National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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OVERCOMING CHALLENGES TO DEVELOP COUNTERMEASURES AGAINST AEROSOLIZED BIOTERRORISM AGENTS

APPROPRIATE USE OF ANIMAL MODELS

Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents

Board on Life Sciences

Institute for Laboratory Animal Research

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, DC
www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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THE NATIONAL ACADEMIES PRESS

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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 Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by the Department of Health and Human Services, National Institutes of Health through Contract No. N01-OD-4-2139 Task Order 152. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for the project. The content of this publication does not necessarily reflect the views or policies of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

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Additional copies of this report are available from

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Copyright 2006 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine


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 Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone 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 engineers. 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 engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president 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 congressional 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 Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.


www.national-academies.org

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

COMMITTEE ON ANIMAL MODELS FOR TESTING INTERVENTIONS AGAINST AEROSOLIZED BIOTERRORISM AGENTS

Charles H. Hobbs (Chair),

Lovelace Respiratory Research Institute, Albuquerque, New Mexico

David C. Dorman,

CIIT Center for Health Research, Research Triangle Park, North Carolina

Diane E. Griffin,

Johns Hopkins University, Baltimore, Maryland

Jack R. Harkema,

Michigan State University, East Lansing, Michigan

Beth L. Laube,

Johns Hopkins University, Baltimore, Maryland

David E. Lenz,

U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland

Stephen S. Morse,

Columbia University, New York, New York

Robert F. Phalen,

University of California, Irvine, California

Staff

Jennifer Obernier, Study Director

Kerry Brenner, Study Director (through August 2005)

Joe Larsen, Postdoctoral Fellow

Seth Strongin, Senior Program Assistant

Anne Jurkowski, Senior Program Assistant

Karen Imhof, Administrative Assistant

John Horigan, Christine Mirzayan Science and Technology Policy Graduate Fellow

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

BOARD ON LIFE SCIENCES

Corey S. Goodman (Chair),

Renovis, Inc., South San Francisco, California

Ann M. Arvin,

Stanford University School of Medicine, Stanford, California

Jeffrey Bennetzen,

University of Georgia, Athens, Georgia

Ruth Berkelman,

Emory University, Atlanta, Georgia

Deborah Blum,

University of Wisconsin, Madison, Wisconsin

R. Alta Charo,

University of Wisconsin, Madison, Wisconsin

Dennis Choi,

Merck Research Laboratories, West Point, Pennsylvania

Jeffrey L. Dangl,

University of North Carolina, Chapel Hill, North Carolina

Paul R. Ehrlich,

Stanford University, Stanford, California

James M. Gentile,

Research Corporation, Tucson, Arizona

Jo Handelsman,

University of Wisconsin, Madison, Wisconsin

Ed Harlow,

Harvard Medical School, Boston, Massachusetts

David Hillis,

University of Texas, Austin, Texas

Kenneth Keller,

University of Minnesota, Minneapolis, Minnesota

Randall Murch,

Virginia Polytechnic Institute and State University, Alexandria, Virginia

Gregory A. Petsko,

Brandeis University, Waltham, Massachusetts

Stuart L. Pimm,

Duke University, Durham, North Carolina

James Tiedje,

Michigan State University, East Lansing, Michigan

Keith Yamamoto,

University of California, San Francisco, California

Staff

Fran Sharples, Director

Denise Grosshans, Financial Associate

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL

Stephen W. Barthold (Chair),

University of California, Center for Comparative Medicine, Davis, California

William C. Campbell,

Drew University, Madison, New Jersey

Jeffrey I. Everitt,

GlaxoSmithKline Research and Development, Comparative Medicine and Investigator Support, Research Triangle Park, North Carolina

Michael F. Festing,

Leicestershire, United Kingdom

James G. Fox,

Massachusetts Institute of Technology, Division of Comparative Medicine, Cambridge, Massachusetts

Estelle B. Gauda,

Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Maryland

Janet Gonder Garber,

Pinehurst, North Carolina

Coenraad F.M. Hendriksen,

Netherlands Vaccine Institute, Bilthoven, The Netherlands

Jon H. Kaas,

Vanderbilt University, Nashville, Tennessee

Jay R. Kaplan,

Wake Forest University School of Medicine, Department of Pathology, Winston-Salem, North Carolina

Joseph W. Kemnitz,

University of Wisconsin, Primate Research Center, Madison, Wisconsin

Leticia V. Medina,

Abbott Laboratories, Abbott Park, Illinois

Abigail L. Smith,

University of Pennsylvania, University Laboratory Animal Resources, Philadelphia, Pennsylvania

Stephen A. Smith,

Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology, Blacksburg, Virginia

Peter Theran,

Massachusetts Society for the Prevention of Cruelty to Animals, Angell Animal Medical Center, Boston, Massachusetts

Staff

Joanne Zurlo, Director

Kathleen Beil, Administrative Assistant

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

Preface

The terrible events of September 11, 2001, and the dissemination of Bacillus anthracis by mail in October 2001, markedly increased awareness of the possibility of bioterrorism attacks and of the need for new vaccines and therapeutics to protect U.S. citizens from them.

Following this, Congress markedly increased the funding for research for new vaccines and therapeutics to protect the United States from a bioterrorist attack. Such research had largely been conducted by the U.S. Army Medical Research Institute of Infectious Diseases at Ft. Detrick, Maryland. Much of this research is now being directed by the National Institute of Allergy and Infectious Disease of the National Institutes of Health.

