Chapter 1

Passive Smoking and

Lung Cancer

'Passive smoking' is the inhalation of tobacco smoke produced by other people. Because smoking itself is widely regarded as a cause of ill-health and in particular lung cancer, concern has been expressed that passive smoking also might be harmful. Although both smokers and non-smokers may be passive smokers, most concern has naturally been felt for the non-smoker and that is the question considered here: specifically, does passive smoking cause lung cancer in non-smokers?1 The answer necessarily must come from epidemiology, the study of the frequency, distribution and cause of illness and death. It is quite insufficient to quote the evidence that cigarette smoke contains poisons-it certainly does. The Surgeon General's report marshalls a battery of such evidence, but as such it is circumstantial and incomplete. Rhubarb and spinach contain about one per cent oxalic acid but we need not quail on being offered Eggs Florentine or Rhubarb and Apple Crumble, even though a lethal dose of oxalic acid is only 10 grams (Diem, 1962; Dreisbach, 1977). A properly controlled study would be needed to determine the incidence of rhubarb and spinach poisoning in the community. So too with passive smoking and lung cancer. If the purpose is to frame public policies which may limit individual freedoms then it is of particular importance that a correct and reliable answer be obtained.

There are two important kinds of study. In a case-control study, people with lung cancer are examined and compared to similar individuals without lung cancer. How do the individuals in the 2 groups differ? For example, if 100 non-smokers with lung cancer had all been exposed to tobacco smoke while 100 disease-free neighbours matched for age, sex, race etc had never been so exposed then this would constitute a strong link between passive smoking and lung cancer. In practice no one expects such clear cut results. If 60 of the lung cancer cases had been exposed compared with 40 of the healthy group then the result would be less clear. The methods of statistics are used to determine whether such a result is 'significant'. Here 'significant' means 'statistically significant'. It has nothing to do with the magnitude of the effect observed. A study which showed that passive smokers were 1% more likely to contract lung cancer than non-exposed individuals might still have found a significant effect.

The second kind of study is the prospective study. For example, select a group of healthy people married to non-smokers and follow them for 10 or 20 years. Compare them with a similar group of people married to smokers. Which group has the highest incidence of lung cancer and, once again, is the difference significant? A major difficulty with such studies is the time and money required to obtain a result. According to the orthodox view, it takes on average 40 to 50 years of cigarette smoking to induce lung cancer (Smoking and Health, 1962: 20). Only a small proportion will succumb much sooner. Therefore a large population must be studied over a long period if any significant effect is to be detected.

Table 1.1 summarises the results of prospective studies in men and women, with the duration of the trial and the number of subjects who were followed.

The tables summarise the results of 26 studies of lung cancer in nonsmoking men, women, and men and women. Of these, 20 revealed no association. Of 51 separate exposure situations (spouse, leisure, etc.), 45 revealed no association. The failure to find a positive association in most examples suggests a tenuous connection at most, unless the minority studies are of convincing persuasiveness.

The most widely quoted results are perhaps those of Hirayama. Hirayama (1981a) analysed his data with a test devised by N. Mantel. Mantel (1981) replied in a letter to the British Medical Journal in which he expressed concern about ambiguities and omissions in Hirayama's paper. In particular it appeared that in Mantel's test Hirayama had mistaken c for c2. Mantel provided an arithmetically detailed criticism including Mantel's own calculated values. He concluded 'The question then is whether he has conducted a more refined analysis, about which he is giving us no clues, or he has mistakenly interpreted his c2 value as a c value'. In other words, had Hirayama simply blundered, as even the best of us can do. Hirayama (1981b) replied to Mantel in the British Medical Journal, 3 October 1981 with the sentence: 'The validity of the significance test used in my paper was kindly confirmed by prominent statisticians in many institutes, including the US National Cancer Institute and the Massachusetts Institute of Technology.' With an appeal to unnamed authorities Hirayama therefore dismissed Mantel's queries without answering. In any other area of science-or indeed intellectual discourse generally-this would be enough to negate Hirayama's contribution. However he went further and added new information in the form of a histogram (Figure 1.1). This revealed some extraordinary results. Rutsch (1981) showed that from Hirayama's data it could be deduced that lung cancer was commoner for non-smoking unmarried women than for the non-smoking wives of smokers. Hirayama (1981d) agreed with Rutsch but noted that most of the 'unmarried' women were widows, adding 'Although their late or former husbands' smoking habits were not asked about at the time of enrolment there is little doubt that the majority of them were smokers'. Sloppy data collection, it appears, leaves little room for doubt.

Other strange features were described. Non-smoking men with smoking wives were as likely to get lung cancer as occasional smokers, if not more so. Lee (1981) pointed out that in effect this meant that a cigarette apparently had the same carcinogenic effects on a person whether it was smoked by him or by someone else! Because 'active' smokers must necessarily breathe the same air as 'passive' smokers this would be a remarkable result indeed.1 Surely 'active' smokers should get a double dose smoke they inhale while their cigarette is in their mouth, plus the polluted air they breathe between puffs. Lee went further and showed that Hirayama's 11 printed confidence intervals1 were all in error by factors of up to 1000%.

