Biological warfare, bioterrorism, biodefence and the biological and toxin weapons convention

Edgar J. DaSilva
Director, Division of Life Sciences UNESCO, France
E-Mail: e.dasilva@unesco.org

Biological warfare is the intentional use of micro-organisms, and toxins, generally of microbial, plant or animal origin to produce disease and death in humans, livestock and crops. The attraction of bioweapons in war, and for use in terroristic attacks is attributed to easy access to a wide range of disease-producing biological agents, to their low production costs, to their non-detection by routine security systems, and to their easy transportation from one place to another. In addition, novel and accessible technologies give rise to proliferation of such weapons that have implications for regional and global security. In counteraction of such threats, and in securing the culture and defence of peace, the need for leadership and example in devising preventive and protective strategies has been emphasised through international consultation and co-operation. Adherence to the Biological and Toxin Weapons Convention reinforced by confidence-building measures sustained by use of monitoring and verification protocols, is indeed, an important and necessary step in reducing and eliminating the threats of biological warfare and bioterrorism.

• vaccines against a wide variety of bacteria and viruses identified in core control and warning lists of biological agents used in biowarfare (Table 3)
• rapid detection, identification and neutralisation of biological and chemical warfare agents
• antidotes and antitoxins for use against venoms, microbial toxins, and aerosol sprays of toxic biological agents
• development of genetically-modified organisms
• development of bioweapons with either incapacitating or lethal characteristics
• development of poisons e.g. ricin, and contagious elements e.g. viruses, bacteria
• development of antianimal agents e.g. rabbit calcivirus disease (RCD) to curb overpopulation growth of rabbits in Australia and New Zealand
• development of antiplant contagious agents e.g. causative agents of rust, smut, etc.

Bioweapons

Bioweapons are characterised by a dual-use dilemma. On a lower scale, a bioweapons production facility is a virtual routine run-of the-mill microbiological laboratory. Research with a microbial discovery in pathology and epidemiology, resulting in the development of a vaccine to combat and control the outbreak of disease could be intentionally used with the aid of genetic engineering techniques to produce vaccine-resistant strains for terroristic or warfare purposes. The best known example, reported by UNSCOM (Table 3), is the masquerading of an anthrax-weapon production facility as a routine civil biotechnological laboratory at Al Hakam. In summary the dual-use dilemma is inherent in the inability to distinctively define between offence -and defence- oriented research and development work concerning infectious diseases and toxins. Whilst progress in immunology, medicine, and the conservation of human power resources are dependent on research on the very same agents of infectious diseases, bans and non-proliferation treaties are associated with the research and production of offensive bioweapons.

Genetic engineering and information are increasingly open to misuse in the development and improvement of infective agents as bioweapons. Such misuse could be envisaged in the development of antibiotic-resistant micro-organisms, and in the enhanced invasiveness and pathogenicity of commensals. Resistance to new and potent antibiotics constitutes a weak point in the bio-based arsenal designed to protect urban and rural populations against lethal bioweapons. An attack with bioweapons using antibiotic-resistant strains could initiate the occurrence and spread of communicable diseases, such as anthrax and plague, on either an endemic or epidemic scale.

The evolution of chemical and biological weapons is broadly categorised into four phases. World War I saw the introduction of the first phase, in which gaseous chemicals like chlorine and phosgene were used in Ypres. The second phase ushered in the era of the use of nerve agents e.g. tabun, a cholinesterase inhibitor, and the beginnings of the anthrax and the plague bombs in World War II. The Vietnam War in 1970 constituted the third phase which was characterised by the use of lethal chemical agents e.g. Agent Orange, a mix of herbicides stimulating hormonal function resulting in defoliation and crop destruction. This phase included also the use of the new group of Novichok and mid-spectrum agents that possess the characteristics of chemical and biological agents such as auxins, bioregulators, and physiologically active compounds. Concern has been expressed in regard to the handling and disposal of these mid-spectrum agents by "chemobio " experts rather than by biologists (Henderson, 1999).

