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Making the Nation Safer: The Role of Science and Technology in Countering Terrorism (2002)

Chapter: 3. Human and Agricultural Health Systems

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Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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3
Human and Agricultural Health Systems

INTRODUCTION

Biological pathogens (for example, anthrax bacteria or the smallpox virus) or toxins produced by biological organisms (for example, botulinus toxin or staph enterotoxin) that are released intentionally or accidentally—or that occur naturally—can result in disease, fear, disruption to society, economic harm, diminished confidence in public and private institutions, and large-scale loss of life.

People or livestock can be exposed to these agents from inhalation, through the skin, or by the ingestion of contaminated food, feed, or water. After exposure to a pathogen or toxin used as a biological weapon, physical symptoms can be delayed and prove difficult to distinguish from naturally occurring illnesses. Similarly, crops can be exposed to biological weapons in several ways—at the seed stage, in the field, or after harvest.

The deciphering of the human genome sequence and elucidation of the complete genomes of many pathogens, the rapidly increasing knowledge of the molecular mechanisms of pathogenesis and of immune responses, and the development of new strategies for designing drugs and vaccines offer unprecedented opportunities for using science to counter bioterrorist threats. But these advances also allow science to be misused to create new agents of mass destruction.

Two kinds of biological terrorist threats must be envisioned. The first is the release of communicable infectious agents—like smallpox, Ebola, or foot-and-mouth disease—that can spread rapidly within communities and farmland through contact and have the potential, as does influenza, to spread around the world and cause epidemics. The second kind of threat consists of biological agents that may cause disease or death in individuals but generally may not be transmitted between

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

individuals—the most familiar example being anthrax. In either case, some agents may persist in the environment, as do anthrax spores, and continue to cause problems long after their release.

In addition to naturally occurring pathogens, biological agents used offensively can be genetically engineered to resist current therapies and evade vaccine-induced immunity. Though it is vital that the molecular mechanisms by which classes of organisms cause disease (pathogenesis) be elucidated in order to understand and counter their effects, this is no simple matter. Preparedness for a biological attack against people, crops, or livestock is complicated by the large number of potential agents, the long incubation periods of some agents, and their potential for secondary transmission.

Biological agents do not need to be weaponized for effective dissemination. Deliberate contamination of food looms as perhaps the easiest method, despite the recent focus on release of these agents as small-particle aerosols or volatile liquids. Moreover, because of its size and complexity, the U.S. food and agriculture system is vulnerable to deliberate attacks, particularly with foreign diseases that do not now occur domestically. Even without actual attack, plausible threats to infect populations or poison the food supply could, in and of themselves, damage the U.S. economy and reduce public confidence in the government’s ability to safeguard health and security.

Recent experiences with the West Nile virus and anthrax spores in the United States, and with foot-and-mouth disease in the United Kingdom, offer practical lessons in human and agricultural outbreak detection, laboratory diagnosis, investigation, and response that might be useful in planning for future attacks involving biological terrorism (Fine and Layton, 2001). The experience with the West Nile virus outbreak highlighted the importance of communication and coordination between responding agencies (U.S. General Accounting Office, 2000). The GAO study noted that although the system worked, there were several obvious places for improvement. A single alert physician at a local hospital initiated the investigation early enough that an effective intervention was possible before the outbreak became widespread, but the investigation subsequently found many other cases, which were either not properly diagnosed or not reported to the health department. The GAO report concluded that much more systematic surveillance and reporting at the local level is needed. Similarly, improved communication among public health agencies, including those dealing with animal health, is needed. Increased laboratory capacity will also be important to an efficient and effective response to disease outbreaks (at first only one public health laboratory in the country was equipped to diagnose West Nile virus) (IOM, 2002). Moreover, these events raise vexing concerns about how many outbreaks could be managed at one time.

The attacks of September 11, 2001, and the intentional release of anthrax spores shortly afterward also revealed vulnerabilities that are the results of long-term declines in the nation’s public health and agricultural infrastructures. The

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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decline in the U.S. public health system is the result of its systematic dismantling over time by Congress and the executive branch. In fact, the response of the Centers for Disease Control and Prevention (CDC) to the anthrax attacks was admirable given its limited resources and outdated communications system. CDC, together with state and local health departments, has provided this nation with an outstanding cadre of people who understand how to perform surveillance, prevention, and detection of infectious agents, whether they are endemic, emerging, or a result of bioterrorism. These agencies must be supplied with the tools and resources taken away from them in the past. Restoring the public health system of the United States should be the first order of business in the efforts to defend the nation against bioterrorism.

The Need for Approaches with Multiple Benefits

Bioterrorism poses a unique challenge to the security of the U.S. population. A state-sponsored enterprise, or just a few individuals with specialized scientific skills and access to a laboratory, could easily and inexpensively produce a panoply of lethal biological weapons, although it is no trivial matter to disseminate or disperse such agents across large populations. Such operations may be difficult to detect because, in contrast to nuclear weapons, biological agents can be manufactured with ordinary pieces of equipment that are listed in commercial catalogues and are legitimately purchased for producing such things as chemicals, pharmaceuticals, or even beer.

Fortunately, investments made to protect the country against bioterrorism will help protect the public’s health and the U.S. food supply from naturally occurring threats as well. Although it may be difficult to distinguish an introduced infectious disease from a naturally occurring one, the strategies to protect against either—requiring preparation and new scientific and technological approaches to surveillance, prevention, response, recovery, decontamination, and forensics—must be the same. Similarly, investments made to protect the country’s food supply against bioterrorism have the potential, and are even necessary, to protect it from more routine threats as well. Because the most likely break-throughs will come from the study of both pathogenic and nonpathogenic bacteria and viruses, they should be studied together—indeed, the study of bioterrorism agents alone is likely to give a low return on investment.

There are also indirect benefits associated with investments in protecting ourselves from bioterrorism. Money spent on research to develop new types of sensitive detectors and related monitors for biowarfare agents will almost certainly carry over to the public health sector in the form of rapid, improved diagnostics for disease. Money spent on coordinating and developing emergency response teams at the federal, state, and local levels will also bring better mechanisms for dealing with natural outbreaks of emerging diseases. Money spent on innovative surveillance approaches for detecting biowarfare attacks should improve

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

medical epidemiology. Money spent on vaccine research and delivery may help to buttress our limited capacity to protect civilian and military populations.

Changing Research Paradigm

While this report was being prepared, the National Institute for Allergy and Infectious Diseases (NIAID) released a bioterrorism research agenda for rapidly addressing the most threatening biological agents (NIAID, 2002).1 Though important and commendable, this agenda lacks several major components—such as surveillance strategies, epidemiology of transmission, and the entire range of agricultural threats—needed for a comprehensive plan to counter bioterrorism. Consideration must also be given to preparing for still-uncharacterized threats and to assuring investment in long-term, broad-range strategies. These gaps must be filled, where not appropriate for NIAID action, by other federal agencies. CDC is the logical place for surveillance efforts, given its expertise, and therefore it will require additional resources.

NIAID’s expanded role in bioterrorism research demands a focused effort to coordinate activities with other agencies—CDC, the Department of Defense (DOD), the Department of Energy (DOE), the Environmental Protection Agency (EPA), the U.S. Department of Agriculture (USDA), and the very recently proposed new Department of Homeland Security, for example. All of the governmental entities must seek expertise from private organizations, such as industry and professional societies with relevant expertise, for example, the Infectious Diseases Society of America and the American Society for Microbiology. It also demands that NIAID’s parent, the National Institutes of Health (NIH), find new mechanisms to fund research in this area, particularly for taking on long-range, highly managed, higher-risk projects and for moving the research at a faster pace. Likewise, CDC’s role is critical to the nation’s preparedness, but it must have the resources to improve its focus, strengthen its extramural capacity, and extend its international collaborations. National security also depends on public-private sector cooperation and communication and on an increased willingness to collaborate.

Organization of This Chapter

This chapter is organized into three sections: (1) intelligence, surveillance, detection, and diagnosis; (2) prevention, response, and recovery; and (3) policy and implementation. Each section describes the desired capabilities that could soon exist through better application of existing science and technology (and that might therefore have a near-term payoff) as well as desired capabilities that

1  

See March 14, 2002, press release “NIAID Unveils Counter-Bioterrorism Research Agenda” at <http://www.niaid.nih.gov/newsroom/releases/biotagenda.htm>.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

cannot now be provided through existing science and technology (S&T) but might be available in the future, given longer-term research and possibly more innovative funding and organizational approaches. The chapter focuses on research needs related to both human and agricultural health. Many of the recommendations apply equally to both areas while others are specific to one area or the other. In general, recommendations focus on R&D goals or organizational goals. The chapter concludes with recommendations about education and information dissemination, strengthening the public health and agriculture infrastructures, and organizing the research and development effort through improved policies, new funding models, and public–private partnerships.

INTELLIGENCE, DETECTION, SURVEILLANCE, AND DIAGNOSIS

A comprehensive approach to coping with bioterrorism must incorporate efforts to prevent the proliferation of biological weapons; methods for detecting covert biological weapons programs; strategies for deterring their use if biological weapons do proliferate; and mechanisms for protecting civilian and military populations if deterrence fails. The emphasis in this multitiered approach should be on defense, simply because the proliferation of biological weapons is difficult to control (biotechnology equipment and expertise are now available globally), covert biological weapons programs (e.g., those of the former Soviet Union and Iraq) are difficult to detect, and deterrence will likely be less effective against suicidal terrorist groups than against states. Consequently, in addition to improving intelligence and information management, the S&T community should be focused on improving defenses against biological weapons. The means to do so include environmental detection of biological agents together with preclinical, clinical, and agricultural surveillance and diagnosis.

Intelligence and Information Management

Increased awareness in the S&T community could reduce the inadvertent spread of knowledge that may aid terrorists, although there is a fine balance that must be achieved so as to not quash legitimate exchange of scientific information. Voluntary international and national efforts to share biotechnology information could improve security and safety in the handling, storage, and transport of sensitive biological material and equipment. Information technology could help monitor international trafficking in biotechnology products.

Detection of covert programs will involve technical intelligence (e.g., remote sensing and environmental sampling) as well as human intelligence, which has special importance because it can distinguish the benevolent use of biotechnology from the malevolent. Understanding intent in the area of biotechnology, which requires familiarity with S&T culture, processes, and procedures, is an expertise that scientists and technologists can offer the intelligence community.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Meanwhile, there is a need to teach, reinforce, and strengthen ethical standards of the S&T community against the production and use of biological weapons; this will reduce the likelihood of scientists working in covert programs and increase the chance of them helping to abort malevolent efforts.

Although much has been written about the potential efficacy (or inefficacy) of ways to deter biological attacks, the S&T community has yet to fully explore means for strengthening deterrence. An obvious option is biological forensics (discussed later), because without reliable attribution, most deterrence strategies are likely to fail. Nucleic acid sequence databases for pathogen strain types and advances in chemical-trace analysis and the use of taggants will help the process of attribution, thus discouraging terrorism, but they will by no means guarantee that perpetrators can be identified.

The greatest potential benefit of a counterterrorism strategy might derive from preemptive efforts at earlier points in the bioterrorism-attack timeline—that is, the evolution of a bioweapons program from inception through weapon deployment, before any biological agent is released. The S&T communities have had relatively little input into detection and characterization of terrorist activities during this early stage, yet they could offer significant untapped resources. Opportunities for their involvement in the area of human intelligence should be explored (see Box 3.1).

BOX 3.1
Opportunities for Integrating the Intelligence and S&T Communities

Short Term

  • Recruit members of the S&T community for assistance and advice on the collection and early analysis of relevant human intelligence in bioterrorism activities.

