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Source: BioScience, June 1999 v49 i6 p465(1).

Title: Combating the threat of biowarfare and bioterrorism: defending
against biological weapons is critical to global security.
Author: Ronald M. Atlas

Full Text COPYRIGHT 1999 American Institute of Biological Sciences

Defending against biological weapons is critical to global security

Increasing fear that biological weapons may be used against military and civilian populations is fostering efforts to develop adequate protective response strategies. The threat of biological warfare and bioterrorism is significant. Small quantities of lethal biological agents can be easily concealed, transported, and released into susceptible populations. This fact contributes to both military and civilian vulnerabilities to biological weapons and to the difficulty of providing adequate protection. As Danzig and Berkowsky (1997) noted, minute amounts of some biological agents can cause mass casualties (Table 1); biological weapons agents can easily be obtained; technologies for production and weaponization are readily available; only limited financing and training are needed to establish a biological weapons program; and biological weapons have low visibility and relative ease of delivery.

Biological weapons have been used during warfare in a limited number of cases (Christopher et al. 1997). In the fourteenth century, the Tartars allegedly catapulted dead bodies over the fortified walls of Kaffa (Feodossia, Ukraine) in an attempt to introduce plague (Derbes 1966). During the French and Indian War of 1754-1767, the commander of the British forces in North America, Sir Jeffrey Archer, purportedly suggested using contaminated blankets to introduce smallpox into Native American populations that were sympathetic to the French (Parkman 1901). Germany reportedly used biological weapons during World War I to infect livestock in a number of countries, particularly horses and mules destined for the US Cavalry (Witcover 1989, Hugh-Jones 1992, Robertson and Robertson 1995, Wheelis in press). Japan reportedly attacked at least 11 Chinese cities with biological agents during World War II, contaminating air, water, and food with Bacillus anthracis, Vibrio cholerae, Shigella spp., Salmonella spp., and Yersinia pestis - infected fleas (Williams and Wallace 1989, Harris 1994). It has been asserted that a Japanese biological weapons attack on Changteh in 1941 killed approximately 10,000 Chinese - primarily from cholera - and also caused 1700 deaths among Japanese troops, who were inadequately trained to avoid infection from contaminated water (International Scientific Commission for the Investigation of the Facts Concerning Bacterial Warfare in Korea and China 1952).

These early attempts at biowarfare were rather primitive and caused only "limited" casualties. Britain, the United States, and the Soviet Union built on the Japanese experience with biological weapons and engaged in sophisticated biological weapons programs after World War II. As typified by the US program during the 1950s and 1960s, the focus was on a limited number of biological agents and on aerosol delivery to infect the largest possible number of targeted individuals (Table 2). These programs transformed biological weapons into true weapons of mass destruction.

The United States ended its biological weapons program in 1969 by a unilateral declaration of President Nixon. Other nations followed this lead, and an international agreement was enacted in 1972 - the Biological and Toxin Weapons Convention (BWC) - that prohibited the production and retention of stockpiles of biological weapons. Nevertheless, some nations have continued to develop an offensive biological weapons capability, which some observers have referred to as the "poor man's nuclear arsenal."

The threat of biological warfare therefore remains, as does the fear that a terrorist attack using biological weapons could kill millions. Recent congressional hearings have highlighted the significance of the threat posed by biological weapons. FBI Director Louis Freeh and Secretary of Defense William S. Cohen testified that the use of biological weapons must be viewed as a low-likelihood, high-impact event. Others testifying in Senate hearings, including the head of Minnesota's Public Health Laboratory, Michael Osterholm, and best-selling author Richard Preston, who wrote Cobra Event and other novels about harmful biological agents, have openly expressed fear that it is a matter of when, and not if, biological weapons will be used. President Clinton told the New York Times in an interview immediately after his January 1999 State of the Union Address that he has trouble sleeping because of the threat posed by biological weapons and that he fears that a bioterrorist attack will occur. Clinton has issued several Presidential directives aimed at enhancing deterrence and response capability against a biological weapons attack. He has asked Congress to appropriate $1.4 billion in the FY 2000 budget to protect US citizens against chemical and biological weapons. Table 1. Estimates of casualties from a hypothetical biological attack based on the release of 50 kg of various agents by an aircraft flying along a 2 km path upwind of a city of half a million people?

Agent Casualties Fatalities

Rift Valley 35,000 400 fever

Tick-borne 35,000 9500 encephalitis

Typhus 85,000 19,000

Brucellosis 125,000 500

Q fever 125,000 150

Tularemia 125,000 30,000

Anthrax 125,000 95,000

a Based on WHO (1970) as cited by Christopher et al. (1997).

As discussed by Carus (1998a), several trends in biological weapons proliferation have led to this heightened concern. Pentagon officials, the State Department, and US ambassadors to the United Nations (Peter Burleigh and Bill Richardson) have expressed concern that, despite all efforts to ensure the elimination of Iraqi biological weapons, Iraq may be continuing their development. Similarly, the United States remains concerned about the possible continuation of biological weapons programs in Russia. Although these programs may be smaller than they were a decade ago, weapons technologies developed by the Soviet Union before its breakup may have become accessible to other nations, as well as to terrorists. China, Egypt, Iran, Libya, Syria, Taiwan, Israel, and North Korea all appear to have active biological weapons programs, and there is particular concern that Iran, Syria, and Libya are attempting to enhance their biological weapons capabilities. Defense Secretary Cohen has also expressed concern about the potential of Cuba to use its biotechnology infrastructure to produce biological weapons. Table 2. Biological weapons developed by the US military before 1969.(a)

Type of agent(b) Species or toxin

Lethal agents Bacillus anthracis, botulinum toxin, Francisella tularensis

Incapacitating agents Brucella suis, Coxiella burnetii, staphylococcal enterotoxin B, Venezuelan equine encephalitis virus

Anticrop agents Rice blast, rye stem rust, wheat stem rust

a Based on Christopher et al. (1997).

b The lethal and incapacitation agents were actually weaponized, that is, loaded into bombs and other delivery systems. Some of the anticrop agents were produced in bulk and stockpiled.

Based on an analysis of these trends, Carus (1998a, 1998b) concluded that there is legitimate concern that terrorist groups could acquire biological weapons. He has documented numerous instances in which terrorist groups have studied, acquired, attempted to acquire, or even used biological agents. He has compiled a record of attempts by groups to use biological weapons for terror and by individuals to use them to commit assault and murder (Table 3). The most significant bioterrorist attack in the United States, in terms of the number of individuals affected, occurred in 1983, when members of the Rajneeshees cult contaminated salad bars in Oregon restaurants with Salmonella typhimurium, sickening 753 people (Torok et al. 1997). Fortunately, no fatalities resulted. In other cases, individuals have been murdered with biological weapons for reasons ranging from political assassination to marital disputes. Physicians and disgruntled scientists with access to harmful microorganisms or toxins have carried out some of these attacks.

