control. pV * or the control of particular agents can asbestos to 1 fibre/ml from 1981) they '4differ by one or two orders of leave no reasonable safety margin. Large `The most powerful ' "P4hni;ude, the indirect costs may be I rossly exaggerated, or some major amounts of money are available to mount press or TV publicity campaigns^about the pressure groups in the US maircct costs may be completely * overlooked. Worst of all, we have in t: rrosrai no remotely reliable estimates of the numbers of cancers which particular homely apple-pie virtues of asbestos, journals financed by the tobacco industry run populist articles which misrepresent research results to lay readers; and some have been the large financial interests which have almost always put :>rv;g?E- legislative controls would prevent. US television journalists are explidtlv told financial advantage before ..' Consequently, there is wide scope for always to ce or all refer' *ce pressure groups to have considerable dangers of smoxing. - the human health' iaficcnce on public policy. Even the scientific literature is not Jr- v Historically, the most powerful pressure immune from distortion by financial The vacuum of reliable scientific know St- paups in US society have been the large interests. The decades-long argument that ledge is such that each side can find faincial interests, which have almost ``threshold" dose levels of carcinogens scientists who will maintain in courts, in ; ilnays put financial advantage before must exist below which the general public hearings or in the scientific literature 'll. health. Over the past few years the population is absolutely safe has not been whatever is politically conven' tt, and it is major tobacco companies have launched entirely motivated by the scientific important to recognise that scientists on r tfcusivc sales drives in the Third World, plausibility of the hypothesis. With both sides of this debate now have career, ' .which if successful will kill millions of increasing understanding of the derivation interests at stake in it. '* people. (About one in four regular of tumours from single cells acted on by A particularly good example of the ! ^'ctie smokers is lulled prematurely by mutagenic carcinogens, industry is slowly biased writings of politically active . vtokins.) In the US, where cigarettes abandoning "threshold" arguments in environmentalists is Samuel Epstein's The ..tsiic well over 100,000 deaths every year -J'l fast lung cancer or chronic obstructive `-4 lung disease, the tobacco industry refuses ' i <0 .ccept in public that cigarettes cause .t{ cuks disease, ict alone to collaborate in rious public information, and no epithet ja '-cw suitably describe the collective efforts V. rf .ih'thtu- advertisers. J1*0 othor industry kills people on n3^Si11>,r`s *`KC l*le SC3^e c^at c^c tobacco I^'l-2lUJ!ry <*oes' ',ut w*)ere other industries .**. ?** hcea found to cause cancer (or dust _ u;oh lung disease) in their workers or in favour of arguments1-1 (where the biological fallacies1-4 arc somewhat better concealed by the mathematics) that thousandfold reductions in dose can conveniently be "statistically guaranteed" to produce a million-fold or some other enormous reduction in risk. Even if the scientists who propound sue)* models are disinterested, industrial endorsement of them is not. Much excellent toxicology may be done by industry, and many industrial scientists and managers may be directly and honestly Politics of Cancer (Sierra Club Books, 1978, revised in Anchor Press, 1979). Epstein outlines, for university-educated but not necessarily science-educated readers, his view of our present state of knowledge about prevention of death from cancer. He concludes that the cure rates for the major cancers have not been improving much over recent years, but that we do know enough now about the causes of cancer for the testing and regulation of environmental contaminants to prevent the majority of US cancer deaths, and that o' >4 | 0: y jj i- i i f . 