Toxins: Potential Chemical Weapons from Living Organisms

Toxins: Potential chemical weapons from living organisms

Source: A FOA Briefing Book on Chemical Weapons.

Toxins are effective and specific poisons produced by living organisms. They usually consist of an amino acid chain which can vary in molecular weight between a couple of hundred (peptides) and one hundred thousand (proteins). They may also be low- molecular organic compounds. Toxins are produced by numerous organisms, e.g., bacteria, fungi, algae and plants. Many of them are extremely poisonous, with a toxicity that is several orders of magnitude greater than the nerve agents.

Toxins started to attract military interest already during the first half of the present century. At that time, it was difficult to manufacture sufficiently large amounts of toxin which caused interest to decrease. Many of the toxins discussed at that time were sensitive to heat and light which made them unstable and unpractical to use. The U.S.A. ended its toxin programme in the late 1960's and destroyed its stockpile of, e.g., botulinum toxin.

The Biological and Toxin Weapons Convention of 1972 prohibits the development, production and stockpiling of toxins as weapons. The 1925 Geneva Protocol prohibition of use of chemical and bacteriological weapons also covers the use of weapons based on toxins. Since the definition of chemical weapons includes toxins they are also covered by the Chemical Weapons Convention.

In the late 1970's, there was a rapid development of gene technology together with biotechnology. This led to the threat from toxins as CW agents again arising. Now it became possible to produce greater amounts of many toxins more easily, in some cases even synthetically. Gene technology can be used to modify the toxin genes so that the end product obtains new properties and, for example, may become less sensitive to sunlight.

Together with increased research into toxins, the bioregulators have also been studied and synthesized. Bioregulators are naturally- occurring substances, usually peptides, which participate in the physiological and neurological activities of the body. These substances can also be modified synthetically, whereupon they may obtain new properties.

The scientific and commercial development have together provided increased opportunities to incorrectly utilize biotechnology for military purposes. Recent research, for example, has made it possible to "target" toxins to different body organs or structures. This new knowledge mainly emanates from civilian research into, e.g., the treatment of cancer patients.

Toxins are still considered to be less suitable for dispersal on a large scale. Nonetheless, they could be used for sabotage or in especially designed inputs, e.g., against key persons. Since toxins have low volatility, they are dispersed as aerosols and then taken up foremost through inhalation. The new microencapsulation technology, which is easy to use, makes it possible to protect unstable toxins when dispersed.

Most toxins are unstable in alkaline water solutions and are thus easily destroyed by means of normal decontamination methods.

A few examples of toxins which may be used as chemical warfare agents are listed below. The trichothecenes, mycotoxins obtained from, e.g., Fusarium genera, were alleged in the early 1980's to have been used as CW agents in Southeast Asia ("yellow rain"), but are of no military value today.

Bacterial Toxins

Botulinum toxin, produced by the bacteria Clostridium botulinum, is the most poisonous substance known. The bacteria grows on, e.g., poorly preserved food and causes a severe form of food- poisoning (botulism). The incubation period is between one and three days after which the victim becomes ill with stomach pains, diarrhoea, disturbances to vision, giddiness and muscular weakness. The whole body including the respiratory musculature becomes paralyzed which leads to death by suffocation within a few days.

The toxin is a protein available in seven different forms, where the most poisonous is type A (molecular weight = 150,000 D). The lethal dose to man has been estimated to about one microgram if ingested and even less if inhaled. It is possible to vaccinate against botulism but once the victim has become poisoned there is no antidote. Botulinum toxin is today commercially produced and is used in treating squinting and other muscular disorders.

Not all toxins have a lethal outcome. One of those classified in the incapacitating group is Staphylococcus enterotoxin type B (SEB), which is produced by Staphylococcus aureus bacteria. SEB is the toxin which is most commonly found to have caused food poisoning.

SEB is a protein (molecular weight = 28,500 D), which is easily soluble in water and relatively stable. It can withstand boiling for a couple of minutes and when in freeze-dried state, it can be stored for more than one year. Persons exposed to SEB (20-25 g) fall ill after a few hours with typical food poisoning symptoms, such as stomach cramp, diarrhoea and vomiting. The sufferer frequently recovers without special treatment within 24 h.

Many toxins are produced by marine organisms. One such example is saxitoxin, which is synthesized by a type of blue-green algae (cyanobacteria). These algae provide food for different shellfish, e.g., mussels. The mussels themselves are not influenced by the poison, but human beings who later eat the mussels may become seriously ill.

Saxitoxin attacks the nervous system and has a paralyzing effect, but causes no symptoms in the gastro-intestinal tract. The development of the illness is extremely rapid and at high doses death may occur within less than 15 minutes. The LD50 for man is at about 1 mg. Saxitoxin is a small molecule with a molecular weight of 370 D. It is not sensitive to heat but is destroyed by oxygen.

Saxitoxin is included in Schedule 1 of the Chemical Weapons Convention.

Plant Toxins

The seeds of the castor oil plant can be used to extract a mixture of poisonous proteins, ricin. One of these has also been produced by Escherichia coli bacteria to which the ricin gene has been transferred.

Ricin became of interest as a CW agent at an early stage as it is relatively easy to produce in large quantities. In 1978, it was used in the "umbrella murder" in London where a ricin-treated bullet was used to shoot a Bulgarian defector who died within a day. Ricin is now included in Schedule 1 of the Chemical Weapons Convention.

Ricin poisoning occurs through blockages of the body's synthesis of proteins. The development is slow and includes decreased blood pressure. Death frequently occurs through heart failure.

Ricin has approximately the same toxicity as saxitoxin. Different forms of ricin bound to, e.g., monoclonal antibodies are being studied today in order to treat leukaemia and cancer of the liver.

Bioregulators

During recent years, discussions have started on the risk of bioregulators being used as CW agents. These types of substances do not belong to the group of toxins but are, nonetheless, grouped with them since their possible use is similar. They are closely related to substances normally found in the body and may be algogenic (causing pain), anaesthetic, or influencing blood pressure. A characteristic of them is that they are active in extremely low doses and frequently have rapid effect.

One example of this group of substances is Substance P, a polypeptide (molecular weight = 1,350 D) which is active in doses of less than one microgramme. Substance P causes, for example, a rapid loss of blood pressure which may cause unconsciousness.