Given this background, concern about biological warfare and bioterrorism is clearly justified. This concern has been especially driven by the massive biological weapons program of the former Soviet Union, to which Boris Yeltsin admitted in 1992; by the extensive biological weapons program of Iraq, which was discovered at the time of the Gulf War in 1991; by the biological weapons programs of terrorist groups such as the Aum Shinrikyo cult, whose members carried out a chemical weapons attack using the nerve gas Sarin in the Tokyo subway in 1995; and by the attempts of individuals to acquire biological weapons (e.g., a US citizen associated with a white supremacist group tried to purchase plague bacteria in 1995 and anthrax bacteria in 1998). These revelations indicate that policies are needed to respond to the threats posed by individuals, terrorist groups, developing nations, and nations with advanced biotechnological capabilities.

In this article, I discuss several major efforts that are currently underway to deter biological weapons programs, to make it harder for terrorists to acquire the materials for developing biological weapons, and to build a biodefense infrastructure that will protect military personnel and the public from biological weapons. These efforts include an attempt to strengthen the BWC by developing a mandatory compliance ("verification") regime that makes it harder for nations to conceal biological weapons programs; inspections by the United Nations Special Commission (UNSCOM) to ensure elimination of the Iraqi biological weapons program; support of collaborative alternative research programs in Russia to prevent the dissemination of biological weapons programs by scientists who had been involved in these programs in the former Soviet Union; institution of domestic regulations and the continuance of export regulations for a select list of agents to prevent microorganisms and toxins with the greatest potential for use as biological weapons from reaching those who might seek to use them for that purpose; and development of military and civilian biodefense and public health response systems. These efforts represent a multifaceted approach aimed at lowering the risk that biological weapons will be used and lessening the impact of their use should efforts at deterrence fail. Table 3. Some alleged and confirmed twentieth-century uses of biological weapons as agents of bioterrorism and biocrimes.(a)

Incident Description

Brian T. Stewart, January 1999 Stewart, a phlebotomist, was sentenced to life in prison for deliberately infecting his 11-month-old baby with HIV-infected blood to avoid child support payments.

Serland Squires, January 1999 Squires, a 21-year-old female US soldier infected with the AIDS virus, was sentenced to 3 years in a military prison for having unsafe sex with nine men, none of whom have yet tested positive for HIV. Pfc. Squires pleaded guilty to charges of aggravated assault and disobeying a superior officer, who had told her to tell sex partners of her medical condition and to insist they use a condom.

Catholic churches, November 1998 Letters with Texas postmarks claiming to contain deadly anthrax bacteria were opened at a Catholic parish in Indianapolis and at a Catholic church in suburban Buffalo, New York. The letters did not contain anthrax.

Abortion clinics, November 1998 Letters claiming to contain anthrax were delivered to a Planned Parenthood clinic in Indianapolis and to four other abortion clinics in three states.

Brownsville, Texas, October 1998 Two men accused in an alleged plot to use biological weapons on federal officials were convicted on two counts of sending threatening e-mail to government agencies. The men had purportedly threatened to kill President Clinton and FBI Director Louis Freeh with botulinum toxin.

Richard Schmidt, October 1998 Schmidt, a gastroenterologist, was convicted in Lafayette, Louisiana, of attempted second degree murder and sentenced to life in prison with hard labor for infecting his former lover, nurse Janice Allen, with HIV by injecting her with blood from an AIDS patient.

B'nai B'rith, April 1997 A petri dish labeled "anthrax" was sent to the B'nai B'rith headquarters in Washington, DC. It was later proven to be a hoax.

Diane Thompson, October 1996 Thompson, a laboratory technician, allegedly infected 12 of her coworkers with Shigella dysenteriae Type 2 that she had placed in pastries in the office lunchroom.

Debora Green, August 1995 Green, a physician, was convicted of trying to murder her estranged husband with ricin.

Aum Shinrikyo, April 1990-March 1995 Aum Shinrikyo, a 10,000-member Japanese cult, was responsible for the 1995 dissemination of Sarin nerve gas in the Tokyo subway system, as well as for many failed attempts to disseminate other biological agents. For example, in April 1990, an automobile outfitted to disseminate botulinum toxin was driven around Japan's parliament building; in June 1993, the group attempted to disrupt the wedding of Japan's crown prince by spreading botulinum toxin with the same automobile dissemination system; in late June 1993, an attempt was made to spread anthrax from the roof of a building in Tokyo (dissemination was carried out for 4 days); on 15 March 1995, cult members planted three briefcases designed to release botulinum toxin in the Tokyo subway. Nine failures in nine attempts attest to the ineptness of the cult and to the difficulty of actually deploying biological weapons to cause mass casualties.

Scotland, June 1990 Nine people living in an apartment building in Scotland became ill with a diarrheal disease when feces contaminated with Giardia lamblia were placed in their water tanks

South Africa, 1989 South African government agents failed in an alleged attempt to contaminate a refugee camp's water supply with cholera and yellow fever organisms.

Rajneeshees, August-September 1984 The Rajneeshees religious cult grew Salmonella typhimurium and contaminated the salad bars of 10 local restaurants in Oregon to make opposing voters sick so that they would be unable to vote on Election Day. This contamination resulted in 753 confirmed cases of salmonellosis.

Rhodesia, 1976-1980 The Rhodesian government's Central Intelligence Organization is alleged to have used biological agents in water supplies against black civilians in Rhodesia and Mozambique.

Zimbabwe, November 1979 Rhodesian officials publicly accused nationalist guerrillas of spreading anthrax in 12 districts, killing 20 people. This incident is unconfirmed, and reports may have been spread as propaganda.

Bulgarian Secret Police, The Bulgarian Secret Police London, September 1978 killed Georgi Markov, a Bulgarian dissident, by injecting ricin into his thigh with a pellet shot by a specially designed umbrella.

Bulgarian Secret Police, The Bulgarian Secret Police Paris, August 1978 attempted, but failed, to assassinate Vladimir Kostov, a defector, with a pellet coated with ricin toxin.

Arnfinn Nesset, May 1977 Nesset, who ran a nursing home in Norway, was convicted of murdering 22 of his patients with injections of curacit.

Eric Kranz, February 1970 Kranz, a postgraduate student in parasitology in Canada, nearly killed his four roommates over a rent dispute by intentionally contaminating their food with the parasite Ascaris lumbricoides.

Mitsuru Suzuki, December 1964- Suzuki, a physician with March 1966 training in bacteriology, gave fruits and cakes poisoned with dysentery and typhoid to 120 patients and coworkers (causing four fatalities) over a year's time because he felt he was being discriminated against.

Mau Mau, 1952 In the area now known as Kenya, the Mau Mau, a nationalist liberation movement originating with the Gikuyu tribe, poisoned 33 steers with African milk bush (Synadenium grantii) as part of their revolt against the British.

