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501 STATEMENT OF LEON 0. JACOBSON 19 I am Leon Orris Jacobson from The University of Chicago in Chicago where I continue as a physician-scientist emeritus and have served as Chairman of Medicine, Dean of `fedicine 3n3 Biology and Director of the Argonne Cancer Research Hospital. In February 1942 I became responsible for the medical safety of the personnel of the Metallurgical Laboratory (the atomic bomb project) under the direction of Arthur Obmpton, Norman Hillherry, Enrico Fermi, Leon Szilard and many others who achieved the first self-sustaining chain reaction. Iater I served as Associate Director and then Director of Medicine and biology of this enormously successful national program that brought the war abruotly to an end and in the aftermath provided the tectnology and the radioisotope tracers so enormously important to the revolutionary advances in biologv and medicine that contribute an ever increasing momentum to cur un3erstan3ing of normal as well as disease processes. I joined the Scientific Advisory Board of the Tobacco Industry Research Committee (now called the Council for Tobacco Research - U.S.A. , Inc. ) in 1954 when it was under the leadership of Clarence Cook Little. Dr. Little aooeared before (bngressional committees dealing with smoking an3 health in 1955 and 1969. The mandate of the Scientific Advisory 9oar3 was broad 3nd simple, namely to sponsor independent research in

502 the area of tobacco and health. The Scientific Advisory Board ras and is today composed of individual scientists whose expertise covers those disciplines of the biomedical sciences that are essential to understanding the complexities of chronic diseases and their pathogenesis. In spite of the successful elimination of many diseises caused by infectious agents, we are still groping for an unierstanding of th e inexorabl e proces s o f chroni c d iseases such as arteriosclerosis and cancer. Are we in any better position today to fathom the challenging puzzle of caise and cure of these devastating medical problems? ae are becoming more aware of the fact that cancer, arteriosclerosis, and other chronic diseases are not the result of exposure to a single substance that has been inhaled or eaten. For example, arteriosclerosis is hastened by a concomitant hypertension, but occurs even in peoole who are of normal weight and without hypertension. What causes the arteriosclerosis that leads to coronary occlusions and strokes? Here we have a controversy that will be resolved only when each of the categories of research unravels the cascade of events that leads to death or disability. It would be disastrous, for example, to decide now that arteriosclerosis is primarily a problem relating to blood lipi3 control. Cancer etiology and control have been intensively researched, especially in the past 75 years. We have learned much from the rapidly developing area of molecular biology - 2- 503 which is driving us nearer and nearer understanding the thousand and one cor membranes, within cells and in organs required for maintaining the normal s' beginning to understand the interrela cells, tissues and organs such as the adrenals as well as the brain itself. constituents is not an independently f rather part o f a wonderful organism wc I healthy individual which quite often r abnormalities (or copying mistakes) t} `_rorc injury or disease. Spontaneous s cell division are inevitable because r yield exact copies of the genetic infc t- neir progeny. The body has the abil: of genetic material in which a mistake reoroduction process. If the repair i t~en the newly formed cell might die c a new kind of cell - a cancer cell. Fiow else might cancer occur? We k can be inbred in a deliberate way (by an3 a predictable percentage of their =sncer. This is a very useful laborat carcinogenicity or cocarcinogenicity o other agent. Likewise, epidemiologist =losely observing human "cancer famil i - 3-