  • Promote collaborative research programs that enhance contact between members of the S&T community and scientists from former or current biowarfare or bioterrorism research programs (e.g., cooperative research programs).

  • Develop a database for locating bioterrorism or related expertise in academic and industrial laboratories.

Long Term

  • Recruit and train intelligence analysts in state-of-the-art biology, microbiology, and bioinformatics.

  • Train or sensitize working scientists to recognize malevolent intent, as well as signatures of offensive bioweapons programs, and develop a plan for sharing this information with appropriate parties.

  • Facilitate the development of tools for aiding in the recognition of such signatures.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Recommendation 3.1: All agencies with responsibility for homeland security should work together to establish stronger and more meaningful working ties between the intelligence, S&T, and public health communities.

Identification of Biological Agents in the Environment

At the present time, efforts to identify biological agents in air, soil, and water samples have had only limited success. Ideally, one would hope to be able to collect air samples, for example, and identify a pathogen in those samples in near real time, allowing the population to be warned of the pathogen’s presence. However, existing technologies for rapid and reliable detection (collection and identification) of bioagents have not been widely evaluated or well validated in real-world settings. Much greater attention must therefore be given to the transition between basic laboratory research and field application.

Traditional laboratory approaches include microbial cultivation, immunological (e.g., antibody-based) assays, and nucleic acid detection schemes, especially amplification methods such as the polymerase chain reaction (PCR). The last two approaches seek molecular evidence of agent components, such as characteristic immunological markers and genome sequences. A fourth broad approach relies upon the response of a surrogate host—such as cultivated cells from humans, animals, or plants.

Each of the four approaches has its advantages and disadvantages. It is important to note, however, that even though cultivation is slow, limited in scope (by ignorance of appropriate growth conditions in the test tube and in human tissues for many pathogens), and the least technologically sophisticated approach, it provides the most ready assessment of complex microbial phenotypes (behaviors), such as drug resistance. It also is the most widely used approach in laboratories throughout the world, especially in developing nations, and hence is currently the most common identification method for international surveillance.

A number of challenges must be addressed in order to develop and implement effective methods of environmental identification. An improved understanding of natural background is needed, regarding both the agent (including genetic, antigenic, geographical, and temporal variations) and the setting (including related agents and inhibitors). Additionally, standards must be established by which sampling and detection methods can be rigorously evaluated, validated, and standardized (see Recommendation 3.16 and surrounding discussions). Centralized repositories of diverse, high-affinity binding and detection reagents (e.g., antibodies, peptides, oligonucleotides) should be established, as well as repositories of genomic material and control samples. There are dozens of ways to identify bioterrorism agents that are sensitive and accurate. However, agreement on how a few well-developed platforms are implemented would allow the data to be broadly understood and make the limitations of the test used apparent to all.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

For example, whether one is identifying anthrax on the farm, from the environment, or in a patient’s blood stream, the identification can be quickly made using a fairly easily agreed upon set of standard genomic and immunological reagents. Subsequently, there must be cultures of microorganisms grown in the laboratory using agreed upon standard methods. The identification should be based on uniform standards and not a free-for-all depending on program officers or agencies with differing views.

To date, a disproportionate amount of the effort in the bioagent detection arena has been focused on the development of technology platforms. Efforts on standardization or validation of sample collection and sample processing procedures, as well as on test validation in a real-world setting, have had much lower priority. But the use of genomic and proteomic information, as well as the development of robotic sensing devices that can communicate signals from many environmental sites, offers new possibilities for the early detection of biologic agents in the environment. It also increases the risk of false alarms when sophisticated analysis and decision-making systems are lacking.

Another challenge involves creating broad-spectrum detection tools and methods. Currently a large number of tests rely on a small number of specific antibodies or microbial genomic sequences. This reliance creates vulnerabilities—for example, with respect to bioagents having modified antibody epitopes (binding sites) or sequences. Rather than relying on methods that target specific, known organisms, one would like to have detection methods that target groups of organisms (i.e., all members of these groups) and that can identify specific members of the group, including recognition of those that may not yet have been characterized. Although there are experimental challenges, the expertise exists to immediately begin addressing these problems (Cummings 2000, 2002; Nikkari et al., 2002).

A further challenge is the need for highly sensitive systems, as some highly infectious pathogens require the inhalation of only 1 to 10 organisms to cause disease. In general, much greater attention is needed to translate basic laboratory research into field applications and clinical validation (standards will play an important role; see Recommendation 3.16 and surrounding discussion). Finally, because no test is perfect, it is important to be able to anticipate false-positive test results in a reliable and quantitative fashion. One potential strategy for minimizing the impact of false-positive test results is to create a system of multiple, parallel, independent technical platforms so as to avoid dependence on any one testing procedure. This requires crosscutting, interdisciplinary science (e.g., combining environmental microbiology, cell biology, biophysics, electronics, materials science and microfabrication, microfluidics, and bioinformatics/statistics) and would require collaboration between several federal agencies and industry. However, even the currently available tests could be made significantly more useful by adopting a quality assurance index that would be applied to any positive test result. For example, single positives in tests with high false-positive rates, such

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

as ELISA, would receive a low ranking, whereas successful culture of a known biological agent from a sample would receive the highest ranking. Informed decisions on public action could be made based on the quality of the result rather than simply on the presence of a positive result.

Recommendation 3.2: Federal agencies should work cooperatively and in collaboration with industry to develop and evaluate rapid, sensitive, and specific early-detection technologies.

The types of identification systems needed are likely to be developed by industry, not in an academic laboratory. Federal funding agencies can speed this process by supporting the early stages of the work. The same kind of milestones should be applied to this kind of work as are used in industry to ensure that the technology is valid and meets the expected specifications. There is a role for the mobilization of established detection procedures and for those that might be second-generation detecting devices sometime in the future. The immediate need is acute and very attainable.

Surveillance and Diagnosis of Infection and Disease

Early diagnosis of patients infected with potential biological warfare (BW) agents is complicated by the lack of relevant medical experience with most of these agents in the United States and by the nonspecific symptoms of their associated diseases (e.g., many cause flulike symptoms in the early stages). Systems for effective surveillance and diagnosis of biothreat agents, as well as of many naturally occurring and emerging pathogens, are either unavailable at present or inadequate.

Many of the current challenges in surveillance and diagnosis are quite similar to those described above for identification of pathogens. Surveillance and diagnosis must also address the important distinction between infection and disease—that is, between the colonization or contamination of a host with a potential biothreat agent and the actual manifestation of pathology (disease). Sensitive and specific diagnostic tests are important adjuncts to clinical diagnosis; however, such tests cannot substitute for astute clinical recognition of symptoms to raise the suspicion of a particular diagnosis. Equally vital is the role of classical epidemiological analysis in assessment and recognition of human- and animal-disease patterns.

Preclinical Surveillance and Diagnosis

It would be critical, in the event of a biothreat agent attack, to be able to recognize or identify infected persons, animals, or plants before they develop overt disease. Great benefit could be achieved by rapid intervention in those persons, animals, or plants known to be infected, while avoiding unnecessary

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

intervention in those who are not. It is at this stage that the difficulties and challenges of diagnosis are greatest as well. In recent years, novel biotechnological and biological approaches have opened up new opportunities in this area.

In the interim, while new approaches are developed and refined, assessment of white blood count, fever, and relatively simple observations will remain the first line of defense in protecting human health. A primary focus of diagnostic strategy will continue to be the continuing education of physicians and health-care workers.

An example of a plausible new technological approach is the host-genome-wide gene-expression profile. The availability of a nearly complete human-genome sequence and the power of DNA microarray technology have been harnessed to create an approach for surveying the responses of nearly all known human genes to various infectious agents. Cells are programmed to recognize pathogenic agents and foreign life forms, and they respond with changes in hostgene expression; microbial agents, meanwhile, have evolved strategies for manipulating and subverting these programmed responses. The result is an intricate, choreographed, and time-dependent set of induced and repressed gene-expression patterns that can be detected in small blood samples (Cummings and Relman, 2000).

Although the dominant features of these patterns are common to virtually all infections, regardless of the particular infectious agent, other features may be more specific to the agent or disease. With further research and refinement, one might actually be able to distinguish infections by different pathogens and generate signatures that allow early identification. These patterns reflect how the host “sees” the pathogen, and they also reflect (and perhaps predict) the outcome of the host-pathogen interaction. Research exploring the potential usefulness of this approach is still in its early phases, however.

Host-gene expression patterns are just one complex biological pattern that might lend itself to this kind of diagnostic and prognostic approach. Others include patterns of secreted proteins in host fluids, volatile compounds in breath (analyzed, for example, with mass spectroscopy), and spectral features of host cells and fluids (studied using spectrometers and hyperspectral analysis). The enormous advantage of such technology, should it be able to fulfill researchers’ expectations, is that it could distinguish genuine infection from hysteria or terror, either at the emergency room or in the clinic.

Human Disease Surveillance and Diagnosis

In this country and elsewhere, the recognition of almost all emerging infectious diseases—both naturally occurring and intentional—has depended on an astute clinician contacting a public health agency after suspecting an unusual serious illness (e.g., hantavirus in the Southwest or anthrax in Florida). This traditional system of notifiable human disease surveillance depends on the train-

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

ing of physicians and other health care providers, in terms of both disease awareness and their responsibilities to public health. In addition, the important systems linking hospitals around the country with CDC, known as sentinel surveillance systems, need to be enhanced; they can establish whether a common cause of disease is being seen simultaneously in multiple regions. Research should be conducted on the strategies likely to be most useful in enhancing the notifiable human disease reporting system for the broad range of potential threat agents (strategies such as education, animal sentinels, changes to the surveillance systems, and the use of infection control specialists). Mathematical models of disease transmission and distribution using simulations of a covert release of various agents could be helpful in assessing the potential and relative value of different surveillance systems. An integrated national system that can report diseases electronically in real time is needed to support these networks. Information technology advances should be explored both to automate required reporting (e.g., laboratory reporting of pathogens) and to develop new surveillance tools (e.g., the automated scanning of electronic media, such as that utilized by the Global Public Health Information Network).

Systems of syndrome surveillance—that is, screening for changes in the frequency of cases of flulike illness seen in hospital emergency rooms across a city or town—should be developed to identify outbreak patterns. Relevant computer programs are being developed, but there are known fluctuations in emergency room admissions from season to season and day to day, and it will be important to determine their potential predictive value, specificity, and usefulness. Syndrome surveillance has allowed early recognition of some respiratory and diarrheal disease outbreaks, but it is not clear whether it will be useful for early detection of key threat agents such as smallpox, anthrax, and tularemia.

Because infectious diseases do not respect national borders, international cooperation is vital in the sharing of epidemiological and clinical data, both on emerging infectious diseases and on outbreaks caused by potential bioterror agents. A global network for surveillance of infectious diseases in humans and animals would be strengthened by augmenting the numbers and capabilities of U.S. overseas laboratories and by providing enhanced support for current initiatives on international surveillance (e.g., DOD’s Global Emerging Infectious Diseases program and corresponding Department of Health and Human Services (HHS) initiatives).

Increased support for the development and expansion of public health and agricultural laboratories in other countries, particularly in their capacity to diagnose threat agents, would yield dividends for recipient and donor alike. This means that CDC and other agencies must reach out to educate, train, and collaborate with scientists from many countries on aspects of surveillance and identification of threats. The World Health Organization could play a critical role in building and strengthening international capabilities.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Recommendation 3.3: Create a global network for detection and surveillance, making use of computerized methods for real-time reporting and analysis to rapidly detect new patterns of disease locally, nationally, and—ultimately—internationally. The use of high-throughput methodologies that are being increasingly utilized in modern biological research should be an important component of this expanded and highly automated surveillance strategy.