The fourth phase coincides with the era of the biotechnological revolution and the use of genetic engineering. Gene-designed organisms can be used to produce a wide variety of potential bioweapons such as:

• organisms functioning as microscopic factories producing a toxin, venom or bioregulator
• organisms with enhanced aerosol and environmental stability
• organisms resistant to antibiotics, routine vaccines, and therapeutics
• organisms with altered immunologic profiles that do not match known identification and diagnostic indices
• organisms that escape detection by antibody-based sensor systems

Public attention and concerns, in recent times, have been focused on the dangers of nuclear, biological and chemical-based terrorist threats (Nye, Jr. and Woolsey, 1997). This concern is valid given the significant differences between the speed at which an attack results in illness and in which a medical intervention is made, the distribution of affected persons, the nature of the first response, detection of the release site of the weapon used, decontamination of the environment, and post-care of patients and victims. Pollution and alteration of natural environments occurs with the passage of time, as a consequence of reliance on conventional processes such as dumping of chemical munitions in the oceans; disposal of chemical and biological weapons through open-pit burning; and in-depth burial in soil in concrete containers or metallic coffins (Miller, 1999). Incineration, seemingly the preferred method in the destruction and disposal of chemical weapons, is in the near future likely to be replaced by micro-organisms. Laboratory-scale experimentation has shown that blistering agents, such as mustard mixtures e.g. lewisite and adamsite, and nerve agents e.g. tabun, sarin and saman are susceptible to the enzymatic action of Pseudomonas diminuta, Alteromonas haloplanktis, and Alcaligenes xylosoxidans. In disposing of the chemical weapon stockpile of diverse blister and nerve agents, research now focuses on several microbial processes that are environment-friendly and inexpensive in preference to costly conventional chemical processes in inactivating dangerous chemical agents, and degrading further their residues (Mulbry and Rainina, 1998).

Chemical weapons are intended to kill, seriously injure or incapacitate living systems. Choking agents such as phosgene cause death; blood agents such as cyanide-based compounds are more lethal than choking agents; and nerve agents such as sarin and tabun are still more lethal than blood agents.

The use of bioweapons is dependent upon several stages. These involve research, development and demonstration programmes, large-scale production of the invasive agent, devising and testing of efficiency of appropriate delivery systems, and maintenance of lethal and pathogenic properties during delivery, storage and stockpiling. Projectile weapons in the form of a minuscule pellet containing ricin, a plant-derived toxin are ingenuously delivered through the spike of an umbrella. Well known examples of the use of such a delivery system are the targeted deaths of foreign nationals that occurred in London and Paris in the autumn of 1978.

Small-pox virus has long been used as a lethal weapon in biological warfare. The decimation of the American Indian population in 1763 is attributed to the wide distribution by the invading powers of blankets of smallpox patients as gifts (Harris and Paxman, 1982). More recently, WHO after a 23-year campaign declared the eradication of smallpox world-wide in 1980. A landmark date of June 1999, had been set in 1996, for the destruction of the remaining stocks of smallpox virus that were being maintained in Atlanta, Georgia, USA, and Koltsovo, Siberia, Russia. Current issues, however, such as the emergence of immunosuppressed populations resulting from xenotransplantation and cancer chemotherapy, loss of biodiversity, and the re-emergence of old diseases have necessitated a re-evaluation of the decision to destroy "a key protective resource".

Fundamental research and field tests continue to focus on determining the minimum infective dose of the biological agent required to decimate targeted populations, the time period involved to cause disease instantaneously or over a long period of time, and the exploitation of the entry mechanisms such as inhalation, ingestion, use of vectors, and the contamination of natural water supplies and food stocks.

The institution of food insecurity is a subtle form of economic and surrogate biological warfare. Conflicts over shared water resources in some regions of the world are commonplace. Human health, food security and the management of the environment are continuously being threatened, regionally and globally, by dwindling reserves of water (Serageldin, 1999). Within the framework of a real world perspective of biotechnology and food security for the 21st century, soil erosion, salinisation, overcultivation and waterlogging are other constituents (Vasil, 1998). Deliberately contaminated food containing herbicide, pesticide or heavy metal residues, and use of land for crops for production of luxurious ornamental plants and cut flowers, is another constituent of food insecurity. Again, new and emerging plant diseases affect food security and agricultural sustainability, which in turn aggravate malnutrition and render human beings more susceptible to re-emerging human diseases (DaSilva and Iaccarino, 1999). The deliberate release of harmful and pathogenic organisms, that kill cash crops and destroy the reserves of an enemy, constitutes an awesome weapon of biological warfare and bioterrorism (Rogers et al, 1999).

Anticrop warfare, involving biological agents and herbicides, results in debilitating famines, severe malnutrition, decimation of agriculture-based economies, and food insecurity. Several instances using late blight of potatoes, anthrax, yellow and black wheat rusts and insect infestations with the Colorado beetle, the rapeseed beetle, and the corn beetle in World Wars I and II have been documented. Defoliants in the Vietnam War have been widely used as agents of anticrop warfare. Cash crops that have been targeted in anticrop warfare are sweet potatoes, soybeans, sugar beets, cotton, wheat, and rice. The agents used to cause economic losses with the latter two foreign-exchange earnings were Puccinia graminis tritici and Piricularia oryzae respectively. Wheat smut, caused by the fungus Tilettia caries or T. foetida has been used as a biowarfare weapon (Whitby and Rogers, 1997). The use of such warfare focuses on the destruction of national economies benefiting from export earnings of wheat - an important cereal cash crop in the Gulf region. In addition, the personal health and safety of the harvesters is also endangered by the flammable trimethylamine gas produced by the pathogen. Species of the fungus Fusarium have been used as a source of the mycotoxin warfare in Southeast and Central Asia.

