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Council for Tobacco Research

Report of the Scientific Director [St]

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SCIEhTIFIC ADVISORY BOARD to The Council for Tobacco Research - U.S.A. KENNETH MERRILL LYNCH, M.D., Sc.D., LL.D., Chairman Chancellor and Professor Emeritus of Pathology Medical Collcge of South Carolina, Charleston, South Carolina tHOWARD B. ANDERVONT, Sc.D. Scientific Editor, The Journal of the National Cancer [nstitute Bethesda, Maryland RICHARD J. BING, M.D. Projesssor and Chairmat, Departnxnt of Medicine Wayne State University College of Mcdicinc, Detroit, Michigan McKEEN CATTELL, Pa.D., M.D. ProJessor Emeritus of Pbarntacology Cornell University Medical Colkgc, New York, Ncw York LEON O. JACOBSON. M.D. Dean of the Division of Biological Sciences Regenstein ProJessor of Biological Sciences University of Chicago, Illinois CLAYTON G. LOOSLI, Ph.D., M.D. Hastings Professor of Medicine and Pathology University of Southern California School of Medicinc Los Angeles, California CLARENCE COOK LITTLE, Sc.D., LL.D., L7TT.D. Scientific Director, The Council for Tobacco Research - U.S.A. Director Emeritus, Roscoe B. Jackson Memorial Laboratory Bar Harbor, Maine •STANLEY P. REIMANN. M.D., Sc.D. Director Emeritus. The Institute for Cancer Research Philadolphia, Pennsylvania WILLIAM F. RIENHOFF. Jrt., M.D. Professor Emeritus of S+vgery Johns Hopkins University School of Medicine, Baltimorc, Maryland SHELDON C. SOMMERS, M.D. Professor of Pathology Columbia University Colkyc of Physicians k Surgeons New York, New York ROBERT C. HOCKETT, Ph.D. Auoclate Seltntl fic Director J. MORRISON BRADY, M.D. JOHN H. KREISHER, Ph.D. Associate Sclendfie D4ector Assoeiate Scientific Director VINCENT F. LISANTI, D.M.D. Scitntif.c Associatr tAhlred / Stanley P. Reimann, M.D., Sc.D. 1891-1968 Dr. Stanlcy Philip Reimann, a patho1ogist and widcly-publ'uhcd cancer specialist, died on Wednesday, February 21, 1968. Dr. Rcimann had served as a member of the Scientific Advisory Board to The Council for Tobacco Rcscarch-U. S. A. aince 1954. As- sociatcd throughout the years with the Uni- vcrsity of Pcnnaylvania, Graduate Scbool of Medicine; Hahncmann Medical Collerc, and Lankcnau Hospital, Dr. Rcimann has served as president of the American Assoeiation for Cancer Research and the American Sociery of Clinical Pathology. In 1925, Dr. Rclraann founded the Institute for Cancer Research in Fox Chase, Pcnnsylvania, served as its sd- entific director from 1945-1956 and emeri- tus director. Believing that malignancy was a problem of growth and teaching that the most eflective way to find a are for cancer was to achicvc an undcrstanding of the pro- ccsses of growth, Dr. Rcimann, through his li(c and writings, excrted a widcspread in- Qucncc on canccr research. J 4
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TABLE OF CONTENTS Introduction. . . . . . . . . . . . • • • . . . . 5 The Progress of Research . . . . . . . . • • • • • • 6 Abstracts of Rcporu . . . . . . . . . . . • . • . . 15 Psycho-Physiological Studies . . . . . . . . . . . 16 Cardiovascular Studics . . . . . . . . . • . . • 18 Carcinogenesis Studics . . . . . . . . . . . . . 33 Studia at thc Cellular Lcvcl . . . . . . . . . . . 36 Epidemiology . . . . . . . . . . . • • . . . 39 Pulmonary Physiology . . . . . . . . . . . . . 41 Neurophysiology . . . . . . . . . . . . . . . 46 Chemistry and Biochemistry . . . . . . . . . . . 48 Pharmacology and Psycho-Pharmacology . . . . . . . 52 Pregnancy Studies . . . . . . . . . . . . . . 54 Other Studies . . . . . . . . . . . . . . . . 55 Recipients of Grants . . . . . . . . . . . . . . . . 57 Introduction The Council came into being fourteen years ago (originally as the Tobacco Industry Research Committee) to sponsor financially a wide vari- cty of original independent research studies related to smoking and health. Other agencics, both private and government, undertook also to support rescarch in the samc gcncral arca. Thus, there began a widespread effort to gain more scicntific knowledge of a subject about which little was known. The ramifications of The Council's research program have been and still arc, quite extensive. Many scientists who have rticeived and are receiving support from The Council have turned up knowledge and information of valuc in thc ongoing eftort to solve thc riddles of cancer, heart disease, and other major ailments afilicting mankind. Another benefit to both the general publie and the scientific community of Thc Council's research program is perhaps more obscure but no less im- portant. The fact that reputable, independent scientists at leading research organizations and institutions see the need for more study is a clear indica- tion that the smoking and health situation is not as simple as some people would