2??.s i* a reader in cancer studies at the 7 Oxford. This article developed of Samuel Epstein's book. The concerned with the prevention of hazards. But so many examples of financiallymotivated bias exist that the motives and work fsf tnrirttfrtat the main obstacles to our doing so are political rather than scientific. He therefore reviews the scientific and * > T7 298 ______________________ .Mre Vol. 284 27 March 19*0 dozen or so disputed consumer products or occupational hazards, providing much fascinating political detail, and then describes at length the internal politics of the various agencies which research, regulate and litigate in Washington. have refuted it (see table). This appears to `Scientists on both sides of be a deliberate attempt to deceive the reader. It is not a casual slip in a 600-page the environmentalist >; book, as Epstein devotes tweniy pages and debate now have career ` two full-page tables to saccharin. His entire table 6.4, entitled "Tumours other than the ' interests at stake' Epstein's book has been written to bladder in rodents fed saccharin' ', appears inflame political passions against to be so subject to artefacts ofselection that merely be acting as a vehicle forfat-soluble environmental carcinogens, and parts of it it provides no evidence that saccharin does pesticides and industrial chemicals, which ; ^are well worth reading. However, the cause any rodent tumours other than in the predictably emerge as his villains yet again. political punch is often achieved at the rat bladder. However, his suggestion is implausible ^ expense of scientific accuracy and balance. Saccharin is not an isolated example of countries with high levels of contamination ) Despite this, the book has already gained bias; indeed, 1 found that in many places do not stand out from the general wide and apparently uncritical acceptance where he discussed data with which I was cancer/fat relationship, colorectal and '~even among scientists. For that reason, it is familiar inaccuracies were present, almost breast cancer were common long before the worth considering some of the always in the direction of accentuating the widespread use of pesticides, and in misrepresentations of scientific evidence need for battle with the devils of industry. experimental animals high-fat or low-fat which it contains, and some of the more Turning to more important matters, diets can greatly enhance or reduce the risk general defects in the environmentalist Epstein asserts that any benefits from the of cancer11. Something more interesting is perspective on cancer. "less dangerous" cigarettes which the waiting to be discovered in our diet than First, a few details. Epstein's book is tobacco industry has developed will be simple contamination by carcinogens. very useful as a source of reference to outweighed by people increasing their The fat-associated and smoking-derived original papers, but it is not in itself a consumption to get more nicotine, and he cancers collectively account for more than reliable secondary reference because the is therefore in many places particularly half of all cancer deaths, and people material presented *n often dimrf5i. scathing about (or even downright opposed concernedwith cancer politics should tryto Sometimes this dictortton it due to the to) research into changed cigarette understand them considerably more ite'S-tr: efPSciTofEpStcin'S vigorous campaigning composition. This is a distorted accurately than Epstein appears to. One style" on his scientific judgement and is, perspective on one of the more promising can list many other instances where perhaps, forgivable: at other times it immediate means of preventing fatal Epstein's content or style are misleading or appears to be deliberate, which cannot so cancers, a quarter of which in America are unbalanced. For example: easifybe torgiven. currently due to smoking. The discussion of alcoholism and cancer ' " Toi example, consider the (by now Smokers of "less dangerous" cigarettes is entirely erroneous because of failure to generally agreed) finding that incor poration of about 5% by weight of saccharin into rat diets gives a few rats bladder cancer, but has no generally accepted effects on any other type of cancer. By human standards, 5*vo repre sents a vast saccharin intake (and so, of course, the industrial "Calorie Control have already been found in various epidemiological studies to have disease rates which are materially lower than smokers of other cigarettes*-7; at autopsy they have far fewer "pre-malignant" histological changes in their bronchi* and, perhaps due to the changes in cigarette composition 10 or 20 years ago male lung standardise properly for age. One of Epstein's chapters ends: f ixW "Eisenhower warned against the growiij national threat of the military-industrial complex. The medical-industrial complex -\n< I t 'V' it now appears to be as serious a threat". There is idealisation of the value of long in term animal tests with concomitant Council" have tried to shrug off these cancer death rates in early middle age are denigration of the value of the Ames test findings). To refute the common reaction now decreasing in North America, in and other