The September 11, 2001 terrorist attacks on New York City and Washington, D.C. clearly indicated that massive, coordinated acts intended to cause enormous destruction and loss of life could be carried out within the borders of the United States. The response by the U.S. government to combat future attacks of this nature has been extensive, not only from the military but also from a vast number of agencies within the federal government.
Unfortunately, the anthrax attacks throughout the eastern United States subsequent to September 11 demonstrate an additional component of the terrorist threat facing our nation. Prevention of a conventional attack using high explosives (or in the case of September 11, jet fuel) is not enough. The ability to detect chemical, biological, or radiological toxins before an attack and rapidly and effectively decontaminate facilities and treat individuals should such attacks occur is also a key component in combating terrorism. The possibility of these attacks is no longer considered remote, and our chemists and chemical engineers are presently engaged in research that will strengthen our nation's security and homeland defense capabilities.
Chemical and biological agents present a “dual-use” dilemma. 1 A facility needed to develop vaccines against a biological agent could also be used to produce the agents for warfare. However, the dual-use principle can be turned to advantage; for example, the science and engineering needed for discovery and
1D. R. Franz. 2002, Current Thought on Bioterrorism: The Threat, Preparedness, and Response. Presentation, Workshop on National Security and Homeland Defense, Irvine, CA. (See Appendix D.)
Scientific Success Requires Public Support
K. John Pournoor
In the past century, much scientific work has been accomplished because the public put its support behind particular initiatives. For instance, from the 1940s through the 1960s, the public wanted to overcome the morbidity and mortality associated with infectious diseases, so our entire scientific system geared toward funding the development of the antibiotics that we have today. In the 1970s, the American public supported the fight against cancer, in the 1980s the battleground was viral diseases, especially HIV, and in the 1990s, the focus was on understanding the human genome. Each of these scientific accomplishments was achieved because there was at least a decade or more of sustained focused activity and publicly supported funding.
In this decade, science is and will be focused on developing a repertoire of prevention, detection, and intervention capabilities, as long as the public support for these activities remains strong. To put the fruits of this labor into the hands of the public will require both government and industry support as well as high efficacy, reasonable cost, reasonable complexity, and availability on a routine, everyday basis. So the list of priorities for scientific research related to national security and homeland defense needs to be amplified and channeled in many different directions by academia, government, and industry, to create an overarching cohesive approach.
scale-up of pharmaceutical agents in response to an attack could also be applied to improve the health of our residents in normal times, and vice versa.
Indeed, basic discoveries and inventions in the chemical sciences over the past two decades have been applied to the national security and homeland defense arena. One highly developed branch of science is analytics. Much of the instrumentation developed is being used to detect harmful chemicals and biological agents. For example, mass spectrometers have been fielded by the Department of Defense (DOD) for more than 15 years to monitor chemical and biological agents. Also, in the past 6 years, photon-based detection techniques have been combined with mass spectrometry, and DOD and the Defense Advanced Research Project Agency are heavily supporting development of mobile units for detection of both chemical and biological agents in the field. The development of aerosol time-of-flight mass spectrometry for on-line continuous monitoring of aerosol particles, including the chemistry between particle and gas, was originally
developed 2 for environmental science purposes but could be applied to detect military or terrorist attacks through an airborne delivery system. Other analytical developments with current or potential application to national security are advanced spectroscopic techniques for characterization of volatile and semi-volatile particulates in the atmosphere, microfluidics, chemical signature detection, single particle monitoring, sensor arrays, and high throughput screening. A challenge is to extend this example to other basic discoveries in chemistry and to invent new methodologies for mobile detection.
Materials development and synthesis is another important dual-use type of chemistry. Developments over the past few decades include a number of electronic materials and their processing, fuel cells and batteries, photoresist and semiconductor synthesis, high-performance composites (structural components) and nanocomposite materials, colloidal nanoparticle technology, solid-state lasers, and light-emitting diodes.
Advances in biotechnology have been tremendous. There are many issues in biochemistry and biotechnology that have not yet been completely elucidated; however, progress has been made. For example, antibiotics have evolved, the polymerase chain reaction has been developed, and DNA sequencing, genomics, proteomics, combinatorial synthesis, and selective complexation and recognition chemistry have all advanced.
All of these discoveries of chemistry, chemical engineering, and other collaborative sciences would not have been possible without new synthetic methods and improved theory and modeling capabilities.
Research opportunities for the chemical sciences in combating chemical warfare, biological warfare, and general terrorism are vast. These opportunities can be classified into the following basic processes:
Systems and analysis
The skills and knowledge of those in all chemical and chemical engineering disciplines are needed for these processes. Additionally, collaboration among the disciplines must be cultivated—especially between researchers who synthesize new chemicals and materials and those who develop new processes to manufacture them. There must be parallel integration of fields, so that discoveries quickly lead to useful technology. In a terrorist attack, a quick response is essential, whether it be decontamination of a site or scale-up of drug or vaccine production.
2K. A. Prather. 2002, Overview of Real-Time Single Particle Mass Spectrometry Methods. Presentation, Workshop on National Security and Homeland Defense, Irvine, CA. (See Appendix D.)
Chemistry and chemical engineering have much to contribute to many aspects of national security and homeland defense. Some of these contributions are obvious and in many cases already underway. These are areas in which the basic science is largely in hand and development is the next important step.
