Research and Development to Improve Civilian Medical Response

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Chemical and Biological Terrorism

Research and Development to Improve Civilian Medical Response

Committee on R&D Needs for Improving Civilian Medical

Response to Chemical and Biological Terrorism Incidents

Health Science Policy Program

INSTITUTE OF MEDICINE

and

Board on Environmental Studies and Toxicology

Commission on Life Sciences

NATIONAL RESEARCH COUNCIL

NATIONAL ACADEMY PRESS

Washington, D.C. 1999

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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 this report were chosen for their special competences and with regard for appropriate balance.

The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in

the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter

responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth

I. Shine 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

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Research Council.

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This support does not constitute an endorsement of the views expressed in the report.

Library of Congress Cataloging-in-Publication Data

Chemical and biological terrorism: research and development to improve civilian medical response / Committee on R&D Needs for Improving

Civilian Medical Response to Chemical and Biological Terrorism Incidents, Health Science Policy Program, Institute of Medicine, and Board on

Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council.

p. cm.

Includes bibliographical references and index.

ISBN 0-309-06195-4 (hardcover)

1. Chemical warfare—Health aspects. 2. Biological

warfare—Health aspects. 3. Civil defense—United States. 4.

Terrorism—Government policy—United States. 5. Disaster

medicine—United States. I. Institute of Medicine (U.S.). Committee

on R & D Needs for Improving Civilian Medical Response to Chemical

and Biological Terrorism Incidents. II. National Research Council

(U.S.). Board on Environmental Studies and Toxicology.

RA648 .C525 1999

358'.3—dc21 98-58069

Additional copies of this report are available for sale from the National Academy Press, 2101 Constitution Avenue, N.W., Box 285, Washington, DC

20055. Call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area).

This report is also available online at http://www.nap.edu.

For more information about the Institute of Medicine, visit the IOM home page at http://www2.nas.edu/iom.

Copyright 1999 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America.

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Committee on R&D Needs for Improving Civilian Medical Response to Chemical and Biological

Terrorism Incidents

PETER ROSEN (Chair), Director, Emergency Medicine Residency Program, School of Medicine, University of

California, San Diego

LEO G. ABOOD, Professor of Pharmacology, Department of Pharmacology and Physiology, University of

Rochester Medical Center*

GEORGES C. BENJAMIN, Deputy Secretary, Public Health Services, Department of Health and Mental Hygiene,

Baltimore, Maryland

ROSEMARIE BOWLER, Assistant Professor and Fieldwork Coordinator, Department of Psychology, San

Francisco State University

JEFFREY I. DANIELS, Leader, Risk Sciences Group, Health and Ecological Assessment Division, Earth and

Environmental Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California

CRAIG A. DeATLEY, Associate Professor, Department of Emergency Medicine and Health Care Sciences

Program, The George Washington University, Washington, D.C.

LEWIS R. GOLDFRANK, Director, Emergency Medicine, New York University School of Medicine and Bellevue

Hospital Center, New York

JEROME M. HAUER, Director, Office of Emergency Management, City of New York

KAREN I. LARSON, Toxicologist, Office of Toxic Substances, Washington Department of Health, Olympia

MATTHEW S. MESELSON, Thomas Dudley Cabot Professor of the Natural Sciences, Department of Molecular

and Cellular Biology, Harvard University, Cambridge, Massachusetts

DAVID H. MOORE, Director, Medical Toxicology Programs, Battelle Edgewood Operations, Bel Air, Maryland

DENNIS M. PERROTTA, Chief, Bureau of Epidemiology, Texas Department of Health, Austin

LINDA S. POWERS, Professor of Electrical and Biological Engineering, and Director, National Center for the

Design of Molecular Function, Utah State University, Logan

PHILIP K. RUSSELL, Professor of International Health, School of Hygiene and Public Health, Johns Hopkins

University, Baltimore, Maryland

JEROME S. SCHULTZ, Director, Center for Biotechnology and Bioengineering, University of Pittsburgh

ROBERT E. SHOPE, Professor of Pathology, University of Texas Medical Branch, Galveston

ROBERT S. THARRATT, Associate Professor of Medicine and Chief, Section of Clinical Pharmacology and

Medical Toxicology, Division of Pulmonary and Critical Care Medicine, University of California, Davis Medical

Center, Sacramento

*Deceased, January 1998.