short-term tests. This is one of that "anything given in large enough doses Britain and in Finland. Epstein's most inexplicable errors of cal will cause cancer in animals", Epstein's chief argument is to report that 0.01 V After lung, the next commonest fatal cancers in the US are those of the breast scientific judgement, unless be wants cancer tests to be difficult and expensive ''-vlivscl saccharin has also been shown to be and the large intestine, for which the most for industry. carcinogenic. In support of this extra striking epidemiological finding to dateis a He is irritatingly puritanical, sneering at ordinary claim, he presents in tabular form 90% correlation between fat consumption "the plastic age which symbolises bow the ,-r tO | the control and 0.01% data for selected in different countries and their breast or value of our lifestyle has been degraded". cancers from certain multi-group feeding experiments, leaving out the observations from those same experiments which would colon cancer rates (see figure; similar correlations exist for colon cancer10). Epstein suggests that dietary fat may He seeks by stylistic tricks to attribute to oral contraceptives some of the established hazards of hormone replacement therapy and of diethylstilboestrol. thi "v; mq Table: Data from OTA report* on the tumour sites selected for presentation in Epstein's book to substantiate the claim that 0.01 % saccharin is carcinogenic. Croups selectively omitted in Epstein's book are marked with an asterisk. These omissions substantially alter the implications of the original data. Saccharin dose (9e in rat diet; these doses have no material effect on longevity) . Male or female lymphosarcomas (FDA, 1948) Female breast (FDA, 1973) . Male breast (FDA, 1973) He claims that cancer costs the US economy over S25 billion per year, (in fact, [ -#| cancer must be prevented for humane, not for economic reasons; without cancer, there would be three or four million more V tZLTfc inti retired North Americans to support, costing over S2J billion per year). And so on. He seems so certain about everything -- how can anybody be justified 0 (control) 0.01 ';o.i , 0.J Jit ' i'5 0/20 '"(0%) ' . 8/14(57%) 5/16(31%)* 2/15(13%)* . 1/18 (6%)* 10/17 (59%) 6/26(23%) 14/30 (47%) 13/34(38%)* 12/30(40%)* 12/27 (44%)* 6/29(21%) 14/25 (56%) 9/27(33%)* 8/27 (30%)* 7/25 (28%)* Omitted in Epstein's book. 'In addition to these 20, since some other sweeteners were being tested concurrently, 34 other control animals were studied in the same experiment, and the 1977 OTA review of these data, considering all the control animals to be equivalent, cited 9/54 control lymphosarcomas. (0/10 . saccharin controls of each sex were studied, not 0 '10 as Epstein inadvert y indicated.) 0024IM/BO/))29i42Sot.OO ~TM in being so certanrgWSrecnitan)idetaili? fSometimes,! know he's wrongTBuTfflort often fespeciailyurthe'lflhnVTylaceywhere inconclusive!cicntlficrcsuitsarcpresented as estabCsHeOact) "l kribw-that-nebody knows for-lure. LewisThomaScmcrwratc. in another context:~Trnie sceptics a mc3icjne have a hard.UfflijSr it. It is muck more difficult hg mnvinV? ignorance concerning disease mechanisms ' 71 sUrtasrdEaem ,ttun it to make claims for full -fomprehension. especially when the comprehension leads, logically or not, to 'some sort of action. When it comes to 'serious illness, the public tends, understandably, to be more sceptical about : the sceptics, more willing to believe the true c od additives. Indeed, one of the most ii. .guing animal findings is the effect in many studies of gross aspects of diet on cancer; for example, mice randomised between 5g of food once daily and ad lib consumption averaging 6g/day of the same food, had respectively S7o and f`mA `Pre it day cancer rates and trends are probably not dominated by v occupational carcinogens . or environmental - ^ believers." spontaneous mammary turnout , ana the pollutants' "" Epstein (like many others) is role of dietary fat" has already been unjustifiably definite about three major discussed. issues. He seems certain that even after the Thirdly, Epstein seems certain that at both of whom still seem more ready to effects of cigarettes have been allowed for, least a quarter of all cancer deaths are defend than to repudiate it. 