Foodborne pathogens are estimated to be responsible for some 6.5 to 33 million cases on human illnesses and up to 9000 deaths in the USA per annum (Buzby et al, 1996). The costs of human illnesses attributed to foodborne causes are between US$2.9 and 6.7 billion, and are attributed to six bacterial pathogens-Salmonella typhosa, Campylobacter jejuni, Escherichia coli 0157H:H7, Listeria monocytogenes, Staphylococcus aureus and Clostridium perfringens found in animal products. Consequently, there is the dangerous risk that such organisms could be used in biological warfare and bioterrorism given that Salmonella, Campylobacter and Listeria have been encountered in outbreaks of foodborne infections, and that cases of food poisoning have been caused by Clostridium, Escherichia and Staphylococcus.

Bacterial and fungal diseases are significant factors in economic losses of vegetable and fruit exports. Viral diseases, transmitted by the white fly Bemisia tabaci are responsible for severe economic losses resulting from damage to melons, potatoes, tomatoes and aubergines. The pest, first encountered in the mid-1970s in the English-speaking Caribbean region has contributed to estimated losses of US$50 million p.a in the Dominican Republic. Economic losses resulting from infestation of over 125 plant species, inclusive of food crops, fruits, vegetables and ornamental plants have been severe in St. Lucia, St. Kitts and Nevis, St. Vincent and the Grenadines, Trinidad and Tobago, and the Windward Islands. In Grenada, crop losses in the mid-1990s were estimated at UD$50 million following an attack by Maconnellicoccus hirsutus, the Hibsicus Mealy Bug. (Kadlec, 1995) has explained how "the existence of natural occurring or endemic agricultural pests or diseases and outbreaks permits an adversary to use biological warfare with plausible denial" and has drawn attention to several imaginative possibilities.

The interaction of biological warfare, genetic engineering and biodiversity is of crucial significance to the industrialised and non-industrialised societies. Developing countries that possess a rich biodiversity of cash crops have a better chance of weathering anticrop warfare. On the other hand, the food security of the industrialised societies, especially in the Northern Hemisphere, is imperilled by their reliance on one or two varieties of their major food crops. The use of genetic engineering, whilst enhancing crop yields and food security, could result in more effective anticrop weapons using gene-modified pathogens that are herbicide-resistant, and non-susceptible to antibiotics. Threats to human health exist with the biocontrol and bioremediation agent Burkholderia cepacia during agricultural and aquacultural use (Holmes et al, 1998). Attention has also been drawn to the new and potential threats arising from the uncontrolled release of genetically modified organisms (Av-Gay, 1999).

Another aspect of biological warfare involves the corruption of the youth of tomorrow -the bastion of a nation's human power with cocaine, heroin and marijuana derived from drug and narcotic plantations reared by conventional and/or genetically engineered agriculture. On the other hand, the eradication of such drugs plant crops through infection with plant pathogens could prove counterproductive in yielding more knowledge and skills to wipe out food crops, and animal-based agriculture.

Bioterrorism

Popular scenarios of bioterrorism, that may have some mythical origins and cinematic Hollywoodian links, include the use of psychotic substances to contaminate food; the use of toxins and poisons in political assassinations; raids with crude biological cloud bombs; use of dried viral preparations in spray powders; and low-flying cruise missiles adding destruction and havoc with genetically-engineered micro-organisms.

Public awareness of the growing threat of bioterrorism in the USA is gathering momentum (Henderson, 1999). Development of national preparedness and an emergency response focus in essence, on the co-ordination of on-site treatment of the incapacitated and wounded, on-spot decontamination of the affected environment, detection of the type and character of the biological agent, and its immediate isolation and neutralisation. The rise of bioterrorism as a priority item on the agendas of international concern and co-operation is now being reflected in the establishment of verification procedures to guard against contravention of the Biological and Toxin Weapons Convention, and in efforts in institutionalising a desirable and much needed state of preparedness. In the USA, there has been a boost in funding for such research and defensive measures (Marshall, 1999). International workshops and seminars focus on the peaceful use of biotechnology and the Convention on Biological Weapons (Table 3). In addition several other measures are in force to monitor the development and use of bioweapons (Pearson, 1998). Data generated by the Human Genome Project helps in the use of genomic information

• to develop novel antibiotics and vaccines,
• to enhance national and civil defence systems to contain and counteract the use of biological agents in the manufacture of bioweapons,
• to minimise and eliminate susceptibilities of different peoples, cultural and ethnic groups to hitherto unfamiliar or unknown diseases such genomic research could fuel the production of ethnic or peoples' specific weapons.