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Committee Liaisons

JUDITH H. LAROSA, Professor and Chair, Department of Community Health Services, Tulane University School

of Public Health and Tropical Medicine, New Orleans, Louisiana, and Liaison to the Board on Health Science

Policy

WARREN MUIR, President, Hampshire Research Institute, Alexandria, Virginia, and Liaison to the Board on

Environmental Studies and Toxicology

Study Staff

FREDERICK J. MANNING, Project Director

CAROL MACZKA, Senior Program Officer

C. ELAINE LAWSON, Program Officer

JENNIFER K. HOLLIDAY, Project Assistant (May 1997 through May 1998)

THOMAS J. WETTERHAN, Project Assistant (June 1998 through November 1998)

Institute of Medicine Staff

CHARLES H. EVANS, JR., Head, Health Sciences Section

ANDREW POPE, Director, Health Sciences Policy Program

LINDA DEPUGH, Section Administrative Assistant

JAMAINE TINKER, Financial Associate

National Research Council Staff

JAMES REISA, Director, Board on Environmental Studies and Toxicology

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Independent Report Reviewers

This 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 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 content of 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

participation in the review of this report:

JOHN D. BALDESCHWIELER, Professor of Chemistry, California Institute of Technology, Pasadena

DONALD A. HENDERSON, University Distinguished Professor, School of Hygiene and Public Health, Johns

Hopkins University, Baltimore, Maryland

DAVID L. HUXSOLL, Dean, School of Veterinary Medicine, Louisiana State University, Baton Rouge

JOSHUA LEDERBERG, Sackler Foundation Scholar, Rockefeller University, New York

H. RICHARD NESSON, Senior Consultant, Partners Health Care System, Inc., Boston

MICHAEL OSTERHOLM, Chief, Acute Disease Epidemiology Section, Minnesota Department of Health,

Minneapolis

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ANNETTA P. WATSON, Research Staff, Health and Safety Research Division, Oak Ridge National Laboratory,

Oak Ridge, Tennessee

MELVIN H. WORTH, Clinical Professor, State University of New York-Brooklyn and Uniformed Services

University of Health Sciences, and Institute of Medicine Scholar-in-Residence

The committee would also like to thank the following individuals for their technical reviews of single chapters of

the draft report:

ROBERT E. BOYLE, Formerly Technical Advisor, Chemical Warfare and NBC Defense Division, Office of the

Deputy Chief of Staff for Operations, Plans, and Policy, Department of the Army, Washington, D.C.

GREGORY G. NOLL, Hildebrand and Noll Associates, Inc., Lancaster, Pennsylvania

ROBERT S. PYNOOS, Professor and Director, Trauma Psychiatry Service, Department of Psychiatry and

Biobehavioral Sciences, University of California, Los Angeles

JOSEPH J. VERVIER, Senior Staff Scientist, ENSCO, Inc., Melbourne, Florida, and formerly Technical Director,

Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, Maryland

Although the individuals listed above have provided many constructive comments and suggestions, it must be

emphasized that responsibility for the final content of this report rests solely with the authoring committee and the

institution.

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Preface

American military forces have been struggling with the issue of chemical and biological warfare for decades—a

1917 National Research Council Committee laid the groundwork for the Army Chemical Warfare Service—but it

was the attack of the Tokyo subway with the nerve gas sarin in March 1995 that suddenly put the spotlight on the

danger to civilians from chemical and biological attacks. The Federal Emergency Management Agency (FEMA)

and the Department of Health and Human Services' Office of Emergency Preparedness (OEP), which is responsible

for medical services, have an admirable record of helping state and local governments cope with floods, storms, and

other disasters, including terrorism, but, fortunately, no direct experience with the consequences of chemical or

biological terrorism. In May 1997, the Institute of Medicine was asked to help OEP prepare for the possibility of

chemical or biological terrorism, and, with help from the National Research Council's Board on Environmental

Studies and Toxicology, formed this committee to provide recommendations for priority research and development

(R&D).

In the ensuing year and a half, the committee met four times, heard presentations on existing technology and

ongoing R&D, attempted to absorb a virtual mountain of information, and formulated their recommendations. In

the process, a number of things became clear to me. I suspect the rest of the committee would agree, but I will

exercise the chair's prerogative at this point, and share the view from my perspective.

First, there is no way to prepare in an optimal fashion for a terror incident. There is too low an incidence to justify

the enormous financial

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outlay it would take to optimally prepare every community for every possible incident. Furthermore, there are not

enough incidents for any community to acquire enough experience to make a significant impact on response to the

next episode.

Second, although there is a sophisticated technology, described within the body of the report, for in-line detection

of an opposing forces chemical agent, it will not be possible to select the sites to protect in a civilian setting with

such technology, even if the expense could be borne. At best, it might be possible to selectively protect a public

arena where the President was to give an address.

