COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY

VOLUME XXVIII

COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOG Y

Founded in 1933

by REGINALD G. HARRIS

Director of the Biological Laboratory

1924 to 1936

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

The Symposium Volumes are published by the Cold Spring Harbor

Laboratory of Quantitative Biology Cold Spring Harbor, L.I., New York

COLD

ON

SPRING HARBOR SYMPOSIA

QUANTITATIVE BIOLOGY

VOLUME XXVIII

Synthesis and Structure of Macromolecules

Upsala College Library

East Orange, N. J.

COLD SPRING HARBOR LABORATORY OF QUANTITATIVE BIOLOGY COLD SPRING HARBOR, L.I., NEW YORK

1963

COPYRIGHT �9 1964 BY

THE COLD SPRING HARBOR

LABORATORY OF QUANTITATIVE BIOLOGY

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 in the U.S .A .

8 1 4 8 1

The Symposium Volumes are published by the Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York, and may be purchased directly or through booksellers.

Price of Volume 28 $15.00; (inc. postage) price subject to change without notice.

FOREWORD

The 28th Cold Spring Harbor Symposium on Quantitative Biology "Syn- thesis and Structure of Macromolecules" was held from June 7 to 13, 1963. Although the topic was chosen from a field which has provided the subject for so many symposia in this country and abroad, two factors led to the further exploration of this area at this time. One was that developments in this field are occurring extremely rapidly. Secondly, since this is an area of molecular biology that the laboratories at Cold Spring Harbor have played a key role in developing, this institution was able to draw upon a large number of active workers in the field for a coverage never before achieved. This was undoubtedly the largest symposium yet held at Cold Spring Harbor, being at tended by 65 scientists from overseas and about 250 scientists from within the United States.

That the meeting was a successful one can be attested to by the enthusiasm of those who were able to a t tend and by reading the papers that follow. I t is unfortunate, perhaps, that the published volume does not record completely the extensive discussions that arose during and after the formal sessions. The benefits derived from these were necessarily reserved for those in attendance.

Although some areas covered by this symposium were similar to those discussed/~t the 1961 symposium (Cellular Regulatory Mechanisms), signifi- cant advances were reported in every session. A far greater amount of cellular activity was interpretable in terms of enzymic action. Nevertheless, it was clear tha t there are some very obvious gaps in the picture which the biochemist has yet to fill.

The broad coverage of the field and the greater participation by our colleagues from overseas were made possible by the fact that the Symposium was jointly sponsored by the Long Island Biological Association and the Commission on Molecular Biophysics of the International Organization for Pure and Applied Biophysics. This organization had been invited to hold its first international meeting in the United States. Because of the similarity in selected topics, union of the two meetings seemed desirable. The invitation extended by the Commission to some of the younger investigators from overseas was most valuable in making the meeting an exciting one.

As with Cold Spring Harbor Symposia in the past, the meeting owes its success to many individuals and groups. In the early planning, the wise counsel of Drs. C. B. Anfinsen, R. D. Hotchkiss, S. Ochoa, and W. Szybalski was particularly valuable. Special thanks are due to Dr. Aaron. Novick, whose suggestions for the session on the Regulation of Synthesis of Macromolecules and on Allosteric Interactions were adopted with only minor modifications. The one person on whose advice the Laboratory relied most heavily for formulating the program was Dr. Charles Gilvarg. The value of the meeting, therefore, to those who at tended and to those who will read the proceedings,

vi FOREWORD

is due in no small part to Dr. Gilvarg's judgment. For the implementation of the program, the Biological Laboratory is indebted to Dr. A. K. Solomon, Secretary General of IOPAB, and to Dr. R. C. Williams, Convenor for the Commission on Molecular Biophysics of IOPAB; to Miss Inger Hermann of the National Academy of Sciences; and to the administrative staff of the Biological Laboratory. Special thanks are also due to the following partici- pants who served as chairmen of the various sessions: Drs. R. D. Hotchkiss, P. Berg, M. B. Hoagland, A. D. Hershey, H. Borsook, P. Zamecnik, O. Maaloe, A. B. Pardee, B. Magasanik, N. Giles, H. Dintzis, and G. Gamow. Our editor was assisted in the production of this volume by Harriet D. Hershey and Janet Wimbert.

Support for this year's Symposium was obtained by the Long Island Biological Association and by the National Academy of Sciences on behalf of the Commission on Molecular Biophysics from the following agencies: National Institutes of Health, National Science Foundation, National Air and Space Administration, Office of Naval Research, United States Atomic Energy Commission, and through a contract (AF-AFOSR-426-63) monitored by the Air Force Office of Scientific Research of the Air Research and Development Command, the United States Air Force.

H. Edwin Umbarger Editor: Leonora Frisch

LIST OF PREVIOUS VOLUMES

Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume

Volume

Volume Volume

Volume

Volume Volume Volume Volume

I (1933) Surface Phenomena, 239 pp. I I (1934) Aspects of Growth, 284 pp. I I I (1935) Photochemical Reactions, 359 pp. IV (1936) Excitation Phenomena, 376 pp. V (1937) Internal Secretions, 433 pp. VI (1938) Protein Chemistry, 395 pp. VII (1939) Biological Oxidations, 463 pp. VIII (1940) Permeability and the Nature of Cell Membranes, 285 pp. IX ( 1941) Genes and Chromosomes: Structure and Organization, 315 pp. X (1942) The Relation of Hormones to Development, 167 pp. XI (1946) Heredity and Variation in Microorganisms, 314 pp. XI I (1947) Nucleic Acids and Nueleoproteins, 279 pp. XI I I (1948) Biological Applications of Tracer Elements, 222 pp. XIV (1949) Amino Acids and Proteins, 217 pp. XV (1950) Origin and Evolution of Man, 425 pp. XVI (1951) Genes and Mutations, 521 pp. XVII (1952) The Neuron, 323 pp. XVII I (1953) Viruses, 301 pp. XIX (1954) The Mammalian Fetus: Physiological Aspects of Develop-

ment, 225 pp. XX (1955) Population Genetics: The Nature and Causes of Genetic

Variability in Populations, 346 pp. XXI (1956) Genetic Mechanisms: Structure and Function, 392 pp. XXII (1957) Population Studies: Animal Ecology and Demography,

437 pp. XXII I (1958) Exchange of Genetic Material Mechanisms and Conse-

quences, 450 pp. XXIV (1959) Genetics and Twentieth Century Darwinism, 321 pp. XXV (1960) Biological Clocks, 524 pp. XXVI (1961) Cellular Regulatory Mechanisms, 408 pp. XXVII (1962) Basic Mechanisms in Animal Virus Biology, 535 pp.

