Saturday, 13 June 2009

Introduction to Biological Weapons



Biological weapons (BWs) deliver toxins and microorganisms, such as viruses and bacteria, so as to deliberately inflict disease among people, animals, and agriculture. Biological attacks can result in destruction of crops, temporarily discomforting a small community, killing large numbers of people, or other outcomes.

The way that a biological weapon is used depends on several factors. These include: the agent itself; its preparation; its durability in the environment; and route of infection. Some agents can be disbursed as an aerosol, which can be inhaled or can infect a susceptible spot on the skin, like a cut or wound. Attackers can also contaminate food or water with some agents.

Biological weapons have a long history of use. In 1346, the invading Tartar army catapulted the bodies of plague victims into the Crimean Peninsula city of Kaffa and infected its citizens. In 1763, British troops under General Jeffrey Amherst gave the Delaware Indians blankets used by people with smallpox, possibly infecting the susceptible native population. Japan contaminated food and released plague-infected ticks during their conflict with China during World War II. The 2001 anthrax letter attacks in the United States infected 22 people and killed five.

Several differences set BWs apart from other weapons of mass destruction like nuclear and chemical weapons. The release of an agent is not immediately detectable. There are systems that detect biological agents, but most have a delay between acquiring the agent and identifying it.

The effects of an attack also are not immediately detectable. People may become exposed to an agent soon after its release, but the infection requires time to cause illness (the incubation period). Thus, one of the first indicators of a BW attack could be disease outbreaks.



The effect of BWs, disease, can continue after its release. If a transmissible agent, such as the smallpox or Ebola virus, infects a person at the site of its release, that person could travel and spread the agent to others. This would result in secondary infections at areas far from initial release and unprepared for the disease.

Two treaties have placed restrictions on biological weapons. The 1925 Geneva Protocol prohibits the use of chemical and biological weapons in warfare. Some signing countries declared that they would not honor it if their enemies, or the allies of their enemies, did not adhere to its prohibitions. The United States ratified the Protocol in 1975 after President Richard Nixon renounced the use of biological weapons in 1969.

The 1972 Biological and Toxin Weapons Convention restricts countries from developing, producing, stockpiling, or acquiring biological agents, weapons, and equipment outside of peaceful purposes. However, some signatory countries may be continuing weapons development, as the former Soviet Union did before its massive program was discontinued in 1992.

Although developing and using biological weapons once required support by nations, recent advances in biotechnology have made it easier to develop dangerous viruses, bacteria, and toxins with fewer resources. This has increased concerns that individuals and groups could resort to bioterrorism to attack a population.



Biological Weapon Production

Biological weapon production can be divided into several, general stages:
1) A biological agent must first be chosen and acquired. In the case of toxins, the production method must be acquired.
2) After growing and multiplying to sufficient quantities, various selection and modification procedures can alter certain traits and characteristics of the microorganism.
3) The agent is then prepared for delivery.

Choosing an agent requires matching the desired results of an attack with an agent's characteristics. Those characteristics may include: how much of an agent can cause disease (pathogenicity); time between exposure and illness (incubation period); how debilitating the resulting disease is (virulence); its lethality; and how readily the disease spreads to others (transmissibility). Countermeasures to the disease such as treatment and vaccination are also considered.

A pathogen can be obtained from two major sources: its natural environment and a microbiology laboratory or bank. When acquired from environmental sources such as soil, water, or infected animals, enough of the microorganism would have to be obtained to allow purification and testing of its characteristics. The difficulty in acquiring agents stored in labs and banks, such as the American Type Culture Collection, depends on accessibility to the pathogens, security for the facility, or security measures for the bank's ordering process. These agents are purified and of a known quality.



An alternative to acquiring agents is creating them. Toxins can be produced by adding the DNA coding for its production to bacteria. Also, advances in biotechnology have made it possible to synthesize certain viruses based on its genome, or an organism's genetic instructions, and using basic materials such as DNA. Dr. Eckard Wimmer first demonstrated this by re-creating the poliovirus in 2001, which was followed by Dr. Craig Venter's synthesis of the bacteriophage phiX174 in 2003 and the 2005 re-creation of the 1918 flu virus by Dr. Jeffrey Taubenberger and Dr. Terrence Tumpey.

