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THE COUNCIL FOR TOBACCO RESEARCII - U.S.A.

ANNUAL REPORT oJ the SCIENTIFIC DIRECTOR CLARE;NCF, COOK LITI'LF., Se.D.

I SC.ih;NTIFIC ADVISORY BOARD to The Council for Tobacco Research - U.S.A. St(t'Lf)ON C. SOMMf_•RS, M.D.,Chainrran Rr.rarch 1);rrctor, The Council for Tobacco Research - U.S.A. Director of Laboratories, Lenox Hill Hospital Professor of Pathology ~ 1 Columbia University College of Physicians and Surgeons New York, New York HOWARD B. ANDERVONT. Sc.D. Scientific Editor (rtfirtd), The Journal of the National Cancer Institute Bethesda, Maryland RICHARD M. BING, M.D: Director of Cardiology and fntramurol Medicine Huntington Memorial Hospital, Pasadena, California Profes.ror of Medicine University of Southern California School of Medieine Los Angeles, California McKEEN CATTELL, Prt.D., M.D. Professor Emeritus of Pharmacoloay Cornell University Medical College, New York, New York ROBERT J. HUEBNER, M.D. Chief, Viral Carcinogenesis Branch National Cancer Institute Bethesda, Maryland LEON O. JACOBSON. M.D. Dean of the Division of Biologfcnl Seitncrt Regenstein Profesrorof Biological Sdenees University of Chicago, Illinois CLARENCE COOK LIT1'LE, Sc.D., LL.D., Ltrt.D. Scientific Director, The Conncil for Tobacco Research - U.S.A. Director Emcritw, Roscoe B. Jackson Memorial Laboratory Bar Harbor, Maine CLAYTON G. LOOSLi, Prt.D., M.D. Ifastings Professor of llledkint and Pathology University of Southern California School of Medidne Los Angeles, California ..3~ KENNETH MERRILL LYNCH, M.D., Sc.D., LL.D. Chancellor and Professor Emerftrrs of Pathology Medical College of South Carclina, Charleston, South Carolina WILLIAM F. RTENHOFF, Ju., M.D. Professor Emeritus of Surgery Johns Hopkins Univer:ity School of Medidne Baitimore Maryland ...,. , , ROBERT C. HOC?CETT, Ptt.D. Associate Sdentihc DfrMor 0 CP J. MORRISON BRADY, M.D. JOHN H. KREISHER. Pn.D. 0 rt, Associate Scientific Director Astadalt Scientific Director f0*34 G.: VINCENT F. LiSANTT, D.M.D. XIA ~t-D g~ Scirntific Associate ~#1

CONTENTS Introduction . . . . . . . . . . . . . . . . . . Status of Current Research . . . . . . . . . . . . . . The Cancer Program . . . . . . . . . . . . . Cardiovascular Research . . . . , , , , , , , . 5 6 6 9 Introduction The research program of The Couneil for Tobacco Research - U.S.A. continued to move ahead in 1969-70 with additional suppcxt for studies into emnking and health. The Council's efrort to help develop more scien- tific data was further expanded during the year with the inauguration of scvcral contracts for research with institutions and laboratories geared to Chronic Respiratory Diseases . . . . . . . . . . . Neuropharmacology and Psychology . . . . . . . . Other Studies . . . . . . . . . . . . . . . . Abstracts of Reports . . . . . . . . . . . . . . . . Psycho-Physiological Studiea . . . . . , , , , , . Carcinogenesia Studies . . . . . . . . . . . . . Cardiovascular System . . . . . . . . . . . . . Respiratory System . . . . . . . . . . . . . . Neurophyaiology . . . . . . . . . . . . . . . Tissue and Organ Culture . . . . . . . , . . . . Pharmacology . . . . . . . . . . . . . . . Metabolic Studiea . . . . . . . . . . . . . . Chemistry and Biochemistry . . . . . . . . . . . ReViews . . . . . . . . . . . . . . . . . Recipients of Active Projects . . . . . . . . . . . . . Recipients of Completed Projects . . . . . . . . . . . . 12 13 14 16 1(i IS 25 32 45 50 52 63 (.5 67 69 79 9 pcrform the required work in the shortest possible time. The Council, by augmenting its regular arant-in-aid program with rescarch contracts, is re-emphasizing its desire to speed up the search for the answers to lung cancer, heart diseases, chronic respiratory ailments, and other diseases. The process is naturally slow and painstaking because thcse diseases are immensely complex and have been atflicting mankind for hundreds, even thousands, of years. While bits and pieces of information about them are reported by scientists almost every day, the time when the nurncrouc parts of the full puzzle will he assembled into a cohesive picture cannot be predicted. Claims that the puzzle has been solved are totally unrcalistic by scientific standards and misleading to the public. There are tar too many questions that remain unanswered at this time. It is noteworthy that in 1955, one year after the Scientific Advisory Board to The Council began its research program, a progress report was issued that said in part: "The history of cancer research is a record of slow but steady progress. There