Another important area for applied research is the development of improved clinical diagnostics—rapid assays for the detection of common pathogens and BW agents—that could be used in primary care settings as well as referral laboratories. In addition, the kinds of needs that were described above for preclinical detection also apply to the field of clinical diagnostics. Standards are needed by which diagnostic methods and technology can be rigorously evaluated and validated, and centralized repositories of standardized reagents and samples are needed as well. Because the development and evaluation of diagnostics require interdisciplinary applied research, it is currently difficult to find targeted sources of support for these efforts. NIAID, CDC, and USDA should consider providing extramural funding programs to stimulate research in this area.

Because of the low likelihood of infections with BW agents compared to common, widely circulating agents like influenza viruses, routine application of rapid diagnostics for potential BW agents in a primary care setting in the absence of clinical suspicion will face problems with false-positive and false-negative results, for which rapid adjunctive standards do not exist. A triage system could be applied in which patients with relevant symptoms who test negative for a panel of expected pathogens would be sent to a referral laboratory for a second round of diagnostic tests, which could include suspected BW agents and broad-range methods.

High-throughput automated laboratory technology can now be applied to assist in these efforts. Positive samples could be forwarded to central public health laboratories for more comprehensive characterization. A laboratory designed, for example, to address influenza surveillance (Layne et al., 2001) could be dual use: Not only would it enhance public health by providing more accurate and timely information about the emergence of novel influenza strains, but it could also provide surge capacity to detect other agents if outbreaks occurred as a result of a terrorist attack. Continued development of effective networks of such referral laboratories (private, academic, local, state, and federal) is thus vital.

It should be noted that the first suspicion of the outbreaks of anthrax and of West Nile virus came not from sophisticated computer technology but from thoughtful and perceptive physicians. Tools to help all health professionals make the appropriate inferences from small numbers of patients must be developed so that the likelihood of missing a new outbreak is markedly reduced. Principal responsibility for this work should rest with CDC, NIH, and DOD.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Recommendation 3.4: Use knowledge of complex biological patterns and high-throughput laboratory automation to classify and diagnose infections in patients in primary care settings.

Agricultural Surveillance and Diagnosis

The protection of the nation’s food supply presents several unique challenges related to surveillance and diagnosis of disease. The U.S. livestock industry, with revenues of approximately $150 billion annually, is extremely vulnerable to a host of highly infectious and often contagious biological agents (insects and other pests, viruses, and microbes) that have been eradicated from the United States. Unlike traditional biological agents that can be used against humans, many of these animal-targeted agents need not be weaponized to cause an outbreak. Their simple point-introduction into herds could immediately halt all movement and export of U.S. livestock and livestock products.

Although most agents that affect animals are not human pathogens, introduction of any of the agents on the A List of the World Organisation for Animal Health would have wide-ranging and devastating impacts on the U.S. economy—not to mention psychological effects on the country’s human population—from which it could take years to recover. These disease agents are readily available in many countries. Although USDA’s Animal and Plant Health Inspection Service (APHIS), as currently constituted, has proven adequate for naturally occurring disease, it would probably be unable to help eradicate intentional introduction, especially if this were done at multiple sites. There is a need for USDA to develop a research and surveillance capability for plant and animal diseases comparable to the one that CDC oversees for human diseases.

Animal agriculture would seem to be increasingly vulnerable to intentional biological attacks, given recent trends toward concentration and specialization in the livestock industries (MacDonald et al., 1999). For example, tens of thousands of animals can be housed in relatively close quarters in concentrated feedlots prior to slaughter. If the introduced agent is highly contagious, as is the foot-and-mouth disease virus, this concentration creates the potential for greater impact from a single infected animal, as aerosol transmission of pathogens is common within herds. Likewise, animals move across great geographic distances. For example, during September 2001, nearly a million of the swine imported into Iowa came from 24 states and Canada (communication from the Iowa State Department of Agriculture).

Given these vulnerabilities, there is a need to recognize an infected animal immediately. At present, however, although there are well-operated state and federal animal diagnostic laboratories, there is no integrated national system that can report diseases and infestations electronically in real time. In addition, there are no rapid field diagnostic assays for most animal pathogens and pests.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Crops, too, are vulnerable. They are grown over very large areas (e.g., some 75 million acres for soybeans) and there is very little surveillance or monitoring. Likewise, plant diagnostic laboratories are scattered across the country and are underresourced and understaffed. In addition, great variability exists in the capabilities of these laboratories from state to state. This situation means that a long time could elapse from the introduction of a crop pathogen to its detection. Remote sensing, particularly satellite imagery, may have value in monitoring crops for disease outbreaks, including those resulting from bioterrorism.

Other factors heighten the vulnerability of U.S. crops: (1) many hybrid crop species exhibit low levels of genetic diversity; (2) there are few restrictions on trade, and large volumes of agricultural products are imported and exported each year; (3) a substantial proportion of the seed used for growing U.S. crops is produced in other countries, presenting a possible route for the introduction of dangerous plant pathogens as well as contaminated fertilizers and pesticides; (4) fungi, viruses, and bacteria cause more than 50,000 diseases of plants in the United States; (5) for any given crop, there are several pathogens that are not yet found in the United States but that cause major losses elsewhere; and (6) the biological agents that could affect crops are more numerous than the pathogens that affect humans, making it more difficult to focus the research funding available for efforts to counter agricultural bioterrorism.

Threats to crops intersect with threats to livestock in the case of animal feed, and there is a particular concern about the timing of ultimate effects. The delay between the time at which a bioterrorist contaminates animal feed and the time the human food product becomes adulterated would cause more uncertainty about the source of the contamination and could minimize the possibility of apprehending the terrorist. The less obvious and the more natural the source of biological contamination, the greater the likelihood that the contamination of the animal feed will be mistaken as a natural phenomenon. Rapid testing of feed and separation of contaminated feed are important steps, followed by the more specific identification of the contaminant to determine the source of adulteration and the possibility of decontamination. The development of specific antibodies for the production of sensitive and specific test kits is the key to identifying contamination. This would allow one to deal effectively with the disposal or decontamination of the animal feed and, ultimately, to prevent the contamination of animal-derived human food products (Von Bredow et al., 1999).

Rapid containment of agricultural pathogens is dependent on an effective system for diagnosis and the coordinated action of various state and federal agencies. Although these agencies, including USDA’s APHIS, have dealt successfully in the past with the natural introduction of several foreign pathogens of plants and animals, they are not properly organized to deal with the massive, multiple introductions that terrorists are likely to attempt. In essence, the game has changed, and this requires a substantial restructuring of the nation’s agricultural response systems.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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Recommendation 3.5: USDA should create an agency for control and prevention of plant disease. This agency should have the capabilities necessary to deal effectively with biothreats.

For animal disease, USDA operates several laboratories—Plum Island and Ames among them—that perform diagnoses, carry out research, and provide training for veterinarians. CDC is the central agency for the control and prevention of communicable human disease, but no center currently exists to serve the same function for plant disease. Such a center is desperately needed.2 Departments of plant pathology at various state universities, APHIS, and a wide variety of other agencies, all of which often depend on outside experts, currently deal with new and unusual plant pathogens as best they can.

A major research, development, and training center is called for that would address fungal, bacterial, and viral diseases of plants. Programs would focus on genomics and proteomics, databasing and informatics, forensics, pathogenesis, host-parasite interactions, diagnostics, sensors, food safety, analytical methods, epidemiology, modeling of disease outbreaks, intervention, and management. Other efforts could include outreach, technology transfer, collections of pathogens, and epidemiological intelligence and response. Close linkages could be established with other federal and state agencies, as well as with academic institutions, international agencies with responsibilities for surveillance of plant diseases and bioterrorism, and industrial, extension, and professional organizations. These collaborators could, among other functions, provide advice on containment and control procedures.

PREVENTION, RESPONSE, AND RECOVERY

We can never create a perfect system to safeguard against terrorist use of a biological agent. But conscientious preparation—to the greatest extent that budgets and available methods allow—will reduce anxiety and greatly mitigate the consequences of an actual attack. Part of that preparation should involve research and development on needed tools and approaches. These include modeling techniques, bioforensics, methods for defining threats, specific and broad-spectrum antibiotic and novel antiviral agents, and means for rapid vaccine fielding. Once an attack has occurred, a better prepared and reinforced health and agriculture response system will be needed, as will be a reliable and consistent communications plan. For those exposed, protocols for treatment and decontamination must be available. And for animal and plant exposures, an effective disposal and decontamination plan must be in place.

2  

A similar recommendation was made in February 2002 by the American Phytopathological Society. The white paper “American Phytopathological Society: The First Line of Defense—Biosecurity Issues Affecting Agricultural Crops and Communities: Genomics, Biotechnology, and Infrastructure” is available for review at <http://www.apsnet.org/media/ps/BiosecurityWhitepaper2-02.pdf>.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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For communicable diseases in particular, given the potential for initial exponential growth in the number of cases from a single diseased individual, it is crucial that a variety of methodologies, both prophylactic and reactive, be developed for limiting spread. These include vaccination, treatment, quarantine, movement restrictions, isolation and, in the case of nonhuman populations, culling. Because the potential for spread is determined by the number of secondary infections per primary infection, success in management can be achieved by a combination of reducing the infectious period and reducing transmission.

Studies must be done to develop decision rules and procedures for quarantine. These studies must be conducted with the goal of ultimately involving active participation of communities well before any event occurs. This will help reduce panic and irrational behavior in the case of an actual or suspected bioterrorism event. Quarantined communities must know where they will get medical care, antibiotics and vaccines, clean water, food, and mortuary service if the need arises.

A systems-level approach to dealing with bioterrorism threats, especially those involving communicable diseases, is needed. This approach must consider the integration of multiple modes of management, risk analysis in the face of inherent uncertainties concerning what agents will be introduced, and potential interactions among multiple biological agents. Such research is likely to rely heavily on the techniques of operations research, especially models that can be used for scenario development and training, for rapid response following detection of infected individuals, and for redesigning current systems (including possible patterns of movement) in order to make societies less susceptible to catastrophic outbreaks. Indeed, all of this argues for major development of modeling capabilities.

Uncertain Understanding of the Effects of Biological Weapons

Modeling the likely outcomes of different bioterrorism attacks is important for two reasons. It provides insight into the severity of the threat posed by the proliferation of biological weapons, and it allows one to estimate the effectiveness of different defensive responses (and hence the priority one should assign to each). Modeling efforts over the past decade, at least those publicly available, tend to emphasize worst-case scenarios—broadscale attacks involving millions of human casualties, if not fatalities. While such scenarios may be possible under the right circumstances, they probably are less likely than localized threats. In any case, a wider range of simulations is required to capture the range of possible outcomes. Here there is a major need for training; a critical mass of competent scientific expertise in epidemiological modeling has not to date been adequately supported. Such efforts should become major responsibilities of NIH, CDC, and DOD.

Constructing models may be easier, however, than supplying them with

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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meaningful data. There are gaps in our understanding of the factors that affect biological agents’ dispersal and uptake by humans, animals, and plants. For example, uncertainties of a factor of 10 or more in the LD50 values and a factor of 2 or more in the probit slopes (i.e., the dose-response curves) for different agents are common. These uncertainties are even greater if strain type is not known or the mechanism and magnitude of environmental decay rates for different agents are not well understood. Moreover, the incubation period (and its dose dependence) for different agents can vary by factors of 2 or more; and diurnal and weather variations can easily affect the contaminated area by an order of magnitude or more for open-air releases (typically the highest-casualty scenarios). Finally, uncertainties surrounding the amount and purity of the agent, the aero-solization efficiency for 1- to 5-micron particles, reaerosolization for agents that have settled onto the ground versus other surfaces, protection factors associated with buildings, and breathing rates can easily affect the inhaled dose by an order of magnitude or more.