'Americans live in an era of rapidly attributable to occupational exposure to Entitled "Estimates of the fraction of increasing cancer rates. But trends in carcinogens. There is as vet no good cancer in the US related to occupational ' recorded cancer death rates (ana, perhaps evidence for hazards ot anything like this factors", i.t shows how a roup of 'more so. recorded incidence rates'! over the magnitude, and there is clear evidence that reasonable men can collectively generate k oast Quarter century are biased upwards . many of his particular claims, are an-unreasonable report. The group exaggerated. For example, he says that by ' asbestos has led to approximately 50,000 in any way in 1972-4 to any of asbestos, As, ^ improvements in medical care and cancer . deaths per year in the US from cancer and Ni, Cr, benzene or petrochemicals by the ^counting. These improvements have related disease (referencing a paper by very large risk factors (e.g. fivefold lung Selikoff11 which actually neither makes nor ' cancer excesses) typical of much more JJ`The NCI-NIEHS report pshows how a group of t reasonable men can j: collectively generate ah ^unreasonable report' . implies any such claim). This is sheer nonsense; of 50,000 asbestos deaths, several thousand should be certified as being due to pleural mesothelioma, yet only several hundred per year are thus certified. Likewise, Epstein cites with approval extensively exposed industrial populations, finally multiplying again by "4-5" to allow for the additional cancers that will be caused by these six agents among workers exposed to them at times other than 1972-4. (In casual disregard of dosimetry, this whole process is very like predicting --------------------------------------------- (indeed, he describes it as being of 100.000 occupational lung cancer deaths, Jraffccted all sectors of US society, but most "epochal significance") Health, per year among non-smokers due to their ]j* particularly old people and previously poor Education and Welfare Secretary exposure to other people's cigarette smoke ^(.people, especially blacks. Epstein, along Califano's absurd 1978 estimate, in a at work, "since 207a of heavy smokers get ^with most otherlUS commentators, does speech to labour union leaden, that as lung cancer"). not allow for these biases even to the many as half of the 8-11 million workers These assumptions "predict" over ?A limited extent of restricting his attention to who have been exposed to asbestos could 200.000 extra respiratory tract cancers per ^trends in age-specific mortality rates develop serious diseases such as cancer or year in the near future due to the above six v-' smong middle-aged whites, where they asbestosis. In his second edition, Epstein agents alone (and are the sole source of the might be expected to be least prominent. draws extensively on Califano's source, a currently widespread prediction of .-: Among middle-aged whites during the curious but extremely influential document "20-387o" of cancers being due to tv past quarter century, cancer cure rates have which has been circulating privately for the occupation). But, in reality', fewer than [aot materially improved, but some US past year or more. This unpublished 90.000 males/year get respiratory tract cancer mortality trends seem to be typescript, with no listed authors, was cancer in the US (and most of these are due ip. genuinely down (stomach, cervix) while prepared by a working group of nine well- to cigarettes and not to occupation at all), ii'fome seem to be genuinely up (pancreas, known scientists including Arthur Upton and moreover the US male rates in the first ^melanoma, and certain lymphomas). I can and David Rail, the National Cancer 25 years of working life are currently ^discern no net pattern other than that due Institute and National Institute of decreasing! A prediction of 100-200,000 lo the massive effects of smoking on lung Environmental Health Sciences directors. extras due to the above six agents is clearly 17cancer, although no extension to 1978 yet tv exists of the excellent 1950-67 trend Figure: data plotting for 39 countries age-versus total dietary fat (animal or standardised breast yi analyses in NCI monograph 33. In Britain, cancer death rate vegetable). .. -- t' the same is true12.as long as we examine mortality in middle age. (Interestingly, f' although Epstein emphasises that bladder 25 NCTHEPLANOS l cancer death rates among whites in the \ industrial north-eastem US are high, this iy may not be chiefly due to any current t.'