India, 1933 Benoyendra Chandra Pandey and Dr. Taranath Bhatacharya were convicted of murdering Benoyendra's half-brother by injecting a lethal dose of plague bacteria (Yersinia pestis) into his arm during a dispute over their father's estate.

Japan, 1932 The Japanese military unsuccessfully attempted to poison members of the Lytton Commission with cholera-laced fruit.

Germany, 1913 Karl Hopf was convicted of murdering his father, two of his children, and his first wife with arsenic; of attempting to murder his second and third wives and his mother with arsenic; and of attempting to murder his third wife with cholera and typhus organisms.

France, 1909-1918 Henri Girard, his wife, his mistress, a chauffeur, and a wine merchant were arrested for having poisoned several people with Salmonella typhi and poisonous mushrooms to collect on life insurance policies.

Mexico, 1910s According to the novelist William Burroughs, supporters of Pancho Villa used botulinum toxin against Mexican federal troops by poisoning either foods or thornbushes with the toxin.

Poland, May 1910 Patrick O'Brien de Lacy, a Polish nobleman of Irish descent, plotted to murder his wife's entire family for the inheritance; he also paid a Polish physician to murder his brother-in-law using an injection of diphtheria toxin.

a Based largely on Carus (1998b).

The Biological and Toxin Weapons Convention

The BWC of 1972, to which the United States is a State Party, is an important international agreement aimed at reducing the threat of biological warfare. The BWC prohibits the development, production, stockpiling, or other methods of acquiring microbial or other biological agents or toxins, whatever their origin, method of production, or types, in quantities that have no justification for prophylactic, protective, or other peaceful purposes. It also prohibits the development or stockpiling of biological weapons, equipment, or means of delivery designed to use such agents or toxins for hostile purposes or in armed conflict. The BWC enjoins participating states from transferring any of the agents, toxins, weapons, equipment, or means of delivery to any recipient for nonpeaceful purposes or otherwise abetting the proliferation or acquisition of biological agents or weapons.

Unlike the case with the Chemical Weapons Convention (CWC), however, there is no accurate verification mechanism for ensuring compliance with the BWC. The CWC requires declarations based on classes of chemicals that pose varying degrees of threats and various levels of inspections to ascertain compliance. The revelations about the former Soviet Union's biological weapons program show that without such compliance measures, the BWC cannot prevent nations from carrying out a massive biological weapons program. The former Soviet Union's biological weapons program was enormous, with at least 30,000 people working in as many as 50 research and production facilities. Even after the unusual outbreak of anthrax at Sverdlovsk in 1979, when there was an accidental release of spores of B. antbracis from a biological weapons facility, the international community did not immediately recognize that the Soviet Union was continuing its biological weapons program (Meselson et al. 1994). It took years of investigation and human intelligence gathering to expose Soviet biological weapons activities. In 1992, Boris Yeltsin ultimately admitted that the Soviet Union had clandestinely continued its biological weapons program in violation of the BWC and confirmed the source of the 1979 anthrax outbreak.

The discovery of the Iraqi biological weapons program also indicated the

failure of the BWC to keep nations from developing biological weapons. Compared to the large Soviet program, Iraq's biological weapons program was small. It probably employed fewer than 300 scientists, engineers, and technicians. Nevertheless, small bioreactors can easily produce sufficient quantities of biological weapons to have threatened military troops on the battlefield and civilian populations in the region of conflict during the Gulf War. Thus, the scale of what constitutes significant production capacity was driven downward, and the need to develop protective measures heightened, by the recognition that small amounts of easily produced biological agents could pose a significant threat.

The revelations about the biological weapons programs of Iraq have added critical impetus for taking additional steps to ensure compliance with the BWC and to preclude biological weapons programs that threaten global security. President Clinton, in his January 1998 State of the Union Address, proclaimed that the United States will actively try to strengthen the BWC by supporting the adoption of a mandatory compliance regime. The aim of such a regime is to increase transparency, making it more difficult to hide a clandestine and illicit biological weapons program and bolstering confidence that nations are in compliance with the provisions of the BWC. Clearly, the BWC must be strengthened in this way if it is to help expose and effectively deter biological weapons programs. It is an important component in the effort to achieve biological weapons control (Kadlec et al. 1997).

An Ad Hoc Group of State Parties to the BWC has met periodically since 1994 in Geneva with the aim of developing a legally binding protocol that could monitor compliance with the BWC. In delineating the extent of the expanded scope for reporting activities, the Ad Hoc Group has been trying to strike a balance between guarding against the development of biological weapons, protecting intellectual property, and ensuring the performance of essential biomedical research - all of which will enhance national and global security. Many protocol provisions have been proposed and debated by the Ad Hoc Group. The draft version of the compliance regime, which is known as the "rolling text," is updated periodically by the Ad Hoc Group to incorporate these proposals. (The Federation of American Scientists' [FAS] Web site [www.fas.org] has the current version of the rolling text and other information about the Bwc.) An Ad Hoc Group of Government Experts to Identify and Examine Verification Measures from a Scientific and Technical Standpoint has evaluated the limitations and benefits of numerous measures aimed at strengthening the BWC (Table 4). The value of each of these measures has been discussed by Zilinskas (1998).

Currently, the United States and other parties to the BWC file annual declarations of past biological weapons programs and human vaccine production as part of voluntary confidence-building measures. The compliance regime being negotiated in Geneva would expand the scope of these voluntary declarations. Specifically, it would include a system for mandatory annual declarations, visits to verify the accuracy of the information supplied, and inspections to ensure compliance with the provisions of the BWC.

Despite extensive negotiations, agreement has not yet been reached on which equipment or activities at an institution might "trigger" the need to file declarations under the BWC or what information should be mandated for inclusion in those declarations. Yet certain themes are emerging that would expand the current voluntary reporting activities by requiring declarations from institutions possessing or working with those pathogenic microorganisms and biological toxins that are likely candidates for biological weapons use. Also, institutions with high-level containment and production facilities that have the potential to be used in biological weapons production, and those conducting activities that might be an integral part of a biological weapons program, such as genetic manipulation, vaccine production, and aerobiology, could be required to file annual declarations. Table 4. Measures that have been evaluated for inclusion in a Biological and Toxin Weapons Convention (BWC) verification regime.(a)

Verification activity Description

Surveillance of publications Researching the open literature for indications of research that might have biological weapons-related applications.

Surveillance of legislation Collecting information about national legislative actions that might bear on biological weapons-related work, such as enactment of biosafety laws or regulations.

Surveillance of economic data Collecting and analyzing information on exports and imports of such things as equipment and supplies, culture collections, and industrial production statistics.

Examination of information commonly Analyzing information shared among nations relating to medical, veterinary, agricultural, and environmental safety standards; to biological waste management; and to other activities that might be associated with biological weapons programs.