T o p row: F. Ryan, J. Fincham - G. Cantoni, H. Eagle - J. Changeux, J. Patte.

Second row: W. Wood, C. Richardson, L. 0 k u n - H. Schachman, R. Haselkorn-V. Ingram, M. Nirenberg, M. Staehelin.

Th i rd row: F. C. Crick, A. Rich, G. Gamow, J. D. Watson, M. Calvin - R. Williams, A. Novick - G. Pontecorvo, C. Levinthal, J. Butler.

Fourth row: L. Gorini, 0. Maaloe, P. Hofschneider - P. Berg, B. Hall; V. Allfrey, J. Marmur.

(Photographs by Raymond Gesteland.)

T o p row: M. Spencer , J . t I u r w i t z - L. Szilard, D. P e r r i n - A. D. Hershey , F. J acob .

Second row: K. B u r t o n , E . Borek , L. Szi lard - F. Bol lum, C. T h o m a s - J . Speyer , M. Ni renberg .

T h i r d row: N. Sueoka, C. T h o m a s - J . Darnel l , F. J acob , G. T o m k i n s - C. Yanofsky , R. Clowes, M. Demeree .

F o ~ r t h row: N. Andreeva , A. S. Spir in, M. N i r enbe rg - M. Calvin, J . Fresco - P. Margolin, B. Magasan ik , J . Ge rha r t ,

M. U m b a r g e r , E . U m b a r g e r .

List of Those Attending the Symposium ADLER, JULIUS, Department of Biochemistry,

University of Wisconsin, Madison 6, Wisconsin ALLFREY, VINCENT G., The Rockefeller Institute,

New York 21, N.Y. AMATI, PAOLO, Harvard University, Cambridge,

Massachusetts AMES, BRUCE, National Institute of Arthritis and

Metabolic Diseases, National Institutes of Health, Bethesda 14, Maryland

ANDREEVA, N. S., Laboratory of Physics of Bio- logical Polymers, Institute of Biophysics, Academy of Science, Moscow, U.S.S.R.

APOS~IAN, H. V., Tufts University School of Medicine, Department of Microbiology, Boston 11, Massachusetts

ATTARDI, GIUSEPPE, Division of Biology, California Institute of Technology, Pasadena, California

AUGUST, J. T., Department of Microbiology, New York University School of Medicine, New York 16, N.Y.

BACON, DONALD F., Institute of Microbiology, Rutgers University, New Brunswick, New Jersey

BALDWIN, ROBERT L., Department of Biochemistry Stanford University, Stanford, California

BALTIMORE, DAVID, The Rockefeller Institute, New York 21, N.Y.

BAUERLE, RONALD, Long Island Biological Associ- ation, Cold Spring Harbor, New York

BAUTZ, EKKEHARD, Department of Microbiology, Rutgers University, New Brunswick, New Jersey

BECKMANN, CHARLES O., Department of Chemistry, Columbia University, New York 27, N.Y.

ROGER-BECKMANN, MURIEL, The Rockefeller Insti- tute, New York 21, N.Y.

BENACERRAF, B., Department of Pathology, New York University School of Medicine, New York 16, N.Y.

BENNETT, PETER, The Rockefeller Institute, New York 21, N.Y.

BENZER, SEYMOUR, Department of Biological Sciences, Purdue University, Lafayette, Indiana

BERG, PAUL, Department of Biochemistry, Stan- ford University Medical Center, Palo Alto, California

BERGMAN, FRED, National Institutes of Health, Heart Institute, Bcthesda, Maryland

BLUME, DORIS, Long Island Biological Association, Cold Spring Harbor, New York

BOLLUM, F. J., Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee

BOLTOlV, ELLIS T., Department of Terrestrial Magnetism, Carnegie Institution of Washing- ton, Washington 15, D.C.

BOREK, ERNEST, Columbia University College of Physicians and Surgeons, Department of Biochemistry, New York 32, N.Y.

BORSOOK, HENRY, Department of Biochemistry, California Institute of Technology, Pasadena, California

BORSTEL, R. C., VON, Department of Biology, Oak Ridge National Laboratory, Oak Ridge, Tennessee

BOSCH, LEENDERT, Biochemistry Department, University of Leyden, Leyden, Holland

BUCHANAN, JENNY, Carnegie Institution of Wash- ington, Cold Spring Harbor, New York

BUCHANAN, JOHN M., Division of Biochemistry, Massachusetts Institute of Technology Cam- bridge 39, Massachusetts

BURGI, ELIZABETH, Carnegie Institution of Washington, Cold Spring Harbor, New York

BURNS, RICHARD, Long Island Biological Associ- ation, Cold Spring Harbor, New York

BURTON, KENNETH, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, England

BUTLER, J. A. V., Chseter Beatty Research Insti- tute, Institute of Cancer Research, London S.W.3, England

BYRNE, WILLIAM L., Duke University, Durham, North Carolina

CAIRNS, JOHN, The Biological Laboratory, Long Island Biological Association, Cold Spring Harbor, New York

CALVIN, MELVIN, Donner Laboratory, University of California, Berkeley 4, Calif.

CALVO, JOSEPH, Long Island Biological Association, Cold Spring Harbor, New York

CANTONI, G. L., Laboratory of Cellular Pharma- cology, National Institute of Mental Health, National Institutes of Health, Bethesda 14, Maryland

CARHART, ANNE K., Carnegie Institution of Wash- ington, Cold Spring Harbor, New York

CHAMBERLIN, M., Department of Biochemistry, Stanford University Medical Center, Palo Alto, California

CHAMPE, SEWELL P., Department of Biological Sciences, Purdue University, Lafayette, Indiana

CHANDLER, BARBARA, Zoology Department, Uni- versity of Wisconsin, Madison, Wis.

xi LIST OF THOSE ATTENDING THE SYMPOSIUM

CHANGEUX, JEAN-PIERRE, Service de Bioehimie Cellulaire, Institut Pasteur, Paris 15e, France

CHOVNICK, ARTHUR, Institute of Cellular Biology, The University of Connecticut, Storrs, Con- necticut

CLARK, ALVIN J., Department of Bacteriology, University of California, Berkeley 4, California

CLOWES, ROYSTON C., M. R. C., Microbial Genetics Research Unit, Hammersmith Hospital, Lon- don Wl2, England

COHEN, J. A., Medical Biological Laboratory RVO- TNO, Rijswijk (Z.H.), The Netherlands

COOPER, STEPHEN, The Rockefeller Institute, New York 21, N.Y.

