Terrorism can be most simply defined as “warfare deliberately waged against civilians with the purpose of destroying their will to support either leaders or policies” (2); however, the term, as commonly used, includes the implicit connotations that some weaker group attempts to gain international support or tumble the government targeted in order to achieve their goals and that it often employs an element of fear in the targeted noncombatant population (3).
The use of these tactics is probably as old as organized governments and has been traced back as far as the 3rd century BCE tactics of Hannibal or the spectacular murders by the 11th century Assassin cult. In any case, this approach has continued to the present day and is evolving according to available technology. Today’s terrorists use the Internet and cellular phones and incorporate the most modern destructive weapons. When we talk of bioterrorism, we refer to terrorism carried out using biological weapons. The international definition of biological weapons includes replicating microorganisms such as bacteria and viruses as well as toxins derived from microorganisms.

This definition includes a wide variety of attacks using any of a huge selection of microorganisms. Of course, many of these events would be of lesser impact and might be of little more consequence than a crime or assassination executed with firearms (4,5). However, the element of terror is an important part of the impact. For example, the consequences of cyanide poisoning of analgesics or of imported grapes (3) had far-reaching consequences in the public mind and economy. Only 21 anthrax cases with 5 deaths in 2001 resulted in a great deal of fear in the involved areas, paralyzed mail communications, and handicapped government functioning. Even hoaxes can be highly disruptive and expensive.

There is a much more serious side to the threat of bioterrorism, and it is best understood through the history of biological warfare. Attempts at biological attacks date back far in history. For example, in the 1300s, the bodies of plague-infected victims were catapulted over the city walls during the Tatar siege of Kaffa. In the 1700s, during the French and Indian War, native American adversaries were given “gifts” of smallpox contaminated blankets by the British that decimated their numbers (6).

The development of a more modern approach to biological weapons dates to the early decades of the 20th century. During the 1930s and 1940s, the Japanese conducted extensive experiments and large-scale field trials— primarily involving contaminated food and water supplies—on unwitting civilians and prisoner of wars (POWs) in occupied Manchuria. In fact, during World War II, every major combatant had a biological weapons program, although Japan is the only country that is generally agreed to have used biological weapons during the course of the conflict (6,7). We began our own bioweapons program in 1943, partially in response to the research programs established by the Japanese and the Germans as well. But in 1969, President Nixon renounced the use of biological weapons and ordered that our offensive program be ceased and all stockpiles destroyed (8,9). This decision paved the way for negotiation of the Biological and Toxin Weapons Convention (BWC) treaty, which prohibits possession, or stockpiling, and transfer of bioweapons. The treaty was concluded in 1972 and subsequently ratified by more than 140 nations. The signing of the BWC represented a very important commitment to abandon pursuit of biological agents as weapons, but it did not—and still does not—contain explicit monitoring, inspection, or enforcement requirements (10).

As the 20th century closed, several events gave bioweapons greater prominence on the national security agenda. The first strong indication came from the accident at a Soviet bioweapons factory in Sverdlovsk; a human error led to the accidental release of weaponized anthrax, with resulting cases in humans and cattle in the city. The source of the epidemic was suspected in the military and intelligence community but was denied by the Soviets and some American academics. Later investigations and Soviet admissions confirmed that it was, indeed, an epidemic of inhalation anthrax, practically pathognomonic of a biological weapon in the pattern observed (9,11). As the Soviet Union broke up in the 1980s, there were startling revelations about the magnitude and scope of the bioweapons program in the former Soviet Union—which began in full force the same year as they signed on to the BWC. At the height of their program, they had more than 50 institutes, employed tens of thousands of workers (including an estimated 7,000 scientists deemed “security risks” on the basis of their knowledge and expertise; Ref. 12), and made literally ton quantities of weaponized anthrax, smallpox, and other microorganisms. In addition they were developing resistant strains and new pathogen variants; and experimenting with innovative strategies to cause disease including recombinant microorganisms such as Escherichia coli expressing neuromodulators (9,13).