Examination of the results of off-site Debriefing scientists exchange visits who have visited specific facilities.

Ground-based technical surveillance Gathering information (off-site) from direct surveillance of a site of interest conducted from a point located at some distance from that site.

Observation (off-site) Monitoring activities at a site of interest by observers located at that site's perimeter. Unlike ground-based surveillance, off-site observation could yield information about disease outbreaks in the vicinity of the site or environmental damage caused by site activities, among other things.

Formal audits (off-site) Examining records pertaining to a site of interest.

Analysis of the results of exchange visits Collecting information arranged by international agreement from official exchange visits between similar facilities located within the territories of BWC State Parties. These visits might be arranged under the auspices of Article X of the BWC, which encourages nations to collaborate in peacefully directed microbiological research.

Declarations Periodic reports prepared by governments, in which they disclose information that could have relevance for the BWC.

Interviewing (on-site) Interrogating personnel of the facility being inspected to elicit information about the facility's activities.

Visual inspection (on-site) Determining staffing patterns and institutional configuration, including instrumentation, equipment, supplies, security, safety measures, animal facilities, containment, and waste disposal.

Identification of "key" equipment (on-site) In coordination with on-site inspections, identifying the presence of "key" equipment essential for biological weapons development, testing, and manufacture. Such equipment has dual-use capabilities, but it may serve as a marker in cases where other concerns exist.

Formal audits (on-site) Examining a facility's documentary record, including laboratory log books, research protocols, and manuals, as well as records pertaining to safety, processing, waste discharge, transport, inventory, stored agents, and finances. If available a facility's electronic data could also be audited. In cases of challenge inspections, the resumes of the suspect facility's scientific and technical staff should be reviewed to clarify areas of expertise and past research history.

Sampling and identification (on-site) Collecting samples from sources such as equipment used for research and development, manufacture, and storage; dust within buildings; soil from outside buildings; the facility's waste stream; its air filters; and animals and plants used in research and development and product testing. Portable instruments, microscopes, stains, and supplies would allow inspectors to screen samples on-site for well-characterized agents and material, but more definitive analyses would have to be conducted at international reference laboratories equipped with sophisticated instrumentation, such as gamma counters, nuclear magnetic resonance imagers, spectrophotometers, biosensors, and equipment to conduct polymerase chain reaction and restriction fragment length polymorphism analysis.

Medical examination (on-site) Collecting health-related information about a facility's staff during an on-site inspection. Some of this information can be collected using nonintrusive means, such as analyzing epidemiological data or reviewing vaccination protocols affecting personnel working in high-security laboratories. Other types of information require more intrusive procedures, such as medical examinations, X-rays, detailed personal histories, and collection of blood and urine pecimens.

Continuous monitoring by instruments Placing film, video, (on-site) or closed-circuit television cameras at strategic locations in a facility to directly observe or record all activities taking place within each camera's field of vision, or placing sensors to monitor industrial processes and facility usage.

Continuous monitoring by personnel Stationing a team of (on-site) observers at a facility where they have complete freedom of movement. Observers could monitor all steps of a facility's development, testing, and manufacturing processes; check the consumption of raw materials and chemicals; verify that the manufactured products match product specifications; and maintain the integrity and operations of instruments installed to monitor key equipment. For verification purposes, the advantages derived from continuous monitoring are substantial - during the time a facility is being monitored, any illicit activity should be detected.

Surveillance by satellite or aircraft Aircraft could be either piloted or operated by remote control. As the distance between the surveillance platform and the facility under surveillance increases, area coverage expands but resolution declines.

Sampling and identification (off-site) Collecting samples without inspectors entering the site. Air and soil samples may be taken from the surrounding environment, including the facility's waste stream. Epidemiological studies may be undertaken to detect uncommon disease outbreaks among human, animal, and plant populations in the vicinity of the facility of interest.

Epidemiological surveillance An epidemiological field investigation may reveal the etiology of suspicious or unusual disease outbreaks and whether they resulted from an accidental release from a biological weapons facility.

a Based on Zilinskas (1998).

Instituting mandatory declarations could, however, have a significant impact on the US biomedical and biotechnology community. A survey of nearly 1500 US academic institutions indicates that 22% work with pathogenic microorganisms and toxins that could be used in biological weapons development, 12% have high-containment laboratories (BL4/BL3), 10% do aerobiology research, 7% perform biopesticide research and development, 5% perform biodefense research and development, and 3% have high-production microbiology facilities (Weller et al. in press). Because only 33% of US academic institutions maintain

centralized inventories of agents and equipment that might trigger declaration requirements, providing accurate information will be difficult. Cost estimates for compliance among US academic institutions average $5000 per year ($28,000 for institutions with medical schools), and time estimates average 500 hours (2250 hours for institutions with medical schools). Despite the costs and difficulties inherent in providing accurate information, a nation's declarations should be the principal starting point for reviewing its activities relevant to biological weapons compliance and assessing its seriousness about honoring the BWC (Zilinskas 1998).

In addition to declarations, various levels of inspections - including routine inspections to increase the transparency of activities and challenge inspections to investigate allegations of violations of the BWC - are being contemplated as part of a mandatory compliance regime. Such inspections involve varying degrees of intrusiveness and costs, depending on which, if any, of the different proposals for verification of compliance with the BWC are eventually adopted. Current proposals envision that inspections could be triggered as a result of an unusual outbreak of disease that could be related to biological weapons development, as a result of allegations of biological weapons development or use, as a result of inconsistencies with other verification procedures, and as a routine practice to assure other nations of the accuracy of declarations made under the BWC. Each proposal for inspections has distinct costs and benefits.

Reaching decisions on the types of inspections to include in verification procedures for ensuring compliance with the BWC has proven difficult. Inspections are of great concern to US industry because of the enormous economic consequences of the potential loss of confidential business information. US industry favors limiting inspections and allowing the facility to control what the inspectors may do on site to limit potential loss of confidential business information, a process called managed access. FAS favors an approach in which inspectors directly control their activities. Such an approach would increase transparency and build confidence in compliance with the BWC but could have a significant impact on US industry and biodefense activities.

As President Clinton outlined in his 1998 State of the Union Address, the US government favors clarification visits only when there is a need to answer questions about compliance with the verification protocol and challenge inspections only when there is reason to believe that there has been an actual violation of the BWC. The current US position is that only accusations of actual BWC violations, with adequate documentation, warrant conducting a challenge inspection. President Clinton has charged the US delegation to the BWC Ad Hoc Group with negotiating a compliance regime that protects US business interests at the same time as it achieves greater protection of the United States and global security.