Growing microorganisms requires providing optimal conditions. Living cells are required for the replication of viruses and some bacteria. Fungi, most bacteria, and other microorganisms can be grown in Petri dishes or fermentation vats. Although growing large amounts of an agent is possible, it can be limited by factors such as equipment, space, and safety concerns that arise from handling dangerous germs without appropriate safeguards. However, large amounts of an agent may not be necessary if the target population is small.



Modification of microorganisms through selection techniques and advances in genetic engineering could alter an agent so it will function in a particular manner. Agents modified for increased pathogenicity and a shorter incubation period could result in a more severe, fast-acting disease. Microorganisms that, under normal circumstances, do not infect potential targets could be modified to do so. Other changes could make treatments, vaccines, or the body's immune system useless.

Delivering an agent requires preparing it to remain effective when outside of its optimal growing conditions. Exposure to environmental stresses such as temperature, ultraviolet radiation, and drying can reduce the agent's activity. Some pathogens, like the anthrax bacteria, can encapsulate itself into a hardy, long-lasting spore not easily susceptible to those conditions.

Other agents require further processing that minimizes damage to it and allows it to retain its activity when dispersed. These procedures include: direct freeze drying (lyophilization); formulation into a special stabilizing solid, liquid, or gaseous solution; deep freezing; and powdering and milling. Once stabilized, the pathogens are ready for dispersal.



Many of the above manipulations require techniques and procedures that have been published in scientific literature. In addition, the equipment required for most procedures is available since legitimate researchers require them as well. This represents the "dual-use" problem, where the same knowledge and equipment used for beneficial work could also be used for more malevolent deeds.

The use of biological and chemical weapons is considered the most heinous type of warfare. When it was first tried on a large scale in 1915 at Ypres, France, against French, Algerian and Canadian troops, the German High Command had a hard time finding officers who would participate in the use of poison gas against an enemy. It was considered unchivalrous, indiscriminate, dangerous and possibly setting a precedent for reprisal. Not to mention illegal, under The Hague convention on rules of warfare.

Nowadays, the idea of taking advantage of the ability of bacteria to reproduce, mutate and produce toxins makes some experts fear the use of biological weapons more than nuclear weapons.



Here's a look at biological and chemical weapons, their history and application in warfare.

What are biological and chemical weapons?

Biological weapons are based on naturally occurring organisms that cause disease. The two most common examples are the bacteria Bacillus anthracis, which produces a toxin, and smallpox, a highly infectious viral disease.
Chemical weapons are poisons such as mustard gas and nerve gases like sarin.

How do biological and chemical weapons work?

Anthrax bacteria produce shell-like spores that allow them to live in a dormant state in soil. When used as a weapon, the spores enter the lungs where they are carried into the blood and immune systems. The spores become active, reproduce in large numbers and release a devastating toxin that is lethal to cells. If enough spores are inhaled, it can kill.


Chemical/
Organism
Symptoms Mortality Treatment
Sarin gas

Colourless, odourless gas. Attacks nervous system
Blurred vision, chest tightness, nausea, vomiting, convulsion, heart rate fluctuations, loss of consciousness, seizure, eventual paralysis and death Can kill within two to 15 minutes of exposure. Extremely toxic Compressed oxygen, forced oxygen mask. Immediate decontamination and life support
Anthrax

Two forms: pulmonary (more deadly) and cutaneous, relatively large, spore-forming bacteria found in soil
Initial symptoms are fever, malaise, fatigue then respiratory distress, septic shock If vaccinated before exposure and treated with antibiotics after exposure then good chance of survival. Death within 24 or 36 hours without vaccine and very quick, heavy dose of antibiotics Penicillin but bacteria may be resistant. Vaccines available
Smallpox

Highly infectious viral disease. Last recorded naturally-occurring case eradicated in 1977 after aggressive worldwide vaccination campaign
Influenza-like symptoms. Rash spreading over body. Pus-filled blisters develop. Complications: blindness, pneumonia, kidney damage Unvaccinated mortality rate is about 30 per cent Early treatment with vaccine (availability limited)
Ricin

Toxin derived from castor bean
Toxicity only exceeded by botulinus and tetanus toxins Nausea, muscle spasms, fever vomiting, convulsions, death. Fluid build-up in lungs leads to respiratory distress Takes effect in few hours, can kill in three days. No antitoxin or vaccine available
Botulism

