Tobacco Documents Online

C RESEARCHIPROGRAM PROJECTIDN by W. U. Gardner November 10, 1972 The Council for Tobacco Research is concerned with those phases of human use of tobacco that, in one way and another are implicated~with health, and well-being,. No one really knows why manienjoys smoking tobacco. It is a uniquely human characteristic. Smoking is apparently a source of pleasure to many, a means for release of tensions to many, and to some a"pick-me-up." Evi'dence exists that persons who smoke cigarettes are more liikely to require some additionalisupport, to take drugs more frequently such as stimulants, vitamins, aspirin, sedatives, etc.,, in fact all drugs except the antihistamines, than are non-smokers. Some types of individuals seem to have more need for supportive supplementation that can be supplied by tobacco smoke than others. Numerous reports of effect of excessive smoking on the impairment of health are extant. They are too numerous to ignore. Excessive eating, exercise, drinking or work can also be detrimental to health. The difficulty is defining what is excessive or what is marginal in any objective way. This is again not unique to tobacco. At a recent international meeting on the biologicaL effects of asbestos, much discussion related to levels of asbestos "dust"' that might assure no more than a 1% risk of asbestosis. The health areas associated with smoking are disease of the respiratory system,, the coronary arterial and general arteriovascular systems. The disease entities are named by descriptions of their symptoms and progression rather than by their causes. Respiratory diseases include lung cancer and chronic bronc?!itis or emphyscms. Corcnary arterial' ?i:;cWsc is the major vascular component but peripheral and cerebral vessels are aLso implicated'. `_=

-z- C We have saidithese diseases are of unknown etiology. They certainly occur in persans who do not smoke as well as those who do, but the frequency of symptoms and disease may be greater in the latter. They are age-associated diseases. "Aging is an increased susceptibiliity to disease which leads to decreased power of survival andladj;ustment"' or "a reduction in reserve capacities in organ systems which increase probabiLity of environmental demands exceeding the capacities." Much is known about how these diseases progress with age, and with and without exposure to smoke. We know many details of the progressive changes but we apply descriptive rather than causal terms. Most effective controlihas always been against the cause rather than symptoms. Modern experimental medicine has made great progress in the prevention, control and treatment of most bacterial and many viral diseases. The age-associated'diseases are the ones that become increasingly important as the others decrease in preval'ence and it is with these that we must be concerned. The present research program of The Council'.is effective and comprehensive. Many of the projects are worthy of extension. In planning new research what are the priorities? What areas of new research needithe greatest emphasis at this time? Although I am a newcomer in The Council, at this time I am inclined to place them as follows: Model Experiments Using Laboratory Aniinalis Exposure of these animals, from mice to monkeys, to fresh tobacco smoke by inhalation. Apparatus is now avail'ablie that should~present smoke to animals in much the same state as presented to the respimatory tract of man. The different smoking,apparatuses are being carefully tested'.mechanically, and willisoonibe tested by well-desi!gnediexperiments to determine pulmonary and upper respiratory deposition of particulates andigas phase components of

- 3 - i cigarette smoke. This wi11 permit, if the animal models should prove satisfactory, the determination of the effects of different degrees of exposure to smoke on ~ respiratory and'circulatory functions. Consideration is being given to the selection of a standard filter cigarette and cigarettes that are more comparable to those being used most abundantly today to compare them with the standardireference cigarettes. Because man does not smoke in a pure air, consideration will be given to more experiments involving "smog," dusts, asbestos, etc., in conjunction with smoking and areas of residence and types of employment. Epidemiology Animal experiments alone are not sufficient. Emphasis must be placed onitttre effects of smoking upon human beings. These studies,,again, are not easy to do well but they must be done well or they can be misleading. The Council is now supporting,three epidemilological studies. In design and conduct epidemilological studies must be carefully thought out;, they may be either prospective or retrospective; they must consider the many environmental, raciali, constitutional and other variables. The Council has supported a conference on studies of twins, identilal and fraternal,, in the Swedish Twin Registry and from the National Research Council group imithe U.S.A. The variables were numerous; the numbers are small in some categories -- in some instances, too small to be above question. Plans are now being made to do a massive twin study including up to eight countri!es;, hopefiully, populiations from thos countries that show differences in incidence of arteriovascular and pulmonary diseases. At this time it is not known why the incidence of lung cancer in Scotland is more than two times that in the U.S. or why lung cancer is only 67.7/100,0001i.n the U.K., 60.7/100,000 in Finland;. 56.4'in Czechoslovakia in contrast to 37/100,000 in the U.S. (1969-65 figures.Y It is possible that asbestos contributes im Finland. Twin studies in these. 4

