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THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. Pd~MARKS OF DR. LEON O. JAOOBSON DECEMBER 9, 1983 The Scientific Advisory Board of CTR has since its origin sought and found a ccmbination of talented individuals who bridge and enrich the ccmbination of clinical and molecular science. Although each board member has a special niche of interest and expertise that provokes the ideas that must appear in order to make steady progress or breakthroughs in an area, they must also have a depth and breadth of knowledge that spans or relates to others on the board. We are engaged in a search for truth, good, bad or indifferent based on the mandate to undertake a research effort to "ex- plore and learn the causes of disease, including the role if any played by tobacco use" in causation or cocausation. To acccmplish this goal or mandate, we as a board must have a diversity and a balance of special talents that provoke a lively discus- sion of our applicants' proposals.These relate to the increasingly ccmpli- cated biologic interactions that arise from external or internal souroes and lead to such problems as cancer, pulmonary disease, hypertension, arterio- sclerosis in general and coronary heart disease in particular. We can not rely on gross anatnmy or the light microscope to tell us what is right or wrong with a cell, a group of cells or organs. We are at a point in science wherein we have to look at the cell surfaces, normal and abnormal chemical reactions at these surfaces, or within the cell, take apart the double helix and find the mutations, the deletions, the substitutions as well as the gene repair system. We must and do study normal and abnormal tissue from every organ syst~n simply because no cell or group of cells in the body functions independently of each other. Maintenance of the so called steady state of our entire body is dependent on thousands of messages originating in various cells and tissues. These messages direct normal function and may also produce cellular malfunction and thus a disease state. Our mandate is a broad one. Our Board is balanced and incredibly talented. Our Board and our applicants are major contributors to medical science, our Chairman Mr. Hobbs, President Hoyt and Gertenbach are suoeess- ful seasoned executives and our in-house scientific staff constitute an overall resource without equal. It is a rewarding and stimulating exper- ience to serve on the Board and I truly believe it cannot be equalled in the Halls of NIH, in the private foundations or national disease oriented associations such as the American Cancer Society. Today I wish briefly to identify our board members and summarize their particular area of expertise. Henry Lynch from Creighton is one of our speakers today as is Dr. Bowden, who hails from the University of Manitoba. Their presentations

THE COU~CtL FOR TOBACCO RESEARCH--U.S.A., INc. Page 2 will highlight their area of expertise. Our Scientific Director Sheldon Scmmers and our former Scien- tific Director William Gardner, both of whcm serve on our Board, require no further introduction. DR. RICHARD J. BING Dr. Richard J. Bing was born in Bavaria, received his medical education at Munich Germany and Bern Switzerland. He migrated to the United States in the late 30's and over the years has been on the faculty of Coltlnbia, Johns Hopkins, Medical College of Alabama, Washington Uni- versity at St. Louis and became Chairman of Medicine at Wayne State Col- lege of Medicine before beouning Director of Experimental Cardiology at the Hunt/ngton Medical Research Institutes in Pasadena. He lives in two worlds - music and medical practice and research. His creativity is widely recognized in both - he composes symphonies and has appeared in many cities in the United States and Europe as a guest con- ductor. Similarly his scientific achievements so relevant to clinical problems relate to coronary heart disease, congenital heart disease, and hypertension. More recently he has studied the microcirculation of the heart as well as the brain. Most physician-scientists remember him be- cause he was the first person to catheterize the coronary vessels of human beings to determine the degree, location and the severity of the atherosclerotic obstructive process and measure coronary blood flow. I consider him as one who has always been at the forefront of science as it applies to the circulatory system. Dr. Bing has been selected to receive the 1984 Distinguished Sci- entist Award of the American College of Cardiology. DR. ROSWELL K. BOUTWELL Dr. Roswell K. Boutwell received his master~ and his Ph.D. in biochemistry frcm the University of Wisconsin. He now serves as Professor in Oncology at the famous McArdle Institute for Cancer Research and has devoted his research efforts to the chemical and biological interaction of carcinogens with tissue constituents and the metabolic and growth se- quences of these interactions. He has been a productive and stimulating leader trying to unravel the cumplicated chemistry of carcinogens such as benzopyrine as the molecular alteration occurs when this powarful carcinogen enters the body. The final form of the molecule must be known in order to understand and hopefully control the event of changing a normal cell to a malignant cell.

