Tobacco Documents Online

Acknowledgement The AMA-ERF Committee for Research on Tobacco and Health wishes to thank the manv individuals both in this countrv and abroad who participated in the rNsearch which resulted in this publication. Special thanks goes to Edward Domino. \i.D.. Professor of Pharmacologx-. University of Michigan Medical Sc:hool. who assisted the Committee in summarizing Section IV. Central and -\utonomic: \ervous Sx-stem, following the death of Doctor Seevers. We also wish to thank Dr. John C. Ballin and Dr. Ira Singer who served as scientific ~ secretaries to the Committee. and Mr. Leo E. Brown who provided the final stimulus for the production of this publication. Special appreciation is due Ms. Barbara Newkirk. Mrs. Susan Remlev. and Mrs. Shirlev Sullivan of the AMA secretarial staff. and to the personal svcretaries of our Committee members. To Mr. Ralph Linnenburger, Director. and to Ms. Irene Parks Foster. Production Editor of the AMA Department of Creati\e Servic:es. and \ir. Joseph Giacalone. we are indebted for the design and the t%-pc,graph}- of this publication. TIMN 0115739 T200230 I iv

' AMA House of Delegates Action December 1963 "A Res r(:h Studv on Toba(.(u and Ht~,illh - devoted tn the study of human ailmwnts th,+t mav be :aused or aggravated bx sniokiil,. I}I,. t)arti(:ul r element or t+le(nentti that m,i\ he tVl causal r aggraxatin' agents and thr• m('( of their a(:tloll.- T'Il\rIN 0115740 T200231 ~•

Contents preface <ontributor` ~ommittee ~lemh "~hip <<)mmitttt ~tatt,n„ ~r ycitinn Section VI Sumn~1ti~~n F\cwtiuii. 3 Abstr'l( l, 4, tiummar\ Abstracts 52 tiO ti Carcinu~enr~sis Summarv Abstracts 45 i, Ih t ?~ Section X'II Respirator\ S\stt"» "~1 1 ,9 Su mmar% "1 3 31 Abstracts 172 49 Authors Index Secaion III Cardio~~ascular S~~stem 59 Summarv 77 Abstracts 262 367 Participating Institutions Index Section IV Central and .~utonomic 171 \en-ous Srstem 177 Summar}~ Absirm t, 145 182 231 Section V Gastrointestinal Tract Summarv 235 Abstracts 72 237 TIMN 0115741 T200232 vii

P r i ~ v S _,i.110 ~I'4.p A ('up% ri:;ht • P+'3h\ ~tnwrii ~ n \trcii ,ti .~:,m i,itiwn Erlui,itir~n inil Rr-<ui li Fmuml.ilinn LC -H- -IriH1 Reprints of published research reports are not available through the Publisher. Please contact each author directly. Grantee's name is in bold face type in abstract. r t American Medical Association Education and Research Foundation 535 \orth Dearborn Street Chicago. lllinois 60610 TIMN 0115737 T200228

Contributors American Brands. Inc. Bron•n and Williamson Tobacco Corporation Li;gett Group Inc. Lorillard. A Division of Loex%,s Theatres. Inc. Philip Morris Incorporated R. J. Rex•nolds Industries. Inc. T2pp234 TIMN 0115743 x

) , TOBACCO AND HEALTH Compiled by the AMA-ERF Committee for Research on Tobacco and Health 1978 American Medical Association Education and Research Foundation TIMN 0115736 T200227

Dedication This book is dedicated to Maurice H. Seevers. M.D.. Ph.D.. who served <)s Chairman of the AMA-ERF Committee for Research on Tobacco and Health from the time of its inception in 1964 until his death in Mav 1977. Doctor Seevers was Professor and Chairman of the Department of Pharmacologx- at the l'ni.•ersitv of Michigan Medical School from 1942 until his retirement. He distinguished himself as an authority on drug and drug abuse not onlt- at the medical school level but as a consultant to state. federal and foreign governments. private industrv. medical publications, the American Medical Association and health organizations around the world. During his career. he served as a member of the Surgeon General's Committee on Smoking and Health. the President's Committee on \,larihuana and Drug Abuse. the White House Conference Drug Abuse Panel on Narcotics and Drug .'rbuse, the National Research Council's Committee on Problems of Drug Abuse. the AtilA Committee on Alcohol and Drug Dependence, the AMA Council on Drugs. and as a consultant on Drug Abuse to Japan. Thailand. Austra4ia and the United States. The AMA-ERF Committee for Research on Tobacco and Health is pleased to have had the privilege of serving with Doctor Seevers and herewith dedicates this publication to his memory as a physician, scientist, educator, leader and humanitarian. Richard 1. Bing, Zi. D. Stuart Bondurant. ~I. D. Earl A. Evans, Ph. D. Robert J. Hasterlick, M. D. Paul Kotin. tii. D. Marvin Kuschner. M. D. Paul S. Larson. Ph. D. Richard D. Remington, Ph. D. Ira Singer, Ph. D. TIMN 0115738 T200229 ll]