In reply to this new criticism Hirayama (1981c) admitted that his evidence appeared to show that it mattered not whether a cigarette was actively or passively smoked. His response to the errors pointed out by Lee was 'I regret that errors have been found in the 95% confidence intervals shown in the Figure in my last letter. The correct values are given in the accompanying Figure [Figure 1.2]. The errors do not, however, influence the substance of my letter'. After such a comedy of errors it is difficult to take seriously either his work of 1981 or his later paper (Hirayama, 1984). There can be few authors in the history of science who have distinguished themselves by replying to a published criticism with a reply which itself contains 11 errors of between 100% and 1000%.

Trichopolous et al. (1981) originally presented the results of his study for 40 non-smoking women with lung cancer. He compared them with 149 controls who did not have lung cancer. The results as risk-ratios1 for women whose husbands were non-smokers, ex smokers, 1-20 cigarettes/day and 21+/day are shown in Table 1.5.

Burch (1981) drew attention to a puzzling feature of the original Trichopolous data, one similar to that found by Hirayama: the non-smoking wives of heavy smokers were more likely to contract lung cancer than wives who actively smoked. Burch made the pointed comment: 'It is difficult to imagine that passive smokers-even with husbands smoking more than 20 cigarettes per day-could breathe in more carcinogens than active smokers.' There comes a point at which the case against passive smoking becomes too strong: it has been reached when evidence shows-or appears to show-that passive smoking is more dangerous than active smoking.

Trichopolous continued to add to his observations. By 1983 he had almost doubled his number of cases and controls. He published the results for the combination of new and old subjects and controls (Trichopolous et al., 1983) (Table 1.5). Remarkably, in spite of the increase, the risk-ratios were virtually unchanged: with ex-smoking husbands, 1.8 became 1.9, with 1-20 cigarettes/day husbands the risk-ratio remained at 2.4, and for 21+ cigarettes/day husbands the risk-ratio remained at 3.4. Such resistance to change in the risk-ratios, though possible, is most unlikely and suggests there might be another explanation for the results. There is indeed, as Heller (1983) showed. From the published data (Trichopolous, 1983) Heller recalculated the ratios (Table 1.5). Trichopolous (1984) replied to Heller in the Lancet March 24, 1984: 'He is right and we apologise for our typing error (which was pointed out by others including Dr Gosta Axelson of Goteborg, Sweden)'. Once again, a most casual response to a most serious criticism of the principal conclusion to his 1983 statement. Although published scientific results are normally taken on faith, such casualness in this case makes them at best dubious.

In my opinion the results of Hirayama and Trichopolous have been vitiated both by the devastating criticisms which have been made of them and by the casual and indeed inadequate responses by their two authors.

How then have such august authorities as the Surgeon-General of the United States of America (Koop, 1986) and the National Health and Medical Research Council of Australia (NHMRC, 1986) arrived at the conclusion that the epidemiological evidence is 'strongly suggestive' (NHMRC, 1986: 38) or 'compelling' (Koop, 1986: 97)? The answer may lie in a quite uncritical evaluation of the evidence. Consider the results of Trichopolous. The NHMRC in its Report grasped the nettle firmly (NHMRC, 1986: 33). Only the original and incorrect calculations of risk ratios given by Trichopolous et al. (1983) were quoted: no mention was made of the total recalculation of risk-ratios produced by Heller (1983) and accepted by Trichopolous (1984). The Surgeon-General of the USA (Koop, 1986: 71) gave the corrected values but attributed them to 'Trichopolous et al., 1983', where they do not appear, rather than to Heller (1983) who had corrected the faulty homework of Trichopolous et al. For his trouble, Heller (1983) does not even get mentioned by the Surgeon-General. This avoidance of published corrections leads to a quite natural sense of security in acceptance of erroneous published conclusions.

The results of Hirayama receive a similarly curious treatment. The Surgeon-General in a discussion of Hirayama's critics made no mention of the enormous errors in Hirayama's 1981b paper. On the contrary, he said (page 76) that in response to Lee's (1981) criticism 'the calculations were later confirmed', but did not mention the fact that Hirayama himself admitted making errors of a magnitude which put them more in the realm of cosmology than epidemiology. The NHMRC Report on the other hand simplified the issue by not even mentioning the question of error.

