Advancing Prion Science - Guidance for the Natl Prion Research Pgm - R. Erdtmann, et al (NAP, 2004) WW

285 Pages·2004·7.47 MB·English

ADVANCING PRION
SCIENCE: Guidance for

the National Prion
Research Program

Rick Erdtmann
Laura B. Sivitz,
Editors

THE NATIONAL ACADEMIES PRESS

Committee on Transmissible Spongiform Encephalopathies:
Assessment of Relevant Science

Rick Erdtmann and Laura B. Sivitz, Editors

Medical Follow-up Agency

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing
Board of the National Research Council, whose members are drawn from the councils of
the National Academy of Sciences, the National Academy of Engineering, and the Insti-
tute of Medicine. The members of the committee responsible for the report were chosen
for their special competences and with regard for appropriate balance.

Support for this project was provided by the U.S. Department of Defense (Contract No.
DAMD17-02-C-0094). The views presented in this report are those of the Institute of
Medicine Committee on Transmissible Spongiform Encephalopathies: Assessment of
Relevant Science and are not necessarily those of the funding agencies.

Library of Congress Cataloging-in-Publication Data

Institute of Medicine (U.S.). Committee on Transmissible Spongiform Encephalopa-
thies: Assessment of Relevant Science.
Advancing prion science : guidance for the national prion research program / Com-
mittee on Transmissible Spongiform Encephalopathies: Assessment of Relevant Science ;
Rick Erdtmann and Laura B. Sivitz, editors.
p. ; cm.
Includes bibliographical references.
ISBN 0-309-09060-1 (pbk.) — ISBN 0-309-52714-7 (PDF)
1. Prion diseases. 2. Prion diseases—Government policy—United States.
[DNLM: 1. Prion Diseases—prevention & control—United States. 2. Food Supply—
standards—United States. 3. Health Policy—United States. 4. Prion Diseases—
diagnosis—United States. WL 300 I591ad 2003] I. Erdtmann, Rick. II. Sivitz, Laura.
III. Title.
RA644.P93I55 2003
616.8’3—dc22
2003027266

Additional copies of this report are available from the National Academies Press, 500
Fifth Street, N.W., Lockbox 285, Washington, DC 20055; [phone] or (202) 334-
3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.

For more information about the Institute of Medicine, visit the IOM home page at:
www.iom.edu.

Copyright 2004 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America.

The serpent has been a symbol of long life, healing, and knowledge among almost all
cultures and religions since the beginning of recorded history. The serpent adopted as a
logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by
the Staatliche Museen in Berlin.

COVER: The cover photograph, provided by Dr. David Asher, is a histopathology slide
of brain tissue from a patient with a prion disease. Stained with the chemicals eosin (red)
and hematoxylin (blue), the magnified tissue manifests microscopic holes (white circles)
that illustrate why prion-infected tissue is described as spongiform. This report aims to
guide scientists beyond histopathology toward new strategies to diagnose prion diseases
noninvasively, rapidly, and early.

Shaping the Future for Health

“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe

The National Academy of Sciences is a private, nonprofit, self-perpetuating society
of distinguished scholars engaged in scientific and engineering research, dedicated
to the furtherance of science and technology and to their use for the general welfare.
Upon the authority of the charter granted to it by the Congress in 1863, the Acad-
emy has a mandate that requires it to advise the federal government on scientific and
technical matters. Dr. Bruce M. Alberts is president of the National Academy of
Sciences.

The National Academy of Engineering was established in 1964, under the charter of
the National Academy of Sciences, as a parallel organization of outstanding engi-
neers. It is autonomous in its administration and in the selection of its members,
sharing with the National Academy of Sciences the responsibility for advising the
federal government. The National Academy of Engineering also sponsors engineer-
ing programs aimed at meeting national needs, encourages education and research,
and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is presi-
dent of the National Academy of Engineering.

The Institute of Medicine was established in 1970 by the National Academy of
Sciences to secure the services of eminent members of appropriate professions in the
examination of policy matters pertaining to the health of the public. The Institute
acts under the responsibility given to the National Academy of Sciences by its con-
gressional charter to be an adviser to the federal government and, upon its own
initiative, to identify issues of medical care, research, and education. Dr. Harvey V.
Fineberg is president of the Institute of Medicine.