have us believe. The incidence of the various and sundry diseases attributed by some to cigarette smoking would be a major public health problem even if smoking were not a worldwide custom and had never existed. Many people who have never smoked now die and will continue to die from the same diseases as do those who do smokc. Many pcoplc who smoke do not die from the statistically implicated diseases. Whether smoking, as such, is or is not involved in disease or death of ccrtain individuals is still not the solution to the major problem. This solu- tion depends on research which, it is hoped, will lead to the dctoction of those individuals who, with or without smokinf, face in common a greater risk of devcloping or contracting any of the diseases which have become the major survival threats to mankind. There is increasing and significant evidence that complex, genetically, innate individual dificrenccs in susceptibility and non-susctptibility, which affect the rate of aging and the imbalance of various organ and tissue func- tions underlie and profoundly afl'cct the three major public health problems - cancer, cardiovascular disease, and meatal health. 5 ~
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The Progress of Research The Council for Tobacco Research is and has bccn engagcd in suptx)rt- ing studies of those diseases that arc currently the greatest causes of illncss and of death. Of course, all these diseases occurred, and most were well known, before the usc of cigarcttes became prevalent, and they continuc to occur among noosmokcrs. Hence, any hypothetical or even real ef[cct of smoking could, at most, be no more than a contributory or aggravating factor in these dis- cases rather than an "all or nothing" cause of any. Epiderniological studies have been and still are the subject of debate by statisticians with respect to their reliabiliry on technical grounds. Addi- tional research aimed at rectifying some of their deficiencies and clarifying some of the curious contradictions and peculiarities are needed. It is a fact of history, nevertheless, that these epidcmiological reports provided the im- petus for abundant research relating in one way or another to "tobacco and health" that has subsequently been undertaken by many scientists. This re- search has been sponsored by government departments and by a number of voluntary health associations and foundations including The Council for Tobacco Research and the Ameriean Medical Association Educational and Research Foundation. This was a logical development since a recognized - indeed, the major - role of epidemiological research is to idcntify areas in which more minute and extended studies of other kinds may be needed in the laboratory or clinic. Within the last half century, notable progress has been made in the control of the infoctious diseases with a consequent great rise in life cxpccta- tion. 71m average infant born in this country today can expect to live almost half again as long as one born in 1900. This medical triumph has produced a population containing a larger proportion of older persons than any hcrc- tofore encountered in history. With this increase in the older population, disability and death due to chronic or degenerative ailments such as cancer, disorders of the heart and arteria, and chronic respiratory diseasa have shown a refarive increase. Furthcr progress in improving life expectancy must therefore come largely 6 cZO "a+ from ncw methods for preventing or deferring the development of such disd4 cases, which characteristically have a slow and insidious onset. Experts in these ficlds point out the complexities that are to be expected in the causation of such diseases. Their origin and development involve various degrees of host susceptibility or of resistance which are deep-seated in the constitutional or genetic nature of each human individual. This "built- in" susceptibility or resistance may then be modified importantly during the life span by such (actors as aging, sex, relative activity of the several gland$N of internal sccrction, and the individual characteristics of food absorption,a utilization, storage and excretion. Daily life practicc such as exercise, hours ~ of slccp, use of coffcc, tca, tobacco, alcohol, and the common household drugs, exposures to all kinds of materials and substances on the job, psycho- logical characteristics, and the stresses that assail the psycho-physiological systcm, may play a role. So may also the numerous bacterial and virus infections, mild or acute, which all persons still expericnce even though these are much less often crippling or fatal than formerly. Great bodies of data concerning such factors of internal and external environmental origin, have been and are being collected in studies of eancer, cardiovascular diseases, chronic pulmonary