is every reason to expect marked advances in the prevcntion, treatment and cure of cancer. This also is true of the other constitutional diseases, such as heart ailments, which arc our greatest present and future health challenges. "But this will take time, and we eannot count on shortcuts. Neither the generating of unnecessarr fears, nor the arousing of unfounded hopes, will hasten the coming of aignificant discoveries. "Progrcss in the battle against these great health problems has depended and will dePend on solidly planncd and well- executed scientific research.' These words are still true today. The Council for Tobacco Research - U.S.A. will continue its research program in the belief that valid acientifie eonclasiom can come only from unbiascd and complete research. • 5

Status of Current Research Since 1954, when The Council for Tobacco Research - U.S.A. began to support studies by independent investigators on tobacco use and hcalth, reports of its activities have been made annually to the scientific and lay publics. This is such a report for 1969-70. Through the years, the staff of The Council and the members of the Scientific Advisory IIoard have seen the research program develop and mature along lines and into fields which give an opportunity for much more objcctive results. It remains clear that the complexity of the origin of different cancers, cardiovascular diseases and chronic respiratory diseases is very great and stifl little undcrstood. Hence, as heretofore, The Council's emphasis is still upon the etiology or pathogencsis of these diseases, since any possible effects of tobacco use can be interpreted only in this context. A summary and overview of the current status of The Council's pro- gram are bricfly presented in the following sections. The Cancer Program Virnses and Cancer Several present studies are directly related to the recent theory that cancer is one of several possible expressions of a latent C-type RNA viral genome, or genetic potential, found in all mammalian cells. The genome, according to the theory, is normally repressed and inactive, and there is a complex interplay o( internal and external factors that detcrmines whether, when and how the repression control mechanism is somehow broken and active expression occurs in the form of cancer or uncontrolled growth. One study in this area is aimed at developing more realistic, as well as more sensitive, test systems to illuminate the interactions between exter- nal agents and internal influences affecting the susceptibility of the biological substrate as determined by the state of the viral genome. Biological test systems for this purpose are expected to be of three kinds: ( I) in vitro studics nf cells that are controlled and standard'v.ed with respect both to source and statc, (2) skins of intact animals irr vivo from standardized, controlled and state-dcfined strains, and (3) lungs of intact animals in vivo from similarly dcfincd and standardized sources exposed to monitored inhalation of external agents. One immediate objective is to develop rapid yet realistic test systems that may "magnify" the effects of external agents so that the systems can be used to guide fractionation of complex mixtures and isofation of the ingredients most likely to be active in a susceptible host. Such assay systems should also provide new information on the components of host suscepti- bility through study of step-by-step modifications in the substrate system. An ultimate hope, of course, is to contribute toward disoovery of methods for inhibiting or delaying derepression o( the latent cancer genorne as a means of preventing or deferring cancer in the human popufation. Other Council-sponsored studies are aimed at filling gaps and round- ing out necded basic knowledge about the nature and applications of the virus-cancer hypothesis. These include studies of epithelial cell transforma- tiim and carcinoma induction by C-type RNA vitnses; the behavior of avian tumor viruses in mammalian hosts; and oncogenesis in the rabbit In terms of genetic susceptibility, vertical transmission of vinn, and environ- mental influcnces. Tlre lmnennolo6icol System The concept that cancer may result from vitus activity has renewed interest in studying the body's complex immunological maehinerY to tue whether stimulating it will help prevent the induction of cancer. Researdt supported in this field includes studies oft the adion of tnterferon as one type of virus-reprrssing substance; the function ot the reticutotndotheliaf system as it may be related to tumor Induction and growth; the possible effect of tobacco smoke inhalation on the immunological system in animals and man; and how carcinogenic hydrocarbons may possibly svppress ceiln- lar immunological mechanisms. Tobacco Smoke Studies Smoking Machines After an extensive period of experiments and teaN, progress was made in the last year toward devetoprnent of ineehanicaf devices for exposing experimental animals to the monitored inhalation of whole, fresh, normal 6 7

