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GENERAL MOTORS CANCER I:~.,SEARCH FOUNDATION GENERAL ROTORS CANCER RESEARCH FOUNDATION AWARDS BACKGROUNDER June 16, 198l 767 FI[~h AverIue. New Yor~ New Yorlg 101.53 oZ J ,.~ ~,

GENERAL MOTORS CANCER RESEARCH FCUNDATIO~ #I~'ARDS BACKGRCUNDER INTRODUCTION This year, according to the American Cancer Society, 805,000 Americans will be diagnosed as having cancer and another 420,000 will die from the disease. Thus cancer remains the second leading cause of death in the United States as well as major cause of death in many other countries. While much remains unknown about the causes, prevention, diagnosis and treatment of cancer, real progress has been made. More accurate diagnostic methods and more effective treatment ranging from surgery, chemotherapy and radiation therapy to a combination thereof have improved a victim's chance for survival. In the first decade of this century few cancer patients had any hope of long-term survival. During the lg3Os, less than one cancer patient in five was alive five years after treatment. Now the survival ratio is 1-in-3, a gain from 1-in-4 in the 1940s -- representing about 67,000 people cured this year alone. The causes of cancer are gradually being revealed. There now appears to be reasonable hope that cancer can be prevented in the future. T[ 10I 52070

-2- RECOGNITION OF THE IMPORTANCE OF CANCER RESEARCH These advances would not be possible without the concerted efforts of scientists, researchers and physicians around the world, many of whom have individually made major contributions in cancer research. Recognition of these individuals would appear to enhance these much needed efforts. The Nobel Prize has seldom been given for cancer research, and the other prizes available to the tens of thousands of cancer research workers do not provide comparable recognition. THE GENERAL MOTORS CANCER RESEARCH FOUNDATION The General Motors Cancer Research Foundation was formed with a $2 million grant from General Motors to meet the need for recognition of cancer research. The Foundation established three awards, each consisting of a gold medal and $100,000 in cash, to recognize accomplishments of scientists around the world in basic and clinical cancer research, with the hope of stimulating further efforts to control the disease. The president of the Foundation is Joseph G. Fortner, M.D. A pioneer in surgical oncology (tumor study), Dr. Fortner is Professor of Surgery, Cornell University Medical College; Associate Chairman for Laboratory Affairs, Depart- ment of Surgery, and attending surgeon at Memorial S|oan-Kettering Hospital; and Chief of the General Motors Surgical Research Laboratory at the Sloan- Kettering Institute. Dr. Fortner's career has included the creation and development of o~e of the three clinical liver transplantation centers in the T11015207I

-3- world. Presently, one of his principal interests is in a m:Itidisciplinary approach to pancreatic cancer with specific e~phasis on a mew operation for this disease. The Awards The three General Motors Cancer Research Foundation Awards, given annually since 1979, honor scientists in three basic areas of cancer research: diagnosis or treatmeflt of cancer; prevention of cancer; and basic scientific contributions to cancer, particularly in the areas of etiology and pathogenesis. The Ketterin~ Prize The Charles F. Kettering Medal for outstanding recent contribution to the diagnosis or treatment of cancer was n~med for the former General Motors Director and co-founder of the S1oan-Kettering Institute of Cancer Research. A strong supporter of fundamental research in industry and medicine, the late Mr. Kettering believed research should be a cooperative enterprise involving the integrated talents of a wide variety of specialists. The Mort Prize Named for the noted philanthropist and public benefactor, the Charles S. Mott Medal is given for the most outstanding recent contribution to the prevention of cancer, including environmental influences. The late Mr. Mort, longtime General Motors officer and a financial wizard, had co~passion fc~ the sick which was more than evidenced by his dedication and significant contribution toward health i~prove~ent. T110152072

-4- The Sloan Prize The Alfred P. Sloan Medal is given for the most outstanding recent basic science contribution, particularly in the areas of etiology and patho- genesis. Mr. Sloan, who is credited with building the General Motors Corpor- ation as it exists today, had a strong personal cor~itment to finding a cure for cancer. He fir~nly believed that given time, facilities and talent, there is no problem which is beyond the reach of aggressive scientific attack. The late Mr. Sloan was co-founder of the Sloan-Kettering Institute for Cancer Research. Additional Honors In addition to the gold medal and cash award, recipients of General Motors Cancer Research Foundation awards are invited to deliver a lecture concerned with the work for which the prize is given. The lectures are then published as part of a monograph series--"Accomplishments in Cancer Research," and in a special issue of the Journal Cancer. PROCEDURES FOR SELECTION OF PRIZEWINNERS Criteria for the Awards Each 6eneral Motors Cancer Research Foundation award is given to one or more individuals who have been judged by peer review as having made the most noteworthy recent contribution in the field of cancer. Recency is defined by the Foundation as falling within the past 15 years. Earlier work may be honored if its significance has only recently been recognized. Each award is given to one individual with rare exception. Two or ~ore indivi- duals may be ~onored for the same ~ward if they have worked so closely together that it is i~ossib~e to separate their contributions.