r , I countries, as well as those in which lung cancer is lower than in the U.S. should also prove of,value. Because of the reported'prevalence of the much rarer bliadder cancers,, and pancreatic cancers among.smokers, these sites should also probably be included. In the first study angina pectoris was reported as a manifestation of chronic cardiac disease, and actually the non.smoking twins more frequently showed symptoms. Body constitution was of more predictive value. Emphysema In Chronic Obstructive Pulmonary Disease (Chroni!c Bronchi'tis), I'm~including emphysema as a separate category although it has been mentioned above. The incidence is increasiing. Although it was not a reportable cause of death until a rather short time ago, it is not a new disease or group of diseases. Since it has becor„e reportable and since many more peeple survive acute diseases, because of the application of antibiotics, or prevented from having acute disease by preventive measure, the prevalence of chronic disease is increasiing,probably more than incidence. Genetic factors have been shown to predispose to emphysema and often emphysema;aii early ages. It has been estimated that in some areas 1 of 200 persons is genetically homozygous for a bioliogical'ly-active specific protein deficiency that predisposes to earliy emphysema. Other factors must predispose to emphysema and smoking,has been implicated. Model experiments wilil be important and animal inhalation experiments may lead to important observations. The effect of fresh smoke on pulmonary macrophages, auto-immune manifestations, and~recurrent pulmonary infectilons must be studied more extensively. Some such experiments are now in progress. The importance of emphysema as a chronic debilitating disease directs more attention to this condition.

r ! C -s- Again, other environmental influences may contribute greatly to the manifestation`of this disease. The twin studies may be of considerable value im contributing to our knowledge of human disease. Psychophysiological and'Psychopharmacological Studies No one really knows why man smokes or otherwise uses tobacco. What component or components of smoke contribute to the desire or need:for tobacco? Nicotine is a powerfuli drug,that has pharmacologzcalieffects on peripheral nervous tissues and also parts of central nervous tissues. Yet nicotime,, when administered„ will not more than partially reduce smoking motivation. I have not found other significant leads in this area. The Council has several explioratory researches underway. Most investigators interested in motivational aspects of human response have not submitted project applications unless prejudiced to counter established motivation. I deliberately used the term psychopharmacological because the pharmacologicali aspects are being studied in model systems. I hope that more interest may be generated in this area. Funds To my knowledge the funding of The Council!has not increased in recent years. This means that it has less functional research support resource yearly because of infliation. For the past 6 to 8 years this has probably been 8 to 10% per year, not an insignificant amount, because the iincreased costs of research instrumentation and supplies, and especially since underpaid technical assistants andistaff have finalilyhad salaries incrcased.to.levels more nearly comparable to peers in other positions. Twn years or so ago, it was considered that it required in biomedical research $60,000 to $70,000 to maintain a senior investigator,, assistants, laboratory rental, supplies, instrumentation. These estimates have:doubled. If one pays the full costs for research it is expensive -- approximately twice as expensive as a few years ago. Fortunately, C on== ~ ~

r . d C - 6 - one does not pay fulil costs on most research projects; the host institutiom pays toward them, but now research institutes and universities are less able to meet such costs. If this is to be a program worthy of great planning effort there should be some assurance of the possibility of support. For example, the exposure of animals to smoke is going to be expensive. Animals of several species and', in some species severalistrains, will have to be exposed chronically. They must be kept in pathogen-free conditions. Sufficiently large numbers must be used to get significant results, always a problem in chronic experiments. ~ ~. N `=