History, Likely Agents, Perpetrators, and Dissemination

Historical Perspective
Most Likely Biological Agents
Potential Perpetrators
Means of Dissemination
Outbreaks of Weaponized Anthrax
References

Historical Perspective

Use of biological agents as weapons of war has occurred throughout history. Notable examples include these these (see References: Osterholm 2000):

In 184 BC, Hannibal ordered that pots filled with serpents be thrown onto the decks of enemy ships.
In 1346, the Tartar army catapulted bodies of plague victims into the city of Caffa.
In 1763, the British army provided the Delaware Indians with blankets that had been used by smallpox patients.
During World War I, the Germans used various human and animal pathogens as agents of germ warfare in Europe.
During World War II, the Japanese used germ warfare against the Chinese and the Soviets.

Following World War II, several countries maintained biological weapons programs, including the United States, the Soviet Union, Canada, and the United Kingdom. However, the United States, Canada, and the United Kingdom all ended their programs by the early 1970s. In 1972, more than 140 countries signed the Biological and Toxin Weapons Convention, which called for termination of all offensive biological weapons research and development and destruction of existing biological weapons stocks.

Despite these positive events aimed at curtailing the availability of biological weapons, the Soviet Union continued to expand its biological weapons program throughout the 1980s and early 1990s (see References: Miller 2002). Key aspects of the program included the production of large amounts of smallpox virus and the development of mechanisms to weaponize it. Eradication of naturally occurring smallpox and the cessation of routine vaccination against the disease in 1980 was seen by the Soviet Union as an opportunity to use smallpox virus as a biological weapon (see References: Alibeck 1999). Anthrax was another disease actively studied by the Soviet Union, as evidenced by the outbreak of inhalational anthrax that followed release of aerosolized anthrax from the Sverdlosk bioweapons production facility in 1979 (see References: Meselson 1994). Seventy-seven cases of anthrax were identified and 66 of the patients died.

After the demise of the Soviet Union, many of the scientists who worked in the biological weapons program left the country. The status of many of those scientists remains unknown; however, Iraq, Iran, Syria, Libya, and North Korea actively have recruited such experts (see References: Henderson 1999). After the Gulf War, it became clear that Iraq had developed an extensive biological weapons program, predominantly involving anthrax and botulism toxin (see References: Zilinskas 1997). Experts also are concerned that Iraq, and possibly North Korea, may have gained access to smallpox virus.

Because weaponized forms of certain biological agents have been developed, the threat of using such agents against civilian populations through bioterrorism attacks has emerged over the past few years. Bioterrorism, which had been largely a topic of speculation, became a serious reality for the United States in October 2001, when anthrax cases following exposure to contaminated mail occurred in New York, New Jersey, and Washington, DC.

The Most Likely Biological Agents

The Centers for Disease Control and Prevention (CDC) published a list of critical biological agents in 2000 (see References: CDC: Biological and Chemical Terrorism). The list is divided into categories A, B, and C.

Category A agents:

Can be easily disseminated or transmitted person-to-person
Cause high mortality with potential for major public health impact
Might cause public panic and social disruption
Require special action for public health preparedness

Category B agents:

Are moderately easy to disseminate
Cause moderate morbidity and low mortality
Require specific enhancements of diagnostic capacity and disease surveillance

Category C agents:

Include emerging pathogens that could be engineered for mass dissemination in the future because of:

Availability
Ease of production and dissemination
Potential for high morbidity and mortality and major health impact

Critical Biologic Agents for Use in Bioterrorism

Category A agents
Bacillus anthracis (anthrax)
Clostridium botulinum toxin (botulism)
Yersinia pestis (plague)
Francisella tularensis (tularemia)
Variola major virus (smallpox)
Ebola, Marburg, Lassa, and South American hemorrhagic fever viruses (viral hemorrhagic fever)

Category B agents
Coxiella burnetti (Q fever)
Brucella species (brucellosis)
Burkholderia mallei (glanders)
Alphaviruses (Venezuelan encephalomyelitis and eastern and western equine encephalomyelitis)
Ricin toxin from Ricinus communis (castor beans)
Epsilon toxin of Clostridium perfringens
Staphylococcus enterotoxin B

Foodborne or waterborne agents also are included under Category B. These pathogens include but are not limited to:
Salmonella species
Shigella species
Escherichia coli O157:H7
Vibrio cholerae
Cryptosporidium parvum

Category C agents
Nipah virus
Hantaviruses
Tickborne hemorrhagic fever viruses
Tickborne encephalitis viruses
Yellow fever virus
Multidrug-resistant Mycobacterium tuberculosis

Source: CDC. Biological and chemical terrorism (see References).