-5- Candidates are nominated by invited individuals who are themselves leaders in the field of cancer research. Rominees must have had their works published in a recognized scientific or medical journal. Award winners Must be living at the time of official public announcement of the award. Nominations for the Awards Invitations to nominate candidates are sent out on a rotational basis worldwide to provide a broad representation of countries, universities and institutions. Nominations are sought from individuals holding the rank or its equivalent of Professor or Associate Professor in universities or insti- tutions selected for a given year~s nominations. Current and previous Assembly members, Selection Comittee members and previous prizewinners are invited to nominate on an annual basis. Nominations must be submitted on official forms, typewritten in English, Personal applications for an award are not considered. Prizewinners are selected from nominations of the current year and from exceptionally well qualified candidates of the prior two years. The selec- tions are made by an Awards Assembly upon recomendation by the selection committee. The Awards Assembly The Awards Assembly is composed of 32 internationally prominent basic and clinical scientists. Awards Assembly me~bers are appointed by the Board of Trustees of the General Motors Cancer Research Foundation, Terms of appointment are three to five years. Chairman of the Awards Assembly is Jonathan E. Rhoads, M.D. A leading surgeon, Dr. Rhoads is Professor of Surgery at the University of Pennsylvania Medical Center. He is also editor of the Journal Cancer. T110I 52074

-6- The 1981 Awards Assembly is cc~posed of distinguished medical and scientific leaders from the United States, England, Japan, Italy, Brazil, Sweden, Australia and the Netherlands. Three members of the Awards Assembly are Nobel Laureates. The Selection Committee It is the aim of the General Motors Cancer Research Foundation that the selection process be impartial and that the judgements be based on a thorough study of the candidates' contributions. To this end the Awards Assembly brought into being three selection committees composed of special- ists in the three areas encompassed by the prizes. The committees are composed, in part, of members of the Assembly and, in part, of other scientists. The selection committees may add associate members and employ consultants where additional expertise is needed in special areas of knowledge. The Selection Process Selection committees go through a three-step selection process, beginning with an initial evaluation of all nominations submitted. The large list of nominees is reduced to approximately I0-to-15 candidates for each prize. After preliminary evaluation, the list is further reduced at a second meeting to about four or five candidates for each prize. For these finalists an in-depth study is carried out of the contribu- tions of the individuals and the contributions of other persons who have worked on the same or related projects. At the third meeting, after selection committee members and awards assembly members have reviewed all the pertinent material, the selection cor~nittees make their first and second choices by secret ballot. These 7"1 "~ 0"~ 52075

-7- n~mes, with the candidates' qualifications, are later presented to the Awards Assembly for their consideration. Prize winners are selected by a majority decision of Awards Assembly members present. SCIENTIFIC RESEARCH HONORED BY GENERAL MOTORS CANCER RESEARCH FOUNDATION Research Awarded For Diagnosis and Treatment of Cancer (The Kettering Award) In 1979 Henry S. Kaplan, M.D., professor of radiology and director of the Cancer Biology Research Laboratory at Stanford University, was awarded the first Charles F. Kettering prize. Dr. Kaplan received the award for his leadership in developing a highly effective therapeutic program for Hodgkins disease. The program itself is based on solid advances by Dr. Kaplan and his colleagues in the understanding of the biology of this kind of cancer. Prior to Dr. Kaplan's work, Hodgkin's disease, a cancer of the lymph nodes, was considered to be invariably fatal. Today as a result of high- voltage radiation treatment developed by Dr. Kaplan and his associates, using a linear accelerator (originally intended only for atomic research), Hodgkin's disease is among the most curable of all cancers. High voltage radiation applied to affected lymph nodes and other areas, produces less damage to normal tissues because the radiation beam can be more precisely targeted o~ the tumor. Dr. Kaplan and his colleagues found a direct relationship between the dose of radiation given and the patient's response to treatment. His studies also demonstrated that the disease had a predictable natural course which can be arrested by preventive treatment of apparently normal tissue near the tu~or. T/10152076