THE COUNCIL FOR TOBACCO RESEARCH--U.S.A., INC. P~GE 3 DR. MI~ ~ ~N~ Dr. Michael James Brerm~n received his bachelor's, degree frcm the University of Detroit and his M.D. frcm Loyola University in Chicago in 1947. He holds three major positions, all of which are related - I. President and Medical Director, the Michigan Cancer Foundation. 2. Professor of Medicine, Wayne State School of Medicine 3. Director, Comprehensive Cancer Center of Metropolitan Detroit. He and his ecworkers have consistently been at the forefront of the experimemtal and clinical cancer diagnosis and treatment. Additionally Dr. Brennan has maintained an extensive clinical cancer research program involving cancer chemotherapy in general, investigation of prcmising now anti cancer drugs as %~ii as a program of molecular biology searching for markers of inherited disposition or predisposition. His knowledge of the cancer field has great breadth and depth and he thrives in an atmosphere of diverse but related activities - a superb physician, a dedicated clinical researcher and a natural administrator. DR. JOSEPH ~ Dr. Joseph Feldman was until recently Professor of ~thology at the Scripps Research Institute in La Jolla. Scripps has the most respected department of Lmmunology in the v~rld. In Dr. Feldman's hundreds of publications we find a central research theme - seek understanding of disease by studying structure and function as well as the molecular reactions of nonm~l and disease states. He oun- bined immunologic techniques with electron microscopy to unravel the path of development of two types of kidney disease. He clarified the immunolo- gical inflammation resulting from delayed hypersensitivity; he worked out the cellular immunology of graft rejections; he has shown that cancer can be cured by proper manipulation of the hosts own cellular elements and immune system and finally, he has demonstrated that our lymphocytes, the cells that control immune reactions, gradually lose some of their reactive power as we grow older. Finally, Dr. Feldman is the Editor in Chief of the Journal of Immunology - the most prestigious journal in a field that has exploded and revolutionized our knowledge and understanding of a host of hLm~%n dis- eases. DR. PEYER M. HOWLEY Dr. Peter M. Howley who got his M.D. at Harvard in 1972 and has since then been located at the Laboratory of Pathology at the National Cancer Institute in Bethesda. His youthful appearance would suggest that he had

THE COUNCIL FOR TOBACCO RESEARCH-- U.S.A., INC. Page 4 only just begun his research career. Hc~=ver, in but a few years, he has published extensively in the fields of molecular virology and pathology. Viruses play an important role in many diseases including cancer. His creative incisive mind has ooncentrated on the socalled papovaviruses BK and JC and the papillcmaviruses. Cloning cell lines, gene mapping, se- quencing of viral gencmes and successful inhibition or blocking of trans- formation of bovine papillumaviruses by interferDn represent only a few of his striking revelations on the molecular events that are involved in viral infection. DR. G. BARRY PIERCE Dr. G. Barry Pierce received his undergraduate degree from Alberta (Canada) and his medical degree from the College of Physicians and Surgeons also in Canada. His career in pathobiology took him to Alberta, Pittsburgh, The University of Michigan and finally to The University of Colorado where he is Professor of Pathology. He holds the distinction of being selected as a Markle Scholar and American Canoer Society Career Professor, and more recently he was appointed the American Cancer Society Centennial Professor. He has been President of the American Association of Pathologists and Pre- sident of the Federation of American Societies for Experimental Biologies. His scientific observations have always been based on novel approaches that attest to his originality. For example he reasoned that if normal cells could be prodded into turning into malignant cancer cells then why couldn't he reverse the process and change the now malignant cancer cells back to normal non dange- rous cells. This is exactly what he accumplished and it has led him into a vast area of unexplored possibilities of controlling or altering cell differentiation into paths of righteousness. DR. GO~ H. SATO Dr. Gordon H. Satoreceivedhisbaccalaureate degree inchemistry frcm theUniversityof Southern Californiain 1951 and his Ph.D. in Biophysics frcm the California Institute of Technology in 1955. He has been on the faculty as a microbiologist, virologist, molecular geneticist, biochemist at such institutions as University of California, Berkeley, University of Colorado, Brandeis University and the University of California in San Diego. Until recently when he became the Director of the W. Alton Jones Cell Science Center Inc. in Lake Placid, New York. Before 1960 grc~ing functionally differentiated cell lines outside the body in a test tube so to speak was only a dream. Today functionally differentiated cell lines from almost all organs and tissues of othe body are available in large part to Dr. Sato's insight that the media for success- ful tissue culture must contain all those things that normally involve normal cell growth and function within the body - for example cell specific hormones, vitamins and dozens of other necessary nutrients. He has created and nurtured an area in medical science that has already revolutionized our knowledge of what makes us tick. But the application of cell culture is still in its infancy and we are yet to reap harvest after harvest of vast abundance.