...~. 171 . ® cigarette smoke under conditions simulating actual human exposure as closely as possiMe. Previous Annual Reports have described the numerous and complex criteria necessary for realistic smoke inhalation studics. The aim in the design of such machines is to gcqerate the smoke under defined conditions and to permit delivery of the whole smoke to the res- piratory tracts of the animal in the same physical and chemical condition as that which reaches the respiratory tract of a human. Mechanical and biological evaluations have been made of several such deviccs developed through the years by various organizations. Also, analyti- cal data were obtained for the gaseous and particuiate phases of cigarette smoke generated by each device. Some of the machines are now being used in preliminary studies by various Council grantees for inhalation tests with animals. Full descriptions of these devices will be published with operational details as soon as the progress of thcse preliminary tests and trials justifies. Exposure of Animels to Smoke 1n all cancer-oriented projects involving direct exposure of whole animals to smoke, including virus-cancer studies, some of which involve work with tobacco smoke, it is now Council policy to require defininF, standardizing and controlling the virus content of all animals being uced. In one investigation aimed at elucidating the possible significance of freshness and physical state of smoke, a concentrated stream of whole, fresh, normal cigarette smoke is blown directly on the skins of mice of the same strain that had been used prev'rously in a conventional skin-painting experi- ment with tobacco-smoke condensate. All components of the smoke impinge on the skin and many of the constituents condense upon the surface. The treatment is being carried out with and without acetonc, which has been generaliy used as a solvent for "tars" in skin-painting work, and in one group of animals a "promoting" agent is also being used to intensify any possible "arcinogenic" effects that may exist. This experiment has been under way for a year. While the study sti)1 involves the "wrong tissue of the wrong animal," it does use natural smoke in the condition encountered in normal human smoking, and it should pro- vide further insight into the widely prevalent mouse skin-painting with statc, artificially prepared "tari" in a solvent. No Squamons Cell Tumors Found fn a long-term chroeic smoke inhalation experiment, two strains of mice are being exposed to smoke with the use of improved equipment. Mice g thue exprxed to inhalation of whole smoke, or of the gas phase aione, have developed only the types of lung tumors - adenomas and adenoearcino- mas - that develop in the same mice without any exposure. No squamous ce11 tumors of the type considered by some to be associated with smoking have been found in any of the hundreds of mice that have so far been exp",ed and then subjected to pathological examination. To study the incidence and appearance of lung tumors and pneumo- nitis in mice, a Councit-supported researcher exposed three inbred strains of mice to prolonged inhalation of ambient and filtered Los Angeles air. Mice in the ambient air group showed no lung pathology while lung adeno- mas were found in one strain exposed to filtered air. Autopsy examination of the animais' lungs showed that lengthy expostm to the ambient atmos- phere seemed to be associated with an increased susceptibility to pulmo- nary infection but not to an increased incidence of pulmonary neoptasia. This particular project is relevant both to cancer and to chronic respiratory diseases. In studying the eRects on the lungs of mice of chronic inhalation or several pure gases that are present in polluted urban air, and certain mix- tures of these, the same researcixr has developed a remarkably elegant technique for inflating, fixing and differentially staining the lung tissues. Among the gases studied were oxides of nitrogen, r»ont, carbon ntonoxide, and sulfur dioxide at various dosages and over various periods of time. Other CancPr Stredies Other