Assessing the Spectrum of Biological Risks

Abstract

From naturally occurring disease threats to the deliberate creation of biological weapons, the field of biosecurity encompasses a broad swath of life science research and the associated risks.

This special issue of the bulletin explores a range of biological risks, with each contribution examining a specific aspect of the field and the challenges that life scientists face when their work intersects with national and international security. But first, it is important to understand how broad the field of biosecurity has become. This introduction explores the spectrum of biological risks–from naturally occurring diseases in humans, animals, and plants to the unintended consequences of research or laboratory accidents to the deliberate misuse of biological agents as weapons. Then it highlights the implications of scientific and technological advances and raises key issues for assessing their risks.

Naturally occurring risks.

Naturally occurring diseases–particularly diseases with global reach, such as pandemic influenza–present the greatest international biological risk due to the enormous number of people who could be infected and the potentially catastrophic mortality levels that might arise from an outbreak. 1 Common infectious diseases (e.g., HIV/AIDS, malaria, measles, pneumonia, and tuberculosis) are responsible for approximately 14 million deaths each year. 2 Clearly, improving public health and disease prevention is the highest priority for addressing the spectrum of biological risks.

In recent years, several new and reemerging diseases have tested public health responses. For example, the SARS epidemic in 2002–2003 infected more than 8,000 people in 26 countries and caused 774 deaths. 3 And between 2003 and 2009, avian influenza infected 442 people and caused 262 deaths. 4 Recently, the swine influenza outbreak has resulted in more than 622,000 infections throughout the world and at least 7,800 deaths reported to the World Health Organization (WHO) as of November 22. 5 Thus, disease detection and surveillance systems are crucial to countering naturally occurring diseases (and to countering the whole range of biological risks, in fact). Article X of the Biological Weapons Convention (BWC) encourages international cooperation in disease prevention. At the BWC Meeting of Experts in August 2009, States Parties discussed the importance of “common understanding and effective action on promoting capacity building in the fields of disease surveillance, detection, diagnosis, and containment of infectious diseases.” 6 Of course, detection and surveillance is only the first step. For containment, developing broad-spectrum treatments including vaccines, antibiotics, antiviral drugs, and immune modulators is also necessary. Complicating factors such as antimicrobial resistance require new antibiotics and possibly radically new approaches to drug treatment. 7 In short, there is much to be done on a global level to tackle both common infections and new and emerging diseases.

Unintended risks.

The unintended consequences of scientific research are commonly described as dual-use risks. The U.S. National Science Advisory Board for Biosecurity defines dual-use research of concern as “research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health, agriculture, plants, animals, the environment, or materiel.” 8 In 2004 the U.S. National Research Council highlighted seven general classes of experiment that carry the greatest risk of misuse. 9 The challenge facing the scientific community is to manage dual-use risks without jeopardizing advances in research and the associated benefits for combating naturally occurring infectious diseases. Central to this is the need to maintain openness and transparency in scientific knowledge while raising awareness and developing a culture of responsibility among life scientists worldwide. 10 Greater awareness of dual-use risks and knowledge of the BWC's prohibitions can contribute to managing these risks and limiting negligence.

A 2009 U.S. National Research Council survey of American scientists, for instance, found that there is a need to expand the dual-use dialogue within the wider life sciences community. 11 However, in developing constructive dialogue it will be important to weigh the likely benefits of scientific research against any potential risks of misuse. The survey also identified a critical need to better define the scope of what is considered dual-use research of concern. 12 This suggests another problem: Scientists and other interested parties may come to different conclusions about the risks associated with a given piece of research–making it all the more difficult to convey a clear message to policy makers and to agree upon a standard set of guidelines.

Just as the risks posed by dual-use research can be countered in part by education and communication, the risks that laboratory accidents pose to the public and the environment can be mitigated with good training, proper laboratory design and management, and the appropriate maintenance of high-containment facilities. The process of “Good Laboratory Practice” also limits the risk to those who work there. Of course, when these procedures are not adhered to, risks will necessarily be greater–regardless of where the lab is located. Although concerns over the implementation of proper biosafety practices focus largely on the developing world, the potential for accidents in countries with advanced biotechnology infrastructure and safety regulation has been illustrated by a number of incidents; the British foot-and-mouth disease outbreak in 2007, in which live virus escaped into the environment from a vaccine facility due to an ill-maintained drainage system, is only one such example. 13

The challenge facing the scientific community is to manage dual-use risks without jeopardizing advances in research and the associated benefits for combating naturally occurring infectious diseases.

