Knowledge, materials, and technologies with applications to the life sciences enterprise are advancing with tremendous speed, making it possible to identify and manipulate features of living systems in ways never before possible. On a daily basis and in laboratories around the world, biomedical researchers are using sophisticated technologies to manipulate microorganisms in an effort to understand how microbes cause disease and to develop better preventative and therapeutic measures against these diseases. Plant biologists are applying similar tools in their studies of crops and other plants in an effort to improve agricultural yield and explore the potential for the use of plants as inexpensive manufacturing platforms for vaccine, antibody, and other products. Similar efforts are underway with animal husbandry. Scientists and engineers in many fields are relying on continuing advances in the life sciences to identify pharmaceuticals for the treatment of cancer and other chronic diseases, develop environmental remediation technologies, improve biodefense capabilities, and create new materials and even energy sources.
Moreover, other fields not traditionally viewed as biotechnologies—such as materials science, information technology, and nanotechnology—are becoming integrated and synergistic with traditional biotechnologies in extraordinary ways enabling the development of previously unimaginable technological applications. It is undeniable that this new knowledge and these advancing technologies hold enormous potential to improve public health and agriculture, strengthen national economies, and close
the development gap between resource-rich and resource-poor countries. However, as with all scientific revolutions, there is a potential dark side to the advancing power and global spread of these and other technologies. For millennia, every major new technology has been used for hostile purposes, and most experts believe it naive to think that the extraordinary growth in the life sciences and its associated technologies might not similarly be exploited for destructive purposes.
This is true despite formal prohibitions against the use of biological weapons and even though, since antiquity, humans have reviled the use of disease-causing agents for hostile purposes. In its most recent unclassified report on the future global landscape, the National Intelligence Council predicted that a major terrorist attack employing biological agents will likely occur by 2020, although it suggested that most future (i.e., over the course of the next 15 years) terrorist attacks are expected to involve conventional weapons. Official U.S. statements continue to cite around a dozen countries that are believed to have or to be pursuing a biological weapons capability. In addition to the efforts by terrorists or states with malevolent intent, we must be concerned about the grave harm that may result from misuse of the life sciences and related technologies by individuals or groups that are simply careless or irresponsible.
The continuing threat of bioterrorism, coupled with the global spread of expertise and information in biotechnology and biological manufacturing processes, has raised concerns about how advancing technological prowess could enable the creation and production of new threats of biological origin possessing unique and dangerous but largely unpredictable characteristics. The Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats, an ad hoc committee of the National Research Council and the Institute of Medicine, was constituted to examine current trends and future objectives of research in the life sciences, as well as technologies convergent with the life sciences enterprise from other disciplines, such as materials science and nanotechnology, that may enable the development of a new generation of biological threats over the next five to ten years, with the aim of identifying ways to anticipate, identify, and mitigate these dangers.
Specifically, the charge to the committee was to:
Examine current scientific trends and the likely trajectory of future research activities in public health, life sciences, and biomedical and materials science that contain applications relevant to the development of “next generation” agents of biological origin five to ten years into the future.
Evaluate the potential for hostile uses of research advances in ge-
netic engineering and biotechnology that will make biological agents more potent or damaging. Included in this evaluation will be the degree to which the integration of multiple advancing technologies over the next five to ten years could result in a synergistic effect.
Identify the current and potential future capabilities that could enable the ability of individuals, organizations, or countries to identify, acquire, master, and independently advance these technologies for both beneficial and hostile purposes.
Identify and recommend the knowledge and tools that will be needed by the national security, biomedical science, and public health communities to anticipate, prevent, recognize, mitigate, and respond to the destructive potential associated with advancing technologies.
