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Progress Report N O V E M B E R 1 9 5 4 It is the practice of the Institute to issue interim reports describing in detail a research program of particular interest and irnportance. A summary statement of the entire scientific program is presented biennially. This Progress Report presents a review of the Institute's effort to achieve prevention and the better control of cancer of the lung. SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH 410 EAST 68TH STREET, NEW YORK 21, N. Y. Research Unit of MEMORIAL CENTER FOR CANCER AND ALLIED DISEASES Division of CORNELL UNIVERSITY MEDICAL COLLEGE

J The 100-laboratory Sloan-Kettering Institute for Canrer Research. Memorial and James Ewing Hospitals, other units of Memorial Center, adjoin the Institute.

SLOAN-KETTERING IN STITUTE FOR CANCER RESEARCH OFFICERS ALFRED P. SLOAN, JR. ELLMORE C. PATTERSON Chairman of the Board Treasurer FRANK A. HOWARD HARRISON V. SMITH President llssistant Treasurer EDWARD C. DELAFIELD H. LAWRENCE HESS Secretary fl ssistant Secretary BOARD OF TRUSTEES ALBERT BRADLEY Executive Vice President, General Motors Corporation DETLEV W. BRONK, Ph.D. President, Rockefeller Institute f or Itiledical Research REGINALD G. COOMBE Vice President, The Hanover Bank L' DWARD C. DELAFIELD Senior Partner, Delafreld and Delafeeld JOSEPH C. HINSEY, Ph.D. Director, The New York Hospital- Cornell Medical Center FRANK A. HOWARD Research Consultant, Standard Oil Company (N.J.) CHARLES F. KETTERING Research Consultant, General Motors Corporation EUGENE W. KETTERING tlssistant Chief Engineer, Electro-Motive Division, General Motors Corporation DEANE W. MALOTT President, Cornell University W. ALBERT NOYES, JR., Ph.D. Chairman, Department of Chemistry, University of Rochester ELL-MORE C. PATTERSON Vice President, J. P. Morgan & Company, Inc. JOHN L. PRATT Engineer and Philanthropist LAURANCE S. ROCKEFELLER Rockefeller Brothers, Inc. ALFRED P. SLOAN, JR. Chairman of the Board, General Motors Corporation RAYMOND P. SLOAN Vice President and Editorial Director, The 11-lodern Hospital Publishing Co. LEWIS L. STRAUSS Chairman, U. S. !1 tomic Energy Commission GEORGE WHITNEY Chairman of the Board, J. P. Morgan & Company, Inc. THEODORE P. WRIGHT, D.Sc. Vice President for Research, Cornell University COIXIMITTEE ON SCIENTIFIC POLICY FRANK A. HOWARD, Chairman DETLEV W. BRONK, Ph.D. CHARLES F. KETTERING JOSEPH C. HINSEY, Ph.D. W. ALBERT NOYES, JR., Ph.D. LEWIS L. STRAUSS SCIENTIFIC CONSULTANTS PAUL R. BURKHOLDER, Ph.D. Head, Department of Bacteriology, University of Georgia ROBERT C. ELDERFIELD, Ph.D. Professor of Chemistry, University of Michigan SIDNEY FARBER, M.D. Director, Children's Cancer Research Foundation, Inc. CHOH HAO Li, Ph.D. Professor of Experimental Endocrinol ogy, The Institute of Experimental Biology, University of California E. HucH LUCKEY, M.D. Dean, Cornell University Medical College RICHARD E. SHOPE, M.D. Member, Rockefeller Institute for Medical Research HOWARD EARL SKIPPER, Ph.D. flssistant Director, Southern Research Institute WARREN WEAVER, Ph.D. Director, Division of Natural Sciences and tlgriculture, Rockefeller Foundation DIRECTOR C. P. RHOADS, M.D. BERNHARD L. MECKE A.R.T. DENUES, Ph.D. ROBERT R. WHITE ,4dministrator Issistant to the Director Fiscal Officer

New telecobalt unit. Its effectiveness in radiation treatment of cancer of the lung is under study.

5 S L O A N- K E T T E R I N G I N S T I T U T E F O R C A N C E R R E S E A R C H Introduction The rapid increase in deaths from cancer of the lung is a matter of concern to those who guide the policy of the Sloan-Itettering Institute. The Institute is a research organization dedicated solely to the alleviation of cancer in man. It is dependent upon and responsible to the public. The pages that follow constitute.the Institute's report tQ._ the public on its work on lung cancer, some of the progress that has been made to date, and further gains that may be expected. Without being diverted from our main lines of progress toward better under- standing and control of cancer in all of its forms, we are hopeful of being able to contribute substantially to the intensive work now under way in so many places on this special problem. The progress report here presented differs somewhat from its predecessors. Whereas each of the seven previous progress reports has dealt with some special phase of the program, the present state- ment cuts across all the lines of effort to summarize the relation of the work to the control of lung cancer. For this reason, this report shows the Institute in action perhaps more clearly than any of the others, illustrating the team work among the many scientific disci- plines, the constant focusing of the research effort on the practical day-to-day problems of cancer control, and the unusual cooperative effort linking the laboratory scientist with the surgeon and clinician. Evolution of the Institute The type of organization and effort here depicted is the fulfill- ment of the concept of the Institute's founders that the better control of cancer could best be approached by a large-scale laboratory pro- gram in the experimental sciences carried out in direct conjunction with the treatment of cancer in man. Realization of this concept was made possible by the Alfred P. Sloan Foundation which provided