Potential Perpetrators

With the breakup of the former Soviet Union and movement of scientists out of the country, it is likely that the knowledge necessary to create biological weapons has become widespread. Furthermore, a number of countries are presumed to have supplies of aerosolizable organisms suitable for bioterrorism. Therefore, essentially any group with sufficient resources could likely find an avenue to purchase supplies of such organisms and acquire the necessary expertise for disseminating them (see References: Henderson 1999).

Examples of potential perpetrators of bioterrorism include:

State-sponsored terrorist groups (those sponsored by rogue nations such as Iraq)
Independent terrorist organizations (eg, al Qaeda or other extremist groups)
Cult groups (eg, the Japanese religious cult Aum Shinrikyo)
Lone offenders (eg, Timothy McVeigh)

Means of Dissemination

Biological agents used in a bioterrorism attack would likely enter the human body through one of several routes:

Inhalation of small particles into the lungs
Ingestion of contaminated food or water
Contamination of the skin or absorption of toxins through the skin

The inhalational route is of greatest concern, since all of the Category A agents listed above can be effectively disseminated through aerosolization. Furthermore, use of aerosols is an efficient way to affect the maximum number of people with a single attack. Aerosolized particles of 1 to 5 microns in size can easily be inhaled deeply into the lungs of intended victims.

Aerosols can be delivered in either wet or dry form. For example, the 2001 outbreak of anthrax on the East Coast of the United States involved use of a fine, dry, anthrax-containing powder. Equipment to disperse both wet and dry aerosols can be purchased today on the Internet. Mechanisms to disseminate aerosols include:

Wide-scale dissemination out-of-doors through use of crop-dusting planes and equipment
Use of small aerosol-generating devices in closed spaces (eg, subway systems, shopping malls, theaters)
Installation of aerosols into the ventilation systems of buildings
Contamination of items in the environment with fine powders that are easily aerosolized when disrupted (as with the recent anthrax cases in the United States, which have been caused by contaminated mail)

Although not as efficient as aerosol transmission, ingestion of contaminated food or water remains a concern. Two disease outbreaks in the United States have been caused by deliberate contamination of food. The first occurred in The Dalles, Oregon, where members of the Rajneashee religious cult contaminated salad bars with Salmonella; over 700 people became ill (see References: Torok 1997). A second outbreak occurred in a laboratory in Texas where an employee contaminated bakery goods with Shigella dysenteriae; 12 people became ill (see References: Kolavic 1997).

A large-scale bioterrorist attack involving ingestion of food and water is less likely than an attack involving the airborne route for the following reasons:

Most of the Category A agents are not transmitted via food and water.
Most of the illnesses transmitted through food and water involve short-term vomiting and diarrhea with relatively quick recovery, so these agents are of less interest to terrorists.
Current water treatment procedures effectively kill biological agents and rapidly inactivate botulism toxin.
Chemical contamination of water is unlikely because very large amounts of toxin would be needed to effectively contaminate a water supply because of the dilution factor.
Thorough heating and cooking of food destroys biological agents and botulism toxin, and widespread contamination of an uncooked food item is relatively unlikely.

Transmission of infection via the skin was demonstrated with the 2001 cases of cutaneous anthrax that resulted from direct contact with contaminated mail. Most other biological agents are not effectively transmitted via this route.