CONWAu THOMAS, The Rockefeller Institute, New York 21, N.Y.

CRAVEN, GARY R., Department of Biological Chemistry, Harvard University Medical School, Boston 15, Massachusetts

CRICK, F. H. C., M. R. C. Laboratory of Molecular Biology, University Postgraduate Medical School, Cambridge, England

CUKIER, REGINE, National Institutes of Health, Bethesda, Maryland

DARNELL, JAMES E., Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

DAVIES, JULIAN, Department of Bacteriology & Immunology, Harvard Medical School, Boston 15, Massachusetts

DANEK, JOHN, New Hyde Park, New York DAvis, BERNARD D., Department of Bacteriology

& Immunology, Harvard Medical School, Bos- ton 15, Massachusetts

DAvis, BRIAN K., Department of Chemistry, Harvard University, Cambridge 38, Massa- chusetts

DAVISON, PETER F., Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

DEMEREC, MILISLAV, Department of Biology, Brook- haven National Laboratory, Upton, New York

DIGIROL~O, MARIO, Mrs. International Laboratory of Genetics and Biophysics, Naples, Italy

DIGIROLAMO, MARIO, Mrs. c/o Dr. M. DiGirolamo, International Laboratory of Genetics and Biophysics, Naples, Italy

DINTZIS, HOWARD, Department of Biology, John Hopkins University, Baltimore, Maryland

DIRKSEN, M. L., Massachusetts Institute of Tech- nology, Cambridge 39, Mass.

DUBERT, J. M., Institut Pasteur, Paris, France EAGLE, HARRr, Department of Cell Biology, Albert

Einstein College of Medicine, New York 61, N.Y.

EDELMAN, GERALD M., The Rockefeller Institute, New York 21, N.Y.

EDINGTON, C. W., Division of Biology and Medicine, U. S. Atomic Energy Commission, Washington 25, D.C.

EGAMI, FUJIO, Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Hongo, Tokyo, Japan

EHRENSTEIN, GUNTER VON., Department of Bio- physics, John Hopkins University School of Medicine, Baltimore 5, Maryland

EIGNER, JOSEPH, Department of Biological Chem- istry, University of Michigan Medical School, Ann Arbor, Michigan

EMMONS, SUSAN, Long Island Biological Associ- ation, Cold Spring Harbor, New York

ENGLESBERG, ELLIS, Department of Biological Sciences, University of Pittsburgh, Pittsburgh I3, Pennsylvania

ENGSTRSM, ARNE, Karolinska Institutet, Stock- holm 60, Sweden

EPSTEIN, C. J., National Institutes of Health, Laboratory of Biochemistry, Section on Cell- ular Physiology, Bethesda 14, Maryland

EPSTEIN, R. H., Laboratoire de Biophysique, Universit6 de Genbve, Gen~ve, Switzer- land

FIERS, WALTER, Laboratory of Physiological Chemistry, University of Ghent, Ghent, Belgium

FINCHAM, JOHN R. S., John Innes Institute, Bay- fordbury, Hertford, Herts., England

FISHER, K. W., Princeton University, Princeton, N.J.

FITZOERALD, P. J., Pathology Department, State University of New York College of Medicine, Albany, New York

FOSTER, M. A., Microbiology Unit, Department of Biochemistry, University of Oxford, Oxford, England

FR&NKEL, FRED, Carnegie Institution of Wash- ington, Cold Spring Harbor, N.Y.

FRANKLIN, NAOMI, Massachusetts Institute of Technology, Cambridge 39, Mass.

FREESE, ERNST, Laboratory of Molecular Biology, National Institutes of Health, Bethesda 14, Maryland

FREESE, ELIZABETH BAUTZ-Laboratory of Molec- ular Biology, National Institutes of Health, Bethesda 14, Maryland

FRESCO, JACQUES R., Department of Chemistry, Princeton University, Princeton, New Jersey

FREUNDLICH, M., Long Island Biological Associ- ation, Cold Spring Harbor, N.Y.

FRIEDEN, CARL, Dept. of Biological Chemistry, Washington University School of Medicine, St. Louis, Missouri

FlUSCH, LEONORA, Long Island Biological Associ- ation, Cold Spring Harbor, New York

LIST OF THOSE ATTENDING THE SYMPOSIUM xii

FROMAGEOT, PIERRE, Service de Biochimie, Dept. de Biologie, Commissariat a l'Energi Atomique, B.P. 2, Gif-sur-Yvette (S. et 0.) France

FRONTALI, LAURA, Istituto di Filiologia Generaie, Universita Roma, Roma, Italia

FUKASAWA, T., Institute for Protein Research, Osaka Univ., Osaka, Japan

GAMOW, GEORGE, Dept. of Physics and Astro- physics, University of Colorado, Boulder, Colorado

GARDNER, ROBERT S., Biochemistry Department, NYU School of Medicine, 550 First Avenue, New York, N.Y.

G~E~, ALA~, Division of Biology, University of Pennsylvania, Philadelphia 4, Pennsylvania

GAREN, SUE, Division of Biology, University of Pennsylvania, Philadelphia 4, Pennsylvania

GARSTENS, M. A., Physics Branch, Office of Naval Research, Department of the Navy, Washing- ton 25, D.C.

GERHART, JOHN C., Virus Laboratory, University of California, Berkeley 4, California

GEST, HOWARD, Henry Shaw School of Botany, Washington University, St. Louis, Missouri

GESTELAND, RAYMOND F., Biological Laboratories, Harvard University, Cambridge 38, Massa- chusetts

GILBERT, WALTER, Biological Laboratories, Har- vard University, Cambridge 38, Massa- chusetts

GILES, NORMAN H., Department of Biology, J. W. Gibbs Research Laboratory, Yale University, New Haven, Conn.