Curators and conservationists of biological diversity, public health officials, and biosecurity personnel, developing emergency preparedness provide convincing arguments to continue to maintain live viral stocks for the preparation of new vaccines in guarding against the re-emergence of small-pox as a result of either accidental release or planned use in bioterrorism. The microbiological community, and especially culture collections have an important role to play in educating the public to contain unexpected and sudden outbreaks of diseases through minimising the easy acquisition of microbial cultures for use in bioterrorist threats. To offset the illegitimate use of microbial cultures, obtained through either fraudulent or genuine means, the microbiological community naturally occupies a central role in answering the challenges posed in the production of bioweapons Biological agents may be obtained from culture collections providing microbial species for academic and research purposes; supply depots of commercial biologics; field samples and specimens; and application of genetic engineering protocols to enhance virulence (Atlas, 1998). An example is the acquisition by a laboratory technician, of the causative agent of bubonic plague through the routine mailing system. In addition to expanding and safeguarding the planet's microbial genetic heritage, certified microbiologists can contribute to the building up of the defences of peace through the development of educational and public health training programmes, and surveillance protocols in counteracting bioterrorism.

A recent survey of over 1400 research institutions, universities, medical colleges, and health science centres in the USA focused on research activities, production capabilities and containment facilities that may necessitate compliance declarations with the protocols of the Biological and Toxin Weapons Convention (Weller et al, 1999). However, in the absence of a systematised infrastructure, the administrative, educational, economic and legal costs are burdensome and considerable. Compliance declarations and regimes are of direct consequence with institutions that are engaged in routine and genetically-engineered research with specialised groups of microbial pathogens and toxins; that possess high-level containment facilities and laboratories; that are engaged in the design and engineering of high-production capacity bioreactors with fermentation volumes of 100-litres and above; and that do contract research for government and industry with biological agents that could serve as potential triggers of biological warfare and bioterrorism (Weller et al, 1999).

In brief, the very skills and technologies that are used by industry to screen, process and manufacture drugs and vaccines could be used to develop bioweapons. Given the increasing risks to pertaining to the threats of bioterrorism and bioweapons, and the dilemma of dual-use technologies, site-verification of existing facilities and data assemblage and monitoring activities seem to be necessary. Nevertheless, despite bio-industrial concerns based on potential risks pertaining to loss of confidential biotechnological data and proprietary genetic holdings, compliance with the Biological and Toxin Weapons Convention is a must. The role of industry in designing apt verification measures is a crucial element in the strengthening of the convention (Department of Foreign Affairs and Trade, 1999). Doing so, as a fundamental and primary step, provides recognition of the utility of the convention, and at the same time strengthens its importance and authority in the outright banning of the production, stockpiling and manufacture of undesirable bioweapons (Monath and Gordon, 1998). The practice of such investigations emphasises the growing need for the development of a verification protocol that deters and discourages violation of the Convention (Butler, 1997).

The necessity of producing and stockpiling the small-pox vaccine has been emphasised in testimony by the author of the Hot Zone and Cobra Event (Preston, 1998). These are entertainment scenarios about the outbreaks of the Ebola virus in the nearby surroundings of Washington, D.C., and a bioterroristic event in New York City respectively. The potential outbreak of an epidemic of the now eradicated small-pox, in a population that has not been vaccinated since the registration of the last known case in Somalia in 1977, is a human disaster waiting to happen and which can be contained and avoided well ahead in time.

Another aspect of bioterrorism is to disrupt agriculture, to decimate livestock, to contaminate the environment, and to seed food insecurity through intentional food poisoning and food infection. Concerns, recently, have been expressed about the possible outbreak of gastrointestinal anthrax in Badakhshan, Afghanistan (Scott and Shea, 1999), and in the border areas neighbouring Tajikistan, following first reports of symptoms which are also common to cholera, gastrointestinal anthrax, plague, tularaemia and listerosis.