Neurotoxin released by bacteria Clostridium botulinum
Most poisonous substance known. Associated naturally with rotting food in infected cans If toxin is ingested or breathed in, symptoms of nerve disruption occur. Cold, flu-like symptoms with trace of numbness in lips, fingertips, double vision, chest paralysis. Death from respiratory failure Untreated mortality nearly 100 per cent. Treated mortality 25 per cent. Recovery complete but slow (months). Quick administration of antitoxin essential
Pneumonic plague

Rare result of bubonic plague
Caused by infected flea bite. If turns into pneumonic plague then becomes contagious and virulent form of pneumonia. Symptoms include fever, chills, cough, difficulty breathing, and rapid shock 50 to 90 per cent if untreated; 15 per cent when diagnosed and treated for all plagues Antibiotic treatment as soon as possible
Tularaemia or rabbit fever

Biological infection of wild animals in the Northern Hemisphere in humans bitten by ticks by contact with infected animal tissue
Incubation period of 2 to 10 days. High fever, skin reaction where bitten or scratched, aching, swollen glands Fatal in about 5 per cent of cases. Without treatment, risk of death can jump to more than 30 per cent, depending on the form of the disease Treated with antibiotics. No vaccine available
Sources: AP, EPA, CDC

Who were the first to use biological weapons?

The history of biological weapons is surprisingly long. Almost as soon as humans figured out how to make arrows, they were dipping them in animal feces to poison them.



The Roman Empire used animal carcasses to contaminate their enemies' wells. This had the effect of both demoralizing their enemies and making them sick. And a demoralized, sick army is an easier one to beat. This strategy was used again in Europe's many wars, in the American Civil War and even into the 20th century.

Carthaginian leader Hannibal is credited with an interesting use of biological weapons in 184 BC. In anticipation of a naval battle with the Pergamenes, he ordered his troops to fill clay pots with snakes. During the battle, Hannibal sent the pots crashing down on the deck on the Pergamene ship. The confused Pergamenes lost the battle, having to fight both Hannibal's forces and a ship full of snakes.

In 1346, Tartar forces led by Khan Janibeg attacked the city of Kaffa, catapulting the plague-infected bodies of their own men over the city's walls. Using dead bodies and excrement as weapons continued in Europe during the Black Plague of the 14th and 15th centuries. Even as late as the early 18th century, Russian troops fighting Sweden resorted to catapulting plagued bodies over the city walls of Reval.

Biological warfare came to the New World in the 15th century. Spanish conquistador Pizarro gave clothing contaminated with the smallpox virus to natives in South America. Britain's Lord Jeffery Amherst continued the practice into the late 18th century, spreading smallpox among Native Americans during the French-Indian War by giving them blankets that had been used at a hospital treating smallpox victims.

In the First World War, the Germans used poison gas on their Eastern and Western fronts after 1915. They were also accused of infecting livestock with the bacteria that cause anthrax and glanders and shipping them to enemy countries, but no hard evidence of this could be found.

In 1918, the Japanese military formed a special unit to investigate biological weapons. Britain and the United States followed in 1942, even after the signing of the Geneva Convention prohibiting the use of chemical and biological weapons, because of fears that the Germans and Japanese were developing them. The U.S. ended its program in 1969.

In 1972, 103 countries signed the Biological Weapons Convention, which prohibited the development of biological and chemical weapons, as well as their use. Even so, both Russia and Iraq are known to have developed biological weapons since the convention.

The Biological Weapons Convention still allows for research into defences, such as vaccines, against biological weapons. Early in September 2001, the Pentagon announced it was developing a deadly new form of anthrax, for defensive research.



How easy are biological weapons to get and use?

The agents of biological warfare are surprisingly easy to find. Anthrax and botulism are caused by common soil bacteria. The smallpox virus, on the other hand, was eradicated in 1977, the only remaining cultures kept under tight security in Atlanta, Georgia and Koltsovo, Russia. Despite this, experts in biological weapons still consider smallpox a threat.

Some experts say the ease with which biological weapons can be created is their most frightening property. Dr. Leonard Cole, author of The Eleventh Plague told CBC Radio's Quirks and Quarks in 1998 that anyone with a basic understanding of microbiology and several thousand dollars' worth of equipment can start a bio-weapons lab.

