Cancer Today: Origins, Prevention, and Treatment (1984)

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REFERENCE COPY FOR LIBRARY UoE ONtY Origins, Prevention, and Treatment Written by Leslie Roberts Foreword by Lewis Thomas, M.D. OCT ?, 1 LIBRARY INSTITUTE OF MEDICINE /NATIONAL ACADEMY PRESS Washington, D.C. 1984

National Academy of Sciences • 2101 Constitution Avenue, NW • Washington, DC 20418 This publication is based on presentations at the annual meeting of the Institute of Medicine held in Washington, D.C. on 26 October 1983. The views expressed are those of the participants and do not necessarily reflect those of the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of appropriate professions in the ex- amination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government, and its own initiative in identifying issues of medical care, research, and education. Library of Congress Cataloging in Publication Data Roberts, Leslie, 1950- Cancer today. Contains summarized report of the 1983 Institute of Medicine Annual Meeting, held in Washington, D.C. Includes index. 1. Cancer—Congresses. I. Institute of Medicine (U.S.). Meeting (1983: Washington, D.C.) II. Title. [DNLM: 1. Neoplasms. QZ 200 R645c] RC261.A2R6 1984 616.99'4 84-19031 ISBN 0-309-03436-1 Copyright © 1984 by the National Academy of Sciences No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted or otherwise copied for public or private use, without written permission from the publisher, except for the purposes of official use by the United States government. Printed in the United States of America

Preface and Acknowledgments Of all the afflictions of humankind, cancer inspires a particular dread. Perhaps because it carries a tradition of hopelessness that is not dispelled even by new reports of better cure rates, cancer seems to pose a mystery that defies our otherwise remarkable scientific skills. In truth, however, we have never been closer to understanding exactly how cancer gets its start. This promise carries with it the increasingly good prospect that in a large number of cases the disease can be prevented and possibly cured completely. To provide a forum on today's optimism about cancer, the Institute of Medicine devoted its 1983 annual meeting to an ex- amination of the scientific advances underlying that optimism. The program, "Implications of New Developments in Science: Can- cer," presented some of the newest discoveries in tumor biology, evidence linking diet to cancer, and aspects of treatment and care. This book, prepared by science writer Leslie Roberts, is based on the presentations given at the 1983 meeting. The chapters on the biology of cancer derive from the talks of J. Michael Bishop, 111

PREFACE AND ACKNOWLEDGMENTS Philip Leder, and Mariano Barbacid. Anthony Miller, Bruce Ames, and Richard Merrill contributed the bases for the chapters on diet and cancer. Emil Frei, Jimmie Holland, and David Greer provided material for the chapters on chemotherapy, psychosocial aspects of cancer, and American hospices. Finally, the summarizing com- ments of Paul Marks and Maureen Henderson set the framework for the book's introduction. For the readers' convenience, the back of the book contains a glossary of terms frequently used in the areas of cancer research discussed here. The Institute of Medicine wishes to thank all the speakers who addressed the 1983 meeting—a complete list follows—for their cooperation throughout the preparation of this book, and to ex- press special gratitude to Lewis Thomas for the foreword, crafted with the grace characteristic of all his writings. We also are very grateful to division director Enriqueta Bond for her guidance in planning and implementing last year's annual meeting. Cancer Today is an experiment, a new form for communicating the current interests of the Institute of Medicine to the public. We hope for its successful reception and for future opportunities to share our work with a wider audience. Frederick C. Robbins, M.D. President, Institute of Medicine IV

Contents Participants vi Foreword vii Lewis Thomas 1. Introduction 1 Biology of Cancer 2. Genes Gone Awry 17 3. Oncogenes in Human Cancer 29 4. Broken Chromosomes 39 Diet and Cancer 5. The Epidemiology of Diet and Cancer 49 6. Dietary Carcinogens and Anticarcinogens ... 63 7. Diet and Cancer: New Policy Questions .... 73 Cancer Treatment 8. Cancer Medicine: Chemotherapy 81 9. The Psychological and Social Effects of Cancer 91 10. Alternative Care for the Dying: American Hospices 103 Glossary 117 Index 121

Participants MAUREEN HENDERSON, Meeting Chairman, Professor of Epidemiol- ogy and Medicine, University of Washington BRUCE N. AMES, Professor of Biochemistry, University of California- Berkeley MARIANO BARBACID, Head, Developmental Oncology Section, Na- tional Cancer Institute-Frederick Cancer Research Facility J. MICHAEL BISHOP, Professor of Microbiology and Immunology, University of California-San Francisco EMIL pREI III, Director and Physician-in-Chief, Dana-Farber Cancer Institute DAVID S. GREER, Dean of Medicine, Professor of Community Health, Brown University JlMMIE C. HOLLAND, Chief, Psychiatry Service, Memorial Sloan-Ket- tering Cancer Center PHILIP LEDER, John Emory Andrus Professor and Chairman, Depart- ment of Genetics, Harvard University School of Medicine PAUL A. MARKS, President, Memorial Sloan-Kettering Cancer Center RICHARD A. MERRILL, Dean and Professor, School of Law, University of Virginia ANTHONY B. MILLER, Director, National Cancer Institute of Canada Epidemiologic Unit, University of Toronto Staff ENRIQUETA C. BOND, Director, Division of Health Promotion and Disease Prevention, Institute of Medicine VI