These factors produce an irreducible uncertainty of several orders of magnitude in the number of people who will be infected in an open-air release. Moreover, the onset of disease may occur several times faster or more slowly than predicted, and this can have a significant impact on the efficacy of medical prophylaxis administered at a specific time after release. When bounds on these uncertainties are taken into account, the mean and variance of different attack outcomes may yield a different picture of the magnitude of the medical response required to cope with attacks—it is possible, in other words, that response options may be relatively insensitive to these uncertainties. However, the psychosocial consequences of a biological warfare attack (i.e., the disruption and terror caused by the event) will likely remain very large and difficult to quantify. Other transmission modes (water, food, animal vectors) create similar uncertainties, as do attacks directed at livestock or crops. Nonetheless, modeling and scenario building will be essential for cities and states to evaluate and improve their capacity to respond.

Recommendation 3.6: Agencies with relevant expertise (such as NIH, CDC, and DOD) should develop and support the development of models—taking into account a range of incubation periods, transmission dynamics, and variables of climate, population, and migration—to simulate the release of contagious and noncontagious agents. Such modeling may resolve many of the uncertainties about the effects of biological weapons.

Substantial uncertainties regarding mechanisms of pathogenesis would still remain, however; the only way to resolve them is through new experiments that involve virulent organisms and animal models of human disease. This fundamental work, which has been neglected in the age of molecular biology, underlies much of what must be done to develop new vaccines, broad-spectrum antibiotics and antivirals, and preclinical and traditional diagnostics. And, work must

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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proceed in parallel on nonpathogenic bacteria and viruses, where many of the molecular mechanisms essential to our understanding of pathogenic organisms can most readily be deciphered. For example, new antibiotic discovery is dependent on an understanding of fundamental cellular mechanisms that are held in common among bacterial pathogens and nonpathogens. Careful oversight of experiments with pathogenic organisms is essential to ensure that they are not in violation of the Biological Weapons Convention of 1972.3

Recommendation 3.7: Expand investigations into the pathogenesis of infectious agents. Review the state of knowledge on the mechanisms of pathogenesis of all bioterrorist agents and of host responses to them, and initiate an action plan to conduct laboratory research using the latest molecular biology tools. This research will enhance understanding of the points at which these threats are most susceptible to useful intervention and will help identify new targets for developing diagnostics, drugs, and vaccines.

Microbial Forensics and Analysis of Trace Evidence

The overall lack of knowledge about how to respond to a given attack, together with the lack of intelligence information to help identify the organisms or chemical agents used in an attack, presents major vulnerabilities. But the importance of microbiological forensics in reducing these vulnerabilities was largely overlooked until the recent outbreak of anthrax. Its importance is that the sophisticated scientific and organizational mechanisms of forensics can be the means for determining the states or persons responsible for the attack and for formulating strategies to deter future attacks (Cummings and Relman, 2002).

The U.S. criminal justice, national security, public health, and agricultural communities have more than adequately demonstrated that physical evidence and subsequent forensic investigations are crucial to the investigation of a crime. Similarly, preventing the use of biological weapons, responses to their use, and adequate defenses against them depend in large part on the ability of forensic analyses to attribute (or exclude) the source of a material with a high degree of scientific certainty. The ability to characterize biological weapons might also contribute to deterrence. But although advances have been made in forensics for specific biological agents that may pose a threat, a far more aggressive, compre-

3  

From the Web site of the Harvard Sussex Program on CBW Armament and Arms Limitation: “The Harvard Sussex Program on CBW Armament and Arms Limitation, with advice from an international group of legal authorities, has prepared a draft convention that would make it a crime under international law for any person knowingly to develop, produce, acquire, retain, transfer or use biological or chemical weapons or knowingly to order, direct or render substantial assistance to those activities or to threaten to use biological or chemical weapons.” More information is available online at <http://www.fas.harvard.edu/~hsp/cbwcrim.html>.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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hensive, and coordinated R&D program is needed. Such a program could then lead to fully tested forensic capabilities for all known biological agents that might be used in an attack.

Lessons should be drawn from the forensic community’s experience with human DNA over the past few decades, and alternative approaches to microbial forensics should also be explored. For example, knowledge of microorganisms, the methods used to profile them, and the responses of mammals (particularly humans, domesticated species, and sentinel species) to infections with these microorganisms can be used to determine whether an attack with a biological agent can be effectively correlated with a particular place, event, process, or time. Biological trace evidence, microchemical analysis (analysis of information about the agent carried along with the biological weapon during manufacture, storage, handling, and release), and the feasibility of using tagged organisms should be comprehensively investigated to determine their value in the characterization and comparison of the biological agents used in different weapons. Many in the biological warfare defense community believe that it should be possible to use a combination of DNA sequence information (occurring naturally) and/or deliberately introduced additional DNA sequences (stegnographic tags) to uniquely mark and identify all known pathogenic species. In this way, it may eventually prove possible to assign a unique code to every strain and variant, which would help in forensics, attribution, and defense. Such tags might even be encrypted.

Recommendation 3.8: Develop and coordinate bioterrorism forensics capabilities. Federal agencies with missions in defense and national security should lead in establishing this new multidisciplinary, multilayered field. A comprehensive study should be performed to determine the capabilities of and needs for bioterrorism forensics, and an integrated national strategy and plan formulated.

Investments and outcomes in the new field of bioterrorism forensics should be fully coordinated among agencies, with the program design, implementation, management, and oversight involving those agencies that actually have expertise in relevant sciences—including, of course, forensic science. The new field should cover human, animal, and plant pathogens. The information resident in the genomes and proteomes of organisms should be fully exploited, as should trace materials and chemical evidence associated with those organisms.

The strategic objective of a bioterrorism forensics program is to establish systems for the high-resolution analysis and specific identification of all materials and substances used (or intended for use) in bioterrorism. Although the committee recognizes the extreme difficulty of the task, the desired outcome is the absolute attribution of a biological weapon to its source—the identification of persons, places, processes, or instruments involved in the attack. The ability to substantially reduce the number of possible sources or individuals involved in bioterrorism, and the ability to completely exclude the possibility of an act of

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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bioterrorism, are equally important. So is the ability to understand the limits of the bioterrorism forensics process at any given moment and to accurately interpret and communicate results.

An Approach to Defining Bioterrorist Threats

Pathogenic microorganisms and the toxins produced by living organisms pose a threat to national security whether they occur in their natural state or are released in bioterrorism attacks. In either case, the greatest threats to human health in the United States come from emerging and reemerging infectious agents that sporadically occur in nature. The population is highly susceptible to such infectious agents, and the mortality rates among infected individuals can be high. Such agents in a bioterrorism attack could easily be spread to large numbers of individuals (Peters, 2002).

As part of a risk analysis, one can classify infectious agents and diseases in relation to these sorts of factors. Thus an eradicated disease agent to which there is currently a high degree of susceptibility, for which there is a high rate of mortality among infected individuals, that can be spread as an aerosol, and that can continue to be spread via contagion—in effect, a worst-case disease—could inflict the most casualties. Smallpox is such a disease, and it is at the top of the list of biological agents that may pose a threat. Once measles is eliminated (Hilleman, 2001) it will join smallpox in this category if immunization against measles is halted (as was done for smallpox) and the population becomes highly susceptible. This has important policy implications for the continuation of immunization against a disease agent after elimination of its natural occurrences.

Previously circulating pandemic influenza strains, most notably the 1918 Spanish influenza (Taubenberger, 2000) and the 1957 Asian influenza (Cox and Subbarao, 2000), and influenza strains of novel subtypes—e.g., the 1997 H5N1 strains from Hong Kong—have pandemic potential in humans. Ebola and hemorrhagic fevers (the causative viruses of which, however, are less easily spread from person to person than influenza viruses) would also have the characteristics of rare diseases that are communicable, to which there is a high degree of susceptibility, and for which there is a high rate of mortality among infected individuals. A genetically engineered pathogen could also have these characteristics and would need to be viewed as being among the most serious potential biological threats. The difficulty is that such genetically engineered pathogens could be created from virtually any biological pathogen or even vaccine strain; thus it will be challenging to develop vaccines or therapeutic antimicrobial agents in advance of a bioterrorism attack.

Because eradiated or genetically engineered agents often do not occur naturally or are difficult to obtain from nature, the best source for terrorists is a research facility. It is thus appropriate to impose significant restrictions in terms of oversight and apply stringent security precautions for biological agents that

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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pose high-level risks. Security guards, surveillance systems, personnel checks, and testing of personnel can be used to ensure that such biological agents are not removed from research facilities.

In contrast, biological agents with the potential to damage U.S. agriculture most often occur naturally in some part of the world. These agents can easily be obtained (domestically or overseas) and can readily be released, given the general lack of security on farms and fields and their formidable size. For example, foot-and-mouth disease was widespread in the United Kingdom in 2001. A shoe from someone who walked on an infected farm would have been able to carry enough of the agent into the United States to cause an outbreak. Although U.S. border inspections for such potential introductions were heightened during the outbreak in the United Kingdom, the methods used were heavily dependent on the honest answers and voluntary compliance of the traveling public. It is likely that a determined terrorist could circumvent such an interdiction approach.

Similar issues arise for plant pathogens and pests. For example, citrus canker is a bacterial disease of woody perennials that is endemic in several parts of the world where citrus is grown. It has recently been reintroduced into the United States, in Florida, and has had significant adverse impacts on the state’s citrus industry. For agriculture, given that would-be terrorists have access to various naturally occurring threats, it will also be important to consider the possibility of the intentional release of multiple types of agents at multiple sites.

For biological agents that may be used by terrorists and that occur naturally, it is appropriate to use lower levels of security and less direct oversight. The level of such oversight may still be significant and should be designed to offer real protection against the acquisition of biological agents that may be used as weapons. Significantly higher levels of security should be applied to any weaponized biological agents—for example, anthrax spores that have been treated to make them easily aerosolized.

Developing Antimicrobials and Antivirals

The diversity of existing biological weapons and the ever-increasing number of possibilities through use of genetic recombination preclude simple therapeutic countermeasures to bioterrorism. The Soviets are known to have developed at least 30 biological agents. While it might only take 1 to 3 years to develop a new biological weapon, the average development time of a new drug or vaccine is 8 to 10 years. Thus with respect to development of countermeasures for biological weapons, a great need exists for broad-spectrum antibiotics and antivirals. Based on current knowledge, technology, and genomic databases, the goal of broad-spectrum anti-infectives is achievable.

Existing countermeasures for known threats are limited. For the potential biological weapons on the CDC “A” list, there are only two vaccines available or in production (anthrax and smallpox), one antiviral, and a limited number of

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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classes of antibiotics. Supplies of both vaccines are currently limited. While smallpox vaccination is effective, it elicits dangerous and potentially lethal complications in a number of individuals, and because it is a live-attenuated vaccine, it poses a significant risk for all immunocompromised individuals. The limited antibiotic armamentarium is an even greater concern with respect to future threats, especially in light of an increase in the number of new and reemerging infectious diseases and a marked rise in resistance to existing antibiotics. When the issue of resistance is laid against the dearth of new classes of antibiotics being developed and commercialized today, it becomes clear that no public health response to bioterrorism is likely to prove effective without a wider range of antimicrobials to draw on.

Work must proceed in parallel on nonpathogenic bacteria in the same class as the pathogen. New antibiotic discovery is dependent on an understanding of fundamental cellular mechanisms that are held in common among pathogens and nonpathogens. In most cases, the nonpathogenic cousin has far superior genetics and a deeper database of gene function and regulatory networks allowing discovery and development to proceed at a faster pace. Most antibiotic discovery is, in fact, based on work in nonpathogens that is then directly applicable to the pathogens on the list of biological warfare agents.