A similar lack of critical zeal has been effected with other papers on passive smoking. The study of Correa et al., (1983) is described in the Report as showing 'Positive association in both males and females statistically significant'. As shown by Correa et al., in their Table 1, it was in fact significant only for females. The Report also states that Correa et al., found a positive trend in lung cancer in non-smokers with passive smoking. They did not and nowhere say so. Garfinkel et al., (1985) are described in the Report's Table 1 as having reported a 'Positive association in non-smoking females; statistically significant'. Garfinkel et al. in fact summarise their results by saying 'In conclusion, we found an elevated risk of lung cancer, ranging from 13 to 31%, in women exposed to the smoke of others, although the increase was not statistically significant' (emphasis added); the justification for the Report's claim seems to be that the small subset of women whose husbands smoked more than 20 or more cigarettes per day were significantly more likely to develop lung cancer (NHMRC, 1986: 35). The danger of such selective presentation of data is readily demonstrated: another subset of women, those who had been exposed to passive smoking for 1-2 hours per day over the last 25 years were significantly less likely to develop lung cancer (Garfinkel et al., 1985: Table 4). It is possible to go through the multiple analysis of Garfinkel et al. and find as many significant negative associations as positive associations but the overall result remains as stated by the authors and not by the NHMRC Report. Perhaps this discrepancy due to selective presentation is not surprising. The terms of reference of the NHMRC Committee required 'a thorough review of the literature'. Yet their Section 7, 'Passive smoking and cancer', in its 34-item bibliography includes no reference to Burch (1981), Heller (1983), Hirayama (1981b), Hirayama (1981c), Lee (1981), Mantel (1981), Rutsch (1981), or Trichopolous (1984)

.

Conclusion

It is evident from what has been presented that drawing a conclusion from the mass of published data on passive smoking and lung cancer is bound to be exceedingly difficult. One way of doing so is to consider the data at three successive levels of analysis. First, examine the results taken at face value. Second, examine the criticism of the work and the responses of the authors. Third, examine the reviews of experts.

1. At face value the published studies do little to inspire confidence in anything stronger than a 'not proven' verdict, if not one of 'not guilty'. The great majority have produced no association between passive smoking and lung cancer. Any true correlation must be so small as to be scarcely detectable by even the most expensive and time consuming of trials.

2. The criticisms levelled at some of the most important studies have been both justified and convincing, and the responses of the authors have often been inadequate and inappropriate. It is in the nature of science that errors are made and published but few scientists make errors of the kind and order of those described here. There comes a point at which the most trusting reader, scientist or not, is justified in treating some published data with profound reserve.

3. It is the duty of experts whether in committee or not, to critically assess the evidence on which they will base their conclusions. That has not in general happened. Rather there has been what can only be described as a cover-up. Even when the critical assessment and recalculation of the data have been done by others, the corrected amendments have been either ignored or incorporated without mention of the criticisms. Results have been selectively presented with unwelcome results left unpresented.

Ultimately, with the results presently available, any judgement must be subjective. But there is a way of obtaining a new perspective on the available material. Suppose the results described in this chapter referred not to cigarette smoke but to barbecue smoke wafted into a neighbour's backyard, or the vapour from deodorised family members and workmates. Would such results lead to the banning of barbecues or the exclusion of the deodorised from public society? The notion would, I think, be dismissed as absurd and resting on quite inadequate evidence, even though both meat smoke and deodorants may contain carcinogens (McGee, 1984; Selinger, 1989). But barbecues and the deodorised are not scapegoats. Not yet.

Bibliography

Adlersberg, D., L.E. Schaefer and A.G. Steinberg (1956), 'Age, sex, serum lipids and coronary atherosclerosis', Journal of the American Medical Association, 162, pages 619-622.

Akiba, S., H. Keto and W.J. Blot (1986), 'Passive smoking and lung cancer among Japanese women', Cancer Research, 46, pages 4804-4807.

Anderson, Digby (ed.) (1986), A Diet of Reason: Sense and Nonsense in the Healthy Eating Debate, London: The Social Affairs Unit.

Anderson, Digby (1988), The Megaphone Solution: Government attempts to cure social problems with mass media campaigns, London: The Social Affairs Unit.

Anon (1984): Office of Road Safety, Alcohol and road usage, Canberra: Department of Transport.

Anon (1986): 'Alcohol and the motorist', The Road Patrol, December 1986-January 1987, pages 2-6.

Armstrong, B.K. (1988), 'The epidemiology and prevention of cancer in Australia', Australian and New Zealand Journal of Surgery, 58, pages 179-187.

Berkson, J. (1960), 'Smoking and cancer of the lung', Proceedings of the Mayo Clinic, 35, page 367.

Birrell, J.H. (1974), Drinking, driving and you, Melbourne: Sun Books.

Borkenstein, R.F., R.F. Crowther, R.P. Shumate, W.B. Ziel and R. Zylman (1964), The role of the drinking driver in traffic accidents, Bloomington: Department of Police Administration, Indiana University; second edition (re-edited by R.F. Borkenstein) published in Blutalkohol, Supplement 1 Volume II, 1974.

Broad, William and Wade, Nicholas (1983), Betrayers of the Truth, New York: Simon and Schuster.

Browning, Bob (1990), The Network: A Guide to Anti-Business Pressure Groups, Melbourne: Canonbury Press.

Buchan, A.P. (1818), Venus sine Concubitu: De Pollutione nocturna et diurna eorumque Sequelae et Curatio, London: J. Callow.