Foreword There was a time within easy memory when cancer was regarded within the upper circles of basic biomedical science as an unapproachable and therefore not very interesting research problem. Twenty years ago it was generally viewed as an essentially unsolvable puzzle, too profound and complex to be attacked by any imaginable research technology, simply beyond the reach of science. Not to say that excellent research was not going on. It was, and indeed the groundwork was then being laid by the molecular biochem- ists, virologists, immunologists, and cell biologists for what was to follow. But at that time, in the 1960s, the cancer problem had not yet engaged the full force of intellectual attention in biomedical science at large, as is the case today. It was not yet perceived that there could be ways into the very depths of the problem. The time, it was said, was not at hand. In the early 1970s the magnitude of the problem as a cause of in- capacitation and death in human beings was recognized as an increas- ingly serious matter, and pressures were brought on and by the Wash- ington administration and Congress to do something much more ambitious in the way of research. Advisory committees and panels Vll

FOREWORD went to work, putting together what soon emerged as the "Conquest of Cancer" plan, backed by the assurance of greatly expanded budgets for cancer research. The arguments over how to go about it were intense and sometimes bitter. Some of the scientific advisers asserted that it was just too early for a full-scale attack; too much fundamental information was lacking. Others believed that the country should invest heavily in applied science, in an endeavor to improve what already existed in therapeutic, diagnostic, and preventive medicine. This was, as it turned out, one of the luckier turning points in the history of biomedical science and the inevitable politics associated with science. Two things happened at about the same time. Research funds became available on a scale to attract many investigators, especially the youngest and brightest, into a field that they might otherwise not have chosen to enter. This in itself was an important event, but if it had occurred by itself we would not find ourselves where we are in the mid-1980s. Money is of course crucial for the progress of science, but money alone cannot make science. Science makes itself, grows itself, and is transformed by its own upheavals and surprises, and this is what began to happen, quite co- incidentally and spontaneously, at just the time when the new cancer research program was launched. The biological revolution, as it was then termed, which had begun with the discovery that DNA was the essential genetic material, possessing a molecular structure to account nicely for replication and duplication, was suddenly transformed into a new revolution superimposed on the old one. First came the discovery of cellular enzymes specifically designed to clip segments of DNA at predictable sites along the molecule, and at the same time an array of vastly improved instrumentation techniques for sequencing the molec- ular fragments, and finally, like a burst of drums, the brand new, unpredicted and astonishing technology of recombinant DNA. Cancer had become, almost overnight, a new kind of adventure for the cell biologists, experimental pathologists, virologists, immunologists, and geneticists, and it moved to the center of biomedical science as the most fascinating and engaging of puzzles. And so it is today. The recombinant DNA technology, surely the most important scientific advance of the century in biology, was soon reinforced and supplemented by the invention of hybridomas and the elaboration of monoclonal antibodies, now indispensable for the iden- tification of gene products and surface markers in transformed cells. viii

FOREWORD The role of oncogenes and their mobile geometric localization at dif- ferent sites within the genome, the existence of enhancing genes and the crucial role of their location in relation to oncogenes, the mode of action of cancer viruses, the complex defense mechanisms mediated and modulated by the various T-lymphocyte populations—all these and more breakthroughs still to come have changed everything about the cancer problem. I have never known a time of such high confidence and exhilaration within the community of biomedical scientists, especially among the youngest investigators just coming on the scene at the postdoctoral level. Cancer research has turned into something like a running hunt. The fox is not yet within sight, but it is at least known that there is indeed a fox, and this is a great change from the sense of things twenty years ago. At that time it was generally believed that cancer was not one disease but a hundred, all fundamentally different and each requiring its own unique penetration. Today it seems much more likely that a single mechanism, or a set of mechanisms, lurks at the deep center of every form of cancer. It is even conceivable, in this writer's optimistic view, that when all the facts are in there may emerge a totally new, still unpredictable combination of applied pharmacology and immu- nology for reversal of the process and for its prevention. The way ahead is now open for the clinical scientists and epide- miologists to begin asking questions, unthinkable a generation back, about the role of environmental factors, including nutrition, in the causation of cancer. Very likely, the rising generation of oncology investigators will become even more dependent on experimental animal models for answers, but in vitro cell culture systems will also have more to offer than ever before. The book before you is a brief but comprehensive summary—an overview—of where things stand today in cancer research. If the work goes on at its present pace, some things will change next week or next month, and everything may look quite different next year. But the drift of events laid out in the chapters of this volume should convey a sense of the ways in which progress has been made up to now, and also some sense, cautious as it should be, of the hopes for the future. Lewis Thomas, M.D. President Emeritus, Memorial Sloan-Kettering Cancer Center ix