developing multi-drug-resistant anthrax. Although a vaccine strain was used for this experiment, it could just as easily have been done with virulent anthrax.
Reconstruction of viable 1918 pandemic influenza virus (Tumpey et al., 2005). The virus responsible for the most notorious influenza pandemic in recorded history (with an estimated 50 million human deaths worldwide) was recently reconstructed from several different sources using molecular techniques. This tour-de-force of molecular biology (by Jeffery Taubenberger and colleagues) made it possible to study the 1918 pandemic virus for the first time. The virus could be grown and tested in several animal species, in which it caused severe disease. The purpose of the work was constructive, to better understand how the 1918 pandemic virus caused such serious disease. Even more recently, it was shown that two specific amino acid changes in the hemagglutinin (HA) surface protein of the H5N1 avian influenza virus would enable it to bind to human, rather than avian, tissues, a necessary first step in being able to readily infect humans (Yamada et al., 2006).
The motives for all the work cited here are ostensibly benign: to better understand these dangerous pathogens. But it is easy to imagine how the same techniques could be applied to other uses. At present, conducting this work requires specialized laboratory expertise at the postgraduate level or above, and the influenza genetic system is currently beyond the technical capabilities of all but a few experts. However, advances in biotechnology will make all of these techniques more accessible in the future (IOM and NRC, 2006). The powerful molecular technique for selectively copying deoxyribonucleic acid (DNA) known as the polymerase chain reaction (PCR) was so esoteric in the early to mid-1990s that performing it required painstaking technique by experienced scientists. PCR has now become so widely used and routine that it is commonplace in high school science projects and is even taught to schoolchildren visiting museum exhibitions. As another example, the complete chemical synthesis of the poliovirus genome (a small ribonucleic acid [RNA] virus) required several years of work by experts, including overcoming a number of technical difficulties (Cello et al., 2002). Since then, the George Church Laboratory at Harvard University has devised microchips that could be used to synthesize even larger genomes with far less effort (Tian et al., 2004), and other large-scale rapid DNA synthesis methods are at the advanced development stage. There has also been academic interest in “synthetic biology,” a kind of engineering using biological component parts to make entities with desired functions (Bio FAB Group et al., 2006). It is clear that future possibilities will be limited more by imagination than by technical obstacles.
Very few individuals today are capable of using these techniques, and it is likely to be some time before other than state-sponsored terrorists will be able to take advantage of such technological advances. In the meantime, conventional threats are likely to predominate. Nevertheless, if the history of PCR and other scientific advances is any indication, the use of biotechnology to engineer novel threats will come in time. It has been suggested that engineering “advanced bioweapons” is a natural extension of advancing biotechnology. In the words of the authors of a recent publication on this subject (Petro et al., 2003, p. 161):
Advances in biological research likely will permit development of a new class of advanced biological warfare (ABW) agents engineered to elicit novel effects…. Such new agents and delivery systems would provide a variety of new use options, expanding the BW paradigm. Although ABW agents will not replace threats posed by traditional biological agents such as Bacillus anthracis (anthrax) and Variola (smallpox), they will necessitate novel approaches to counterproliferation, detection, medical countermeasures, and attribution.
In consideration of these possibilities, the White House recently released Homeland Security Presidential Directive 18 (HSPD-18): Medical Countermeasures Against Weapons of Mass Destruction (The White House, 2007) as a follow-up to the original biodefense strategy embodied in HSPD-10 (The White House, 2004). HSPD-10 is the document that, among other tasks, instituted the regular threat assessment that constitutes the main thrust of this committee’s work. Setting out the outlines of the U.S. biodefense strategy, HSPD-10 states that “[t]he essential pillars of our national biodefense program are: Threat Awareness, Prevention and Protection, Surveillance and Detection, and Response and Recovery.” HSPD-18 takes this strategy a step farther, mandating that “[o]ur Nation will use a two-tiered approach for development and acquisition of medical countermeasures, which will balance the immediate need to provide a capability to mitigate the most catastrophic of the current CBRN (chemical, biological, radiological, and nuclear) threats with long-term requirements to develop more flexible, broader spectrum countermeasures to address future threats.” The biodefense tasks are divided into “Tier I: Focused Development of Agent-Specific Medical Countermeasures” for current and anticipated biological threats and “Tier II: Development of a Flexible Capability for New Medical Countermeasures” (The White House, 2007). The latter specifically recognizes the diversity of possible future biological threats, both natural and engineered, and the need for broad-spectrum solutions.
The BTRA of 2006 does not lend itself readily to the rapid assessment of new threats. Cybersecurity presents similar contrasts of comprehensiveness versus flexibility. Buckshaw et al. (2005) developed a quantitative risk model based on the adversary’s attack preferences instead of the adversary’s probabilities of attack. This has certain advantages (e.g., Buckshaw at al. [2005, p. 24] note, “Adversary attack preferences are easier to measure and help develop the mitigation strategy. We need to consider all attacks since a capable and adaptive threat will constantly change their actions in