United Nations Special Commission in Iraq

The settlement of the Gulf War demanded a system for ensuring the disarmament of Iraq's weapons of mass destruction, including the elimination of its biological weapons program. UNSCOM was established in April 1991 by the United Nations Security Council when it adopted Resolution 687 (UNSCR 687). UNSCOM was to work in tandem with the International Atomic Energy Agency to eliminate Iraq's weapons of mass destruction. In October 1991, its mandate was extended by UNSCR 715 to include the establishment of a monitoring system to ensure that Iraq's strategic weapon programs were not rebuilt. UNSCOM inspectors in Iraq were to have the right to go anywhere at any time, to seize any document or record, and to photograph anything they wanted.

Iraq has, however, stymied UNSCOM's attempts to confirm that its weapons of mass destruction have been eliminated. Nevertheless, during 7 years of work in Iraq, UNSCOM was able to clarify a number of aspects of Iraq's biological weapons program (Zilinskas 1998). It decisively established that Iraq had an extensive biological weapons program that may have produced up to 10 billion doses of anthrax, botulinum toxin, and aflatoxin (SIPRI 1998).

The lead agency for Iraqi biological weapons research was the Biological Research Center for Military Defense at Salman Pak. The small core team at Salman Pak, approximately 10 scientists, conducted applied research with B. anthracis (the bacterium that causes anthrax), Clostridium botulinum (the bacterium used to produce botulinum toxin), and Clostridium perfringens (the bacterium that causes gangrene). The research generated by the Salman Pak group was transferred to the Al Hakam Single-Cell Protein factory for development and production. After large-scale production of B. antbracis, botulinum toxin, and other biological weapons agents commenced, the agents produced were stored in refrigerated tanks at Al Hakam until they were loaded into munitions. The actual filling of bombs, missiles, and other munitions with pathogens or toxins took place at the Muthanna State Establishment, which also served as Iraq's major chemical warfare production and testing facility.

UNSCOM's success at exposing Iraq's biological weapons program depended on the quality of the inspectors (Barton 1998). Finding discrepancies in Iraq's extensive and well-concealed biological weapons program was the key to exposing the extent of the Iraqi biological weapons program. UNSCOM ultimately concluded that a variety of biological weapons was developed, including 155 mm artillery shells, 122 mm rockets, 166 aircraft bombs, 25 warheads for the Al-Hussein ballistic missiles, and specialized spray tanks for disseminating aerosols. UNSCOM was, however, unable to conclude that all of these weapons had been destroyed.

After a year of confrontations, Iraq expelled UNSCOM inspectors in late 1998. This event led to Operation Desert Fox, in which the United States and Britain bombed Iraqi facilities from 16 December through 19 December. Three sites associated with biological weapons were destroyed - two airfields where drone aircraft equipped to deliver biological weapons were based, and the offices of the head of the biological weapons program at Baghdad University. But even after this military intervention, it is impossible to confirm that biological weapons have been totally eliminated from Iraq. The diplomatic fray over how to ensure complete elimination of Iraq's biological weapons capability and to prevent its return continues.

Collaborative alternate research programs in Russia

The scope of the Soviet biological weapons program, as described by the former deputy director of the Biopreparat arm of the program, Ken Alibek, after his defection to the United States, apparently involved the production and stockpiling of tens of tons of powdered smallpox virus, anthrax bacteria, and other biological warfare agents (Alibek 1998). Ensuring that Russia has discontinued its biological weapons program and preventing the dissemination of the tons of agents that had been made and of the knowledge of those who produced them in the wake of the breakup of the Soviet Union is especially challenging. Serious concerns remain that Russia and other former Soviet states have continued their biological weapons programs.

At its peak, the research and development component of the Soviet biological weapons program supported basic research in both military and nonmilitary institutions to ensure the availability of fundamental knowledge and expertise; maintained a network of specialized institutions, the Biopreparat complex, which was responsible for weapons-related research and production of agents as well as for the development and production of vaccines and other defensive measures; and maintained highly secret research and production facilities within the Ministry of Defense, about which little is known publicly, even now. When the Soviet Union collapsed in 1991, Russia inherited most of the Soviet military complex, including this vast biological weapons program, which it cannot afford to maintain. This situation has heightened concern about the fate of dangerous materials, equipment, technical data, and know-how.

Leitenberg (1994, 1997) has examined various aspects of converting the biological weapons research and development programs of the former Soviet Union to peaceful purposes. He points out that before looking at the technical aspects of biological weapons conversion, one must know who and what there is to convert. In the case of Russia, it is necessary to identify the large remaining institutions and researchers involved in biological weapons programs. Once these are identified, Leitenberg contends, conversion should be manageable because alternative research areas and products are numerous and require the same technologies and skills as biological weapons activities.

In particular, Leitenberg asserts that many of the Russian biological weapons facilities can be readily converted to biomedical research institutes and vaccine production facilities employing many scientists. This conversion paradigm follows the model established by the United States when it abandoned its biological weapons program and converted the facilities and workers at Fort Detrick and Pine Bluffs to peaceful biomedical and biodefense activities. But such conversion might be more difficult for Russia because the many years of focus on military research and development, with limited commercialization potential and the lack of business experience, requires a high degree of competency in this conversion process.

The US National Academy of Sciences (NAS) has been involved in trying to reduce the threat posed by the former Soviet Union's weapons of mass destruction (NAS 1997). NAS established a Committee on International Security and Arms Control (CISAC), which has a special working group on biological weapons. Beginning in 1993, the working group became concerned about the potential proliferation of biological weapons capabilities as a result of the economic difficulties afflicting the former Soviet biological weapons complex. Responding to these concerns, the US Department of Defense, in 1995, asked CISAC for assistance in designing a blueprint for United States-Russian cooperation.

In 1997, NAS issued a report to the Cooperative Threat Reduction Program of the US Department of Defense on a program for controlling dangerous pathogens through United States-Russian cooperation (NAS 1997). The plan outlined ways to increase cooperation in research directed to the public health aspects of dangerous pathogens while furthering US nonproliferation objectives. The plan is intended to foster collaboration on the epidemiology, prevention, diagnosis, and therapy of diseases associated with dangerous pathogens that pose serious public health threats, as well as related fundamental research about infectious disease.

As designed, the breadth and scope of the program should engage a substantial number of highly qualified specialists from the former Soviet biological weapons complexes, thereby meeting the goal of helping contain proliferation from the former Soviet biological weapons program and diverting activities from biological weapons programs to activities that benefit humankind. A precursor to the current program actually began in 1996 with pilot projects funded by the Cooperative Threat Reduction Program of the Nunn-Lugar Initiative. Table 5. Organizations and programs involved in conversion of biological weapons-related activities of the former Soviet Union to peaceful purposes in Russia.(a)

Organization or program Description of program activity

International Science and ISTC, established by the United States, Technology Center (ISTC) European Union, Japan, and Russia, has supported projects at a variety of institutes that were involved in the former Soviet biological weapons program.

Initiatives for Proliferation Prevention IPP, a program of the US Department of (IPP) Energy, supports biotechnology proposals at Russian institutes, particularly Biopreparat Institutes, which have potential for commercial markets.

