Biological and chemical weapons have been used for waging war since the dawn of recorded history. Recently, these agents have been used on civilian populations by terrorist groups. Terrorist attacks using biological or chemical weapons have far-reaching implications, as they cause widespread fear, anxiety, and panic among the public. Biological agents have particular appeal for use in terrorist attacks because they are reasonably easy to acquire, are inexpensive to produce, and have the potential to affect large populations of people. Biological agents are selected based on their toxicity, ease of production and stability, and ability to be dispersed in respirable aerosols. The most common biological agents that have been weaponized include anthrax, plague, tularemia, botulism toxin, and smallpox. Chemical agents are more expensive and more difficult to manufacture and deploy and are therefore more likely to be used in conventional warfare. Mustard gas and nerve agents are the favored chemical agents of mass destruction.
Global proliferation of weapons of mass destruction. Hearings before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, US Senate, 104th Cong, 1st sess, part 1, October 31, 1995.
2.
US Congress, Office of Technology Assessment. Proliferation of weapons of mass destruction: assessing the risks. Washington, DC: Office of Technology Assessment , 1993. Document OTA ISC 559.
3.
US Congress, Office of Technology Assessment. Technologies underlying weapons of mass destruction. Washington, DC: Office of Technology Assessment, 1993. Document OTA ISC 115.
4.
Fee E., Brown TMPreemptive biopreparedness: can we learn anything from history? Am J Public Health2001;91:721-726.
5.
Khan AS, Morse S., Lillibridge S.Public-health preparedness for biological terrorism in the USA. Lancet2000;356: 1179-1182.
6.
Haines JD, Pitts K., Crutcher JMMedical response to bioterrorism: are we prepared? J Okla State Med Assoc2000;93:187-196.
7.
Henderson DAThe looming threat of bioterrorism. Science1999;283:1279-1282.
8.
Henderson DAWeapons for the future. Lancet1999;354(suppl):SIV64
9.
Wetter DC, Daniell WE, Treser CDHospital preparedness for victims of chemical or biological terrorism . Am J Public Health2001;91:710-716.
10.
Woodall J.Tokyo subway gas attack. Lancet1997 ;350:296.
11.
Derbes VJMussis and the great plague of 1348: a forgotten episode of bacteriological war. JAMA1966;196:5962.
12.
Christopher GW, Cieslak TJ, Palvin JA, et al. Biological warfare: a historical perspective . JAMA1997;278:412.
13.
Stearn EW, Stearn AEThe effect of smallpox on the density of the Amerindian. Boston, MA: Bruce Humphries, 1945 .
14.
Harris S.Japanese biological warfare research on humans: a case study of microbiology and ethics. Ann N Y Acad Sci1992;666:21-52.
Zilinskas RAIraq's biological weapons: the past as future ? JAMA1997;278:418-424.
17.
Orient JMChemical and biological warfare: should defenses be researched and deployed ? JAMA1989;262:644-648.
18.
US Congress, Office of Technology Assessment. Proliferation of weapons of mass destruction: assessing the risks . Washington, DC: Office of Technology Assessment, 1993. Document OTA ISC559.
19.
Torok TJ, Tauxe RV, Wise RPA large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA1997;278:389-395.
20.
Centers for Disease Control Prevention.Biological and chemical terrorism: strategic plan for preparedness and response-recommendations of the CDC strategic planning workgroup. Morb Mort Wkly Rep2000;49:1-14.
21.
Arita I.Virological evidence for the success of the smallpox eradication program . Nature1979;279:293-298.
22.
Alibek K., Aria I.The confirmation and maintenance of smallpox eradication. N Engl J Med1980;303:1263-1273.
23.
Ferrer F., Henderson DA, Arita I., et al. Smallpox and its eradication. Geneva: World Health Organization, 1988.
24.
Henderson DA , Inglesby TV, Bartlett JGSmallpox as a biological weapon: medical and public health management. JAMA1999;281:2127-2137.
25.
Ellner PDSmallpox: gone but not forgotten. Infection1998;26:263-269.