studies related to cancer include one dealing wittt host factors, especially abnormalities of the endocrine system, as they may be related to lung cancer in humans. Another researcher is completing a study of bfadder cancer in man. This particular project has produced (indings to the effeet that, contrary to some reports, there Is no parallelism between reported disturbances in tryptophan metabolism In bladder cancer patknts and reputed cRects of nicotine on the same metabolk function. Support is also being continued for research on the mechanisms by whieh urethan affects cells in the alveoli of certain mice. Cardio'vascular Research There are now two key problems considered to be of first priority in regard to cardiovascular ailments and any possible relationship to tiganette smoking: 9

1. Sincc arteriosclerosis, including atherosclcrosis, is widely considcrcd to he the basic factor underlying most of the cardiovascular discaccs that arc the Ieading causes of death in the United Statcs, the ques- tion of preventing, delaying or reversing the process is piramount. As rcgards tobacco, a prime question is whether smoking and/or nicotine have any effect in speeding the development of arterio- sclerosis, especially of the coronary arteries. Though there are many studies that question whether smoking can aRect the process, there is a need for more research. Still lacking is a really satisfactory animal model for reproducing the human coronary disease under reasonably physiological conditions and such a model is being sought. 2. Once arteriosclerosis or atherosclerosis has been cstabiished, par- ticularly at an advanced age, another question is what factors or influences may possibly trigger an acute event such as a heart attack or a stroke. Here too a prime question is whether smoking or nico- tine can be involved. Especially important are the basic ditferences between the kinds of people who like or need to smoke and those who do not. The issue is eonfused, particularly in epidemiological investigations, because people predisposed to cardiovascular disease may also be of the type or types who feel a need for tobacco and, consequently, sepa- rations of populations on the basis of smoking behavior may produce statistically non-equivalent groups. Various twin studies have sup- ported the concept that epidemiological studies have generally pro- duced and attempted to compare non-equivalent groups. Method for Measuring Blood Flow The Council has helped support research for several years from which a method has been developed for measuring blood flow in the arteries that feed the heart muscle without inserting tubes or resorting to surgery. By this new approach, it has been shown that nicotine does not reduce blood flow in normal arteries that supply the myocardium, but generally increases it after the manner of mild exercise. In addition to an increase in "mechani- cal" coronary blood flow, there Is an Increase in "nutritional" flow as well. This method, repeated and confirmed in the past year with tests on animals and humans, has important implications in the entire field of heart disease. The same research project, with continued support from The Council, is now approaching the atherosclerosis problem by studying human arteries in tissue culture by perfmion methods. The purpose is to determine whether nicotinc affects dFpcxition of fatty materials in the artery wall from serum or plasma. The conditions are made to resemble those in life, with control and variations in pressure on the vessel wall and in the concentration of albumin, cholecterol, free fatty acids, ete., in the serum. Blood ftow, in the microcirculation is also being studied to see whether k is affected by nicotine. Among other studies that have been contribtrting knowledge in various phases of the complex cardiovascular problem are: one suggesting a nega_ tivic effect of nicotine on thrombus formation: the relationship of blood- sugar level to nicotine eRects; measurement of carbon monoxide in the bha)d; the interrelationship between carbon monoxide and oxygen elution from hcmoglobin; the degree of fibrous thickening of blood vessels in smokers and nonsmokers; and possible prediction of early heart disease by longitudinal study of precursor tonditions. These and other interesting flndings of The Cotmcii's grant-in-aid program are presented in more technical form In the various summaries of research included later in this Report. I'rrdictora of F,orly Thart Di.caaw Being continued is a long-term study of medical students to learn what