Biological warfare threat the understanding of its history and science for deterrence, detection, containment, treatment and mitigation

The list of critical agents

A Critical Agents List of biological agents published by the Centers for Disease Control and Prevention (CDC)⁷ highlights the most likely ones that might be used in the event of a bioterrorist attack. These agents are classified in three categories: Category A agents includes high- priority agents (such as Bacillus anthracis-anthrax , Variola major-smallpox, Yersinia pestis- plague, and Francisella tularensis- tularemia). These most likely cause mass casualties when dispersed as as small, stabilized micro particle aerosols. They can be easily transmitted from person to person or disseminated further, causing high mortality, public panic and require special action for public-health preparedness. Category B includes the second highest priority agents (e.g. Coxiella burnetti- Q-fever, Brucella spp- brucellosis, Burkolderia mallei- glanders etc. and pathogens such as Salmonella spp) that can be employed to contaminate food or water sources. They are moderately easy to disperse where moderate morbidity and low mortality may be caused. Category C agents (such as nipah virus, yellow fever, etc.) are emerging infectious diseases or agents with characteristics that could be exploited for deliberate dispersion due to their availability and ease of production and dissemination.

In general there are many potential human biological pathogens. Agents including bacteria, viruses and toxins can be used as biological weapons. In order for an agent to be used as a biological weapon it must be highly lethal and easily produced in large quantities or it must be communicable from person to person and have no treatment or vaccine⁸.

The history of biological weapons⁹

Although the history of biological warfare is difficult to access due to the incidence of naturally occurring endemic or epidemic diseases during hostilities, the use of allegations of biological attacks for propaganda purposes etc., a review of this history indicates that the use of biological weapons has persisted throughout history and is likely to continue in the future.

One of the earliest documented cases of an intentional use of biological pathogens to kill or incapacitate one’s enemies occurred at the Crimean port city of Kaffa (Ukraine) in 1346. Besieging Tatar armies were stricken with bubonic plague and decided to catapult the cadavers of their deceased into the city to initiate a plague endemic. Genovese defenders in the city subsequently contracted plague and fled to Italy, carrying the disease to Europe. Ships carrying plague-infected refugees sailed to many Mediterranean ports. As a result, in the middle of the fourteenth century, plague (the Black Death) wandered all over Asia, the Middle East, North Africa and Europe for seven years and killed twenty to fifty percent of the population wherever it passed.

In the 18^th century smallpox was used as a biological weapon against Native Americans. During the French and Indian War (1754-1767), Sir Jeffrey Amherst, commander of British forces in North America took advantage of an outbreak of smallpox to execute his plan to deliberately use smallpox to reduce Native Americans tribes hostile to the British.

Nonetheless, in the siege of Kaffa as well as in the case of the French and Indian War it is rather difficult to distinguish between the results of the use of a biological weapon and the results of naturally occurring epidemics as caused indirectly by fighting, poor sanitary condition, etc.

As a result of the development of modern microbiology during the 19^th century powerful countries around the world initiated ambitious biological warfare programs. Germany was one of those countries that had developed operations of this kind during the World War I.

After the war especially due to the fear of chemical warfare there was the first attempt at limiting biological warfare with the Geneva Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases, and of Bacteriological Methods of Warfare. Although the treaty prohibited the use of biological weapons, it did not provide a program for inspection and it did not prohibit the basic research, production or possession of biological weapons¹⁰.

During the World War II U.S., Japan, Germany, U.S.S.R. and Great Britain were secretly developing anthrax and other bioweapons. Although Hitler had issued orders prohibiting biological weapons development in Germany, German scientists had used prisoners in Nazi concentration camps to experiment on pathogenesis and to develop vaccines. However the only known offensive use of biological weapons by Germany was the pollution of a large reservoir in Bohemia with sewage in May 1945. Meanwhile, the allies had also developed biological weapons. Bomb experiments of weaponized spores of B. anthracis were conducted on Gruinard Island near Scotland.

Between 1937 and 1945 General Ishii of the Japanese Army used thousands of Chinese nationals to develop weaponized anthrax aerosols at a complex in Manchuria called Unit 731 (a biological warfare research facility). Almost three thousand deaths were documented after the war. There is evidence that the Japanese military killed thousands of Chinese prisoners by subjecting them to experimental doses of anthrax, cholera, plague and other pathogens.

