COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXVI COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

Founded in 1933 by REGINALD G. HARRIS Director o/ the Biological Laboratory 1924 to 1936

The Symposia were organized and managed by Dr. Harris until his death. Their continued use- /ulness is a tribute to the soundness o/ his vision.

The Symposium volumes are published by the Long Island Biological Association as a part of the work of the Biological Laboratory Cold Spring Harbor, L.I., New York COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXVI

Cellular Regulatory Mechanisms

THE BIOLOGICAL LABORATORY COLD SPRING HARBOR, L.I., NEW YORK

1961 COPYRIGHT 1962 BY

THE BIOLOGICAL LABORATORY

LONG ISLAND BIOLOGICAL ASSOCIATION, INC.

Library of Congress Catalog Number: 34-8174

All rights reserved. This book may not be reproduced in whole or in part except by reviewers for the public press without written permission from the publisher

PRINTED BY WAVERLY PRESS, INC., BALTIMORE,MARYLAND, U.S.A. FOREWORD

During the past twenty years, research in genetics and biochemistry, while superficially directed toward an understanding of different aspects of cell behavior, has been moving to a union which appears to have been completed in the presen- tations at this symposium on Cell Regulatory Mechanisms. Sessions were devoted to the role of the genetic material as an information code in protein synthesis and the mechanism of information transfer from DNA to the site of synthesis. Major attention was devoted to cellular mechanisms governing the rates of enzyme ac- tivity and enzyme synthesis. While most of the research presented dealt with microorganisms, the significance of these efforts for questions of normal and ab- normal growth and development in multicellular forms is quite apparent. I wish to express our appreciation to Bernard D. Davis, Eugene W. Knox, Jacques Monod, Van R. Potter, Gordon M. Tomkins, and H. Edwin Umbarger, whose generous and thoughtful advice provided the basis for organization of this program, and to H. A. Itano, Erwin Chargaff, A. D. Hershey, Elliot Volkin, Fritz Lipmann, Joseph F. Gots, Edward L. Tatum, H. O. Halvorson, Efraim Racker, Van R. Potter, Claude Villee, Eugene W. Knox, and Leo Szilard, who served as chairmen of the various sessions. The meetings this year were held from the 4th through the 12th of June, and were attended by approximately 200 participants, including 25 from abroad. In addition to the support of the Long Island Biological Association, I am pleased to acknowledge the support of this program by The National Institutes of Health, U.S. Public Health Service, National Science Foundation, Rockefeller Foundation, United States Atomic Energy Commission, and The United States Air Force under Grant AF-AFOSR-61-73; monitored by The Air Force Office of Scientific Research of the Air Research and Development Command. This year our editor was assisted in the preparation of the volume by Ruth Schalet, Eleanor Chovnick and Hildegarde Mukai. We are grateful to them and to the staff members of the Biological Laboratory who assisted in the difficult task of indexing the volume. Arthur Chovnick, Laboratory Director Editor: Leonora Friseh LIST OF PREVIOUS VOLUMES

Volume I (1933) Surface Phenomena, 239 pp. Volume II (19341 Aspects of Growth, 284 pp. Volume III (1935) Photochemical Reactions, 359 pp. Volume IV (1936) Excitation Phenomena, 376 pp. Volume V (1937) Internal Secretions, 433 pp. Volume VI (1938) Protein Chemistry, 395 pp. Volume VII (1939) Biological Oxidations, 463 pp. Volume VIII (1940) Permeability and the Nature of Cell Membranes, 285 pp. Volume IX (1941) Genes and Chromosomes: Structure and Organization, 315 pp. Volume X (1942) The Relation of Hormones to Development, 167 pp. Volume XI (1946) Heredity and Variation in Microorganisms, 314 pp. Volume XII (1947) Nucleic Acids and Nucleoproteins, 279 pp. Volume XIII (1948) Biological Applications of Tracer Elements, 222 pp. Volume XIV (1949) Amino Acids and Proteins, 217 pp. Volume XV (1950) Origin and Evolution of Man, 425 pp. Volume XVI (1951) Genes and Mutations, 521 pp. Volume XVII (1952) The Neuron, 323 pp. Volume XVIII (1953) Viruses, 301 pp. Volume XIX (1954) The Mammalian Fetus: Physiological Aspects of Development, 225 pp. Volume XX (1955) Population Genetics: The Nature and Causes of Genetic Varia- bility in Populations, 346 pp. Volume XXI (1956) Genetic Mechanisms: Structure and Function, 392 pp. Volume XXII (1957) Population Studies: Animal Ecology and Demography, 437 pp. Volume XXIII (1958) Exchange of Genetic Material: Mechanisms and Consequences, 450 pp. Volume XXIV (1959) Genetics and Twentieth Century Darwinism, 321 pp. Volume XXV (1960) Biological Clocks, 524 pp. SOME SYMPOSIUM PARTICIPANTS

