Biological toxins: A bioweapon threat in the 21st century

Security Dialogue

Volumn 33, Issue 2, 2002, Pages 141-156

  Gorka, Sebestyèn ^a   Sullivan, Richard ^b  

^a Ctr EuroAtlantic Intgn and Democr   (Hungary)

^b NONE

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[No Author keywords available]

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EID: 0040669947     PISSN: 09670106     EISSN: None     Source Type: Journal    
DOI: 10.1177/0967010602033002003     Document Type: Article

References (55)

1. Swedish National Defence Research Establishment (FOA) briefing book on chemical weapons, June 2001; available at http://www.opcw.nl/chemhaz/toxins.htm.
2. Graham S. Pearson, 'The Prohibition of Chemical and Biological Weapons', in Malcolm R. Dando, Graham S. Pearson & Tibor Toth, eds, Verification of the Biological and Toxin Weapons Convention (Dordrecht: Kluwer Academic, 1998), pp. 1-5.
3. At the fourth review conference of the BTWC in 1996, the Final Declaration reaffirmed that Article 1 of the Convention included 'all microbial and other biological agents or toxins, naturally or artificially created or altered, as well as their components, whatever their origin or method of production of types and in quantities that have no justification for prophylactic, protective or other peaceful purpose'. A comparable general-purpose criterion for the CWC is embodied in the definition of chemical weapons in Article 2 as 'toxic chemicals and their precursors, except where intended for purposes not prohibited under this Convention, as long as the types and quantities are consistent with such purposes'.
4. One the most serious limiting factors in state deployment of BWs would be the extensive problem of infecting one's own troops; Ron Kupperman, 'Countering High Technology Terrorism', Scandinavian Journal of Development Alternatives and Area Studies, vol. 4, no. 3, September 1984, pp. 73-83.
5. Ricin was used in Virginia in 1980 to assassinate CIA agent Boris Korczak; also, in addition to the assassination of Bulgarian Georgi Markov, there was an unsuccessful assassination attempt against Bulgarian defector Vladimir Kostov in Paris by the Bulgarian Intelligence Services; Joseph D. Douglass & Neil C. Livingstone, America the Vulnerable: The Threat of Chemical and Biological Warfare (Lanham, MD: Lexington, 1987).
6. A recent example of this is the reported use of various BW agents by Aum Shinrikyo. Although Aum Shinrikyo (now renamed as 'Aleph') and Aum leader Fumihiro Joyu admitted in their website that they had disseminated a 'harmless' strain of anthrax in 1993 from their building in Tokyo (Masaaki Sugishima, personal communication), there is no evidence to support the reports that they developed and/or attempted to deploy Q fever or tularaemia; Milton Leitenberg, 'Aum SinriKyo's Efforts to Produce Biological Weapons: A Case Study in the Serial Propagation of Misinformation', Terrorism and Political Violence, vol. 11, no. 4, Winter1999, pp. 149-158.
7. William Kucewicz, 'Beyond "Yellow Rain": The Threat of Soviet Genetic Engineering', Wall Street Journal, April-May 1984, pp. 1-18.
8. John van Courtland Moon, 'Introduction', in Erhard Geissler & John van Courtland Moon, eds, Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945, SIPRI Chemical & Biological Warfare Studies No. 18 (Oxford: Oxford University Press, 1999) pp. 5-7. Offensive and defensive research programmes into botulinum toxin were continued by both the Allies and Germany throughout the war.
9. With regard to the USSR, it was not until 1984, some five years after the anthrax leak from Sverdlovsk, that US intelligence finally confirmed what many had suspected -there were 'at least seven biological warfare centres in the USSR' and these 'have the highest security and are under the strictest military control'; Milton Leitenberg, 'The Biological Weapons Program of the Former Soviet Union', Biologicals, vol. 21, no. 3, September 1993, pp. 187-191. In the USA, Fort Detrick was by 1960 a major player in the BW programme. The USA also carried out vulnerability assessments by analysing dispersal through the release of non-lethal biological agents, such as Serratia marcescens and Bacillus globigii; John Mobley, 'Biological Warfare in the Twentieth Century: Lessons from the Past, Challenges for the Future', Military Medicine, vol. 160, no. 11, November 1995, pp. 547-553.