GILVARG, CHARLES, Department of Biochemistry, New York University School of Medicine, New York 16, New York

GODSON, G. N., Chester Beatty Research Institute, Pollards Woods Research Station, Chalfont, St. Giles, Buckinghamshire, England

GOLD, MARVIN, Department of Microbiology, New York University School of Medicine, New York 16, New York

GOLDBERG, EDWARD, Carnegie Institution of Washington, Cold Spring Harbor, New York

GOLDBEROER, ROBERT F., Cellular Physiology Section,National Heart Institute, Bethesda 14, Maryland

GONANO, FABIO, Johns Hopkins School of Medicine, Baltimore, Maryland

GOODGAL, SOL, Department of Microbiology, Uni- versity of Pennsylvania School of Medicine, Philadelphia 4, Pennsylvania

GORINI, LVIGI, Harvard Medical School, Boston 15, Massachusetts

GORINI, ANNAMARIA TORRIANI-, Department of Biology, Massachusetts Institute of Tech- nology, Cambridge 39, Massachusetts

GOTS, JOSEPH S., Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

GREENBERG, G. ROBERT, Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan

GRos, FR~COIS, Institut de Biologie Physico- Chimique, Paris 5e, France

GROSS, S~soN R., Dept. of Bacteriology, Duke University School of Medicine, Durham, North Carolina

GRUBER, MAX, The University, Biochemisch Labor- atorium, Groningen, Netherlands

GUNSALUS, I. C., Department of Chemistry & Chemical Engineering, Division of Biochem- istry, University of Illinois, Urbana, Illinois

GUTTMAN, BU~TON, University of Oregon, Eugene, Oregon

HABERMANN, VLASTIMIL, Institute for Medical Chemistry, Charles University, Plzen, Czecho- slovakia

HALL, BENJAMIN D., Department of Chemistry, University of Illinois, Urbana, Illinois

HARTMAN, PHILIP E., Department of Biology, Johns Hopkins University, Baltimore 18, Maryland

HASELKORN, ROBERT, Committee on Biophysics, The University of Chicago, Chicago 37, Illinois

HAYASttI, MASAKI, Department of Microbiology, University of Illinois, Urbana, Illinois

HEDEGAARD, JENS, College de France, Biochimie Generale et Comparee, Paris 17e, France

HERMXNN, INGER, National Academy of Science, Washington D.C.

HERSHEY, A. D., Carnegie Institution of Washing- ton, Cold Spring Harbor, N.Y.

HERSHEY, H. D., Long Island Biological Associa- tion, Cold Spring Harbor, New York

HIATT, HOWARD, Harvard Medical School and Beth Israel Hospital, Boston 15, Massachusetts

HINEGA~RDNER, RALPH, University of California, Berkeley, California. After July lst--Columbia University, New York, N.Y.

HOAGLAND, MAttLON B., Department of Bacteri- ology & Immunology, Harvard Medical School, Boston 15, Massachusetts

HOFSCHNEIDER, P. H., Max-Planck-Institute fiir Biochemie, Goethestr. 31, Munich, Germany

HOLLEY, ROBERT W., Plant, Soil & Nutrition Laboratory, U. S. Department of Agriculture, Cornell Univ., Ithaca, New York

HOLLOWAY, BRUCE, Department of Bacteriology, University of Melbourne, Melbourne, Australia

HOTCHKISS, ROLLIN D., Rockefeller Institute, New York 21, New York

HURWITZ, JERARD, Dept. of Microbiology, New Yorl~University School of Medicine, New York 16, New York

xiii LIST OF THOSE ATTENDING THE SYMPOSIUM

IHLER, GARRETT M., Biological Laboratories, Har- vard University, Cambridge 38, Massachusetts

IrCGRAHAM, LAURA, Carnegie Institution of Wash- ington, Cold Spring Harbor, N.Y.

INORAM, V. M., Division of Biochemistry, Massa- chusetts Institute of Technology, Cambridge 39, Massachusetts

JXCOB, FRANCOIS, Institut Pasteur, Paris 15e, France

JEHL~, HERBERT, George Washington University, Washington, D.C.

JO~NS, H. E., Department of Medical Biophysics, University of Toronto, Toronto 5, Canada

JUK~S, P. H., American Cyanamid Company, Princeton, New Jersey

KALCKAR, HERMANN, Mass. General Hospital & Harvard Medical School, Boston, Mass.

KAZIRO, YOSHITO, Department of Biochemistry, New York University School of Medicine, New York, N.Y.

KELLER, ELIZABETtf D., U.S. Nutrition Laboratory and Department of Biochemistry, Cornell University, Ithaca, New York

KEPES, ADA~I, Service de Biochimie Cellulaire, Institut Pasteur, Paris 15e, France

KHORANX, H. GOrIND, Institute for Enzyme Re- search, The University of Wisconsin, Madison 6, Wisconsin

KIT, SAUL, Division of Biochemical Virology, Baylor University College of Medicine, Texas Medical Center, Houston, Texas

KJELDGAARD, N. 0., University Institute of Micro- biology, Copenhagen K, Denmark

KL~NOW, HANS, Biokemisk Afdeling, Fibiger- Laboratoriet, Copenhagen, Denmark

KONINOSBEROER, V~CTOR V., State University of Utrecht, van't Hoff Laboratorium, Utrecht, The Netherlands

KOSHLAND, D. E. JR., Department of Biology, Brookhaven National Laboratory, Upton, New York

I~EAM, J., Department of Biochemistry, Hospital for Joint Diseases, New York 35, New York

KRUO, ROBERT, Rockefeller Institute for Medical Research, New York 21, New York

KUEHNERT, Dept. of Biology, University of Saskatchewan, Canada

LANGELAND, TOR, Dept. Biophysics, J. W. Gibbs Research Labs., Yale University, New Haven, Connecticut

LEDINKO, NADA, Carnegie Institution of Washing- ton, Cold Spring Harbor, N.Y.

LENGYEL, PETER, Department of Biochemistry, New York University School of Medicine, New York 16, New York

LEDERBERG, SEYMOUR, Brown University, Provi- dence 12, Rhode Island

LEVINTHAL, CYRUS, Department of Biology, Massa- chusetts Institute of Technology, Cambridge 39, Massachusetts

LEVrST~AL, FRANCOISE, Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

LEWIS, HERMAN W., Genetics Biology Program, National Science Foundation, Washington 25, D.C.

LIEB, M~_R~ARET, Department of Medical Micro- biology, University of Southern California, Los Angeles, California

LITTAUER, URIEL, C/O Biological Laboratories, Har- vard University, Cambridge 38, Massachusetts

LUBORSKY, SAM, National Institute Mental Health, National Institutes of Health, Bethesda 14, Maryland

LURIA, S. E., Department of Biology, Massachusetts Institute of Technology, Cambridge 39, Massachusetts

LYMAN, Dept. of Physics, University of Illinois, Urbana, Illinois

MAALOE, OLE, University Institute of Microbiology, Copenhagen, Denmark

MAC~, BERN,~RD, The Rockefeller Institute for Medical Research, New York 21, New York

MAOASASIK, BORIS, Department of Biology, Massa- chusetts Institute of Technology, Cambridge 39, Massachusetts

MXRGOLIN, PAUL, Long Island Biological Associ- ation, Cold Spring Harbor, N.Y.

