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	Submitted By: Erin Curran
	Toxicology Spring ’00
	Dr. Jaeger

WEAPONS OF MASS DESTRUCTION – BIOLOGICAL WARFARE- CHEMICAL WARFARE. These words have become a familiar and frightening part of American vocabulary recently. We have witnessed some of their destructive power and live in fear of even more attacks with these weapons. There are large-scale efforts underway to stop the use of such weapons and protect ourselves in the event of their use. To fully understand the scope of the problem and the weapons themselves is a task in itself. They have many varieties and mechanisms of action. Recent events in the Persian Gulf and incidents of terrorism both in the US and abroad have brought chemical weapons into the focus of mainstream consciousness. Vigorous research is also being done to find medicinal values for some chemicals previously used as weapons. Ricin is an example of this.

What is a chemical weapon? In 1969 a UN report defined chemical warfare agents as "…Chemical substances, whether gaseous, liquid or solid, which might be employed because of their direct toxic effects on man, animals and plants…". The Chemical Weapons Convention made a further definition of chemical weapons. They included in the definition not only the toxic chemical itself, but the ammunition and equipment used for its dispersal. A toxic chemical is defined as "…Any chemical, which, through its chemical effect on living processes, may cause death, temporary loss of performance, or permanent injury to people or animals…" (OPCW).

Poisons produced by living things or synthetic equivalents thereof are considered chemical weapons if they are used for military purposes. These substances have a special characterization as the Biological and Toxin Weapons Convention of 1972 cover them. This convention put a ban on developing, producing and stockpiling these substances when they are not required for peaceful purposes (OPCW).

Chemical weapons are incorrectly termed war gasses. This came about because of the use of chlorine and phosgene during WWI. These chemicals are gasses at room temperature and atmospheric pressure. The chemical warfare agents of today are normally liquids or solids. There is still always some amount of the substance in gas form depending on the evaporation rate of the chemical. The liquids and solids can be dispersed in air in aerosol form. Just as gas, an aerosol can enter the body through the respiratory tract. Solids can penetrate the skin when mixed with the proper solvent (OPCW).

There are literally thousands of poisonous substances known today, but only a few of them that are deemed suitable for chemical warfare. There are about seventy chemicals that have been stockpiled or used as chemical warfare agents during the twentieth century. Today only a few of those are still being considered of interest for use as a weapon. This is because there are a number of criteria a chemical must meet if it is going to be used as a chemical warfare agent (OPCW).

A possible chemical weapon must be highly toxic, but not so much so that it cannot be easily handled. It must also be able to be stored for long periods of time without corroding its container. The chemical must be resistant to atmospheric water and oxygen so as not to be degraded during its dispersal. The chemical must also be able to withstand the heat generated during its dispersal (OPCW).

When a chemical agent is used against humans it is divided into lethal and incapacitating categories. A substance is considered incapacitating if less than 1/100 of the lethal dose will cause incapacitation. The division between incapacitating and lethal is not definite, but refers to a statistical average. For comparison, the ratio between the incapacitating and lethal doses of nerve agents is about 1/10. Chemical warfare agents are also characterized by the effects they have on the target organism (OPCW).

A chemical weapon can attack the body’s nerves, lungs, skin or blood and chemical weapons are loosely classified as to the effects they cause. They can cause tearing, blistering or vomiting, or cause hallucinations or loss of nervous control. Lethal chemical agents include vesicants that burn and blister the skin, eyes, and respiratory tract. Examples of vesicants are sulphur mustard and lewsite. Choking agents such as chlorine and phosgene irritate the eyes and respiratory tract. A blood agent such as hydrogen cyanide will starve the tissues of oxygen. Nerve agents will interfere with the nerve impulse transmission and cause convulsions and death due to respiratory paralysis. Examples of nerve agents include sarin and VX (CDISS).

Probably the most devastating effect that a chemical weapon attack may have, however, is the panic and terror caused by an attack or even the threat of an attack. Wholesale disruption or even paralysis of civil and economic activity occurs in the effected area (CDISS).