There remain, however, fundamental issues that depend on advances in basic science. As the workshop has revealed, there are many aspects of our basic knowledge that must be improved in order for us to solve these problems. For example, our ability to detect specific chemicals, or mixtures of chemicals, without false positive responses will require improvements in our understanding and implementation of many basic spectroscopies in a variety of frequency regions. Knowledge of the spectroscopic signatures of common environmental interferences will also require improvement. Miniaturization of equipment will depend on new materials and new ways of handling small amounts of materials. This is true both in the chemical and biological sectors. Our response to attacks depends on our knowledge of how chemicals interact with decontaminating agents and the development of new methodologies for cleanup that solve the decontamination problem without significant human and environmental degradation. Finally, our ability to anticipate new threats and problems depends critically on our understanding of what is possible and what we can do to prevent attacks. For example, new methods of manufacturing that make use of nontoxic materials are critical. Similarly, the synthesis of new drugs, antidotes, and other pharmaceuticals is clearly necessary, and if attacked, faster, more efficient clinical testing and regulatory approval might be needed.
The general societal benefits of all of these basic advances are substantial. Indeed, it can be argued that the overall value to our society will extend well beyond national security issues and will far exceed the initial investments, because many of these advances will result in improved quality of life and health for all of society.
SYSTEMS AND ANALYSIS
Miniaturization—chemistry and biology on a chip—has resulted only because of the confluence of science and engineering. The development of microfluidics technology has mainly been driven by the need to miniaturize, integrate, and automate biochemical analysis to increase speed and reduce costs. 3 We are experiencing a revolution in the miniaturization of chemical systems for detection and analysis of hosts of chemical and biological materials and agents. Applications of basic principles of electrokinetics, hydraulics, and surface science have
3A. W. Chow. 2002, Microfluidics: Development, Applications, and Future Challenges. Presentation, Workshop on National Security and Homeland Defense, Irvine, CA. (See Appendix D.)
permitted advances in microfluidics for moving nanovolume fluid elements to targeted destinations for chemical reaction and analytical chemistry. The complex chemical and physical processing that can now be done on a square-centimeter chip required an entire laboratory 10 years ago.
The use of detectors in the field, whether military or civilian, demands more robust, smaller, lighter, and lower power instrumentation than laboratory use requires. Field instruments will require high levels of redundancy and orthogonality in order to provide the users with high confidence. The term “orthogonality” here refers to the existence of different types of sensors in the same instrument targeted to the same analyte, whose operating principles are so different that they are unlikely to provide a false positive signal. False positive readings lead to a loss of confidence in the instrument, sometimes with disastrous consequences. 4 Spectroscopic sensing devices will need to depend on multivariate sensing, comparing specific, targeted portions of the spectrum of the detected molecule to similar portions of the target molecule spectrum to overcome multiple environmental interferences. Although not important for laboratory instruments, field instruments will require real-time, or instantaneous, response. Reliable on-line detectors will require multiple schemes of analysis and associated data handling that are uncorrelated through both model and measurement. This is a new paradigm for detection.
The need for improved or new technologies for a multitude of purposes exists. For practical use, these technologies must be incorporated into a larger instrument containing other components. Systems integration will be of great importance as science progresses with national security and homeland defense. In addition to the discussion in this report, information on this topic can be found in Chapter 10: Complex and Interdependent Systems of Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. 5
The creation and scale-up of processes to make sufficiently large quantities of drugs, vaccines, and other biological agents for testing and distribution challenges the creativity and knowledge of scientists and engineers. Here it is crucial that synthetic, physical, and analytical chemists, and process chemical engineers work in parallel to not only achieve the desired yield and purity, but also to greatly reduce the time from discovery to production. The emphasis of pharmaceutical production will be on continuous processing. Today, the timeline from discovery to scale-up of a pharmaceutical agent is 1 to 3 years (not including clinical trials);
4D. H. Stedman. 2002, A Skeptical Analysis of CBW Detection Schemes. Presentation, Workshop on National Security and Homeland Defense, Irvine, CA. (See Appendix D.)
5National Research Council. 2002. Making the Nation Safer: The Role of Science and Technology in Countering Terrorism. Washington, D.C.: National Academy Press.
Continuous Quality Control
Currently, testing of an operation (fermentation, reaction, separation, etc.) in the pharmaceutical industry requires taking a sample, bringing it to the laboratory, running the test, and analyzing the results. Only then is the operation approved or rejected. Not only is that process inefficient for the industry in general, but it also prohibits the rapid development, scale-up, and production of drugs in a national emergency. Instead, the industry needs continuous quality verification: it needs the controls and measurements of the process integrated into the process so that the quality of the product is known in real-time. Instituting this change will call for organic chemistry, chemical engineering, and analytical science all to play a role.
in a national emergency, this time must be reduced by a factor of four, which will require a new culture of interdisciplinary research, collaboration among companies, and government intervention. 6
A subtle but important consideration in the development of technology to meet chemical and biological threats is the different requirements for homeland versus military security. The tools and methods are similar, but the deployment strategies might be very different. Research in the chemical sciences must address these differences.
This workshop is one of six organized by the Board on Chemical Sciences and Technology of the National Research Council. The report is organized under three major headings: Grand Challenges, Specific Challenges (barriers), and Research Opportunities. Participants formed breakout groups to discuss each of these topics, and the next three sections summarize their discussions and conclusions. Discussions focused on how the chemistry and chemical engineering communities could assist with biological and chemical national security issues; although radiological issues were not a focal point of the workshop, the organizing committee recognizes the importance of this topic. The findings of the organizing committee are presented at the end of the report.
6M. Futran. 2002, Challenges in Rapid Scale-up of Synthetic Pharmaceutical Processes. Presentation, Workshop on National Security and Homeland Defense, Irvine, CA. (See Appendix D.)