26.
Mopp SL, Knight JC, Massung RF, et al. PCR strategy for identification and differentiation of smallpox and other orthopoxviruses. J Clin Microbiol1995;33:2069-2076.
27.
Franz DR, Jahrling PB, Friedlander AMClinical recognition and management of patients exposed to biological warfare agents. JAMA1997;278:399-411.
28.
Lew DPBacillus anthracis (anthrax). In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious disease. Philadelphia: Churchill Livingstone, 2000:2215-2220.
29.
Swartz MNCurrent concepts: recognition and management of anthrax-an update . N Engl J Med2001;345: 1621-1626.
30.
Myenye KS, Siziya S., Peterson D.Factors associated with human anthrax outbreak in the Chikupo and Ngandu villages of Murewa district in Mashonaland East Province, Zimbabwe . Cent Afr J Med1996;42:312-315.
31.
Watson A., Keir D.Information on which to base assessments of risk from environments contaminated with anthrax spores. Epidemiol Infect1994 ;113:479-490.
32.
Taylor JP, Dimmitt DC, Ezzell JW, et al. Indigenous human cutaneous anthrax in Texas. South Med J1993;86:1-4.
33.
Brachman PSAnthrax. Ann N Y Acad Sci1970;174:577-582.
34.
Brachman PSInhalational anthrax. Ann N Y Acad Sci1980;363:830-89.
Albrink WSPathogenesis of inhalation anthrax. Bacteriol Rev1991;25:268-273.
37.
Penn CC, Klotz SAAnthrax pneumonia. Sem Respir Infect1997;12:28-30.
38.
Lincoln RE, Hodges DR, Klein F.Role of the lymphatics in the pathogenesis of anthrax. J Infect Dis1965;115:481-494.
39.
Vessal K., Yeganehdoust J., Dutz W., et al. Radiologic changes in inhalation anthrax. Clin Radiol1975;26:471-474.
40.
Amramova FA , Grinberg LM, Yampolskaya O., et al. Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak in 1979. Proc Natl Acad Sci USA1993;90:2291-2294.
41.
Inglesby TV , Henderson DA, Bartlett JGAnthrax as a biological weapon: medical and public health management. JAMA1999;281:1735-1745.
42.
Harrison LH , Ezzell JW, Abshire TGEvaluation of serological tests for the diagnosis of anthrax after an outbreak of cutaneous anthrax in Paraguay. J Infect Dis1989;39: 578-581.
43.
Turnbull PC , Doganay M., Lindeque PMSerology and anthrax in humans, livestock, and Etosha National Park wildlife. Epidemiol Infect1992;108:299-313.
44.
Black JD, Dolly JOInteraction of 125I-labeled botulism neurotoxins with nerve terminals: II: autoradiologic evidence of its uptake into motor neurons by receptor mediated endocytosis. J Cell Biol1986;103:535-544.
45.
Herrero BA, Ecklung AE, Street CS, et al. Experimental botulism in monkeys: a clinical pathological study . Exp Mol Pathol1967;6:84-95.
46.
Scott AB, Suzuki D.Systemic toxicity of botulinum toxin by intramuscular injection in the monkey . Movement Disord1988;3:333-335.
47.
Shapiro RL, Hatheway C., Swerdlow DLBotulism in the United States: a clinical and epidemiologic review . Ann Intern Med1998;129:221-228.
48.
United Nations Security Council.Tenth report of the executive chairman of the special commission established by the secretary-general pursuant to paragraph 9(b)(1) of Security Council Resolution 687 (1991), and paragraph 3 of Resolution 699 (1991) on the Activities of the Special Commission. S/1995/1038. New York: United Nations Security Council, 1995.
49.
Gordesman AHWeapons of mass destruction in the Gulf and greater Middle East: force trends, strategy, tactics and damage effects. 18-52 . Washington, DC: Center for Strategic and International Studies , 1998.
50.
Burrows WD, Renner SEBiological warfare agents as threats to potable water. Environ Health Perspect1999;107:975-984.
51.