This report is part of a larger body of work that the National Academies has undertaken in recent years on science and security and the contributions that science and technology could make to countering terrorism, beginning with Scientific Communication and National Security in 1982 and continuing with Chemical and Biological Terrorism: Research and Development to Improve Civilian Medical Responses (1999), Firepower in the Lab: Automation in the Fight Against Infectious Diseases and Bioterrorism (2001), Making the Nation Safer: The Role of Science and Technology in Countering Terrorism (2002), Biological Threats and Terrorism: Assessing the Science and Response Capabilities (2002), and Countering Agricultural Terrorism (2002). Most recently and of particular relevance to this report is the National Research Council report Biotechnology Research in an Age of Terrorism (2004). The principal difference between that report and the present report is that the former revolves around issues pertaining to the regulatory oversight of research employing biotechnology and the flow of scientific knowledge derived from the use of biotechnology, with a focus on the United States. In contrast, this report adopts a more global perspective, addressing the increasing pace of advances in the life sciences and related convergent technologies likely to alter the biological threat spectrum over the next five to ten years and broadly considering ways to prevent or mitigate the consequences of malevolent exploitation or naïve misapplication of these technologies.
While many readers might hope to find a well-defined, prioritized list or set of lists of future threats, the pace of research discovery in the life sciences is such that the useful lifespan of any such list would likely be measured in months, not years. Instead, the committee sought to define more broadly how continuing advances in life sciences technologies could contribute to the development of novel biological weapons and to develop a logical framework for analysts to consider as they evaluate the evolving technology threat spectrum. The committee concluded that there
are classes or categories of advances that share important features relevant to their potential to contribute to the future development of new biological weapons. These shared characteristics are based on common purposes, common conceptual underpinnings, and common technical enabling platforms. Thinking of technologies within this framework should help in evaluating the potential they present for beneficial and destructive applications or technological surprise(s).
The committee classified new technologies according to a scheme organized around four groupings: (1) technologies that seek to acquire novel biological or molecular diversity; (2) technologies that seek to generate novel but pre-determined and specific biological or molecular entities through directed design; (3) technologies that seek to understand and manipulate biological systems in a more comprehensive and effective manner; and (4) technologies that seek to enhance production, delivery, and “packaging” of biologically active materials. This classification scheme highlights commonalities among technologies and, by so doing, draws attention to critical enabling features; provides insight into some of the drivers behind life sciences-related technologies; facilitates predictions about future emerging technologies; and lends insight into the basis for complementarities or synergies among technologies and, as such, facilitates the analysis of interactions that lead to either beneficial or potentially malevolent ends.
To a considerable extent, new advances in the life sciences and related technologies are being generated not just domestically but also internationally. The preeminent position that the United States has enjoyed in the life sciences has been dependent upon the flow of foreign scientific talent to its shores and is now threatened by the increasing globalization of science and the international dispersion of a wide variety of related technologies. The increasing pace of scientific discovery abroad and the fact that the United States may no longer hold a monopoly on these leading technologies means that this country is, as never before, dependent on international collaboration, a theme that is explored in depth in Chapter 2.
Foreign scientific exchange is an integral and essential component of the culture of science. The training of scientists from other countries in the United States has played an important role in fostering these interactions and has contributed substantially to the productivity of the American scientific enterprise. It has, however, been threatened recently by increased scrutiny of visa applications as well as the growing attractiveness of science and technology training opportunities outside of the United States. As technological growth becomes increasingly dependent on the global commons, international scientific exchanges and collaborations become an ever more vital component of U.S. technological capacity, including
biodefense technological capacity. Weakening this link by prohibiting or discouraging bi-directional foreign scientific exchange—including the engagement of foreign students and scientists in U.S. laboratories, meetings, and business enterprises—could impede scientific and technological growth and have counterproductive, unintended consequences for the biodefense research and development enterprise.
Although this Report is concerned with the evolution of scientific and technological capabilities over the next five to ten years with implications for next-generation threats, it is clear that today’s capabilities in the life sciences and related technologies have already changed the nature of the biothreat “space.” The accelerating pace of discovery in the life sciences has fundamentally altered the threat spectrum. The immune, neurological, and endocrine systems are particularly vulnerable to disruption by manipulation of bioregulators. Some experts contend that bioregulators, which are small, biologically active compounds, pose an increasingly apparent dual-use risk. This risk is magnified by improvements in targeted delivery technologies that have made the potential dissemination of these compounds much more feasible than in the past.