US Civilian Research and CRDF is a private foundation that was Development Foundation founded by Congress in 1992 and (CRDF) established by the National Science Foundation in 1995 to support biomedical research projects submitted by Russian scientists.

National Aeronautics and NASA has funded several projects at Space Administration Biopreparat Institutes. (NASA)

Centers for Disease CDC has collaborative projects and Control and Prevention carries out personnel exchanges and (CDC) training with Russian institutes, including some that were extensively involved in the Soviet biological weapons program.

National Institutes of NIH provides support for US Health (NIH) investigators to involve Russian scientists in joint projects and for Russian scientists to train at NIH, including Russian scientists from former Soviet biological weapons programs.

US Department of USDA supports a limited number of Agriculture (USDA) biotechnology projects in Russia.

National Academy of With funds from the Department of Sciences (NAS) Defense and Russian institutions, NAS is sponsoring pilot biodefense projects on various dangerous pathogens at institutes previously involved in the Soviet biological weapons program.

a based on NAS (1997).

Although the NAS program focused initially on converting former Soviet biological weapons researchers to civilian work, the goal has since been expanded to include developing broad transparency that might deter further biological weapons research. In addition to advancing the public health agendas of the two countries, such cooperation could also build confidence at both the scientific and government levels regarding compliance with international arms control agreements. Because there is no provision for continuous on-site monitoring, however, some scientists and politicians worry that the program could be inadvertently financing continued offensive biological research in Russia. Nevertheless, the administration has made the NAS program part of overall US policy to deter Russian weapons of mass destruction programs. The success of the NAS program will depend on the adequacy of funding and on its ability to integrate the conversion programs sponsored by various US government agencies (see Table 5). The United States has spent over $30 million during the last 5 years to reduce the threat of proliferation of biological weapons expertise within nations of the former Soviet Union. President Clinton has proposed spending more than $150 million to expand these efforts over the next 5 years.

Curbing terrorist acquisition of biological weapons

After the discovery that the Aum Shinrikyo cult had developed biological weapons and had actually carried out several unsuccessful attacks, the scope of concern expanded to preventing terrorists from acquiring agents for biological weapons. The Aum Shinrikyo cult had acquired cultures of the bacteria that cause plague and anthrax and had also attempted to acquire Ebola virus from Zaire. In the United States, the FBI has twice arrested Larry Wayne Harris, who reportedly is associated with extremist groups, for attempting to acquire cultures of agents that could be used as biological weapons. In 1995, Harris tried to purchase a culture of Y. pestis, which causes plague, from the American Type Culture Collection. Then, in 1998, he acquired an isolate of B. anthracis by culturing it from the environment, but fortunately it turned out to be the harmless Stern vaccine strain. These incidents raise questions of how to prevent terrorists and psychopaths from acquiring microorganisms and toxins that could be used as biological weapons.

To prevent international terrorists and rogue states from easily acquiring the agents for biological weapons from the United States, the Commerce Department employs export controls. The amended Export Administration Act of 1979 prohibits the export, to certain proscribed countries, of any substance or technology that facilitates development or delivery of a biological weapon (Ferguson 1997). Any company or individual that knowingly exports materials used for biological weapons to one of these countries faces severe civil and criminal penalties. The Chemical and Biological Weapons Control Act of 1991 also establishes an elaborate system of economic sanctions and export controls to curb the proliferation of biological weapons. This act was enacted in an attempt to curb the transfer of biological weapons to rogue nations.

Export control through export licensing is an essential element in the overall strategy to limit the spread of biological weapons (Roberts 1998). Yet export controls are difficult to administer, in part because of the dual nature of the agents and equipment that might be used for producing biological weapons. Before the Gulf War, the Department of Commerce had approved the shipment of cultures of B. anthracis to Iraq for peaceful biomedical and diagnostic purposes, but these cultures may subsequently have been misused by Iraq and incorporated into its biological weapons program. Modifications of existing export control systems will be needed to maximize their usefulness for limiting the threat of biological warfare and bioterrorism. Given that there are hundreds of culture collections around the world - many in nations with no export controls - the utility of export controls will be limited. Even if international accords establish uniform regulations for the transfer of dangerous pathogens, rogue arms dealers supplying these agents could remain a threat.

To curb the domestic acquisition of biological weapons, Congress passed the Biological Weapons Act of 1989 and the Anti-Terrorism Act of 1996. These statutes impose severe criminal penalties for the possession, manufacture, and use of biological weapons. They authorize the federal government to seize any pathogens or other materials used to develop a biological weapon or its delivery system. The federal government need only establish that someone is attempting to acquire a biological agent that can be used as a biological weapon with no apparent legitimate purpose. The 1996 Anti-Terrorism Act permits the federal government to act quickly to prevent the potential use of a biological weapon.

The Anti-Terrorism Act of 1996 also established a regulatory framework for controlling the distribution of agents that could be used as biological weapons. Congress directed the Centers for Disease Control and Prevention (CDC) to develop a regime to identify those biological agents that could pose a high threat to human health as bioweapons and to institute a procedure that controls the transfer and use of those agents. CDC's regulations governing hazardous biological agents went into effect 15 April 1997. CDC identified 30 infectious agents and 12 toxins (Table 6) and established procedures that must be followed for tracking the transfer of these agents. Some transfers, namely those involving some vaccine strains and toxins for medical use and those to diagnostic laboratories, were exempted from regulation. Some law enforcement officials have proposed limiting possession of dangerous pathogens to a few researchers and laboratories licensed to have them. Congress and CDC are still assessing whether additional oversight for possession of certain agents is necessary to enhance the protective network against domestic bioterrorism. Table 6. Select agents whose shipment is regulated by the CDC under the Anti-Terrorism and Effective Death Penalty Act of 1996.

Type of agent Examples

Viruses(a) Crimean-Congo hemorrhagic fever virus, Eastern equine encephalitis virus, Ebola virus, equine morbillivirus, Lassa fever virus, Marburg virus, Rift Valley fever virus, South American hemorrhagic fever (Junin, Machopa, Sabia, Flexal, Guanarito), tickborne encephalitis complex viruses, variola major virus (smallpox virus), Venezuelan equine encephalitis virus, viruses causing hantavirus pulmonary syndrome, yellow fever virus

Bacteria(b) Bacillus anthracis, Brucella abortus, Brucella melitensis, Brucella suis, Burkholderia (Pseudomonas) mallei, Burkholderia (Pseudomonas) pseudomallei, Clostridium botulinum, Francisella tularensis, Yersinia pestis

Rickettsiae Coxiella burnetii, Rickettsia prowazekii, Rickettsia rickettsii

Fungi Coccidioides iminitis

Toxins(c) Abrin, aflatoxins, botulinum toxins, Clostridium perfringens epsilon toxin, conotoxins, diacetoxyscirpenol, ricin, saxitoxin, shigatoxin, staphylococcal enterotoxins, tetrodotoxin, T-2 toxin

a Some vaccine strains of viral agents (Junin virus strain candid #1, Rift Valley fever virus strain MP-12, Venezuelan Equine encephalitis virus strain TC-83, Yellow fever virus strain 17-D) are exempt from regulation.

b Vaccine strains as described in Title 9 CFR 78.1 are exempt from regulation.

c Toxins for medical use, toxins that have been inactivated for use as vaccines, or toxin preparations for biomedical research whose [LD.sub.50] for vertebrates is more than 100 nanograms per kilogram body weight are exempt, as are national standard toxins required for biological potency testing as described in Title 9 CFR Part 113.