Top row: R. Quayle, H. Holzer, H. Kornberg, H. E. Umbarger; M. Schaechter, F. Neidhardt; T. F. Anderson, S. Brenner, J. Watson, A. D. Hershey, F. Jacob, F. Stahl. Second row: A. Koch, V. Potter; H. Kalckar, 0. MaalCe, Miss Maal~e, F. Lipmann; B. Nisman, S. Spiegelman. Third row: G. Streisinger, S. Benzer; F. Jacob, L. Szilard; D. Perrin, J. Changeux, F. Jacob. Bottom row: A. Novick, P. Margolin; C. Yanofsky, N. Franklin, J. D. Watson, N. H. Horowitz, F. J. de Serres; T. F. Anderson, J. Monod, A. Garen. SOME SYMPOSIUM PARTICIPANTS

Top row: H. Halvorson, B. D. Davis, J. Hurwitz, S. Luria; E. Englesberg, B. P. Kaufmann; M. Yarmolinsky, G. Buttin. Second row: A. Chovnick, E. Glassman; H. Vogel, R. Vogel, L. Gorini; J. D. Watson, E. Lennox, L. Szilard, H. Eagle. Third row: D. Shemin, J. Waller, G. Cohen; M. Meselson, S. Benzer; E. Freese, B. Strauss, M. Demeree. Bottom row: B. Magasanik, W. Maas, M. Umbarger, A. Magasanik; I. Zabin, G. Tomkins; E. Racker, B. Chance. (Photographs by Robert P. Beaumont and Ilse Schwinck) List of Those Attending the Symposium

ADLER, J., Department of Biochemistry, University of CHAMPE, SEWELL, Department of Biological Sciences, Wisconsin, Madison, Wisconsin Purdue University, W. Lafayette, Indiana AKEY,ALICE, Adelphi College, Garden City, New York CHANCE, BRITTON, Johnson Foundation, University of ANDERSON, RICHMOND I~., Rockefeller Foundation, Pennsylvania, Philadelphia, Pennsylvania New York City CtL4NGEUX, JEAN-PIERRE, Service de Bioehimie Cellu- ANDERSON,T. F., Institute for Cancer Research, Phila- laire, Institut Pasteur, Paris, France delphia, Pennsylvania CHARGAFF, ERWIN, Columbia University, New York BAKEMEIER,RICHARD, Dept of Medicine, University of City Rochester, Rochester, N. Y. CHARGAFF, ERWIN, MRS., c/o Dr. Erwin Chargaff BENZER, SEYMOUR,Department of Biological Sciences, CHOVNICK, ARTHUR, Long Island Biological Associa- Purdue University, Lafayette, Indiana tion, Cold Spring Harbor, New York BERNHEIMER, HARRIET, State University of New COHEN, GEORGES, Centre National de la Recherche York, Downstate Medical Center, Brooklyn, New Scientifique, Gif-sur-Yvette, France York COHEN, GEORGES,MRS., C/O Dr. Georges Cohen BLUME, DORIS, Long Island Biological Association, COLEMAN, DOUGLAS L., R. B. Jackson Laboratories, Cold Spring Harbor, New York Bar Harbor, Maine BOYER, SAMUEL H., Department of Medicine, Johns COLLAZO,ANA M. DIAL, Department of Biology, Uni- Hopkins Hospital, Baltimore, Maryland versity of Puerto Rico, Rio Piedras, Puerto Rico BRENNER, SYDNEY,M. R. C. Unit for Molecular Biol- COWIE, DEAN B., Department of Terrestrial Magnet- ogy, Cavendish Laboratory, Cambridge, England ism, Carnegie Institution of Washington, Wash- BRESCH, CARSTEN,Abt. fiir Mikrobiologie, Botanisehes ington, D. C. Institut, Universitat KSln, KSln-Lindenthal, DAs, C. C., Department of Genetics, Carnegie Institu- Germany tion of Washington, Cold Spring Harbor, New BRESCH, CARSTEN,MRS., e/o Dr. Carsten Breseh York BRITTEN, ROY J., Department of Terrestrial Magnet- DAVIS, BERNARD D., Department of Bacteriology & ism, Carnegie Institution of Washington, Wash- Immunology, Harvard Medical School, Boston, ington, D. C. Massachusetts BROWN, DONALDD., Department of Embryology, Car- DEMEREC, M., Brookhaven National Laboratory, Up- negie Institution of Washington, Baltimore, Mary- ton, New York land DINTZIS, HOWARD M., Biology Department, Massa- BURGI, ELIZARETtt,Department of Genetics, Carnegie chusetts Institute of Technology, Cambridge, Institution of Washington, Cold Spring Harbor, Massachusetts New York DOI, RoY HIROSHI, Department of Microbiology, Uni- BURR, W. W., JR., Biology Branch, Division of Biology versity of Illinois, Urbana, Illinois & Medicine, U. S. Atomic Energy Commission, DREYER, WILLIAM J., National Heart Institute, Be- Washington, D. C. thesda, Maryland BUTTIN, GERARD, Service de Biochimie Cellulaire, In- EAGLE, HARRY, National Institutes of Health, Be- stitut Pasteur, Paris, France thesda, Maryland CAMPBELL, A., Department of Biology, University of EAGLE, HARRY,MRS., C/O Dr. Harry Eagle Rochester, Rochester, New York ECHOES, HARRISON H., Department of Biochemistry, CAMPBELL,A., MRS., C/O Dr. A. Campbell University of Wisconsin, Madison, Wisconsin CANFIELD, ROBERT E., National Heart Institute, Na- tional Institutes of Health, Bethesda, Maryland ECKER, RICHARD E., Department of Microbiology, CAR~ART, ANNE, Department of Genetics, Carnegie College of Medicine, University of Florida, Gaines- Institution of Washington, Cold Spring Harbor, ville, Florida New York EHRENSTEIN, GUNTHER VON, Rockefeller Institute, CARLSON, ELOF A., Department of Zoology, University New York City of California, Los Angeles, California ENGLESBERG, ELLIS, Department of Biological Sci- CASPARI, ERNST, Department of Biology, University of ences, University of Pittsburgh, Pittsburgh, Penn- Rochester, Rochester, New York sylvania CATLIN, B. W., Marquette Medical School, Milwaukee, FEIGELSON, PHILIP, Department of Biochemistry, Co- Wisconsin lumbia University, New York City ix X LIST OF THOSE ATTENDING THE SYMPOSIUM