Toxins are specific poisons made by living organisms. They are highly effective due to their specificity. Toxins generally consist of an amino acid chain of several hundred to a thousand in molecular weight. They can be low-molecular organic carbons as well. Bacteria, fungi, algae and plants all produce toxins. These toxins can be very poisonous, some have toxicity orders of magnitude greater than nerve agents. The 1925 Geneva Protocol prohibited the use of chemical and bacteriological weapons. This protocol also covers the use of weapons based on toxins (CDISS).

The advances in gene technology and biotechnology in the 1970’s led to a resurgence in the threat of toxins being used as chemical warfare agents. This is due to the fact that the technology now made it possible to produce larger amounts of toxin more easily. Some toxins could even be made synthetically. Gene technology allowed the modification of toxin genes to make the toxin obtain new properties. Toxins are still not considered very suitable for large-scale dispersal. Most toxins are also unstable in alkaline water solutions and therefore decontamination is easy (CDISS).

Chemical weapons have many limitations. They depend heavily on the geographic and atmospheric conditions where they are released. Temperature, weather and terrain will affect the persistence of a chemical weapon. Large amounts of chemical are needed to produce a high lethality, and a majority of the chemical weapons degrade rapidly. The use of persistent chemicals prevents the use of the area unless decontamination is performed or protective equipment is used. This can be a problem if an army intends to invade an area they have just attacked. The area also cannot be used for peaceful purposes until the chemical is removed. Warning systems against chemical attacks tend too be fairly accurate and sensitive. They are better than the warning systems for biological weapons (CDISS).

In the past decade there has been a surge of terrorism. We’ve learned that terrorism can hit anywhere from a federal building in Oklahoma City to the World Trade Center to Israel or the Persian Gulf. A terrorist can look like your neighbor or an angry foreigner on a TV news report. We’ve learned that terrorism can be in the form of a bomb, a chemical or a bacterium. Chemical and biological agents are the new generation of terrorist weapons. The terrorist groups have proven that they can plan and execute attacks of this nature. The production of biochemical weapons appears to be spreading worldwide. FBI sources say that the scope of the threats is more complex and dynamic than those faced in the past. Several incidents in the recent past have led authorities to believe that would-be terrorists are trying to obtain and use chemical and biological weapons (ABC).

Recent Uses of Chemical and Biological Weapons

There have been some recent incidents of biological agents being used as potential weapons. In 1997 a national Jewish organization received in the mail a petri dish oozing a substance that was labeled Anthrax. A whole city block was cordoned off and people were quarantined in the building for a day. The incident luckily turned out to be a hoax. A microbiologist with ties to white supremacist groups ordered three vials of the bubonic plague by mail in 1995. The FBI seized the samples before he could do anything with it however. Federal laws were tightened in 1996 to avoid this kind of incident. It was reported Saddam Hussein had ordered supplies for his biological weapons program from the same supply house (ABC).

Chemical weapons have not been ignored. In 1995 Disneyland received a threatening note along with a video of someone mixing chemicals. The same year a religious cult killed a dozen people and injured many more with a release of Sarin into the Tokyo subway. The cult was found to be stockpiling other weapons and planning to attack New York and Washington D.C. (ABC).

One weapon that was used in the past and has once again gained popularity is ricin. In 1995 members of a Patriot organization were convicted of manufacturing ricin for the intent of killing law enforcement officers. They could have killed more than a hundred people with the amount of toxin they had. Authorities arrested a man in 1993 trying to enter Alaska with weapons, racist literature and a quarter pound of ricin. According to a federal anti-terrorism statute the unlicensed possession of ricin is a severe crime (ABC).

Ricin is an interesting poison. It is found in the seeds of the castor bean plant and is poisonous to animals and insects as well as humans. It is a potent cytotoxin, as little as one milligram can kill an adult. Ricin will inhibit the synthesis of protein by specifically and irreversibly inactivating ribosomes. The ribosome inactivating proteins are usually N-glycosylated with a molecular weight of 30 kDa. These monomers cannot enter the cell however. They require a second monomer, which is a galactose-binding lectin. These two monomers are joined by a disulfide bridge to form the toxic heterodimer. Once inside the cell the ricin will bind and depurinate a specific adenine of the 28s rRNA. The adenine ring will then be sandwiched between two tyrosines and be hydrolyzed. The lectin portion of the hetrodimer will bind glycoproteins and glycolypids on cell surfaces that terminate with a galactose. It has two galactose binding sites. As many as 106-108 ricin molecules can bind on a single cell. It only takes one molecule in the cytosol to inactivate over 1500 ribosomes per minute however (ANSCI).