Preface In fanuarN of 1964. the American Medical Association Education and Rrsr,u-c h Foundation (AMA-ERF) entered into a five vear agreernent with six tubmc co companies' to conduct a comprehensive program of research on Toba( co ~)ncl Health. The research was to be devoted to the studv (if human aiiments that ma,' be caused or aograt-ated bv smoking. the particular elc,ment or element." that may be the causal or aggravatino agents and the mechanisms of their action. The six participating tobacco companies pledged to contribute a total of ten million dollars to the AMLA-ERF to finance this five-vear research effort, The ALIA-ERF Board of Directors appointed an eminentlv qualified Scientific Committee' to develop guidelines and suggestions on research policies and procedures. identifv significant areas of research and screen applications for research grants. The agreement was renewed in 1969 for another five vears, terminatin, in December 1973. On July 18. 1972, it was altered to eliminate indusM 's financial commitment in 1972 and 1973 with no new grant applications being accepted in 1973 although grants funded in 1972 were continued to com- pletion. Betcveen 1964 and 1975, 844 researchers in 85 United States and 13 foreign research institutions produced 795 publications and reports on the relation- ships of tobacco and health on (1) Absorption. Distribution. Metabolism, Excretion and Toxicology: (2) Carcinogenesis: (3) Cardiovascular S%-stem: (4) Central and Autonomic Nervous Sy'stem; (5) Gastrointestinal Tract: (6) Re- production: and (7) Respiratorv S}'stem. The content of this publication includes a summary of the research projects conducted in each of the above sections. abstracts of the research projects and the names of the participating researchers and institutions. It is hoped that this information will stimulate additional research in the field of tobacco and health. The American Medical Association and its Education and Research Fmunclation wish to express its gratitude to the Tobacco Industrv for its tin,cnc.ial support, the members of the Scientific Committee, the participating institutions and the 196 researchers without whose dedication and intellect this hook ivould not have been possible. James H. Sammons. M. D. Executive Vice President American Medical Association Education and Research Foundation ' see page x 2 see page xi T200233 TIMN 0115742 ix

The summarv statements in this volume draw attention to the research which has been done in each area supported through the funds awarded by this project. The summaries are intended to be neither complete nor comprehensive but to indicate trends and results. The Committee is proud of and satisfied with the work that has been completed under the sponsorship of the American Medical Association's Projec:t for Research on Tobacco and Health. Important contributions have been made to basic medical science as well as to problems associated with tobacco usage. Valuable information has been obtained relating to distribution, metabolism, excretion and toxicity of nicotine absorbed bv the human bodr via cigarette smoking. In the area of carcinogenesis, the Committee restricted the number of awards because cancer research was being generouslv financed bv the National Institutes of Health and other agencies. Nevertheless, the demonstration of potent co-carcinogens in tobacco tar and the potential ~alue of the measure of inducibilitv of arvl hvdrocarbon hvdroxalase as a de- terminant of susceptibilit}• to lung cancer represent some of the more significant contributions in this area. Emphasis .vas placed on the impact of cigarette smoking on the physiology of the cardiovascular, respiratory and central autonomic nervous svstems. The Committee believes that the bulk of research sponsored by this project supports the contention that cigarette smoking pla}•s an important role in the development of chronic obstructive pulmonarv diseases and constitutes a grave danger to individuals with preexisting diseases of the coronarv arteries. On the central and autonomic nervous svstem important findings %vere made related to effects on behavior and on biochemical mediators elicited bv nicotine. Gastrointestinal tract studies include new mechanisms by which nicotine may influence production of peptic ulcer. In studies in reproduction important insights were gained into the mechanisms of higher center control of releasing factors for pituitary hormone. The Committee wishes to express its appreciation to the American Medical Association and the tobacco industry for sponsoring this effort and to the manv ;rantees and institutions who participated in attempting to develop in- formation and find solutions to gaps in knowledge in this complicated area of scientific inquiry. Mav 27, 1977 T200237 TIMN 0115746 _ Seci Abs Exci Sun Abs A. 11 1; 1! 2( 2 2: 2: 2, 2` 2( X,V

Statement AN(A-ERF Committee for Research on Tobacco and tlealth On Ianuar~. 31. 1964, the American Jledical Association-Education and Research Foundation established the Committee for Research on Tobacco and Health. At its first meeting. the Committee agreed to commit available resources to support projects of high scientific interest undertaken b% in- vestigators in universitv and institutional centers. These studies were to he devoted to human ailments thought to be caused or aggravated by smokin,, and to the particular elements that might be the causal or aggravating agents. The Committee planned to allocate its resources primarilv to three broad categories of research in which there %vere important gaps in knowledge of the effects of smoking: 1) cardiovascular. 2) respiratorv and 3) central and autonomic nervous systems research. the latter because of its relationship to habituation. In all of its funding endeavors, the Committee attempted to support innovative research. Although the individual research projects were av,-arded on the basis of specific targeted investigations inevitably manx- investigators found interesting and fruitful areas for digression which developed during the course of their research. Agreements between investigators and the American Medical Association-Education and Researc'. Foundation required publication of reports in the open scientific literature. During the ten vear active life of the Committee, the membership varied from five to ten. The Committee met on an average of four times per vear to consider applications for new grants and to review the progress of the research being funded. The Committee was active in recruiting scientists to participate in Tobacco and Health research, an area in which they had not been previouslv scientifically active. As further encouragement, a post-doctorate fellowship program was instituted in order to stimulate young scientists to participate in this research program. Throughout its life, the Committee maintained liaison with the National Institutes of Health and The Council for Tobacco Research. U.S.A. keeping th(,se organizations apprised of current trends in the Committee's work and to minimize duplication of effort. The Committee is grateful for the free exchange nf information and the close liaison which was established with these organizations. To further stimulate informational exchange, the Committee convened three workshops. These also served as a measure of progress among its grantees. The workshops proved to be highly successful. In addition, a scientific presentation of the work of the Committee's grantees was held in conjunction with the American Medical Association Annual Meeting in San Francisco in 1968. This meeting constituted a report of progress and in- formation to the profession. At that time a statement was issued to indicate tl;a; the research completed under the aegis of the project had not altered the conclusions of the 1963 report of the Surgeon General. T200236 TIMN 0115745 X111