Biological Weapons Defense: Infectious Diseases and Counterbioterrorism

594 Pages·2005·5.334 MB·English

by  Anna Johnson-Winegar PhD, Karl Semancik COL (ret.) BS, MBA, Robert S. Borowski PhD (auth.), Luther E. Lindler PhD, Frank J. Lebeda PhD, George W. Korch PhD (eds.)

Biological Weapons Defense
I
n f e c t i o u s . D i s e a s e
SERIES EDITOR: Vassil St. Georgiev
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Biological Weapons Defense: Infectious Diseases and Counterbioterrorism, edited
by Luther E. Lindler, PhD, Frank J. Lebeda, PhD, and George W. Korch, PhD,
2005
Microbial Genomes, edited by Claire M. Fraser, PhD, Timothy D. Read, PhD, and
Karen E. Nelson, PhD, 2004
Management of Multiple Drug-Resistant Infections, edited by Stephen H.
Gillespie, MD, 2004
Aging, Immunity, and Infection, by Joseph F. Albright, PhD, and Julia W.
Albright, PhD, 2003
Handbook of Cytokines and Chemokines in Infectious Diseases, edited by Malak
Kotb, PhD, and Thierry Calandra, MD, PhD, 2003
Opportunistic Infections: Treatment and Prophylaxis, by Vassil St. Georgiev, PhD,
2003
Innate Immunity, edited by R. Alan B. Ezekowitz, MBChB, DPhil, FAAP, and Jules A.
Hoffmann, PhD, 2003
Pathogen Genomics: Impact on Human Health, edited by Karen Joy Shaw, PhD,
2002
Immunotherapy for Infectious Diseases, edited by Jeffrey M. Jacobson, MD, 2002
Retroviral Immunology: Immune Response and Restoration, edited by Giuseppe
Pantaleo, MD, and Bruce D. Walker, MD, 2001
Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New
Directions in Drug Discovery, edited by Philip J. Rosenthal, MD, 2001
Drug Interactions in Infectious Diseases, edited by Stephen C. Piscitelli, PharmD,
and Keith A. Rodvold, PharmD, 2001
Management of Antimicrobials in Infectious Diseases: Impact of Antibiotic
Resistance, edited by Arch G. Mainous III, PhD, and Claire Pomeroy, MD,
2001
Infectious Disease in the Aging: A Clinical Handbook, edited by Thomas T.
Yoshikawa, MD, and Dean C. Norman, MD, 2001
Infectious Causes of Cancer: Targets for Intervention, edited by James J. Goedert,
MD, 2000
II nn ff ee cc tt ii oo uu ss .. DD ii ss ee aa ss ee
Biological Weapons Defense
Infectious Diseases and Counterbioterrorism
Edited by

Luther E. Lindler,
PhD
National Biodefense Analysis and Countermeasures Center, Fort Detrick, MD,
and Department of Bacterial Diseases, Walter Reed Army Institute of Research,
Silver Spring, MD

Frank J. Lebeda,
PhD
Department of Cell Biology and Biochemistry,
US Army Medical Research Institute of Infectious Diseases,
Fort Detrick, MD
George W. Korch,
PhD
Director, National Biodefense Analysis and Countermeasures Center
Fort Detrick, MD
Forewords by
David R. Franz, COL (RET.), DVM, PhD
Florida Division, Midwest Research Institute,
Palm Bay, FL
Matthew Meselson, PhD
Belfer Center for Science and International Affairs,
Department of Molecular and Cellular Biology, Harvard University,
Boston, MA
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Cover Illustration: Images of macrophages infected with Bacillus anthracis spores. DiIC (3) labeled RAW264.7
16
macrophages (red) were infected with Green Fluorescent Protein-expressing spores of B. anthracis (Sterne strain) and
repeatedly imaged by confocal microscopy. Multiple separate focal planes were collapsed into a single fluorescence
images that were then overlayed into corresponding brightfield images. The frames shown here represent 5 h
postinfection. The green-colored spores develop into bacilli over the course of the infection. Image courtesy of Gordon
Ruthel, Wilson Ribot, and Timothy Hoover (United States Army Medical Research Institute of Infectious Diseases).
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Library of Congress Cataloging-in-Publication Data
Biological weapons defense : infectious disease counterbioterrorism / edited by Luther E. Lindler, Frank J. Lebeda, George Korch.
p. ; cm. -- (Infectious disease)
Includes bibliographical references and index.