The viruses, microbes, and toxins listed as “select agents” or “category A/B/C agents” and on which U.S. biodefense research and development activities are so strongly focused today are just one aspect of the changing landscape of threats. Although some of them may be the most accessible or apparent threat agents to a potential attacker, particularly one lacking a high degree of technical expertise, this situation is likely to change as a result of the increasing globalization and international dispersion of the most cutting-edge aspects of life sciences research.
The committee concluded that a broad array of mutually reinforcing actions are required to successfully manage the threats that face society. These must be implemented in a manner that engages a wide variety of communities that share stakes in the outcome. As in fire prevention, where the best protection against the occurrence of and damage from catastrophic fires comprises a multitude of interacting preventive and mitigating actions (e.g., fire codes, smoke detectors, sprinkler systems, fire trucks, fire hydrants, and fire insurance) rather than any single “best” but impractical or improbable measure (e.g., stationing a fire truck on every block), the same is true here. The committee, therefore, envisions a broad-based, intertwined network of steps—a web of protection—for reducing the likelihood that the technologies discussed in this report will be used successfully for malevolent purposes. It believes that the actions suggested in its recommendations (Box ES-1), taken in aggregate, will likely decrease the risk of inappropriate application or unintended misuse of these increasingly widely available technologies.
1. The committee endorses and affirms policies and practices that, to the maximum extent possible, promote the free and open exchange of information in the life sciences.
1a. Ensure that, to the maximum extent possible, the results of fundamental research remain unrestricted except in cases where national security requires classification, as stated in National Security Decision Directive 189 (NSDD-189) and endorsed more recently by a number of groups and organizations.
1b. Ensure that any biosecurity policies or regulations implemented are scientifically sound and are likely to reduce risks without unduly hindering progress in the biological sciences and associated technologies.
1c. Promote international scientific exchange(s) and the training of foreign scientists in the United States.
2. The committee recommends adopting a broader perspective on the “threat spectrum.”
2a. Recognize the limitations inherent in any agent-specific threat list and consider instead the intrinsic properties of pathogens and toxins that render them a threat and how such properties have been or could be manipulated by evolving technologies.
2b. Adopt a broadened awareness of threats beyond the classical “select agents” and other pathogenic organisms and toxins, so as to include, for example, approaches for disrupting host homeostatic and defense systems and for creating synthetic organisms.
3. The committee recommends strengthening and enhancing the scientific and technical expertise within and across the security communities.
3a. Create by statute an independent science and technology advisory group for the intelligence community.
3b. The best available scientific expertise and knowledge should inform the concepts, plans, activities, and decisions of the intelligence, law enforcement, homeland security, and public policy communities and the national political leadership about advancing technologies and their potential impact on the development and use of future biological weapons.
3c. Build and support a robust and sustained cutting-edge analytical capability for the life sciences and related technologies within the national security community.
3d. Encourage the sharing and coordination, to the maximum extent possible, of future biological threat analysis between the domestic national security community and its international counterparts.
4. The committee recommends the adoption and promotion of a common culture of awareness and a shared sense of responsibility within the global community of life scientists.
4a. Recognize the value of formal international treaties and conventions, including the 1972 Biological and Toxin Weapons Convention (BWC) and the 1993 Chemical Weapons Convention (CWC).
4b. Develop explicit national and international codes of ethics and conduct for life scientists.
4c. Support programs promoting beneficial uses of technology in developing countries.
4d. Establish globally distributed, decentralized, and adaptive mechanisms with the capacity for surveillance and intervention in the event of malevolent applications of tools and technologies derived from the life sciences.
5. The committee recommends strengthening the public health infrastructure and existing response and recovery capabilities.
5a. Strengthen response capabilities and achieve greater coordination of local, state, and federal public health agencies.
5b. Strengthen efforts related to the early detection of biological agents in the environment and early population-based recognition of disease outbreaks, but deploy sensors and other technologies for environmental detection only when solid scientific evidence suggests they are effective.
5c. Improve the capabilities for early detection of host exposure to biological agents, and early diagnosis of the diseases they cause.
