Defense Against Bioterror: Detection Technologies, Implementation Strategies and Commercial Opportunities--Proceedings of the NATO Advanced Research Workshop on Defense against Bioterror held in Madrid, Spain from 8 to 11 April 2004 (NATO Security through

Defense against Bioterror Detection Technologies, Implementation Strategies and Commercial Opportunities

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Defense against Bioterror Detection Technologies, Implementation Strategies and Commercial Opportunities

edited by

Dennis Morrison Institute of Engineering Research & Applications, New Mexico Tech, Albuquerque, NM, U.S.A.

Fred Milanovich Lawrence Livermore National Laboratory, Livermore, CA, U.S.A.

Dmitri Ivnitski Institute of Engineering Research & Applications, New Mexico Tech, Albuquerque, NM, U.S.A. and

Thomas R. Austin The Boeing Company, U.S.A.

Published in cooperation with NATO Public Diplomacy Division

Proceedings of the NATO Advanced Research Workshop on Defense against Bioterror: Detection Technologies, Implementation Strategies and Commercial Opportunities Madrid, Spain 8 -11 April 2004 A C.I.P. Catalogue record for this book is available from the Library of Congress.

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Table of Contents PREFACE

9

LIST OF CONTRIBUTORS

13

Strategic Actionable Net-Centric Biological Defense System S. KORNGUTH

17

Natural Toxins: The Past And The Present E. GRISHIN

29

Biological Weapons Inspections- The Iraq Experience E. B. MYHRE

47

Integrated, Secure And Sustainable Disease Surveillance System In Uzbekistan: Aspects Of Laboratory Research Networks F. T. ADILOVA

51

A Network-Ready, Broad Spectrum, Environmental Pathogen Detection System 67 F. P. MILANOVICH, J. DZENITIS, B. J. HINDSON, A. J. MAKAREWICZ, M. T. MCBRIDE, AND B. W. COLSTON Concept Design Of Anautonomous Biological Agent Detector System (Abads) R. BARTON, R. COLLINS, AND R. STARNES

77

Role Of Prototype System Demonstrations In The Development Of Detection-Based WMD Defenses L. BRANDT

91

Validation Testing For Biological Threat Organisms T. L. HADFIELD

105

Development Of Bioaerosol Alarming Detector A. V. WUIJCKHUIJSE, C. KIENTZ, B. V. BAAR, O. KIEVIT, R. BUSKER, M. STOWERS , W. KLEEFSMAN AND J. MARIJNISSEN

119

Biodetection Using Micro-Physiometry Tools Based On Electrokinetic Phenomena 129 R. PETHIG 5

6 Electro-optical Technique For Detection And Identification Of Biological Agents 143 VICTOR BUNIN Detection Of Microbial Cells With Electrooptical Analysis O. V. IGNATOV, O. I. GULIY, V. D. BUNIN, A. G. VOLOSHIN, D. O’NEIL, AND D. IVNITSKI

147

Recent Advances In Electrochemical And Photochemical Transduction Strategies For Immunosensors Based On Electropolymerized Films165 S. COSNIER Technological Platforms Based On Micro/Nanobiosensors As Early Warning Systems For Biological Warfare 175 L.M. LECHUGA, J.TAMAYO, A.CALLE, M. CALLEJA AND C. DOMINQUEZ Catalytic Beacons For The Detection Of DNA And Telomerase Activity199 Y. XIAO, V. PAVLOV, T. NIAZOV, A. DISHON, M. KOTLER AND I. WILLNER Critical Elements Of Biological Sensor Technology For Deployment In An Environmental Network System D. IVNITSKI, D. MORRISON AND D. J. O'NEIL

207

Electrochemical Immunosensor For Detection Of Francisella 221 tularensis P. SKLADAL, Y. SYMERSKA, M. POHANKA, B.SAFAR, AND A. MACEL Biosensors And Nanotechnological Immunochips For The Detection And Monitoring Of Chemical And Biological Agents S. VARFOLOMEYEV, I. KUROCHKIN, A. EREMENKO, E. RAININA 233 AND I. GACHOK Biosensor For Defence Against Terrorism M. MASCINI AND I. PALCHETTI

245

Biosensors And Biomimetic Sensors For The Detection Of Drugs, Toxins And Biological Agents 261 A. P. F. TURNER AND S. PILETSKY Chemical Multi-Sensor Arrays For Liquids Monolithic Integration Using Microelectronic Technology 273 A.BRATOV AND C. DOMINGUEZ

7 Immunochemical Approaches For Rapid Detection Of Biologically Active Compounds 291 B. B. DZANTIEV, A.V ZHERDEV, AND N.A. BYZOVA Multifunctional Liquid-Crystalline DNA Based Biosensing Units Capable Of Detecting Biologically Relevant Compounds 303 YU. M. YEVDOKIMOV Subject Index

335

PREFACE

Instability in warfare arises when offense significantly outstrips defense. After a half century of vaccine and antibiotic successes in the war against infectious diseases, the advantage has shifted back to the pathogen. Infectious diseases are again the leading cause of human mortality worldwide. To compound matters, the possible intentional spread of disease is not only possible but also it is reality. For instance, in the past two decades, the United States alone has had three biological attacks or incidents against civilians: 1984 salmonella, 1999 West Nile-like Virus, and 2001 anthracis. In addition, several foreign natural epidemics (the recent United Kingdom foot and mouth virus pandemic and the mad cow disease outbreak) have shown the potential for both serious economic and political harm. Indeed, the events of 2001 exposed civilization’s vulnerability to the covert introduction of harmful biological agents. Bioterroism and biological warfare employs living agents or toxins that can be disseminated/delivered by infected individuals, insects, aerosols, and by the contamination of water and food supplies. Most biological agents can be thousands of times more lethal per unit than the most lethal chemical warfare agents. Unlike chemical agents, biological agents attack people stealthily with no observable reaction until after an incubation period (days to weeks). Current disease surveillance and response systems rely on post-symptomatic reporting. However, many infectious agents such as smallpox have a long latency to clinical symptoms, thereby eluding early detection potentially resulting in widespread, uncontrolled contagion. Consequently, the threat of deliberate dissemination of biological agents is the most complicated and problematic of the weapons of mass destruction facing mankind today. 9