An offensive biological program was also begun in the United States (in 1942) under the direction of the War Reserve Service, which included a research and development facility at Camp Detrick, testing sites in Mississippi and Utah, and a production facility in Terre Haute, Indiana. After the war the program continued with the help of Japanese scientists that were granted immunity from war crimes on the condition that they would provide information obtained during their program. The American program was expanded during the Korean War (1950-1953). In fact, the Soviet Union, China and North Korea accused the United States of using biological warfare against North Korea and China. By the late 1960s the US military had developed a biological arsenal that included bacterial pathogens, toxins and fungal pathogens.

During the cold war era there were repeated allegations of use of biological weapons both by the Soviet Union and the United States. Whether they were a part of these countries’ propaganda, or whether they actually occurred, a goal of the use of biological weapons was achieved, and that was to create fears among the nations of a potential disaster due to its use.

As a result, diplomatic efforts led to the 1972 Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction (BWC)¹¹. The treaty prohibits the development, possession, and stockpiling of pathogens or toxins in quantities that have no justification for prophylactic, protective or other peaceful purposes.

The offensive biological weapons program of the United States was terminated by President Nixon with the issuance of executive orders in 1969 and 1970. The US Army Medical Research Institute of Infectious Diseases (USAMRIID) was established and research efforts were exclusively directed to the development of defensive measures such as diagnostic tests, vaccines, and therapies for potential biological weapons threats. However it should be noted that the BWC did not stop nations such as the former Soviet Union or Iraq from using biological weapons.

In 1978, Bulgarian exile and BBC announcer Georgi Markov was assassinated by the Bulgarian secret service in London by placing a spring-loaded device inside an umbrella, which injected a tiny metal pellet into Markov’s leg. The pellet was through bored, filled with ricin (a toxin derived from the common castor bean), and sealed with wax intended to melt at body temperature. Similar weapons may have been used for at least six other assassinations.

In April 1979 an epidemic of anthrax occurred among people who lived or worked within a distance of 4 km from a Soviet military microbiology facility in Sverdlovsk, which was suspected of being a biological warfare research facility. As it was proved much later, the Soviets continued an offensive biological warfare program after the BWC of 1972 under an organization of their Ministry of Defense, Biopreparat. After the Persian Gulf War of 1991 and during the UN weapons inspections, it was discovered that Iraq had an offensive biological weapons program that included research on Bacillus anthracis and Botulinum toxins.

As far as terrorist attacks are concerned, in 1984, the Rajneeshee cult infected local salad bars in Dalles, Oregon, with Salmonella typhimurium in an attempt to influence the outcome of local elections. This incident resulted in 751 cases of enteritis and 45 hospitalizations. The most serious threat occurred in March 1995 (the Aum Shinrikyo sarin attack of the Tokyo subway system) when it was discovered that the Japanese cult had a basic biological weapons program.

Possible Bio-Terrorist Attacks

The most dangerous use of biological weapons could occur from large terrorist organizations either well funded or state-supported. Terrorists’ target may be the general civilian population or a symbolic building, an organization or a government. Their motivations are to promote nationalist objectives, to take revenge for a real or perceived injury, to protest government policies, etc. Monterey’s Database conclusions predict that future incidents of bioterrorism will involve hoaxes and relatively small-scale attacks, such as food contamination. However, it also indicates that the threat of mass-casualty bioterrorism has increased due to the diffusion of dual-use technologies relevant to the production of biological and toxin agents, and the potential availability of scientists and engineers formerly employed in sophisticated biological warfare programs (in the former Soviet Union, Eastern European countries, or South Africa).

Anthrax and smallpox

1. 
   Both are highly lethal
   
2. 
   Both are stable for transmission in aerosol and capable of large-scale production
   
3. 
   Both have been developed as agents in state programs
   
4. 
   Both potential use could result in a devastating psychological effect on the target population
   
5. 
   Initial recognition of both diseases is likely to be delayed.
   
6. 
   Availability of human vaccines for either disease is limited¹³.
   

According to Block, a professor of biological sciences and applied physics at Stanford, the agent of choice for most biological warfare programs is anthrax¹⁵. At the same time, Anthrax is considered to be one of the most serious diseases that appear as a result of a bioterrorist attack and could cause deaths in sufficient numbers to cripple a city or region. As we have already noted, anthrax has caused disease in animals and serious illness in humans throughout the world, for centuries. Naturally occurring anthrax is a disease acquired following contact with anthrax-infected animals or anthrax-contaminated animal products. The disease most commonly occurs in herbivores, which are infected by ingesting spores from the soil.