An Interagency Task Force on Antimicrobial Resistance has set forth recommendations for judicious use of existing antibiotics; they appeared in the Federal Register almost 2 years ago.4 Although the recommendations were widely endorsed, funds have yet to be appropriated by Congress to implement the plan. Given the long lead time required for development of new antibiotics, we must preserve those we have. Thus it is essential that the recommendations of the task force be implemented without further delay.

Unfortunately, the complacency associated with infectious diseases in the 1960s and the general confidence in existing antibiotics largely arrested the production of new classes of antimicrobials. There has been only one new class in the past three decades, and resistant strains emerged prior to its launch. But the situation may be changing for the better. The public attention to the antibiotic crisis in the early 1990s, coupled with the potential for discovering new antibiotics using genomics, high-throughput screening, microarrays, combinatorial chemistry, and structural biology, has resulted in industry’s reinvestment in antibiotic research.

At first glance, the current antibiotic pipeline looks encouraging. There are more than 18 antibiotics in Phases I through III of clinical development. However, there are no new classes or targets for antibiotics. In particular, there are no new classes of broad-spectrum antibiotics, and the outlook for antivirals, particu-

4  

A Public Health Action Plan to Combat Antimicrobial Resistance appeared in the Federal Register on June 22, 2000 (Volume 65, Number 121). The report is available online at <http://www.cdc.gov/drugresistance/actionplan/html/index.htm>.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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larly broad-spectrum agents, seems even more distant. These deficiencies are critical, as the chances for use of a multi-drug-resistant recombinant organism in future attacks is high. Here again, the deciphering of the genomes of major pathogens and the analysis of their function by the new field of bioinformatics will reveal new potential drug targets—most notably, targets that are present only in bacteria or viruses and not in human cells (such that broad-spectrum drugs can be developed that are likely to have few adverse effects on the human host).

The need has never been greater for research, in both the public and private sectors, aimed at development of novel antimicrobials. However, recent analysis indicates that most, if not all, major pharmaceutical companies have over the past 3 to 5 years decreased their investments in drug discovery related to antibiotics, and few are exploring antiviral agents. These changes have resulted from higher regulatory hurdles, competing priorities, and a shrinking market. Thus, new classes of antimicrobials will not emerge in the next decade without a major strategic shift.

Rapid Vaccine Development

Bioterrorism attacks might not be restricted to the dissemination of known pathogens. Variants that have been engineered by current molecular-biology-based methods to alter or mask surface antigens—so as to avoid detection by the immune system—could also be used in such attacks. The following question arises: How quickly and by what means could a new vaccine be developed and deployed to protect against a novel pathogen?

Before that need is upon us, we should act now to tackle several challenges to overcome the critical shortfall of research in vaccinology:

  • The genome sequences of all plausible organisms that could potentially be used in a bioterrorism attack, including naturally occurring variants, need to be determined. This information will greatly facilitate the identification of any engineered variations in a weaponized strain.

  • DNA-based vaccines (including vaccines that use defective viruses as carriers) should be more fully investigated for human application, as their use represents a potential quick path from determination of the genome sequence to the availability of a vaccine. Recombinant human antibody technologies should be explored, including novel delivery systems.

  • Recombinant protein expression provides another pathway for the development of relevant antigens, but more research is needed to determine ways to make recombinant proteins as effective as immunogens.

  • More effective adjuvants are needed.

  • The development of vaccines against toxins, as opposed to pathogenic organisms, should also be explored.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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  • Better surrogate animal models are needed for testing vaccines against novel pathogens.

  • Improved vaccines against known agents (like smallpox virus) are necessary if immunocompromised subjects are to be safely protected.

  • A low cost per dose and stability at ambient temperature are important goals if vaccines are to be shipped to troops in remote locations or to populations in developing countries.

  • Antibodies produced for medical use may provide an effective way to ameliorate the effects of a toxin or an infectious agent.

  • The regulatory, legal (liability), and ethical issues associated with new vaccines are complex and must be addressed. Could vaccines developed by certain standard protocols be preapproved by the Food and Drug Administration (FDA) to streamline vaccine deployment, even if only at times when a certain high threshold of infection or mortality had been surpassed?

  • Vaccines must be produced and stored in multiple secure locations, as the vaccine itself could be a target in a terrorist attack to disable our ability to respond.

  • The possibility of using vaccines effective against combinations of antigens from different viral pathogens needs to be investigated.

  • Further work in basic immunology needs to be done to obtain an understanding of whether it will be possible to develop drugs that will up-regulate an immune response to pathogens, including organisms used for bioterrorism (immune modulation).

The application of microbial genomics to the development of a novel meningococcal vaccine is one instructive model to consider here (Pizza et al., 2000). In addition, over the past several decades there has been an explosion of basic knowledge about virus structure, the genetic organization of viral genomes, and the mechanisms of viral replication. This knowledge presents us with many potential targets for antiviral therapy. Only a tiny fraction of such targets has been exploited to date. An informative example of success in this area is development of protease inhibitors, such as anti-HIV drugs. The discovery that processing of certain HIV proteins by the protease is essential for virus multiplication came out of basic research on viral proteins. The demonstration that the protease is essential for infectivity was published in 1988. The first protease inhibitor was approved by FDA in 1995. It is highly likely that similar approaches would result in useful therapeutics to counter viruses that might be used for bioterrorism.

Recommendation 3.9: Increase research and development on therapeutics and vaccines. Support basic and clinical research to discover molecular targets in bacteria and viruses, develop broad-spectrum antivirals and antibiotics, and devise treatments that enhance or stimulate protective host responses (both innate and acquired). Similarly, continue to expand and

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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deploy the capability to use genomics to rapidly identify engineered mutations or altered virulence factors, create a generic platform to develop a vaccine against recombinant pathogens, and employ streamlined testing and regulatory processes to assure adequate efficacy and safety while expediting delivery.

Improvement and Testing of Environmental and Personal Protective Equipment

As described in Chemical and Biological Terrorism (IOM, 1999), personal protective equipment (PPE) includes clothing and respiratory apparatus designed to shield an individual from chemical, biological, and physical hazards. Availability (and even knowledge of availability) of such devices can reduce anxiety among first responders, health-care providers, and potential victims. In general, PPE is more effective against chemical agents, because biological agent incidents are not likely to be evident until well after release of the agent.

Protective methods aimed at preventing the pathogen from entering the body are usually physical rather than biological and do not depend on the detailed structure of the pathogen. Available filtering methods depend only on particle size. Like most physical methods, filtering methods available today have the characteristic that they are not 100 percent effective, but they are able to sharply reduce the number of casualties. What is remarkable is that a capability exists based on existing products that can be put into service rapidly. HVAC filters in large buildings can be upgraded at minimal cost (see Chapter 8); other similar filtering devices can be used in the home. Simple cheap masks, about the size of a folded handkerchief, are available and probably provide a high degree of protection. These devices must be tested by government agencies and information must be provided to citizens about their effectiveness.

An array of equipment currently exists (e.g., gloves, gowns, masks, eye protectors, respirators, protective suits), but technical problems remain—for example, heat stress in suits, permeable respirators, and difficulty of use. Also, there is no uniform testing standard for some of this equipment. In particular, testing is needed for antipathogen devices in order to distinguish personal protective equipment that is truly protective from items that generate a false sense of security (and that could increase people’s risks by unknowingly putting them in harm’s way).

There is also a need for research on environmental protection devices that safeguard buildings and homes from biological and chemical-aerosol threats. For example, less expensive HEPA (high-efficiency particulate-arresting) filters for heating, ventilating, and air-conditioning systems could provide a real defense against terrorist attack on buildings and landmarks; they could also prevent exploitation of ventilation systems by terrorists. Such research might have non-

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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counterterrorism application as well; it could provide knowledge about the use of filters for reducing the current epidemic of asthma in U.S. cities, particularly among children.

Recommendation 3.10: Improve environmental and personal protective equipment. Agencies such as EPA, NIOSH, CDC, DOD, and DOE should perform and support research on new technologies that increase the protection factors of such equipment, and ensure uniform testing oversight to certify efficacy.

Approaches to Preparing the Health Care System for Response and Recovery: The Need for Surge Capacity

The U.S. health care system has focused on efficiency in the past decade. Redundancies have been eliminated through hospital closures, decreases in the numbers of physicians in many specialty practices, and consolidation of traditional public health activities within health care delivery organizations. Furthermore, the budgets of many agencies that could deal with significant epidemics have been curtailed because no such incidents have occurred in the United States in recent years.

Efficient systems use resources to deal with predictable health problems, but almost by definition they lack the resilience (in the form of excess capacity) to deal with unusual episodes of disease, particularly large-scale outbreaks or those that may result from an act of bioterrorism. The challenge is to devise a system that would create capacity on demand to cope with sporadic and potentially very large demands on the health care infrastructure without destroying the efficient use of resources that characterizes the current situation.

It is probable that the given medical capacity in any community can respond immediately to a terrorist attack, providing the following two conditions are met:

  • The attack does not destroy the hospitals and emergency departments in that community. A chemical attack might destroy multiple hospital emergency departments or contaminate them so completely that they could no longer be used; a biological attack could quickly spread to medical personnel, thereby effectively destroying their capacity to respond.

  • The attack is short-lived and can be handled within a short time frame (less than 24 hours). For example, during the attack with sarin on the Tokyo subway in 1995, there were few fatalities and a small number of serious cases. Yet the total number of patients (of all types) created an overwhelming workload for the emergency departments of Tokyo hospitals, though only for a short period of time. Had the attacks continued on a daily basis (as in the case of a biological agent that would spread over time, such as the plague bacterium or smallpox virus), there would have been a need to divert some capacity to care for the usual

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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daily workload—thereby reducing the number of staff medical professionals for handling the bioterrorism-related workload.

In most urban communities of the United States, a bioterrorism attack could pose major problems for the hospital emergency departments, which are already close to their maximum utilization capacities. Some capabilities do exist for reducing the usual workload under such circumstances: patients with marginal cases of illness or minor injuries could be quickly discharged from specialty-care units; elective cases of treatment or surgery could be delayed; and incoming emergency patients could be triaged. However, a large number of patients would continue to need care so that they did not deteriorate into a more serious state. Numerous off-duty medical personnel could be pressed into longer hours of service in a crisis, but the amount of time during which they could respond without relief is still finite. Thus, although the prehospital care agencies might be able to gear up quickly into a disaster mode and accommodate a sudden influx of patients with illnesses related to an acute attack, there is not high confidence that emergency departments in most cities could do the same.

The initial symptoms of the illnesses caused by virtually all infective agents, be they bacterial, viral, or fungal in nature, are very similar. In fact, in everyday clinical practice it is common to confuse a serious bacterial infection with a trivial viral infection, with a loss of opportunity for effective intervention and curative treatment. If individuals or government agencies outside the medical community have knowledge about a pending attack with a specific agent, they may still not be able to dispel such confusion; no mechanism currently exists for the transmission of that information to the medical community so that it can recognize infected individuals and respond to their needs more quickly.

The federal government already has systems in place for responding to disasters. HHS coordinates Disaster Medical Assistance Teams, Disaster Mortuary Operational Response Teams, Veterinary Medical Assistance Teams, and other medical specialty teams located throughout the country. These units can be deployed immediately in the event of natural disasters. In addition, HHS coordinates the National Medical Response Teams for Weapons of Mass Destruction—weapons of mass destruction include chemical, biological, radiological, nuclear, or explosive (CBRNE) agents—to deal with the medical consequences of such incidents, and it is helping metropolitan areas across the nation prepare to deal with such incidents through the Metropolitan Medical Response System.

