Human Pathogens of Potential Use in Bioterrorism
Toxins
Biodefenses
Agroterrorism
Recommendations
Final Considerations
Bioterrorism is the term used to descibe the offensive employment of biological substances or toxins with the objective of causing harm to an individual or a group of individuals. These activities, in general, cause damage, intimidation, or coercion, and are usually associated with threats causing public panic. The most common biological agents used as weapons are microorganisms and their associated toxins, which can be used to promote disease or death in people, animals, and even plants. The agents of contamination can be dispersed in the air, water, food, and elsewhere.
Bioterrorism has been a problem throughout human history. One of the first reports of bioterrorism dates back to the 6th century B.C., when the Assyrians poisoned the wells of their enemies with ergot, a toxin-producing fungus often found in rye. A more recent report suggests that in the 1500s, Pizarro, in the conquest of South America, gave clothes contaminated with smallpox to native Indians. Another similar report alleges that Britain might have used pathogens to weaken their opponents during the colonization of North America. The country might have deliberately distributed blankets contaminated with smallpox to Native Americans. Terrorism using chemical or biological weapons often spreads quietly, but it can have devastating impacts.
The first convention banning biological weapons was signed in Geneva in 1925. In 1972, under United Nations leadership, 103 countries signed the Convention on Biological Weapons, which prohibits the development, production, stockpiling, and use of biological weapons. The objective of this convention was to completely eliminate the use of biological agents and toxins as weapons of mass destruction.
During a conference on bioterrorism held in San Diego, California in early 2000, experts concluded that the United States was not prepared for a biological attack with pathogens such as smallpox, anthrax, Ebola, botulism, and others. At the second National Symposium on Bioterrorism in Washington, DC in 2000, one of the conclusions was that the American public health system was not prepared to respond to an attack with biological weapons. Additionally, in March 2001, researchers at the Center for the Study of Bioterrorism and Emerging Infections at the St. Louis University School of Public Health revealed that 75 percent of health agents feared that some city in the United States would suffer an attack with biological weapons within the next 5 years. The forecasts by the experts were correct: In October 2001, just four months after the meeting, the United States had its anthrax attack.
Anthrax and especially smallpox are considered the most serious threats of biological bioterrorism, due to the high fatality rate among infected individuals, the possibility of transmission in an aerosol form, and the relative ease of large-scale production. Various government-sponsored biological warfare programs have researched many other pathogens as well (Table 13-1).
Table 13-1. Biological Warfare Programs in Different Countries
Country | Status | Period | Disease | Observation |
|---|---|---|---|---|
Canada | Stopped | 1941–1960? | Anthrax, bovine pest | Exact date of termination not known |
Egypt | Stopped | 1972–present | Anthrax, brucelosis, mormo (Malleomyces mallei), psittacoses, equine encephalitis | |
France | Stopped | 1939–1972? | Potato beetle, bovine pest | Exact date of termination not known |
Germany | Stopped | 1942–1945 | Anthrax, foot and mouth disease, mormo (Malleomyces mallei), potato beetle | During World War II also used other agents |
Iraq | Active | 1980–present | Aflatoxin, anthrax, camel smallpox, foot and mouth disease, wheat rust | Suspected to still have an on-going program |
Japan | Stopped | 1937–1945 | Anthrax, mormo (Malleomyces mallei) | During World War II also used other agents |
North Korea | Active | ?–present | Anthrax | |
Rhodesia | Stopped | 1978–1980 | Anthrax | An anthrax epidemic resulted in 182 human deaths |
Syria | Active | ?–present | Anthrax | |
United Kingdom | Stopped | 1937–1960? | Anthrax | Exact date of termination not known |
United States | Stopped | 1943–1969 | Anthrax, brucelosis, equine encephalitis, foot and mouth disease, mormo, potato blight, new castle disease, psittacoses, rice blight, bovine pest, wheat rust | |
Soviet Union | Stopped | 1935–1992 | Anthrax, African swine fever, poultry flu, brucelosis, contagious bovine pneumonia, contagious ectima, foot and mouth disease, mormo (Malleomyces mallei), corn rust, new castle diseases, potato virus, psittacoses, bovine pest, rice blight, TMV, Venezuelan equine encephalitis, wheat and barley viruses | Also researched with insects and other agents |
The list of pathogens with potential terrorist applications ranges from salmonella to supervirulent (highly infective) strains of the bacteria that causes bubonic plague (Yersinia pestis) genetically modified by recombinant DNA technology. There are also toxins such as ricin, the organic phosphorous sarin gas, or the Ebola virus. Recently, the North Atlantic Treaty Organization (NATO) listed 39 biological agents that could be used as weapons by terrorists.