Appropriate control measures in combating bio- and chemical terrorism, and the production of bioweapons would involve:

• Enactment of national laws that criminalize the production, stockpiling, transfer and use of chemo- and bioweapons
• Enactment of national laws that monitor the use of precursor chemicals that lend themselves to the development of chemical and bio-weapons
• Establishment of national and international databanks that monitor the traffic of precursor chemicals, their use in industry outreach programmes, and their licensed availability in national, regional and international markets
• Establishment and use of confirmatory protocols in the destruction and dispersal of outdated stockpiles, and chemical precursor components.

Incidents of bioterrorism in the last two decades, fortunately were rare. In the USA, the most publicised case is that of the deliberate contamination of salad bars in 1984, with Salmonella typhimurium, an intestinal pathogen. The bioterroristic act, carried out by members of the Rajnaashee cult in Oregon, was aimed at securing an electoral result by incapacitating voters lacking empathy with the cult's preferential candidate (Torok and Tauxe, 1997). This outbreak of salmonellosis, and that of shigellosis (Kolavic and Kimura, 1997) are documented examples of bio-threats to public health. Reporting of such cases is often rare since credence is generally attributed to the more common occurrence of food infection or food intoxication rather than to the criminal, and intentional, contamination of food supplies and catering facilities.

In another well publicised case, the Japanese Aum Shinrikyo sect released the nerve agent sarin in a Tokyo subway in 1995 following failure to obtain the Ebola virus for weaponisation in 1992 from (then) Zaire, and inability thereafter to release anthrax spores from a building, and botulinum toxin from a vehicle.

Bioterroristic risks are minimised through effective responses built around the development of preventive and control measures to contain, control, minimise, and eradicate outbreaks of travel-related vaccine preventable diseases. Tropical medical practitioners, public health personnel, immunologists, microbiologists, and quarantine authorities have an important role to play in safeguarding against potential bioterrorism in the future through timely detection of hepatitis A and B, yellow fever, Japanese encephalitis, rabies, typhoid, anthrax, plague and meningitis. To counter possible bioterrorist attacks using stolen or illegally acquired stocks of the dreaded small-pox virus, the WHO has postponed the agreed upon destruction date of June 1999 to December, 2002. It is likely at that time, that yet another postponement may occur.

Control, monitoring and reporting systems

Reporting of outbreaks of disease, often attributed to natural causes, should always be taken seriously since such outbreaks often result from non-compliance with the prohibitions embodied in international conventions in force. Potential nosocomial transmission of biological warfare agents occurs through blood or body fluids (e.g. haemorrhagic fever and hepatitis viruses); drainages and secretions (e.g. anthrax, plague, smallpox); and respiratory droplets (e.g. influenza plague, smallpox). The obligatory notification and reporting of outbreaks of diseases in humans, animals and plants helps to contain and neutralise the threats of biological warfare and bioterrorism. Such practice, in accordance with existing health codes and complementary reporting systems (Table 3), helps to develop a reservoir of preparedness capacity.

The development of a response strategy and technology in monitoring the control of weapons is at the core of a state of preparedness in the USA (New York Academy of Sciences, 1998). Current anti-bioterrorism measures involve the devising of unconventional effective countermeasures to combat misuse of pathogens encountered either naturally or in a genetically modified state. Such a strategic response involves:

• the use of bacterial RNA-based signatures and corresponding structural templates through which all pathogens can be potentially identified through appropriate trial and error testing, and verification;
• development of a data base of virtual pathogenic molecules responding to the bacterial signature templates;
• development, evaluation and use of effective antibacterial molecules that eliminate pathogens but do not harm humans nor animals (Ecker and Griffey, 1998).

Guidelines and recommendations have been formulated for use by public health administrators and policy-makers, medical and para-clinical practitioners, and technology designers and engineers in developing civilian preparedness for terrorist attack (Institute of Medicine, 1999). Areas covered deal with rapid detection of biological and chemical agents, pre-incident analysis of the targeted area, protective clothing, and use of vaccines and pharmaceuticals in treatment and decontamination of mass casualties.

The lack of basic hygienic procedures accompanying the use of domestic and public health facilities in the discharge, and disposal of human wastes has contributed to a large extent of the state of unpreparedness in responding to obnoxious biological weapons. Furthermore, the indiscriminate use of chemotherapeutics, and the overuse of antibiotics, has contributed to a complacent sense of invincibility in confronting once easily eradicated causative agents of disease.(Henderson,1999) in summarising important distinctions between chemical and biological terrorism emphasised the need for an awareness and allocation of resources in devising appropriate responses to threats of bio- and chemoterrorism. Crucial elements of appropriate and timely responses are the renovation and modernisation of the public health infrastructure, the necessary networking of the para-clinical and specialised medical forces involving nurses, general health practitioners, epidemiologists, quarantine specialists and experts in communicable diseases. In brief, an appropriate optimal response constitutes a co-ordinated management of medical capability and restorative efforts backed up by supporting extension services.

