Concerns are increasing about the possibility of bioterrorism against U.S. civilian and military facilities and personnel. Early detection and warning will play a significant role in minimizing the consequences of such attacks. Today, it is possible to detect and identify biological agents in time to pretreat victims before the onset of symptoms. In the future, increased emphasis will be placed on the ability to "detect-to-warn" (the detection of an agent cloud in time to alter air movement within a building; the ability to treat the air before it reaches the occupants; or the ability of personnel to protect themselves from exposure with physical barriers to the hazards).
Analyses of representative scenarios of biological attacks indicate that if one desires to detect the agent cloud in time to warn personnel who are at risk, it is necessary to complete the sample collection, preparation, analysis, and initiation of protective measures in less than 3 to 5 minutes, and preferably in about 1 minute. This time line is extremely challenging for technologies that are available today.
ORGANIZATION OF THE STUDY
Two scenarios of biological agent attack are considered: an indoor release against the population of a building and an outdoor release against an extended military installation. Many aspects of the ability to detect-to-warn are important for these two scenarios, including time lines; defensive concepts including passive as well as active protective measures; and the trade-offs among detection times, sensitivities, and false alarm rates. Detection architectures and systems that could be deployed by 2010 are a particular focus.
Because a detection system depends critically on how samples are collected and prepared, sampling strategies (where and how many) and the current status of collector and concentrator technologies are critical. Attainable detection levels and false alarm rates are also strongly influenced by the nature and variability of naturally occurring outdoor and indoor aerosols. The role that rapid, nonspecific standoff and spectroscopic point detectors might play must be considered along with the role of more specific technologies that offer a means of identifying biological agents used in an attack.
The four main categories of identification technologies are nucleic acid sequence-based methods; structural (antibody or artificial ligand capture and identification) methods; chemical (molecular or composition-sensitive) methods; and functional methods (based on the sensitivity of living cells, organs, or organisms). In each case, two key questions are important:
What level of detection (sensitivity and false alarm rate) can one hope to attain by 2010 given
about 1 minute for detection; and
What is the shortest detection time one can hope to attain by 2010 if one insists on maintaining performance at a level comparable to that currently achieved in the 30-minute time frame?
Based on the committee's assessment of state-of-the-art technology, various detection architectures must be considered—that is, combinations of detectors to provide improved confidence of detection; protective responses appropriate to the various confidence levels; and alternative ways of distributing the detection systems within a building or base.
A PHASED IMPLEMENTATION STRATEGY
Before the anthrax attacks of 2001, many scientists were highly skeptical that effective detect-to-warn systems could be deployed by 2010. Today, there appears to be a growing consensus that detection systems that provide warning for a significant portion of the threat space could be deployed for high-value buildings and probably even for military bases. However, it is impossible to quantify the probability of the effectiveness of such systems against real terrorist attacks because this would depend on specific attack scenarios, specific sensor architectures, and the robustness of the concept of operations.
Major conclusions regarding the feasibility of detect-to-warn capabilities in both the indoor and outdoor release scenarios are outlined below. These conclusions lead to a proposed phased implementation strategy for each scenario by which some protective steps can be taken in the next few years while more capable systems are being developed.
Each of the phases includes the following elements: passive improvements to the physical security and air handling systems of the facility, a detection system (including a collector/concentrator if needed), an information management system to relay the data to the facility manager, and appropriate building responses, ranging from turning off the heating, ventilating, and air conditioning (HVAC) system to facility evacuation. With the exception of the detection systems, most of the other elements are within the current state of practice for modern facilities and are not discussed further here.
Protection of Buildings
In the confined spaces of buildings, even small releases of biological agents can result in very high local concentrations in a typical air handling zone. For these scenarios, relatively simple and rapid nonspecific bioaerosol particle detection systems may provide a baseline facility detect-to-warn capability in the next 1 to 2 years (Figure ES.1). Such a system would have the advantage of being independent of the detailed nature of the agent and hence would provide broad-spectrum coverage, but without specificity. Importantly, even though the bioaerosol concentrations are high in the vicinity of the detector—making detection feasible—subsequent transport losses and filtration will reduce these concentrations by several orders of magnitude prior to the circulation of contaminated air to adjacent rooms or air handling zones.
Over the next 5 years, one can increase the capabilities of this system so as to detect even lower levels of attack (Figure ES.2). At these more sensitive detection thresholds, however, a bioaerosol detector will be increasingly prone to false alarms. In this case, the addition of another detector that can rapidly identify specific agents and hence discriminate them from ambient backgrounds becomes important.
Of all the identification technologies, structure-based detection (e.g., immunoassays) appears to offer the greatest potential for identification in two minutes or less with very low false alarm rates. Nucleic acid sequence-based assays such as those involving polymerase chain reaction (PCR) technology could then provide definitive confirmation of an attack and of the species of the biological agent.