10 This volume contains papers presented at the NATO Advanced Research Workshop “Defence against Bioterror: Detection Technologies, Implementation, Strategies and Commercial Opportunities” held at the Hotel Wellington, Madrid Spain from 26 May to 29 May 2004. The objective of the workshop was to contribute to the critical assessment of state-of-the-art of emerging (“breakthrough”) biosensor technologies that will allow for the rapid identification of biological threat agents in the environment and human population; to identify directions for future research, and to promote close working relationships between scientists from different countries and with different professional experience. The volume is devoted to a comprehensive overview of the current state of biological weapons threat; challenges confronting biodetection technologies and systems; ongoing research and development; and, future requirements. Following the structure of the NATO Advanced Research Workshops, the special section starts from the threat overview and current art, then followed detection platforms, networked alarm-type biodetector systems, implementation strategies, electro-optical and electrochemical biosensors. A strategy and commensurate technology to detect a bioagent release at the earliest moment is an essential element of a defense against bioterrorism. The strategy should include: (1) systems of networked biodetectors that provide wide area monitoring for the early warning of a bioagent release; (2) a medical surveillance system that provides early (detection of the presence of disease in the population at large; and, (3) a concept for integrating these technologies into the public sector. In (1) the development of networked alarm-type biodetection systems is extremely important for detecting, tracking and responding to threats. By fielding a network of alarm-type biodetectors, civilian and military defense officials can obtain early warning in the event of a biological attack. The networked alarm-type biodetectors will provide generic discrimination, i.e., pathogenic vs. non-pathogenic bacteria and may be used as a “trigger” for a more sophisticated detector/identifier system. A desired performance requirement of networked alarm-type biodetectors is real-time, pre-exposure detection, discrimination, and identification of biological threats. The sensing element should be able to detect the presence of biological agents at below threshold concentrations in 5-10 min and be sensitive to a broad range of bioagents (multiplex capable). Obviously the incorporation of all these features within one biodetector based on current technology is a very complicated task. Most commercially available biodetectors are inherently bulky, utilize complex instrumentation, multistep assays and other time consuming procedures. The solution may be based on application of new emerging sensor technologies such as array-based biochips, liquid arrays, artificial olfaction and microfluidic systems, ion-channel switches and magnetoresistance technology. In (2) a science base that will provide for

11 biomarkers in human body fluids that indicate the presence of disease must be established. These markers must be able to distinguish pathogen type and be present at the very onset of disease (presymptomatic). Once established, detection technologies and application strategies need to be developed to bring presymptomatic detection to practical application. (3) strategies need to be developed to bring these advances to the public. Indeed, all levels of government are seeking to improve their capability for dealing with the effects and consequences of a biological incident or attack. In particular, cities recognize that their personnel will play a major part in a bioterrorist attack. Each small community is faced with the daunting problem of developing a bio-terrorism response plan with limited resources and limited local expertise. Transportation bioterror security presents an extremely complex problem (alarms, indications, situational awareness, level of response, large probability of false positive detection, effectiveness/performance, cost, politics, limited protection). No accurate and rapid “silver bullet” technology or system in existence can meet this challenge., We recommend the continued development of sensing technologies and the approach of employing multiple, layered detection systems with orthogonal technologies. Biological Warfare Agent (BWA) sensor for defense purposes may also be designed to offer “dual use” capability in the civil sector, including public health environmental air and water monitoring as well as drug discovery. Approach and preparation for biological terrorism can be compared to existing civilian methods for earthquake protection – very low probability of occurrence but with very high consequence. Continued collaboration among NATO members is recommended due to risk of BWA attack against both existing member countries (USA, UK and others) as well as emerging member countries (Russia). We would like to acknowledge the NATO Science Committee for their contributions. Special acknowledgement goes out to Cynthia Hernandez for providing technical document production and preparing the camera-ready version of the text.

The editors: Dennis Morrison, Fred P Milanovich, Dmitri Ivnitski, and Tom R Austin

LIST OF CONTRIBUTORS Dennis Morrison Institute of Engineering Research & Applications 901 University Blvd. SE Albuquerque, NM 87106 USA Phone 505 272 7235 Fax 505 272 7203 [email protected] Fred P. Milanovich Lawerence Livermore National Labs 7000 East Avenue -174 Livermore, CA 94550 USA Phone 925 422 6838 Fax 925 422 8020 [email protected] Tom R. Austin The Boeing Company 2201 Seal Beach Blvd MC 110-SC45 Seal Beach, CA 90740 USA Phone 562 797 3798 Fax 562 797 4778 [email protected] Shawn H . Park The Boeing Company 5301 Bolsa Ave MC-H013-B319 Huntington Beach, CA 92657 USA Phone: 704 896 1606 Fax: 704 896 6417 [email protected] John C Stammreich The Boeing Company 2201 Seal Beach Blvd MC-110-SA32 Seal Beach, CA 90740 USA Phone 562 797 3252 Fax 562 797 4778 [email protected] Oleg VIgnatov Institute of Biochemistry & Physiology of Plants & Microorganisms Russian Academy of Sciences Entuziastov av.,13 Sartov, 410049 Russia Phone 7 8452 970 383 Fax 7 8452 970 383 [email protected] Dmitri Ivniski Institute of Engineering Research & Applications, New Mexico Tech 901 University Blvd. SE Albuquerque, NM 87106 USA Phone 505 272 7255 Fax 505 272 7203 [email protected] Laura M Lechuga Biosensor Group Centro nacional de Microelectronica (IMM-CNM-CSIC) Isaac Newton , 8 28760 Tres Cantos (PTM) Madrid, Spain Phone 34 91 806 0700 Fax 34 91 806 0701 [email protected] Anthony. Turner 13

14 Cranfield University Silsoe Bedfordshire, MK45 4DT UK Phone 44 0 1525 863005 Fax 44 0 1525 863360 [email protected] Steven Kornguth Institute of Advanced Technology 3925 West Braker Lane Suite 400 Austin, TX 78759 USA Phone 512 232 4486 Fax 512 471 9103 [email protected] Robert G. Barton Midwest Research International 425 Volker Blvd. Kansas City, MI 64110 USA Phone 816 360 5268 Fax 816 531 0315 [email protected] Larry D. Brandt Sandia National Laboratories PO Box 969 MS 9201 Livermore, CA 94551 USA Phone 925 294 2969 Fax 925 294 1559 [email protected] Andrey Bratov Centro Nacional de Microelectronica Campus UAB. Bellaterra E -08193 Cerdanyola del Valles Barcelona, Spain Phone 34 93 594 77 00 Fax 34 93 580 14 96 [email protected] Victor D. Bunin State Research Center of Applied Microbiology Obolensk Moscow region, 142253 Russia Phone 7 0967 705716 Fax 7 0967 705716 [email protected] Fatima T. Adilova Inst. of Cybernetics Academy of Sciences 34, F. Khodjaev str. Tashkent, 700125 Uzbekistan Phone 99871 162 71 62 Fax 99871 162 73 21 [email protected] James M. Clark GL Detection Dstl Porton Down Salisbury SP4 OJQ UK Phone 44 1908 613 405 Fax 44 1980 613 987 [email protected] Bob V. Collins Midwest Research International 425 Volker Blvd. Kansas City, MI 64110 USA Phone 816 360 5322 Fax 816 531 0315 [email protected] Serge Cosnier Laboratory of Organic Electrochemistry and Redox Photochemistry UMR CNRS 5630 Institute of Molecular Chemistry FR CNRS 2607 Batiment Chimie Université Joseph Fourier Grenoble 1 301 rue de la Chimie,BP 53 38041 Grenoble Cedex 9 France [email protected] Boris B. Dzantiev