But Michael Moodie, president of the Chemical and Biological Arms Control Institute, speaking with CBC Morning in September, said that developing biological weapons is not as easy as it is portrayed in the media.

Moodie says the resources of a government and scientific expertise are needed for a viable biological weapons program. Not only would a group have to isolate and culture an agent, but they would have to contain and deliver the agent.

Containing an agent is the most troublesome part of using biological weapons, and one of the most important reasons they haven't been widely used. The bacteria and viruses don't discriminate between an ally and a foe, and the so-called boomerang effect, the biological agent affecting those who released it, is a common occurrence.

Delivering a biological agent is difficult, as well. Spreading a disease through the air would most likely involve delivering it in an aerosol cloud. Any change in the weather would make the behaviour of that cloud completely unpredictable.



Threat

The list of agents that could pose the greatest public health risk in the event of a bioterrorist attack is short. However, although short, the list includes agents that, if acquired and properly disseminated, could cause a difficult public health challenge in terms of our ability to limit the numbers of casualties and control the damage to our cities and nation.

The use of biological weapons has occurred sporadically for centuries, culminating in sophisticated research and testing programs run by several countries. Biological weapons proliferation is a serious problem that is increasing the probability of a serious bioterrorism incident. The accidental release of anthrax from a military testing facility in the former Soviet Union in 1979 and Iraq's admission in 1995 to having quantities of anthrax, botulinum toxin, and aflatoxin ready to use as weapons have clearly shown that research in the offensive use of biological agents continued, despite the 1972 Biological Weapons Convention. Of the seven countries listed by the U.S. Department of State as sponsoring international terrorism , at least five are suspected to have biological warfare programs. There is no evidence at this time, however, that any state has provided biological weapons expertise to a terrorist organization .

A wide range of groups or individuals might use biological agents as instruments of terror. At the most dangerous end of the spectrum are large organizations that are well-funded and possibly state-supported. They would be expected to cause the greatest harm, because of their access to scientific expertise, biological agents, and most importantly, dissemination technology, including the capability to produce refined dry agent, deliverable in milled particles of the proper size for aerosol dissemination. The Aum Shinrikyo in Japan is an example of a well-financed organization that was attempting to develop biological weapons capability. However, they were not successful in their multiple attempts to release anthrax and botulinum toxin . On this end of the spectrum, the list of biological agents available to cause mass casualties is small and would probably include one of the classic biological agents. The probability of occurrence is low; however, the consequences of a possible successful attack are serious.



Smaller, less sophisticated organizations may or may not have the intent to kill but may use biological pathogens to further their specific goals. The Rajhneeshees, who attempted to influence local elections in The Dalles, Oregon, by contaminating salad bars with Salmonella Typhimurium, are an example. Rather than having a sophisticated research program, these organizations could use biological pathogens that are readily available.

The third type are smaller groups or individuals who may have very limited targets (e.g., individuals or buildings) and are using biological pathogens in murder plots or to threaten havoc. The recent anthrax hoaxes are examples of this. Many biological agents could be used in such instances and the likelihood of their occurrence is high, but the public health consequences are low.

There are many potential human biological pathogens. A North Atlantic Treaty Organization handbook dealing with biological warfare defense lists 39 agents, including bacteria, viruses, rickettsiae, and toxins, that could be used as biological weapons. Examining the relationship between aerosol infectivity and toxicity versus quantity of agent illustrates the requirements for producing equivalent effects and narrows the spectrum of possible agents that could be used to cause large numbers of casualities. For example, the amount of agent needed to cover a 100-km2 area and cause 50% lethality is 8 metric tons for even a "highly toxic" toxin such as ricin versus only kilogram quantities of anthrax needed to achieve the same coverage. Thus, deploying an agent such as ricin over a wide area, although possible, becomes impractical from a logistics standpoint, even for a well-funded organization . The potential impact on a city can be estimated by looking at the effectiveness of an aerosol in producing downwind casualties. The World Health Organization in 1970 modeled the results of a hypothetical dissemination of 50 kg of agent along a 2-km line upwind of a large population center. Anthrax and tularemia are predicted to cause the highest number of dead and incapacitated, as well as the greatest downwind spread .