The National Research Council was organized by the National Academy of Sciences
in 1916 to associate the broad community of science and technology with the
Academy’s purposes of furthering knowledge and advising the federal government.
Functioning in accordance with general policies determined by the Academy, the
Council has become the principal operating agency of both the National Academy
of Sciences and the National Academy of Engineering in providing services to the
government, the public, and the scientific and engineering communities. The Coun-
cil is administered jointly by both Academies and the Institute of Medicine. Dr.
Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the
National Research Council.

www.national-academies.org

COMMITTEE ON TRANSMISSIBLE SPONGIFORM
ENCEPHALOPATHIES: ASSESSMENT OF RELEVANT SCIENCE

Richard T. Johnson, Chair, Distinguished Service Professor of Neurology,
Microbiology, and Neuroscience, Johns Hopkins University School of
Medicine and Bloomberg School of Public Health

Harvey J. Alter, Chief of the Infectious Diseases Section and Associate
Director for Research, Department of Transfusion Medicine,
National Institutes of Health

Dean O. Cliver, Professor of Food Safety, Department of Population
Health and Reproduction, School of Veterinary Medicine, University
of California, Davis

Linda D. Cowan, George Lynn Cross Research Professor, Epidemiology,
Department of Biostatistics and Epidemiology, University of
Oklahoma Health Sciences Center, and Liaison from the Board of the
Medical Follow-up Agency

Roger Y. Dodd, Executive Director for Biomedical Safety, American Red
Cross Holland Laboratory

Frederick A. Murphy, Professor and Dean Emeritus, Department of
Pathology, Microbiology, and Immunology, School of Veterinary
Medicine, University of California, Davis

Michael B.A. Oldstone, Professor, Department of Neuropharmacology,
Division of Virology, The Scripps Research Institute

David Relman, Associate Professor of Medicine and of Microbiology and
Immunology, Stanford University

Raymond P. Roos, Marjorie and Robert E. Straus Professor in
Neurological Science, and Chairman, Department of Neurology,
University of Chicago Medical Center

David M. Taylor, SEDECON 2000 and retired Senior Scientist,
Neuropathogenesis Unit, Institute for Animal Health, Edinburgh

Reed B. Wickner, Chief, Laboratory of Biochemistry and Genetics,
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health

Robert G. Will, Professor of Neurology, University of Edinburgh;
Director, National Creutzfeldt-Jakob Disease Surveillance Unit; and
Consultant Neurologist and Part-Time Senior Lecturer, Department
of Neurosciences, Western General Hospital, Edinburgh

v

Consultants

Adriano Aguzzi, Professor and Associate Dean for Research, Department
of Pathology, Institute of Neuropathology, University Hospital at
Zurich

David M. Asher, Chief, Laboratory of Bacterial, Parasitic, and
Unconventional Agents, Division of Emerging and Transfusion
Transmitted Diseases, Office of Blood Research and Review, Center
for Biologics Research and Evaluation, Food and Drug
Administration

Pierluigi Gambetti, Professor and Director, Division of Neuropathology,
Case Western Reserve University, and Director, National Prion
Disease Pathology Surveillance Center

David A. Harris, Professor, Department of Cell Biology and Physiology,
Washington University School of Medicine

Stanley B. Prusiner, Director, Institute for Neurodegenerative Diseases,
and Professor of Neurology, University of California, San Francisco

Elizabeth S. Williams, Professor, Department of Veterinary Science,
University of Wyoming

Project Staff

Rick Erdtmann, Study Director, Medical Follow-up Agency
Laura B. Sivitz, Research Associate, Medical Follow-up Agency
Reine Y. Homawoo, Senior Project Assistant, Medical Follow-up Agency
Karen Kazmerzak, Research Associate, Medical Follow-up Agency
(through December 2002)