15 Institute of Biochemistry RAS Leniskii Prospect 33 Moscow, 110971 Russia Phone 7 095 954 2804 Fax 7 095 954 2804 [email protected] Eugene V. Grishin Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Ul. Miklukho-Maklaya, 16/10, 117997 GSP Moscow, V-437 Russia Phone 7 095 3305892 Fax 7 095 3350812 [email protected] Ted L. Hadfield Midwest Research International 1470 T reeland Blvd, SE Palm Bay, FL 32909 USA Phone 321 723 4547 ext. 300 Fax 321 722 2514 [email protected] Jay Lewington Smiths Detection 459 Park Ave Bushey Watford, Herts WD23 2BW UK Phone 44 0 1923 658206 Fax 44 0 1923 658025 [email protected] Marco Mascini Universita di Firenze Sesto Fiorentino Dipartimento di Chimica, Polo Scientifico Via della lastruccia 3 Firenze, 50019 Italy Phone 39 055 457 3283 Fax 39 055 457 3384 [email protected] Sebastain Meyer-Plath Smiths Detection 59 Park Ave Bushey Watford, Herts WD23 2BW UK Phone 44 0 1923 658193 Fax 44 0 1923 221361 [email protected] Michael Moniz Circadence Corporation 4888 Pearl East Circle, Ste. 101 Bolder, CO USA Phone 303 413 8837 Fax 303 449 7099 [email protected] Louis Montulli Midwest Research International 613 Rolling Hills Rd Vista, CA 92081 USA Phone 760 977 9601 Fax 760 598 6488 [email protected] Petr Skladal Masaryk University Kotlarska 2 CZ 61137 Brno Czech Republic Phone 420 5 41129402 Fax 420 5 41211214 [email protected] Ronald Pethig School of Informatics University of Wales, Bangor Dean Street Bangor, Gwynedd LL57 1UT UK Phone 44 1248 382 682 Fax 44 1248 361 429 [email protected] Erling B. Myhre Dept. of Infectious Diseases, University Hospital SE-221 85 Lund Sweden

16 Phone 46 46 17 18 67/17 11 30 Fax 46 56 13 74 14 [email protected] Arjan van Wuijckhuijse Dr. Ir. A.L. van Wuijckhuijse TNO Prins Maurits Laboratory Detection Identification and Analytical Chemistry PO Box 45, 2280 AA Rijswijk, THE NETHERLANDS Phone +31 15 284 3343 Fax: +31 15 284 3963 www.pml.tno.nl Sergey D . Varfolomeyev The M.V.Lomonosov Moscow State University Vorobiovy Gory 1, Bldg. 11 119992 Moscow Russia Phone 7 095 939 3589 Fax 7 (095) 939 5417 [email protected] Itamar Willner The Hebrew University of Jerusalem Jerusalem 91904 Israel Phone 972 2 658 5272 Fax 972 2 652 7715 [email protected] Yuri M. Yevdokimov Head of Laboratory of condensed state of nucleic acids of Engelhardt Institute of Molecular Biology RAS Engelhardt Institute of Molecular Biology RAS Vavilov str. 32 Moscow, 119991 Russia Phone 7 095 135 97 20 Fax 7 095 135 14 05 [email protected]

Part 1

CURRENT PROBLEMS OF CHEMICAL TERRORISM

Chapter 1 PROBLEMS OF CHEMICAL TERRORISM AND WAYS OF ITS OVERCOMING

Christophor Dishovsky Department of Military Toxicology, Military Medical Academy, Sofia , Bulgaria

Abstract:

The main problem connected with chemical terrorism is that, beside chemical weapons, terrorists can use different toxic chemicals from the chemical industry, from agriculture or products of industrial facilities released after the terrorist act. An attack to a chemical plant can instantly liberate a number of different chemicals. Studies should be made on incidents occurring in the facility, during transportation, storage or other processes and these are important points in the preparation for protection against chemical terrorism. An important corner-stone of the anti-terrorist organization in any country is to set a Health & Disaster/Anti Terrorist Acts Management system. Country antiterrorist

protection will be improved by the introduction of a universal

strategy on basic therapeutic trends against chemical terrorism. Chemical terrorism can be responsible not only for the spread of large amounts of toxic chemical compounds, but also for chronic and delayed effects of these agents. Intoxication with small doses of toxic agents is also a possibility used by terrorists. The variety of characteristics of a chemical agent used by terrorists needs demands improvement in the detection, personal protection and decontamination procedures, including that of the medical personnel and equipment. Antidote treatment, with the exception of the medical units and organization of national stockpiling which are adequately supplied for, needs a new and extensive study for new antidotes and for improvement of the medical treatment on the area of the terrorist act.

3 C. Dishovsky et al. (eds.), Medical Treatment of Intoxications and Decontamination of Chemical Agents in the Area of Terrorist Attack, 3–11. © 2006 Springer. Printed in the Netherlands.

4

Problems of Chemical Terrorism and Ways of Its Overcoming

Keywords:

antidotes; Anti Terrorist Management Centers; chemical; chemical industry; chemical weapons; decontamination; delayed effects; detection; terrorism

1.