For further indication of which pathogens make effective biological weapons, one could look at the agents studied by the United States when it had an offensive biological weapons research program. Under that program, which was discontinued in 1969, the United States produced the following to fill munitions: Bacillus anthracis, botulinum toxin, Francisella tularensis, Brucella suis, Venezuelan equine encephalitis virus, staphylococcal enterotoxin B, and Coxiella burnetti . As a further indication of which pathogens have the requisite physical characteristics to make good biological weapons, one need only look next at the agents that former Soviet Union biological weapons experts considered likely candidates. The agents included smallpox, plague, anthrax, botulinum toxin, equine encephalitis viruses, tularemia, Q fever, Marburg, melioidosis, and typhus . Criteria such as infectivity and toxicity, environmental stability, ease of large-scale production, and disease severity were used in determining which agents had a high probability of use. Both the United States before 1969 and the former Soviet Union spent years determining which pathogens had strategic and tactical capability.



The National Defense University recently compiled a study of more than 100 confirmed incidents of illicit use of biological agents during this century (W.S. Carus, pers. comm. [4]). Of the 100 incidents, 29 involved agent acquisition, and of the 29, 19 involved the actual nongovernmental use of an agent, and most were used for biocrimes, rather than for bioterrorism. In the context of this study, the distinguishing feature of bioterrorism is that it involves the use of "violence on behalf of a political, religious, ecologic, or other ideologic cause without reference to the moral or political justice of the cause." The balance of incidents involved an expressed interest, threat of use, or an attempt to acquire an agent. In the 1990s, incidents increased markedly, but most have been hoaxes. The pathogens involved present a wide spectrum, from those with little ability to cause disease or disability, such as Ascaris suum, to some of the familiar agents deemed most deadly, such as B. anthracis, ricin, plague, and botulinum toxins. During this period, the number of known deaths is only 10, while the total number of casualties is 990. However, the numbers should not give a false sense of security that mass lethality is not achievable by a determined terrorist group. The sharp increase in biological threats, hoaxes, information, and Internet sources on this subject seen in recent years indicates a growing interest in the possible use of biological pathogens for nefarious means .

In general, the existing public health systems should be able to handle most attempts to release biological pathogens. A working group organized by the Johns Hopkins Center for Civilian Biodefense Studies recently looked at potential biological agents to decide which present the greatest risk for a maximum credible event from a public health perspective. A maximum credible event would be one that could cause large loss of life, in addition to disruption, panic, and overwhelming of the civilian health-care resources .



To be used for a maximum credible event, an agent must have some of the following properties: the agent should be highly lethal and easily produced in large quantities. Given that the aerosol route is the most likely for a large-scale attack, stability in aerosol and capability to be dispersed (17 micro m to 5 micro m particle size) are necessary. Additional attributes that make an agent even more dangerous include being communicable from person to person and having no treatment or vaccine.

When the potential agents are reviewed for these characteristics, anthrax and smallpox are the two with greatest potential for mass casualties and civil disruption.
1) Both are highly lethal: the death rate for anthrax if untreated before onset of serious symptoms exceeds 80%; 30% of unvaccinated patients infected with variola major could die.
2) Both are stable for transmission in aerosol and capable of large-scale production. Anthrax spores have been known to survive for decades under the right conditions. WHO was concerned that smallpox might be freeze-dried to retain virulence for prolonged periods.
3) Both have been developed as agents in state programs. Iraq has produced anthrax for use in Scud missiles and conducted research on camelpox virus, which is closely related to smallpox . A Soviet defector has reported that the former Soviet Union produced smallpox virus by the ton . 4) Use of either agent would have a devastating psychological effect on the target population, potentially causing widespread panic. This is in part due to the agents' well-demonstrated historical potential to cause large disease outbreaks.
5) Initial recognition of both diseases is likely to be delayed. For anthrax, this is secondary to the rare occurrence of inhalation anthrax. Only 11 cases of inhalation anthrax have been reported in the United States from 1945 to 1994 , and recognition may be delayed until after antibiotic use would be beneficial. For smallpox, given that few U.S. physicians have any clinical experience with the disease, many could confuse it for more common diseases (e.g., varicella and bullous erythema multiforme) early on, allowing for second-generation spread.
6) Availability of vaccines for either disease is limited. Anthrax vaccine, licensed in 1970, has been used for persons at high risk for contact with this disease. The U.S. military has recently begun vaccinating the entire force; however, there is limited availability of the vaccine for use in the civilian population. Routine smallpox vaccination was discontinued in the United States in 1971. Recent estimates of the current number of doses in storage at CDC range from 5 to 7 million , but the viability of stored vaccine is no longer guaranteed.