diseases and general mortality. ]n such studics scrious fallacies in perspective can result from over- interpretation of one-to-one correlations even though these may be valid mathematically. Because of the lack of multivariatc analysis, emphasis on the single factor of smoking in a number of epidem'ological situations involv- ing numerous unanalyud factors may well have masked other possibly im- portant facton and misstated or overstated any possible significance of smoking. The pressing problem is therefore to bring the methods of multivariate analysis to bear for weighting these various factors relatively, in a mathe- matical sense, as contributors to the final evaluation of causation and devcl- opmcnt of a disease. The laborious classical mcthod of multiple rearession analysis is now being superseded by new computer methods capable of handling a large number of variables simultaneously and rapidly for "clustering tendencia." Such methods need to be applied comprehensively to many large bodies of data that have already been and will be collected in the search for clues to the ctioloRy of degenerative disease by cpidemiological methods. The Council is aiding in the development of such computer techniques and their application experimentally to certain bodies of data that have been collected in its sponsored projects. There is also a great need for studies that will show ho.v the many otAerr 7 4
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habits and practices of life tend to bc associated with smoking or nonsmoking. Only as wc'devclop a picture of how smokers and nonsmokers diffcr in such ways, will it bccome possible to distinguish between possiblq cfkcts of smok- ing per se and thc effccts of other associated habits in the causation or aggra- vation of the various constitutional diseases. In this kind of rescarch also, computcr techniques for multivariatc analysis should be very hclpful and timc-saving. Cancer of the Lung In a sense, lung cancer carries a particular emphasis in tobacco and health investigations because of the reputed "strength" of its association with cigarette smoking on monofactorial epidemiological studics. Another reason is the rate at which this disease is reportcd to have increased in incidence within recent decades. Trends in Incidence " It is certain that the rate of increase reported for this disease during recent decades has been exaggerated considerably by the progressively in- creasing skill of clinicians in diagnosis. A number of autopsy studies have shown that whereas lung carcinoma was missed clinically as often as nine times out of ten early in this century, it is presently diagnosed clinically in eighty to ninety percent of cases. Indeed, there are indications now that gen- cral awareness of the discase is leading to overdiagnosis. Even so, in spite of the fact that diagnosis has approached a high level of efficicncy, the curves of reported incidence have begun to show signs of approaching a plateau rather than a continuing steep increase. Claasi fiQation o f Lung Tumors Human lung cancer tissues, still living after surgical removal, are now being observed with respect to their behavior in standardized culture media. Such wide behavioral ditierusoes arc being aeen in a single medium as io suggest that there arc many more dilfercnt types and probably more different causes than previously suspected from the classification of fixed and staincd scctions on the basis of appeuance. Cell and Tissue Culture Conference A conference that placed special emphasis upon the histopathological changes induocd in cells and tissue cultures by csrcinogeni5 and other agents I I I in virro, was held March 6, 1967. In addition to staff and members of the Scicnti(ic Advisory Board, the following investigators participated: T. TIMOTHY CROCKER, M.D., Professor of Medicine, Department of Internal Medicine, University of California Medical Center, San Francisco, California. LEILA DIAMOND, Ph.D., The Wistar Institute, Philadelphia, Penn- sylvania. BERLE J. NIELSL•N, A.B., Associate Specialist (Oncology), Cancer Research Institute, University of California Medical Center, San Francisco, California. DONALD M. PACE, Ph.D., Director of Cellular Research, Depart- ment of Physiology and Pharmacology, University of the Pacific, Stockton, California. RUSSELL P. SHERWIN, M.D., Hastings Associate Professor of Path- ology, University of Southern California School of Medicine, Los Angeles, California. BARBARA K. WATSON, Ph.D., Assistant Bacteriologist, Massachu- setts General Hospital, Boston, Massachusetts. CHARITY WAYMOUTH, Ph.D., Senior Staff Scientist, The Jackson Laboratory, Bar Harbor, Maine. ; Cell and tissue culture studies hope for the in vitro production and anal- ysis of such histopathological changes as arc observed in the lungs of animals subjected