The different strengths and weaknesses of these various kinds of sensors lead naturally to the concept of a system of detectors: a bioaerosol detector that can detect all bioagents (known and
unknown) with low false alarm levels for modest to large-size attacks, backed up by a rapid, structure-based identifier that can detect very small attacks—all on the order of 1 to 2 minutes. Ideally, both the bioaerosol detector and the rapid identifier would be operating continuously, making measurements every 1 to 2 minutes. When either or both devices alarm at a high signal-to-noise level, high-regret responses such as sheltering in place or evacuating the building would be initiated. If the detection or identification signal is of a lower signal-to-noise level, then low-regret options such as HVAC shutoff or air sterilization would be initiated. In all alarm cases, an air sample would be collected and passed to a sequence-based analyzer for confirmatory analyses on a 15-minute time scale.
Because of the costs of the associated detectors, the above concept leads naturally to a centralized detection architecture in which a detection system comprising a suite of detectors is placed in—or takes samples from—the HVAC system of each air handling zone in a facility. The fact that the agent concentration level can be higher in a given room or region near the release point than in the air handling unit also raises the intriguing possibility of a distributed detection system, composed of less capable but less expensive detectors. Additional systems analysis as well as research and development on such low-cost sensors is needed to better evaluate the potential of this option.
Protection of Extended Military Installations
The concept of using a nonspecific detector for biological agent attacks backed up by a rapid identifier can also be applied to a perimeter monitoring system to detect outdoor attacks on military bases. The agent concentrations will likely be lower in an outdoor attack than in an interior release in confined spaces—how much lower depends on whether the attack is aimed only at personnel who are outdoors or if it is also aimed at personnel within buildings, in which case it must be sized to overcome the passive building defenses (e.g., dilution and filtering). Also, the outdoor ambient background is
generally—but not always—expected to be higher and to fluctuate more than the ambient background in a filtered building. This will tend to produce a higher rate of false alarms with nonspecific detectors.
The combination of the lower agent concentration levels and the higher backgrounds associated with an outdoor release means that an array of nonspecific, spectroscopic point detectors at the base perimeter will cover a smaller portion of the threat space than it would in the building defense architectures. It may be that a standoff detection system using a combination of IR and ultraviolet lasers to interrogate an incoming bioaerosol cloud from a distance of several kilometers could address this deficiency. However, suitable concepts of operations for standoff detectors have yet to be developed.
In an outdoor release scenario, many of the potential agents can be treated with postexposure prophylaxis, presumably initiated by detect-to-treat systems, which can often provide effective alternatives to a detect-to-warn system. Collective protection systems can also provide safe interior zones to maintain critical functions. While detect-to-treat systems will likely be the foundation of installation defense against outdoor releases in the near term, the employment of Phase 1 concepts may enable detect-to-warn capability for larger outdoor and multifacility attacks. This could add value in several areas, including the following:
Even partially effective detect-to-warn systems can enable response options that might avoid or reduce exposure to organisms engineered for antibiotic resistance or for other agents (e.g., toxins) for which no prophylaxis exists.
Initial detect-to-warn systems will provide options for that portion of the population that is contraindicated for prophylaxis.
Some detect-to-treat warning may enable protective responses even in areas (particularly interior spaces) in which more complete collective protection measures are not implemented. This could provide partial, but much less costly, defense of a much larger population.
A nonspecific detection component will provide some capability against those agents not included in the few to tens of pathogens addressed by specific detect-to-treat assays.
If Phase 1 is skipped, the first detect-to-warn capability will be delayed for at least 5 years until rapid
identifiers become available. In this scenario, it appears that more of the warning burden will fall on the rapid identifiers, which are about 5 years away. Fortunately, the rapid identifier need not be quite as rapid as for building protection. For typical wind speeds of 5 meters per second, each kilometer of standoff distance of the detector from the actual target area to be protected results in an additional 3 minutes to take action.
TECHNICAL FINDINGS AND RECOMMENDATIONS
The phased implementation strategies suggested above reflect one path forward that is judged to be most likely to lead to success. However, technologies that appear less applicable today may experience breakthroughs in the future, and totally unforeseen technologies may emerge. Thus, it is prudent to group technical findings and recommendations into two categories: the most probable path and a technology watch list. The most probable path consists of those technologies whose currently demonstrated capabilities provide the basis for a reasonably well understood path to desired sensor system capabilities. The technology watch list consists of promising technologies that have yet to demonstrate one or more critical features before use in detect-to-warn applications. If these breakthroughs are achieved, however, the technologies on the watch list could become very attractive.
Most Probable Path
The committee finds that protection of buildings and military installations from biological attack requires the careful integration of detection capabilities with response options and procedures. Therefore, the committee recommends that military planners take a systems approach to facilities protection.