A wake-up call for the risk of bioterrorism occurred when sarin, a gas affecting the nervous system, was used in an attack carried out by the religious cult Aum Shinrikyo in a Tokyo subway in 1995. Interestingly, according to the Monterey Institute of International Studies (http://www.miis.edu), of more than 100 other terrorism acts recorded since 1960, the great majority has failed. However, interest in bioterrorism has increased significantly after the anthrax cases that occurred in late 2001. The U. S. Department of Health spent, as of the last decade, about $160 million annually on bioterrorism prevention. After the September 11 terrorist attack and the anthrax cases that followed, it is believed that investments in this area will rise substantially with an increase in the reality of terrorist threats.
As discussed, biotechnology can be used in the development of pathogens with higher virulence and increased antibiotic resistance, when in the wrong hands, but the science can also be used in the development of biodefenses as well. Early warning indicators, more precise diagnostic procedures, therapy, vaccines, pathogen identification, and new pharmaceuticals are only some of the areas in which biotechnology can be of help in the area of bioterrorism.
The main objectives in preventive bioterrorism are the production and stockpiling of vaccines and the development of early warning systems in the event of an attack. Genome sequencing also promises to facilitate the development of biodefenses and decontamination. An ongoing project at the University of Michigan is developing a mechanism to kill anthrax, using a solution of droplets of soybean oil in aqueous suspension. The droplets of this emulsion fuse with the bacterial membrane by means of a chemical reaction, thereby generating sufficient energy to destroy bacterial spores. Another interesting area of research is the production of synthetic antibodies to improve the treatment of infection.
Experts know that most of the progress in biotechnology is not only useful to combat biological agents spread intentionally, but also for naturally occurring disease epidemics. Considering that the real threat of bioterrorism is present worldwide, preventative measures are catching the attention of governments and of the public.
The use of bioweapons requires the cultivation, purification, stabilization, and large-scale production of the pathogen, as well as the development of an efficient means for dispersal. For instance, the dispersion of bacterial spores with a size ideal for uptake into the bronchioles of the lung can be an additional challenge for terrorists without scientific knowledge. Experts believe, however, that it is not difficult to find leads to bioterrorism programs in the international market. It is widely believed that thousands of trained scientists with expertise in biological warfare lost their jobs after the collapse of the former Soviet Union in December 1991.
The most dangerous bioweapons are contagious organisms with tolerance to extreme climatic variations and a long incubation period. This could include human viruses, bacteria, and fungi. Although the epidemic risk is significant with some of these microorganisms, past attempts to use biological agents have had limited success, mainly due to the complexity of the interaction of these microorganisms with the environment. Air humidity and temperature do not always favor the development and growth of the pathogen. The following sections cover pathogens with the potential to be involved in bioterrorism.
The bacterium Bacillus anthracis is an infectious and deadly pathogen, but it is not contagious. This bacterium can be easily found in farms, where it infects cattle and other animals. Children and adults can show three clinical forms of the disease: cutaneous (Figure 13-1), inhalation, or gastrointestinal. The symptoms and signs of anthrax in children and adults are similar, and they usually are seen about seven days after the infection. Because symptoms mimic those of the flu, the correct clinical diagnosis could be difficult, requiring specific laboratory analyses.