to controlled exposures to various agents. Subsequent direct obser- vations of the proliferative capacities of such tissues when replanted into the host animal may help relate microscopic appearance to tissue behavior. Studiea with Cigarette Smoke Condenaatei Ezperimcnts involving the painting of mouso-skins with cigarette smoke condensates (often erroneously called "tan") have been the chief basis for thc view of some invcstigators that cigarette smoke is to be regarded u a contact carcinogen for thc human lung. However, the relevance of such ob- scrvations to thc problem of human lung is questionable. First of 4, there arc great diffcrences betwecn rodents and primates (monkeys and man) in sus- ccptibitity to known carcinogens. Secondly, the skin is a very different tissue from the lung and shows very different responses to various irritating agents. Thirdly, condensates of smoke collected by passing smoke through cold traps at very low tcmpcratures, such as -80° centigrade, are not equivalent in either physical or chemical properties to whole smoke. Chemical and physical changes occur in smoke, some rapidly, following its formation In the burning zone and these continue in the condensate after collection. Moreover, such 9 cl~ yw"" U
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condcnsates lack all ihe gaseous components of smoke and some of thc vapors that arc not condensed or that evaporate after collection. The physical states of whole smokc and of condensate are obviously quite diffcrent. Finally, ccr- lain smoke conslitucnts are disproportionately concentrated in the condcnsate. Whole Smoke lnhalation The controlled inhalation of whole fresh cigarcttc smoke by experimental animals seems to come much cloau to the ideal of bringing the right material, in the right form and right concentration into contact with the right organ, cven though the wrong animal must still be employcd. Numerous inhalation studies were undertaken by many investigators in the early days following publication of the reports linking cigarette smoking to lung cancer. These added up to an impressive failure insofar as the appcar- ance of lung cancers was concerned. Little account of this efTort has been described in print, so that the extent of the work is relatively unknown today. The Council has continued to sponsor such studies with effort toward improvement of tcchniques. Ttxse are now approaching the point where a more comprehensive program can be dcvcloped. Among the many other factors which need extensive study arc: Predisposing factors in lung cancer. Animal models for lung carcinogcncsis. Lung clearance phenomena. The Cardiovascular Diseases Atheroacleroaia Tlure is broad agreement that the process of atheroscacrosis tends in general to predispose to ischemie discascs of the heart and blood vessels. This gradual thickening and degeneration of the vessel walls occurs in all persons but at widely different rates. A number of different kinds of evidence have combirxd to suggest that nicotine or smoking do not contribute toward any acceleration of this process: (I) the fact that these diseases arc not appre- ciably more frequent among pipe and cigar smokers than among nonsmokcrs, (2) the inconclusive results ln animal studies where nicotine was added to an athcrogcnic diet, (3) the occurrence of angina poctoris no more often in smokers than in nonsmokers, and (4) post morrem studia showing no sig- nificantly increased pr+cvaleaoe of infaretions of the heart among smokers. One recently reported post mortem study has, on the contrary, found 10 some rclation between thickening of arterial walls and cigarette smoking history. Nevertheless, since so many other habits and practices of life tend to cluster with smoking, it cannot be concluded that the smoking per se was responsible. Furthcr study of these life patterns, or new and better animal studies as well as suitably controlled twin studies, may help to bring a definite solution. Smoking and llypertension There is little evidence that smoking causes chronic hypertension (i.e., high blood pressure). Although smoking ordinarily causes a small rise in blood pressure of a few minutes duration, many studies show the resting blood pressures of habitual smokers to be lower generally than those of non- smokers. Nicotine and Smoking in Relation to Blood Flow A number of studies have shown that nicotine or smoking tend to in- crrcue the flow of blood in most of the vascular bods including those of the hcart, brain and skcletal muscle. An exception is blood flow in the skin of the extremitics. Pharmacology of Nicotine There is a vast litcrature on the pharmacology of nicotine and Council projects have added a great deal to it. Though many transient effects have been more fully described and measured in out program, no evidence has emerged