FINCHAM, JOHN R. S., Department of Biology, Massa- HALL, BENJAMIND., Department of Chemistry, Noyes chusetts Institute of Technology, Cambridge, Laboratory, University of Illinois, Urbana, Illi- Massachusetts nois FUSCALDO, KATHERINE,St. Johns University, Jamaica, HALVORSON, H. O.,University of Wisconsin, Madison, New York Wisconsin FRANKEL,FRED, Department of Genetics, Carnegie In- HAMERS,R., University Libre de Bruxelles, Belgium stitution of Washington, Cold Spring Harbor, HAMILTON,L. D., Sloan-Kettering Institute, New York New York City FRANKLIN,RICHARD, Rockefeller Institute of Medical HANLY,WILLIAM, University of Texas, Austin, Texas Research, New York City HARTMAN, PHILIP E., Department of Biology, Johns FREESE, ERNST, Department of Genetics, University Hopkins University, Baltimore, Maryland of Wisconsin, Madison, Wisconsin HARTMAN,ZLATA, C/O Dr. Philip E. Hartman FRISCH, LEONORA, Long Island Biological Association, HATTMAN, STANLEY,Massachusetts Institute of Tech- Cold Spring Harbor, New York nology, Cambridge, Massachusetts FURTH, JOHN J., Department of Microbiology, New HAUOE, JENS G., Department of Bacteriology, Uni- York University School of Medicine, New York versity of Wisconsin, Madison, Wisconsin GAREN, A., University of Pennsylvania, Philadelphia, HERSHEY, A. D., Department of Genetics, Carnegie Pennsylvania Institution of Washington, Cold Spring Harbor, GAY, HELEN, Department of Genetics, Carnegie In- New York stitution of Washington, Cold Spring Harbor, HIATT, H., Department of Medicine, Harvard Medical New York School and Beth Israel Hospital, Boston, Massa- GERSH~'~',DAVID, Department of Plant Breeding, Cor- chusetts nell University, Ithaca, New York HIRSCH, MARIE-LouiSE, Department of Microbiology, GILBERT, WALTER, Biological Laboratories, Harvard University of Illinois, Urbana, Illinois University, Cambridge, Massachusetts HOAGLAND, MAHLON B., Department of Bacteriology GILVARC, CHARLES, Department of Biochemistry, & Immunology, Harvard Medical School, Boston, New York University School of Medicine, New Massachusetts York City HOAGLAND, MAHLON B., MRS., e/o Dr. Mahlon B. GINSB~RG, HAROLD S., Department of Microbiology, Hoagland School of Medicine, University of Pennsylvania, HOFFEE, PATRICIA, University of Pittsburgh, Pitts- Philadelphia, Pennsylvania burgh, Pennsylvania GLASSMAN, EDWARD, University of North Carolina, HOLZER, HELMUT, Physiologisch-Chemisches Institut Chapel Hill, North Carolina der Universit~t im Breisgau, Freiburg, Germany GOLDSTEIN,IRWIN, Department of Microbiology, New HOLZER, HELMUT,MRS., C/O Dr. Helmut Holzer York University School of Medicine, New York HOPKINS, J. W., Biological Laboratories, Harvard City University, Cambridge, Massachusetts GOODGAL, SOL H., Department of Biochemistry, Johns HORIUCHI, TADAO, Institute of Molecular Biology, Hopkins University School of Hygiene & Public University of Oregon, Eugene, Oregon Health, Baltimore, Maryland GORINI, LUmI, Department of Bacteriology & Im- HOROWITZ, NORMAN H., Division of Biology, Cali- munology, Harvard Medical School, Boston, Mas- fornia Institute of Technology, Pasadena, Cali- sachusetts fornia GORINI, ANNAMARIATORRIANI, Department of Biol- HOTCHKISS, ROLLIN D., Rockefeller Institute, New ogy, Massachusetts Institute of Technology, Cam- York City bridge, Massachusetts HURWITZ, JERARD, Department of Microbiology, New GOTS, JOSEPH S., School of Medicine, University of York University School of Medicine, New York Pennsylvania, Philadelphia, Pennsylvania City GROS, FRANCOIS,Institut Pasteur, Paris, France INGRAHAM, LAURA, Department of Genetics, Carnegie GRoss, SAMSON R., Department of Microbiology, Institution of Washington, Cold Spring Harbor, Duke University Medical Center, Durham, North New York Carolina ITANO, H. A., National Institutes of Health, Bethesda, GUTTMAN, BURTON, Institute of Molecular Biology, Maryland University of Oregon, Eugene, Oregon JACOB, FRANCOIS, Services de Genetique Microbienne HAQERMAN, DWAIN D., Harvard Medical School, Bos- et de Biochimie Cellulaire, Institut Pasteur, Paris, ton, Massachusetts France HAHN, HOLGER P. YON, Institute of Cellular Biology, JUNGWIRTH, C., Long Island Biological Association, University of Connecticut, Storrs, Connecticut Cold Spring Harbor, New York LIST OF THOSE ATTENDING THE SYMPOSIUM xi