Ricin is toxic by a number of exposure routes. It can be used to poison water supplies or food products. Projectiles can be laced with it. Liquid or powdered ricin can also be aerosolized. The aerosol will cause cell death in the lung tissues and pulmonary capillaries. This will lead to edema and hypoxic respiratory failure. Symptoms will appear about eight hours after the inhalation. The symptoms will include fever, cough, dyspnea, nausea and chest tightness. Sweating, edema, cyanosis and hypotension will develop later. Finally circulatory collapse and respiratory failure will lead to death within 36-72 hours. There is no specific treatment or antitoxin (Thinkquest).

The symptoms of oral ricin poisoning may manifest a few hours after ingesting the poison. The patient will suffer abdominal pain, be vomiting and have diarrhea. Within a few days after the ingestion of the poison the patient will suffer sever dehydration. The patient will also have a decrease in the output of urine and a drop in blood pressure. If the victim is not dead after 3-5 days they will usually recover (ANSCI).

Ricin is a favorite of terrorists and assassins because it is easy to make and ricin poisoning looks like pneumonia. All you need to make ricin is some castor beans, alcohol and paper towels. It is very risky to make ricin. People have been known to get some on their skin and die while trying to make it. The finished product can be put in anything from an air conditioner unit to a salt shaker. It is a suspected cause of Legionaires’ disease. Ricin is also almost impossible to determine as a cause of death (Coyote).

Ricin may be used for peaceful, medical purposes in the future. This is due to its incredible cytotoxic properties. When combined with a monoclonal antibody it can become a potent chemotherapy agent. The antibody is targeted to specific receptors on the cancer cell. When ricin is coupled to the antibody it will enter the cell when the antibody binds. This brings a level of specificity to chemotherapy that is not very common. This treatment has been effective for lymphoma and liver cancer. Phase I clinical trials of the ricin drug have been going on for ten years. Out of 200 patients treated 60% show evidence of tumor shrinkage with 30 to 40% of those showing partial or complete reduction (ScienceDaily).

One problem with growing caster bean for the ricin or the castor oil is the danger to the grower and processor from the ricin. Researchers at Texas Tech. are developing, by cross breading, a castor plant with a seed that has very little or no toxin and a bean with high levels of toxin. This would protect the growers and increase the yield of ricin. A two-acre plot of castor beans could possibly produce enough ricin to supply the pharmaceutical needs for chemotherapy (Coyote).

Research is also being done on a vaccine against the toxic monomer of the ricin protein. A second-generation vaccine is prepared using the deglycosylated subunit as an immunogen. This vaccine is being developed at the U.S. Army Medical Materiel Development Center at Fort Detrick in Maryland. Its purpose is to protect the U.S. forces from the use of ricin as a biological weapon (Thinkquest).

Hopefully a vaccine like this will never have to be used. We hope to live in a world where things like ricin and other chemical and biological weapons will not be used in war or for terrorist acts. Until that day comes we can only educate ourselves about these weapons in an effort to avoid the panic and hysteria that surround them.

http://abcnews.go.com/sections/us/terrorism_incidents/. Suspicious Incidents Raise

Concern. Accessed 3/16/00.

http://www.ansci.cornell.edu/plants/toxicagents/ricin/ricin.html. Ricin Toxin From Castor

Bean Plant, Ricinus Communis. Accessed 4/8/00.

http://www.cdiss.org/cw.html. Devil’s Brews in Detail. Accessed 3/16/00.

http://coyote.accessnv.com/tamonten/castor-bean.html. Castor Bean, Ricin and Assasins.

Accessed 4/8/00

http://library.thinkquest.org/21659/agents/ricin.html. Ricin. Accessed 4/8/00.

http://www.opcw.nl/chemhaz/cwagents.htm. Chemical Warfare Agents: An overview of

chemicals defined as chemical weapons. Accessed 3/16/00.

http://www.sciencedaily.com/releases/1998/10/981021075544.htm. Researchers Know Beans About Cancer Treatment. Accessed 4/8/00.