of any significant contribution by nicotine, at the levels smokers receive, to causation, aggravation or precipitation of any cardiovascular dis- case that contributes significantly to mortality. Chronic Pulmonary Diseases Chronic and progressive diseases of the lung, such as bronchitis, asthma and emphysema arc attracting increasing attention as causes of disability and death. Clinicians report that such ailments arc being seen more frequently and they arc appearing more often on death certificates as causes of death. The rise in chronic and progres.sive pulmonary diseases has been at- tributed in part to the now frequent cure of acvte lung infections by anti- biotics so that more people with damaged or susceptible lungs arc alive today than formerly. Also, as has been pointed out, the component of oider people in the total population is greater than cvcr before in history. In this apc group, and cspecially in males, these discasa are most frequent. 11 o0 Itiq IRM+ IZ .... +,..r 0 "7' ~ ~ n= F-~ :,~.. ~ 1~
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In this area, the statistics are even more confused and of more dubious accuracy than they are in the case of cancer or cardiovascular diseases, by reason of problems of diagnosis and nomenclaturc. The term "emphyscma" has anatomical definitions and the pathologist uses the term to describe con- ditions that can be recognized under the microscope, classified as to type and estimated in extent. The general practitioner, howcvcr, has come to use thc term as practically synonymous with a clinical report of difficulty in brcathing. There is an abundant testimony that persons diagnosed clinically as having severe "emphysema" often show little or none anatomically, when examined porr morrtm. Conversely, patients who have had little brcathing trouble in life may show extensive anatomical emphysema at autopsy. In view of such variances in definition and diagnosis, statements con- ccrning the extent to which "emphysema" has increased over any given period as a cause of death have limited meaning. Conference on Allergic and Immunological Arpecra of Smoking A conference on allergic and immunological aspects of tobacco smoking was held on March 3, 1967. In addition to staff and members of the Scicn- tific Advisory Board, the following investigators participated: HARRY S. I3ERNTON, M.D., Attending Allergist, Providence Hos- pital, Washington, D.C. RICHARD S. FARR, M.D., Head, Division of Allcrgy. Immunology and Rheumatology, Scripps Clinic and Research Foundation, La Jolla, California. PAUL GOLDHABER, D.D.S.. Associate Professor of Pcriodontology, Harvard School of Dental Medicine, Boston, Massachusetts. DAVID W. TALMAGE, M.D., Professor of Microbiology and Asso- eiate Dean, University of Colorado School of Medicine, Denvcr, Colorado. Nicotine and the Central Nervous System There is a recurring question as to whether certain kinds of people especially need or want to smoke under the conditions of modern life because of a special need for relief of tcnsioa. Is there any evidence that such relief is actually provided by smoking? In the past, dcpendcnoc has had to be placed largely upon the subjcc- tive statements of smokers as to why they like or need lo smoke. Among the recurring reports are such as these: (1) "lt gives me pleasurc," (2) "lt gives me a pickup and helps me get going," (3) "It helps me relax when I am tcnse." 12 t Such statenunts raise the questions whether evidence to check their import could be provided by any experimental method. Some answers may perhaps be furnished by psychological investigations and any promising approaches along such lines should be encouraged. Another approach is through the methods of psycho-pharmacology, a relatively new licld of science. By thc study of clectrocncephalognms it has been shown that, both in animals and man, nicotine has a brief stimulatory or "arousal" effect on the brain, especially when this was originally in a state of what might be called repose. Whcn the brain is in the kind of state associated with agitation, nico- tine has an effect on brain waves resembling that of some of the tranquilizers. Thus psychopharmacology is providing some scientific substantiation for the seemingly contradictory subjective testimony of smokers. Nicotine may both arouse the lethargic and calm the agitated. Since direct electrical stimulation of certain parts of the brain produces an cffcct that is pleasurable, animal studies are being made to determine whether nicotine also stimulates the pleasure centers. Techniques that permit monkeys to inject themselves with nicotine at will, not only show that they find this agreeable, but are shedding light on the effects of cnvironmental conditions on the amounts the animals will take spontaneously. In no case has any of the animals done damage