INTRODUCTION

The main problem connected with chemical terrorism is that, beside chemical weapons, terrorists can use various toxic chemicals from the chemical industry, from agriculture or products of industrial facilities released after the terrorist act. An attack to a chemical plant can instantly liberate a number of different chemicals. Studies should be made on incidents occurring in the facility, during transportation, storage or other processes and these are important points in the preparation for protection against chemical terrorism. An important corner-stone of the anti-terrorist organization in any country is to set a Health & Disaster/Anti Terrorist Acts Management system. Country antiterrorist protection will be improved by the introduction of a universal strategy on basic therapeutic trends against chemical terrorism. Chemical terrorism can be responsible not only for the spread of large amounts of toxic chemical compounds, but also for chronic and delayed effects of these agents. Intoxication with small doses of toxic agents is also a possibility used by terrorists. The variety of characteristics of a chemical agent used by terrorists needs demands improvement in the detection, personal protection and decontamination procedures, including that of the medical personnel and equipment. Antidote treatment, with the exception of the medical units and organization of national stockpiling which are adequately supplied for, needs a new and extensive study for new antidotes and for improvement of the medical treatment on the area of the terrorist act. 2.

DISCUSSION

The main problem connected with chemical terrorism is that beside chemical weapons, terrorists can use different toxic chemicals from the chemical industry, the agriculture or products released from industrial facilities following a terrorist act. An attack on a chemical plant can immediately release a number of different kinds of chemicals [6]. Some differences exist between chemical weapons (CW) and the chemicals released after destruction of a chemical plant following a terrorist act [4]: • industrial chemicals are less toxic than CW, but will be present in much higher quantities for a longer period of time; • contamination with the hazardous industrial chemicals eventually covers a bigger area;

Christophor Dishovsky •

5

CW represent a relatively small number of potential agents; on the contrary - toxic industrial chemicals – tens of thousands; • for the known CWs, relatively simple detection and identification equipment and methods have been developed; the potential variety of industrial chemicals makes the detection process very difficult; • decontamination some times may be a long-lasting and expensive procedure; • the products of the decontamination can also damage the environment; • military protective filters are optimized against CW and BW; some hazardous industrial chemicals are not very well filtered by military filters; The study of the accidents in chemical facilities, during transportation, storage and others, the research of the chemical products, which are produced and stored, are important points in the preparation of the defence against chemical terrorism. An example of such an accident is the explosion at the Union Carbide pesticide manufacturing plant (Dec. 3, 1984), which scattered toxic methyl isocyanate (MIC) over the city of Bhopal, India. During the first few days up to 4000 people died of painful, harrowing deaths [10]. The precise knowledge of the chemicals, produced and stored in the factories, is a necessary condition for modeling of the accidents. However, it should be taken into account that in real conditions and especially when the accidents are accompanied with fire, new toxic compounds may be formed. Such is the case with the fire, which occurred on July 13, 1993 in the "Alen Mak" factory in the town of Plovdiv, Bulgaria. During the GC-MS analysis of the air, soil and various parts of the incident site, over 120 different chemical compounds were identified, some of which identical to the ones present on the premises before the fire, while others had obviously formed during the process of combustion. For a great number of these compounds, toxicological data was not found in the accessible information banks, such as IRIS of EPA and others [5]. United Nations APELL (Awareness and Preparedness for Emergencies at the Local Level) [15] chemical accident database (storing information on about 300 major chemical accidents between 1970 and 1998) shows that: - 38% of the accidents occur with hydrocarbons (fuel gases, fuel liquids, oil, or refined petroleum products); - 15% - explosive industrial chemicals; - 8% - chlorine; - 6% - ammonia; - 6% - industrial acids and bases; - 3% - pesticides and chemical intermediates;

6

Problems of Chemical Terrorism and Ways of Its Overcoming

- 21% - polychlorinated biphenyls (2 %), unspecified chemicals (5%) and others. Hydrocarbon production, storage, transportation and distribution facilities are at the top of the list of potential targets. Some of the more common types of chemicals that could be used as improvised weapons against a community include (data from ATSDR [16]: - eye, skin and respiratory irritants (acids, ammonia, acrylates, aldehydes, and isocyanates); - choking agents (chlorine, hydrogen sulfide, and phosgene); -flammable chemical industry gases (acetone, alkenes, alkyl halides, amines); - aromatic hydrocarbons that could be used as water contaminants (benzene, etc.); - oxidizers for improvised explosives (oxygen, butadiene, and peroxides); - aniline, nitrile, and cyanide compounds that could be used as chemical asphyxiants; - compressed hydrocarbon fuel gases that could be used as incendiaries or simple asphyxiants (liquified natural gas, propane, isobutane); - liquid hydrocarbon fuels that could be used as incendiaries or water contaminants (gasoline, jet fuel); - industrial compounds that could be used as blister agents (dimethyl sulfate), and - organophosphate pesticides that could be used as low-grade nerve agents. According to the conclusions reached by some experts, terrorist acts apply a new strategy in the use of chemical weapons and other chemical agents, i.e.: • the use of low doses of toxic chemicals; • to aim at a delayed and unknown effect of intoxication. Investigations in Bhopal, 20 years later, showed that thousands of Bhopal residents suffered from serious long-term side effects such as blindness, and liver and kidney failure. Estimates of total deaths reach up to 20000. Injuries probably exceeded 100000 [10]. The data from terrorist acts in Matsumoto city and Tokyo underground in Japan are important for the understanding that the consequences of a terrorist act bring long lasting troubles [12, 13]. Some investigations showed that allied troops had been exposed to sarin during the first Gulf War and that might have caused the development of the “Gulf war syndrome” in some of the exposed soldiers [7 ]. The main problems caused by OPC are neuro-toxic delayed effects [8]. Shulga [14] suggested also the presence of delayed neuro-endocrine toxicity after intoxication with such compounds. Planning and preparation of anti terrorist measures should be focused on the following specific points [4]: • risk assessment for the use of chemical agents as terrorist agents with particular attention to toxic industrial chemicals and toxins;

Christophor Dishovsky •

7

update assessment of the effective toxic levels that should cover both the known chemical weapons in view of the modern technologies of their use and toxic compounds and chemicals of industrial origin; • inventory and assessment of the available means for medical treatment of chemical intoxications; assessment of the required amounts and types of antidotes (in view of the broader range of potentially toxic agents) and their update with development and introduction of new compounds; • modernization and optimization of individual protection with particular focus on respiratory protection and protective clothing; • creation of new National Pharmaceutical Stockpile, which ensures the availability of medicines, antidotes, medical supplies and medical equipment necessary to counter the effects of biological pathogens and chemical agents; • creation of effective system of information and supply to the site of the terrorist act; • assessment of the available means for indication and control of chemical contamination and the effectiveness of decontamination. It should include a broader range of potentially toxic agents and the available state-of-the-art technologies; • acquires particular significance for the readiness of all levels of civil institutions and the army to counteract chemical terrorism. It should incorporate and implement the latest achievements of computer simulation and virtual reality technologies; • intensive education and training of first responders and physicians is needed for meeting the medical challenges imposed by chemical and other weapons of terrorism. A country’s antiterrorist protection system should also incorporate a general State Strategy against chemical traumatism and terrorism [11]: • medical chapter; • universal program for diagnosis and treatment; • organizational and medical program; • social and informative chapter; • social information regarding chemical traumatism; • knowledge on chemical traumatism and terrorism. Investigations of Wetter et al. [17] showed that hospital emergency departments generally are not prepared to treat victims of chemical or biological terrorism. Some countries have introduced a Health & Disaster/Anti Terrorist Acts Management system, which includes: • Health & Disaster Anti Terrorist Management Centers. They can be a structure of already existing facilities – for example - of the Civil Defense. Some countries created new independent structures. Such centers could act independently, their task being to manage the situation after disasters or terrorist acts. • Facilities for indication of toxic chemicals;