ISBN 1-58829-184-7 (alk. paper)
1. Bioterrorism. I. Lindler, Luther E. II. Lebeda, Frank J.
III. Korch, George. IV. Series: Infectious disease (Totowa, N.J.)
[DNLM: 1. Bioterrorism--prevention & control. 2. Communicable Disease Control--methods. 3. Disaster Planning. WA 295
B615
2004] RC88.9.T47B544 2004
303.6'25--dc22
2004004125
Foreword
In 2003, the President’s budget for bioterrorism defense totalled more than $5
billion. Today, the nation’s top academic scientists are scrambling to begin work to
understand Bacillus anthracis and develop new vaccines and drugs. However, just five
years ago, only the US Department of Defense (DOD) seemed concerned about these
“exotic” agents. In 1997, the DOD spent approximately $137 million on biodefense to
protect the deployed force, while academe, industry, local governments, and most of
our federal leadership was oblivious to, and in some cases doubtful of, the seriousness
of the threat.
The National Institutes of Health (NIH) received the largest budget increase in the
organization’s history. Fortunately, during this time of national urgency, a sound base
exists on which to build our defenses against this new threat. A relatively small cadre
of dedicated scientists within the US Army Medical Research and Materiel Command
(USAMRMC) laid this foundation over the past 20 years.
While the nation as a whole slept, bacteriologists, virologists, immunologists, and
clinicians—both military and civilian—were busy studying the pathogenesis of
“exotic” organisms; developed vaccines, drugs, and diagnostics; educating health care
providers; supporting state and federal law enforcement in the development of
bioforensics; and contributing technical expertise to international arms control and
national defense policy. During the 1990s, as the nation’s military forces were being
downsized, the US Army Medical Research Institute of Infectious Diseases, the DOD’s
lead laboratory for medical biodefense, lost approximately 30% of its personnel
authorizations. Yet, the scientists within the command developed new vaccine
candidates and recombinant delivery systems for anthrax, smallpox, plague,
brucellosis, the botulium neurotoxins, and staphylococcal toxins along with the viral
encephalitides. They established the nation’s finest biological forensic diagnostics
capability, demonstrated the efficacy of an antiviral drug against smallpox, and led the
nation in medical biodefense education.
The dedicated scientists of the USAMRMC and the several other outstanding
contributors from the Centers for Disease Control and Prevention, academia, and
international organizations to this volume are recognized worldwide as experts in
biological weapons defense. They were hard at work in the laboratory before the public
even realized there was such a threat, and they stood in the gap for all of us after
October 4, 2001, when the United States experienced its first biological terrorism
attack in modern history. It was an honor for me to serve with them.
David R. Franz, COL (RET.), DVM, PhD
Florida Division
Midwest Research Institute
Palm Bay, FL
v
Foreword
Biological Weapons Defense: Infectious Disease and Counterbioterrorism focuses
on measures for dealing with the possible deliberate causation of disease and on the
underlying science. The fundamental advances in molecular biology of the last several
decades are only beginning to find relevant application in the development of effective
sensors, rapid early diagnostics, vaccines, antimicrobials, antitoxins, and other relevant
prophylactic, therapeutic, and supportive measures. Advances will also come with the
increased understanding of pathogenesis and of the mechanisms by which contagious
diseases spread from person to person, leading to improved practical measures to limit
outbreaks, including measures that can be taken by an informed public.
Such advances will certainly be useful against naturally occurring diseases,
including those that are newly emerging or re-emerging and, in the eventuality, against
deliberately caused disease as well. Still, experience suggests that practical applica-
tions available to the public, although sure to come, will most likely come at a slower
pace and at greater cost than legislators and the general public may expect. Unlike the
conquest of certain naturally occurring communicable diseases, effective protection
against deliberately caused disease will remain problematic.