to itself by such unrestricted sclf-administration. Several studies have also explored the effects of nicotine on the learning process in rats, using various rewards to stimulate the animals to learn their way through a maze, press levers in some pattern or avoid an electric shock by jumping to a wooden pole on signal. Several such experiments show that nicotine stimulates the lcarning process, more particularly among the animals that arc originally relatively slow learners. Oral Cavity Research The oral cavity is subjected to direct contact with smoke derived from pipes, cigars and cigarettes more quickly and in greater conocntrationa than thc lungs. Despite this, the incidence o(canccr of the oral cavity has shown oo significant increase in amount, or incidence at an earlier age, during the decades in which per capita exposure to cigarette smoke has risen greatly. It is important to find the explanation for this fact. As reported elsewhere, Council studies have shown that the oral tissues of mice are far more resistant to certain carcinogens than arc their skins. In mice, liver damage considerably increases the susceptibility of the oral tissucs to certain recognized carcinogenic substances, but painting of 13 ~ .i..,. ~.r 00
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cigarctte smoke condensates inside the mouths of liver-damagcd mice has not been followed by appearance of any tumors. Much more study of the oral cavity is recommcnded by the fact that it resembles the lung more than does the skin, yet is relatively accessiblc. Sincc the saliva, oral structures and especially the ora1lcucocytcs also scrve as a first line of defense against external agents entcring the body, they mcrit attention in their own right. The effects of in vivo and in vitro czposurc of oral lcucocytcs to whole smoke and to smoke constituents arc being studied in recently inaugurated Council projects. Abstracts of Reports Each recipient of a grant-in-aid from The Council for Tobacco Re- search - U.S.A. is responsible for the initial presentation or publicatioo of the results of his research at scientific meetings or in appropriate scientific journals. Following are abstracts, approved by tht authors, of rrports on new® experimcntal research acknowledging support from The Council that have • appeared in scientific journals since publication oi the 1965-66 Report of ~ the Scicnti6c Director. These abstracts have been grouped under the following headinas: U I. Psycho-Physiological Studies, 11. Cardiovascular Studies, I11. Carcino- genesis Studies, IV. Studies at the Cellular Lerel, V. Epidcmioloay, VI. Pul- monary Physiology. VII. Ncurophysiology, VIII. Chemistry and Biochcm- istry, IX. Pharmacology and Psycho-Pharmaeology, X. Pregnancy Studies, and XI. Other Studies. A number of grantoes of The Council for Tobacco Research - U.S.A. participated in The Third Perugia Quadrennial International Conference on Cancer held at the University of Perugia, June 24-29. 1965. "Lung Tumoun In Animals; " the proceedings of this confercnce, was published in June, 1966, by the Division of Cancer Research, Perugia, Italy. Grantee contributions to the conference are as follows: "EPIDEMIOLOGIC STUDIES OF LUNG CANCER IN DOGS," by D. Cohen, J. S. Rcif and W. H. Rhodes. 'THE ROLE OF INFLUENZA VIRUS IN THE DEVELOPMENT OF MALIGNANT TRANSFORMATION IN VITRO AND IN THE RES- PIRATORY TRACT OF MICE, WITH AND WITHOUT EXPOSURE TO CIGARETTE SMOKE," by C. Lcuchrenbergcr and R. Lcuchtcnbcrgcr. I "THE RELATIVE EFFECI'S OF SOME AIR POLLUTANTS ON THE HUMAN RESPIRATORY EPITHELIUM," by W. f!. Carnes and L. E. Moses. •'EFFECTS OF INTRAVENOUS CARCINOGEN AND TOBACCO CONDENSATE INJECTIONS UPON THE INCIDENCE OF LUNG TUMORS IN A/Hc MICE," by F. llornburgcr and A. Trcgcr. "TUMORS PRODUCED BY METRYLCNOLANTHRENE IN THE RESPIRATORY TRACT OF THE WHITE PEKIN DUCK," by R. H. Ripdon. 15
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I. Paycho-Physiological Studies "IIIOLOGICAL ASPECTS OF GUSTATION." By Arnold R. Kaplan, PhD, Laboratory of Medical Genetics, Cleveland Psychiatric lnstitute, Ohio. "Mutation in Population: Proceedings of a Symposium held in Prague in August 9-11, 1965," pp 146-153, Czechoslovak Academy of Sciences, Prague, 1966. This paper presents a survey and summation of early and recent studies of taste sensitivity. DiHerences in taste thresholds have been found to be related to many faaors, including medication, phases of the menstrual rycle, pregnancy, smoking habits, occurrence of duodenal (vs. gastric) ulcer, and dietary prrferences. Tests in monozygotic and dixygouc twins and in sibliag pain indicate that genetic factors arc involved in tastc thresholds. OtJ..r gnsnwrr National Instituies of Health. "STUDIES IN TASTE ACUITY." By Arnold R. Kaplan, PhD, Laboratory of Modicsl Genetia, Cleveland Psychiatric