10. With regard to the USSR, it was not until 1984, some five years after the anthrax leak from Sverdlovsk, that US intelligence finally confirmed what many had suspected - there were 'at least seven biological warfare centres in the USSR' and these 'have the highest security and are under the strictest military control'; Milton Leitenberg, 'The Biological Weapons Program of the Former Soviet Union', Biologicals, vol. 21, no. 3, September 1993, pp. 187-191. In the USA, Fort Detrick was by 1960 a major player in the BW programme. The USA also carried out vulnerability assessments by analysing dispersal through the release of non-lethal biological agents, such as Serratia marcescens and Bacillus globigii; John Mobley, 'Biological Warfare in the Twentieth Century: Lessons from the Past, Challenges for the Future', Military Medicine, vol. 160, no. 11, November 1995, pp. 547-553.
11. Two human genome sequences were published at the same time. For the Celera sequence, see Science, vol. 291, no. 5507, 2001, pp. 1304-1351, and for the publicly funded sequence see Nature, vol. 409, no. 6817, February 2001, pp. 813-964.
12. Two human genome sequences were published at the same time. For the Celera sequence, see Science, vol. 291, no. 5507, 2001, pp. 1304-1351, and for the publicly funded sequence see Nature, vol. 409, no. 6817, February 2001, pp. 813-964.
13. Although many toxins are prohibited under the present BTWC, Graham Pearson and colleagues consider these four toxins to have the appropriate characteristics for use as BWs; see 'The Threat of Deliberate Disease in the 21st Century', a 1998 report from the Henry L. Stimson Centre, available at http://www.brad.ac.uk/acad/sbtwc/other/ disease.htm. The US Army considers T-2 mycotoxins to be a greater threat than saxitoxin; see article on 'Biological Toxins', US Army Medical Field Manual; available at http://www.nbc-med.org/SiteContent/MedRef/OnlineRef/FieldManuals/medman/chap3. htm.
14. Although many toxins are prohibited under the present BTWC, Graham Pearson and colleagues consider these four toxins to have the appropriate characteristics for use as BWs; see 'The Threat of Deliberate Disease in the 21st Century', a 1998 report from the Henry L. Stimson Centre, available at http://www.brad.ac.uk/acad/sbtwc/other/ disease.htm. The US Army considers T-2 mycotoxins to be a greater threat than saxitoxin; see article on 'Biological Toxins', US Army Medical Field Manual; available at http://www.nbc-med.org/SiteContent/MedRef/OnlineRef/FieldManuals/medman/chap3. htm.
15. Ali Khan, Stephen Morse & Scott Lillibridge, 'Public-Health Preparedness for Biological Terrorism in the USA', Lancet, vol. 356, no. 9236, September 2000, pp.1179-1182. There is a difference between biological lists for preparedness (i.e. defence) vis à vis prohibition/control. Legally defined lists of biological agents (including various toxins) have been created under the US Select Agent List (Section 511, Antiterrorism and Effective Death Penalty Act, Public Law 104-132, Section 511) and the Australia Group List, available at http://www.state.gov/www/global/arms/factsheets/wmd/bw/auslist.html.
16. Streptolysin-O works by forming channels through cholesterol-rich areas. All toxins must interact with the plasma membrane in some form, either treating it as a final target (i.e. pore-forming) or in order to gain access to the cell interior; Clare Schmitt, Karen Meysich & Alison O'Brien, 'Bacterial Toxins: Friends or Foes?', Emerging Infectious Diseases, vol. 5, no. 2, March-April 1999, pp. 224-234.
17. Both these bacterial toxins target an essential secretory protein; Gianpietro Sciavo & Caesare Montecucco, 'Neurotoxins Affecting Neuroexocytosis', Toxicology Letters, vol. 80, no. 2, April 2000, pp. 717-766.
18. For the many examples of biomedical applications, see 'Clinical Use of Botulinum Toxins', National Institutes of Health Consensus Development Conference Statement, section 83, November 1990; available at http://text.nlm.nih.gov/nih/cdc/www/83txt.html.
19. Clostridial toxins target the multifunctional Rho family of proteins; Klaus Aktories, 'Microbial Toxins and the Glycosylation of Rho Family GTPases', Current Opinion on Structural Biology, vol. 10, no. 5, April 2000, pp. 528-535.
20. Abrin A and Ricin D isofroms have LD50s of 10ug/kg and 248 pg/kg, respectively (intraperitoneal route, mice). For a list of LD50s of BW-relevant toxins, see 'Registry of Toxic Effects of Chemical Substances', available at http://ftp.cdc.gov/niosh/rtecs.html.
21. Abrin A and Ricin D isofroms have LD50s of 10ug/kg and 248 pg/kg, respectively (intraperitoneal route, mice). For a list of LD50s of BW-relevant toxins, see 'Registry of Toxic Effects of Chemical Substances', available at http://ftp.cdc.gov/niosh/rtecs.html.
22. There are a number of factors that relate to the stability and persistence of toxins, including the intrinsic biological nature of the toxin (stabile tertiary and quaternary structure), formulation (freeze-drying, specialized stabilizing fluid, liquid, etc.), delivery method and environmental parameters. Some toxins, such as botulinum, are not stable in chlorinated water, whereas ricin, T-2 mycotoxins and SEB are very stable; see Department of Defense, 'Militarily Critical Technologies', available at http:// www.dtic.mil/mctl/mctlp2.html.