Several examples of scientific societies, and of national, regional and global initiatives addressing the global threats of emerging infections and disease have been documented (DaSilva and Iaccarino, 1999). The African biotechnological community is aware of the need of safety considerations and risk assessment in the development and use of bioengineering micro-organisms (Van der Meer et al, 1993). Activities in Uganda, Kenya, Zimbabwe, Tanzania, South Africa, and the Southern African Development Community (Angola, Botswana and Zimbabwe) constitute a revelation of regional academic capacity and competence in addressing issues formulating guidelines, and programming initiatives concerning food security, recombinant DNA biosafety guidelines, and environmental biosafety protocols.

Destruction and deterioration of the environment is usually preceded by the emergence and spread of infectious diseases. In Southern Africa, beset by war-plagued conditions, migration of tribal populations and overnight development of nomadic villages, the loss of life and erosion of human resources results from the occurrence of AIDS, malaria, tuberculosis, meningitis and dysentery. Academic and affluent societies are often stricken by outbreaks of hamburger disease. The causative agent is a virulent commensal Escherichia coli.

AIDS in South Africa is likely to become a notifiable disease as a consequence of governmental concern in containing the widespread occurrence of the disease (Cherry, 1999). The Department of Industrial Health in Singapore, in fostering a favourable workplace environment, requires the reporting of an outbreak or occurrence of anthrax listed amongst 31 notifiable industrial diseases. The rare outbreak of encephalitis in Malaysia, more recently, reached alarming proportions of concern with severe economic and health implications for other Southeast Asian countries e.g. Laos and Vietnam, thus prompting the destruction of large numbers of the porcine population suspected of harbouring the virus.

The role of chemical protective clothing in the performance of military personnel in combat and surveillance situations has been reviewed (Krueger and Banderet, 1997). The performance and output of military and auxiliary personnel is severely affected following exposure to chemical weapons using nerve agents and disabling chemicals. Interference with a loss of physiological functions such as loss of muscle control, paralysis of body movements, loss of memory, dermal discoloration, prolonged deterioration of vision, speech intelligibility, and the like result in loss of psychological confidence, and professional competence.

The development of chemical protective clothing incorporating chemical and biochemical protectants, such as hypochlorites, phenolics, soap waxes, and antidotes, helps offset psychological stress and trauma, and combat anxiety. Anti-biowarfare and anti-bioterrorism research has led to the development of rub-on polymer creams and anti-germ warfare lotions that provide protection also against the influenza virus (Dobson, 1999a,b). Chemical protection in the form of rubberised hoods and tunics, gloves, boots, and gas masks helps guard against tear gas agents, nerve agents and chemical irritants delivered either by aerosols or liquid sprays. Recently, the incorporation of antibiotics in routine textiles as anti-odour and anti-infection agents has been reported (Barthélémy, 1999).

Weapons of mass destruction, be they nuclear, chemical or biological in nature, constitute a threat to national security, and to regional and international co-operation (New York Academy of Sciences, 1998). Civilian and military vulnerability to biological weapons can be overcome by resorting to the development of biosensors, fast-reacting bio-detection agents, advanced medical diagnostics, and effective vaccination and immunisation programmes.

Bio-detection has been spurred on through the development of biorobots (Treindl, 1999). Mechanised insects with computerised artificial systems mimic through microchips or biochips certain biological processes such as neural networks that gather and process neural impulses that influence behavioural sensitivities to stress and dangerous responses to substances of biological and chemical origin. These micro-gadgets can carry out in a single operation tasks such as DNA processing, screening of blood samples, scans for the presence and identifications of disease genes, and monitoring of genetic cell activity normally carried out by several laboratory technicians.

Furthermore, the ability to incorporate such dual-use cyberinsects and biorobots in the potential weaponnization of biological agents needs to be addressed and curbed. Biorobots of the household pest-the cockroach, Blaberus discoidalis, the desert ant- Cataglyphis, and the cricket- Gryllus bimaculatus are already the subject of in situ research. The cricket robot is being developed, in the USA, through academic research within the framework of the Defence Advanced Research Projects Agency (DARPA) robotics program. The main raison d'être of robobiology is the development of miniaturised models with biomechanised minds that could be used also in space biology exploration. Moreover, like humans and other living systems, their life span is not limited by the deleterious effects of toxic chemicals and wastes.