The Metropolitan Medical Response System emphasizes enhancement of local planning and response capabilities, as well as that of local hospital capacities, tailored to each jurisdiction so that it can best apply local resources to care for victims of a terrorist incident involving a weapon of mass destruction. The resulting systems are characterized by a concept of operations; specially trained responders; a special stockpile of pharmaceuticals; equipment for the detection of biological, chemical, and nuclear agents along with personal protective equip-

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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ment; decontamination capabilities; communications equipment, medical equipment, and other supplies; and enhanced emergency-medical-transport and emergency-room capabilities. The program focuses on responses to a biological attack, including early warning and surveillance, mass-casualty care, and plans for the management of mass fatalities. The concept of operations also includes the local jurisdiction’s plan for augmentation of health and medical assistance by the federal, state, and neighboring governments, including the movement of patients (when local health-care systems become overloaded) via the National Disaster Medical System (NDMS). Each major medical center in cities across the nation must have response plans in place. These should include designated hospital areas that can be converted into isolation zones and decontamination areas, triage plans, and ongoing training sessions for disaster response teams among the medical personnel.

The Office of Emergency Preparedness leads the NDMS, a partnership of four federal agencies (HHS, DOD, the VA, and FEMA) and the private sector. The system has three components: direct medical care, patient evacuation, and nonfederal hospital care. NDMS also includes more than 7,000 private sector medical and support personnel organized into 80 disaster-assistance teams. These teams provide immediate medical attention to sick and injured individuals during disasters, as well as mortuary and veterinary care when local emergency-response systems become overwhelmed.

All of these systems (e.g., NDMS and the Metropolitan Medical Response System) should be supplemented with additional local capacities for responding to attacks on humans, animals, and plants. A national, regional, and local planning process should identify human and other resources that could be brought out of reserve during such times. In addition, public health laboratories need to build surge capacities as well as expertise in containment. Microbiology laboratories are the first lines of defense for the detection of new cases of antibiotic resistance, outbreaks of food-borne infection, and a possible bioterrorism event. Maintaining high-quality clinical microbiology laboratories on site or near the institutions and communities that they serve is the best approach at present for managing infectious diseases and detecting resistance to antimicrobial agents. However, a public health reserve system, consisting of certified laboratory personnel with the ability to provide expertise when the health care system becomes overloaded, needs to be created. In addition, before a crisis occurs, it is critical to have in place agreements between public health and emergency response agencies across jurisdictions. Drills using both threats and scenario models can test the full range of capabilities and assure the availability within a short distance of Level 4 public health laboratory capability.

Recommendation 3.11: Create a public health reserve system and develop surge capacity. As part of a broader planning process, create a health reserve system of health care professionals (modeled on the military reserve

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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system), and prepare local and regional laboratories for deploying surge capacity to supplement and enhance disaster-response capabilities.

Approaches to Preparing the Food and Agriculture System for Response and Recovery

The U.S. food and agriculture system has undergone profound changes since World War II that have increased the vulnerability to plant and livestock diseases and to widespread human illnesses caused by food-borne pathogens. Food processing and distribution have become increasingly concentrated. For example, four companies now slaughter and process 85 percent of the domestically produced meat, livestock is raised in large, centralized feeding operations, and vast amounts of land are devoted to one or two crops, such as corn and soybeans.

Meanwhile, government support for agricultural research has remained flat (in constant dollars) for nearly 25 years. The private sector supports more agriculture research than the state and federal governments combined, but most of these industry initiatives are in the development of biotechnology products, pesticides, and other inputs to agricultural production.

A USDA-state system of laboratories that investigates outbreaks of livestock diseases does exist, but it varies somewhat in structure from state to state, with some relying on state laboratories and others on colleges of veterinary medicine or agriculture, usually located at land-grant universities. Within USDA, the Animal and Plant Health Inspection Service (APHIS) leads efforts to prepare for and respond to outbreaks of crop and livestock diseases, both indigenous and exotic. APHIS develops the basic emergency-response plans, while state agriculture departments extend the plans to apply to the conditions and administrative structures within their domains.

Recommendation 3.12: Create an agricultural health reserve system and develop surge capacity. As part of a broader planning process, create a reserve system of veterinarians and plant pathologists (modeled on the military reserve system), and prepare local and regional laboratories for deploying surge capacity to supplement and enhance disaster-response capabilities.

Communicating Risks and Responses to the Public

In 2000, a workshop cosponsored by the Defense Threat Reduction Agency (DTRA), the FBI, and the U.S. Joint Forces Command was held on the communication of risk resulting from a weapons of mass destruction (WMD) attack. A report published in March 2001 describes the results of the workshop and recounts lessons learned from past experiences, addresses unresolved issues that were identified by the expert participants, and presents prioritized recommendations for future research, analysis, and other activities (DTRA, 2001).

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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A disaster response program should include many elements if it is to be successful in dealing with the effects of a WMD attack and restoring public order. In the United States, several agencies at the federal, state, and local levels have been assigned to handle contingencies such as natural disasters, chemical spills, and nuclear mishaps. The Federal Response Plan, a signed agreement among 27 federal departments and agencies, and including the American Red Cross, provides a mechanism for coordinating delivery of federal assistance and resources to augment state and local efforts in major disasters or emergencies. This plan, however, does not describe an integrated, comprehensive blueprint for crisis/risk communications in the event of a large-scale disaster such as a WMD attack. It should be noted that in the 1918 pandemic of influenza, there was a severe lack of mortuary services and facilities, which must also be provided for by the plan.

To help fill the gap, research and analysis on communication and awareness campaigns, and training and preparation, are needed (see Chapter 9). However, it is essential that all federal agencies involved in response develop, through a panel of outside experts, a plan for analyzing data, developing a response, coordinating the response with other agencies and the Office of Homeland Security, and communicating with the public.

Development of Treatment Protocols

In most cases, there is insufficient research and information on which to base a sound public health protocol and medical response in the event of a biological attack. We cannot, for example, answer the following questions with confidence: How long should individuals continue antibiotic treatment after exposure to biological agents? How long after exposure will vaccination be effective? What other types of interventions will increase survival rates and decrease spread of the disease?

Sound protocols are a necessary prerequisite for communicating information about appropriate postattack responses to the public, physicians, and public health officers. The anthrax attacks of 2001 illustrated the lack of preparedness in this area.

Recommendation 3.13: Develop protocols for public health responses to bioterrorist attack. OHS should develop a plan for achieving this objective, and HHS, through its various agencies, should support the necessary research.

Development of Decontamination Protocols

At present there are few data on which to base decontamination procedures, particularly for biological agents. A review of the literature shows that dose-response information is often lacking or controversial, and that regulatory limits

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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or other industrial health guidelines (which could be used to help establish the maximum concentrations of such agents for declaring a “decontaminated” environment) are generally unavailable or not applicable to public settings (Raber et al., 2001). Moreover, the correct means for identifying the presence of many biological agents are not known, nor is the significance of the presence of biological agents in the natural environment (e.g., anthrax spores are found in the soil in some parts of the United States). Research is therefore needed to determine what level of cleanup will be required to meet public health needs in the aftermath of a bioterrorist attack.

Although the lack of dose information, cleanup criteria, and decontamination protocols presents challenges to effective planning, several decontamination approaches are available. Such approaches should be combined with risk-informed decision making to establish reasonable cleanup goals for the protection of health, property, and resources. Efforts in risk assessment should determine what constitutes a safety hazard and whether decontamination is necessary. Modeling exercises are needed that take into consideration the characteristics of a particular pathogen, public perceptions of the risk that the pathogen poses to their health, the level of public acceptance of recommendations based on scientific criteria, levels of political support, time constraints in responding to the threat posed by a pathogen, and economic concerns (Raber et al., 2001). Specialized robots may have to be developed and used in highly contaminated or extremely hazardous situations.

Agricultural Decontamination

For agricultural biological threats, critical components of the response include quarantines, disposal of contaminated plant or animal material, and decontamination of products, facilities, equipment, and, in some cases, soil (especially for agents that are persistent and can survive in the environment) (NRC, 2002). The disposal or decontamination procedures used, as well as their effectiveness and acceptability, are highly specific to each biological agent: They depend on the nature of the agent, the commodity affected, and the extent of disease or infestation. For example, foot-and-mouth disease (FMD) is so highly contagious that large numbers of infected and potentially exposed animals may need to be slaughtered and disposed of at the farm of origin. Mass burial and burning are the major alternative means for disposal. Both methods are expensive, repugnant to many people, and raise environmental concerns. Novel methods for carcass disposal, for inactivation of FMD virus in and on carcasses, and alternatives to mass slaughter during FMD outbreaks are urgently needed. Decontamination of products, equipment, or facilities is less of a problem because FMD virus is inactivated by heat, irradiation, or treatment with chemicals at high or low pH.

Similar issues apply to plant pests and pathogens. In general, decontamination of seeds and combines, trucks, or other field or handling equipment is pos-

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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sible by fumigation with appropriate chemicals, but this is costly, from both an economic and environmental perspective. Eradication, especially of soil-borne spores of plant pathogens, is virtually impossible. Methyl bromide, one of the few standard chemicals used for fumigation of soil and containers, will be banned after 2005 in developed countries and 2010 in developing countries as the result of an international agreement made in response to evidence that the chemical depletes the ozone layer. Live steam can be used to clean up facilities and handling equipment, but its cost and damage to the equipment can make this method unappealing. Alternative methods for decontamination and eradication of biological threats to plants are needed (NRC, 2002).

Recommendation 3.14: Develop methods and standards for decontamination. Develop standards for levels of decontamination and certification of products to ensure safety.

Research is needed on chemical fumigation and irradiation as methods for decontamination of buildings and mail; development and evaluation of novel decontaminants; disposal of crops and livestock carcasses; and decontamination of trucks, railroad cars, container ships, and warehouses used to transport and store contaminated crops, livestock, food, and feed. This effort will require collaboration among all agencies with expertise and a mission in this area, including HHS, EPA, USDA, the Coast Guard, and DOD. Because cross-agency collaboration is often challenging, the Office of Homeland Security should designate a lead agency on these issues and ensure that collaborating agencies provide the necessary resources to identify and support research efforts in this area.

POLICY AND IMPLEMENTATION

Effective preparedness for countering bioterrorism will not only require focused and sustained efforts to build the nation’s public and agricultural health infrastructures (including the training of health care professionals in detection, surveillance, prevention, and response); it will also require substantial changes in the way government-supported research is executed. Several overarching strategies are needed to provide the necessary funding for research and development (R&D), mechanisms for response, integration of efforts, and translation of findings into application. The recommendations listed below, which support and facilitate the R&D priorities outlined in previous sections of this chapter, are offered in that spirit.

Develop Scientific and Technological Human Resources

The public and private sectors should explore new funding mechanisms that select for the best ideas and the most productive scientists, that offer great flexibility, and that provide the freedom to pursue bioterrorism-related research in a

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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protected environment (i.e., not subject to 1- or 2-year budget fluctuations or constraints). The traditional system of reviewing and funding grants and contracts can be lengthy and averse to highly focused, highly managed research initiatives. Although basic and discovery science will continue to be a critical underpinning of all research in countering bioterrorism, a more focused, outcomes-based approach is also warranted. Balance between basic and applied research approaches will be crucial.

One model worth considering is a central organization that directs R&D projects whose risks and payoffs are very high—that is, whose successes may provide dramatic advances—and that pursues these projects with both flexibility and speed. There is a real need for NIH, particularly NIAID, to adopt an approach like this for funding the kinds of high-payoff, high-risk projects that might create innovative scientific tools for addressing bioterror threats.