In humans, three types of anthrax infection occur: inhalational, cutaneous and gastrointestinal, among which cutaneous anthrax is the most common naturally occurring form.

Inhalational anthrax: It is caused by inhalation of spores in the dimension of 1-10μm that might be stabilized with silicon encapsulation. Although the naturally occurring spore colonies are substantially larger than the aforementioned range cited, albeit less penetrating through inhalation, when developed as a biological weapon, the organism is encapsulated in silicon, clay or materials envelopes that are sufficiently small to increase their penetrating effectiveness via the nasal canal and the pulmonary system¹⁶. The initial symptoms seem to be the symptoms of a common cold or flu. When untreated in time these symptoms can worsen and result in serious breathing and convulsion problems or even detrimental breathing. Usually, the disease fully manifests itself as a bacterial pneumonia after several days. The mortality rate, if left untreated, could be up to 100%. Cutaneous anthrax is the most common one with an estimated 2000 cases reported annually. Upon skin contact with the organism or its spores, an itchy papule that resembles an insect bite is induced within 1-2 days, which then leads to a painless ulcer 1-3 cm in diameter, black severely swollen with a characteristic dying area in the center which eventually crusts over. The mortality rate of cutaneous anthrax, if untreated is about 20%. Gastrointestinal anthrax is very rare and manifests itself by the ingestion of spores. Signs could be nausea, loss of appetite, vomiting and fever. The mortality rate is about 25% to 60% if untreated. Note that anthrax is not transmitted from patient-to-patient. Once there is a suspicion of an anthrax illness, there must be a notification of the local and state health department and epidemiologist. Then rapidly all the necessary tests by an appropriate laboratory can be made. Rapid diagnostic tests include an enzyme-linked immunosorbent assay for protective antigen and polymerase chain reaction, which unfortunately are available only at national reference laboratories. B anthracis can also be demonstrated by microbiologic studies. The most useful microbiologic test is the standard blood culture, which shows growth in 6 to 24 hours.

There is a US anthrax vaccine, which was licensed in 1970 and is produced by Bioport Corp, Lansing, Mich. It has to be given in a 6-dose series and has recently been mandated for all US military duty personnel. The vaccine is made from the cell-free filtrate of a nonencapsulated attenuated strain of B anthracis. Unfortunately vaccine supplies are limited and the US production capacity is modest and cannot satisfy civilian use¹⁷. As far as a therapy is concerned, early antibiotic administration is essential, because a delay even by hours could result to death.

In general, the recent events that followed the September 11^th terrorist attacks demonstrate the need for a responsible and organized program against anthrax, when used as a biological weapon¹⁸,¹⁹. When dealing with anthrax the important thing to know is that if the disease is rapidly diagnosed, a lot of lives can be saved. The focus is mainly on the medical community, which is expected to obtain all the necessary knowledge of the organism and then develop diagnostic techniques and prophylactic as well as therapeutic measures.
Smallpox²⁰,²¹

Smallpox is one of the most ancient diseases in human history. The first recorded epidemics were in China in 1122 B.C. The last case of endemic smallpox was reported in 1977 in Somalia. Today it is rated among the most dangerous of all potential biological weapons²². Compared to other agents such as anthrax, plague and botulinum toxin, obtaining smallpox is rather difficult. Yet if obtained and intentionally released, it could cause a major public health catastrophe due to its communicability. Smallpox is a viral disease. A single case could lead to 10 to 20 others. Smallpox is a part of the family of pox viri , Variola major. Smallpox virus causes systemic disease with rash. Fever and macular rash appear after an average incubation period of 12 days, with a progression to typical vesicular and pustular lesions over 1 to 2 weeks. Rash generally appears first on the face and spreads to the extremities. The patient remains febrile throughout the evolution of the rash and experiences considerable pain. Gradually, scabs form, which eventually separate, leaving pitted scars. Death usually occurs during the second week. Smallpox spreads easier during the cool, dry winter months but can be transmitted in any climate and, or in any part of the world. The only therapy against the disease is vaccination, which, before the exposure or within 2 to 3 days after the exposure, results in complete protection, and early detection.