THE COUNCIL FOR TOBACCO RESF~RCH-U.S.A., INC. Page 5 Supplementary ER. D~ H. BOWD~q Dr. Drummond H. Bcwden received his undergraduate and M.D. degrees at Bristol University in England. After several appointments abroad he came to St. Louis University in the USA where he served as Professor of Experimental Pathology until 1968 when he joined The University of Manitoba as Professor of Pathology with particular interest in normal and abnormal pulmonary patho- physiology. His knowledge of normal and abnormal disease states of the pulmonary system and the interrelationship of other organs and tissues to pulmonary func- tion exemplifies the new thinking, n~nely that practically no organ be it heart, brain, or lung is indepemdent. Virtually hundreds of messages are continuously cuning in to any given organ to advise it on the state of the body as a whole. Finally, he has been a pioneer in opening up the importance of the pulmonary macrophage and polymor~honuclear cell in defense of injury or induction of inj . 1~. WIILIAM GARDNER The ways and works of Dr. Gardner are known to all of you but I have been a fan of his researd% career at Yale for 40 years. His unequaled ability to fairly but vigorously examine and evaluate research proposals is based on a world of experience during his career. He is not an ordinary ana~st. He is a functional anatnmist who understands the chemistry, the physiology and the molecular med%animns of the cells, tissues and organs that make up our anatcmy. He made many contributions to science but his work on the physiology of reproduction and the influence of hormones in the cause as well as the control of malignant growth %~_re breakthroughs that introduced a whole new approach to the cancer problem. Dr. Gardner is a past president of both The International Union Against Cancer and The American Association of Anatomists. DR. H~qRY T. LYNCH Dr. Henry T. Lynch got his undergraduate degree among the oil wells on the campus of the University of Oklahoma. He received his M.D. fruu the University of Texas. After several years in such institutions as the M.D. Anderson Hospital in Houston, he was appointed Professor and Chairman of Pre- ventive Medicine and Public Health at Creighton University. His findings in carefully controlled studies involved astuteness in medical diagnosis, epidemiology and statistics and a thorough knowledge of ge- netics frcm not only the observed hereditary factors but molecular genetics as well.

THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. Page 6 He has been particularly interested in all etiologic facts which are contributory to cancer susceptibility, particularly hereditary factors. He has described eight hereditary cancer syndrcmes most noteworthy of which has been the cancer family syndzrm~s such as hereditary nonpoly poris site specific colorectal cancer, hereditary colorectal cancer in combination with carcincma of the endcmetrium and very recently a familial atypical mole mela- noma syndru~. These and other studies involving tens of thousands of family members have shown that host factors have a host factor effect of significance even when pedigrees reveal a hereditary characteristic. DR. SHEUX~ C. SOMMERS Dr. Sheldon Summers graduated frcm Harvard Medical School in 1941, cum laude. He was a Captain, Medical Corps, United States Army, 1943-6 and was awarded the Silver Star, Bronze Star, Croix de Guerre and Presidential Unit Citation. Dr. SQmmers is a pathologist par excellence, and his international reputation relates to his magnificent studies in microsoopic and experimental pathology. His publications since the beginning have involved areas of re- search that were always at the forefront such as tu~or transplants, histo- chemistry of normal and diseased tissue, and the ultimate in classification of malignant tumors but particularly of the lung. These acccmplishnents plus his broad knowledge of immunology, carcinogens and cocarcinogens and molecular biology supplements and enhance his inherent leadership of our board. Dr. Strainers is currently Scientific Director of the CIR prior to which he was Director of Laboratories, Lenox Hill Hospital. He is a Past President of The New York Pathological Society and has been Editor of the Pathology Annual since 1966. He has 311 publications in the scientific literature.