KALCKAR,HERMAN, McCollum Pratt Institute, Johns MAAS, WERNER K., Department of Microbiology, New Hopkins University, Baltimore, Maryland York University School of Medicine, New York KATO, YOSHIHIRO,Department of Embryology, Car- City negie Institution of Washington, Baltimore, Mary- MAAS, WERNER K., MRS., C/O Dr. Werner K. MaRs land MAGASANIK,BORIS, Massachusetts Institute of Tech- KAUFMANN, BERWIND N., Moore Clinic, Johns Hop- nology, Cambridge, Massachusetts kins Hospital, Baltimore, Maryland MAGASANIK,ADELE, C/O Dr. Boris Magasanik KAUFMANN, BERWIND P., Department of Genetics, MARGOLIN, PAUL, Long Island Biological Association, Carnegie Institution of Washington, Cold Spring Cold Spring Harbor, New York Harbor, New York MARKS, PAUL, College of Physicians & Surgeons, Co- KERNAGHAN, R. PETER, Long Island Biological As- lumbia University, New York City sociation, Cold Spring Harbor, New York MARUYAMA,KEIZO, Department of Genetics, Carnegie KNOX, EUGENEW., New England Deaconess Hospital Institution of Washington, Cold Spring Harbor, and Harvard Medical School, Boston, Massa- New York chusetts MAXWELL, ELIZABETH,National Institutes of Health, KOCH, ARTHURL., Department of Biochemistry, Uni- Bethesda, Maryland versity of Florida, Gainesville, Florida MENNINGER, Jo~--'~ R., Department of Biology, Har- KORNBERG,H. L., Dept. of Biochemistry, University of vard University, Cambridge, Massachusetts Leicester, Leicester, England MESELSON, M., Biological Laboratories, Harvard Uni- KOSTELLOW,ADELE, Department of Physiology, Albert versity, Cambridge, Massachusetts Einstein College of Medicine, New York City MESELSON,M., MRS., e/o Dr. Mathew Meselson KRAUSS, MARION, Long Island Biological Association, MILLER, BEA, Long Island Biological Association, Cold Cold Spring Harbor, New York Spring Harbor, New York LAHR, ERNEST L., Department of Genetics, Carnegie MODERSOHN, HELLA,Laboratory of Microbiology, In- Institution of Washington, Cold Spring Harbor, stitute of Botany, University of Cologne, Cologne, New York Germany LANDMAN, OTTO E., Microbial Genetics Branch, Fort MOLOMUT, NORMAN, Waldemar Medical Research Detrick, Frederick, Maryland Foundation, Inc., Port Washington, New York LARSEN, VICTORR., Department of Genetics, Carnegie MONOD, JACQUES, Services de Genetique Microbienne Institution of Washington, Cold Spring Harbor, et de Biochimie Cellulaire, Institut Pasteur, Paris, New York France LEAVITT,RICHARD, Long Island Biological Association, MONRO, ROBIN, Rockefeller Institute, New York City Cold Spring Harbor, New York MORRILL, DR., C/O Dr. Adele Kostellow, Department LEDERMANN, MURIEL, 419 W. 119 Street, New York of Physiology, Albert Einstein College of Medi- 27, New York cine, New York City LEHRER, HARRIS I., Graduate Department of Bio- MOSlG, GISELA, Division of Molecular Biology, Van- chemistry, Brandeis University, Waltham, Massa- derbilt University, Nashville, Tennessee chusetts LENNOX,EDWIN S., Department of Microbiology, New MOYED, HARRIS S., Harvard Medical School, Boston, York University School of Medicine, New York Massachusetts City MUKAI, FRANK, Long Island Biological Association, LESTER, GABRIEL, Worcester Foundation for Experi- Cold Spring Harbor, New York mental Biology, Shrewsbury, Massachusetts McCARTHY, BRIAN J., Department of Terrestrial LEWIS, HERMANW., Massachusetts Institute of Tech- Magnetism, Carnegie Institution of Washington, nology, Cambridge, Massachusetts Washington, D. C. LIN, EDMUNDC. C., Department of Biological Chem- McCLINTOeX, BARBARA,Department of Genetics, Car- istry, Harvard Medical School, Boston, Massa- negie Institution of Washington, Cold Spring Har- chusetts bor, New York LIPMANN, FRITZ, Rockefeller Institute, New York McDONALD, MARGARET,Department of Genetics, Car- City negie Institution of Washington, Cold Spring Har- LONDON, IRVING M., Department of Medicine, Albert bor, New York Einstein College of Medicine, New York City MOFALL, KENNETH, Long Island Biological Associa- LURIA S. E., Department of Biology, Massachusetts tion, Cold Spring Harbor, New York Institute of Technology, Cambridge, Massachu- NATHANS, DANIEL, Rockefeller Institute, New York setts City MAAL~E, OLE, University of Copenhagen, Copenhagen, NEIDHARDT, FREDERICKC., Department of Biological Denmark Sciences, Purdue University, Lafayette, Indiana xii LIST OF THOSE ATTENDING THE SYMPOSIUM