Institute, Ohio. Technical Quarterly 4/2:138-144, April-June 1967. Intrapair thresbold diHercnoes for hydrochloric acid. L-quininc sulfatc, and PROP (6-n-propylthioutacil) were investigated in pairs of onc-cgg t..ins, two-egg twins, and non-twin siblings. There were no significant diffcr- eaccs in intrapair variations between the two-egg twin pairs and the non-twin siblings. There were, also, no significant differcnces between the onc-cgg and two-egg twinpurs for hydrochloric acid and quinine, but there was a very significant diSerenoe for PROP. Thueforc, the involvement of genetic factors in etioiogy of taste threshold was not demonstrated for sour-tasting hydrochloric at>Q or for bitter-tatiing quinine. but was emphatically demon- strated for bitter-tasting PROP. Sensitive tast.ers of quinine tesd PROP indicated relatively large numbers o; food d'ulikes and prefenenee for relatively mild-tasting foods, compared to itucnsitive tasten, who indicated re.Iatively fcw dislikes and picfcrencc for more strongly-tasting pr'cparations. The sensitive tasters included a rcla- tively high proportion of nonsmokers, compared to the insensitive tasten, who incJudcd a relatively high proportion of heavy smokers. Taste threshold was not found to be related to age or to sex when the data were controlled for di8crenas in smoking habits. The heavy smokers, howevcr, showed dc- crcased taste sensitivtty assoaated with tncreased age. Other faaon indoenciaa taste sensitivity include phases of the men- strual cycle and ulcer pathology. Otlsw sr+o.rorr National Institutes of Health. "ORALITY, IMPULSIVITY AND CIGARE.'I"I-E SMOKING IN MEN: FURTHER FINDINGS IN SUPPORT OF A T1iEORY." By Mutin A. Jaoobs, PhD, Lulocn S. Anderson, PhD, Emily Champagne, MD, Nathanicl 16 Karush, MD, Stephen J. Richman, MD, and Peter H. Knapp, MD, Division of Psychiatry, Boston University School of Medicine, Massachusetts. The Journal o/ Nervous and Mental Disease 143/3:207-219, 1966. (Grantee: Knapp) 76 college studcnts and 58 industrial workers, average age 26 years, served as subjects in this third of three studies designed to test the hypothesis that heavy cigarette smoking in men reflects part of a pattern of underlying oral craving dcfcnded against by active, impulsive behavior. The paid vol- untccr subjects in this study took part in personal interviews after which they filled out a Parent-Child Questionnaire (PCQ), a personality inven- tory (BUPI), and a form specially designed to directly test responsc-set and social desirability. Volunteers in the previous investigations were unpaid and impersonally sent the completed forms by mail. The first two studies revealed significant differences between smokers and nonsmokers in the parental concepts of maternal control, eoldncss and harshness, and in self-dcscriptions of defiance, impetuousness, thrill-and dangcr-sceking, neurotic emotional Iability, and oral preoccupations. In the - last study, statistical comparison ol mean scores for 54 cigarette cmoken and 80 current nonsmokers supported thc previous findings with the exception of the maternal malevolence concept. On an individual prediction basis, overall 62.7 percent of the sample was correctly designated as eithcr smokcrs or nonsmoken using this psy- chologic measure alone (chi square = 9.45, 1 df, P <.01). Presumably other factors, such as sociologic and physiologic, enter into the determina- tion of who will become a cigarctte smoker and continue with the habit, but this theory seems significantly related to this outcome and accounts for an important portion of the variance. "AN ATLAS OF FIGURE DRAWINGS: STUDIES ON THE PSYCHO- LOGICAL CIiARACTERISTICS OF MEDICAL STUDENTS - Ifl:- By Carolinc Bedell Thomas, MD, Johns Hopkins University School of Medicine, Baltimore, Maryland. Published by the Johns Hopkins Press, 1966. This third volume in the series, Studies on the Psychological Chararter- istics of Medical Studcnts, presents the oaly oompendium of figure drawings by healthy subjects to be found in the prycbological literature. The figures in this volume were all drawn by 870 Johns Hopkins med- ical students who were participants in tlx long-term study of the Precursors of Hypertension and Coronary Disease. Drawings in this atlas are graded by degree of sophistication, and within such a grouping are arranged accord- ing to different parental histories in regard to coronary diswe and hypu. tension, stroke, diabetes and obesity. Smokit~ habits and var{ovs othcr factors arc also given, arxl a Strong Vocational Interest Tcst is included for each subject. Thus, this Atlas provides a definitive denominator for figurc- drawing studies involving hcaltAy young adults of superior intelligence. Orb.•r granror.r Vctcrans Administration and the National Heart institute. 17 ti

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