*.industrial hazard, for they have been decreasing both relatively and absolutely ]rr. for a quarter of a century11.) Epstein also seems certain that the ^..majority of human cancer is caused by ^`chemical and physical agents in the v environment and could be prevented by -their testing and regulation. There is no | sound scientific basis for this certainty. ivSince the cancers (lung, breast, large & L 20- 15 a p 10 ' Female iBElatc^I^ ' -AUbSeTlU&AuUmA .. i SAEOEN ADSTB-A* #*OEBMAW ITALY NOBWAY EBANCE- CZECh POBTuOia. YUNGABY PiNUV'O "OyxONG POLAND Cj'LE VENEZZuUEElLaAV* * %&wanSa Panama YUGOSLAVIAuBEECE PUECTD BiGO -oryf:, | intestine) which are commonest in the US JAPAN "TAIWAN t tte rare in certain other countries, and vice i v3a, they probably really are preventable, hut (see figure) not necessarily by |- Kgulaiior. of any environmental pollutants Z _*-*J*24.M/IJ29.02JO|.0O TH0H.&NO l$AwV40C1P 1 1 40 60 SO 100 TaT Tout dietary fai intake ({.'day) lir Tw- 'X 'rsmrr. pasrnK"" .- " .............. -i ,*t- *> y ' Tl ------- jov - Tli '=- -- --'- K'ature Vol. 284 27 Marc. i +:0 /teg $ /unrealistic. .ath rates12 should be more widely more man the equivalent amount of T?.e unreality, of the whole method is known. dietary saccharin would have done15). ^further highlighted by the fact that the My criticisms of Epstein's science, Also, any chemical which causes prolifer '/assumptions `predict" 7,300 x 4.5 nickel- however, must be viewed in the light of the ation or necrosis in any organ that is oxide induced occupational lung cancers/ continued resistance of many industries to subject to spontaneous cancers is likely to / year. Since nickel refining causes a lot of reasonable controls. One has only to read modify the onset rate of tumours in that /.nasal as well as lung cancer, we would some of his descriptions of industrial organ, and since the aim of most animal itr. ^` /presumably then also soon "expect" . behaviour to see where his passion comes experiments is to study a dose which is li >. something like 13,000 nasal cancer death from, and a suitably sceptical reader could nearly, but not quite, sufficient to cause In certificates per year among nickel workers. derive much important information from significant weight loss or mortality within X Nickel has already been widely used for the dozen or so detailed case-histories of three months, it is not surprising that decades, so many thousands of these particular carcinogens that make up the many chemicals at such doses can cau; -Tv-eSs}? i?should presumably already be evident. In bulk of this book. But, although I cannot, cancer in animals. S .'/reality, each year in the US population prove it, I suspect that environmentalists^ However, it may be that where adversary '322SrW there are only 300-odd male and 200-odd a whole (including Epstein and those US politics operate one needs views at both f female nasal cancer death certificates. The and' British ' traci'e'*unions wKtcfi~have extremes in order to get a balanced out- mm f majority of these are not ex-nickel workers - alrcady~mo<feffccf'their publicjtlatemeats corne. And there is a possibility that over- tri &S$r f: and no marked trends are evident. This closeIy~'bn"Eis book) would be better emphasis on the avoidance of scientific _ j* demonstrates the unsoundness of the NCI-- error would emasculate the environmental-. uNIEHS methodology..." if ' Unfortunately. such_ exaggerated estimates are so much what many people tfant io believe ot modern society that they X hstveTToVachieved a ufeoTtheTr own, and. "The politics of cancer is dominated on both sides by exaggeration' V ist passions and merely lead to my own' rather inactive conservatism. (After all, no scruples about scientific certainty of safety _u_s__u_a_l_l_y__p__r_e_c__e_d.e the _w_idje_s__p__re__ajd introdj.u.c.,'.Vfr!t3S . tion of new chemicals, so should the C although_j.Kcy'jir e~~utTet!T**mfhQut imposition of prudent restrictions require. f foundation tKcy._are__q.upjedJ.yidely, respected and could thercforcjrcss more absolute proof?) ;i ^ repeatedly andj;eoutabiy both <n 'effebtively'fd^onrroJsjn.jartigular Environmentalists with biased judge- */ana^Sc\entific^press. In Geneva the instances If tKeir ^rview'of cancer was ments and a quasireligious certainty of -.j/ '^nifeTnational Labour Organisation more Balanced in thVfoilo.wihglways: right will fight more battles than acy'';|.:'-^ '/reportedly endorsed them, as did the Toxic - If th'ey'accepted~that present-day cancer reasonable sceptic .would do, and even if -rfs[Substances Strategy Committee in their rates and trends are probably not their victories confer 10 or 100 times less ; .f ? [recent draft report to the US president16, ' dominated by occupational carcinogens or. benefit on humanity than they imagine,; '-. I f/1 fand they have been used in OSHA to environmental pollutants (especially since they will in the long run probably do more [emphasise the need for stricter laws. Most they could still warn that future rates