5d. Provide suitable incentives for the development and production of novel classes of preventative and therapeutic agents with activity against a broad range of biological threats, as well as flexible, agile, and generic technology platforms for the rapid generation of vaccines and therapeutics against unanticipated threats.
The committee endorses and affirms policies and practices that, to the maximum extent possible, promote the free and open exchange of information in the life sciences.
Overall, society has gained from advances in the life sciences because of the open exchange of data and concepts. The many ways that biological knowledge and its associated technologies have improved and can continue to improve biosecurity, health, agriculture, and other life sciences industries are highlighted in Chapter 2. Conversely, restrictive regulations and the imposition of constraints on the flow of information are not likely to reduce the risks that advances in the life sciences will be utilized with malevolent intent in the future. In fact, they will make it more difficult for civil society to protect itself against such threats and ultimately are likely to weaken national and human security. Such regulations and constraints would also limit the tremendous potential for continuing advances in the life sciences and its related technologies to improve health, provide secure sources of food and energy, contribute to economic development in both resource-rich and resource-poor parts of the world, and enhance the overall quality of human life.
The potential to develop effective countermeasures against biological threats is strongly enhanced by the nation’s leadership position in the life sciences. However, implementation of the regulatory regime imposed by the PATRIOT and Bioterrorism Response acts on the life sciences community has raised concerns that qualified individuals may be discouraged from conducting biomedical and agricultural research of value to the United States for a variety of reasons. Moreover, many features of these statutes are considered unlikely to be effective in accomplishing their desired effect—limiting access to select agents by would-be terrorists—and may, in fact, lead to unintended consequences.
The committee recommends adopting a broader perspective on the “threat spectrum.”
U.S. national biodefense programs currently focus on a relatively small number of specific agents or toxins, chosen as priorities in part because of their history of development as candidate biological weapons agents by some countries during the 20th century. The committee believes that a much broader perspective on the “threat spectrum” is needed. Recent advances in understanding the mechanisms of action of bioregulatory compounds, signaling processes, and the regulation of human gene expression—combined with advances in chemistry, synthetic biology,
nanotechnology, and other technologies—have opened up new and exceedingly challenging frontiers of concern.
The limitations of the current select agent lists, and indeed any list, point to the need for a broadened awareness of the threat spectrum. Mechanisms must be put in place to ensure regular and deliberate reassessments of advances in science and technology and identification of those advances with the greatest potential for changing the nature of the threat spectrum. The process of identifying potential threats needs to be improved. This process needs to incorporate newer scientific methodologies that permit more rigorous assessment of net overall risks. Rather than adopting a static perspective, it will be important to identify and continually reassess the degree to which scientific advances or current or future biological “platforms” hold the potential for being put to use by potential adversaries. This will require the engagement of the scientific community in new ways and an expansion of the science and technology expertise available to the intelligence community.
The committee recommends strengthening and enhancing the scientific and technical expertise within and across the security communities.
A sound defense against misuse of the life sciences and related technologies is one that anticipates future threats that result from misuse, one that seeks to understand the origins of these threats, and one that strives to preempt the misuse of science and technology. It would be tragic if society failed to consider, on a continuing basis, the nature of future biological threats, using the best available scientific expertise, and did not make a serious effort to identify possible methods for averting such threats. Interdiction and prevention of malevolent acts are far more appealing than treatment and remediation. The committee, therefore, urges a proactive, anticipatory perspective and action plan for the national and international security communities.
There are several existing problems within the national security community and national political leadership related to the task of anticipating future biological threats. First, these groups have not developed the kinds of working relationships with the “outside” (non-governmental) science and technology communities that are needed (and are feasible). Second, “inside” groups (national security community and national political leadership) have been unable to establish and maintain the breadth, depth, and currency of knowledge and subject matter expertise in the life sciences and related technologies that are needed. The number of analysts in the national security community that have professional training in the life
sciences and related technologies is small and insufficient; these analysts lose touch with the cutting edge of science and technology over time and tend to be moved from position to position, preventing them from developing any particular depth of expertise and experience. To the degree that the right kinds of expertise do exist in the analysis sectors, they do not adequately penetrate the intelligence collection process, and the expertise is distributed unevenly across these inside communities without sufficient coordination and integration. Moreover, intelligence assessments are not always shared among the different member agencies of the national security community. Finally, historical, political, and cultural barriers have prevented the national security community from working closely with counterparts from other nations and regions of the world. Yet the life sciences and related technologies are globally distributed in a seamless fashion, and future threats that arise from this science and technology will be globally distributed as well.