8

Problems of Chemical Terrorism and Ways of Its Overcoming •

Stationary centers for indication of toxic chemicals that work online and are connected to the Health & Disaster Anti Terrorist Management Centers. • Mobile facilities for indication of toxic chemicals for investigating a potential area of a terrorist act. • Regional Medical Centers. They can be Primary or Secondary – depending on the size and type of organization. These can be district hospitals with developed emergency units. • Poison information centers. Regional Medical Centers can play this role. • Mobile Medical units with Clinic for First aid treatment; Laboratory & Diagnostic units; operating theater; hospital, specifications for treatment of patients affected by chemical agents (indication, decontamination). • Satellite communications; • Independent energy supply; • Mobile decontamination facilities; • Training Centers (Center) for Mass Casualties Events. This system will have a dual function. It will enhance not only emergency preparedness, antiterrorist activity but also the public health system. Such a view is suggested by Marmagas et al.[10] about possible connection between preparedness against biological terrorism, public health infrastructure, chronic disease and environmental health tracking network. With a view to improve the level of security of the population from incidents and disasters, a Scientific Coordination Council was created in Bulgaria as an adjunct to the Permanent State Commission for Protection of the Population from Disasters and Incidents [5]. Attached to the Council are several expert committees which organize and conduct research and analysis, give expertise and make risk assessments for nuclear security, radiation, chemical and biological defense, emergency, seismic danger, meteorological and hydrologic problems and physical steadiness, suggest measures for securing and protecting objects which may add to the dangerous conditions. One of the first tasks of the Expert Committee for Chemical Defense was to identify the dangerous chemical conditions on the territory of Bulgaria. At present over 3400 chemical substances are produced in Bulgaria, among which mineral fetilizers, plastics, drugs, and others. The basic criteria for the assessment concern the quantity of reserve of industrially dangerous chemical compounds and compounds which form during fires or through the reactions of these compounds. The classification is also concerned with the existence of storage facilities, product conductors, transportation communications, and others, where risky situations, including terrorist actions, may be expected. The criteria for the above mentioned analysis may be defined as follows [5]: • research of the object as a potential danger; • analysis of the possible terrorist act;

Christophor Dishovsky •

9

analysis of the available system for defense, security and protection; • development of a project for improvement of a new system for defense, security and protection; • organizing of the defense, security and protection of some chosen objects, and consideration and use of the experience; • coordination of the efforts of the various departments, ministries and others in solving the problems of defense, security and protection of the potentially dangerous objects. The country’s antiterrorist preparedness will be improved with the introduction of a universal doctrine (strategy) suggested from Monov [11], with the basic therapeutic trends against chemical terrorism which includes mainly: • antidotes; • detoxication; • reanimation-substitution and correction; • immunobiological activity; • antiviral and antibacterial activity; • organoprotective activity. A great number of severely injured people, after using organophosphorus compounds (OPC) like sarin for example, will need skilled medical help, enough antidotes, preparedness for decontamination and medical equipment such as breathing apparatuses or supplied air-line respirators. Some ideas exist how to solve these problems. In the Military Medical Academy, Sofia, a special antidote, which can be used after fires and a buddy aid antidote – for severe cases of intoxication were created. It can be introduced also as the first and buddy aid antidote. This antidote was prepared in ampoule form bearing the name NEMICOL 5T [9]. It is a multi component preparation which was tested with animals. The investigations show that this antidote very quickly recovers the breathing, the arterial pressure and the EKG in the intoxicated animals. The anticonvulsant activity was very strong and was demonstrated also with EEG experiments. Neuromuscular transmission blocked after OPC intoxication recovered 1-3 minutes after introduction of the Nemicol 5T. All investigated parameters stayed very stable. Cowan et al. [1, 2] suggest the Multi-Threat Medical Countermeasure (MTMC) hypothesis – investigations for developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical agents. Serine protease inhibitors can prolong the survival of animals intoxicated with the nerve agent soman and can also protect against vesication caused by the blister agent sulfur mustard. Poly (ADP-ribose) polymerase (PARP) inhibitors can reduce both soman-induced neuronal degeneration and sulfur-mustard-induced epidermal necrosis. Accordingly, the drugs with antiinflammatory action against either nerve or blister agent might also

10

Problems of Chemical Terrorism and Ways of Its Overcoming

display multi-threat efficacy for the inflammatory pathogenesis of both classes of chemical warfare agent [1,2]. 3.

CONCLUSION

Nowadays, terrorists have changed their tactics. Beside chemical weapons, they may use different toxic chemicals produced by the industry, the agriculture or failures in the industrial facilities during transportation, storage, fires and the like. They may take advantage also of the application of low doses of toxic chemicals which can provoke delayed and unknown effects of the intoxication. Thorough studies of the chemical products, investigations of the incidents in chemical factories, storehouses and transportation dealing with chemical products are important points in the protection plan against chemical terrorism. A country’s antiterrorist preparedness should include also a State strategy against chemical traumatism and terrorism. The elaboration of Organization of Health & Disaster/Anti Terrorist Acts Management system is an important part of this preparedness. The scientific research in the field of toxicology gains new dimensions and priorities. The introduction of a universal strategy for the basic therapeutic trends against chemical terrorism is necessary. REFERENCES 1.

2. 3. 4.

5.

6. 7.