Buffler, P.A., L.W. Pickle, T.J. Mason and C. Content (1984), 'The causes of lung cancer in Texas' in M. Mizell and P. Correa (eds), Lung Cancer: Causes and Prevention, Deerfield Beach: Verlag Chimie International.

Burch, P.R.J. (1981), 'Passive smoking and lung cancer', British Medical Journal, 282, page 1393.

Burch, P.R.J. (1985), 'Lifetime passive smoking and cancer risk', Lancet, 1, page 866.

Chan, W.C. and S.C. Fung (1982), 'Lung cancer in non-smokers in Hong Kong' in E. Grundmann (ed.), Cancer Campaign, Volume 6, Cancer Epidemiology, New York: Gustav, Fischer, Verlag, pages 199-202.

Cheyne, C. (1745), An Essay of Health and Long Life, 9th edn, London: George Strahan.

Christakis, G., S.H. Rinzler, M. Archer and A. Kraus (1966), 'Effect of the anti-coronary club program on coronary heart disease risk-factor status', Journal of the American Medical Association, 198, pages 597-604.

Committee of Principal Investigators (1978), 'A cooperative trial in the primary prevention of ischaemic heart disease using clofibrate', British Heart Journal, 40, pages 1069-1118.

Committee of Principal Investigators (1980), 'WHO cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up', Lancet, 2, pages 379-385.

Committee of Principal Investigators (1984), 'WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up', Lancet, 2, pages 600-604.

Cook, R.P. (1958), Cholesterol: chemistry, biology and pathology, New York: Academic Press.

Coronary Drug Project Research Group, The (1970), 'The coronary drug project: initial findings leading to modifications of its research protocol', Journal of the American Medical Association, 214, pages 1303-1313.

Coronary Drug Project Research Group, The (1972), 'The coronary drug project: findings leading to further modifications of its protocol with respect to dextrothyroxine', Journal of the American Medical Association, 220, pages 996-1008.

Coronary Drug Project Research Group, The (1973), 'The coronary drug project: findings leading to discontinuation of the 2.5 mg/day estrogen group', Journal of the American Medical Association, 226, pages 652-657.

Coronary Drug Project Research Group, The (1975), 'The coronary drug project: clofibrate and niacin in coronary heart disease', Journal of the American Medical Association, 231, pages 360-381.

Correa, P., L.W. Pickle, E. Fontham, Y. Lin and W. Haensze (1983), 'Passive smoking and lung cancer', Lancet, 2, pages 595-597.

Dalager, N.A., L.W. Pickle, T.J. Mason, P. Correa, E. Fontham, A. Stenhagen, P.A. Buffler, R.G. Ziegler and J.E. Fraumeni, Jr (1986), 'The relation of passive smoking to lung cancer', Cancer Research, 46, pages 4808-4811.

Dawber, T.R. (1980), The Framingham study: the epidemiology of atherosclerotic disease, Cambridge Mass.: Harvard University Press.

Dawber, T.R., F.E. Moore and G.V. Mann (1957), 'Coronary heart disease in the Framingham study', American Journal of Public Health, 47, pages 4-24.

Dayton, S. and M.L. Pearce (1969), 'Prevention of coronary heart disease and other complications of atherosclerosis by modified diet', American Journal of Medicine, 46, pages 751-762.

Dayton, S., M.L. Pearce, S. Hashimoto, W.J. Dixon and U. Tomiyasu (1969), 'A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis', Circulation, 40, (Suppl. II), pages 1-63.

Diem, K. (ed) (1962), Documenta Geigy Scientific Tables, St Leonards, N.S.W.: Geigy Pharmaceuticals.

Dreisbach, R.H. (1977), Handbook of Poisoning: Diagnosis and Treatment, Los Altos: Lange Medical Publications.

Dyer, A.R., J. Stamler, O. Paul, R.B. Shekelle, J.A. Schoenberger, D.M. Berkson, M. Lepper, P. Collette, S. Shekelle and H.A. Lindberg (1981), 'Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies', Journal of Chronic Diseases, 34, pages 249-260

Eysenck, H.J. (1986), 'Smoking and Health' in Robert Tollison (ed.), Smoking and Society, Massachusetts: Lexington Books, pages 17-88.

Finch, Peter D. (1990a), 'The Lalonde Doctrine in Action: The Campaign Against Passive Smoking', Policy, 6 (2), [Sydney: The Centre for Independent Studies], pages 22-25.

Finch, Peter D. (1990b), 'The Health Effects of Smoking: Misreading the Evidence', Policy, 6 (3), [Sydney: The Centre for Independent Studies], pages 22-25.

Frick, H., O. Elo, K. Haapa, O.P. Heinonen, P. Heinsalmi, P. Helo, J.K. Huttunen, P. Kaitaniemi, P. Koskinen, V. Manninen, H. MSenpSS, M. MSlksnen, M. MSnttSri, S. Norola, A. Pasternack, J. Pikkarainen, M. Romo, T. Sjsblom and E.A. NikkilS (1987), 'Helsinki heart study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia', New England Journal of Medicine, 317, pages 1237-1281.