characteristics, measured at an early age, will turn out to be ptrdictors of early cardiovascular disease. Part of this project includes determining the patterns of measurable characteristia that correlate with a family his- tory of cardiovascular disease. During the year, the investigator conducting this study reported that 16 of the mature men originally studied as students had developed elinipi hypertension by 1968 while 89 othen had exhibited transitory hypertension. In 62.5 percent of the subjects with dinical hypertension, both parents evidenced hypertension and/or coronary disesse as compared with 21.9 percent of the parents of the control group. Another development reported from this attdy was that there have been 31 premature deaths among the subjects, 14 of them from suicide. The other 17 deaths were due to accidents, coronary heart discase, neo- plasm, chronic alcoholism, nephritis with hypertension, acute uleerative colitis, and subacute bacterial endoearditis. Statistical evidence was reported that certain precursora of suicide, accident, fatal heart attack, and fatal stroke are already present and can be identified in youth. Other research is being supported to learn whether changes In calcium ion mobility, Induced by nicotine, play a role In addition to that of eatecho- lamines in bringing about the short-term cardio+bcular changes that follow smoking; and to measure the short-term effects of smoking upon regional blood flow in the brain. ' . 11 10

Chronic Respiratory Diseases A basic problcm involved in the study of chronic respiratory discascs, particularly in detcrmining their cause or causcs, is the lick of gcncralty accepted clinical distinctions among the various respiratory difficultics. These include emphysema, bronchitis, asthma, and even certain heart ailments. Inadequate definitions and the lack of uniform clinical distinction of these conditions have confused attempts at epidemiologicat studics of causation or aggravation. Further, it appears that diagnoctie uncertainties and doubts, as well as changes in the popularity of such terms as "emphy- sema;' may have resulted in a fictitious increase in reported prevalence rates. Hence, The Council is supporting a long-tcrm study in a pulmonary disease clinic where comprehensive and repetitive observations can be car- ried out on many chronic patients over a long period of time. The hope is that numerous biochemical, pathological and radioloRical observations can eventually be correlated with the clinical course to produce better definition as well as improved diagnosis and treatment of chronic lung disease entities and also provide new etiological insights. Metaplaiia in NoRsrreokert A Council grantee examined the bronchial epithelia of 500 apparently "healthy" adults who died suddenly and unexpectedly, after living and working in an urban area noted for its air pollution, but who had had no known disease history. Metapiasia was found in the lungs of both smokers and nonsmokers. Of great importance, however, was the observation that various degrees of mctaplasia were present in a surprisingly high proportion (50 percent) of "healthy" adult men who had never smoked cigarettes, cigars or pipes. There were no casea of carcinoma in situ in either the smokers or non- smokers. Thus, in the study of lung tissue at autopsy, it is important to distinguish between patients who die suddenly and those who die following wasting or chronic ailments in a hospital after being treated with drugs and other therapies. The Council has supported several studies through the years that have contributed evidence showing that a deficiency of atpha,-antitrypsin appears to predispose to emphysema. Other research inclades: the effects of hypoxia on function of the respiratory system: the bioehemkal aetivities of sputum cells from patients with various types of chronic lung disease; and how lung cells and other prndvcts rccovcrcd by lavage from normal smokers and normal nonsmok- crs mny differ. One invcstipator ic studying the cyclic changes in the structure of lung cc)ts of young women, recovered by lavage, that correlate with the men- strual cyclc. An invcstigator is conducting a long series of studies on the effects of cigarette smoke inhalation on lung function, especially pulmonary ttsist- ance, in several species of animals. He has found short-term effects that dificr among species and that a female sex hormone, progestervne, reduces or blocks them. fVo permanent changes of the kind that occur in emphy- scma have been found in these chronic smoke inhalation