Cowan F. M., Broomfield C.A., Lenz D. E., Smith W. J., Putative role of proteolysis and inflammatory response in the toxicity of nerve and blister chemical warfare agents: implications for multi-threat medical countermeasures. J. Applied Toxicology, 2003, 23, 3, 177-86. Cowan B. S., Broomfield C. a., Stojiljkovic M. P., Smith W. J., A Review of Multi-Threat Mrdical Countermeasures against Chemical Warfare and Terrorism, Military Medicine, 2004, 169, 11, 850-55. Dishovsky C., “The problems of Chemical Terrorism.” In Technology for Combating WMD Terrorism, Peter J. Stopa, Zvonko Orahovec, ed’s, NATO Science Series, Kluwer Academic Publishers, 2004. Dishovsky C., “The problems of Chemical and Biological Terrorism.” In Medical Aspects of Chemical and Biological Terrorism – Biological Terrorism and Tramautism, Alexander Monov and Christophor Dishovsky, eds, Publishing House of the Union of Scientists in Bulgaria, 2004. Dishovsky C., Belokonsky I., Panchev N., The problems of defence in chemical industryresults of special investigation. Proceedings of the CB Medical Treatment Symposium Industry I; 1998 October 25-31; Zagreb-Dubrovnik, Croatia, MOD of Croatia, 1999, 6973. Eifried G., Terrorism against chemical plants:hazards and risks. Proceedings of the CB Medical Treatment Symposium Industry I; 1998 October 25-31; Zagreb-Dubrovnik, Croatia, MOD of Croatia, 1999, 84-88. Haley, R.W., and Kurt, T.R., Self-reported exposure to neurotoxic chemical combinations in the Gulf War, J. Am. Med. Assos., 1997, 277,231-37.

Christophor Dishovsky 8. 9. 10. 11.

12. 13. 14.

15. 16. 17.

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Haley, R., W., Billecke, S., S., and La Du, B., N., Association of low PON1 type Q (type A) arylesterase activity with neurological symptom complexes in Gulf War veterans, Toxicol. Appl. Pharmacol., 1999, 157, 227-33. Kotev G., DSc Work , Military Medical Academy, Sofia, 1973. ( in Bulgarian ). Marmagas S.W., Kind L. R.,Public Health’s Response to a changed World: September 11, Biological Terrorism, and the Development of an Environmental Health Tracking Network. Amer. J. of Public Health, 2003, 93, 8, 1226-30. Monov Alexander, “Biological Traumatism and Terrorism – unified Medical and Organizational Doctrine”. .” In Medical Aspects of Chemical and Biological Terrorism – Biological Terrorism and Tramautism, Alexander Monov and Christophor Dishovsky, eds, Publishing House of the Union of Scientists in Bulgaria, 2004. Morita, H., Yanagisawa, N., Nakajima, T., et al., Sarin poisoning in Matsumoto, Japan, Lancet, 1995, 346, 290-93. Ohbu, S., Yamashina, A., Takasu, N., et al., Sarin poisoning on Tokyo subway. South. Med. J., 1997, 90, 587-93. Shulga V., “Delayed neuro-endocrine toxicity indused by organophosphorus compoundsnatural consequence of poisonous substances application for terrorist purpose”, In Medical Aspects of Chemical and Biological Terrorism –Chemical Terrorism and Tramautism, Alexander Monov and Christophor Dishovsky, eds, Publishing House of the Union of Scientists in Bulgaria, 2005 ( in press). United Nations APELL (Awareness and Preparedness for Emergencies at the Local Level) http://www.uneptie.org/pc/apell/. U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry (ATSDR) http://www.atsdr.cdc.gov/about.html. Wetter D.C., Daniell W. E., Treser C. D., Hospital preparedness for victims of chemical or biological terrorism. Amer. J. of Public Health, 2001, 91, 5, 710-1

1

A SUMMARY OF THE DISCUSSIONS

Paul Tempest Director of Windsor Energy Group and Vice President of the British Institute of Energy Economics

An emerging energy demand/supply imbalance The IEA expect global energy demand to rise by 66% by 2030 with 90% of the increment supplied by fossil fuels, mainly oil. The Gulf oil producers, holding two thirds of total global proven oil reserves, would have to account for most of this increment and for the replacement of depleting production elsewhere. Such a doubling or even tripling of Gulf oil production capacity would require a massive infusion of external capital and new technology. This looks in present circumstances to be highly unlikely, given the degree of political turbulence in the area, the reluctance of the capital and financial markets to take on such risks and the determination of several governments to protect their own national companies to the point of failing to provide adequate incentives for the international oil companies to participate fully.

“The end of cheap oil” Competition for Gulf oil exports is therefore likely to be intense with South-East Asia taking the bulk and an increasing share. US expectations that US oil imports will double to 24 mbd by 2030 will further distort the market and can only be achieved at the cost of denying supply to the developing world. Oil prices have remained broadly within the US$22-28 OPEC band for the last four years and are now moving beyond the upper limit. Yet industry 3 H. McPherson et al. (eds.), Emerging Threats to Energy Security and Stability, 3–8. © 2005 Springer. Printed in the Netherlands.

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estimates of the global clearing price for oil is mainly within the US$ 16-18 range, implying that the difference is an anxiety premium caused mainly by political turbulence in the Middle East.

Dangerous impacts on the global economy - a nonsustainable energy prospect Periods of high oil prices have always had adverse impacts on global economic growth, just as low oil prices have always acted as a stimulus. Already, continuing high oil prices are seen to be hindering growth for later this year. Whereas the rest of OECD (Organisation for Economic Cooperation and Development) industrialised countries are partly shielded by the weakening of the US $, the impact on the US economy, which is already slowing, and on most developing countries could be severe. One quarter of the world population has no access to electricity and many more rely on wood, residues and dung for cooking and heating. Even on assumptions of the persistence of the average GNP growth over the last 25 years, the number of people without access to electricity is 2030 is unlikely to be below the current level. The steeper the economic rollercoaster caused by oil price spikes, the less chance there will be to reach the IEA target of 75 million new connections per year and the greater the likelihood that global energy poverty will increase rather than decrease.

Changes in oil market leadership Russia (9.0 mbd this year) has overtaken Saudi Arabia and the USA (each about 7.8 mbd this year) as the leader in oil production. Iraq is widely thought to be capable of producing 4-5 mbd by 2010 and possibly 15-20 mbd by 2030. Many of the discussions pivoted around the issue of political stability in Russia and Saudi Arabia. Most contributors considered the IEA assumption of a rapid rise in Saudi production to 19 mbd to be highly unlikely, and indeed, an industry report which is soon to be published predicts the contrary: imminent collapse. Yet the consensus view, although vigorously challenged, was that Saudi Arabia would remain the indispensable provider of surge capacity until 2010 at least.