-8- In lg~O, the Kettering Prize was awarded to Elwood V. ,lensen, Ph.D., director of the Ben May Laboratory for Cancer Research, The University of Chicago. The prize was awarded for the role Jensen played in the discovery of estrogen binding, including the identification of estrogen receptors in human breast cancer, and his early recognition of the receptors' relevance to endocrine management of the disease. Until recently, the radical mastectomy, first initiated by William S. Halstead of the Johns Hopkins School of Medicine in 1894, was considered the ~ost effective surgical treatment for breast cancer. Today, less deforming operations are commonly utilized. Other types of treatment have also been introduced, such as radiation therapy, chemotherapy and hormone therapy, with important advances in the use of the latter contributed by Jensen. In 1966 Dr. ,lensen began a collaborative study with Dr. George Block seeking to correlate the clinical response of breast cancer patients to endocrine removal. Radioactively labeled estradiol (one of the three main female estrogens) was inserted into breast tumor slices and the tumor's specific estrogen uptake was observed. Jensen and Block found that certain tumors had estrogen receptors and others did not. Those with estrogen receptor-rich cancers were found more likely to respond to endocrine therapy; those with receptor-poor tumors proved unlikely to respond. The latter group, according to the study, would benefit most from chemotherapy. Based on these and other studies, ,lensen devised a test -- the estrophilin (estrogen receptor) assay -- to be used on a primary breast tumor once it was removed. The purpose of the test was to determine whether the tu~r would be sensitive to endocrine therapy. Quite unexpectedly, it TIt0152077

-g- was found also that valuable information concerning the probability of recurrence or ~etatastic disease could be obtained by the test. The prog- nostic capabilities of the test have proven to be invaluable. Research Awarded in the Area of Cancer Prevention (The Mott Award) It has become increasingly evident in recent years that prevention of cancer offers one of the most promising long-range solutions to controlling death from cancer. Researchers are making cancer prevention more and more possible by identifying various kinds of environmental factors that are important in the etiology of human cancers. In 1979 the General Motors Cancer Research Foundation awarded Sir Richard Dot1, M.D., Regius Professor of Medicine and Master of Green College, Oxford University, England, the first Charles S. Mott prize for his recent contribution to the prevention of cancer. Sir Richard received the award for his leadership in relating environmental factors to cancer in man. The epidemiological study of cancer has a history dating back more than 200 years to Ramazzini's observation that breast cancer occurred more often in nuns than in other women and to Percival Port's conclusion in 1775 that chimney sweeps' cancer of the scrotum was caused by their prolonged contact with soot. In the 1950s, Sir Richard conducted studies in which he compared the s~oking habits of lung cancer patients to patients with other diseases. Re and his colleague, the late Bradford Hill, discovered that lung cancer patients were more frequently smokers and smoked more heavily than patients with other diseases. These studies marked the beginning of the modern investigation of the relationship between s~oking and cancer risk. A later study Drs. Doll and Hill conducted with 1,400 lung cancer patients confirmed the strcng relaticnship notecl in their earlier work. T[I O~ 5207~-5

-10- Since that time, Dr. Doll has continued to investigate the relatienship between lung cancer and other forms of smoking (specifically cigars and pipes). Because of his work we now know that this relationship is linear -- all s~oking, whether heavy or light, can cause lung cancer. His studies have also show~ that at least some of the effects of s~oking are reversible. Smokers who quit had, after five years, lung cancer rates only slightly higher than those of non-smokers. Dr. Doll was the first investigator to quantify the increased risk of lung cancer among asbestos workers. He has also been a pioneer in the appli- cation of modern statistical methods to the study and ~easurement of such risks. Dr. Doll has also contributed importantly to knowledge of the carcino- ginic effects of radiation in humans. He has helped to clarify the relation- ship between radiation dose and leukeumogenic and carcinogenic effects. The Charles S. Mott prize was awarded in 1980 to James A. Miller,. Ph.D., professor of oncology, and Elizabeth C. Miller, Ph.D., professor of oncology and associate director of the McArdle Laboratory for Cancer Research, Univer- sity of Wisconsin, Madison. They were jointly awarded the prize for their contribution to knowledge of the metabolic stages that are required for the interaction of environmental carcinogens and cellular constituents in the body. The Millers' contributions have provided not only a unifying concept of the mechanism of chemical carcinogenesis, but the basis for the development of effective short-ter~ tests for carcinogenecity. They have therefore contri- tributed in a most unique way to both the understanding of carcinogenic mechan- ist, s at their ~ost fundamental level and to the practical technique that is now being widely applied towards the control of carcinogens in the environment. Tl10152079