The expansion of high-containment laboratories worldwide has the potential to reduce laboratory risks if best practices and regular maintenance are followed, since more work can be carried out at high-containment levels with fewer risks of laboratory infection or pathogen escape. Of course, if biosafety is not strictly enforced, such an expansion could exacerbate laboratory risks. Lessons from the management of existing high-containment laboratories and associated accidents should undoubtedly inform this expansion.

Deliberate misuse.

The risk of misuse of knowledge, products, or technology in the life sciences applies both to states and non-state groups or individuals. Therefore, the potential threat of bioterrorism by non-state actors should not obscure concerns that states may remain interested in, or consider revisiting, biological weapons research–particularly considering the many military programs that have developed biological weapons against humans, animals, and plants in the past. 14

The potential for state-sponsored biological weapons programs is exacerbated by existing weaknesses in the BWC, which has a very limited institutional base–in the form of the Implementation Support Unit–and no mechanism to verify compliance with its prohibitions. 15 A June 2009 report by the British Institute for Public Policy Research's Commission on National Security in the Twenty-First Century called on the British government to help revitalize efforts to develop an effective verification regime for the BWC and establish an Organization for the Prohibition of Biological Weapons akin to the institution that underpins the Chemical Weapons Convention. 16 While strategic or operational concerns could lead a country to breach its commitments under the BWC, one particular concern is the persistent operational interest of some countries–including Russia, the United States, and the Czech Republic–in the development of “mid-spectrum” agents as incapacitating weapons for use in law enforcement and counterterrorism. The focus has been on chemical agents, such as potent anesthetic and sedative drugs, but consideration also has been given to biological agents, including bioregulatory neuropeptides, which modulate cognition, perception, mood, motivation, and consciousness. 17

A separate dimension of such state-related biological risks is the potential for defensive biological weapons research to unintentionally increase the risk of the deliberate development of biological weapons. The history of biological weapons programs shows that misperceptions of capability and intent on the part of state intelligence organizations can lead to arms races and “mirror imaging.” 18 Of course, this implies that transparency is vital to avoiding mis-perceptions of national biodefense research programs among other states and a way of improving this would be for States Parties to the BWC to improve their Confidence-Building Measure submissions and to make them publicly available. 19

Non-state groups with particular political aims may not find the use of biological weapons (especially highly transmissible agents whose spread cannot be confined to one particular geographic area) compatible with their political goals. Nevertheless, the overall risk becomes more acute in cases of extremists with apocalyptic ideologies or sociopathic tendencies. Despite widespread attention to the risks of bioterrorism during the last few decades, there have been very few incidents. Notable exceptions include the 1984 contamination of restaurant salad bars with salmonella by the Rajneeshee cult in Oregon, an event that sickened more than 700 people; the failed 1995 attempt by the Aum Shinrikyo cult to spread anthrax in Japan involving the use of a non-pathogenic strain; and the 2001 anthrax letter attacks in the United States that infected 17 people and killed five. 20

Despite the low number of deaths from bioterrorism in comparison to the large mortality rates from infectious diseases, the United States and other countries have invested significantly in biodefense research and preparedness, particularly focusing on responding to bioterrorism. Subsequently, this has increased the legislative burden for those working with certain microorganisms (so-called select agents). Some researchers and policy experts have raised concerns about the potential for expanded research on diseases such as anthrax and restrictive legislation to adversely affect investment in naturally occurring infectious disease research. 21 Similarly, concern over a potential “insider threat” from laboratory workers has increased since the FBI concluded in 2008 that a U.S. government scientist was responsible for the 2001 anthrax letters. 22 This has, in fact, led to a more specific focus on vetting the people permitted to access high-containment laboratories and select agents–what are called personnel reliability programs, which have long been a feature of access to sensitive military sites. Although there is pressure to expand these programs in the aftermath of the FBI investigation, there is also some skepticism of their value, particularly since the perpetrator of the U.S. attacks was subject to such a program. In short, it is important to meet these security concerns–both international and domestic–in a manner that does not hamper scientific research while also ensuring that the assessment of international researchers is managed in such a way that it does not unnecessarily restrict collaborative research and obstruct international cooperation.