which is driving us nearer and nearer to the ultimate goal of understanding the thousand and one continuous reactions in cell membranes, within cells and in organs and tissues that are required for maintaining the normal steady state. We are just beginning to understand the interrelationships of individual cells, tissues and organs such as the lung, kidney, and adrenals as well as the brain itself. Each of these body constituents is not an independently functioning entity, but rather part of a wonderful organism working in harmony in the healthy individual which quite often reverses or corrects abnormalities (or copying mistakes) that result spontanously or from injury or disease. Soontaneous mistakes in the process of cell division are inevitable because millions of cells must yield exact copies of the genetic information they possess to their progeny. The body has the ability to reoair the strands of genetic material in which a mistake occurred in the reproduction process. If the reoair is incomplete or fails then the newly formed cell might die or it may go on to develop a new kind of cell - a cancer cell. Ebw else might cancer occur? We know that selected mice canbe inbred in a deliberate way (by 20 generation crosses) and a predictable percentage of their progeny will develop cancer. This is a very useful laboratory tec`lnique for testing carcinogenicity or cocarcinogenicity of a given chemical or other agent. Likewise, epidemiologists have found and are closely observing human "cancer famil ies" in which the genetic

role is clear. Thus, a full understanding of the complex process of carcinogenesis must consider not only abnormal inherited genes or chemical expceure of the genetic material of a cell but also the possible imaact, involvement or participation of ionizing radiations and ultraviolet rays, viruses and many internal derangements. In the laboratory animal, when studying tucor induction with a given chemical substance or virus, one has better control of the various factors which may play a role in carcinogenesis, but inhumanepidemiological studies it is very difficult to isolate one factor from another. Human beings are exposed to a variety of environmental impingements. They also have d i ffering l i fe s tyles i nvolving v3rious s tres ses, eating habits, drinking or smoking habits, as well as different genetic or constitutional backgrounds. We are seeking ways and there are promising leads in the search for the members o`_ our population who may be susceptible or likely to develop cancer. We have found families with genetically transmitted susceptibility to emphysema. Likewise in the field of cancer, we are now looking for markers to identify peoole who might be susceotible. Whl have I stressed the importance of soontaneous, inherited or induced genetic aberration in the development of disease? SimpLy because many of our dread diseases seem to originate after a lesion occurs in a DNA strand, which may actually lead to the development of an individual cancer or -4 - become an inherited problem in successi• example, molecular biology has already 1 sequence in the double helix responsible anemia. Genetic engineering is a thing promises rapid progress. Malignant cells carry unique and ide their surfaces that are characteristic a malignancy. With current techniques imm Killer 'P lymphocytes that recognize and e molecules of malignant cells and destroy attacking the surface molecules of the ta Many have heard of the hybridoma - a revolutionizing biology. In the test tub tumor cells and antibofly-forming cells re that can generate, perhaps immortally, la a:lt1bo31°_s that will react with small pep part of a large protein. These hybridoma be used to treat tumors. This is an exam engineering can and is doing. We shali sE in fact, we are alrea9y witness to a genetic engineering procedures. ^cven as I stand here at age 70, I am Y 3ee the answers before the end of this cer. aiseases that pLague us. We are in the mi `-rsitfui fields of molecular genetics. We 3`-Z7raalities and we can even splice in ne -5-

become an inherited problem in successive generations. For example, molecular biology has already located the particular sequence in the double helix responsible for sickle cell anemia. Genetic engineering is a thing of the present that promises rapid progress. Malignant cells carry unique and identifying molecules on their surfaces that are characteristic of the specific malignancy. With current techniques immunologists can develop Killer P lymphocytes that recognize and seek out the specific molecules of malignant cells and destroy the malignancy by attacking the surface molecules of the target malignant ce11s. Many have heard of the hybridoma - a powerful tool that is revolutionizing biology. In the test tube a fusion o f mouse tumor cells and antibody-forming cells results in a hybrid cell that can generate, perhaps immortally, large quantities of antibodies that will react with small pepti3P chains that are a part of a large protein. 'Eaese hybridoma antibodies may also be used to treat tumors. This is an example of what genetic engineering can and is doing. We sha11 see in the next decade, 3n'9, in fact, we are already witness to a wide spectrum of genetic engineering procedures. Even as I stand here at age 70, Z am hopeful that we shall see the answers before the end of this century to many of the diseases that plague us. We are in the mid9le of vast and fruitful fields of moleailar genetics. We can find the genetic •5normalities and we can even solice in new gers segments. We