MARKS, PAUL A., Department of Medicine, Colum- bia University College of Physicians & Sur- geons, New York 32, New York

MARMUR, JULIUS, Department of Biochemistry, Brandeis University, Waltham,, Massachusetts

MARTIN, ROBERT G., National Institute of Arthritis & Metabolic Diseases, National Institutes of Health, Bethesda 14, Maryland

McCLINTOCK, BARBARA, Carnegie Institution of Washington, Cold Spring Harbor, N.Y.

McDoNALD, MARGARET, Carnegie Institution of Washington, Cold Spring Harbor, N.Y.

MEISS, H., Department of Biology, Massachusetts Institute of Technology, Cambridge 39, Massachusetts

MENNINGER, JOHN, The Biological Laboratories, Harvard University, Cambridge 38, Massa- chusetts

MILLER, B., Long Island Biological Association, Cold Spring Harbor, New York

MIURX, KIrC-mHIRO, Institute of Molecular Biology, Faculty of Science, Nagoya University, Na- goya, Japan

MORA, P~TER T., National Cancer Institute, National Institutes of Health, Bethesda 14, Maryland

LIST OF THOSE ATTENDING THE SYMPOSIUM xiv

MOSiG, GISELA, Department of Genetics, Carnegie Institution of Washington, Cold Spring Harbor, New York

MUELLER-HiLL, Indiana University, Bloomington, Indiana

MUIRItEAD, HILARY, MRC Lab. of Molecular Biol- ogy, University Postgraduate Medical School, Hills Road, Cambridge, England

MUKAI, FRANK, Long Island Biological Association, Cold Spring Harbor, N.Y.

MUNDRY, K. W., Max-Planck-Institut fiir Biologic, 74 Tiibingen, Germany

NAGATA, T., Biological Laboratories, Harvard Uni- versity, Cambridge, Massachussetts

NAKAMOTO, TOKUMASA, The Rockefeller Institute for Medical Research, New York 21, New York

NATHANS, DANIEL, Johns Hopkins University School of Medicine, Baltimore 5, Mary- land

NAZARIO, MAttAFUD, Department of Biology, Facultad Ciencias, Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

NIRENBERG, MARSHALL W., National Institute of Arthritis, National Institutes of Health, Bethesda 14, Maryland

NOMURA, MASAYXSU, Institute for Protein Re- search, Osaka University, 36, Joancho Kita-ku, Osaka, Japan

NOTANI, N. K., Biology Division, Atomic Energy Est. Trombay, Byculla, Bombay 8, India

NOTANI, G. W., Genetics Department, Rockefeller Institute, New York 21, N.Y.

NOVOGRODSKY, ABRAHAM, Department of Bio- chemistry, Tufts University School of Medi- cine, Boston, Massachusetts

NOVICE, A-~RON, e/o Dr. F. Jacob, Institut Pasteur, Paris 15e, France (Permanent address: Univ. of Oregon, Eugene, Oregon)

NYGAtkRD, AGNAR P., c/o Department of Micro- biology, University of Illinois, Urbana, Illinois

OKUN, LARRY, Department of Genetics, Stanford University Medical Center, Palo Alto, Cali- fornia

OTSUJI, NozoMu, Biology Department, University of Pennsylvania, Philadelphia, Pennsylvania

PXmEN, KENNETH, Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York

PARDEE, ARTHUR B., Biology Department, Prince- ton University, Princeton, N.J.

PATTE, JEAN-CLAUDE, C.N.R.S. Laboratoire d'Enzymologie, Gif-sur-Yvette, (S. et O.) France

PENMAN, SHELDON, Biology Department, Massa- chusetts Institute of Technology, Cambridge 39, Massachusetts

PERKINS, Biology Department, Stanford Univer- sity, Stanford, California

PERRIN, DAVID R., Institut Pasteur, Paris 15e, France

PHILIPS, JOHN, Long Island Biological Association, Cold Spring Harbor, N.Y.

POLJAK, R. J., Johns Hopkins University School of Medicine, Baltimore, Md.

PONTECORVO, G., Department of Genetics, The University, Glasgow, Scotland

POUYET, JEAN, Service de Biologic, Centre de Recherches sur les Maeromolecule, Strasbourg (Bas Rhin) France

PRITCHARD, ROBERT, M.R.C. Unit-Microbial Gen- etics, London, England

PTASHNE, MARK, The Biological Laboratories, Harvard University, Cambridge 38, Massa- chusetts

REICHARD, PETER, Department of Medical Chem- istry, Uppsala University, Uppsala, Sweden

REISSIG, JOSE LUIS, Department of Biology, Facultad Ciencias Exactas y Naturales, University of Buenos Aires, Buenos Aires, Argentina

REVEL, HELEN, Massachusetts Institute of Tech- nology, Cambridge 39, Mass.

RICH, ALEXANDER, Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

RICHARDSON, CHARLES C., Department of Bio- chemistry, Stanford University, Palo Alto, California

RILEY, MONICA, Dept. of Bacteriology, University of California at Davis, Davis, Calif.

RIs, HANS, Department of Zoology, The University of Wisconsin, Madison 6, Wis.

ROIZMANN, BERNA~RD, Johns Hopkins Medical School, Baltimore, Maryland

ROSENBERG, M., Dept. of Biology, State University, Stony Brook, New York

ROTHMAN, FRANK, Biology Department, Brown University, Providence, R.I.

RUFFILLI, ANNA, The Biological Laboratories, Harvard University, Cambridge 38, Massa- chusetts

RYAN, FRANCIS J., Department of Zoology, Colum- bia University, New York, N.Y.

SAGER, RUTH, Department of Zoology, Columbia University, New York, N.Y.

SCARANO, EDUARDO, International Laboratory of Genetics and Biophysics, Department of Biochemistry, Naples, Italy

SCHACHMAN, HOWARD K., Virus Laboratory, University of California, Berkeley 4, California

SCHLESINGER, MILTON J., Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

xv LIST OF THOSE ATTENDING THE SYMPOSIU~I

SC~LESINGER, SON~)RA, Department of Biology, Massachusetts Institute of Technology, Cam- bridge 39, Massachusetts

SC~WEET, RICHARD S., Department of Biochem- istry, University of Kentucky College of Medicine, Lexington, Kentucky

SEKIGUCHI, MUTSUO, c/o Department of Bio- chemistry, University of Pennsylvania School of Medicine, Philadelphia 4, Pennsylvania

SHOOTER, K. V., Chester Beatty Research Institute, London, England

SIMINOVITCH, LOUIS, Division of Biological Re- search, Ontario Cancer Institute, Toronto 5, Canada

SIU, PATRICK, Long Island Biological Association, Cold Spring Harbor, N.Y.