Most scientists agree that only individuals with access to advanced biological resources can produce anthrax for aerosol dispersion. The literature reports that an accidental dispersion of Bacillus anthracis spores in 1979 in the former Soviet Union caused the death of 68 people. The U.S. Centers for Disease Control and Prevention (CDC), the governmental agency in charge of monitoring public health, recorded 18 confirmed cases of anthrax in 2001, including seven cutaneous infections and 11 cases of inhalation infections, five which resulted in death. These cases were associated with mail contaminated with spores of the pathogen, sent to different governmental and television personalities (Figure 13-2). The FBI has not ruled out the possibility that international terrorists or domestic fanatics sponsored these events. This agency is also following up on the possibility that the anthrax cases could be associated with individuals who might have profited from the attacks.
Smallpox is a contagious viral disease that has been virtually eradicated from the world since 1980. Since that time vaccinations have nearly ceased around the world, placing the entire population at risk of epidemics. This single disease caused the death of 300 million people during the 20th century. A small stock of this virus was maintained in the United States and in Russia for biomedical research. According to the World Health Organization (WHO), it was supposed to be destroyed in 2002. Scientists believe that smallpox represents the single largest risk of human mortality in case of an outbreak of the disease. In the United States, vaccination for smallpox ceased in 1972. Therefore, the current American population under the age of 30 doesn't have the benefit of the vaccination at all. An enormous portion of the population would thus be susceptible to the disease.
Currently there are about 12 million doses of smallpox vaccines in the United States, which is enough for less than 5 percent of the population. However, it is expected that by the end of 2002 government will have approximately 280 million doses, produced through the benefits of biotechnology.
Vibrio choleare, the bacterium that causes cholera, was endemic in many parts of the world until a few decades ago. This bacterium is frequently found in untreated water. Usually, this disease is not transmitted from infected patients.
In 1997, the Rajneeshee cult in Oregon contaminated salads with Salmonella enteritis with the goal of affecting the results of the presidential election. However, this bacterium is not considered dangerous enough to be used as a serious weapon by terrorists. Contaminated food can be quickly removed from the market, and the mortality rate is low among patients.
There are different avenues of infection by the bacterium Clostridium botulinum: through food, in intestinal ulcers, or by inhalation. This inhalation form causes facial paralysis after the third day of infection. An effective treatment depends on early diagnosis and the administration of an antidote. If undiagnosed, the botulism toxin produced by the bacteria can be fatal.
Most developed countries have eradicated poliomyelitis, the disease also known as polio. However, some countries in Africa still struggle to wipe out this disease. The WHO estimates that polio will be eradicated from the world by 2005.
The Ebola virus was first detected in 1976 in the Democratic Republic of Congo (formerly Zaire) near the Ebola River. This virus destroys the human immune system, causing death in about 90 percent of those infected. Unfortunately, there is no known cure for this disease. The principal symptoms are fever, chills, anorexia, nausea, exhaustion, hemorrhagic conjunctivitis, and widespread hemorrhaging. Recently, two epidemics were identified in Gabon and in the Democratic Republic of Congo.
For hundreds of years Indians have added bacteria, fungi, algae, and plant and animal toxins and venoms to weapons to increase their efficacy. These substances started to draw the attention of military forces before World War II. However, the military soon lost interest because of the low stability of these substances and the difficulty of large-scale use. However, recombinant DNA technology, when improperly used, could be applied to modify genes that code for these toxins, so that the recombinant toxin is more stable, more potent, and consequently more destructive. Although toxins are not considered substances for large-scale use, they have been used in some isolated incidents and in a few common crimes. These toxins are listed in Table 13-2.