To help the medical community save lives during and in the immediate aftermath of bioterrorist attack, DARPA has sponsored projects that rapidly identify pathogens for treatment either with a combination of antimicrobial substances or nannobombing with potent biosurfactant emulsions (Alper, 1999).

The development of advanced biological and medical technologies aim at saving the 30 to 50 per cent of lives that are traditionally lost in frontline battlefield areas, and, reducing drastically the 90 per cent combat deaths that occur in close combat prior to medical intervention. Such technologies involve the development and use of surgical robot hands, trauma care technology, and remote teledecontamination of biologically polluted environments.

Tissue-based biosensors provide reliable alerts and assessments of human health risks in counteracting bioterrorism and biowarfare. Comprised of multicellular assemblies, and wide-ranging antibody templates, such sensors detect. and predict physiological consequences arising from biological agents that have not been fingerprinted nor identified at the molecular level. Alerts and assessments are made through the use of reporting molecules that express themselves through the phenomena of luminescence, fluorescence, etc. For example, the pigment bacteriorhodopsin obtained from the photosynthetic Halobacterium salinarum is used as a sensor for optical computing, artificial vision, and data storage. Defensive and deterrent technologies are being developed to afford maximum protection to civilian and military personnel; and to reduce to a minimum the fall-out damage resulting from bioweapons that use unconventional pathogen countermeasures, controlled biological systems and biomimetics in the defence against biowarfare and bioterrorism (Table 4 a, b, c).

DARPA's Unconventional Pathogen Countermeasures program focuses on the development of a powerful and effective deterrent force that limits, reduces and eliminates damage and spread out resulting from use of bioweapons. Such countermeasures focus on:

• Impeding and eliminating the invasive mechanisms of pathogens that facilitate their entry through inhalation, ingestion, and skin tissue
• Devising broad-spectrum medical protocols and treatments that are effective against a wide range of pathogenic organisms and their deleterious products
• Enhancement of external protection using polyvalent adhesion inhibitors in protective clothing, biomimetic pathogen neutralising materials, and personal environmental hygienic protection systems

A novel challenge for the biotechnological industry is the development of effective biological defence programmes based on novel fundamental research in biotechnology, genetics and information technology. Biosensor technology is the driving force in the development of biochips for the detection of

• pesticides, allergens, and micro-organisms;
• gaseous pollutants e.g. ammonia, methane, hydrogen-sulphide, etc
• heavy metals, phosphate and nitrates in potable water
• biological and chemical pollutants in the dairy, food and beverage industries

using the tenets of reliability, selectivity, range of detection, reproducibility of results, and, standard indices of taxonomy, contamination and pollution. Biodefence programs are now being developed around the unique sensorimotor properties of biological entities. Bees, beetles, and other insects are being recruited as sentinel species in collecting real-time information about the presence of toxins or similar threats.

Biosensors, using fibre optic or electrochemical devices, have been developed for detecting micro-organisms in clinical, food technology, and military applications (King et al, 1999; Mulchandani et al, 1999). An immunosensor is used for the detection of Candida albicans (Muramatsu et al, 1986). Bacillus anthracis, and bacteria in culture are detected by optical sensors (Swenson, 1992). In addition, several systems have been developed in the USA to detect biological weapons. Generic and polyvalent immunosensors have been devised to detect biological agents that cause metabolic damage and whose antigenic structure has been specifically genetically altered to avoid detection by antibody-based detection systems. Other biodetection systems functioning as early warning/alert systems involve the detection of biological particle densities by laser eyes and electronic noses with incorporated alarms. Emphasis in such systems is less on the identity of the biological agent, and more on the early warning aspect which constitutes an effective arm in counteracting the threat of bioterrorism in daily and routine peace time environments (Schutz et al, 1999).

Such electronic noses result from a combination of neural informational networks with either chemical or biological sensor arrays and miniaturised spectral meters. Compact, automated and portable, electronic noses offer inexpensive on-the-spot real-time analysis of toxic fuel and gas mixtures, and identification of toxic wastes, household gas, air quality, and body odours (Wu, 1999).

The goal of such programmes is to prevent unpleasant technological surprises arising from misuse of biological agents, chemicals, ethical pharmaceuticals, and obnoxious gases. The preparedness involves the intelligence monitoring of the capabilities, intentions, and resource materials of potential opponents, and terrorists.

In testimony to the U.S. Senate Public Health and Safety Committee, it was emphasised that:

a) the strategy of developing and producing dual purpose diagnostics, therapeutics, and vaccines that protects public health and defends against biological weapons

b) the control and elimination of infectious diseases through improved surveillance, early warning, communication and training networks, and

c) the availability of front line preparedness and response in responding to bioterrotism and biological warfare (ASM, 1999) are integral constitutive elements of a preparedness domestic capacity against bioterrorism (Preston, 1998).