NEMER, MARTIN, Institute for Cancer Research, SARKAR, SIDDI-IARTI-IA,Department of Biology, Massa- Philadelphia, Pennsylvania chusetts Institute of Technology, Cambridge, NIERLICH, DONALD, Massachusetts Institute of Tech- Massachusetts nology, Cambridge, Massachusetts SAVELY, HARVEYE., Air Force Office of Scientific Re- NISlVI~N,BENTION, Laboratoire D'Enzymologie Micro- search, United States Air Force, Washington, bienne, Groupe de Laboratoires du CNRS, Gif- D.C. sur-Yvette (S & 0), France SCHAECHTER,MOSELIO, University of Florida, College Niu, MAN CHIANG, Rockefeller Institute for Medi- of Medicine, Gainesville, Florida cal Research, New York City SCHALET, ABRAHAM:,Long Island Biological Associa- NOMURA,MASAYASU, Osaka University, Osaka, Japan tion, Cold Spring Harbor, New York NOVELLI, G. DAVID,Biology Division, Oak Ridge Na- SCI-IALET, RUTH, Long Island Biological Association, tional Laboratory, Oak Ridge, Tennessee Cold Spring Harbor, New York NOVICK, AARON,Institute of Molecular Biology, Uni- SCHIM:I(E, ROBERT T., National Institutes of Health, versity of Oregon, Eugene, Oregon Bethesda, Maryland 0RTIZ, EDNA M., Department of Biology, University SC~VlNCK, ILSE, Abteilung fiir Entwicklungsphysiolo- of Puerto Rico, Rio Piedras, Puerto Rico gie, Max-Planck-Institut fiir Tierzucht, Mariensee, PERREAULT, WILLIAM,Department of Genetics, Car- Germany negie Institution of Washington, Cold Spring Har- SCOTT, JESSE F., Huntington Laboratories, Massachu- bor, New York setts General Hospital, Boston, Massachusetts PERRIN, D., Department of Biochemistry, Stanford SERRES, F. J. DE, Oak Ridge National Laboratory, Oak University Medical Center, Palo Alto, California Ridge, Tennessee PITOT, HENRY, MeArdle Memorial Laboratory, Medi- SHAPARD, PAULINE, National Science Foundation, cal School, University of Wisconsin, Madison, Wis- Washington, D. C. consin SHEMIN, DAVID,Columbia University, New York City PIZER, LEWIS, Department of Microbiology, Univer- SIDDIQI,OBAID, The University, Glasgow, Scotland sity of Pennsylvania, Philadelphia, Pennsylvania SIDDIQI,OBAID, MRS., e/o Dr. Obaid Siddiqi PLESNER, PAUL, Carlsberg Foundation Laboratories, SIEXOVlTC~, PmLIP, Rockefeller Institute, New York Copenhagen, Denmark City PLESNER,PAUL, MRS., C/O Dr. Paul Plesner SIMON, EDWARD,Department of Biology, Purdue Uni- PORTER, KEITH R., The Rockefeller Institute for versity, Lafayette, Indiana Medical Research, New York City SOKOLOFF, ALEXANDER, Long Island Biological As- POTTER, VAN R., McArdle Memorial Laboratory, sociation, Cold Spring Harbor, New York Medical School, University of Wisconsin, Madison, SPIEGELMAN, S., Department of Microbiology, Uni- Wisconsin versity of Illinois, Urbana, Illinois PROKOP, BARBARA,Long Island Biological Association, STADLER, DAVID R., Department of Genetics, Univer- Cold Spring Harbor, New York sity of Washington, Seattle, Washington QUAYLE, J. R., Dept. of Biochemistry, University of STA:ttL, FRANKI,INW., Institute of Molecular Biology, Leicester, Leicester, England University of Oregon, Eugene, Oregon RACKER, EFRAIM, Public Health Research Institute, STEVENS, A., Department of Pharmacology, St. Louis New York City University School of Medicine, St. Louis, Missouri RALL, T. W., Western Reserve University, Cleveland, ST. LAWRENCE, PATRICIA, Department of Genetics, Ohio University of California, Berkeley, California RICKENBERG, H. V., Department of Bacteriology, In- STRAUSS, BERNARD S., Department of Microbiology, diana University, Bloomington, Indiana University of Chicago, Chicago, Illinois ROBERTS, R. B., Department of Terrestrial Magnet- STREISINGER, GEORGE,Institute of Molecular Biology, ism, Carnegie Institution of Washington, Wash- University of Oregon, Eugene, Oregon ington, D. C. SUEOKA, NOBURO, Department of Microbiology, Uni- ROTH~AN, F., Biology Department, Massachusetts In- versity of Illinois, Urbana, Illinois stitute of Technology, Cambridge, Massachusetts SUEOKa, TAMIKO, Department of Microbiology, Uni- RUDKIN, GEORGE T., Institute for Cancer Research, versity of Illinois, Urbana, Illinois Philadelphia, Pennsylvania SUSKIND,S. R., McCollum Pratt Institute, Johns Hop- SAGER, RUTH, Department of Zoology, Columbia Uni- kins University, Baltimore, Maryland versity, New York City SUSSMAN, MAURICE,Department of Biology, Brandeis SAGIK, BERNARD P., Department of Microbiology, University, Waltham, Massachusetts University of Illinois, Urbana, Illinois SUSSMAN, MAURICE, MRS., e/o Dr. Maurice Sussman SANDERSON,KENNETH, Department of Plant Breeding, SUTHERLAND, EARL W., Western Reserve University, Cornell University, Ithaca, New York Cleveland, Ohio LIST OF THOSE ATTENDING THE SYMPOSIUM xiii