Table 13-2. Biological Agents Used as Weapons
Agent | Traditionally Used in Warfare | Used in Bioterrorism and Common Crimes | |
|---|---|---|---|
Pathogen | Bacillus anthracis | Ascaris suum | Salmonella typhi |
Brucella suis | Bacillus anthracis | Vibrio cholerae | |
Coxiella burnelli | Coxiella burnelli | Ebola virus | |
Francisella turalensis | Giardia lambia | Yellow fever virus | |
Smallpox virus | Rickettsia prowazekii | Yersinia enterocolica | |
Viral encephalitis | Salmonella typhimurium | Yersinia pestis | |
Ebola virus | |||
Yersinia pestis | |||
Toxin | Botulin | Botulin | Snake venom |
Ricin | Cholera | Tetradotoxin | |
Staphylococcal | Ricin | ||
Produced by Clostridium botulinum (mentioned previously), this is the most dangerous known toxin. C. botulinum usually grows in spoiled canned food. The incubation period of botulism is from one to three days, after which the victim manifests stomach aches, diarrhea, vision problems, and muscular fatigue. Eventually, the respiratory system becomes paralyzed, resulting in suffocation and death a few days after contamination. The toxin exists in seven different forms. The LD50 (or lethal dose for 50 percent of the population) for an average man is estimated to be less than 1 µg if ingested, and even less if inhaled. Just 1 g of botulism dispersed in the air can kill 1 million people. Vaccines for botulism are available, and they are the best form of protection for the population. But once an individual has inhaled the toxin, an effective antidote does not yet exist. The antidote is effective only in cases of ingestion, and it should be taken immediately after contamination. Despite its toxicity, forms of the botulism toxin have been produced for treatment of some muscular disorders.
This is a toxin present in the seeds of the castor bean (Ricinus communis). In 1978, it was used in the case of the “Umbrella Murder” in London, when it was used in a bullet to kill a fugitive from Bulgaria. Ricin inhibits protein synthesis in the human body. Through genetic engineering, ricin has also been produced in Escherichia coli transformed with the toxin gene. This is being used in the investigation of liver cancer therapies.
These fungal toxins are produced by Fusarium species of fungus. It is believed that these were used in the 1980s in Southeast Asia under the name yellow rain.
Produced by the bacteria Staphylococcus aureus, this is the most common substance associated with food poisoning. The toxin is water soluble and relatively thermally stable, withstanding boiling. Individuals exposed to 20 to 25 g of this toxin manifest colic, nausea, and diarrhea within a few hours after ingestion.
This small toxic molecule is produced by cyan-blue algae. It attacks the nervous system and can cause paralysis. LD50 for humans is 1 mg. Marine scientists have observed mass deaths of humpback whales and other sea life caused by saxitoxin. Although the cause of death has been initially blamed on pollution, as none of the animals showed any signs of disease following postmortem examination, death was later associated with saxitoxin poisoning. Symptoms include dizziness, diarrhea, vomiting, disorientation, respiratory distress, and eye irritation.
Sequencing the genome of pathogens allows the development of more efficient vaccines. In April 2000, the Pasteur Institute in France sequenced the genome of the bacterium Mycobacterium leprae, the causal agent of leprosy. The genomic sequence was also obtained for many pathogens, including Plasmodium falciparum (malaria), Corynebacterium diphteriae (diphtheria), Neisseria meningitidis (meningitis), and Enterococcus faecium (an antibiotic-resistant infectious bacteria), promising to accelerate the development of new weapons against these diseases. The knowledge of the genomic sequence of the pathogens allows scientists to identify their weaknesses, making it possible to develop not only vaccines but also more efficient therapies.
The production of vaccines in recombinant microbes, animals, or plants has been drawing great interest from public health agencies. The WHO has been recommending the use of vaccines as one of the most efficient strategies for disease prevention. Although vaccine research represents only 3 percent of total pharmacological research and development funds, it is considered to possess an excellent cost–benefit ratio.
Plants have been considered an excellent means for the production of recombinant vaccines because they are easily propagated and the vaccines can be expressed and in seeds or fruits. This method bypasses any risks of contamination from animal pathogens such as viruses that can also infect humans. Plant tissue expressing the vaccine can be used directly for human consumption, as an edible vaccine. This alternative would also eliminate the need for purification and refrigeration, which is currently required for most vaccines.