Several published experiments have been highlighted as illustrations of the dual-use risks associated with scientific advances–including the engineering in 2001 of a recombinant ectromelia virus (the causative agent of mousepox) to express interleukin-4 protein that inadvertently created a more virulent strain.

Keeping pace with science and technology.

The nature of biological risks is constantly changing as advances in the life sciences and the increasing accessibility of associated biotechnologies create new dual-use risks and possibilities for deliberate misuse that need to be reassessed regularly. 23 The likely benefits, however, should be weighed with any potential risks since these same advances are central to developing more effective responses to the whole spectrum of biological risks, naturally occurring diseases in particular. Several published experiments have been highlighted as illustrations of the dual-use risks associated with scientific advances–including the engineering in 2001 of a recombinant ectromelia virus (the causative agent of mousepox) to express interleukin-4 (IL-4) protein that inadvertently created a more virulent strain, the construction in 2002 of live poliovirus using synthetic DNA segments and the available viral genome sequence, and the reconstruction in 2005 of the 1918 Spanish influenza pandemic virus. 24 While dual-use discussions have brought these scientific developments to a wider audience, some experiments portrayed as “surprises” can be found in the prior scientific literature: A 1981 paper described the recreation of infectious polio virus from DNA, for example, and a 1998 paper described the role of IL-4 on poxvirus virulence. 25

Whether planned or unplanned, advances in science and technology have the potential to expand the scope of deliberate misuse of biological agents and ultimately make it easier for both states and non-state groups or individuals to develop and use biological weapons. 26 In the near term, state interest in biological weapons would present a more significant risk given the available resources and access to science and technology. Over the longer term, however, the risk from non-state groups and individuals may increase as access to relevant technologies broadens and disperses and associated costs decrease, potentially lowering the barriers to deliberate misuse.

Of course, as science advances, the attention paid to biological risks should not be limited to a particular list of agents. In fact, the U.S. National Research Council recommended a “broadened awareness of threats beyond the classical ‘select agents’ and other pathogenic organisms and toxins.” 27 Non-pathogens can be engineered to be pathogenic, and advances in DNA synthesis may even enable the development of novel pathogens. Considering how quickly knowledge of the molecular basis underlying biological processes is expanding, the boundaries between chemical and biological agents are blurring. In the context of deliberate misuse, such increased understanding may enable interference with specific biological processes in order to exert a wide range of effects on the human body, leading to a shift in focus from particular agents to specific targets in the human body. Neuropeptides, for example, are of great interest to the pharmaceutical industry. Such agents might be used deliberately for harmful purposes, and the risk could be exacerbated by advances in drug-delivery technology that facilitate the targeting of peptides in the body. 28

Developments in DNA sequencing and synthesis technologies particularly relevant to the advancing field of synthetic biology–the deliberate design of novel biological systems with applications in diverse fields such as medicine, energy, and the environment–demonstrate the overall pace of change and spread of biotechnologies, where speed and productivity are increasing while costs are reducing. 29 The cost of sequencing an entire human genome is expected to decrease to $1,000 in the coming years. As the most reliable and fastest tool for identifying pathogens, DNA sequencing is central to the future development of effective vaccines and drugs and could play a significant role in assessing an individual's susceptibility to disease. As development continues, the field will draw upon advances in automation and smaller DNA synthesis and genome assembly technologies. Such advances are enabling significant achievements, as illustrated by MIT's International Genetically Engineered Machine competition (commonly referred to as iGEM). 30 Meanwhile, lower costs and increasingly broad access to technology has allowed biotechnology to become an amateur pursuit among a growing community of so-called do-it-yourself biologists. 31

The technology and knowledge that emerge from these and other scientific advances will raise further dual-use concerns over the potential risks, both unintended and deliberate. 32 The wide availability of sequencing technology (providing the knowledge of genomes of pathogens) and synthetic biology (providing the tools for synthesis of pathogens) will facilitate wider access to dangerous pathogens that could be used for harmful purposes, and ultimately may enable the development of novel human-made pathogens. Furthermore, as these technologies become more “user-friendly” and portable, the manipulation of genomes may require less scientific and technical knowledge. However, it is important not to exaggerate the risk of misuse. To wit, much remains to be understood about the mechanisms underlying virulence in microorganisms and links to transmissibility. Thus any future attempt to design a novel pathogen that both causes disease and is easily transmissible will no doubt be extremely complicated.