Concluding remarks

Biological warfare can be used with impunity under the camouflage of natural outbreaks of disease to decimate human populations, and to destroy livestock and crops of economic significance.

Attempts to regulate the conduction of warfare and the development of weaponry using harmful substances such as poisons and poisoned weapons are enshrined in conventions drawn up with respect to the laws and customs on land (Table 1). These early instruments of war -prevention measures, and eventual confidence-building and peace-building measures, have evolved from normal practices and characteristic usages established amongst, civilised peoples; from the basic laws of humanity; the tenets of long established and widely accepted faiths, and the dictates of public conscience.

In that context, the conventions outline steps and measures to safeguard buildings and historic monuments dedicated to art, religion and science, and to clinics and hospitals housing the sick and wounded, provided they are not engaged in combat. Use of such personnel in experiments designed to enhance the lethality of weaponry containing harmful substances such as poisons, disabling chemicals and ethical pharmaceuticals is implicitly and strictly prohibited. In the history of the interactions between science, culture and peace, the term Unit 731 is associated with the demeaning of science and humanity, their values and ethics. The activities carried out by Unit 731 in World War II were prohibited as far back as 1907 (Table 1).

In neutralising the effects of biological agents and rendering them ineffectual for use as bioweapons, bioindustries are now concentrating on the development of a wide range of biotherapeutics - antibiotics and vaccines (Stephanov et al, 1996; Perrier, 1999; Russell, 1999; Zoon, 1999) through development of biologically-based defence science and technology programmes. Current bioweapons defence research is now focusing on developing biosensors containing specific antibodies to detect respiratory pathogens likely to be dispersed through sprays and air cooling systems. Also contract research centres around the use of biotechnologies to remediate environmental areas contaminated with heavy metals, herbicides, pesticides, radioactive materials, and other toxic wastes.

The genetic screening of human diseases and drug discovery have been facilitated by research advances in the field of bioinformatics (Lehrach et al, 1997). The automated and computerised study of shared information in the genomic DNA of biological resources in tandem with digital processing and graphic computation techniques, offers a base for the development of devices for monitoring environmental degradation and development of biodefence programmes (Table 4 a, b, c). The aim of such research in developing sensors for the timely detection and neutralisation of biological weapons is reflected in "Sherlock Holmes' dog that doesn't bark", i.e the silence of the sensor indicates the presence of a biological agent (Morse, 1998).

Development of national preparedness and emerging responses to biological agents, either in bioterroristic or combat situations, is dependent upon the rapidity of intervention by trained antiterroristic personnel comprised of microbiologists, doctors, hospital staff, psychologists, military or law-enforcing forces, and public health personnel. In this regard, the economic impact of a bioterroristic attack has recently been assessed (Kaufmann et al, 1997). Investing in public health surveillance helps enhance domestic preparedness in dealing with, bioterrorism, emerging diseases and foodborne infections.

The likelihood of genetically engineered micro-organisms contributing to the emergence of new infections cannot be ignored. Public reaction to the introduction of genetically engineered crops into Europe, at this time, is accompanied by controversy and fears for environmental safety. The uncertainty accompanying the potential outbreaks of new scourges is another complicating factor. Increasing public awareness and understanding of safety issues and the release of genetically engineered organisms into the environment helps to overcome unsubstantiated fears and misconceptions, and to secure confidence through a state of preparedness. On such strategies, a ready and effective response exists to combat potential catastrophes and outbreaks of emerging diseases. The science and value of environmental safety evaluations constitute a right step in this direction (Käppeli and Auberson, 1997).

New threats from weapons of mass destruction continue to emerge as a result of the availability of technology and capacity to produce, world-wide, such weapons for use in terrorism and organised crime (Department of Defence, 1996). Novel and accessible technologies give rise to proliferation of such weapons that have implications for regional and global security and stability. In counteraction of such threats, and in securing the defence of peace, the need for leadership and example in devising preventive and protective responses has been emphasised through the need for training of civilian and non-civilian personnel, and their engagement in international co-operation. These responses emphasise the need for the reduction and elimination of bioterrorism threats through consultation, monitoring and verification procedures; and deterrence, through the constant availability and maintenance of a conventional law and order force that is well-versed in counterproliferation controls and preparedness protocols (American Society for Microbiology, 1999).

Adherence to the Biological and Toxin Weapons Convention, reinforced by confidence-building measures (United Nations, 1997) is indeed, an important and necessary step in reducing and eliminating the threats of biological warfare and bioterrorism (Tucker, 1999).

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