-11- The importance of the Miller's work has been highlighted in recent years by growing public awareness and concern about human exposure to food additives and contaminants, drugs, environmental pollutants and industrial chemicals which may play a role in the development of cancer. Knowledge of environmen- tally-induced cancer has been accumulating at a continuously increasing rate since the 1940s. Two of the foremost contributors to their body of informa- tlon have been the Millers. Awards Given For Basic Scientific Contributions to Understanding Cancer ('The Sloan Award) In lgTg the first Alfred P. Sloan prize was awarded to George Klein, M.D., Ph.D., professor of tumor biology and head of the Institute for Tumor Biology at the Karolinska Institute Medical School in Stockholm, Sweden, for his work m the interrelationship between cancer and the immune system in manmalian species. Studies by Dr. Klein and his associates have clarified important infor- matio~ about how viruses transform normal cells into cancer cells and what immunological mechanisms prevent normal cells from becoming cancerous. Particularly important are Dr. K1ein's observations regarding the only fo~m of human cancer thus far indisputably linked to the presence of specific viruses. He found that Burkitt's ly~phoma and nasopharyngeal carcinoma ceils contain both integrated and non-integrated Epstein-Barr DNA sequences. The Epstein-Barr virus (EBV) is a herpes-type virus. An integrated EBV-DNA sequence is one that has become a part of the genetic information of a target cell. T110152080

-12- Klein found that only integrated EBV-DNA sequences are responsible for tumorgenesis because integration causes a genetic change in the makeup of the host cell. The Epstein-Barr virus is widespread in humans but appears to live in harmony with host individuals because the EBV-DNA sequences are present as free plasmids (non-intergrated). They usually remain latent during a lifetime. Dr. Klein also demonstrated in man~nalian species, other than humans, that several forms of cancer have specific virus-related antigens associated with them. In most cases, Dr. Klein found, that tumor resistance was mediated through "T" cell-dependent (from th~nnus gland cells) mechanis~s. The 1980 Sloan Award was made to Isaac Berenblum, M.D., professor (emeritus) in the Department of Experimental Biology, Weizman Institute, Rehovot, Israel. It was given for his contribution to the concept that carcinogenesis is a two-stage process. The belief that cancer can indeed be prevented was based upon Dr. Berenblum's discovery of a two-step mechanism, called initiation and promo- tion, that is necessary to induce cancer in a cell. This was discovered as follows: Investigating the notion that chemical irritation might be responsible for cancer, Dr. Berenblum applied the chemical benzopyrene to mouse skin. This was the chemical found in soot associated with cancer of the scrotum in chimney sweeps in England in the 1700s. He found the chemical caused a few, small tumors. Dr. Berenblum then applied an irritant, croton oii, which comes from East Indian shrubs, and is not capable by itself of producing cancer. TI10152031

-13- After further investigation, Dr. Berenblum discovered that large tumors occurred only when croton oil was applied after exposure to benzopyrene. The reverse was ineffective. He concluded that one chemical caused a change in cells (initiation) that only became apparent when a second chemical (a promoter) was applied. The initiation substance caused cell mutations which might stay silent forever unless a promoter appeared. Today it is known that cell mutation, which takes place during the ini- tiation stage, is irreversible, while changes during promotion, a slow process, are reversible, l~e recognized that this finding might have profound implications for human cancer. THE 1981 GENERAL MOTORS CANCER RESEARCH FOUNDATION AWARDS Invitations to nominate candidates for the 1981 General Motors Cancer Research Foundation Awards were sent out July 1, 1980. The deadline for receipt of the nominations was Oct. 6, the day the selection process officially began. Final decisions on the award winners were made in May, 1981, by the Awards Assembly. An awards ceremony will be held in Washington, D.C. on June 17, 1981. Washington, D.C. was also the setting for the two previous awards ceremonies held on May 2, 1979 and June 18, I980. T[10152082

-14- Collusion Founders of the General Motors Cancer Research Foundation realized the prestige of the awards would derive from: a distinguished selection panel, worldwide eligibility for the awards, the severity of the selection process and the generosity of the gifts. Roger Smith, Chairman of the Board of General Motors, and CEO, is the originator of the Foundation. ~e hoped the prize would not only be an impetus for further scientific research, but would demonstrate to the public that progress is being made in the fight against cancer. The award, he anticipated, would also encourage more public support for cancer research. Tl10152033