Communicating clear scientific advice about these risks to policy makers is paramount and complementary to any risk assessment methodology. Particularly salient in these communications is the extent to which reliable estimations of risk can be formed in the face of uncertainty.

New approaches to risk assessment.

The current methodologies for assessing the wide range of biological risks would benefit from harmonization across sectors, both within countries and internationally, to enable more effective policy making, resource allocation, international cooperation, and sharing of best practices. Development of such a unified methodology to inform biological risk assessment would require multidisciplinary involvement and wide international representation, drawing on the existing work of national and international organizations. Any such comprehensive risk assessment model should recognize a series of “framing assumptions”–the variety of viewpoints and uncertainties that give context to assessing risk–which may include socioeconomic, security, and political factors. 33 Another important component to incorporate into any risk assessment is the timescale. While extrapolations are required for assessing naturally occurring, unintended, and deliberate risks, over long timescales the potential for new risks may increase most markedly in the context of deliberate misuse due to the pace of scientific and technological advances.

Communicating clear scientific advice about these risks to policy makers is paramount and complementary to any risk assessment methodology. Particularly salient in these communications is the extent to which reliable estimations of risk can be formed in the face of uncertainty. Given the varied nature of risks and the varying availability of data against which to test mathematical models, a common approach should incorporate a range of specific assessments at points on the spectrum coupled with an overarching model to unify the resulting risk assessments. This overarching risk assessment model would build on similarities across the spectrum and might focus on common uncertainties, both naturally occurring and deliberate, such as the specific properties of biological agents posing the greatest risk. It is worth noting that a key issue in judging the risk of deliberate misuse is the need to assess and model intent, which includes an assessment of what informs the decision to acquire and use a biological weapon, the target selection, and the scale of an attack.

Risk assessments also must incorporate an evaluation of the consequences of different countermeasures to ascertain whether they actually reduce risks, potentially create new risks, or exacerbate existing risks. This net assessment approach would highlight the most effective countermeasures and show where responses to risks at one part of the spectrum can mitigate risks at another. An overall cost-benefit analysis of different countermeasures would strengthen the risk assessment process and inform a mutually reinforcing patchwork of measures to manage risks. While no single countermeasure can be a silver bullet, this approach may provide a blueprint for prioritizing the responses that will have the most impact on the full range of biological risks on a global level. Due to limited data there will be less certainty of risk assessments associated with the deliberate misuse of biological agents as weapons. For this reason, countermeasures that can be applied across the spectrum are likely to be less risky investments, since their effectiveness can be better determined. Such countermeasures include increased preparedness (e.g., stockpiles of therapeutics and vaccines), early detection measures (e.g., disease surveillance and diagnostics), and rapid response measures (e.g., genome sequencing and rapid vaccine production).

Within biological risk assessment it is also important to recognize the role that epidemiological modeling of disease, economic modeling, and qualitative social science modeling of human behavior can play and to link these models together. Public perceptions and media reactions may influence policy makers' decisions on biological risks, particularly in the context of risk management and communication. Therefore, any risk assessment methodology needs to include an evaluation of human behavior and motivations and feedback loops that address the public's reaction to government risk management policies. Lessons from the modeling of pandemic flu in Britain highlight the importance of understanding social and economic factors–and particularly their interconnectedness–in the progression of a pandemic in order to inform response measures. For naturally occurring diseases, public behaviors and perceptions are relevant at the level of groups and populations. Yet when it comes to deliberate misuse, attention must be focused on the behaviors at the level of the individual, as illustrated by the 2001 anthrax letter attacks. As emerging biotechnologies become more widely available and diffuse, understanding behaviors at the individual level may become increasingly relevant to assessing deliberate biological risks. In this context, the analogy of cybersecurity may be useful, particularly with regard to the motives and behavior of computer hackers and insights this may give for the emerging community of “biohackers.” 34

Moving forward.

Reviewing the spectrum of biological risk highlights the everyday dangers posed by naturally occurring diseases and reinforces the need to meet security concerns associated with unintended or deliberate risks in a way that does not negatively impact scientific and technological research aimed at strengthening public health. In this sense it is important both to keep pace with advances in science and technology and to balance the benefits against any potential risks associated with these advances. Approaches to biological risk assessment that address the whole spectrum will help identify measures that can mitigate risks across the spectrum while highlighting counterproductive strategies. Internationalizing this approach will be central to concentrating efforts on approaches that have the greatest impact on reducing risks at a global level.