Obtaining smallpox virus as opposed to other agents (e.g., anthrax, plague, and botulinum toxin) would be difficult, but if obtained and intentionally released, smallpox could cause a public health catastrophe because of its communicability. Even a single case could lead to 10 to 20 others. It is estimated that no more than 20% of the population has any immunity from prior vaccination . There is no acceptable treatment, and the communicability by aerosol requires negative-pressure isolation. Therefore, these limited isolation resources in medical facilities would be easily overwhelmed.

Anthrax can have a delayed onset, further leading to delays in recognition and treatment. In the outbreak of inhalation anthrax in Sverdlovsk in 1979, some patients became ill up to 6 weeks after the suspected release of anthrax spores . The current recommendation for prophylaxis of persons exposed to aerosolized anthrax is treatment with antibiotics for 8 weeks in the absence of vaccine or 4 weeks and until three doses of vaccine have been given . The amount of antibiotics required for postexposure prophylaxis of large populations could be enormous and could easily tax logistics capabilities for consequence management.

Other bacterial agents capable of causing a maximum credible event include plague and tularemia. Plague, like smallpox and anthrax, can decimate a population (as in Europe in the Middle Ages). An outbreak of plague could easily cause great fear and hysteria in the target population (as in the 1994 outbreak in India), when hundreds of thousands were reported to have fled the city of Surat, various countries embargoed flights to and from India, and importation of Indian goods was restricted . Both plague and tularemia are potentially lethal without proper treatment; however, the availability of effective treatment and prophylaxis may reduce possible damage to a population. Both are infectious at low doses. Pneumonic plague's person-to-person communicability and untreated case-fatality rate of at least twice that of tularemia make it more effective than tularemia as an agent to cause mass illness.



Other agents of concern include the botulinum toxins and viral hemorrhagic fevers. Once again, both are highly lethal. Botulinum toxin is a commonly cited threat, and Iraq has admitted to producing it. Since intensive care would be required in treating both illnesses and ventilator management is life-saving for botulinum, both would easily tax existing medical care facilities. However, botulinum toxin may be a less effective agent because of relatively lower stability in the environment and smaller geographic coverage than other agents demonstrated in modeling studies. Producing and dispensing large amounts are also difficult .

A number of different viruses can cause hemorrhagic fever. These include (but are not limited to) Lassa fever, from the Arenaviridae family; Rift Valley fever and Crimean Congo hemorrhagic fever, from the Bunyaviridae family; and Ebola hemorrhagic fever and Marburg disease, from the Filoviridae family. These organisms are potential biological agents because of their lethality, high infectivity by the aerosol route shown in animal models, and possibility for replication in tissue culture .



In summary, we know that biological pathogens have been used for biological warfare and terrorism, and their potential for future use is a major concern. Therefore we must be prepared to respond appropriately if they are used again. The technology and intellectual capacity exist for a well-funded, highly motivated terrorist group to mount such an attack. Although the list of potential agents is long, only a handful of pathogens are thought to have the ability to cause a maximum credible event to paralyze a large city or region of the country, causing high numbers of deaths, wide-scale panic, and massive disruption of commerce. Diseases of antiquity (including anthrax, smallpox, and plague), notorious for causing large outbreaks, still head that list. In addition, other agents, such as botulinum toxin, hemorrhagic fever viruses, and tularemia, have potential to do the same. By focusing on a smaller list of these low-likelihood, but high-impact diseases, we can better prepare for potential intentional releases, and hope to mitigate their ultimate impact on our citizens.

Many other pathogens can cause illness and death, and the threat list will always be dynamic. We must, therefore, have the appropriate surveillance system and laboratory capability to identify other pathogens, and we must improve our public health and medical capabilities to respond to the short list of the most dangerous naturally occurring biological pathogens that could be used as bioterrorism weapons.

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