Until recently, smallpox was not considered as a biological weapon threat mainly because of the availability of a vaccine and the high level of population immunity to the disease. Unfortunately, today only 20% of the population has any immunity from prior vaccination, because routine vaccinations in the United States ended in 1980 (this was the year the virus was officially eradicated)²³,²⁴. Therefore virtually all children born after 1980 and many adults are now susceptible again to smallpox²⁵. Although in 1980, the WHO’s international commission recommended that all institutions maintaining stocks of variola virus destroy or transfer these stocks to WHO centers, there are still two known laboratories that retain the virus. The Centers for Disease Control Prevention in Atlanta, and the Russian State Research Center of Virology and Biotechnology in Koltsovo. These laboratories are collaborating with WHO and have biosafety facilities. However there are speculations that unreported stocks of the virus could be held elsewhere. There are indications for example that other laboratories in Russia and perhaps Iraq maintain smallpox virus.

The measures against the use of smallpox as a biological weapon should begin with an effort by WHO to call on all countries to destroy immediately all their stocks. Besides these efforts it is now essential to realize the need for a large-scale manufacture of additional smallpox vaccine. Although smallpox vaccination is associated with some risk for adverse reactions such as postvaccinal encephalitis and progressive vaccinia, a stockpile of vaccinia vaccine (the licensed vaccine for smallpox) is needed to respond to the possible threat of a deliberate release of smallpox virus. The good news is that the Department of Defense program is now developing a cell-culture vaccine by using a cloned strain of vaccinia derived from another strain.

Other Bio-agents

The Era of Biotechnological Revolution

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.

Detections

As we have seen the threat of the use of biological weapons either in the field of warfare or in the field of terrorism continues to exist and increases due to the availability of new technology. Therefore there is a need for an organized international and national defense strategy to respond to any potential threat or harm.

A first step towards this plan is the creation of an international and national legal framework that will provide the nations with the necessary instruments to combat the biological warfare threat. In fact this strategy was initiated in 1972 when more than 100 countries signed the Biological Weapons and Toxin Convention (BWC). In Article I of the BCW the nations pledged that their governments would refrain from developing, producing, stockpiling, or acquiring any biological or toxin weapon. United States during the past decades has initiated an international effort to control the army policy of other nations, as far as acquiring biological weapons is concerned. At a national level, Congress has passed the Biological Weapons Act of 1989, the Anti-terrorism Act of 1996 and the Chemical and Biological Warfare Control Act of 1991. These statutes impose criminal penalties for the possession, manufacture, or use of biological weapons and give law enforcement agencies the power to issue all the necessary regulations. Also federal law enforcement agencies are vested with broad civil and investigative powers. Furthermore, Congress has directed the Centers for Disease Control and Prevention to establish a regulatory regime to monitor the location and transfer of hazardous biological agents and to insure that their use complies with the appropriate biosafety requirements. Besides the existence of a regulatory legal program to control the use of potential biological weapons, there is a need for an organized and well coordinated response to this challenging dilemma, which must involve responsible actions from public health officials, biosecurity personnel, scientific research personnel and the law enforcement.

A proposed number of defensive measures for consideration and discussion might include:

• 
  Surveillance systems that are able to identify an event rapidly
  
• 
  An organized response by health care providers ranging from prophylaxis to treatment
  
• 
  More supplies of the anthrax and smallpox vaccines²⁷
  
• 
  The development of new technologies to improve the speed and accuracy of methods for detecting and diagnosing biological agents
  
• 
  The organization of several response teams either civilian or military
  

Especially in combating biological terrorism the most important role is played by the medical and health communities. In general a well-prepared response to this problem should include education of all medical personnel and special training. These communities will not only have to deal with an immediate response to a potential attack in order to save lives, but they also will be the first to deal with the psychological reactions of their patients and of the general public. For the latter it should be noted that there is a need for contingency plans to deal with public hysteria. Policy makers and law enforcements, scientists and the media must develop an organized communication plan to inform the public about the potential risks and diminish the rumors. Finally, for the preparedness it is essential to have a program of control, monitoring and reporting systems. Scientists are currently working on the development of biosensors containing specific antibodies or enzymes to detect respiratory pathogens likely to be dispersed through sprays and air-cooling systems.
Conclusion

History has taught us that biological agents have been used in warfare for centuries. Today besides the threat of their use in warfare there is a greater fear that they could be used as weapons by terrorists’ organizations in civilian zones and urban centers. Due to their properties they seem to be more attractive than any other weapon and at the same time their use could be catastrophic for any target group.

