ACADEMIC PRESS RAPID MANUSCRIPT REPRODUCTION Proceedings of a Conference on Membranes, Viruses, and Immune Mechanisms in Experimental and Clinical Diseases, Held at the University of Minnesota, June 5-7, 1972. Membranes and Viruses in Immunopathology Edited by StaceyB.Day, M.D.,PII.D.,D.SC. Bell Museum of Pathobiology and Departments of Pathology and Research Surgery University of Minnesota Medical School Minneapolis, Minnesota Robert A. Good, M.D., Ph.D. Departments of Pathology, Pediatrics, and Microbiology University of Minnesota Medical School Minneapolis, Minnesota Academic Press · New York · London · 1972 COPYRIGHT © 1972, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Ill Fifth Avenue, New York, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. 24/28 Oval Road, London NW1 LIBRARY OF CONGRESS CATALOG CARD NUMBER: 72-7346 PRINTED IN THE UNITED STATES OF AMERICA PARTICIPANTS Stuart A. Aaronson, Molecular Biology Section, Viral Leukemia and Lymphoma Branch, National Cancer Institute, NIH, Bethesda, Maryland Norman G. Anderson, Molecular Anatomy (MAN Program), Oakridge Laborato ries, Oakridge, Tennessee Fritz H. Bach, Division of Medical Genetics and Medicine, University of Wisconsin, Madison, Wisconsin Marilyn L. Bach, Division of Medical Genetics and Medicine, University of Wisconsin, Madison, Wisconsin David Baltimore, Department of Microbiology, Massachusetts Institute of Technology, Cambridge, Massachusetts Edward B. Blau, Department of Pediatrics and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Edward A. Boyse, Immunology Section, Sloan-Kettering Institute for Cancer Research, and Department of Biology, Cornell University, New York, New York Roscoe 0. Brady, Laboratory of Neurochemistry, National Institute of Neurological Diseases and Stroke, NIH, Bethesda, Maryland Gilbert C. H. Chang, Department of Pediatrics, Infectious Disease and Immunology Section, Department of Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia Yong Sung Choi, Department of Pediatrics, Biochemistry, and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota J. H. Coggin, Jr., Molecular Anatomy (MAN Program), Oakridge Laboratories, Oakridge, Tennessee Susan E. Cullen, Department of Microbiology and Immunology, and Depart ment of Cell Biology, Albert Einstein College of Medicine, Bronx, New York IX PARTICIPANTS Noorbibi K. B. Day, Department of Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Stacey B. Day, Bell Museum of Pathobiology and Departments of Pathology and Surgery, University of Minnesota Medical School, Minneapolis, Minnesota Frank J. Dixon, Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California Carl Eklund, Rocky Mountain Laboratories, Hamilton, Montana Astrid Fagraeus, Department of Immunology, National Bacteriological Laboratory, Karolinska Institute School of Medicine, Stockholm, Sweden Michael E. Fritz, Department of Pediatrics, Infectious Disease and Immunology Section, Department of Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia Larry D. Frye, National Institute of Neurological Diseases and Stroke, NIH, Bethesda, Maryland D. Carleton Gajdusek, Laboratory of Slow Latent and Temperate Virus Infections, Central Nervous System Studies Branch, NIH, Bethesda, Maryland Clarence J. Gibbs, Jr., Laboratory of Slow Latent and Temperate Virus Infec tions, Central Nervous System Studies Branch, NIH, Bethesda, Maryland Raymond V. Gilden, Viral Carcinogenesis Branch, National Cancer Institute, NIH, Bethesda, Maryland Norton B. Gilula, Department of Anatomy, Harvard Medical School, Boston, Massachusetts Robert A. Good, Departments of Pathology, Pediatrics, and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota Daniel A. Goodenough, Department of Anatomy, Harvard Medical School, Boston, Massachusetts Beulah Holmes Gray, Department of Microbiology and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Maurice Green, Molecular Virology Institute, St. Louis University School of Medicine, St. Louis, Missouri x PARTICIPANTS William J. Hadlow, Rocky Mountain Laboratories, Hamilton, Montana Ingegerd Hellstrom, Department of Pathology, University of Washington Medical School, Seattle, Washington Karl Erik Hellstrom, Department of Pathology, University of Washington Medical School, Seattle, Washington Sylvia Hoffstein, Department of Medicine, New York School of Medicine and Cancer Research, Health Research Council of the City of New York, New York , New York John R. Hoyer, Department of Pediatrics and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Sreerama M. Jagarlamoody, Department of Surgery and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota John H. Kersey, Department of Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Stuart Kornfeld, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Carlos Lopez, Department of Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Charles F. McKhann, Department of Surgery and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota S. Michael Mauer, Department of Pediatrics and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Alfred F. Michael, Department of Pediatrics and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Donald L. Morton, Department of Surgery, Division of Oncology, University of California School of Medicine, Los Angeles, California Hans J. Müller-Eberhard, Division of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California André J. Nahmias, Department of Pediatrics, Infectious Disease and Immunology Section, Department of Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia XI PARTICIPANTS Stanley G. Nathenson, Department of Microbiology and Immunology, and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York Garth L. Nicolson, Department of Biology, University of California, San Diego, California Michael B. A. Oldstone, Division of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California Wade P. Parks, Viral Carcinogenesis Branch, National Cancer Institute, NIH, Bethesda, Maryland Angelyn Rios, Department of Surgery and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota Kenneth J. Rothschild, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, and Harvard-MIT Program in Health Science, Boston, Massachusetts Benjamin D. Schwartz, Department of Microbiology and Immunology, and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, Edward M. Scolnick, Viral Carcinogenesis Branch, National