Gardner, Martin (1957), Fads and Fallacies in the Name of Science, New York: Dover Publications.

Garfinkel, L. (1981), 'Time trends in lung cancer mortality among non-smokers and a note on passive smoking', Journal of the National Cancer Institute, 66, pages 1061-1066.

Garfinkel, L., O. Auerbach and L. Joubert (1985), 'Involuntary smoking and lung cancer: a case-control study', Journal of the National Cancer Institute, 75, pages 463-469.

Gillis, C.R., D.J. Hale, V.M. Hawthorne and P. Boyle (1984), 'The effect of environmental tobacco smoke in two urban communities in the west of Scotland', European Journal of Respiratory Diseases, 65 (Suppl. 133), pages 121-126.

Goldbourt, U., E. Holtzman and H.N. Neufeld (1985), 'Total and high density lipoprotein cholesterol in the serum and risk of mortality: evidence of a threshold effect', British Medical Journal, 290, pages 1239-1243.

Hatton, W.M. (1987), Cancer Projections: Projections of numbers of incident cancers in Western Australia to the Year 2001, Perth: Epidemiology Branch, Health Department of Western Australia.

Hatton, W.M. and M.D. Clarke-Hundley (1987), Cancer in Western Australia: an analysis of age and sex specific rates, Perth: Health Department of Western Australia.

Heady, J.A. (1973), 'A cooperative trial on the primary prevention of ischaemic heart disease using clofibrate: design, methods, and progress', Bulletin of the World Health Organisation, 48, pages 243-256.

Heller, W.-D. (1983), 'Lung cancer and passive smoking', Lancet 2, page 1309.

Herbert, D.C. (1982), 'The size of the drink-driving problem for road safety in New South Wales-update 7 June 1982', TARU Special Report No SR 82/118, Traffic Accident Research Unit, Canberra

Hirayama, T. (1981a), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan', British Medical Journal, 1, pages 183-185.

Hirayama, T. (1981b), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer', British Medical Journal, 2, pages 916-917.

Hirayama, T. (1981c), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer', British Medical Journal, 2, page 1466.

Hirayama, T. (1981d), 'Passive smoking and lung cancer', British Medical Journal, 282, pages 1393-1394.

Hirayama, T. (1984a), 'Cancer mortality in nonsmoking women with smoking husbands based on a large-scale cohort study in Japan', Preventive Medicine, 13, pages 680-690.

Hirayama, T. (1984b), 'Lung cancer in Japan: Effects of nutrition and passive smoking' in M. Mizell and P. Correa (eds), Lung Cancer: Causes and Prevention, Deerfield Beach: Verlag Chemie International.

Hjermann, I., K. Velve Byre, I. Holme and P. Leren (1981), 'Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo study group of a randomised trial in healthy men', Lancet, 2, pages 1303-1310.

Holme, I., I. Hjermann, A. Helgeland and P. Leren (1985), 'The Oslo study: diet and anti-smoking advice. Additional results for a 5-year primary preventive trial in middle-aged men', Preventive Medicine, 14, pages 279-292.

Humble, C.G., J.M. Samet and D.R. Pathak (1987), 'Marriage to a smoker and lung cancer risk', American Journal of Public Health, 77, pages 598-602.

Hurst, P.M. (1973), 'Epidemiological aspects of alcohol in driver crashes and citations', Journal of Safety Research, 5, pages 130-148.

Johnstone, J.R. (1981), 'The myth of immortality', The Australian Surgeon, 4, pages 8-10.

Johnstone, J.R. (1982), 'In pursuit of ill-health', Chelwood Review, 12, pages 13-16.

Johnstone, J.R. (1988), 'Life styles and controlled trials', in N.W. Bruce, L. Freedman and W.F.C. Blumer (eds), Perspectives in Human Biology, [Proceedings of the Australasian Society for Human Biology No. 1], Perth: Centre for Human Biology, University of Western Australia, pages 121-128.

Johnstone, J.R. (1989), 'Controlled trials, cholesterol, coronary heart disease and health', in W.J. Cliff and G.I. Schoefl (eds), Coronaries and Cholesterol, London: Chapman and Hall, pages 115-135.

Kabat, G.C. and E.L. Wynder (1984), 'Lung cancer in non-smokers', Cancer, 53, pages 1214-1221.

Kagan, A., D.L. McGee, K. Yano, G.C. Rhoads and A. Nomura (1981), 'Serum cholesterol and mortality in a Japanese-American population: the Honolulu heart program', American Journal of Epidemiology, 114, pages 11-20.

Kaji, H., Y. Asanuma, O. Yahara, H. Shibue, M. Hisamura, N. Saito, Y. Kawakami and M. Murao (1984), 'Intragastrointestinal alcohol fermentation syndrome: report of two cases and review of the literature', Journal of the Forensic Science Society, 24, pages 461-471.

Karvonen, M.J., H. Klemola, J. Virkajarvi and A. Kekkonen (1974), 'Longevity of endurance skiers', Medicine and Science in Sports, 6, pages 49-51.