The committee finds that a successful detect-to-warn system requires that the local bioaerosol background be well understood. Therefore, the committee recommends that local aerosol backgrounds and their sources be characterized using the same methods that detectors would use. Within buildings where detectors are to be placed, steps should be taken to reduce these backgrounds.
The committee finds that the greatest disadvantage of using rapid, nonspecific detectors such as bioaerosol detectors is their potentially high false alarm rate at very low levels of detection. Therefore, the committee recommends that the false alarm rate of bioaerosol detectors be characterized in relevant facility environments as a function of detection threshold. Research should be supported on additional spectral and physical signatures and improved algorithms and techniques to further decrease the false positive rates.
The committee finds that structure-based assays appear to have the greatest potential for identifying biological agents with the speed, sensitivity, and specificity required for detect-to-warn applications. Therefore, the committee recommends that research be supported that would lead to an improved structure-based detector. The goal of this program should be a system with very low false alarm rates and a 2-minute or less overall detection time.
Although a detect-to-warn system has its highest impact if it can initiate responses within approximately 1 minute of an attack, even response times on the order of 5 to 15 minutes can be useful. The committee finds that technologies that provide confirmation of the attack and identify the organisms involved will serve a vital function in the overall defensive architecture. Therefore, the committee recommends that research be continued on the development of an integrated, fully automated PCR system, including sample collection, preparation, and analysis.
The committee finds that while prototype instruments for standoff detection of biological agents have been developed and tested, there is no currently fielded capability for such standoff detection, nor is there a clear concept of operations for the use of such systems. Therefore, the committee recommends that a clear concept of operations be developed for standoff detection in support of base protection and, if appropriate, that the development of a hybrid infrared/ultraviolet laser-induced fluorescence system be expedited for these applications.
Technology Watch List
The committee finds that mass spectrometry has the potential to identify biological agents based on a biofingerprint matching method and has the potential to do so with limited reagent consumption. Therefore, the committee recommends that the use of laboratory mass spectrometry be investigated to better understand the performance of biofingerprinting in complex mixtures of naturally occurring microorganisms and other background contaminants. This should be done with parallel development of improved sample preparation methods.
The committee finds that the biological smoke alarm concept offers intriguing potential for rapid detection. This concept uses networked, low-cost, semiselective detectors distributed throughout the rooms in a building. Therefore, the committee recommends that research be conducted to develop and characterize the performance of low-cost arrays of semiselective sensors that can be used as a biological smoke alarm for triggering low-regret response measures.
The committee finds that ribosomal RNA assays might be capable of biothreat agent identification in one to several minutes. This approach, with a major development effort, could avoid the time-consuming amplification cycles of many nucleic acid sequencing assays. Therefore, the committee recommends that the potential and the limitations of rRNA detection for rapid identification of pathogens be explored.
The committee finds that function-based sensors are one of the few promising candidates for detecting unknown hazardous agents—that is, agents that had not been anticipated. Their response time is inherently tied to the time it takes an agent to have a physiological effect on sentinel organisms or tissues. For certain chemical agents and toxins, this effect can be very rapid, but for bacteria and viruses, it can take much longer. These longer response times for bacteria and viruses make it unlikely that function-based sensors will play a significant role in detect-to-warn applications for these agents, but they could nevertheless play a valuable detect-to-treat role in the overall biodetection architecture. Therefore, the committee recommends that studies be conducted to better understand the role of function-based sensors in overall biodetection architectures and to provide goals to focus research and development activities on those areas for which function-based sensors have the highest leverage.
Detection systems that could provide rapid warning for a significant portion of the threat space could be deployed by 2010 to high-value buildings and probably even to military bases. The development and deployment of these systems can significantly reduce the number of casualties associated with a biological attack. Typical requirements are for detection of a broad spectrum of agents in a time approaching 1 minute (including sample collection and preparation) with a very low false alarm rate (about one false alarm per million sampled, corresponding to approximately one false alarm per year). The most promising approach for attaining this uses a combination of advanced detectors: for example, a nonspecific detector capable of detecting any and all biological agents and suitable for defense against medium to large attacks; a rapid, structure-based identifier capable of identifying 10 to 20 of the leading threat agents and suitable for discriminating a low-level attack from the natural background; and an autonomous PCR capability for rapid confirmation of an attack.
The independent use of three different detection techniques results in a very low false alarm rate and a high level of robustness against potential countermeasures. Critical crosscutting needs include rapid and autonomous sample preparation and better characterization of ambient bioaerosol backgrounds and sources, as well as ways to reduce these backgrounds in current and future buildings.
Finally, it should be noted that preventive and passive defenses (including measures such as improved security and threat assessment, as well as improved filtering and balancing of HVAC systems) play a significant role in reducing exposures and in raising the minimum attack level needed to produce significant casualties, thereby making it easier to detect biological agents and to initiate protective responses.