SZILARD, LEO, Enrico Fermi Institute for Nuclear WALKER, J. B., Department of Biochemistry, College Studies, The University of Chicago, Chicago, of Medicine, Texas Medical Center, Baylor Uni- Illinois versity, Houston, Texas SZILARD, LEO, MRS., C/O Dr. Leo Szilard WALLACE, BRUCE, Department of Plant Breeding, TALSMA, Jot, Long Island Biological Association, Cold Cornell University, Ithaca, New York Spring Harbor, New York WALLER, JEAN-PIERRE, Biological Laboratories, Har- TATUM, EDWARDL., Rockefeller Institute, New York vard University, Cambridge, Massachusetts City WARREN, KATHERINE BREHME, Division of Research TAUB, STEPHAN" R., Biological Laboratory, Harvard Grants, National Institutes of Health, Bethesda, University, Cambridge, Massachusetts Maryland TESSMAN, IRWIN, Department of Biological Sciences, WATSON, J. D., Biological Laboratories, Harvard Uni- Purdue University, Lafayette, Indiana versity, Cambridge, Massachusetts THOMAS, CHARLES A., JR., Biophysics Department, WEINGART, ANN, Department of Genetics, Carnegie Johns Hopkins University, Baltimore, Maryland Institution of Washington, Cold Spring Harbor, THOMAS, MYRNA, Department of Genetics, Carnegie New York Institution of Washington, Cold Spring Harbor, WEINSTEIN, I. BERNARD, Department of Biology, New York Massachusetts Institute of Technology, Cam- TISSII~RES, ALFRED, Biological Laboratories, Harvard bridge, Massachusetts University, Cambridge, Massachusetts WEISEROT, DAVID,Department of Zoology, Columbia TISSIERES, ALFRED, MRS., C/O Dr. Alfred Tissi~res University, New York City TOMKINS, GORDONM., National Institute of Arthritis WHITFELD, P. R., Virus Laboratory, University of and Metabolic Diseases, National Institutes of California, Berkeley, California Health, Bethesda, Maryland WILSON', KATHERINES., Division of Research Grants, TOOTLE, MARTHA, Institute of Cellular Biology, Uni- National Institutes of Health, Bethesda, Mary- versity of Connecticut, Storrs, Connecticut land TRAUTNER, THOMAS, Department of Biochemistry, WILT, FRED, Department of Biology, Purdue Uni- versity, Lafayette, Indiana Stanford Medical School, Palo Alto, California WINTERS, JOAN,Research Lab., Boston Lying-In Hos- UDAKA, SHIGEZO, Department of Biochemistry, Uni- pital, Boston, Massachusetts versity of Chicago, Chicago, Illinois WITKIN, EVELY~ M., State University of New York, UMBARGER, H. EDWIN, Long Island Biological As- Downstate Medical Center, Brooklyn, New York sociation, Cold Spring Harbor, New York WYNGAARDEN, JAMES B., School of Medicine, Duke UMBARGER, MERLE, Long Island Biological Associa- University, Durham, North Carolina tion, Cold Spring Harbor, New York YANOFSKY, CHARLES, Department of Biological Sci- VILLEE, CLAUDEA., Department of Biological Chem- ences, Stanford University, Stanford, California istry, Harvard Medical School, Boston, Massa- YARMOLINSKY, MICHAEL, McCollum Pratt Institute, chusetts Johns Hopkins University, Baltimore, Maryland VOGEL, HENRY J., Institute of Microbiology, Rutgers, YOUNG, WILLIAMJ., School of Medicine, Johns Hop- the State University, New Brunswick, New Jersey kins University, Baltimore, Maryland VOGEL, RUTH H., Institute of Microbiology, Rutgers, ZARIN, IRVING, Department of Physiological Chem- the State University, New Brunswick, New Jersey istry, School of Medicine, University of California, VOLKIN, ELLIOT, Oak Ridge National Laboratory, Oak Los Angeles, California Ridge, Tennessee ZINDER, NORTON, Rockefeller Institute for Medical WALEN, KRISTEN, Tudor Hotel, New York City Research, New York City Contents