Hughes JM, Blumenthal JR, Merson MH, et al. Clinical features of types A and B food-borne botulism. Ann Intern Med1981;95:442-445.
52.
Edell TA, Sullivan CP Jr, Osborn KM, et al. Wound botulism associated with a positive tensilon test. West J Med1983;139:218-219.
53.
Notermans S., Nagel J.Assays for botulism and tetanus toxins. In: Simpson LL, ed. Botulism neurotoxin and tetanus toxin. San Diego, CA: Academic Press, 1989 :319-331.
54.
Cherington M.Clinical spectrum of botulism. Muscle Nerve1998;21:701-710.
55.
Arnon S., Schecter R., Inglesby TVBotulism toxin as a biological weapon: medical and public health management . JAMA2001;285:1059-1070.
56.
Black RE, Gunn RAHypersensitivity reactions associated with botulinal antitoxin. Am J Med1980;69:567-570.
57.
Tacket CO, Shandera WX, Mann JM, et al. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med1984 ;76:794-798.
58.
Schulze J., Toepfer M., Schroff KC, et al. Clindamycin and nicotinic neuromuscular transmission. Lancet1999;354: 1792-1793.
59.
Hopla CEThe ecology of tularemia. Adv Vet Sci Comp Med1974;18:25-53.
60.
Evans ME, Gregory DW, Schaffner W., et al. Tularemia: a 30-year experience with 88 cases. Medicine1985;64:251-269.
61.
Christenson B.An outbreak of tularemia in the northern part of central Sweden. Scand J Infect Dis1984 ;16:285-290.
62.
Warring WB, Ruffin JSA tick-borne epidemic of tularemia. N Engl J Med1946;234:137-140.
63.
Markowitz LE , Hynes NA, de la Cruz CP, et al. Tick-borne tularemia: an outbreak of lymphadenopathy in children. JAMA1985;254:2922-2925.
64.
Young LS, Bickness DS, Archer BG, et al. Tularemia epidemia: Vermont, 1968: forty-seven cases linked to contact with muskrats. N Engl J Med1969 ;280:1253-1260.
65.
Mignani E., Palmieri F., Fontana M., et al. Italian epidemic of waterborne tularaemia. Lancet1988;2:1423.
66.
Teutsch SM, Martone WJ, Brink EW, et al. Pneumonic tularemia on Martha's Vineyard. N Engl J Med1979;301:826-828.
67.
Syrjala H., Kujala P., Myllyla V., et al. Airborne transmission of tularemia in farmers. Scand J Infect Dis1985;17:371-375.
68.
World Health Organization.Health aspects of chemical and biological weapons. Geneva : World Health Organization, 1970 .
69.
Cox SK, Everett EDTularemia, an analysis of 25 cases. Missouri Med1981;78:70-74.
70.
Ohara Y., Sato T., Fujita H., et al. Clinical manifestations of tularemia in Japan-analysis of 1,355 cases observed between 1924 and 1987. Infection1991;19:14-17.
71.
Avery FW, Barnett TBPulmonary tularemia: a report of five cases and consideration of pathogenesis and terminology. Am Rev Respir Dis1967;95:584-591.
72.
Syrjala H., Koskela P., Ripatti T., et al. Agglutination and ELISA methods in the diagnosis of tularemia in different clinical forms and severities of the disease. J Infect Dis1986;153:142-145.
73.
Bevanger L. , Maeland JA, Naess AIAgglutinins and antibodies to Francisella tularensis outer membrane antigens in the early diagnosis of disease during an outbreak of tularemia. J Clin Microbiol1988;26:433-437.
74.
Grunow R., Splettstoesser W., McDonald S., et al. Detection of Francisella tularensis in biological specimens using a capture enzyme-linked immunosorbent assay, an immunochromatographic handheld assay, and a PCR. Clin Diagn Lab Immunol2000;7:86-90.
75.
Higgins JA, Hubalek Z., Halouzka J., et al. Detection of Francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction. Am J Trop Med Hyg2000;62:310-318.
76.