might good than harm -- unless they materially ' ^.recently, the UK trade union the perhaps be so <*'"r\inated unless present- reduce food production, distort research Association of Scientific, Technical a. day expc *esaic regulated20); priorities, or direct attention away from the r Managerial Staffs (ASTMS) released a policy if their chief concern was with the smoking problem in the process. Epstein [ document which appears to have been identification and control of the few major justly quotes, from the 1st century AD, the / strongly influenced by Epstein's book, and determinants of human cancer (or, in an Plutarch chronicles: "He who in time of which is notable for its prominent but industrial context, the few major industrial faction takes neither side shall be disen- ; erroneous assertion, derived solely from carcinogens) rather than the large frachised". So, I feel, should both environ the foregoing unpublished US typescript, multitude ofsins which Epstein denounces; mentalists and industrialists who suppress -that 20-40% of current UK cancer deaths if they discussed the costs and benefits of or deliberately misinterpret data, but they are caused by occupational carcinogens, research into the control of toxic probably won't be. For the moment, the p Epstein now claims that these . substances in the context of other possible `politics of cancer* is dominated on both ^.exaggerated estimates seriously ways of improving longevity (bad diet and sides by exaggeration. ^underestimate the impact of industrial tobacco in rich countries, malnutrition and / carcinogens. There is obviously a valid infective and parasitic diseases elsewhere); .[ political need to exaggerate the importance if they took the costs of imposing ; of the preventive measures we can already restrictions on society more seriously. Tor most toxic chemicals we now have both qualitative and 'quantitative uncertainty about the health benefits 'of restriction'. Epstein's general assertion is that the total - direct and indirect costs of failing to regulate usually exceed the real costs of the testing and regulation, but I suspect that this is a slogan to avoid political embarrassment rather than a carefully researched conclusion; if they accepted that for most toxic chemicals we have.both qualitative and vast quantitative uncertainty about the 1. Cornfield.&v*cr m. 693 (19771. 2. Mantel, N. andSchcedcnzunO. MA Cancrt is?? urn. 3. Cnimp.KS.ett/C4*ctrRem*X.zr)\Wto. 4. Gocu, WA tt at Cenctr Htxwh 37, K>5 (WTfc Office of Technology Aunsncm of the US Coa&m (1977): Canctr Tatvrg Tfehnotogj Saccharin. 6. Hammond, E.C. ft at in Origins o/Human Centre. Coli Spring Harbor NY ( 1977). 7. W>ndcr, E.L. ft/ in US government DMEW puMkstue NIH 76-1221 (1976). I. Auerbach. O. ft of N.EngLJ.Mrd, 300. 311 (1979). ` 9. Caroll. K.K* Cancer Rcuarth 33. JJ7a (1973). 10. Armstrong. 9.K. andDoil, R./at,/.CeAcr'lS.617(irj1. implement, but in the long run we do also still need to discover the main preventable - causes of cancer other than smoking. . Bearing both these needs in mind, there are .. limits beyond which it is not even politically ; wise to distort the science of cancer, and . some of today's exaggerations may well transgress those limits. Reliable reviews of the known and suspected causes'*1-I1I*.'16 of human cancer and of trends in British health benefits of restriction. -Particularly, even if the sort of grossly biased interpretation which Epstein applied to the animal saccharin data is avoided, the results of animal experiments simply are not an uncomplicated key to human hazard identification. First, moderate alteration of gross aspects of the diet of animals greatly modifies their spontaneous tumour onset rates" (so, for example, increasing the sugar content of rat diets may increase their cancer rates 11. jose D.G. Suihtion and Canear UJK }l (1979). (Mur other papen in all the 1979 Luucs ofthis journal art of pt* general interest e.j. 10) 33, 67 and 27. See also pan 2 *f November .1973 Cancel Rtaaarrh devoted ohoUjr u muuuon and cancer). 12. DoU, fc. Proc.*y.Soc.Lond.(8)205.47 (1979). 13. Blot, WJ. and Fraumeni. J.F.J.Sati.Ca*c*rinst. 61.1011 (1971). 14. Roe, F.J.C. and Tucker, M.i. rcnpw Mtdica (laa Congrrn Series) 311.171097*). 13. Seliko^, I.i. in`'Originsof Human Cancer**, Cold Spnae Harbor NY .(1977). Id. Norman. A. tfaturt ltd. 423 (1979). 17. Doll, R. Natytt US. 519 (1977). II. Doll. Jt. hferririOA C*cr IO), 35 (1979), 19. 1ARC working group Ca*<*r Xntirth 49.1 (1910). 20. Davis, D.UaAd Magee, B.H.5nmcr 20*. 1334(1979). ; GOywri sm QQl*-OI)*/O/iSM4Ol.0O C1910MicmiHaajournals 1* a*-'