Together, export control and the CDC regulations may help to reduce the risks of domestic and international bioterrorism. But because the agents that can be used for producing biological weapons are naturally occurring disease-causing microorganisms and toxins, such regulations can only make it more difficult, but not impossible, to obtain biological weapons. Terrorists will still have sources for obtaining agents for producing biological weapons, and the threat of bioterrorism will remain. Human intelligence and cooperation by the scientific and health communities will be essential for helping to expose any such activities and for preventing a bioterrorist attack.

Biodefense systems and public health responses

The best way to combat biological warfare and terrorism is to be prepared to respond to a biological weapons attack (Simon 1997). By improving our readiness to respond to biological weapons, many lives can be saved and terrorists denied their goal of creating panic and crisis throughout the country. Biodefense systems and public health responses are urgently needed to protect against deadly disease outbreaks initiated by bioterrorists.

If biological weapons were used by a terrorist, the current public health system would be overwhelmed. Bioterrorists could inflict mass civilian casualties anywhere in the world. The release of a biological weapon could go undetected for hours, days, or even weeks; the release would then be followed by mass illnesses, necessitating a first line of response by the public health community.

Limiting the spread of disease and minimizing the number of casualties following a biological weapons attack on civilian targets will depend on health care workers and first responders knowing what to do, on ensuring that those individuals are protected themselves, and on having available the right facilities and medicinals in sufficient quantities to treat everyone who has been exposed (Atlas 1998a). Elements of preparedness include vaccinating military personnel against anthrax and other diseases caused by biological weapons; developing methods for the rapid detection of biological threat agents; developing and stockpiling vaccines and antimicrobial drugs that could be used to protect the public against diseases caused by biological weapons; training first responders, who are likely to be physicians and emergency room workers, in how to deal with a biological weapons attack; and improving public health surveillance systems by strengthening diagnostic laboratory capacity and epidemiological capabilities, including enhancing communication within the medical and public health communities (Atlas 1998b).

President Clinton has announced that defending the United States against biological weapons must be a top national priority. He has stated that the possibility that rogue nations and terrorist groups will seek to use biological weapons represents one of the greatest threats to American security in the twenty-first century. At the Administration's request, Congress approved more than $300 million in additional funds in the FY 1999 budget for weapons of mass destruction preparedness. The initiatives include the renovation of the public health surveillance system so medical personnel can save lives via early detection of a biological weapons release and the establishment of civilian medical stockpiles to treat those exposed to biological weapons.

As Russell (1997) discussed, it is harder to protect civilian populations than the armed forces against biological weapons. It is good (i.e., cost-effective) policy to vaccinate military personnel against various biological threat agents and to provide them with detection gear and protective masks and suits to limit the risks of exposure. But vaccinating the entire population would be too costly. Moreover, military medical personnel can be readily trained to recognize and treat casualties of a biological weapons attack; antibiotics, antiviral drugs, and antitoxins can be stockpiled for military contingencies. Providing similar specialized training for the general medical community and having adequate supplies of medicinals in every area that might be attacked by bioterrorists is a far more daunting task.

Additional training and resources are also needed to enhance diagnostic capabilities. Early detection capability is an essential tool in cases of suspected uses of biological weapons. The sooner a bioterrorist attack is detected, the faster the medical community can respond to prevent additional exposure and to begin treatment of those who have been exposed. It has been recommended that the federal government develop and distribute appropriate detection equipment and protective gear to military units, including the National Guard (Tucker 1997). The military may be involved in biodefense efforts to protect the civilian population. The Defense Advanced Research Projects Agency is funding major research programs for the development of early detection units and other ways of protecting against biological weapons (Stephenson 1997). Promising new biological detection technologies, such as chip-based arrays of DNA probes and optical sensors, are currently under development (Cheng et al. 1996). Some new-generation diagnostic methods (e.g., pulsed field gel electrophonesis and polymerase chain reaction [PCR]) are already widely available and used in state and local health departments to subtype and compare strains of infectious agents against national electronic databases (molecular fingerprinting). Field PCR detection kits have been developed, and various other methods are being tested that would provide military troops or first responders with adequate warning of an incoming biological weapon attack to allow them to put on protective gear.

Assuming that detection is rapid enough, medical treatments can greatly lower the mortality rate for most, although not all, biological weapons. Many, if not most, diseases caused by biological weapons present nonspecific signs and symptoms that could be misinterpreted as natural occurrences of these diseases. Although the diseases that are caused by biological weapons are rarely seen by physicians in many countries today, accepted diagnostic and epidemiological principles apply. Franz et al. (1997) at United States Army Medical Research Institute of Infectious Disease (USAMRIID) have produced a primer on 10 classical biological warfare agents to increase the likelihood that medical personnel will properly recognize them.

The medical response to the threat or use of biological weapons differs depending on whether medical measures can be used before or after exposure (Franz et al. 1997). If provided before exposure, active immunization or prophylaxis with antibiotics may prevent illness. Effective vaccines and antitoxins exist for several of the agents most likely to be used in a biological weapons attack. Additional vaccines and new therapies are needed, and some are under development. Active immunization will probably be the best way to protect military forces against a wide variety of biological threats. Consequently, the United States has instituted mandatory vaccination against anthrax for all military personnel, although some have refused the vaccines because of questions about their safety. New vaccines for anthrax, smallpox, and other biothreat agents are in development.

For the general public, there are currently insufficient supplies of medicinals and trained personnel to cope with a terrorist use of biological weapons. Public health officials have been calling for the stockpiling of antidotes, antimicrobials, and vaccines that could be used in the event of a biological weapons attack and for the development of new medical treatments for diseases caused by biological weapons agents (Henderson 1998). It will be especially important for the US Public Health Service and the Food and Drug Administration (FDA) to stockpile necessary medical equipment, nerve agent antidotes, and broad-spectrum antibiotic and antiviral drugs in major metropolitan areas to ensure the prompt treatment of casualties in the event of an incident of chemical or biological terrorism (Tucker 1997). Intervention protocols - developed jointly through federal, state, and local participation - can ensure that vaccine and drug distribution policies are based on scientifically sound criteria.