The committee, therefore, recommends the creation of an independent advisory group that would work closely with the national security community for the purpose of anticipating future biological threats based on an analysis of the current and future science and technology landscape, and current intelligence. In proposing the creation of this group, the committee supports Recommendation 13.1 of The Commission on the Intelligence Capabilities of the United States Regarding Weapons of Mass Destruction (March 31, 2005) that suggests the creation of a similar group, which they named the Biological Sciences Advisory Group. While the committee is mindful of the recent creation of the National Science Advisory Board for Biosecurity (NSABB) by the secretary of the U.S. Department of Health and Human Services, the current charter of the NSABB does not provide for the critical anticipatory and analytical functions that the committee envisions this new advisory group should provide to the intelligence community.
While the exact structure and specific charge of the entity that might fill this role are beyond the purview of this committee, the committee believes that the features of the advisory group, described in more detail in Chapter 4, will address critical unmet needs.
The committee recommends the adoption and promotion of a common culture of awareness and a shared sense of responsibility within the global community of life scientists.
The 1972 Biological and Toxin Weapons Convention (BWC) and the 1993 Chemical Weapons Convention (CWC) serve as cornerstones of the global biological-chemical regime, which has expanded to include rules
and procedures rooted in measures ancillary to the two treaties. The biological-chemical regime as it currently exists—including the BWC, CWC, Australia Group, Security Council Resolution (SCR) 1540, and other measures—must be recognized for its positive contributions and placed within the overall array of measures taken to prevent biological warfare. Such international conventions should not be considered the solution to the issues society confronts today with respect to potential harmful use of advances in the life sciences, nor should they be cast aside and ignored. Despite their limitations, the committee appreciates their value in articulating international norms of behavior and conduct and suggests that these conventions serve as a basis for future international discussions and collaborative efforts to address and respond to the proliferation of biological threats.
The committee also appreciates the potential for codes of conduct or codes of ethics to mitigate the risk that advances in the life sciences might be applied to the development or dissemination of biological weapons. The committee concluded that the primary effect of such codes would be to create an enabling environment that would facilitate the recognition of potentially malevolent behavior (i.e., experiments aimed at purposefully developing potential weapons of biological origin) or potentially inappropriate experiments that might unwittingly promote the creation of a more dangerous infectious agent. The committee also recognized that such codes could generally be expected to achieve their desired effect only when reinforced by a substantial educational effort and appropriate role modeling on the part of scientific leaders. The “informal curriculum” probably drives what students learn and emulate more powerfully than the formal curriculum. Identifying, celebrating, and rewarding senior scientists who through word and deed serve as role models in preventing the malicious application of advances in biotechnology is perhaps the most important element in creating an environment that enables ethical and appropriate behavior.
The committee also envisions the establishment of a decentralized, globally distributed, network of informed and concerned scientists who have the capacity to recognize when knowledge or technology is being used inappropriately or with the intent to cause harm. This network of scientists and the tools they use would be adaptive in the sense that the capacity for surveillance and intervention would evolve along with advances in technology. Such intervention could take the form of informal counseling of an offending scientist when the use of these tools appears unwittingly inappropriate or reporting such activity to national authorities when it appears potentially malevolent in intent. While decentralized and adaptive solutions are potentially limited in effectiveness, they are nonetheless of substantial interest. Their usefulness may be limited to their
ability to engender public opprobrium, but active steps to promote the development of distributed, decentralized networks of scientists will at the least heighten awareness while potentially enhancing surveillance. A good example of such a network is the Program for Monitoring Emerging Diseases, which hosts the ProMED-mail Web site. A similar instrument could be useful in establishing a shared culture of awareness and responsibility among life scientists. Such a distributed reporting and response network would be directed primarily at the community of legitimate scientists, its aggregate aim being to stimulate both creativity in anticipating activity that could be malicious, and vigilance in detecting and reporting such activity.