Civilian populations could be in danger; thence, a well coordinated and organized international response is absolutely necessary. At the same token, every nation should develop defensive and deterring programs for the protection of their civilians mainly focused on public awareness and preparedness.

As our enemies multiply and yet become less well defined we should expect the use of biological weapons against us because they seem to be the “convenient” tools in the hands of people who desire to create chaos and fear in the public. As Kraemer notes: “On a positive note (and this is the best I can come up for a final positive note), unlike those who survived a nuclear holocaust, the survivors of biological warfare would inherit a beautiful world with human infrastructure largely intact.”

References

Christopher, G.W; Cieslak, J.T.; Pavlin,J.A.,; Eitzen E.M., (1997). Biological Warfare: a historical perspective. JAMA. 1997; 278:412-417

DaSilva, E.J. (1999). Biological warfare, bioterrorism, biodefense and the biological and toxin weapons convention, EJB, 1999 December 15, Vol.2 No.3

Harrison’s Principles of Internal Medicine, Part 7: Infectious Diseases

Holloway, H.C.; Norwood, A.E.; Fullerton, C.S.; Engel, C.C.; Ursano, R.J. (1997). The Threat of Biological Weapons, JAMA 1997; 278:425-427

Henderson, D.A., (1999). Smallpox: Clinical and Epidemiologic Features, Emerging Infectious Diseases, July-August 1999, vol.5, no.4

Inglesby, T.V.; Henderson, D.A.; Bartlett, J.G. et al. (1999). Anthrax as a Biological Weapon, JAMA 1999; 281:1735-45

Khan, A.S.; Morse, S.; Lillibridge, S. (2000). Public-health preparedness for biological terrorism in the U.S.A., The Lancet, Sept 30, 2000 v356 i9236 p1179

Kortepeter, M.G.; Cieslak, T.J.; Eitzen, E. (2001). Bioterrorism, Journal of Environmental Health, Jan 2001 v63 i6 p21

Kortepeter, M.G. and Parker, G.W. (1999). Potential Biological Weapons Threats, Emerging Infectious Diseases, July-August 1999, vol.5, no.4

Kraemer, P. (2001). The Theology of biological warfare, World and I, May 2001 v16 i5 p306

Medical Letter on the CDC & FDA (2001). Biological Warfare a Continuing Threat, Feb 4, 2001 pNA

Miller, J. (1999). Killer Germs, New York Times Upfront, Nov 1, 1999 v132 i5 p14

Paddle, B.M. (1996). Biosensors for chemical and biological agents of defense interest, Biosensors and Bioelectronics, 1996, Vol.11. No.11 pp.1079-113

Pavlin, J.A. (1999). Epidemiology of Bioterrorism, Emerging Infectious Diseases, 1999, vol.5, no.4

Rahni, D.N. (2001). Anthrax Insights Journal of Forensic Identification (2002) Vol 52, 86-94.

Russell, P.K. (1999). Vaccines in Civilian Defense against Bioterrorism, Emerging Infectious Diseases, 1999, vol.5, no.4

Simon, J.D. (1997). Biological Terrorism: preparing to meet the treat. JAMA. 1997; 278:428-430

The Columbia Encyclopedia, Edition 6, 2000

The New England Journal of Medicine (1998). Smallpox as a biological weapon, August 20, 1998, Volume 339:556-559 Number 8

Tucker, J.B. (1999). Historical Trends Related to Bioterrorism: An Empirical Analysis, Emerging Infectious Diseases, 1999, vol.5, no.4

1 DaSilva, E.J. Biological warfare, bioterrorism, biodefense and the biological and toxin weapons convention, EJB ISSN:0717-3458, December 15, 1999, Vol.2 No.3