Research with edible vaccines has been focused on gastrointestinal diseases, caused by Escherichia coli, Vibrio cholerae, Norwalk virus, and rotavirus. Hepatitis B, Type I diabetes, and autoimmune diseases have also been subjects of investigation. One of the main aspects still to be understood with edible vaccines is how to gauge the correct dosage of plant tissue that should be ingested to provide sufficient immunity. It is important to recognize that the transgenic varieties in development for production of vaccines, antibodies, or any other pharmaceutical should be considered a medicine and not a food for general use.
Biotechnology can help in the immunization of the population and the consequent eradication of diseases with transgenic edible vaccines. Banana and potato plants genetically modified to express vaccines are being developed in different institutions. These vaccines can have an important role in immunization against disease because they require no special storage conditions and they could be grown and processed in the area in which they are needed. One of the inconveniences with these products is that they should not be cooked before consumption, because cooking tends to break down the vaccine.
Until September 11, 2001, the date of the terrorist attacks on New York City and Washington, DC, the fear of terrorism was limited in the Western world and its risk was associated primarily with airliners. More recently, the government is considering all forms of terrorism. Some of the possible targets of terrorism include nuclear plants, large buildings, national monuments, water reservoirs, and the food supply. This brings up the threat of agroterrorism. Agroterrorism can be defined as the deliberate and malicious use of biological or chemical agents as weapons against agriculture, and more specifically, the food supply. The destruction of the food supply or its contamination with noxious agents can disrupt people and nations.
The safety of the food industry, including farming, processing, and distribution should be considered a matter of national security. Even so, the food industry is vulnerable to sabotage in nearly all steps of the production chain (Figure 13-3). Because of this, most scientists agree that the risk of an agroterrorism act cannot be precisely measured.
Recent epidemics, such as the case of mad cow disease in Britain and of foot and mouth disease in different countries, supply important empirical data for the simulation of impacts from an agroterrorist attack. The mad cow epidemics revealed that the economic impact of this disease reached not only to the agriculture industry, but also to tourism and other industries, and the effects continued outside the borders of the epidemic. It is believed that an agroterrorist attack could have a much larger impact than natural epidemics, because they are deliberately planned to do harm. Experts suggest that the damage from an attack would depend on the time required to diagnose the problem. An early warning system might be as important as the means to counter the attacks. As the food production chain is extremely complex, with several steps (Figure 13-3), there are many vulnerable points that could disrupt the food industry.
Some of the catastrophes that have happened in agriculture might shed some light on the complexity and fragility of this industry. In 1970, the plant pathogen Bipolaris maydis (Helminthosporium maydis; Figure 13-4) destroyed hybrid corn fields across the United States. This disease, resulting in damage of about $1 billion, affected all corn hybrids possessing T cytoplasm. In Belgium, the contamination of beef, dairy products, milk, chicken, pork, fish, and eggs with dioxin, a cancerous substance, resulted in a ban of Belgian produce around the world. The economic loss to Belgium was estimated to be approximately $1 billion.
Source: Courtesy of USDA-ARS, photo by Keith Weller.
Figure 13-4. Healthy corn leaf (left) and one infected with Bipolaris maydis (right).
Several cases of agroterrorism are also worth mentioning:
The 1974 attack by the group Revolutionary Palestinian Commando, which allegedly contaminated a shipment of Israeli grapefruits to Italy.
The 1978 attack by the Revolutionary Palestinian Council on citrus orchards in Israel using mercury.
In 1999 and 2000, eggs produced in Israel were contaminated with salmonella. In this last attack, two people died and many were hospitalized.
There are suspicions that in 1989, a radical group released Mediterranean fruit flies in California to protest the use of insecticides. This insect caused serious financial loss to Californian citrus farmers that year, but no one was charged. There are suspicions that the cotton Boll weevil (Anthonomus grandis) was intentionally introduced into Brazil in the 1980s to interfere with national cotton production. When economic and political interests are involved, one cannot doubt that unscrupulous groups could be willing to use these strategies.