6 S L O A N- K E T T E R I N G I N S T I T U T E F O R C A N C E R R E S E A R C H funds for the construction of the Institute's functional, 13-story lab- oratory building which opened in 1948. The Foundation also pledged $200,000 a year, subsequently increased to $400,000 a year, on a five- year continuing basis, toward the Institute's support. At present, the Foundation's pledge covers about 14 per cent of the current research budget, which is now almost $3,000,000 annually. The Memorial Center, of which the Institute is an integral part, now consists also of the Memorial Hospital, the James Ewing Hos- pital of the City of New York, the Tower Clinic Building, and the Strang Cancer Prevention Clinic. The Institute itself recently has been enlarged by the addition of the Andre and Bella Meyer Physi- ology Laboratory with the Kress Betatron Unit. The Institute stands directly between the two hospitals and is joined with them, both physically and in its organization and activities. Leadership and Staff While the Institute has its own charter, its Trustees are elected by the Board of Managers of the Memorial Center corporation. The Institute laboratories are manned by a staff of over one hundred scientists and about three hundred technically trained sup- porting personnel. Many members of the Institute's staff are also Doctors of Medicine who hold hospital appointments and are directly responsible for the care of patients, especially those being treated by new agents and methods developed under the Institute's program. The research program of the Institute divides along many differ- ent lines of scientific specialties. Since the last report, two new divisions have been added. They are the Division of Pathology, under the direction of Dr. Fred W. Stewart, Chief of the Depart- ment of Pathology of Memorial Center, and the Division of Preven- tive Medicine, under the direction of Dr. Emerson Day, who is also Director of the Strang Cancer Prevention Clinic. An important part of the work described in the scientific report that follows is conducted in these new divisions.

7 S L O A N- K E T T E R I N G f N S T I T U T E F O R C A N C E R R E S E A R C H On June 22, 1954, the Institute suffered a great loss, as did the entire country, with the death of Dr. Karl T. Compton. Dr. Compton had given distinguished service as a member of the Institute's Board of Trustees and Scientific Policy Committee since its organization. In Jcknowledgment The major part of the Institute's support is contributed on a year-to-year basis by the public, either directly in private gifts, or through governmental and voluntary agencies. Among these are the American Cancer Society, the Damon Runyon Memorial Fund, the Black-Stevenson Fund, the Albert and Mary Lasker Foundation, the Samuel H. Kress Foundation, the U. S. Atomic Energy Com- mission, the U. S. Public Health Service, and the Max C. Fleisch- mann Foundation. No less important to the very existence of the Center is the support of hundreds of individuals, foundations, and corporations whose combined gifts make possible a substantial and important share of the Institute's program. To all of these, the Trustees are deeply grateful.

Cancer caused by painting skin of mouse with known cancer-producing agent (above). Cancer caused by painting skin of mouse with cigarette tar condensate (below).

9 S LOAN-ICETTERINC I NSTIT UTE FOR CANCER RESEARC H Scientific Report For twenty years, sporadic scientific communications have referred to an increased rate of death from cancer of the lung. The increase has been observed in most, but not all, countries, and measured by many different methods. Full consideration has been given to factors that might give a false picture of lung cancer inci- dence. The increase is not a statistical fiction, but is real in the opinion of every qualified observer and has taken place in the face of con- sistently dropping death rates from other disorders, and a decline in the death rates from many other forms of cancer when these rates are corrected for the increasing number of individuals coming each year into the cancer age. Neither public, medical profession, nor industry can longer ignore the fact of 20,000 deaths each year from lung cancer alone, a twelve-fold increase over 1928. Since 1950, the problem has crystallized. In that year the publication of Wynder and Graham`1' reported a correlation between smoking and lung cancer. Confirming reports followed from this and other countries. In 19S3, the same authors"' reported the pro- duction of cancer in the skin of mice by long-continued painting with the tar condensed from the smoke of cigarettes, mechanically burned under conditions that simulate human smoking. More recently, new studies have been reported, one by Hammond and Horn`3' of the American Cancer Society and the other by two distinguished British investigators, Doll and Hill."' In both reports, the rate of death from lung cancer in large population groups was found to be predictable on the basis of smoking habits, especially the inhaling of cigarette smoke over long periods. The heavy inhaler clearly has a much greater chance of acquiring lung cancer than does the non-smoker. Whereas other factors, such as air pollution from