507 are literally swimming in new knowledge in immunology and only beginning to ap?ly the fruits of these discoveries. This has been a remarkable era of discovery in the area of peptide hormones which exert tremendous influence on many functions, including lung and cardiovascular. The future challenge is to see whether, and how, these peptides say play a role in the causation of chronic disease. From these continuousLy ®erging discoveries, only a few of which I have touched upon today, the synthesis of disparate ` findings occurs. It is this synthesis whichheral3s the understanding of the aging process. Only such understanding will lead to control of our most formidable and complicated diseases such as arteriosclerosis, heart diseases and cancer, as well as the whole category of other degenerative maladies. LEON ORRIS JACO Born December 16, 1911, in Sims, 1 Tiarried; tvo children, Eric and Ji Degrees: B.S., 1935, North Dakota H.D., 1939, The Universit Honorary Degree of Docto: 2torth Dakota.Stata Unive- Honorary Degree of Docto: Acadia University, Nova : Licensure and Certification: State of.Illinois :i Anerican Board of Iaterai -`acadenic. Eositioasi5;=' ihe IIniversitv o'f Chicastc Intern, 1939-40 Assistant Resident in ISee Assistant in.Hedicine, IS ; - Instructor in Medicine, i Assistant Professor of Hc Associate Dean, Division Sciences, 1945-51 Associate Professor of Hc Professor of Medicine anc Section, 1951-61 Professor and Chairman,.I 1961-65 . Joseph Regenstein Profes: Tledical Sciences, 1965- 8 Dean, Division of the Bic the Prit:ker School of Ttc 0 W 0 0 ~i 0-82--33

- - Sha Uiri-versity of Chicago latera, 1939-40 Medicine Assistant Resident in Medicine, 1940-41 Assistant ia.Medicine, 1941-42 Instructor in Mediciae, 1942-45 Assistant Professor of Medicine, 1945-48 Associate Dean, Division of the Biological 'Sciences, 1945-51 Associate Professor of Medicine, 1948-51 Professor of Medicine and Mead of the Deoatology Section, 1951-61 Professor aod Chalrman,.Department of Medicine, 1961-65 Born Deceaber 16, 1911, in Sims, North Dakota Married; tvo children, Eric and Judith Degrees: B.S., 1935, North Dakota State University M.D., 1939, The University of_Chicago Bonorary Degree of Doctor of Science, 1966, ;' North Dakota. Stata University Bonorary Degree of Doctor of Science, 1972, Acadia University, Nova Scotia Licensure and Certification: State of I1linoia - Amaricaa Board of Internal `Acadenie ~ -7 Joseph Regenstein Professor of Biological and Medical Sciences, 1965- 81 Emeritus 1981 - Dean,- Division of the Biological Sciences and the Pritzker School of Medicine, 1966-1975