Foreword ...... v List of Previous Volumes ...... vi Photographs of Some Participants ...... vii List of Those Attending the Symposium ...... ix

OPENING ADDRESS DAvis, B. D. The Teleonomic Significance of Biosynthetic Control Mecha- nisms ...... 1 THE ROLE OF DNA IN PROTEIN SYNTHESIS YANOFSKY, C., D. R. HELINSKI,AND B. D. MALING. The Effects of Mutation on the Composition and Properties of the A Protein of Escherichia coli Tryptophan Synthetase ...... 11 STREISINGER, G., F. MUKAI, W. J. DREYER, B. MILLER, AND S. HORIUCHI. Mutations Affecting the Lysozyme of Phage T4 ...... 25 SIGNER, E. R., A. TORRIANI, AND C. LEVINTHAL. Gene Expression in Inter- generic Merozygotes...... 31 SUEOXA, N. Compositional Correlation between Deoxyribonucleic Acid and Protein ...... 35 THE CONTROL OF NUCLEIC ACID SYNTHESIS MAAL~E, O. The Control of Normal DNA Replication in Bacteria ...... 45 SCHAECHTER,M. Patterns of Cellular Control during Unbalanced Growth .... 53 NEIDHARDT, F. C., AND D. G. FRAENKEL. Metabolic Regulation of RNA Syn- thesis in Bacteria ...... 63 THE ROLE OF DNA IN RNA SYNTHESIS SI'IEGEL~AN, S. The Relation of Informational RNA to DNA ...... 75 HURWlTZ, J., J. J. FURTH, M. ANDERS, P. J. ORTIZ, AND J. T. AUGUST. The Enzymatic Incorporation of Ribonucleotides into RNA and the Role of DNA ...... 91 THE ROLE OF RNA IN PROTEIN SYNTHESIS BRENNER, S. RNA, Ribosomes, and Protein Synthesis ...... 101 GROS, F., W. GILBERT, H. H. HIATT, G. ATTARDI, P. F. SPAHR, AND J. D. WATSON. Molecular and Biological Characterization of Messenger RNA... 111 NOVELLI, G. D., T. KAMEYAMA, AND J. M. EISENSTADT. The Nature of the System Catalyzing the Synthesis of Induced /~-Galactosidase ...... 133 NISMAN, B., R. COHEN, A. KAYSER, H. FUKUHARA, J. DEMAILLY, C. GENIN, AND D. GIRON. Specific Protein Synthesis in Subcellular Systems of Esch- erichia coli ...... 145 HOAGLAND, M. Some Factors Influencing Protein Synthetic Activity in a Cell- Free Mammalian System ...... 153 PLESNER, P. Changes in Ribosome Structure and Function during Synchron- ized Cell Division ...... 159 REGULATION OF ENZYME SYNTHESIS VOGEL, I-I. J. Aspects of Repression in the Regulation of Enzyme Synthesis: Pathway-wide Control and Enzyme-specific Response ...... 163 GORINI, L., W. GUNDERSEN, AND M. BURGER. Genetics of Regulation of En- zyme Synthesis in the Arginine Biosynthetic Pathway of Escherichia coli... 173 xiv T