23. Ricin has been used as a toxin case study in which details of the worldwide industry are described; see Jonathan Tucker, 'Dilemmas of a Dual-Use Technology: Toxins in Medicine and Warfare', Politics and the Life Sciences, vol. 13, no. 1, February 1994, pp. 51-62
24. Tetrodotoxin is similar in structure and action to saxitoxin, another marine toxin produced by blue-green algae. Both inhibit the activity of the voltage-sensitive sodium channel of the nervous system; further details available at http://fugu.hgmp.mrc.ac.uk.
25. There are a variety of specific peptide conotoxins.
26. The molecular toxicology of marine toxins and the epidemiology, diagnosis and management of paralytic shellfish (saxitoxin), tetrodotoxin, neurotoxic, diarrhoeic and amensic shellfish poisoning are covered in depth in Daniel Baden, Lara Fleming & Judy Bean, 'Marine Toxins', in F. A. de Wolff, ed., Intoxications of the Nervous System, Part II: Natural Toxins and Drugs, Handbook of Clinical Neurology vol. 65, no. 21 (Amsterdam: Elsevier, 1995) pp. 141-175.
27. A history of scientific research into maitotoxins is available at http://www.chbr.noaa.gov/ CoastalResearch/CTXMTXinfo.htm.
28. John Walter & Demitri Panaccione, 'Host-Selective Toxins and Disease Specificity: Perspectives and Progress', Annual Review of Phytopathology, vol. 31, no. 4, May 1993, pp. 275-303. The major classes of fungal toxins that are toxic to humans are cercosporin, HC-toxins, Ptr toxin, T-toxin, Victorin and Fuscicoccin; references and descriptions available at http://www.ca.uky.edu/agcollege/plantphysiology/ppa660/ppa660L27.htm.
29. Mycotoxins can lead to infertility and enhance the pathogenicity of tuberculosis.
30. In small doses, aflotoxins are cumulative carcinogens and eventually lead to carcinoma of the liver.
31. There are at least ten different toxins produced by this snake alone.
32. The snakes that produce these toxins target a wide variety of proteins involved in blood-clotting; Kathyrn Senior, 'Taking the Bite Out of Snake Venoms', Lancet, vol. 353, no. 9168, June 1999, pp. 1946-1947.
33. Venom from Crotalus durissus terrificus and Bothrops jararaca have been found to be potent in vitro inhibitors in certain tumour cell lines.
34. David Franz, 'International Biological Warfare Threat in CONUS', Statement before the Joint Committee on Judiciary and Intelligence, US Senate, 4 March 1998, p. 5.
35. Some toxins are more toxic when inhaled (e.g. ricin, saxitoxin and T2 mycotoxins).
36. The difficulties associated with this approach effectively limit it to state-sponsored BW programmes; Seth Carus, 'Biological Warfare Threat in Perspective', Critical Reviews in Microbiology, vol. 24, no. 3, September 1998, pp. 149-155.
37. Novel functional toxins have been generated by transferring active sites onto new structural contexts to yield well-defined artificial proteins active against specific biological targets; Claudio Vita et al., 'Novel Miniproteins Engineered by the Transfer of Active Sites to Small Natural Scaffolds', Biopolymers, vol. 47, no. 1, February 1998, pp. 93-100.
38. The development of chimeric toxins has its origins in the attempt by the biomedical community to create 'magic bullets' that would target cancer cells; Carol Ezzell, 'Magic Bullets Fly Again', Scientific American, vol. 285, no. 4, October 2001, pp. 34-41.
39. These polymers can act as 'carrier' compounds for toxins that could not otherwise gain access to cells; Patrick Stayton, 'Molecular Engineering of Proteins and Polymers for Targeting and Intracellular Delivery of Therapeutics', Journal of Control Release, vol. 65, no. 1-2, March 2000, pp. 203-220.
40. For example, a fusion of the human IL-2 to the plant toxin ricin; Jonathan Cook, 'Biologically Active IL-2 Ricin A Chain Fusion Proteins May Require Intracellular Proteolytic Cleavage to Exhibit a Cytotoxic Effect', Bioconjugate Chemistry, vol. 4, no. 6, November 1993, pp. 440-447.
41. For instance, in the treatment of cancer either directly or through the use of aflotoxin to screen for chemicals that effectively kill this fungus, thus leading to a reduction in people exposed to aflotoxins.
42. The escalation is evident from the growth in size of the anti-WMD line item within the federal US anti-terrorism budget. In 1998, the USA spent $71.8 million on such programmes. By 2001, the budget had reached a projected $142.5 million. For full details, see 'Federal Funding to Combat Terrorism, Including Defense Against Weapons of Mass Destruction, FY 1998-2001'; available at http://cns.miis.edu/research/cbw/ terfund.htm.