During World War II, the United States, the Soviet Union, Japan, Britain, and Canada studied several animal and plant pests with warfare objectives. Anthrax, brucelosis, foot and mouth disease, equine encephalitis, wheat rust, and several other pests were studied (see Table 13-1). Although the reports in the literature are contradictory, there is evidence suggesting that Japan used animal and plant pathogens against the former Soviet Union during World War II. In 1972 the United States, Soviet Union, England, and Canada signed the Biological and Toxic Weapons Convention, an international treaty to ban an entire class of bioweapons. Some countries, such as Iraq, have not yet signed on to this convention.
The low technological level and simplicity of the equipment required for an agroterrorism program make underground activities extremely difficult to detect and monitor. A technician with limited training in microbiology can isolate and multiply pathogenic microorganisms in a backyard laboratory. However, an efficient attack requires the acquisition, multiplication, and processing of a biological agent. Furthermore, it requires the development of an efficient distribution mechanism and techniques to account for unfavorable environmental conditions (air humidity, temperature, winds, etc.). The failure of most of the previous attacks with biological agents has been attributed to inadequate weather conditions for the released agent to infect its host, multiply, and start secondary cycles of the disease. Although most countries have some type of restriction for the introduction of pathogens, it is possible, under the guise of research, to acquire many of these biological agents from several international laboratories.
Although it is impossible to predict where, when, or what kind of bioterrorism poses the next threat, many scientific societies have come up with recommendations for the government, including the following:
Sequence the biological pathogens that are a risk to be used as a bioweapon. This is useful to determine successful strategies to combat the effects of the pathogen.
Stimulate functional genomics research to understand virulence, pathogenicity, and biology of pathogens.
Develop tools for rapid, accurate diagnosis.
Use broad-based, durable resistance in new crop varieties.
Improve the understanding of host–pathogen interaction at a molecular level.
Perform surveillance of pest outbreaks.
Increase research on pathogens for peaceful purposes.
Establish a real-time disease reporting system.
Develop a list of facilities and experts who are familiar with the pathogens.
Establish a biosafety committee.
Implement training programs for front-line responders and detectors.
Develop a network of diagnostic laboratories.
Develop a national center for agricultural control.
Increase efforts in global surveillance of emerging and high-risk diseases.
Although pathogens can be genetically modified to increase virulence and the capability of promoting an epidemic, there is no evidence that this has already occurred. However, this is no guarantee that the world is free from this risk.
As bioterrorism is a matter of national security, it is the responsibility of intelligence agencies to ascertain its real extension and potential. Some military experts believe that Iraq still possesses an active biowarfare program. A rare disease caused an epidemic in Iraqi wheat fields some years ago, arousing suspicion that a virulent pathogen had escaped from laboratories conducting bioterrorism research. Any preventive program in bioterrorism should involve intelligence, constant monitoring, early warning systems, information sharing among agencies, and cooperation among others. There should be laws in place that would allow the government to enforce quarantines of suspected infected individuals or goods, confiscation of properties, and use of hospitals to provide for the common good.
Finally, no one should assume that biology and the science of biotechnology will always be used for good. In states that sponsor terrorism, biotechnology could be used to develop pathogens and pests for mass destruction. Recent events have awakened our awareness to the global community in which we all live, and local events often have worldwide impact. It is important to be aware that the science of biotechnology, with all of its benefits, could also advance the unfortunate efforts of terrorism.
For more information on bioterrorism, visit the following Web sites:
American Biological Safety Association: http://www.absa.org
Biological Warfare Agents: http://www.emedicine.com/emerg/topic853.htm
Centers for Disease Control and Prevention: http://www.bt.cdc.gov
Department of Peace Studies, University of Bradford: http://www.brad.ac.uk/acad/sbtwc
International Security Information Service: http://www.isisuk.demon.co.uk
Center for the Study of Bioterrorism and Emerging Infections: http://www.slu.edu/colleges/sph/bioterrorism