2 Kortepeter, M.G.; Cieslak, T.J.; Eitzen, E.M., Bioterrorism, Journal of Environmental Health, Jan 2001 v63 i6 p.21

3 DaSilva, supra, note 1.

4 Biological Warfare a continuing threat, Medical Letter on the CDC & FDA, Feb 4, 2001

5 A 1969 United Nations expert panel concluded that the relative cost to produce mass casualties over 1 square kilometer was $600 for a chemical weapon, $800 for a nuclear weapon, $2,000 for a conventional weapon, and $1 for a biological weapon. Kortepeter, supra, note 2

6 Kortepeter, supra, note 2

7 Khan, A.S.; Morse, S.; Lillibridge,S. Public-health preparedness for biological terrorism in the U.S.A., The Lancet, Sept 30, 2000 v 356 i9236 p 1179

8 Among the biological agents involved in bioterrorism or biocrimes and traditional biological warfare are bacillus anthracis, brucella suis, coxiella burnetii, smallpox, Yersinia pestis (pathogens) and botulinum, ricin, staphylococcal enterotoxin B (toxins). Kortepeter, M.G. and Parker, G.W. Potential Biological Weapons Threats, Emerging Infectious Diseases, July-August 1999, vol.5, no.4

9 Biological Warfare a Continuing Threat, supra, note 4, and Christopher GW, Cieslak TJ, Pavlin JA, Eitzen EM. Biological Warfare: a historical perspective, JAMA. 1997;278:412-417

10 Countries that developed research programs about biological weapons after the war included Belgium, Canada, France, Great Britain, the Soviet Union. Note that the United States did not ratify the Geneva Protocol until 1975, due to its knowledge of its offensive biological warfare program.

11 The treaty was ratified in 1972 and went in effect in 1975. More than 100 nations signed this treaty, including Iraq, and the former Soviet Union.

12 Tucker, J.B. Historical Trends related to bioterrorism: an empirical analysis, Emerging Infectious Diseases, 1999, vol.5, no.4

13 Kortepeter, M.G. and Parker, G.W. Potential Biological Weapons Threats, Emerging Infectious Diseases, July-August 1999, Vol 5, No 4

14 For the Working Group on Civilian Biodefense, Anthrax as a biological weapon, medical and public health management, Emerging Infectious Diseases, 1999, Vol 5, No 4

15 Biological Warfare a continuing threat, supra, note 4

16 Rahni, D.N. Anthrax Insights.

17 Russell, P.K. Vaccines in Civilian Defense Against Bioterrorism, Emerging Infectious Diseases, 1999, Vol 5, No 4

18 Note that Iraq and the Former Soviet Union have or had in the past offensive biological weapons research programs. Today a number of countries are believed to have similar programs as well as terrorist groups.

19 Note that anthrax bacteria buried by the Soviets in the Spring of 1988 still pose great danger at least for the surrounding areas (mainly Uzbekistan). Miller, J. Killer Germs (anthrax bacteria buried by Soviets in 1980s poses hazard for Uzbekistan), New York Times Upfront, Nov 1, 1999 v 132 i5 p 14.

20 D.A. Henderson. Smallpox: Clinical and Epidemiologic Features, Emerging Infectious Diseases, July-August 1999, Vol 5, No 4.

21 Harrison’s Principles of Internal Medicine: Part 7, Chapter 186 (Author: Fred Wang).

22 Two European smallpox outbreaks in the 1970s (one in Germany in 1970 and one in Yogoslavia in 1972) illustrate the dangers of a potential use of smallpox as a biological weapon.

23 In 1980 the World Health Organization officially declared that smallpox was worldwide eliminated as a result of a global vaccination program.

24 Kraemer, P. The theology of biological warfare, World and I, May 2001 v 16 I 5 p. 306, also Kortepeter, M.G. and Parker, G.W. Potential Biological Weapons Threats, Emerging Infectious Diseases, July-August 1999, Vol 5, No 4.

25 Smallpox as a biological weapon, The New England Journal of Medicine, Vol. 339:556-559, August 20, 1998, Number 8.

26 Iraq has admitted to producing botulinum toxin.

27 Vaccines cannot be considered a first line defense for the general population due to their very high costs and the great difficulties involved in vaccinating large populations.

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