The committee recommends strengthening the public health infrastructure and existing response and recovery capabilities.
The committee recognizes that all of its recommended measures, taken together, provide no guarantee that continuing advances in the life sciences—and the new technologies they spawn—will not be used with the intent to cause harm. No simple or fully effective solutions exist where there is malevolent intent, even in cases where only minimal resources are available to individuals, groups, or states. Thus, its recommendations recognize a critical need to strengthen the public health infrastructure and the nation’s existing response and recovery capabilities. In keeping with the focus of this report, the committee urges that the insights and potential benefits gained through advances in the life sciences and related technologies be fully utilized in the development of new public health defenses. Although many of the concepts and suggestions embodied in these recommendations were articulated in the 2002 National Research Council report, Making the Nation Safer: The Role of Science and Technology in Countering Terrorism (“Intelligence, Detection, Surveillance, and Diagnosis,” Chapter 3, pp. 69-79), they remain as relevant and needed today as they were then.
An effective civil defense program will require a well-coordinated public health response, and this can only occur if there is strong integration of well-funded, well-staffed, and well-educated local, state, and federal public health authorities. Despite substantial efforts since September 11, 2001, few if any experts believe that the United States has achieved even a minimal level of success in accomplishing this goal, which is as important for responses to naturally-emerging threats, such as pandemic influenza, as for a deliberate biological attack. Current efforts to accomplish these aims have been woefully ineffective and have not provided the nation with the infrastructure it needs to deal rapidly, effectively, and
in a clearly coordinated manner when faced with a catastrophic event such as an overwhelming tropical cyclone, a rapidly spreading pandemic, or a large-scale bioterrorism attack. These efforts need to be enhanced and expanded.
Early and specific diagnosis, even prior to the onset of typical signs and symptoms, should be the goal of research and development efforts. While it is reasonable to hope that improved diagnostic tests will be developed as a result of current federal biodefense research efforts, it is not clear that adequate attention, prioritization, or investment have been devoted to this important area or that all of the potentially useful approaches (e.g., comprehensive monitoring of host-associated molecular biological markers) have been adequately explored. There is a similar need for early recognition and diagnosis of animal and plant diseases. Equally important is the development of broadly active vaccines or biological response modifiers capable of providing protection against large classes of agents. To date, well-established companies in the pharmaceutical and vaccine industries have had little financial incentive to develop new vaccines or therapeutics for biological threat agents for which the market is extremely uncertain and dependent ultimately on government procurement decisions. Continued efforts must be taken to address this failure of the market to produce the countermeasures needed.
Because its members believe that continuing advances in the life sciences and related technologies are essential to countering the future threat of bioterrorism, the committee’s recommendations affirm policies and practices that promote the free and open exchange of information in the life sciences. The committee also affirms the need to adopt a broader perspective on the nature of the threat spectrum and to strengthen the scientific and technical expertise available to the security communities so that they are better equipped to anticipate and manage a diverse array of novel threats. Given the global dispersion of life sciences knowledge and technological expertise, the committee recognizes the international dimensions of these issues and makes recommendations that call for the global community of life scientists to adopt a common culture of awareness and a shared sense of responsibility, including specific actions that would promote such a culture.
It remains unclear how the country’s response to a future biological attack will be managed. How will the responses of many different federal departments (e.g., Departments of Homeland Security, Health and Human Services, Justice, and Defense and the myriad agencies within them)
be effectively integrated, and who will control operations and ensure they are adequately interfaced with local and state governments and public health agencies? Although well beyond the scope of the committee’s charge, the development of an effective means of integrating the responses by multiple government agencies would provide the nation with perhaps the most necessary of “tools” with which to meet any future challenge.