SMELLIE, R. M. S., Department of Biochemistry, The University, Glasgow, Scotland

SMmNOFF, VICTOR, Botany Dept., Indiana Uni- versity, Bloomington, Indiana

SOLOMON, ARTHUR K., Department of Biophysics, Harvard Medical School, Boston 15, Massa- chusetts

SO~LES, JACK, Dept. of Physics, New Mexico State Univ., Alberquerque, N.M.

SPENCER, MICHAEL, MRC Biophysics Unit, Kings College, Strand, London WC2, England

SPEYER, JOSEPH S., Department of Biochemistry, New York University School of Medicine, New York 16, N.Y.

SPIECELMAN, S., Department of Microbiology, University of Illinois, Urbana, Illinois

SPrain, ALEXANDER S., A. N. Bakh Institute of Biochemistry, Academy of Sciences of U.S.S.R., Moscow, U.S.S.R.

SPYRIDES, GEORGE J., The Rockefeller Institute for Medical Research, New York 21, New York

STAE~ELIN, MATTHIAS, Department of Biochemistry & Ciba Research Laboratories, University of Basle, Basle, Switzerland

STARLINGER, PETER, Institut fiir Genetik, Uni- versitat zu KSln, KSln-Lindenthal, Germany

STElgT, GUNTI~ER S., Virus Laboratory, University of California, Berkeley 4, California

STOECKENIUS, WALTHER, Rockefeller Institute for Medical Research, New York 21, New York

ST5RMER, F., Long Island Biological Association, Cold Spring Harbor, N.Y.

STOLLAR, B. DAVID, Biological Sciences Division, Air Force Office of Scientific Research, Wash- ington 25, D.C.

STULBERG, MELVIN P., Division of Biology and Medicine, U.S. Atomic Energy Commission, Washington 25, D.C.

SU~OKA, NOBORV, Department of Biology, P.O. Box 704, Princeton University, Princeton, New Jersey

StrSSMAN, MAVRICE, Department of Biology, Bran- deis University, Waltham 54, Massachusetts

SUSSMAN, RACQUEL ROTMAN, Department of Biology, Brandeis University, Waltham 54, Massachusetts

SzILxRD, LEO, Hotel Dupont Plaza, Dupont Circle & New Hampshire Avenue, N.W. Washington 6, D.C.

SZILARD, Mrs. LEo, c/o Dr. Leo Szilard, Hotel Dupont Plaza, Dupont Circle & New Hamp- shire Avenue, N.W., Washington 6, D.C.

SZYBALSKI, WACLAW, McArdle Memorial Labora- tory, University of Wisconsin Medical School, Madison 6, Wisconsin

TAYLOR, AUSTIN L., Laboratory for Molecular Biology, National Institutes of Health, NINDB Auburn Building, Bethcsda 14, Maryland

TENER, GORDON M., Department of Biochemistry, University of British Columbia, Vancouver 8, B.C., Canada

THOMAS, CHARLES A., JR., Department of Bio- physics, Johns Hopkins University, Baltimore 18, Maryland

THOMAS, RENE, Laboratoire de Genetique, Uni- versite de Bruxelles, Bruxelles 16, Belgium

TlSSI~.R~S, ALFRED, MRC Laboratory of Molecular Biology, University Postgraduate Medical School, Cambridge, England

TOCCHINI-VALENTINI, GLAUCO, University of Chi- cago and International Laboratory of Genetics and Biophysics, Naples, Italy

TOMKINS, GORDON M., National Institute of Arth- ritis & Metabolic Diseases, National Institutes of Health, Bethesda 14, Maryland

UMBARQER, H. E., Long Island Biological Associ- ation, Cold Spring Harbor, N.Y.

UMBARGER, MERLE, Long Island Biological Asso- ciation, Cold Spring Harbor, N.Y.

VELICK, SIDNEY F., Washington University School of Medicine, St. Louis 10, Missouri

VOGEL, HENRY J., Institute of Microbiology, Rutgers State University, New Brunswick, New Jersey

WXHBA, A. J., Department of Biochemistry, New York University School of Medicine, New York 16, New York

WALKER, PETER M. B., Department of Zoology, University of Edinburgh, Edinburgh, Scotland

WARNER, JONATHAN, Dept. of Biology, Mass. Institute of Technology, Cambridge, Mass.

WATANABE, ITARU, Institute for Virus Research, Kyoto University, Kyoto, Japan

WATSON, JAMES D., Department of Biology, Har- vard University, Cambridge, Mass.

WEI~STEIN, I. B., Dept. of Medicine, Columbia Univ. College of Physicans & Surgeons, New York 32, N.Y.

LIST OF THOSE ATTENDING THE SYMPOSIUM xvi

WEISBLUM, BERNARD, Purdue University, Lafay- ette, Indiana

WEISSMAN, CHARLES, Department of Biochemistry, New York University School of Medicine, New York 16, New York

WILLIAMS, ROBLEY C., Virus Laboratory, Uni- versity of California, Berkeley 4, Cali- fornia

WIMBERT, JANET, Long Island Biological Associ- ation, Cold Spring Harbor, New York

WITKIN, EVELYN M., State University of New York, Downstate Medical Center, Brooklyn 3, New York

WlTTMANN, H. G., Max-Planck-Institut fiir Bio- logie, Tubingen, Germany

WOOD, WILLIAM B., Department of Biochemistry, Stanford University, Palo Alto, California

Wv, HENRY CHI-PI~O, Biochemical Research Lab. Massachusetts General Hospital, Boston 14, Massachusetts

WYMAN, JEFFRIES, Istituto Regina Elena, Div. Scientifico, Roma, Italia

YAMANE, T., Department of Biology, Princeton University, Princeton, New Jersey

YANOFSKY, CHARLES, Department of Biological Sciences, Stanford University, Stanford Cali- fornia

YOSHIKAWA, HIROSHI, Department of Biology, Princeton University, Princeton, New Jersey

ZABIN, IRVING, Department of Physiological Chemistry, University of California School of Medicine, Los Angeles 24, California

ZAMECNIK, PAUL C., Massachusetts General Hos- pital, Boston 14, Massachusetts

ZILLIG, W., Max-Planck-Institut fiir Biochemistry, Mtinchen 15, Germany

ZINDER, NORTON, Rockefeller Institute for Medical Research, N.Y. 21, N.Y.

ZIPSER, DAVID, Biological Laboratories, Harvard Univ., Cambridge 38, Mass.