Katz, L.N., and J. Stamler (1953), Experimental atherosclerosis, [American lecture series No. 124], Springfield, USA: Charles C. Thomas.

Keys, A. (1970), 'Coronary heart disease in seven countries', Circulation, 41, (Suppl. 1), pages 1-211.

Keynes, G. (1978), The Life of William Harvey, Oxford: Oxford University Press.

Kirkham, R.W. (1978), Research & Statistics Division Report No. 7, Perth: Road Traffic Authority.

Koestler, A. (1971), The Case of the Midwife Toad, London: Hutchinson and Co.

Kohn, Alexander (1986), False Prophets: Fraud and Error in Science and Medicine, Oxford: Basil Blackwell.

Kolata, G. (1982), 'Heart study produces a surprise result', Science, 218, pages 31-32.

Koo, L.C., J.H.-C. Ho, D. Saw (1984), 'Is passive smoking an added risk factor for lung cancer in Chinese women?', Journal of Experimental and Clinical Cancer Research, 3, pages 277-283.

Koo, L.C., J.H.-C. Ho and N. Lee (1985), 'An analysis of some risk factors for lung cancer in Hong Kong', British Journal of Cancer, 35, pages 149-155.

Koo, L.C., J.H.-C. Ho, D. Saw and C. Ho (1987), 'Measurements of passive smoking and estimates of lung cancer risk among non-smoking Chinese females', International Journal of Cancer, 39, pages 162-169.

Koop, C.E. (1982), The health consequences of smoking. Cancer, Rockville: US Department of Health and Human Services

Koop, C.E. (1986), The health consequences of involuntary smoking: a Report of the Surgeon-General, Rockville: US Department of Health and Human Services.

Kozarevic, D., D. McGee, N. Vojvodic, T. Gordon, Z. Racic, W. Zukel and T. Dawber (1981), 'Serum cholesterol and mortality: the Yugoslavia cardiovascular disease study', American Journal of Epidemiology, 114, pages 21-28.

Krebs, H.A. and J.R. Perkins (1970), 'The physiological role of live alcohol dehydrogenase', Biochemical Journal, 118, pages 635-644.

Landauer, A.A. (1981), 'Alcohol drinking reduces hand tremor', British Journal of Addiction, 76, pages 429-430.

Last, J.M. (1983), A Dictionary of Epidemiology, Oxford: Oxford University Press.

Lee, P.N. (1981), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer', British Medical Journal, 283, pages 1465-1466.

Lee, P.N., J. Chamberlain and M.R. Alderson (1986), 'Relationship of passive smoking to risk of lung cancer and other smoking-related diseases', British Journal of Cancer, 54, pages 97-105.

Leren, P., E.M. Askenvold, O.P. Foss, A. Fršili, D. Grymyr, A. Helgeland, I. Hjermann, I. Holme, P.G. Lund-Larsen and K.R. Norum (1975), 'The Oslo study. Cardiovascular disease in middle-aged and young Oslo men', Acta Medica Scandinavica [Suppl.], 588, pages 1-38.

Lipid Research Clinics Program, The (1979), 'The coronary primary prevention trial: design and implementation', Journal of Chronic Diseases, 32, pages 609-631.

Lipid Research Clinics Program, The (1984), 'The lipids research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease', Journal of the American Medical Association, 251, pages 351-364.

Lyte, H.C.M. (1899), A History of Eton College (1440-1898), London: Macmillan.

Mann, G.V. (1977), 'Diet-heart: end of an era', New England Journal of Medicine, 297, pages 644-650.

Mann, G.V., A. Spoerry, M. Gray and D. Jarashow (1972), 'Atherosclerosis in the Masai', American Journal of Epidemiology, 95, pages 26-37.

Mantel, N. (1981), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer', British Medical Journal, 2, pages 914-915.

Martin, M.J., S.B. Hulley, W.S. Browner, L.H. Kuller and D. Wentworth (1986), 'Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men', Lancet, 2, pages 933-936.

McGee, H. (1984), On Food and Cooking, New York: Charles Scribner's Sons.

Miettinen, M., O. Turpeinen, M.J. Karvonen, R. Elosuo and E. Paavilainen (1972), 'Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes', Lancet, 2, pages 835-838.

Miettinen, T.A., J.K. Huttunen, V. Naukkarinen, T. Strandberg, S. Mattila, T. Kumlin and S. Sarna (1985), 'Multifactorial primary prevention of cardiovascular diseases in middle-aged men: risk-factor changes, incidence and mortality', Journal of the American Medical Association, 254, pages 2097-2102.

Montoye, H.J., W.D. Van Huss, H. Olson, A. Hudec and E. Mahoney (1956), 'Study of the longevity and morbidity of college athletes', Journal of the American Medical Association, 162, pages 1132-1136.

Moore, Thomas J. (1989), Heart Failure: A Critical Inquiry into American Medicine and the Revolution in Heart Care, New York: Random House.

Multiple Risk Factor Intervention Trial Research Group (1982), 'Multiple risk factor intervention trial: risk factor changes and mortality results', Journal of the American Medical Association, 248, pages 1465-1477.