tests. Additional experimental studies include: isolation of functioning ribo- somes from the lungs of animals and relating the speed of their formation to certain lesions produced in animals by high-oxygen exposure known to cause such lesions in humans; the effects of smoke exposure on the pul- monary macrophages; clarification of the relationship between lung lym- phocytes and pulmonary macrophages; and the lymphatics of the lung, their structure and role in fluid transport and in clearance of airborne par- ticulate matter from the lung. Neuropharmacology and Psychology Most of the pharmacological studies currently being supported by The Council are concerned with the e/feets of nicotine and/or smoking on the central nervous system (the brain) with the object of karning more about why people 1ike, want or need to smoke. These should help reveal the basic differcnces between smokers and nonsmokers, which previous work of other character has shown to exist. in a Council-supported study of high school and junior high school students, a psychologist has reported resalts quite similar to those found earlier with adults, namely, that there are persoaality differences between smokers and nonsmokers. Brain: Wace Patterns An ongoing study deals with the effects of t:icotine or amoking on the brain waves of human subjecb. Dy use of computer methods to analyxe these electroencephalograms, the ttteanin6t of the wave patterns ht terms 12 13

of "deep stcep," "arousal," "awake but in repose," etc., have become known. One significant observation from the study so far is the implication that heavy smokers may have a different basic prevailing brain wave p.it- tern from that of nonsmokers. The investigator beiieves that this pattern may be congenital and that it antedates and influences the adoption of tobacco use. ConJerertcp on Nicotine A conference on the effects of nicotine and/or smokinf; on the central nervous system was held June 1, 1970, at The Council's otlice. In addition to staff and memlSers of the Scientific Advisory Board, the following scien- tists participated: Budhdev Bhagat, Ph.D., Professor of Physiology, St. Louis University School of Medicine, St. Louis. Barbara B. Brown, Ph.D., Chiet, Experimental Psychiatry, Veterans Ad- ministration Hospital, Sepulveda, Cal. Edward F. Domino, M.D., Professor of Pharmacology, University of Michigan. Ann Arbor. Walter 13. Essman, Ph.D., Professor of Psychotogy, Ouccns College of the City of New York, Flushing. Leonide (',otdstein, D.Sc., Research Scientist, Bureau of Research in Neurology and Psychiatry, New Jersey Neuropsychiatric Institute. Princeton. Henry B. Murphree, M.D., Associate Professor of Psychiatry, Center of Alcohol Studies, Rutgers University. New Brunswick. N. ). S. N. Pradhan, M.D.. Ph.D., Professor of Pharmacology. Howard Uni- versity College of Medicine, Washington, D. C. Uirieh H. Schacppi, M.D., Director of Neuropharmacoiogy, Mason Re- search Institute, Wotcester, Mass. Thomas C. Westfall, Ph.D., Assistant Professor of Pharmacology, Uni- versity of Virginia School of Medicine, Charlottesville. Other Studies The Council is contributing to a project that is supported mainfy by the Veterans Administration. Its aim is to make numerous periodic exami- nations of a large group of male vetenns, with a high initial level of good health, in order to describe the changes that come during normal aging. Support is being provided for a study of certain biochemic,at effects of chronic smoke inhalation by guinea pigs. Using a smoking machine, the investigator has isolated the mitochondria from lunga of exposed animals and is studying the ekctton tnasport ttystem in these cell components. The Council is continuing sponsonhip of a projeet that has been of great benefit to researchers and others interested in smoking and health: the coliection, abstracting and analysis of the world literature on tobaceo, including experimental and clinical studies. A second supplement to the monograph on this subject, titled'Tobaeco-Experimental and Clinical Studics," first published in 1961, is expected to be published soon. c 14 15