Third, there is no guarantee that the terrorist will announce the attack. Without such an announcement, there will be

no recognition that a biological attack is occurring until enough cases, including a number of fatalities, are observed

and reported to allow recognition of an epidemic of an unusual disease. Since exposed victims will almost certainly

not seek medical care in the same facility, the problem becomes compounded even more greatly. *

Fourth, virtually all the militarily important biologic agents present with early clinical symptoms that resemble viral

flu syndromes. Since these are the most common form of acute illness, and since they are usually mild and

nonserious, it is probable that the early victims of the attack will be unrecognized, and sent home from a physician's

office or Emergency Department as a mild viral syndrome. Therefore, in any response planning, it has to be

acknowledged that it will be impossible to prevent ALL mortality, no matter how good a technology can be

developed, and no matter how much money we are willing to spend to enhance our response.

Fifth, there is a huge gap between detection technology and therapy. There are many biologic agents, and certainly

many chemical agents for which there are no known treatments. We should not expect that terrorists will choose the

agents for which we are prepared, and for which we have effective treatment, even if they are the easiest to create

and disperse, such as anthrax or sarin.

Sixth, the approach that the committee found most useful to consider in making its recommendations was

considering how to superimpose a response

* For example, in Wyoming this year (Summer 1998), there has been an epidemic of E. coli diarrhea from a contaminated spring

that fed the water supply of the small town of Alpine. There were well over a hundred cases that involved 12 states since the

tourists who acquired the disease were from many different locations. It took at least two months to find the source of the

contamination, and the only reason that the epidemic was recognized as early as it was, is that there were only a small number of

medical facilities available to the victims.

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to a terror attack upon the systems that are already in place to deal with nonterror events. For example, an

earthquake, or a chemical spill, or a flu epidemic will all stress and often overload existing medical facilities. There

must be systems in place to deal with these problems, not only on a local basis, but when help must be brought in

from outside the afflicted area. These are the systems that will be most appropriate to build on for an effective

response to an incident of chemical or biological terrorism.

Seventh, communication between the medical community and agencies that gather and analyze intelligence about

potential terrorists and attacks is critical. As alluded to above, it will not only shorten the identification issues and

lead to more effective responses, but will clearly lower mortality.

There are a number of areas that will not be covered in this report. For example, it was not possible for the

committee to discuss every conceivable biological and chemical weapon that might be used in an attack. It is

probable that to prepare only for the list of known weapons and most likely agents will take a commitment and a

financial expenditure that will exceed the resources of virtually all communities.

The committee's charge did not include making recommendations on organization and training of individuals and

groups faced with managing the consequences of a chemical or biological incident, nor on how to equip such

persons or groups, nor on what therapeutic options they should choose. Nevertheless, as noted in our interim report,

the committee believes that it would be irresponsible to focus solely on R&D while ignoring potentially simpler,

faster, or less expensive mechanisms, such as organization, staff, training, and procurement. Examples from our

interim report include:

• Survey major metropolitan hospitals on supplies of antidotes, drugs, ventilators, personal

protective equipment, decontamination capacity, mass-casualty planning and training,

isolation rooms for infectious disease, and familiarity of staff with the effects and treatment of

chemical and biological weapons.

• Encourage the CDC to share with the states its database on the location and owners of

dangerous biological materials. State health departments in turn should be encouraged,

perhaps by education or training on the effects of the agents and medical responses required,

to add infections by these materials to their lists of reportable diseases.

• Convene discussions with FDA on the use of investigational products in mass-casualty

situations and on acceptable proof of efficacy for products where clinical trials are not ethical

or are otherwise impossible.

• Develop incentives for hospitals to be ambulance-receiving hospitals, to stockpile nerve-agent

antidotes and selected antitoxins and put

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them in the hands of first responders (this may require changes to existing laws or regulations in

some states), to purchase appropriate personal protective equipment and expandable

decontamination facilities and train emergency department personnel in their use.

• Supplement existing state and federal training initiatives with a program to incorporate existing

information on possible chemical or biological terror agents and their treatment into the manuals,

SOPs, and reference libraries of first responders, emergency departments, and poison control

centers. Professional societies and journal publishers should be recruited to help in this effort.

• Intensify Public Health Service efforts to organize and equip Metropolitan Medical Strike Teams

in high-risk cities throughout the country. Although MMSTs are designed to cope with terrorism,

because they use local personnel and resources, they also increase the community's general

ability to cope with industrial accidents and other mass-casualty events.

Even though the tasks of being prepared and responding adequately appear at times to contain insurmountable

obstacles, the committee does believe that by utilizing the resources that are present, along with improvements in

communications, monitoring capabilities, detection, and therapeutics, it will be possible to minimize the damage

that a terror attack will cause. It is not our intent to leave the readers of this report with feelings of hopelessness.