The Department of Health and Human Services will receive an additional $43.4 million for research and development to defend against biological weapons if President Clinton's FY 2000 budget is adopted - almost a 150% increase over funding in the FY 1999 budget. The bulk of the new funding - $30 million - will go to research on new vaccines for eventual use in the national medical stockpile. The program will include development of a new vaccine against smallpox, which although totally eliminated as a naturally occurring disease, is now considered a major bioterrorist threat. FDA will receive $13.4 million for enhanced regulatory review of vaccines and therapeutics. In addition, the National Institutes of Health will receive $24 million in new funding for research on diagnostics, vaccines, antimicrobials, and genomic research.

The US government has begun to develop the public health infrastructure for dealing with a bioterrorist attack. A national, coordinated plan of operations for law enforcement and the public health community is being devised that will provide extensive emergency health and medical services responses (Tucker 1997). Subtitle A of the Defense Against Weapons of Mass Destruction Act of 1997 established a Domestic Preparedness Program, which directs the President to enhance the capability of the federal government to prevent and respond to terrorist incidents involving weapons of mass destruction and provides for enhanced training of local first responders and for the formation of metropolitan medical strike teams in major cities around the country. Beginning in FY 1997, the administration initiated a program to equip and train first responders in the nation's 120 largest metropolitan areas. In the FY 2000 budget, President Clinton proposed more than $16 million in funding for the Metropolitan Medical Response Systems program, an increase of almost 400% over FY 1999 funding. Plans are also underway to involve the military in responding to a bioterrorist attack.

However, the real front line of defense will be the medical and public health community. To minimize the effects of a biological terrorist attack, health care professionals and public health authorities must be aware of the threat of biological warfare and terrorism - that is, they must have a heightened awareness that such an attack can occur. Physicians and other health care workers will be in the front line for remediation in the wake of such an attack (Lederberg 1997). They must, therefore, have an understanding of the agents that bioterrorists might use, especially of the different effects that may result from exposure by various routes, such as inhalation. Health care workers should be alert to any constellation of disease that might be the harbinger of an attack. According to CDC, however, the public health capacity to rapidly detect intentional releases of biological agents and respond aggressively to such releases is lacking in many critical aspects of the public health response capacity. The federal, state, and local public health infrastructure must be strengthened to ensure that each level of the system is primed to protect the health and security of US citizens.

In the FY 2000 budget, President Clinton is proposing that funding for improvements in the public health surveillance system and public health infrastructure increase by 22%, to $86 million. This investment in the public health infrastructure will translate to increased lab capacity, strengthened epidemiological capabilities for state and local health departments, and more resources for communications and information technology. For example, CDC will create a network of regional labs to provide rapid analysis and identification of select biological agents.

Clinical and public health laboratories should also be made more capable of making rapid diagnoses so as to minimize the impact of a bioterrorist attack. Consequently, it will be necessary to maintain supplies of diagnostic reagents for use in identifying rare syndromes and potential biological weapons. It is also important to develop and evaluate new diagnostics that will improve the speed and accuracy of the identification of biological weapons.

Rapid epidemiological investigation to identify the nature of the disease outbreak will be critical for limiting casualties in the event of a bioterrorist attack. Coordinated efforts between local and regional clinical public health laboratories and sophisticated diagnostic laboratories at the FBI, CDC, and USAMRIID will also be critical. A sound epidemiological investigation of any disease outbreak, whether natural or arising through bioterrorism, will be necessary to help medical personnel identify the pathogen and institute appropriate medical interventions. Documenting who is affected, possible routes of exposure, and the signs and symptoms of disease, as well as rapidly identifying causative agents, will enhance the ability to plan an appropriate medical and public health response.

Computer networks can aid in epidemiological investigations of unusual disease outbreaks (Woodall 1998). Rapid recognition of a biological weapons attack will be aided by the creation, at the state level, of high-speed computing networks to analyze large volumes of data and to communicate rapidly with local and federal health officials and other government agencies. The Internet provides the means for a truly global early warning system of disease outbreaks to which both government and nongovernment organizations and individuals can contribute. Disease surveillance systems must be electronically seamless, with rapid transmittal of data from clinical settings to local and state health departments and CDC. In addition, a system to ensure secure and coordinated communications between CDC and other government officials responsible for responding to the threat will be necessary.

Concluding remarks

As the public and the scientific community respond to the horrific threats posed by biological weapons, we must continuously evaluate the nature of the threat posed by terrorists and rogue states. We must take prudent steps to protect against biological weapons and to ensure that our responses effectively enhance global security. However, we must also make sure that actions to defend against biological warfare and bioterrorism do not detract from critical biomedical research and public health responses. Difficult political decisions are needed to achieve the right balance of protection. The biomedical and public health communities must provide the scientific underpinnings on which sound policies can be formulated to protect against biological warfare and bioterrorism.

Deterrence efforts will be key to preventing biological weapons attacks. Despite nearly universal international condemnation of biological weapons, several countries, including the former Soviet Union and Iraq, continued to carry out such weapons of mass destruction programs. UNSCOM has been unable to confirm the elimination of all Iraqi biological weapons capability, and despite US support of various programs in Russia, some experts fear a continuance of biological weapons programs begun in the Soviet Union. Strengthening the BWC can contribute to global security, but negotiations are difficult because of the need to balance the security benefits with the economic and political costs, including the need to protect confidential business information, biodefenses, and the continuance of legitimate biomedical research.

Regardless of the deterrence measures that are adopted to prevent biological weapons programs, rogue nations may continue to develop biological weapons, and bioterrorists may acquire these deadly weaponsu The dual nature of biological weapons makes true verification virtually impossible; defensive safeguards to protect military personnel and civilian populations will therefore be needed. There is a growing set of legal statutes aimed at criminalizing attempts to develop biological weapons. The provisions of the statutes and regulations are designed to avoid inhibiting essential biomedical research and diagnostic activities. Achieving this balance means that there will remain some loopholes by which microorganisms and toxins can be acquired for nefarious purposes.

In recognition of the fallibility of deterrence methods, intense efforts are underway to enhance the United States' defenses against biological weapons, including strengthening public health preparedness to deal with any terrorist attack using biological weapons. These efforts provide for training programs for first responders and for stockpiling of antidotes, antimicrobials, and vaccines to mitigate the impact of a bioterrorist attack. New antimicrobials, especially antivirals, and new protective vaccines are important components of biodefenses for both military and civilian populations. Improved detection methods and epidemiological capability to detect unusual disease outbreaks are also critical components of the public health infrastructure needed to protect against biological weapons. Given the threat of catastrophic terrorism, support must be provided to the public health community - its preparedness is essential to prevent mass casualties from bioterrorism. We must take all responsible steps to protect humanity against attacks with biological weapons.

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Ronald M. Atlas (e-mail: r.atlas@louisville.edu) is a professor of Biology at the University of Louisville, Louisville KY 40292. He is co-chair of the American Society of Microbiology task force on biological weapons.

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