Outbreaks of Weaponized Anthrax

Weaponized anthrax has caused two outbreaks of disease (key points from each are outlined in the sections below):

The Sverdlovsk Outbreak—1979

This outbreak in the Union of the Soviet Socialist Republics resulted from accidental release of anthrax spores from a military microbiologic facility where weaponized anthrax was being produced (see References: Meselson 1994).
Seventy-seven human cases were reported and 66 of the patients died, for a case-fatality rate of 86%; 75 cases were inhalational and two were cutaneous (one on the back of the neck and one on the shoulder). A recent statistical analysis of available data suggests that 250 cases with 100 fatalities may actually have occurred (see References: Brookmeyer 2001). The mean patient age for male cases was 42 years and for female cases was 55 years, and no cases occurred in children.
The mean incubation period was 9 to 10 days (range, 2 to 43 days), and the mean time between illness onset and death was 3 days.
Approximately 2 weeks after the presumed date of exposure, a vaccination campaign of 59,000 eligible residents was begun; an estimated 80% of the target population received at least one dose of vaccine.
Investigators postulated that the weight of spores released as aerosol "could have been as little as a few milligrams or as much as nearly a gram."

United States—2001

The outbreak predominantly involved direct exposure to mail that was deliberately contaminated with anthrax spores. Several contaminated letters were sent and one was reported to contain 2 g of powder, with 100 billion to 1 trillion anthrax spores per gram (see References: Inglesby 2002).
Twenty-two cases (11 inhalational and 11 cutaneous) were identified. Five of the patients with inhalational anthrax died, for a case-fatality rate of 45% among that group (see References: Jernigan 2002).
The outbreak demonstrated several important points about weaponized anthrax:

Mail can be an effective vehicle for disseminating anthrax spores.
Cross-contamination of mail likely can occur within postal facilities.
Persons who handle or process unopened contaminated mail are at risk of acquiring anthrax.
Substantial environmental contamination can occur in facilities handling contaminated mail or in offices where contaminated mail is opened.

Following the outbreak, a case of cutaneous anthrax occurred in a laboratory worker in Texas who was working at a private laboratory that was processing environmental samples from the CDC investigations (see References: CDC: Suspected cutaneous anthrax in a laboratory worker).
The source of the anthrax in this outbreak remains unknown, although Federal Bureau of Investigation investigators believe that the perpetrator was domestic and had laboratory access to the Ames strain of B anthracis. The original Ames strain came from a laboratory in College Station, Texas (rather than Ames, Iowa). Several distinct Ames strains have been identified.

References

Alibek K, Handelman S. Biohazard: the chilling true story of the largest covert biological weapons program in the world—told from the inside by the man who ran it. New York: Random House, 1999

Brookmeyer R, Blades N, Hugh-Jones M, et al. The statistical analysis of truncated data: application to the Sverdlovsk anthrax outbreak. Biostatistics 2001;2(2):233-47 [Abstract]

CDC. Biological and chemical terrorism: strategic plan for preparedness and response. Recommendations of the CDC strategic planning workgroup. MMWR 2000:49(RR04):1-14 [Full text]

CDC. Suspected cutaneous anthrax in a laboratory worker—Texas 2002. MMWR 2002;51(13):279-81 [Full text]

Henderson DA. The looming threat of bioterrorism. Science 1999;283(5406):1279-82 [Abstract]

Inglesby TV, O'Toole, T, Henderson DA, et al, for the Working Group on Civilian Biodefense. Anthrax as a biological weapon: updated recommendations for management. JAMA 2002;287(17):2236-52

Jernigan DB, Raghunathan PL, Bell BP, et al. Investigation of bioterrorism-related anthrax, United States, 2001; epidemiologic findings. Emerg Infect Dis 2002;8(10):1019-28 [Full text]

Kolavic SA, Kimura A, Simons SL, et al. An outbreak of Shigella dysenteriae type 2 among laboratory workers due to intentional food contamination. JAMA 1997;278(5):396-8 [Abstract]

Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science 1994;266:1202-8 [Abstract]

Miller J, Engelberg S, Broad W. Germs: biological weapons and America's secret war. New York, NY: Simon & Schuster, 2001

Osterholm MT, Schwartz J. Living terrors: what America needs to know to survive the coming bioterrorist catastrophe. New York: Dalacorte Press, 2000

Torok T, Tauxe RV, Wise RP, et al. A large community outbreak of Salmonella caused by intentional contamination of restaurant salad bars. JAMA 1997;278:389-95 [Full text]

Zillinskas RA. Iraq's biological weapons: the past as future? JAMA 1997;278(5):418-24 [Abstract]


Home	Mission & Activities	About Us	Center Support	Contact Us