Myant, N.B. (1981) The Biology of cholesterol and related steroids, London: Heinemann Medical Books.

Nanikawa, R. and S. Kotoku (1971), 'Medico-legal evaluation of the ethanol levels in cadaveric blood and urine', Yonago Acta Medica, 15, pages 61-69.

National Heart Foundation of Australia (1967), 'Dietary fat and coronary heart disease: a review', Medical Journal of Australia, 1, pages 309-322.

NHMRC (1986): National Health and Medical Research Council, Report of the working party on the effects of passive smoking on health.

Paffenberger, R.S., R.T. Hyde, A.L. Wing and C.-C. Hsieh (1986), 'Physical activity, all-cause mortality, and longevity of college alumni', New England Journal of Medicine, 314, pages 605-613.

Pekkanan, J., B. Marti, A. Nissinen and J. Tuomilehto (1987), 'Reduction of Premature mortality by high physical activity: a 20-year follow-up of middle-aged Finnish men', Lancet, 27 June 1987, pages 1473-1477.

Pershagen, G., Z. Hrubek and C. Svensson (1987), 'Passive smoking and lung cancer in Swedish women', American Journal of Epidemiology, 125, pages 17-24.

Peterson, B., E. Trell and N.H. Sternby (1981), 'Low cholesterol level as risk factor for noncoronary death in middle-aged men', Journal of the American Medical Association, 245, pages 2056-2057.

Pinckney, E.R. and R.L. Smith (1987), 'Statistical analysis of lipid research clinics program', Lancet, 1, pages 503-504.

Polednak, A.P. (1972), 'Longevity and cause of death among Harvard college athletes and their classmates', Geriatrics, 27, pages 53-64.

Polednak, A.P. (ed.) (1979), The longevity of athletes, Springfield: Charles C. Thomas.

Price, F.W. (ed.) (1942), A textbook of the practice of medicine, 6th edition, London: Oxford University Press.

Prout, C. (1972), 'Life expectancy of college oarsmen', Journal of the American Medical Association, 220, pages 1709-1711.

Puska, P., J. Tuomilehto, J. Salonen, L. NeittaanmSki, J. Maki, J. Virtamo, A. Nissinen, K. Koskela and T. Takalo (1979), 'Changes in coronary risk factors during comprehensive five-year community programme to control cardiovascular diseases (North Karelia project), British Medical Journal, 2, pages 1173-1178.

Reilly, R. (1979), William Pitt the Younger, New York: Putnam.

Rinzler, S.H. (1968), 'Primary prevention of coronary heart disease by diet', Bulletin of the New York Academy of Medicine, 44, pages 936-949.

Rook, A. (1954), 'An investigation into the longevity of Cambridge sportsmen', British Medical Journal, 1, pages 773-777.

Rose, G. and P.J.S. Hamilton (1978), 'A randomised controlled trial of the effect on middle-aged men of advice to stop smoking', Journal of Epidemiology and Community Health, 32, pages 275-281.

Rose, G., and M.J. Shipley (1980), 'Plasma lipids and mortality: a source of error', Lancet, 1, pages 523-526.

Rose, G., P.J.S. Hamilton, L. Colwell and M.J. Shipley (1982), 'A randomised controlled trial of anti-smoking advice: 10-year results', Journal of Epidemiology and Community Health, 36, pages 102-108.

Rutsch, M. (1981), 'Non-smoking wives of heavy smokers have a higher risk of lung cancer', British Medical Journal, 282, page 985.

Salmond, C.E., R. Beaglehole and I.A.M. Prior (1985) 'Are low cholesterol values associated with excess mortality?', British Medical Journal, 290, pages 422-424.

Salonen, J.T., P. Puska and H. Mustaniemi (1979), 'Changes in morbidity and mortality during comprehensive community programme to control cardiovascular diseases during 1972-7 in North Karelia', British Medical Journal, 2, pages 1178-1183.

Sandler, D.P., A.J. Wilcox and R.B. Everson (1985a), 'Cumulative effects of lifetime passive smoking on cancer risk', Lancet 1, pages 312-315.

Sandler, D.P., R.B. Everson, A.J. Wilcox and J.P. Browder (1985b), 'Cancer risk in adulthood from early life exposure to parents smoking', American Journal of Public Health, 75, pages 487-492.

Schnohr, P. (1971), 'Longevity and causes of death of male athletic champions', Lancet 2, pages 1364-1366.

Selinger, B. (1989), Chemistry in the Marketplace, Sydney: Harcourt Brace Jovanovich.

Sherwin, R.W., D.N. Wentworth, J.A. Cutler, S.B. Hulley, L.H. Kuller and J. Stamler (1987), 'Serum cholesterol levels and cancer mortality in 361,662 men screened for the multiple risk factor intervention trial', Journal of the American Medical Association, 257, pages 943-948.