Health Officer, Metallurgical Laboratory (Plutoaiun Project),,Sianlxattan District, Medicine and Biology, 1942-43 Consultant, Division of Biological and Medical Research, Argonne National Laboratory Special Cansultant, Bematology Study Section, U.S. Public Health Service, 1949-63 Consultant, Division of Radiobiological Health, University Grant and Training Branch, Department of Health, Education, and Welfare, 1962-65 Consultant, University of•California, xerkeley, 1962- E1SdC'1lSl`S~LIK~hII(iIXf S 4~'f KllfofdX IEdi1'S~,KXI~GD:X K21L`SXI.}$~( ~1(fX NlkVU!` YYdAXKXQRW Boards and Committees: Associate Director of Health, Metallurgical Laboratory (Plutonium Project), Manhattan District, 1943-45 Director of Health, Metallurgical Laboratory (Plutonium Project), Manhattan District, 1945-46 Member, Institute of Radiobiology and Biophysics, 1949-54 Director, Argoaai Cancer Research Hospital (operated by The University of•Chicago for the U.S. Atomic . 'Energy Commission), 1951-67 Director,.Franklia.McLean Memorial Research Institute :'(opara.Lad_3y.The University of Chicago for the U.S. i Atomic.-Energy Coamission/Energy Research and Develop- ,• ment-Ad_iaistratioal, 1974-77 Member, Committee for Radiation Studies, U.S. Public Health Service, 1951-55 Member, Committee on Cancer Diagnosis and Therapy, Panel on Chemotherapy, National Research Council, 1951-55 Member. Advisory Committee on Isotope Distribution, U.S. Atomic Energy Commission, 1952-56 United States Representative, First and Second Internatior.al Conferences on Peaceful Uses of Atomic Enerrv. Ccneva, 1955 and 1958 _ Boards and Committees (cont'd): Member, National Advisory B Medical Research Foundation - Menber of Advisory Cot:_itte II.S..Atomic Energy Commissi State, 1960 :'-.^ _' - Member, Expert Advisory Pan, rHealth Organization, Geneva Member,'Advisory Committee ~ Ceneral of the Army,'1961-7c Luember, Morison:Panal of thE Office of Science and Tachac of_ahe President',:~1963-65', -; Member, ;!edicil'ind Scientif Aill:Rogars Memotial Fund,_1 G :' 'Member;.-.EryCh=opoietin~Comni Znstitute~•:II:S:°;Public Haalt Member, Board of Scientific Cancer Institute, National I 1963-67 . Member,,=Spaee Biology Adviao Space Science and Applicatio .National Aeronautics and Spa 1968-70" Member, National Advisory Ca National Cancer Advisory Boa of Health,.1968-72 • Member,,Subcoamittee of the for Commissioner of Health, .Member, Medical Advisory Comi Commission of Cook County, 1: Member, Environmental Adviso: Edison.Company,.Chicago, 1971 Lfember,.International Board Medicc,.The Netherlands, 1971 Member, Editorial Board, Con2 McGrav-Hill, Inc. ;-~. - . .

509 Boards and Comnittees. (cont'd): Member, National Advisory Board of the Oklahoma Tledical Besearch Foundation,.1959-64 - Hember of Advisory CoL_ittee sent to Yugoslavia, II.S..itomic Energy Comnission and the Department of -'-State, 1960 :Membar; Expert Advisory Panel on Radiation, World rHealth Organization, Ceneva, 1960-65 -Henber;'Advisory Comnittee on Biophysics, Surgeon •General of the Arny, 1961-70 :Menber,- Horison Panel of the Wooldridge Commietee, --'Office-of Scieace-..and Tecbnology, Esecutive Office of.'the= Pre s idea t'; Henber, ;Sedical and Scientific Advisory.Board, i7ill..Hogars Menorial Fund,_1963-66 ,lfember;;7Erythropoietin Committee,'National'.Heart ,`.:Institutr;:II:S:=;Public Haalth Service, 1963-67 Hember, Board of Scientific Counselors, National Cancer Institute, National Institutes of Health. 1963-67 Hember,'=Spaee Biology Advisory Subcommittee,' Space Science and Applications Steering Comnittee, -National Aeronautics and Space Administration, 29fi8-70 Hember, National Advisory Cancer Council and National Cancer Advisory Board, National Institutes of Health,.1968-72 ` of the Hayor's Search Conmittee Member, Subcommittee for Commissioner of Health, Chicago, 1969 2Sember, 2iedical Advisory Committee, Civil Service Commission of Cook County, 1969 Member, Enviranmental Advisory Council, Commonvealth Edison.Company,.Chicago, 1970 Member,.International Board of Editors, Ercerpta Medi.ca;.The Netherlands, 1970-81 Member, 'Editorial Board, Contemporary Ftedicine and Surgery McGrav-Hill, Inc. • .,~.-