Auxiliary Staff

Richard N. Miller, Director, Medical Follow-up Agency
Pamela Ramey-McCray, Administrative Assistant, Medical Follow-up
Agency
Andrea Cohen, Financial Associate
Mary Poos, Senior Program Officer, Food and Nutrition Board
Tina Rouse, Program Officer, Board on Agriculture and Natural
Resources, Division on Earth and Life Sciences

vi

T

his report has been reviewed in draft form by individuals chosen for
their diverse perspectives and technical expertise, in accordance with
procedures approved by the NRC’s Report Review Committee. The
purpose of this independent review is to provide candid and critical com-
ments that will assist the institution in making its published report as sound
as possible and to ensure that the report meets institutional standards for
objectivity, evidence, and responsiveness to the study charge. The review
comments and draft manuscript remain confidential to protect the integrity
of the deliberative process. We wish to thank the following individuals for
their review of this report:

Barbara Alving
Deputy Director
National Heart Lung and Blood Institute
National Institutes of Health

David C. Bolton
Head, Laboratory of Molecular Structure and Function
New York Institute for Basic Research

Bruce W. Chesebro
Chief, Laboratory of Persistent Viral Diseases
Rocky Mountain Laboratories
National Institutes of Health

vii

Reviewers

Robert Finberg
Professor and Chair of Medicine
Professor of Molecular Genetics and Microbiology
University of Massachusetts

Colin Masters
Professor of Pathology
Center for Neuroscience
University of Melbourne

James Mastrianni
Assistant Professor of Neurology
Department of Neurology
The University of Chicago Hospitals

J. Glenn Morris
Chair and Professor
Department of Epidemiology and Preventive Medicine
University of Maryland

John E. Vanderveen
Emeritus Scientist
United States Food and Drug Administration

Gerald A. H. Wells
Consultant Veterinary Pathologist
Head of Neuropathology (Retired)
Central Veterinary Laboratory, United Kingdom

Charles B. Wilson
Senior Advisor
Health Technology Center, San Francisco

Although the reviewers listed above have provided many constructive
comments and suggestions, they were not asked to endorse the conclusions
or recommendations, nor did they see the final draft of the report before its
release. The review of this report was overseen by our coordinator, Morton
N. Swartz, Chief, Jackson Firm of Medical Service, and Chief Emeritus,
Infectious Disease Unit, Massachusetts General Hospital; and our monitor,
Linda Cork, Professor and Chair of Comparative Medicine, Stanford Uni-
versity School of Medicine. Appointed by the National Research Council
and the Institute of Medicine, Drs. Swartz and Cork were responsible for
making certain that an independent examination of this report was carried
out in accordance with institutional procedures and that all review com-
ments were carefully considered. Responsibility for the final content of this
report rests entirely with the authoring committee and the institution.

viii
REVIEWERS

W

hy is the U.S. government concerned about prion diseases?
Known scientifically by the descriptive term transmissible
spongiform encephalopathies (TSEs), these diseases do not cur-
rently represent significant public health problems in the United States.
While it brings incalculable grief to affected families, Creutzfeldt-Jakob dis-
ease (CJD), the primary human prion disease, causes only 1 in 10,000 an-
nual deaths worldwide, and there is no evidence that this rate is growing.
Bovine spongiform encephalopathy (BSE), the epidemic “mad cow” disease
in Europe, has yet to be detected in the United States.1
Nevertheless, several compelling reasons exist for focusing greater re-
search efforts on prion diseases. First, the sudden appearance of BSE in the
United Kingdom in the mid-1980s represented a massive and unforesee-
able contamination of the bovine and human food supplies. Hundreds of
thousands of cattle died, and the infectious agent unexpectedly crossed the
species-barrier to humans. In the past decade, more than one hundred
young adults have developed a variant of CJD from exposure to BSE. The
social, political, and economic impacts of those epidemics of cattle and
human diseases in the United Kingdom and continental Europe have been
enormous. Consequently, a number of policies have been instituted to ex-
clude BSE from the United States and to limit its spread, should it enter the
country.

ix

Preface

1EDITORS’ NOTE: After this report was completed, the first U.S. case of BSE was identi-
fied in Washington State and was announced to the public on December 23, 2003.