Recommendation 3.15: Create special research organizations to build expertise in countermeasures to bioterrorism. Federal agencies must build human resources in threat-agent characteristics, pathogenic mechanisms, and responses to bioterrorism-induced disease. Protected environments that foster innovation must be developed to support a cadre of leaders, scientists, engineers, policy experts, and strategic thinkers. These designated research organizations should address both classified and unclassified issues, and special mechanisms for rapid funding should be created to support external research efforts as the needs and opportunities emerge. New mechanisms for funding high-risk, long-term, high-payoff projects should be created in NIH.

Ideally, the new organizations recommended above would be small but have strong interactions with universities and government agencies. They would work in basic and applied science—specifically, to understand pathogenic (virulence) factors at the molecular level and how they affect mammalian systems. And they would also work in product development—specifically, in diagnostics, antiviral and antibacterial drugs, and all stages of vaccine manufacture, from development to pilot production. Clearly, drugs and diagnostics should have dual use, and the range of pathogens studied will inevitably have dual-use spinoffs. As a companion to this initiative, a mechanism for rapid funding should be established for bioterrorism-related research conducted extramurally; this mechanism would select for creative ideas quickly, with a minimum of bureaucracy.

Need for Standards and Standardization

The goals for research on surveillance and clinical diagnostics include rapid diagnostic assays for common pathogens and biological warfare agents. These assays could be used in primary-care settings (point of care) as well as referral laboratories. But standards are needed by which they may be rigorously evalu-

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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ated and validated, and centralized repositories of standardized reagents and samples are needed as well. Because the development and evaluation of diagnostics require interdisciplinary applied research, however, it is currently difficult to find targeted funding sources and mechanisms.

Recommendation 3.16: Establish laboratory standards. Set up an oversight standards laboratory to evaluate diagnostic and detection tools; to ensure the availability of standard reagents for academia, industry, and government; and to develop appropriate standards on a continuing basis.

The National Institute of Standards and Technology (NIST) is one agency where these sorts of efforts might appropriately be undertaken.

It is to be expected that many new products will be introduced for detecting and responding to bioterrorist threats, but no mechanism currently exists for evaluating them and comparing their effectiveness. An oversight standards laboratory would have the capacity to evaluate biosensors and diagnostic systems for infectious diseases, develop taxonomies of syndromes and data classifications, improve the quality of the expanding DNA and protein databases, validate methods, develop reagents, create internal standards for diagnostic comparisons for the scientific community, and evaluate methods and standards for personal protective equipment and decontamination.

Facilitate Development of Therapeutics and Vaccines: Engagement of Industry

Government has a vital role to play in basic research on countering biological warfare agents through its own institutions, many of which have enormous expertise that has long been brought to bear in the fight against infectious diseases. It would be inefficient, however—and ultimately ineffective—for government to go it alone, without actively engaging private industry in the race to deploy needed biomedical countermeasures. Indeed, the greatest efficiency in this urgent effort is likely to come from working the broadest possible network of synergy among all institutions of established expertise—public sector entities, academic laboratories, private research institutes, biotechnology start-up ventures, and pharmaceutical companies. The fight is big enough and difficult enough to demand that the entire spectrum of available talent and resources be productively engaged. To build this network, a new partnership model for industry and government is needed that goes beyond the current models of government contracting.

Existing mechanisms for government interactions with the private sector cover a wide range: from simply acting as a customer in the marketplace, through NIH grants, to the comprehensive R&D contracting done by DOD. There seems to be no one best way among these mechanisms, nor any clearly better way

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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beyond them. They all have valid applications, and, in practice, different cases will probably require different solutions. However, there is one principle that must serve as the foundation for any partnership aimed at developing countermeasures for bioterrorism. It is the principle of risk sharing.

Drug and vaccine development is an incredibly high-risk business. Front-end costs start big and grow bigger as development proceeds. The total is often something like $800 million by the time a successful drug is launched—10 years or more from the day it was discovered. The odds against success are long—one compound in 5,000 makes it all the way from the test tube to the pharmacy shelf. And even among newly launched products, only one in three earns back its development costs. Public policy makers must consider whether drugs and vaccines could be developed more cheaply, given the compounds that are languishing in the developmental pipeline because bioterrorism is a small and uncertain market.

At the front end, government could help defray some of the costs associated with discovery and early-stage development. Grants and other forms of direct investment might help, especially with smaller organizations. But given the current needs related to antibiotic resistance in naturally occurring pathogens and to the decline of innovation in antibiotic-drug discovery, risk sharing may need to be considered more broadly.

Government could further reduce the risk to industry by providing some form of legal relief from the product-liability issues associated with new countermeasures. Risk sharing could also help to lower the costs of purchasing and storing biodefense drugs—whether existing or to be developed.

The government’s current practice is to determine what quantity of a given material it may need, issue a contract to purchase that quantity, and then stockpile it until needed. This process works well for some products, but it is a very expensive way to purchase pharmaceuticals. A more cost-effective approach would be to contract with drug manufacturers for assured access to the necessary quantities. The manufacturers would have to be able to prove beyond doubt that they could deliver the requisite quantities within the needed time frame. It is essential that production capability occurs at more than one facility and that these facilities be based within the United States. The government would reimburse the cost, build and maintain the inventory, and add a modest profit. In the event of an attack, the government would take control of the inventory at no additional cost. Meanwhile, responsibility for addressing such additional risks as unforeseen spoilage would rest with the manufacturers.

Recommendation 3.17: Facilitate vaccine and therapeutics production. Through public-private partnerships, create research, development, and manufacturing capacities to produce diagnostics, therapeutics, vaccines, and devices to counter terrorism and an oversight laboratory to evaluate, prepare, and standardize methodologies.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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Traditional market mechanisms for the development of new diagnostics and vaccines are failing with regard to pubic health generally and response to bioterrorism in particular, where the principal market is likely to be federal and state governments. National orphan vaccine centers, perhaps created as government-owned, contractor-operated (GOCO) facilities, are needed to help bring vaccines for otherwise rare diseases to the stages of mass manufacture. Such centers could help coordinate extramural R&D activities in the public and private sectors as well as perform critical research. In particular, national orphan vaccine centers could coordinate the clinical trials and studies with animals on which licensing would be based, and could serve as conduits for production at industrial facilities (including development of surge vaccine-manufacturing capacity and the training of personnel to produce vaccines that meet FDA standards). Such collaboration would require the establishment of new relationships between the public and private sectors.

For development of broad-spectrum antibiotics and antivirals, federal funding should encourage the large pharmaceutical and biotechnology companies to enter the field with the expectation that at least some drugs developed for bioterrorist threats will have dual use—that is, they may be applicable to common infectious diseases as well. Such encouragement for undertaking R&D on new drugs against bioterrorism agents could take the form of streamlined grant mechanisms, financial incentives, and regulatory changes.

Regulatory Reform

Maintaining public confidence in vaccines, and in medical products in general, is critical to assuring overall confidence in the nation’s public health programs. But bioterrorism is a moving target, not a single disease of predictable epidemiology, and all potential product uses may not be anticipated. This complicates many decisions about product use.

Current biodefense-related activities at the FDA include meeting with sponsors and sister agencies to encourage interest in developing safe and effective new products, performing research that ultimately facilitates the development of these products, and intensively interacting with product sponsors to expedite availability.

Other steps that the FDA has employed in an attempt to safely speed up the licensure process include the following:

  • Emergency use under investigational new drug (IND) status allows rapid access to products that have not yet completed requirements for licensure. While IND status makes available potentially lifesaving items, a disadvantage of emergency use under this rule is that the product is not licensed, which not only reflects the true scientific limitations of the data but also raises important issues about public perception.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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  • Fast-track processes can speed up the review procedure so that the FDA can evaluate information as it becomes available and as soon as the sponsor submits it.

  • Accelerated approval uses surrogate end points to demonstrate benefit. For bioterrorism agents, this might include protective-antibody levels for vaccines. The use of CD4 cells for assessment of antiviral treatment for HIV was one of the first surrogates to be approved under this rule.

  • The “Animal Rule”5 is extremely important with respect to bioterror agents. It states that where human efficacy trials are not feasible or are unethical, the use of animal-efficacy data may be accepted as they relate to the desired benefit in humans—usually a significant outcome such as mortality or major morbidity. Clinical studies are still required for establishing pharmacokinetics and for assessing safety. The Animal Rule has postmarketing and labeling restrictions, however, and it does not apply if the product could be approved on the basis of any other standard under the FDA’s regulation.

Much more research is needed to establish acceptable criteria for reduction in morbidity and mortality. Human diseases caused by many of the CDC Category A agents are so poorly understood at present that meaningfully defining such criteria for the Animal Rule will be difficult. For some agents—for example, smallpox—appropriate animal models are lacking, and many existing animal models are poorly characterized with respect to lesion character and disease progression.

Animal models (with the exception of those for anthrax) remain poorly characterized with respect to aerosol challenge and disease characteristics in animals receiving sublethal challenge doses. Criteria need to be established with respect to end points that will be acceptable to the FDA for reduction in morbidity and mortality and similarity to human disease—i.e., route of inoculation, challenge doses and strains of organisms to be used, strain and species of animals, and duration of observation periods for reduction in morbidity according the FDA’s Animal Rule regardless of route of challenge.

Recommendation 3.18: Allow regulatory exceptions for development of therapeutics and vaccines against bioterrorism threats. The FDA should convene a broadly based conference to consider options and plausible mechanisms for expedited approvals under specific emergency conditions. In addition, for new drugs and vaccines that cannot be tested in humans, mechanisms for indemnification in the case of adverse effects will need to be

5  

The Animal Rule is Code of Federal Regulation (CFR) Title 21, Parts 314 and 601: “New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs when Human Efficacy Studies Are Not Ethical or Feasible.” The final version of this rule was published in the Federal Register on May 31, 2002, and will take effect June 30, 2002. The final rule can be viewed at <http://www.fda.gov/OHRMS/DOCKETS/98fr/98n-0237-nfr0001-vol1.pdf>

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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developed. The possibility of encouraging collaboration between pharmaceutical companies in this area by waiving antitrust restrictions—in specific cases justified by the national interest—must also be considered. Thus, in addition to the FDA, the Departments of Commerce, Treasury, and Justice should also be involved in these discussions.

Clearly, in an emergency, someone or some agency has to be authorized to decide, for example, that INDs may not be required, that the informed consent process can be modified, that companies might have to be indemnified, or that companies might have to exchange information or work together, which would require a waiver of antitrust law. The factors that go into such decisions should be discussed by government and industry, and possible approaches recommended to federal agencies.

CONCLUDING REMARKS

Understanding of biological agents as threats to human, livestock, and crop health, as well as to the U.S. economy, must be improved. Special emphasis might be placed on an urgent short list of recognized agents, including Bacillus anthracis (the agent responsible for anthrax), variola virus (which causes smallpox), and a few others, for obvious reasons; but much of the preparation should target a broader list and effectively prepare the nation for the unknown.

Appropriate government agencies and scientific organizations must evaluate emerging viruses and the genetic modification of existing viruses. Similarly, they need to consider the impact of genetic manipulations of pathogenic bacteria that enhance their virulence, particularly manipulations that render them resistant to the available antibiotics.

Although there are gaps in the scientific understanding of many potentially deadly biological agents and in the technological advances needed to anticipate and respond to their release, reliance on purely scientific or technological solutions is misguided. A much more inclusive effort is needed to build a seamless system of preparedness and response—one that can exercise the best available tools to counter biological threats.