Perry RD, Fetherston JDYersinia pestis-etiologic agent of plague. Clin Microbiol Rev1997;10:35-66.
77.
Centers for Disease Control and Prevention.Fatal human plague. Morb Mort Wkly Rep1997;278:380-382.
78.
World Health Organization.Health aspects of chemical and biological weapons. Geneva: World Health Organization, 1970.
79.
Butler T.Yersina species, including plague. In: Mandell GL, Bennet JE, Dolin R, eds. Principles and practice of infectious diseases. Philadelphia: Churchill Livingstone, 2000:2406-2414.
80.
Inglesby TV , Dennis DT, Henderson DA, et al. Plague as a biological weapon: medical and public health management. JAMA2000;283:2281-2290.
81.
Wilmoth BA, Chu MC, Quan TJIdentification of Yersinia pestis by BBL crystal enteric/nonfermenter identification system. J Clin Microbiol1996;34:2829-2830.
82.
McCormick JB , Webb PA, Krebs JW, et al. A prospective study of the epidemiology and ecology of lassa fever. J Infect Dis1987 ;155:437-444.
83.
Fulhorst CF , Bowen MD, Ksiazek TG, et al. Isolation and characterization of Whitewater Arroyo virus, a novel NorthAmerican arenavirus. Virology1996;224:114-120.
84.
Maiztegui J. , Feuillade M., Briggiler A.Progressive extension of the endemic area and changing incidence of Argentine hemorrhagic fever . Med Microbiol Immunol1986;175: 149-152.
85.
Johnson KM, Wiebenga NH, Mackenzie RBVirus isolations from human cases of hemorrhagic fever in Bolivia . Proc Soc Exp Biol Med1965;155:113-118.
86.
Stinebaugh BJ, Schloeder FX, Johnson KM, et al. Bolivian hemorrhagic fever: a report of four cases. Am J Med1966 ;40:217-230.
87.
Salas R., de Manzione N., Tesh RB, et al. Venezuelan haemorrhagic fever. Lancet1991;338:1033-1036.
88.
Lisieux T., Coimbra M., Nassar ES, et al. New arenavirus isolated in Brazil. Lancet1994;343:391-392.
89.
Easterday BCRift valley fever. Adv Vet Sci1965;10:65-127.
90.
Enria DA, Briggiler AM, Fernandez NJ, et al. Importance of dose of neutralising antibodies in treatment of Argentine haemorrhagic fever with immune plasma. Lancet1984;2:255-256.
91.
McCormick JB , King IJ, Webb PA, et al. Lassa fever: effective therapy with ribavirin. N Engl J Med1986;314:20-26.
92.
Huggins JWProspects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug. Rev Infect Dis1989;11(suppl 4):S750-S761.
93.
Enria DA, Maiztegui JIAntiviral treatment of Argentine hemorrhagic fever. Antiviral Res1994;23:23-31.
94.
Haley RW, Kurt TISelf-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional epidemiologic study. JAMA1997;277:231-237.
95.
Landrigan PJIllness in Gulf War veterans. JAMA1997;277:259-261.
96.
Haley RW, Hom J., Roland PS, et al. Evaluation of neurologic function in Gulf War veterans. JAMA1997;277:223-230.
97.
Haley RW, Kurt TL, Hom J.Is there a Gulf War syndrome? Searching for syndromes by factor analysis of symptoms. JAMA1997;277:215-222.
98.
Blewett WKTactical weapons: is mustard still king? NBC Defense Technol Int1986;1:64-66.
99.
Medema J.Mustard gas: the science of H. NBC Defense Technol Int1986;1:66-71.
100.
Momeni A., Enshaeih S., Meghdadi M., et al. Skin manifestations of mustard gas: clinical study of 535 patients exposed to mustard gas. Arch Dermatol1992 ;128:775-780.
101.
Emad A., Rezaian GRThe diversity of the effects of sulphur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure. Chest1997;112:734-738.
102.
Dunn MA, Sidell FRProgress in medical defense against nerve agents. JAMA1989;262:649-652.