All of the agents or groups of agents to which specific chapters in Biological
Weapons Defense: Infectious Disease and Counterbioterrorism are devoted were
selected as candidate biological weapons in the old offensive biological warfare (BW)
programs of the United Kingdom, the United States, and the Soviet Union. Some of
these agents were brought to the stage of mass production, were field-tested, and then
stockpiled in bulk and in munitions. It is remarkable how much of the technical base
was foreseen even before the big BW programs got underway, as exemplified, for
example, in the 1942 report of Theodor Rosebury and Elvin Kabat, declassified in
1947 and published that year in the Journal of Immunology (1). By 1960, much of the
technology of selecting, producing, and disseminating disease agents as weapons could
be found in the open literature. Aside from the novel and modified agents that can be
imagined, all of the “select agents” (except for smallpox) designated by the Centers for
Disease Control and Prevention remain accessible from clinics or natural foci. Even
so, despite the industrial-scale preparations that have come and gone and the hundreds
of wars and bitter insurgencies that have transpired in the past half-century, there has
been no BW, and only a few small-scale acts of bioterrorism or, more accurately,
biocrime.
Prudent measures to prepare for a major biological attack and to limit its conse-
quences are certainly in order. However, undisciplined speculation that a major bio-
logical attack is inevitable risks distracting us from measures intended to keep
biological weapons from coming into use in the first place. Inadequate attention is
being given to measures to sustain and reinforce the constraints that protect our species
from exploiting biotechnology for hostile purposes, as it has exploited other major
vii
Foreword viii
technologies (2). Whatever the underlying reasons that have averted BW and
bioterrorism, and whatever the factors that might disrupt this desirable state of affairs,
they deserve closer and more disinterested study and attention than they have received
so far.
As the old Western and Soviet programs recede into the past, the number of persons
with the specific knowledge and skills required to create devastating biological
weapons was rapidly declining. But some biodefense activities, especially secret ones,
have begun to reverse this trend by causing a new generation of scientists, engineers,
and others to turn their attention to vulnerabilities and conceivable future threat agents,
and hence to technologies with offensive potential. The expanded number of facilities
and individuals working with dangerous pathogens also makes access to these agents
easier, and the number of individuals who may become motivated to make hostile use
of them greater.
Beyond that, the impression of extensive secret work risks motivating other states to
initiate or expand secret programs of their own, further multiplying the pool of
potential security risks and perhaps verging into offensively oriented activities. Closer
to home, a further risk of secrecy in biodefense work is that it risks losing the
confidence of the public, essential to the actual implementation of protective measures.
The practice of public health traditionally rests on open discussion and public under-
standing in order to gain the acceptance and trust of those it is intended to benefit.
Considering the great and growing pervasiveness of biotechnology, the key element
in averting bioterrorism and biowarfare is not access but intent, whether on the part of
individuals, groups, or national governments. At the level of the individual scientist
and through our institutions and professional societies there is a modest but easily
practiced way in which we can address the element of intent. That is the customary
openness and professional amicability to which scientists are traditionally accustomed.
Scientific visits, exchanges, joint projects, studies abroad, development of personal
friendships across cultures and across national frontiers are intellectually and
professionally beneficial, as well as personally rewarding. Beyond that, the more
openness within a society as a whole, the more likely it is that improper activities
within it will come to light or, better, be discouraged in the first place.
Matthew Meselson, PhD
Belfer Center for Science and International Affairs
Department of Molecular and Cellular Biology
Harvard University
Boston, MA
REFERENCES
1. Rosebury, T. and Kabat, E. A. (1947) Bacterial Warfare. J. Immunol. 56, 7–96.
2. Meselson, M. (2002) Bioterror: What Can Be Done? In: Striking Terror. (Silvers, R. and
Epstein, B., eds.) New York Review Books, New York, NY, pp. 259–276.
Preface
The attacks on the World Trade Center (WTC) and the Pentagon and the first major use
of bioterrorism that coincided in the fall of 2001 are now infamous. The Al Qaeda
perpetrators of the horrible attacks on the WTC and Pentagon were clear in their intent.
However, to date we have not achieved a similar clear understanding regarding the
distribution of anthrax spores in the US postal system. We know neither exactly who
perpetrated this crime, nor the perpetrators’ exact intent. What is known is that the anthrax
letter attacks cost billions of dollars to clean up, caused major disruptions in the everyday
lives of countless citizens, undermined the trust and confidence that citizens have long held
in this bastion of everyday life, and resulted in the deaths of innocent citizens. The impact
was felt not only in the United States but also in countries around the world, as panic was
precipitated by the possibility of innocuous “white powder” being an infectious agent.