Shurtleff, D. (1974), 'Section 30: Some characteristics related to the incidence of cardiovascular disease and death: Framingham study, 18-year Follow-up', in W.B. Kannel and T. Gordon (eds), The Framingham study: an epidemiological investigation of cardiovascular disease, Washington: US Govt Printing Office (DHEW publication No. (NIH) pages 74-599).

Smoking and Health: Summary of a report of the Royal College of Physicians of London on smoking in relation to cancer of the lung and other diseases (1962), London: Pitman.

Smoking and Health Now (1971), London: Pitman.

Smoking or Health: the third report from the Royal College of Physicians of London (1977), London: Pitman Medical.

Stenhouse, N.S. (1979), Busselton Norms: statistics of the physiological variables measured at the Busselton health survey 1972, Nedlands: University of Western Australia Press.

Stolley, P.D. (1983), 'Lung cancer in women-five years later, situation worse', New England Journal of Medicine, 309, pages 428-429.

Szasz, T. (1977), The Theology of Medicine, Baton Rouge: Louisiana State University Press.

Szasz, T. (1980), Sex: facts, frauds and follies, Oxford: Basil Blackwell.

Taylor, R. (1979), Medicine Out of Control: The Anatomy of a Malignant Technology, Melbourne: Sun Books.

Tollison, Robert (ed.) (1986), Smoking and Society, Massachusetts: Lexington Books.

Trichopolous, D. (1984), 'Passive smoking and lung cancer', Lancet, 24 March 1984, page 684.

Trichopolous, D., A. Kalondidi and L. Sparros (1983), 'Lung cancer and passive smoking: conclusion of Greek study', Lancet, 2, pages 677-678.

Trichopolous, D., A. Kalondidi, L. Sparros and B. MacMahon (1981), 'Lung cancer and passive smoking', International Journal of Cancer, 27, pages 1-4.

Turpeinen, O., M.J. Karvonen, M. Pekkarinen, M. Miettinen, R.O. Elosuo and E. Paavilainen (1979), 'Dietary prevention of coronary heart disease: the Finnish mental hospital study', International Journal of Epidemiology, 8, pages 99-118.

U.S. Congress, Fraud in Biomedical Research, Hearings Before the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, House of Representatives, Washington, 31 March, 1 April 1981.

U.S. Congress, Scientific Fraud and Misconduct and the Federal Response, Hearing Before a Subcommittee of the Committee on Government Operations, House of Representatives, Washington, 11 April 1988.

U.S. Congress, Fraud in NIH Grant Programs, Hearing Before the Subcommittee on Oversight and Investigations of the Committee on Energy and Commerce, House of Representatives, Washington, 12 April 1988.

U.S. Congress, Federal Response to Misconduct in Science: Are Conflicts of Interest Hazardous to Our Health?, Hearing Before a Subcommittee of the Committee on Government Operations, House of Representatives, Washington, 29 September 1988.

Walls, H.J. and Brownlie, A.R. (1985), Drink, Drugs and Driving, London: Sweet and Maxwell.

Westfall, R.S. (1976), 'Sir Isaac Newton', in Encyclopaedia Britannica, 15th edn.

Westlund, K. and R. Nicolaysen (1966), 'Serum cholesterol and risk of mortality and morbidity: a 3-year follow-up of 6,886 men', Scandinavian Journal of Clinical and Laboratory Investigations, 18 (Supplement 87), pages 1-19.

WHO European Collaborative Group (1974), 'An international controlled trial in the multifactorial prevention of coronary heart disease', International Journal of Epidemiology, 3, pages 219-224.

WHO European Collaborative Group (1982), 'Multifactorial trial in the prevention of coronary heart disease: 2. Risk factor changes at two and four years', European Heart Journal, 3, pages 184-190.

WHO European Collaborative Group (1983), 'Multifactorial trial in the prevention of coronary heart disease: 3. Incidence and mortality results', European Heart Journal, 4, pages 141-147.

WHO European Collaborative Group (1986), 'European collaborative trial of multifactorial prevention of coronary heart disease: final report on the 6-year results', Lancet, 1, pages 869-872.

Wilhelmsen, L., G. Berglund, E. Elmfeldt, G. Tibblin, H. Wedel, K. Pennert, A. Vedin, C. Wilhelmsson and L. Werks (1986), 'The multifactor primary prevention trial in Gsteborg', European Heart Journal, 7, pages 279-288.

Woodhill, J.M., A.J. Palmer, B. Leelarthaepin, C. McGilchrist and R.B. Blacket (1977), 'Low fat, low cholesterol diet in secondary prevention of coronary heart disease', in Drugs, lipoproteins and atherosclerosis, New York: Plenum Press, pages 317-330.

Wu, A.H., B.E. Henderson, M.C. Pike and M.C. Yu (1985), 'Smoking and other risk factors for cancer in women', Journal of the National Cancer Institute, 74, pages 747-751.

Zukel, W.J., O. Paul and H.W. Schnaper (1981), 'The multiple risk factor intervention trial (MRFIT). I. Historical perspectives', Preventive Medicine, 10, pages 387-401.