Contents

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v List of Previous Volumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Photographs of Some Symposium Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii List of Those Attending the Symposium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x Francis J. Ryan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xx

T H E SYNTHESIS AND STRUCTURE OF DNA

RIS, H. and B. L. CHANDLER. The Ultrastrueture of Genetic Systems in Pro- karyotes and Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

RICHARDSON, C. C., C. L. SCHILDKRAUT and A. KORNBERG. Studies on the Replication of DNA by DNA Polymerases . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

BOLLUM, F. J. Studies on the Nature of Calf Thymus DNA-Polymerase Products 21 BURTON, K., M. R. LUNT, G. B. PETERSEN, and J. C. SIEBKE. Studies of Nucleo-

tide Sequences in DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 MosIG, G. Genetic Recombination in Bacteriophage T4 During Replication of

DNA Fragments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 CAIRNS, J. The Chromosome of Escherichia cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 SUEOKA, N., and H. YOSHIKAWA. Regulation of Chromosome Replication in

Baci l lus subti l is . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 NXGATX, T. The Sequential Replication of E. coli DNA . . . . . . . . . . . . . . . . . . . . . . 55

THE SYNTHESIS AND STRUCTURE OF RNA

HURWITZ, J., A. Eves, C. BABINET, and A. SKALKA. On the Copying of DNA in the RNA Polymerase Reaction .................................... 59

CHAMBERLIN, M., and P. BERG. Studies on DNA Directed RNA Polymerase; Formation of DNA-RNA Complexes with Single Stranded CX 174 DNA as Template . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

SPENCER, M. X-Ray Diffraction Studies of the Secondary Structure of R N A . . . 77 FRESCO, J. R., L. C. KLOTZ, and E. G. RICHARDS. A new Spectroscopic Approach

to the Determination of Helical Secondary Structure in Ribonucleic Acid.. 83 HASELKORN, R. Actinomycin D as a Probe for Nucleic Acid Secondary Structure 91 AUGUST, J. T., S. COOPER, L. SHAPIRO, and N. D. ZINDER. RNA Phage Induced

RNA Polymerase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 WEISSMANN, C., L. SIMON, P. BORST, and S. OCHOA. Induction of RNA Syn-

thetase in E. coli After Infection by the RNA Phage, MS 2 . . . . . . . . . . . . . . 99 BALTIMORE, D., and R. M. FRANKLIN. Properties of the Mengovirus and Polio-

virus RNA Polymerases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 SPIEGELMAN, S., and R. H. Doz. Replication and Translation of RNA Genomes 109

TRANSFER RNA

HOLLEY, R. W., J. APGAR, G. A. EVERETT, J. T. MADISON, S. H. MERRILL, and A. ZAMm. Chemistry of Amino Acid-Specific Ribonucleie Acids . . . . . . . . . . 117

CANTONI, G. L., H. ISHIKURA, H. H. RICHARDS, and K. TANAKA. Studies on Soluble Ribonucleie Acid. XI. A Model for the Base Sequence of Serine S-RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

INGRAM, V. M. and J. A. SJ()QUIST. Studies on the Structure of Purified Alanine and Valine Transfer RNA from Yeast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

BOREK, E. The Methylation of Transfer RNA: Mechanism and Function . . . . . . 139 GOLD, M., and J. HURWITZ. The Enzymatic Methylation of the Nucleic Acids 149 LITTAUER, U. Z., K. MUENCH, P. BERG, W. GILBERT, and P. F. SP~R. Studies

on Methylated Bases in Transfer RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

xvii

CONTENTS xviii

MESSENGER RNA

SPIEGELI~IAN, S., and M. HAYASHI. The Present Status of the Transfer of Genetic Information and I ts Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

LEVINTttAL, C., D. P. FAN, A. HIGA, and R. A. ZIMMERMXN. The Decay and Protection of Messenger RNA in Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

MARMUR, J., C. M. GREENSPAN, E. PALECEK, F. M. KAtIAN, J. LEVINE, and M. MANDEL. Specificity of the Complementary RNA formed by B. subti l is Infected with Bacteriophage SP 8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

HALL, B. D., M. H. GREEN, A. P. NYGAARD, and J. A. BOEZI. Copying of DNA in T2 Infected E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

BAUTZ, E. K. F. The Structure of T4 Messenger RNA in Relation to Messenger Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

DARNELL, J. E., S. PENMAN, K. SCHERRER, and Y. BECKER. A Description of Various Classes of RNA from Hel l Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

P R O T E I N SYNTHESIS I

HARDESTY, B., R. ARLINGHAUS, J. SHAEFFER, and R. SCHWEET. Hemoglobin and Polyphenylanine Synthesis with Reticulocyte Ribosomes ........... 215

MARKS, P. A., E. R. BURKA, R. RIFKIND, and D. DANON. Polyribosomes Active in Reticulocyte Protein Synthesis ............................. 223

NAKAMOTO, T., T. W. CONWAY, J. E. ALLENDE, G. J. SPYRIDES, and F. LIPMANN. Formation of Peptide Bonds I. Peptide Formation from Aminoacyl-S-RNA 227

BENNETT, T. P., J. GOLDSTEIN, and F. LIPMANN. Formation of Peptide Bonds II. Coding Properties of Leucyl-S-RNAs ................................. 233

WOOD, W. B., and P. BERG. Studies on the "Messenger" Activity of RNA Synthesized with RNA Polymerase .................................. 237

ALLFREY, V. G., and A. E. MIRSKY. Mechanisms of Synthesis and Control of Protein and Ribonucleic Acid Synthesis in the Cell Nucleus . . . . . . . . . . . . . 247

MACH, B. The Biosynthesis of an Antiobotie Polypeptide, as Distinguished from Protein Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263

SPIRIN, A. S. In Vitro Formation of Ribosome-like Particles from CM Particles and Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

P R O T E I N SYNTHESIS I I

RICK, A., J. R. WARNER, and H. M. GOODMAN. The Structure and Function of Polyribosomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269

GILBERT, W. Protein Synthesis in E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 GROS, F., J. M. DUBERT, A. TISSIERES, S. BOURGEOIS, M. MICHELSON, R. SOFFER,

and L. LEGAULT. Regulation of Metabolic Breakdown and Synthesis of Messenger RNA in Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299

NOMURA, M. Mode of Action of Colicines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 KEPES, A. Kinetic Analysis of the Early Events in Induced Enzyme Synthesis 325

REGULATION OF SYNTHESIS OF MACROMOLECULES

J,tcoE, F., S. BRENNER, and F. CUZIN. On the Regulation of DNA Replication in Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

AMES, B. N., and P. E. HXRTMAN. The Histidine Operon . . . . . . . . . . . . . . . . . . 349 MARTIN, R. G. The One 0peron-One Messenger Theory of Transcription . . . . . . 357 ATTARDI, G., S. NXONO, J. ROUVIERE, F. JACOB, and F. GROS. Production of