The scientists and leadership within the US Department of Defense (DOD) played a
unique role in mitigating this event by performing the initial identification of the infectious
material (anthrax) as well as advising and participating in the decontamination process in
the Hart Senate office building. Indeed, it can be argued that the DOD was the only federal
agency capable of fully responding to this threat at that time because of its long-standing
mission to provide the means to defend against a biological weapons attack. This critical
mission has now transitioned into the newly established Department of Homeland Security
(DHS).
The DOD biological defense program and similar defense programs in other countries
have long involved research aimed at countering the use of biological and chemical
weapons. The United States also had an active offensive biological program from the 1950s
until 1969, when it was terminated by President Nixon.
Given the experience and history of the defense-associated programs in the development
of countermeasures and in planning for future research in this area, Biological Weapons
Defense: Infectious Disease and Counterbioterrorismis heavily represented by researchers
who work within the biological defense community. However, we have also included
contributors from other communities, including academia, the Centers for Disease Control
and Prevention, the Department of Energy (DOE), and the Department of Health
and Human Services (DHHS). Most of these groups have been working with various
aspects of bioterrorism for the past four years. The intensity and urgency of those efforts
have increased since the 2001 attacks. Also, within the DHHS, funding has been greatly
increased for bioterrorism research and for the development of medical countermeasures. It
is anticipated that this increase in funding will yield further discoveries that will enhance
national defense.
Even with the warnings of experts and the years of funding and preparation for an act
of bioterrorism, the United States was not fully prepared for the anthrax attacks. Because
of the decades of research and development that DOD scientists and physicians had
accomplished in the treatment, prevention, and diagnosis of these rare diseases, many
individuals and research centers within the DOD were asked to “step up” in that time
ix
x Preface
of national crisis. This is an indication of the professionalism and capabilities of this
relatively small group of people. It was against this backdrop that Biological Weapons
Defense: Infectious Disease and Counterbioterrorism was written. The purpose of this
volume is to cover many aspects of the defense against biological agents that we, as mem-
bers of the human community, must address on a continuing basis. We have divided this
volume into four parts that concentrate on the major areas of interest and research.
Part I, “Preparation and Military Support for a Possible Bioterrorism Incident,” provides
the reader with a view into the behind-the-scenes efforts that many people might not be
aware of because they are outside the government network. This includes the policy and
laws that govern the DOD and its programs. We have also included aspects of event
modeling as well as a general description of the diseases of greatest concern.
Part II, “Medical Countermeasures and Decontamination,” gives an account
of general knowledge of these particular diseases including pathogenesis, treatment, and
the unique aspect of studying the aerosol route of infection.
Part III, “Emerging Threats and Future Preparation,” could have easily been titled
“future directions.” The number of nefarious manipulations or discovery of previously
unknown threats that might be developed into biological weapons is almost unlimited. This
section informs readers of these threats and describes some of the ongoing research that
attempts to counter these unknown agents. This section includes genomic efforts, which
describe the current rapid pace of information that is gleaned from analysis of the genomes
and proteomes of these agents. Following the anthrax letters, there has been a continuing
effort by the National Institutes of Health, DOD, and DOE in the area of biodefense
genomics. This research has the potential to accelerate many aspects of preparation against
the use of biological weapons, including future threats, diagnostics, therapeutics,
vaccinations, pathogenesis, genotyping, and forensics.
Finally, Part IV, “Diagnostic Development for Biowarfare Agents,” discusses the many
aspects of the development and use of our current technology to identify and characterize
these infectious organisms.
Although it was not possible to cover every aspect of biodefense in this volume, we hope
readers will gain a greater understanding of the diseases caused by these organisms and
develop a sense of the scope of issues that must be overcome to develop necessary medical
countermeasures to bioterrorism. Readers should also understand the status of current
programs and future plans regarding specific diseases as well as future technology or future
threats.
A quote from retired US Army Major General Phillip K. Russell could be considered a
theme for this book: “Deficiencies in our scientific knowledge and a paucity of experts will
ultimately limit our capability to rapidly and precisely identify agents and respond
effectively in a crisis” (1). Biological Weapons Defense: Infectious Disease and
Counterbioterrorism is intended to give readers a sense of where we are on this issue and
where we are moving in the future. We hope that you will find our book informative.
Luther E. Lindler, PhD
Frank J. Lebeda, PhD
George W. Korch, PhD
REFERENCES
Russell, P. K. (1997) Biologic terrorism—responding to the threat. Emerg Infect. Dis. 3, 203–204.