43. Corina Dennis, 'The Bugs of War', Nature, vol. 411, no. 726, May 2001, pp. 232-235.
44. W. Seth Carus, 'Unlawful Acquisition and Use of Biological Agents', in Joshua Lederberg, ed., Biological Weapons: Limiting the Threat (Cambridge, MA: MIT Press, 1999), pp. 211-231.
45. W. Seth Carus, Bioterrorism and Biocrimes: The Illicit Use of Biological Agents in the 20th Century, rev. edn (Washington, DC: Center for Counterproliferation Research, July 1999), p. 13.
46. The use of such weapons in the future by 'lone misanthropes, hate groups, cults, or even minor states' would lead humanity down a particularly undesirable route; biomedical science, the saviour and new 'religion' of modernity, would achieve pariah status. See Matthew Meselson, 'Averting the Hostile Exploitation of Biotechnology', CBW Conventions Bulletin, vol. 3, no. 48, June 2000, pp. 16-19.
47. Initiatives by biopharmaceutical firms to 'speed up' the transfer of new chemical entities into the clinic have been enabled by quantum leaps in the availability of raw data on structure (via X-ray crystallography, nuclear magnetic resonance [NMR], circular dichroism spectroscopy [CD], etc.) and data-handling by computational biology, with design focus through medicinal chemistry. These enabling technologies have only been with the R&D community since the mid-1990s; Roger Ulrich & Stephen Friend, 'Toxicogenomics and Drug Discovery: Will New Technologies Help Us Produce Better Drugs?', Nature Reviews Drug Discovery, vol. 1, no. 1, June 2002, pp. 84-88.
48. For example, PC-based software has been utilized to create an in silico chimeric, stabile, potent neurotoxin by transferring the active element of the curare-mimetic neurotoxin a to the scorpion scaffold charybdotoxin; Claudio Vita, 'Engineering Novel Proteins by Transfer of Active Sites to Natural Scaffolds', Current Opinion in Biotechnology, vol. 8, no. 44, August 1997, pp. 429-434.
49. One of the most compelling conclusions from Malcolm Dando's review of the benefits and threats of developments in biotechnology and genetic engineering is the sheer diversity and complexity of the subject material and the inherent difficulties of predictive threat assessments in the area; see SIPRI Yearbook 1999: Armaments, Disarmament and International Security (Oxford: Oxford University Press, 1999), Appendix 13A, pp. 596-611.
50. Dry-powder formulations are considered easier to disperse. For live pathogens, however, this formulation is particularly sensitive to degradation. Many toxins -Staphylococcal Enterotoxin B, for example - can be very stable after freeze-drying. See 'Observations on the Threat of Chemical and Biological Terrorism', GAO/Y-NSAID-00-50 Testimony, US General Audit Office, October 1999.
51. The use of BWs by nation-states does not make rational sense, especially if BWs are deployed against an enemy with nuclear assets. The deterrent threat of retaliation only becomes irrelevant if one considers the non-rational, doomsday-type actor or fundamentalist/nihilistic terrorist groups; Sebestyèn Gorka, '2000AD: Boomtime in the Doom Market?', Jane's Intelligence Review, vol. 12, no. 1, January 2000, pp. 50-54
52. Hillel Cohen, Robert Gould & Victor Sidel, 'Bioterrorism Initiatives: Public Health in Reverse?', American Journal of Public Health, vol. 89, no. 11, November 1999, pp. 1629-1631.
53. According to the Centre for Non-Proliferation Studies, of the $2,000 million in funding for federal anti-terrorism activities (FY 2000), nearly three-quarters went on bioterrorism (see John Parachini, 'Combating Terrorism: Assessing Threats, Risk Management, and Establishing Priorities', available at http://cns.miis.edu/research/terror.htm). However, there has been no coherent policy guiding how the money has been spent on R&D projects; perhaps even worse, some have argued that the R&D supported is of poor scientific merit. Referring to the 'unconventional pathogen countermeasures program', an editorial in Science proclaimed 'Too Radical for NIH? Try DARPA';
54. According to the Centre for Non-Proliferation Studies, of the $2,000 million in funding for federal anti-terrorism activities (FY 2000), nearly three-quarters went on bioterrorism (see John Parachini, 'Combating Terrorism: Assessing Threats, Risk Management, and Establishing Priorities', available at http://cns.miis.edu/research/terror.htm). However, there has been no coherent policy guiding how the money has been spent on R&D projects; perhaps even worse, some have argued that the R&D supported is of poor scientific merit. Referring to the 'unconventional pathogen countermeasures program', an editorial in Science proclaimed 'Too Radical for NIH? Try DARPA';
55. see Science, vol. 275, no. 5301, 1997, pp. 744-746.