This task depends first and foremost on rebuilding the public health infrastructure of the United States, which has been allowed to decay as the nation conquered some of the more common infectious and other disease challenges of the past century. The terrorist events of September and October 2001 should serve as a wake-up call to those in the position of setting science and health policies in the United States. Many of the scientific goals described in this chapter cannot be achieved in the absence of trained and well-equipped public health officers, educated and prepared first responders, and clear communication among leaders, the medical community, and the public.

HHS, CDC, and other federal agencies, along with state departments of

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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health, have begun to consider the best ways to educate health care professionals for effectively responding to bioterrorism. This country’s public health schools and professional societies have a major role to play both in training individuals and in researching ways to build a more responsive public health system. Various entities with some knowledge of bioterrorism, such as medical associations, have already prepared educational materials. The American Medical Association, for example, has produced an excellent primer to help physicians recognize and treat diseases likely to be caused by acts of bioterrorism. Regular updating of physicians and other health care professionals, perhaps through mandatory continuing education courses on the agents that pose the greatest threats, would be prudent. Meanwhile, training in this area should be part of the basic curricula for all aspiring health care professionals. Agencies and other institutions also face a major challenge in training first responders, such as firefighters and police, as well as in educating leaders and influential nonhealth professionals, such as teachers, on the realistic threats of bioterrorism and the ways in which they can be empowered to protect themselves and their communities.

But countering terrorism is not the only incentive for such actions. In 1992, the Institute of Medicine published a groundbreaking report, Emerging Infections: Microbial Threats to Health in the United States (IOM, 1992). It pointed out that “pathogenic microbes can be resilient, dangerous foes. Although it is impossible to predict their individual emergence in time and place, we can be confident that new microbial diseases will emerge” (p. 32). Thus, preparedness is essential not only for countering bioterrorism but also for facing the constantly evolving threat of infectious diseases, particularly the widespread escalation of bacterial pathogens resistant to all known antibiotics.

In reality, humans and the livestock and crops that sustain them are in a perpetual contest with microorganisms and the diseases that they cause—a contest that requires an armamentarium of knowledge gained from research, surveillance, and improved health practices. Humans and animals are not immune to the threat of infectious diseases just because they have been immunized or eat food and drink water that is regulated and evaluated for their safety. Serious, sometimes deadly, outbreaks of infectious diseases continue to occur naturally around the world. Even when they are treatable, these diseases take their toll in pain and suffering, inconvenience, disability, lost time from work and lost wages, and cost to the health-care system and the economy.

But preparing for the once unthinkable—a biological attack—should also prepare the U.S. population for the inevitable: the natural occurrence (or recurrence) of diseases that can affect all living things. Efforts that protect humans, animals, and plants from bioterrorism will also help us prevail in that never-ending contest with natural threats.

The reader is referred to Box 3.2 for Web sites with additional information on bioterrorism.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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BOX 3.2
Resources on the Internet with Bioterrorism Information (Accessed May 2002)

REFERENCES

Anderson, R.M. 2001. “The Application of Mathematical Models in Infectious Disease Research,” Firepower in the Lab: Automation in the Fight Against Infectious Diseases and Bioterrorism, S.P. Layne, T.J. Beugelsdijk, and C.K.N. Patel, eds., Joseph Henry Press, Washington, D.C.


Barbera, J., L. Gostin, T. Inglesby, T. O’Toole, C. DeAtley, K. Tonat, and M. Layton. 2001. “Large-Scale Quarantine Following Bioterrorism in the United States,” JAMA, Vol. 286, pp. 2711-2717.

Bradley, R.N. 2000. “Health Care Facility Preparation for Weapons of Mass Destruction,” Prehospital Emergency Care, Vol. 4, pp. 261-269.

Brinsfield, K.H., J.E. Gunn, M.A. Barry, V. McKenna, K.S. Dyer, and C. Sulis. 2001. “Using Volume-Based Surveillance for an Outbreak Early Warning System,” Academic Emergency Medicine, Vol. 8, p. 492.


Centers for Disease Control and Prevention (CDC). 2001. “Updated Guidelines for Evaluating Public Health Surveillance Systems: Recommendations from the Guidelines Working Group,” Morbidity and Mortality Weekly Report, Vol. 50, No. RR-13, pp. 1-35.

CDC. 2000. “Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response, Recommendations of the CDC Strategic Planning Working Group, Morbidity and Mortality Weekly Report, Vol. 49, No. RR04, pp. 1-14.

Committee on Emerging Microbial Threats to Health, Institute of Medicine, National Research Council. 1992. Emerging Infections: Microbial Threats to Health in the United States, Joshua Lederberg, Robert E. Shope, and Stanley C. Oaks, Jr., eds., National Academy Press, Washington, D.C.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Cox, N.J., and K. Subbarao. 2000. “Global Epidemiology of Influenza: Past and Present,” Annual Review of Medicine, Vol. 51, pp. 407-421.

Cummings, C.A., and D.A. Relman. 2000. “Using DNA Microarrays to Study Host-Microbe Interactions,” Emerging Infectious Diseases, Vol. 6, No. 5, pp. 513-525.

Cummings, C.A., and D.A. Relman. 2002. “Microbial Forensics—When Pathogens Are “Cross-Examined,” Science, May 9.


Defense Threat Reduction Agency. 2001. Human Behavior and WMD Crisis/Risk Communication—Final Report from a Workshop, March. Available online at <http://www.dtra.mil/about/organization/finalreport.pdf>.


Fine, A., and M. Layton. 2001. “Lessons from the West Nile Viral Encephalitis Outbreak in New York City, 1999: Implications for Bioterrorism Preparedness,” Clinical Infectious Diseases, Vol. 32, pp. 277-282.


Gust, I.D., A.W Hampson, and D. Lavanchy. 2001. “Planning for the Next Pandemic of Influenza,” Reviews in Medicine Virology 2001, Vol. 11, pp. 59-70.


Hilleman, M.R. 2001. “Current Overview of the Pathogenesis and Prophylaxis of Measles with Focus on Practical Implications,” Vaccine, Vol. 20, pp. 651-665.


Institute of Medicine. 1992. Emerging Infections: Microbial Threats to Human Health, National Academy Press, Washington, D.C.

Institute of Medicine. 1999. Chemical and Biological Terrorism: Research and Development to Improve Civilian Medical Response, National Academy Press, Washington, D.C.

Institute of Medicine. 2002. Preparing for Terrorism: Tools for Evaluating the Metropolitan Medical Response System Program, National Academy Press, Washington, D.C.

Interagency Task Force on Antimicrobial Resistance. 2000. A Public Health Action Plan to Combat Antimicrobial Resistance. Available online at <http://www.cdc.gov/drugresistance/actionplan/html/index.htm>.


Layne, S.P., and T.J. Beugelsdijk. 1998. “Laboratory Firepower for Infectious Disease Research,” Nature Biotechnology, Vol. 16, No. 9, pp. 825-829.

Layne, S.P., T.J. Beugelsdijk, and C.K.N. Patel, eds. 2001. Firepower in the Lab: Automation in the Fight Against Infectious Diseases and Bioterrorism, Joseph Henry Press, Washington, D.C.

Layne, S.P., T.J. Beugelsdijk, J.K. Taubenberger, N.J. Cox, I.D. Gust, A.J. Hay, M. Tashiro, and D. Lavanchy. 2001. “Global Laboratory Against Influenza,” Science, Vol. 293, p. 1729.


MacDonald, J.M., M.E. Ollinger, K.E. Nelson, and C.R. Handy. 1999. “Consolidation in U.S. Meatpacking,” Agricultural Economics Report, No. 785. Available at USDA-ERS Web site.

Murch, R.S. 2001. “Forensic Perspective on Bioterrorism and the Proliferation of Bioweapons,” Firepower in the Lab: Automation in the Fight Against Infectious Diseases and Bioterrorism, S.P. Layne, T.J. Beugelsdijk, and C.K.N. Patel, eds., Joseph Henry Press, Washington, D.C.


National Institute of Allergy and Infectious Diseases. 2002. NIAID Biodefense Research Agenda for CDC Category A Agents: Responding Through Research, National Institutes of Health, February. Available online at <http://www.niaid.nih.gov/dmid/pdf/biotresearchagenda.pdf>.

National Research Council. 2002. Countering Agricultural Bioterrorism (in press).

Nikkari, S., Lopez, F.A., Lepp, P.W., Cieslak, P.R., Ladd-Wilson, S., Passaro, D., Danila, R., Relman, D.A. 2000. “Broad-Range Bacterial Detection and the Analysis of Unexplained Death and Critical Illness,” Emerging Infectious Diseases, Vol. 8, No. 2, pp. 188-194.


Peters, C.J. 2002. “Many Viruses Are Potential Agents of Bioterrorism,” ASM News, Vol. 68, pp. 168-173.

Pizza, Mariagrazia, et al. 2000. “Identification of Vaccine Candidates Against Serogroup B Meningococcus by Whole-Genome Sequencing,” Science, Vol. 287, pp. 1816-1820.


Raber, E., A. Jin, K. Noonan, R. McGuire, and R.D. Kirvel. 2001. “Decontamination Issues for Chemical and Biological Warfare Agents: How Clean Is Clean Enough?” International Journal of Environmental Health Research, Vol. 11, pp. 128-148.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×

Taubenberger, J.K., A.H. Reid, and T.G. Fanning. 2000. “The 1918 Influenza Virus: A Killer Comes Into View,” Virology, Vol. 274, pp. 241-245.


U.S. General Accounting Office. 2000. West Nile Virus Outbreak: Lessons for Public Health Preparedness, HEHS-00-180, Washington, D.C.


Von Bredow, J., M. Myers, D. Wagner, J.J. Valdes, L. Loomis, and K. Zamani. 1999. “Agricultural Infrastructure Vulnerability,” Annals of the New York Academy of Sciences, p. 894.

Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
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Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 66
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 67
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 68
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 69
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 70
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 71
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 72
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 73
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 74
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 75
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 76
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 77
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 78
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 79
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 80
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 81
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 82
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 83
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 84
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 85
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 86
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 87
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 88
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 89
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 90
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 91
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 92
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 93
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 94
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 95
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 96
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 97
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 98
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 99
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 100
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 101
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 102
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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Page 103
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
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Page 104
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 105
Suggested Citation:"3. Human and Agricultural Health Systems." National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, DC: The National Academies Press. doi: 10.17226/10415.
×
Page 106
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Vulnerabilities abound in U.S. society. The openness and efficiency of our key infrastructures – transportation, information and telecommunications systems, health systems, the electric power grid, emergency response units, food and water supplies, and others – make them susceptible to terrorist attacks. Making the Nation Safer discusses technical approaches to mitigating these vulnerabilities.

A broad range of topics are covered in this book, including:

  • Nuclear and radiological threats, such as improvised nuclear devices and “dirty bombs;”
  • Bioterrorism, medical research, agricultural systems and public health;
  • Toxic chemicals and explosive materials;
  • Information technology, such as communications systems, data management, cyber attacks, and identification and authentication systems;
  • Energy systems, such as the electrical power grid and oil and natural gas systems;
  • Transportation systems;
  • Cities and fixed infrastructures, such as buildings, emergency operations centers, and tunnels;
  • The response of people to terrorism, such as how quality of life and morale of the population can be a target of terrorists and how people respond to terrorist attacks; and
  • Linked infrastructures, i.e. the vulnerabilities that result from the interdependencies of key systems;

In each of these areas, there are recommendations on how to immediately apply existing knowledge and technology to make the nation safer and on starting research and development programs that could produce innovations that will strengthen key systems and protect us against future threats. The book also discusses issues affecting the government’s ability to carry out the necessary science and engineering programs and the important role of industry, universities, and states, counties, and cities in homeland security efforts.

A long term commitment to homeland security is necessary to make the nation safer, and this book lays out a roadmap of how science and engineering can assist in countering terrorism.

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