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China (5.7 mbd) has outstripped Japan as the second largest oil consumer. Chinese oil imports are predicted to rise from 2mbd in 2003 to 6 mbd in 2010 and 15-20 mbd by 2030.

Iraq approaching “boil-over” Despite considerable and mainly unsung progress in restoring Iraq’s economic infrastructure over the past six months, the projected transition to Iraqi control at mid-04 looks precarious unless the proposals are endorsed by the 60% Shi’a majority (see Special Session C). The possibility of a break-up of Iraq, whether sooner or later, becomes clearer. In the light of this eventuality, a serious contingency plan is needed. “While there are now no known national threats to the boundaries of the USA or Europe, there is no boundary to the global threat of Al-Qaida and other international terrorist organisations. Our defence forces are largely equipped for Cold War needs, not for the rapid-response needs we now face.”

Technology transfer stifled The International Oil Companies provide a rapid and efficient transfer of petroleum technology and effective management where they are permitted to operate. Many oil and gas-producing countries overprotect their national companies to the point of denying IOC access on commercial terms.

The Caucasus impasse Rivalries between the USA, Russia and the EU overshadow efforts by the Caucasus States to develop export capacity for their oil and gas. Political meddling and attempts from outside to control the economy of the region explain the numerous development delays.

6

North African surprises Rapid development of North African oil and gas resources following political détente may alleviate the competitive weakness of Europe in securing adequate imported oil and gas. Sanctions on Libya have been easy to impose, most difficult to dismantle. US policy is still based on a “waitand-see” step-by-step policy as Libya demonstrates compliance.

UK energy policy There is little sign of contingency planning as the UK returns to net gas import dependence (2005-6) and oil import dependence (2010) and coal imports (currently 50% of consumption) continue to rise. Nuclear capacity will also have run down sharply by 2010. UK Government expectations that wind-power will be able to provide 10% of UK electricity may be exaggerated.

Threats to ships Shipping of crude oil and products, which are equivalent to 57% of global oil production, is vital to the global economy, vulnerable to terrorists and the problems are poorly understood. Some 90,000 ships move 2,000mn tons pa. The fleet of LNG carriers is likely to triple within 10-15 years and are getting larger – in the next generation of carrier, they will be 150,000 tons each. A vapour cloud from a damaged LNG vessel will, on ignition, have the impact of detonating a hydrogen bomb. The main hazards are: Ship-seizure by pirates who then transfer and sell the cargo, disguise the ship and ransom the crew. SAS simulations indicate that fewer than 8 minutes would be needed for regaining control of a captured vessel between touching the ship’s side and taking over the bridge. x Ramming – this mostly occurs close to shore and often causes massive spills and pollution. x Infiltration of Ship by terrorist cell working among crew.

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x Actions by environmental groups (e.g. the seizure of The Brent Spar by Greenpeace) The four most dangerous choke-points for the oil trade are Hormuz (15.5mbd), Malacca Straits (10.5 mbd), Bab al-Mandab (3.3 mbd) and the Suez (0.8 mbd). Collision in congested waterways is not uncommon: in 2 months recently the IMO reported 8 collisions in the Malacca Straits which, along with Indonesia, heads the IMO list of 445 piracy attacks in 2003. This session examined detailed studies of the impact of a blockage of the Malacca Straits, which might be closed from 3 weeks to 3 months adding 3-5 days to voyage time between the Gulf and Japan. Remedies discussed included security alert systems, electric fences around the decks, enhanced naval protection, stricter vetting of crews and port operatives. There is little enthusiasm for ships to carry weapons and grenades.

Threats to ports x Ship used as a bomb in a port city/area (e.g. Boston or Tokyo Bay) x Inadequate Energy-Related facilities at Ports. x Threats posed by lack of thorough inspection at international ports (2% shipping freight is checked)

Threats to pipelines: an Iraqi case study This session relied on up-to-the-minute reports by security forces and a leading private security company in Iraq. Iraq’s main 669KM oil artery, the North/South pipeline is more or less out of action in the North on account of sabotage. The bulk of Iraqi oil exports now run southwards through the area under British protection: Internal resistance is driven by a complex variety of political and personal motives. There is a general resentment of foreign occupation and an awareness of the risks of power shifts through the period of transition. From outside, resistance is reinforced by radicals pouring into Iraq, many with al-Qaida support. Urban unrest re lack of electricity, water, security etc is rising.

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Tribal unrest on tribal boundaries is endemic. Threats to security are becoming more diverse and complex. Without any control or customs inspection on the Iraqi borders, al-Qaida has almost 100% freedom of movement. Remedies include establishing tight control of the borders, introducing more trunk-road checks, extension of the “cash-for-arms” scheme and the building up of a network of new medical centres and hospitals, all of which provide a stream of valuable local intelligence. The security of the pipelines has been largely handed over to contracted Iraqi companies who complain that the State must be active in supervising overall responsibility, which is currently lacking.

Conclusion The two discernible Middle East flashpoints in the year ahead are Iraq and Saudi Arabia. There are high hopes of normalisation of relations with Iran and Libya. Palestine remains a pan-Arab rallying cry. Oil market leadership is entering a process of change. In the longer-term, acute competition for Gulf oil and gas exports looks extremely likely and will present the lead-consumer governments with new and difficult challenges.

STRATEGIC ACTIONABLE NET-CENTRIC BIOLOGICAL DEFENSE SYSTEM S. Kornguth Director, Countermeasures to Biological and Chemical Threats Institute for Advanced Technology, University of Texas at Austin, USA

Abstract:

1.

Technologies required for strategic actionable net-centric biological defense systems consist of : 1) multiplexed multi-array sensors for threat agents and for signatures of the host response to infection; 2) novel vaccines and restricted access antivirals/bacterials to reduce emergence of drug resistant strains pre- and post-event; 3) telemedicine capabilities to deliver post-event care to 20,000 victims of a biological strike; and 4) communication systems with intelligent software for resource allocation and redundant pathways that survive catastrophic attack. The integrated system must detect all threat agents with minimal false positive/negative events, a seamless integrated broad-band communications capability that enables conversion of data to actionable information, and novel pre- and post-event treatments. The development of multiplexed multi-array sensors, appropriate vaccines and antibiotics, and integrated communication capabilities are critical to sustaining normal health, commerce, and international activities.