MAAS, W. K. Studies on Repression of Arginine Biosynthesis in Escherichia coli. 183 JACOB, F. AND J. MONOD. On the Regulation of Gene Activity...... 193 BVTTIN, G. Some Aspects of Regulation in the Synthesis of the Enzymes Gov- erning Galactose Metabolism ...... 213 YARMOLINSKY, M. B., E. JORDAN, AND H. WIESMEYER. Regulatory Mech- anisms in the Synthesis of Enzymes of Galactose Metabolism. I. Coordi- nate Repression and De-Repression of the "Galactose Sequence." ...... 217 KALCKAR, H. AND T. A. SUNDARARAffAN. Regulatory Mechanisms in the Syn- thesis of Enzymes of Galactose Metabolism. II. Genetic Defects in Ga- lactokinase Activity and Their Relations to its Functions ...... 227 HOROWITZ, 1~. H., M. FLING, H. MACLEOD, AND Y. WATANABE. Structural and Regulative Genes Controlling Tyrosinase Synthesis in Neurospora .... 233 I~OVICK, A. AND T. HORIUCHI. Hyper-Production of/~-Galactosidase by Esch- erichia coli Bacteria ...... 239 HORIUCHI, T. AND A. NOVICK. A Thermolabile Repression System ...... 247 MAGASANIK, B. Catabolite Repression ...... 249 KORNBERG, H. L. Selective Utilization of Metabolic Routes by Escher- ichia coli ...... 257 ENGLESBERG, E., J. A. WATSON, AND P. A. HOFFEE. The Glucose Effect and the Relationship between Glucose Permease, Acid Phosphatase, and Glucose Resistance ...... 261 CONTROL OF ENZYME ACTIVITY: COMPETITION BETWEEN ENZYMES HOLZER, H. Regulation of Carbohydrate Metabolism by Enzyme Com- petition ...... 277 CHANCE, B. Control Characteristics of Enzyme Systems ...... 289 CONTROL OF ENZYME ACTIVITY: FEEDBACK CONTROL UMBARGER, H. E. Feedback Control by Endproduct Inhibition ...... 301 CHANGEUX, J. The Feedback Control Mechanism of Biosynthetic L-Threonine Deaminase by L-Isoleucine ...... 313 STADTMAN, E. R., G. N. COHEN, G. LE BRAS, AND H. DE ROBICHON-SZUL- MAJSTER. Selective Feedback Inhibition and Repression of Two Aspar- tokinases in the Metabolism of Escherichia coli ...... 319 MOYED, H. S. Interference with Feedback Control of Enzyme Activity ...... 323 CONTROL OF ENZYME FORMATION AND ACTIVITY IN ANIMAL SYSTEMS TOMKINS, G. M. AND K. L. YIELDING. Regulation of the Enzymic Activity of Glutamic Dehydrogenase Mediated by Changes in its Structure ...... 331 MARKS, P. A. Glucose-6P Dehydrogenase Stability, Activation, and Inactiva- tion ...... 343 RALL, T. W. AND E. W. SUTHERLAND. The Regulatory Role of Adenosine-3', 5'-phosphate ...... 347 POTTER, V. R. AND T. ONo. Enzyme Patterns in Rat Liver and Morris Hepa- toma 5123 During Metabolic Transitions ...... 355 SCHIMKE, R. W. Studies on Adaptation of Urea Cycle Enzymes in the Rat .... 363 HIATT, H. H. AND T. B. BOffARSKI. The Effects of Thymidine Administration on Thymidylate Kinase Activity and on DNA Synthesis in Mammalian Tissues ...... 367 PITOT, H. C. AND Y. S. CHO. Studies on the Mechanism of Enzyme Induction in Rat Liver ...... 371 BAKEMEIER, R. A Possible Cellular Explanation of the Multiplicity of Steroid Reductases ...... 379 GENERAL CONCLUSIONS MONOD, J. AND JACOB, F. Teleonomic Mechanism in Cellular Metabolism, Growth, and Differentiation ...... 389