Cancer Institute, NIH, Bethesda, Maryland Robert E. Scott, Department of Pathology, University of Minnesota Medical School, Minneapolis, Minnesota John R. Sheppard, Department of Neurology, University of Colorado Medical School, Denver, Colorado Richard L. Simmons, Department of Surgery and Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota S. J. Singer, Department of Biology, University of California, San Diego, California H. Eugene Stanley, Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, and Harvard-MIT Program in Health Science, Boston, Massachusetts John R. Stephenson, Molecular Biology Section, Viral Leukemia and Lymphoma Branch, National Cancer Institute, NIH, Bethesda, Maryland xn PARTICIPANTS Osias Stutman, Department of Pathology and Laboratory Medicine, University of Minnesota Medical School, Minneapolis, Minnesota Gnanasigamoni Sundharadas, Division of Medical Genetics and Medicine, University of Wisconsin, Madison, Wisconsin Thomas W. Tillack, Department of Pathology, Washington University School of Medicine, St. Louis, Missouri George J. Todaro, Viral Leukemia and Lymphoma Branch, National Cancer Institute, NIH, Bethesda, Maryland F. William Tuominen, Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota Robert L. Vernier, Cardiovascular Research and Training Center, University of Minnesota, Department of Pediatrics and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Leonard Warren, Department of Therapeutic Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Gerald Weissmann, Department of Medicine, New York School of Medicine and Cancer Research, Health Research Council of the City of New York, New York, Edmond Yunis, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Robert B. Zurier, Department of Medicine, New York School of Medicine and Cancer Research, Health Research Council of the City of New York, New York, xin PREFACE It was the purpose of the symposium held by the Bell Museum of Pathol ogy, University of Minnesota Medical School, on June 5-7, 1972, to put in focus much of the recent accelerating progress that has derived from constructive interaction of fundamental experiments of membrane structure chemistry, diag nosis and analysis of slow and oncogenic virus infections, and the role of im- munobiologic processes in the pathogenesis, prevention and treatment of disease. The laboratory does and must provide the backdrop for new intellectual activity exploring the basis of disease. Provisos for knowledge upon which are based management and therapy must be crucially tested first in the laboratory. Then may knowledge be applied to disease in the human patient. Striking ex ample of this interplay between clinic and the basic laboratory is to be seen in the application of advancing knowledge of the development of the lymphoid system to the treatment and correction of inborn errors of metabolism that result in immunodeficiency disease. Relevant corrections have been accomplished by organ transplantation and cellular engineering. Inevitably questions are asked of Nature and of men. "Accepted" concepts as frequently as not, must be challenged, updated, discarded. And this address to human disease is weighed intensively in laboratories in many places. It has been the privilege of this symposium to have gathered together in one place so many experts to speak with authority upon matters of membrane structure and disease at the level of molecular pathology. The information, as presented here could not be better cited, nor better stated than by the participants of this symposium. Each author is a leader in his field. Each summarizes the newly developing knowledge of his discipline, and the whole as a complement of each encourages the practicing physician to believe that of the many questions which he so vitally needs to have answered, many indeed are being explored at funda mental levels, both theoretical and practical; and some most fortunately are in the process of being answered. The direction of these questions and answers will, in some measure at least, be pointed out in the following papers. Stacey B. Day Robert A. Good xv ACKNOWLEDGMENTS The convening of the outstanding and distinguished faculty presented here would not have been realized without the generous support and interest of a number of funding bodies and agencies whose grants to the Bell Museum of Pathobiology of the University of Minnesota Medical School made this sympo sium possible. Special thanks and appreciation are therefore extended to the following organizations and corporations: the Office of Postgraduate Medical Education, University of Minnesota (Mr. Stoddard Cortelyou, Associate Director); the National Foundation-March of Dimes for cosponsoring with the Bell Museum of Pathobiology the entire program; Abbott Laboratories; Ayerst Laboratories, Division of American Home Products Corporation; Cutter Laboratories; Hoechst Pharmaceutical Company, Division of American Hoechst Corporation; Johnson and Johnson; The Lilly Research Labs, Eli Lilly and Company; Merck Sharp and Dohme, Division of Merck and Company, Inc.; Merrell National Laboratories, Division of Richardson Merrell, Inc.; Riker Laboratories, Inc.; Roche Labora tories, Division of Hoffman-La Roche, Inc.; Ross Laboratories; Schering Corpora tions Research Division; E. R. Squibb and Sons, Inc.; Strasenburgh Pharmacraft Pennwalt Corporation; Travenol Laboratories; Upjohn Corporation; Wallace Lab oratories, Division of Carter-Wallace, Inc.; and Lederle Laboratories. To all these organizations and agencies we acknowledge their help and interest in our undertaking. A note of acknowledgment is also due our secretary, Miss Patricia McDermott, who with quiet patience and gentle assurance labored at bringing order and form to this typescript, notwithstanding endless changes, rewritings, and late revisions. It goes without saying that the book is due in greatest measure to the many contributors and their coauthors who, for three full days in early June 1972, took time out of their pressing schedules to develop the intensive viewpoints, analyses, and applications of the new pathology so well enunciated in this text. It is due to the conceptual minds of such men that the new, richly developing thrust of pathology at the molecular level is largely possible. To all these colleagues and associations we extend our warmest thanks. Stacey B. Day Robert A. Good xvn