INTRODUCTION

The overarching objectives in developing effective countermeasures to biological threats are to protect the Defense community and citizenry from such threats, and to develop agile responses to unanticipated events considering that successful terrorists do the unexpected. The need for protection against and responses to biological threats has been strikingly demonstrated by the use of anthrax contaminated letters that were sent through the U.S. mail in October 2001. That attack resulted in human illness, the loss of life, and discontinuity of government operations because of contamination of federal office buildings in Washington, DC. A recent report prepared by the Center for Strategic and International Studies (CSIS) and supported by the Defense Threat Reduction Agency (DTRA) of the 17 D. Morrison et al. (eds.), Defense against Bioterror: Detection Technologies, Implementation Strategies and Commercial Opportunities, 17–27. © 2005 Springer. Printed in the Netherlands.

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STRATEGIC NET-CENTRIC BIOLOGICAL DEFENSE SYSTEM

Department of Defense (DoD) came to the conclusion that the U.S. is at present not well prepared for a similar attack using anthrax1. The major problems include a lack of: 1) a clear chain of command, and 2) tools to provide the public with information that permits appropriate responses. The incidence of Congo-Crimean hemorrhagic fever in Afghanistan, an area where coalition forces are being deployed, increases this need. The potential threat posed by emergent disease (e.g., Severe Acute Respiratory Syndrome [SARS] and West Nile Fever virus) or from a major release of a contagious biological agent such as smallpox, has been a growing concern at all levels of the international community. This article outlines and discusses a new strategy that is needed if we are to be fully capable of sensing, preventing, and managing biological threats.

2.

NEW PARADIGM

The current paradigm addresses biological and chemical terrorist threats in a vertical (stove-piped) response. In the arena of developing sensors for the detection of biological agents, the paradigm has been to develop separate detectors for each agent or to develop a platform for detecting 12-24 threat agents using a single probe for each agent. There is a lack of an interactive networked communication system that is capable of managing a devastating emergent disease. To establish a highly networked system that is rapid enough to permit effective protection, it is necessary to evolve from the stove-piped, compartmentalized model currently in use to an integrated, fused, probabilistic, and frequently updated information model. Multiplexed multi-array sensor systems, capable of recognizing all bacterial or viral genomic materials related to pathogenicity or of recognizing antigenic domains that are specific indicators of pathogens are one component of a network needed for rapid detection and identification of biological threats. With respect to therapeutics, modern technologies for vaccine and antibiotic production provide decided advantages over older methods. The traditional vaccines require extensive development times before they become available for human use and undesired side effects commonly result from vaccines produced by these protocols. The cost associated with developing and testing vaccines, using traditional technology, approximates 50-100 million dollars per vaccine. The dissemination of antibiotics and antivirals through the world markets has resulted in the appearance of pathogenic bacteria and viruses that are resistant to these drugs. One approach to reduce the development of antibiotic resistance is to restrict the distribution of newly developed antibiotics. Such an approach presents ethical and social dilemmas. The consideration of options available for reduction of drug

STRATEGIC NET-CENTRIC BIOLOGICAL DEFENSE SYSTEM

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resistance, prior to a threat event, may permit development of a rational policy. A major problem facing our nations in the event of a biological attack or emergent disease is the large numbers of patients that can be anticipated to require medical treatment. Although improvements in emergency medical care and hospital equipment have been achieved during the past two decades, the ability of any community to manage an outbreak of infectious disease affecting >10,000 people is lacking. Rapid progress has been achieved whereby medical care can be provided to patients at sites that are distant from primary caregivers using telecommunication systems (e.g., the Armed Services in theater, large scale HMO providers such as Kaiser Permanente, or the correctional institutions in the U.S.). The funds needed to acquire telecommunication equipment for such distributed medical care delivery are estimated to be less than 100 million dollars for the entire U.S. At the present time such a distributed care system is not readily available. The new paradigm couples a network centric integrated sensor alert system that can detect all threat agents simultaneously, with a seamlessly integrated communication software capability that converts large scale data to actionable information. For this to be effective, the sensor system must yield minimal false positive and false negative results. The new paradigm incorporates large-scale databases on normative values of threat agents in many regions of the world so that significant changes in real time can be detected. The paradigm also includes the development and implementation of novel pre- and post-event treatment capabilities. Attention must be paid to the ability of high level decision makers and operators to recognize that a new state of threat has emerged, based upon output of the sensors, data fusion system, and iconographic display. Ambiguity of data, lack of an autonomous processing system, and high stress on the operator (e.g., sleep deprivation, lack of training) may all compromise the utility of a highly networked system of systems. What is needed for this new paradigm to succeed? The needs include multiplexed multi-array sensors for biological agents that infect people, livestock, and edible crops. The agents of concern include many on the Militarily Critical Technologies List prepared for the Office of the Secretary of Defense. We need multiplexed multi-array sensor systems with high specificity and selectivity for the rapid detection of host responses to infection. We need a new generation of effective therapeutics, including vaccines, antibiotics, and antivirals. A network centric intelligent communication system that can provide accurate comprehensible information to decision makers (from command officers to unit operators) is required. To minimize morbidity and mortality and optimize containment of disease, a biosurveillance system based on archival health databases, statistical models, and data mining strategies that can provide an early alert to a disease outbreak is required.

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STRATEGIC NET-CENTRIC BIOLOGICAL DEFENSE SYSTEM

In many cases the operator may be required to understand the meaning of acquired data in very short time periods (seconds to minutes) if the response is anticipated to change the outcome of an engagement. The Tactical Decision Making Under Stress (TADMUS) program is one example of such a situation. In the biological threat arena, the detection and identification of toxins require rapid analysis and operator comprehension. The large increase in numbers of sensors (for high explosives [HX], biological and chemical agents, meteorological conditions) together with the rapid changes in op tempo required to manage emergence of clinical disease would suggest a need for the development of systems capable of autonomous generation of an alert when threat conditions arise.

3.

CURRENT STATE OF TECHNOLOGY NEEDED FOR THE NEW PARADIGM

In the sensors area, the genomes of most biological threat agents have been sequenced and the signatures of toxins described. Novel multiplexed multi-array sensor-platform systems utilize the genomic datasets to detect the appearance of threat levels of these agents. In the therapeutics area, researchers are working towards identifying critical antigenic epitopes of these agents. New therapeutics can emerge that have an antigen binding capacity significantly greater than antigen-cell receptor binding, resulting in the potential for agent neutralization. Technologies have been developed over the past decade for the development of new drugs and DNA based vaccines. Restricted access antivirals/antibacterials will need to be developed to reduce the emergence of drug resistant strains pre- and post-event. A significant development in our program at The University of Texas at Austin (UT-Austin)2 has been the novel design and production of an antibody that binds the anthrax PA antigen 1000 times stronger (Kd