Messenger RNA and Regulation of Protein Synthesis . . . . . . . . . . . . . . . . . . . 363 GVTTMX~, B., and A. Novice . A Messenger RNA for fl-Galactosidase in E . coli 373 EPSTEIN, R. H., A. BOLLIX, C. M. STEINBERG, E. KELLENBERGER, E. BoY

DE LA. TOUR, R. CHEVALLEY, R. S. EDGAR, M. SUSMAN, G. DENttARDT, and A. LEILAUSIS. Physiological Studies of Conditional Lethal Mutations of Bacteriophage T4 D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375

T~oMAs, C. A. The Arrangements of Nucleotide Sequences in T2 and T5 DNA Molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395

xix CONTENTS

NOVlCK, A., E. S. LENNOX, and F. JACOB. Relationship Between Rate of Enzyme Synthesis and Repressor Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397

REVEL, H., and S. E. LURIA. On the Mechanism of Unrepressed Galactosidase Synthesis Controlled by a Transducing Phage . . . . . . . . . . . . . . . . . . . . . . . . . . 403

SCHACHM,tN, H. K. Considerations on the Tertiary Structure of Proteins . . . . . . 409 ZABIN, I. Proteins of the Lactose System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431 BACON, D., and H. J. VOGEL. A Regulatory Gene Simultaneously Involved in

Repression and Induction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437

TERTIARY STRUCTURE OF PROTEINS

EPSTEIN, C. J., R. F. GOLDBERGER, and C. B. ANFINSEN. Genetic Control of Tertiary Protein Structure: Studies with Model Systems . . . . . . . . . . . . . . . 439

MUIRHEAD, H., and M. F. PERUTZ. Structure of Reduced Human Hemoglobin 451

ALLOSTERIC INTERACTIONS BETW EEN PROTEINS AND SMALL MOLECULES

TOMKINS, G. M., K. L. YIELDING, N. TALAL, and J. F. CURRAN. Protein Structure and Biological Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461

KOSHLAND, D. E., JR. The Role of Flexibility in Enzyme Action . . . . . . . . . . . . 473 WYMAN, J. Allosteric Effects in Hemoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 GERHART, J. C., and A. B. PARDEE. The Effect of the Feedback Inhibitor, CTP,

on Subunit Interactions in Aspartate Transcarbamylase . . . . . . . . . . . . . . . . . 491 CHANGEUX, J. P. Allosteric Interactions on Biosynthetic L-Threonine Deaminase

from E . col i K-12 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 FREUNDLICH, M., and H. E. UMBARGER. The Effects of Analogues of Threonine

and of Isoleucine on the Properties of Threonine Deaminase . . . . . . . . . . . . 505 COHEN, G. N., and J. C. PATTE. Some Aspects of the Regulation of Amino Acid

Biosynthesis in a Branched Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513

COMPLEMENTATION

FINCHA~, J. R. S., and A. CODDINGTON. The Mechanism of Complementation between a m Mutants of ] V e u r o s p o r a c r a s s a . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517

PERRIN, D. Complementation between Products of the fl-Galactosidase Structural Gene of E . coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529

ZIPSER, D., and D. PERRIN. Complementation on Ribosomes . . . . . . . . . . . . . . . . 533 SCHLESINGER, M. J., A. TORRIANI, and C. LEVINTHAL. In Vitro Formation of

Enzymatieally Active Hybrid Proteins from E . coli Alkaline Phosphatase CRM's . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539

GROSS, S. R., and R. E. WEBSTER. Some Aspects of Interallelic Complementation Involving Leucine Biosynthetic Enzymes of N e u r o s p o r a . . . . . . . . . . . . . . . . . 543

AMINO ACID CODE I: EVIDENCE FROM IN VITRO SYSTEMS

NIRENBERG, M. W., O. W. JONES, P. LEDER, B. F. C. CLARK, W. S. SLY, and S. PESTKA. On the Coding of Genetic Information . . . . . . . . . . . . . . . . . . . . . 549

SPEYER, J. F., P. LENGYEL, C. B&SILIO, A. J. WAHBA., R. S. GARDNER, and S. OCHOA. Synthetic Polynueleotides and the Amino Acid Code . . . . . . . . . . . . 559

YAMANE, T., T. Y. CHENO, and N. SUEOKA. Species Specificity of Amino Acid Transfer-RNA and Amino Acyl-T-RNA Synthetase . . . . . . . . . . . . . . . . . . . . 569

WEINSTEIN, I. B. Comparative Studies on the Genetic Code . . . . . . . . . . . . . . 579

AMINO ACID CODE II: EVIDENCE FROM AMINO ACID SUBSTITUTIONS

YANOFSKY, C. Amino Acid R~placements Associated with Mutation and Re- combination in the A Gene and Their Relationship to In Vitro Coding Data 581

WITTMANN, H. G., and B. WITTMANN-LIEBOLD. Tobacco Mosaic Virus Mutants and the Genetic Coding Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589

XX

FRANCIS J. RYAN

Centers of scientific research are what people choose to make them. This is especially true for the Laboratory at Cold Spring Harbor, which has achieved its scientific reputat ion not by some happy accident but as the result of the careful guidance of its loyal friends. A few of these friends have at some time worked here for long periods. Others have been regular summer visitors. And others, though never here for very long, have ye t shown themselves ready to forsake their own affairs on behalf of the Labora tory in times of need.

This last year saw the withdrawal of the Carnegie Inst i tut ion of Washington from Cold Spring Harbor and the creation of arnew organization "The Cold Spring Harbor Labora tory of Quantitative Biology" to control the entire enterprise. Many people have labored to make the transition possible and so ensure the continued survival of the laboratories. No one worked harder at this than Francis Ryan.

Despite his responsibilities as Chairman of the Depar tment of Zoology at Columbia University, he joined with Dr. Edward L. Tatum and Dr. Rollin D. Hotchkiss in carrying out the early negotiations with the Long Island Biological Association and the Carnegie Institution. Later he became one of the most active of the group of Trustees formed to watch over the new Labora tory at Cold Spring Harbor. In this role, he was ready at all times to give his selfless support and counsel, and to exercise his great powers of gentle persuasion.

Francis Ryan died suddenly, one month after the end of this symposium. The news of his death had the unbelievable quality tha t comes with the death of a friend. Time will soften this blow, but it will not lessen the great contribution he made to science--through his own research, through the work he inspired in others, and through his great influence on the course of events during a most critical period in the affairs of the laboratory at Cold Spring Harbor. He was 47 at the time of his death.