An integral part of the development of new vaccines and therapeutics is obtaining the necessary approvals from the U.S. Food and Drug Administration both for their initial use in people and their eventual licensure for general use. The present accelerated pace of development, however, has led to several additional needs: standardization of methods for the generation and characterization of aerosols of bioterrorism agents for use in animal studies (necessary for licensure of vaccines and therapeutics), characterization of the threat to the population, and expansion of the number of laboratories conducting the research. The Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents was convened by the National Research Council to address these issues. It was tasked by its sponsor, the National Institute of Allergy and Infectious Disease, to prepare a short consensus report that articulates the difficulties of testing countermeasures to aerosolized bioterrorism agents and considers whether there are opportunities for improving current approaches to animal testing of countermeasures against aerosols by applying knowledge from other fields of science.

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

Thus, the Committee organized a workshop, titled “Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents,” which was held July 6th – 7th, 2005, in Washington, D.C. The Committee selected as participants scientists, from diverse disciplines, who made presentations that ultimately were integral to the development of this report.

As chairman, I thank the committee members for contributing their expertise and time to the committee, the workshop, and the report. And the entire committee thanks NRC staff members Kerry Brenner and Jennifer Obernier for their organizational skills and hard work in arranging the workshop and preparing the report. Thanks too to Seth Strongin for providing logistical support. The report would not have been possible without their assistance.

The report has been reviewed in draft form by individuals chosen for their diverse perspective 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 comments 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 reviewers’ comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following people for their review of the report:

Lynn Andersen, Johns Hopkins University, Baltimore, Maryland

Chris Gennings, Virginia Commonwealth University, Richmond, Virginia

Michael T. Kleinman, University of California, Irvine, California

Roger O. McClellan, Toxicology and Human Health Risk Analysis, Albuquerque, New Mexico

Matthew S. Meselson, Harvard University, Boston, Massachusetts

Stanley Perlman, University of Iowa, Iowa City, Iowa

David Y. H. Pui, University of Minnesota, Minneapolis, Minnesota

Chad Roy, U.S. Army Medical Research Institute for Infectious Diseases, Fort Detrick, Maryland

Although the reviewers listed above 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 the report was overseen by:

Peter Ward, University of Michigan, Ann Arbor, Michigan

Peter Palese, Mount Sinai School of Medicine, New York, New York

Appointed by the NRC, these individuals were responsible for ensuring that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered.

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

Responsibility for the final content of the report, however, rests entirely with the authoring committee and the institution.

Charles H. Hobbs, Chair

Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Page xiii Cite
Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×
Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×
Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

Glossary

aerodynamic diameter An equivalent diameter for a particle defined as the physical diameter of a smooth solid sphere (of density 1 gram/cm3) that has the same terminal settling velocity in still air (under standard laboratory conditions) as the particle in question.

aerosol A relatively time-stable two-phase system consisting of finely-divided particles (that can be solids or liquids) suspended in a gas (which is usually air). Aerosol particles typically range in diameter from 0.001 to 100 μm.

bioterrorism agent A microorganism or a toxin derived from a microorganism that causes human disease and is used to harm people, or to elicit widespread fear or intimidation, for political or ideological goals.

countermeasure A drug, biological product, chemical, or other therapeutic technology that prevents or treats an illness caused by a bioterrorism agent.

dose The amount (for bioaerosol particles this could be number, mass, viable units, or another metric related to biological effect) of an agent normalized to some property of the biological target (which could be mass, surface area or other

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
×

descriptor of an individual, organ, or tissue). For example: mg of particles deposited in the subject; μg of particles deposited in the respiratory tract; μg of particles in the tracheobronchial region; or number of viable organisms in the alveolar spaces of the lung.

geometric standarddeviation (GSD) A measure of dispersion for a log-normal distribution that is analogous to the standard deviation for a normal distribution. The GSD is the ratio of the 84.13 percentile to the 50 percentile.

mass median aerodynamicdiameter (MMAD) For aerosols, the MMAD equals the particle diameter at which particles larger than the MMAD contribute half of the collected mass and particles smaller than the MMAD contribute the other half.

Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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Suggested Citation:"Front Matter." National Research Council. 2006. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents: Appropriate Use of Animal Models. Washington, DC: The National Academies Press. doi: 10.17226/11640.
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The National Institute of Allergy and Infectious Diseases (NIAID) gives the highest priority to developing countermeasures against bioterrorism agents that are highly infective when dispersed in aerosol form. Developing drugs to prevent or treat illnesses caused by bioterrorism agents requires testing their effectiveness in animals since human clinical trials would be unethical. At the request of NIAID, the National Academies conducted a study to examine how such testing could be improved. Overcoming Challenges to Develop Countermeasures Against Aerosolized Bioterrorism Agents provides recommendations to researchers on selecting the kinds of animal models, aerosol generators, and bioterrorism agent doses that would produce conditions that most closely mimic the disease process in humans. It also urges researchers to fully document experimental parameters in the literature so that studies can be reproduced and compared. The book recommends that all unclassified data on bioterrorism agent studies--including unclassified, unpublished data from U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID)--be published in the open literature. The book also calls on the U.S. Food and Drug Administration to improve the process by which bioterrorism countermeasures are approved based on the results of animal studies.

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