1. Sir Richard Doll (1912- 2005), Physician, Epidemiologist, Teacher, Humanitarian, Legend, Activist, Researcher, Public Health lobbyist Smoking and Health

2. CONDITIONS TREATED WITH TOBACCO 16 th Century Malignant tumours Open woundsStomach cramps Intestinal wormsHeadaches Diseases of womenAsthma GoutCough

4. SÖMMERING 1795 DOCTORAL THESIS “Carcinoma of the lip is most frequent when people indulge in tobacco pipes. For the lower lip is particularly attacked by carcinoma because it is compressed between the pipe and the teeth”

5. PERCENTAGE OF MEN ATTENDING MASSACHUSETTS CANCER CLINICS WITH DIFFERENT CANCERS: BY SMOKING HABIT (Potter & Tulley, 1945) Use of tobacco (no. of men) Cancer of: buccal cavity respiratory tract other sites None(655)3.70.522.4 Slight(357)8.11.125.1 Moderate(1155)11.52.026.0 Excessive(760)17.91.723.4

6. USE OF TOBACCO BY DISEASE CATEGORY: 86 MEN WITH AND 86 MEN WITHOUT LUNG CANCER (after Müller, 1939) Type of smokerN o. of men with lung cancer healthy controls 1 Extreme smoker254 2 Very heavy smoker185 3 Heavy smoker1322 4 Moderate smoker2741 Non-smoker314 1 10-15 cigars, >35 cigarettes, >50g pipe tobacco/day 2 7-9“26-35“36-50g“““ 3 4-6“16-25“21-35g“““ 4 1-3“1-15“1-20g“““

7. SMOKING AND LUNG CANCER CASE-CONTROL STUDIES BEFORE 1950 195519.04.5100134 Wassink, 1948 Holland 275215.93.227093 Schairer & Schöniger, 1943 Germany 366516.33.58636 Müller, 1939 Germany ControlsLung cancer ControlsLung cancer Heavy smokersNon-smokers ControlsLung cancer Percent of:No. of men Author

8. TOBACCO AND CORONARY DISEASE (English, Willius & Berkson, 1940) † Number of smokers and all men in age group in parentheses *P, one-sided 0.0566.3 (663/1000)69.8 (698/1000)40+ 0.2861.8 (202/327)63.8 (275/431)60+ ─73.9 (274/371)71.7 (274/382)50-9 <0.00161.9 (187/302)79.7 (149/187) † 40-9 Others Coronary disease P*Percent smokers Men aged (yrs)

9. TOBACCO AND CORONARY DISEASE (English, Willius & Berkson, 1940) † Number of men with coronary disease and all diseases in age group in parentheses *P, one-sided 0.043.8 (38/1000)5.4 (54/1000)40+ ─6.4 (26/404)5.0 (20/404)60+ 0.012.6 (10/388)6.2 (24/388)50-9 0.011.0 (2/208)4.8 (10/208) † 40-9 Non-smokers Smokers P*Percent coronary disease in: Men aged (yrs)

11. SMOKING AND LUNG CANCER CASE-CONTROL STUDIES PUBLISHED IN 1950 195114.6*1.3*780605Wynder & Graham USA ──317430444 Mills & Porter USA *Lifelong non-smokers, with ex-smokers carefully excluded 13264.2*0.3*649 Doll & Hill UK ──21.715.3481236 Levin et al. USA 91823.914.652282 Schreck et al. USA Controls Lung cancer Controls Lung cancer Heavy smokers Non-smokers ControlsLung cancer Percent of : No. of menAuthor

13. MORTALITY BY AMOUNT SMOKED RELATIVE TO THAT IN NON-SMOKERS (after Hammond & Horn, 1954) 1.11.31.0605 65-69 2.02.21.5594 60-64 coronary heart disease 2.11.91.1571 55-59 2.52.11.7377 50-54 lung cancer 8.842167 50-69 20 or more 10-19 Less than 10 Cause of death Regular cigarette smokers smoking (per day): No. of deaths Age (yrs)

14. BERKSON’S ALTERNATIVES “The findings were the result of the interplay of various subtle and complicated biases or had a constitutional basis, involving people who were non-smokers or relatively light smokers, being the kind who were biologically self- protective and this “correlated with robustness in meeting mortal stress from disease generally”

15. FISHER’S OBJECTIONS (i)Smokers with lung cancer reported inhaling less than smokers without (Doll & Hill, 1950) against causation unless it was concluded that “Inhaling cigarette smoke was a practice of considerable prophylactic value in preventing the disease”

16. FISHER’S OBJECTIONS (ii)Secular changes in smoking habits could not be related to the increase in lung cancer since “lung cancer has been increasing more rapidly in men relative to women” while “it is notorious, and conspicuous in the memory of most of us, that over the last 50 years the increase among women has been great, and that the increase among men (even if positive) certainly small”

17. CANCERS CAUSED IN PART BY SMOKING (International Agency for Research on Cancer, 2004) *Increased more than fivefold Ureter*Oesophagus Liver Stomach Nose & nasal sinuses *Larynx Pancreas Nasopharynx Kidney *Oro- & hypo- pharynx Myeloid leukaemia Cervix Oral (incl. lip & tongue) *Lung Bladder

18. VASCULAR AND RESPIRATORY DISEASE CAUSED IN PART BY SMOKING *Increased more than five-fold *Buerger’s disease Pulmonary tuberculosis*Peripheral vascular disease Asthma*Aortic aneurysm Pneumonia Arteriosclerosis *Chronic obstructive lung disease Hypertension (fatal) Cerebral haemorrhage Myocardial degeneration Cerebral thrombosis Ischaemic heart disease Subarachnoid haemorrhage*Pulmonary heart disease

19. OTHER CONDITIONS CAUSED IN PART BY SMOKING *Increased more than five-fold *Palmoplantar pustulosisReduced growth of fetus Facial skin wrinklingReduced fecundity CataractOsteoporosis Age-related macular degeneration Crohn’s disease *Tobacco amblyopiaDuodenal ulcer PeriodontitisGastric ulcer

20. UK male doctors born 1900-1930: continuing cigarette vs never smokers. 50-year follow-up of mortality, 1951-2001

21. Evaluation