Concerns were further heightened by the disclosure of an ambitious bioweapons’ program mounted by Iraq (14,15) and the findings that Aum Shinrikyo, the Japanese group that released nerve gas in the Tokyo subway, had also experimented with botulism and anthrax, as well as sent teams to Zaire in an effort to obtain Ebola virus for use as a weapon (16,17). Episodes here at home involving extremist groups or individuals who were able to obtain dangerous pathogens such as ricin, anthrax, and Yersinia pestis for dubious purposes added to the growing perception of risk (18). Of course, the final breach of the barrier to use of biological agents for terrorism or weapons came with the anthrax attacks in October 2001.

Any consideration of bioterrorism must begin with a consideration of the scenario: who is executing the attack, why are they doing it, and what are their resources? This delineation will allow us to focus on the scope and sophistication we are concerned with and the possible modalities of the attack or defense. A lone person with little microbiological expertise poses a lower risk with microbes than with an automatic weapon. A state-sponsored program is the other end of the threat spectrum and could result in many thousands of deaths. It is possible that the terrorist’s desired outcome is merely that the turnout for voting is diminished, as occurred with a sect in Oregon that contaminated salad bars with Salmonella (19), or it may be more lethal such as Aum Shinrikyo’s goals (16,17).

Certainly, attacks on a limited scale have occurred and will occur again (17,20). Terrorists or nation states will note the remarkable success of the 2001 anthrax attacks, and they will attempt to repeat them. In fact, anthrax is the most likely agent to be used in the future, because the microorganism is readily available in nature worldwide, the spores are stable on storage and in aerosol without special preparation, and Bacillus anthracis is easily grown
and purified. It is particularly worrisome that we do not understand who prepared the 2001 anthrax weapon or how it was prepared (21).

However, most attention has been focused on attacks that carry the threat of very large numbers of casualties. It is easiest to analyze these according to how the agent would be disseminated (Table 101-1). Direct injection has been used (22) as an assassination tool with ricin, but is impractical in any large scale. Water is often mentioned and of course could be a risk on a small scale, but dilution and residual chlorine make it impractical on a large scale. Arthropods or rodents could be used with some agents such as tularemia or yellow fever and indeed plagueinfected fleas were used by the Japanese in World War II (7). However, the biology of such attacks can be difficult to predict or manage, as anyone who followed the arguments about the persistence of West Nile virus after its introduction into North America can attest. Food sources have been increasingly recognized as sources of multistate outbreaks and must be regarded as a vulnerable link, but we are also responding to them more effectively so that surveillance could give early warning and food lots could be recalled unless the dissemination occurred in a setting in which many consume the product synchronously. Clearly protection of the food supply at the source is an increasingly important consideration (23). The most efficient approach to infecting a large number of target humans would be to use an agent that would spread from person to person after the initial infections; only smallpox can actually do this. Influenza strains have been suggested, but they lack “directionality” toward an enemy and the immediacy required in most scenarios. That does not detract from the fact that influenza A is the greatest natural threat we face and that new strains could be responsible for millions of deaths worldwide (18). Other infections such as plague and viral hemorrhagic fevers have a limited possibility for spread and will not cause secondary infections beyond possibly limited numbers of close personal contacts and a few in the medical setting.

This leaves aerosol dissemination on the list (Table 101-1); however, there are only a few agents that can be grown to high titer, are infectious by the aerosol route, and cause severe and fatal disease. The small particle aerosols are subject to ultraviolet inactivation in most cases, can be carried away by wind currents, and require special preparation and skill in dissemination. They have some advantages: they can be disseminated at night under inversion conditions and with attention to meteorological variables and be carried silently downwind to expose large numbers of people and/or animals. In fact, this approach was exactly that chosen by both the United States and the Soviet Union for their biological warfare programs and the testing suggested that it would be highly effective (24). The US program was tested in each step, ranging from indoor and outdoor tests of aerosols, actual determination of the minimal infectious dose in humans for selected agents, and extensive animal testing. They showed that aerosols of simulant microorganisms (microorganisms that resemble the one to be used as a weapon but of minimal virulence) or powders with similar aerosol properties could be disseminated over large areas and would have the potential to produce tens or hundreds of thousands of casualties (25). Thus, each step of the use of such weapons was in place and there is no doubt that they would have been effective (8,9,22).