Even if preparation for certain attacks only forces the attackers to choose a weapon that we have not prepared for,

we will have developed a system with which we can improvise. The goal, as always in medicine, is to reduce

morbidity and mortality and minimize suffering.

In closing I would like to offer my sincere thanks to the staff of the Institute of Medicine, who made our meetings

as comfortable and efficient as possible and pulled our sometimes splintered efforts into a coherent whole, and to

the members of the committee, busy professionals who volunteered precious time and energy in a highly collegial

manner. It was a privilege to work with this outstanding group.

PETER ROSEN, M.D.

CHAIR

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Abbreviations

AChE Acetylcholinesterase

AEL Acceptable exposure limit

AIDS Acquired immune deficiency syndrome

APA American Psychological Association or American Psychiatric Association

ANL Argonne National Laboratory

ASTM American Society for Testing and Materials

ATP adenosine 5'-triphosphate

ATSDR Agency for Toxic Substances and Disease Registry

BAL British antiLewisite

BChE Butyrylcholinesterase

BDO Battle Dress Overgarment

BIDS Biological Integrated Detection System

BW Biological warfare or biological weapon

CAHBS Civilian Adult Hood Blower System

CAM Chemical agent monitor

CAPS Civilian Adult Protective System

CBDCOM Chemical Biological Defense Command

CBIRF Chemical Biological Incident Response Force

CBMS Chemical Biological Mass Spectrometer

CBNP Chemical and Biological Nonproliferation Program

CBPSS Chemical Biological Protective Shelter System

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C/B-RRT DoD Chemical/Biological Rapid Response Team

CBWCA Chemical and Biological Weapons Control Act

CCHF Crimean Congo hemorrhagic fever

CCP Crisis Counseling Assistance and Training Program

CDC Centers for Disease Control and Prevention

cDNA Complementary (or copy) deoxyribonucleic acid

ChE Cholinesterase

CISD Critical incident stress debriefing

CLS Commission on Life Sciences

CMHS Center for Mental Health Services

CN- Cyanide anion

CNS Central nervous system

CSEPP Chemical Stockpile Emergency Preparedness Program

CSTE Council of State and Territorial Epidemiologists

CW Chemical warfare or chemical weapon

CWA Chemical warfare agent

4-DMAP 4-Dimethylaminophenol

DARPA Defense Advanced Research Projects Agency

DHHS Department of Health and Human Services

DMAT Disaster Medical Assistance Team

DNA Deoxyribonucleic acid

DNTB 5,5'-dithio-bis (2-nitrobenzoic acid)

DoD Department of Defense

DoE Department of Energy

DRN Disaster Response Network

dsRNA Double-stranded ribonucleic acid

DSWA Defense Special Weapons Agency

EDTA Ethylene diamine tetraacetic acid (dicobalt)

EEE Eastern equine encephalomyelitis

EF Edema factor

EIDI Emerging Infectious Disease Initiative

EIS Epidemic Intelligence Service

ELISA Enzyme-linked immunosorbent assay

EMCR Electronic medical care record

EMS Emergency Medical Service

EMT Emergency medical technician

EPA Environmental Protection Agency

ERDEC Edgewood Research, Development and Engineering Center, U.S. Army

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FABS Force-amplified biological sensor

Fab Antibody fragment

FBI Federal Bureau of Investigation

Fc Crystallizable fragment (of antibody)

FDA Food and Drug Administration

FEMA Federal Emergency Management Agency

FOWG Fiber-optic evanescent wave guide

FTIR Fourier Transform Infrared Spectrometry

GA Tabun

GB Sarin

GC/FTIR Gas Chromatography Fourier Transform Infrared Spectrometry

GC/MS Gas Chromatography Mass Spectrometry

GC-MS-MS Gas Chromatography Tandem Mass Spectrometry

GD Soman

GF Cyclosarin

HAZMAT Hazardous materials

HD Sulfur mustard

HIV Human immunodeficiency virus

HMT Hexamethylene tetramine

HPAC Hazard prediction and assessment capability

HPLC High-performance liquid chromatography

HSEES Hazardous substances emergency events surveillance

IDLH Immediately dangerous to life and health

IMS Ion mobility spectrometry

IND Investigational new drug

IOM Institute of Medicine

IPDS Improved Chemical Agent Point Detection System

IU/L International units per liter

JCAD Joint Chemical Agent Detector

JCAHO Joint Commission on Accreditation of Healthcare Organizations

JCBAWM Joint Chemical Biological Agent Water Monitor

JLIST Joint Service Lightweight Integrated Suit Technology

JPOBD Joint Program Office for Biological Defense

JPOCD Joint Program Office for Chemical Defense