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 publication of the results of his research at scientific meetings or in appropriate scientific journats. Following are abstracts, approved by the authors, of reports on new experimental research acknowledging support from The Council that havc appeared in scientific journals since publication of the 1968-69 Report of the Scientific Director. The name of the grantee is in italics. These abstracts have been grouped under these headings: 1. Psycho- Physiolofical Studies, 11. Careinogenesis Studies, I/i. Cardiovascular Sys- tern, IV. Respiratory System, V. Neurophysiology, VI. 1'issue and Organ Culture, VII. Pharmacology. VIII. Metabolic Studies, IX. Chemistry and Biochemistry, X. Reviews. I. Paycho-PhyxioloRical Scudfes EFFECTS OF SMOKING ON PERiPHERAL VISUAL ACUITY A total of 40 male university students, 30 smokers and ten non- smokers was tested on a modified Ferree-Rand Perimeter in order to determine the size of the peripheral visual field as a function of various combinations of smoking, smoking deprivation, and smoking denicotinized cigarettes. The experimental design encompassed two control and two experimental test groups of ten subjects each: one group (CS) smoked regular ciganettes throughout the test period; one (CNS) never smoked; one (ES) smoked standard cigarettes preceding the first two peripheral vision tests, were deprived from smoking for the next eight test scssions, artd smoked again preceding the last two vision tests; the last group (EDS) smoked standard c3garettes preceding the first two tests, smoked denico- tinized cigarettes preceding the next eight test sessions, and smoked stand- ard eigarettes again preceding the last two vision tests. Results indicated that there were no significant long-term effects of smoking on peripheral vision by a comparison of smokers and nonsmokers on the initial two test sessions. Ho..ever, the relative change in performance from the initial tests produced a significant diBeretiee between the experimental and control groups. Specifically, abstinence from smoking increased the size of the visual field. After a period of abstinence, smoking reduced the size of the visual field. The mapr ehanges in peripheral vision were on the temporal meridian. Further, performance of the two experimental groups, i.e., those who were deprived from smokirg and thoee who smoked the denicotinized eigaretta, was fderttical. This indkated that the effect of smoking on periph- eral vision may be attributed to the nicotine component of tobacco smoke. Krippner, R. A. and Tltimsrra, N. W. F.Bccrs of Smoking on Peripherat Visual Acuity, The University of South Dakota: Vermillion, 1969, pp 1-57. From the Department of Psychology, University of South Dakota, Ver- million. A NOTE ON RESPONSES TO ETHYL ALCOHOL BEFORE AND AFTER SMOKING Differential taste sensitivity to ethyl alcohol wtumeasurLd before and after smoking a cigarette by ten smokers; ten nonsmokers served as eontrols. Using a paired comparison method of differential sensitivity, subjeets evalu- nted eight paired sample sets consisting of 8% EtOH vs. 4%. 5%, 696. 70, 9%, 11 o, and 12% EtO1f. No significant di(ferences were observed between smokers and nonsmokers or before vs. after smoking, although slightly higher overall correct responses and correspondingly smaller ft'ust noticeable differences were obtained for the norrsmoken. No practice effects were noted among the control group between the flrst and second set of samples. The findings confirm previous results which had been questioned recently. Martin. S. and PanRborn, R. M. Pcrception & Psychophysics 8(3):169-170, 1970. From the Department of Food Science and Technology, University of California, Davis. RELATIONS BETWEEN PERSONALTTY AND SMOKING BEHAVIOR IN PREADULT SUB7ECTS This study of 562 high school and ~'vrfior high school students has yielded results which are strikingly similar to thoae found earlier with adults. In both studies, smoking status was assigned on the basis of self- report information, and personality scvres wtre derived from peer ratings. With the preadults, as with the adults, smokers scored significantly lower on measures of "AgreeableneM " and "Strength of Character," and scored significantly higher on measures of "Extra.en" In addition, the smokers (in both studies) scored signi8cantly hi than the nonsmokers on the variable "crude," '•happy-go-lucky," "frank." Among prtadnlts, nwl- tiple discriminant analyses permitted kirra status to be assigned with accuracy ranging from 65% to 79%. Although most informatiotS eotreern- ing the psychodynamics of smoking has been obtairxd from stod'xs of adults, the present study supports the use of auch Information in work with preadults. Smlth. G.M. lournat of Consvtrfna and Ctlnkol Paychology 33(6):710-715, 1969. OrRrr Kranror.: American Cancer Sodety and V. 3. Public Health Ser.ice. From the DeQartment of Anesthesia, Masaaeheaetts General Hospital, and Harvard Medical School, Boston. 16 17