•Boards and Committees (cont'd): . '•Nember, President's Advisory Committee on the Puerto Rico Nuclear Center, University of.Puerto'Rico, San Juan,. 1970- Chairman, Committee on the Study of Postdoctoral •' Fellovship'and Trainaeship Programs in the Biomedical . Selencaa, Mational Academy or aClences-n-v.+.+ ;. Rasaarch Couacil, 1971- 72 : . Member,' Report Review Committee, National Academy 0 Sciences, 1971-72 C:K,C IYYi~bYiGiaKxllliClE1L'Si~d(ffHC~K616'('lfa<3~df K~K}l~i.'~lfid~T~'s'S~SI5Xi3CK~d0( . x13f iyu~BYMcX1YKw l4%tW0KJUS6 SXW . - . . . ~ Iastitute of Health and Public Health' oi er, IIli ~_l_ s a Iiamb ? R Advisery Committea 1969- ~ry - . . . ... . _ - . :•., Member, Board of Directors; member, Regional-Aavisory 7 State of Illiaois 14E~ dieal Deana f H o~n iL b ~ ~ i , a o er C °Hem . r~; K _=..-Me•mbar=,=•Dea4's-Advisory Committee for Education ia tha. Health.Flelds. State of Illinois armu.r,+'euolic.neaich Gdvisory Committee, State Illinois,.Board of Higher Education t e , m oa Tobacco and Health. Department of Health, Educatioa, .r:-; . . ,. •. •. -.!lambar; Advisory Committee on Personnel for Research, Americaa Cancer Society Member, Scientific Advisory Board, Institute for Advanced Learning in the Medical Sciences, City of Hope Medical Center, California,.1962- Mamber,-Board of Trustees, La Rabida Children's Hospita•1- and Research Center, Chicago, 1967- Director at Large, Board of Directors, Alpha Omega Alpha Honor Medical Society, 1967=11 Member, Committee on Honorary Memberships, Alpha - Omega Alpha Honor Mediqal Society, 1971- 72 ~c>ox~x~xn~c;~x~cxaxr~x ~xac~~ ~ ucxxa~zK~c Kxt~x~~xKx ~~c Tfid(~(Sr4tK4lKAdC$L~519XKS~i(.lEljiQU(7AU(YYrK . ber Liaison Subcommittee of the Joint Committee M and Welfare 511 ,.rds and Committees (cont'd); Member, Medical Advisory Board, L Foundation Member,-Scientific Advisory Commit Cancer Research, Philadelphia, 19: Hember,-Scientific Advisory Board, :obacco Research•- DSA, New York 1, Membei, Staeriag and Finance Commi Society ozvonatology, 1973 Member. Committee '. Professional : Institute of Medicine ec Chicago, : ,Hember,jEvaluatioa Committee, Na.r,_- pMedical Education;•:1966- Member Subcommittae on Henatopoiet '.System of,aha.Committee oa Ratia c g ;-=PhyaieaL Znpairmeat':=Aaeriea¢ Medic _:_Cbairaan;,:-Committee-oa Science Pol_' -'SeaIth; Tnatitute"of- Medicine, aati Sciencea;J972-73 u~~s.~ *he a__. Contemporary Medicine and Surgeryl5 Chairman;~Section.of Medical Scianc Acadeny.-of.>Sciences, 1974-;77 _-Hember, Committee on Federal Researrh on•Bic -" ',Etfects of Ionizing Radiation (FREIR). Natic tec;~•r: Medical Aspects of Atomic Warfare, : Commissioa Traiaing Program, Chicagc Fifth International Cancer Congress- International Congress of Radiology: Munich, 1959 International Society of Hematology, Cambridge, England, 1950; Munich, 19 American College of Physicians. Univ 1950 •. Symposium on Radiology, Cleveland, 1 Chicago Society of Internal Medicine Chicago Pathological Society, Chicag~ Northern Indiana Medical Society, Fo: