\Lpoison\ls, or toxins, substances that chemically interfere with the normal physiology and behavior of organisms, are pervasive in nature. Some form of poison is produced by almost every major group of organisms. Because plants do not have the options of running, hiding, or fighting to avoid being eaten, many plant species have developed some form of chemical deterrent to prevent their being fed upon by herbivores. Chemical weaponry appears in all major animal groups with the exception of the vertebrate class Aves, the birds. Toxins manufactured by animals are called \Lvenom\ls, plant-synthesized poisons are collectively known as secondary substances, and the toxins generated by microorganisms (algae, bacteria, and fungi) are technically referred to as \Tantibiotics\t, which have proved useful in the development of drugs. Natural poisons are rarely random products of living organisms with little biological activity. They are diverse, usually complex chemicals, many with highly specific modes of action that have evolved by natural selection in the ecological contexts of defense, competition, and exploitation. In most cases, these substances confer advantages on their producers. Natural poisons function in three ways: to prevent predation, to protect resources, and to capture prey. Natural poisons are of enormous importance to humans due to the dangers some pose, but more significantly because of the many benefits humans enjoy that are either directly or indirectly attributable to these substances. Kinds of Poisons Natural poisons may be classified in several ways: by their chemical composition, how they are produced or acquired, by the organisms they affect, by their mode of action, and by their method of delivery. Natural toxins are found in all four of the major classes of organic compounds: carbohydrates, lipids, proteins, and nucleic acids. They range in molecular complexity from cyanide (HCN), a simple compound produced by certain millipedes and found in peach pits, to complex molecules containing scores of carbon atoms. Toxins are synthesized directly from raw materials by both plants and animals, selectively concentrated from the soil by plants, or sequestered from plants by herbivores. Soil nitrates in toxic concentrations are accumulated from the soil by many plant species. The monarch butterfly is noted for its larvae having the ability to sequester certain \Lalkaloid\ls contained in the milkweed plants (Asclepias) upon which they feed. This provides a chemical defense for the larvae, the pupae, and the adult monarch butterfly. Natural poisons directed against animals are called zootoxins; chemicals that are active against plants are called phytotoxins. Most phytotoxins are fungicidal and defend green plants against being parasitized by fungi. Mature creosote bushes produce substances that inhibit the growth of and prevent the establishment of potentially competitive seedlings in their vicinity. Natural poisons range in effect from mild to severe, and are sometimes fatal. They include skin irritants, emetics (vomit-inducing agents), proteolytic (protein-digesting) agents, hemotoxins (blood poisons), neurotoxins (nerve poisons), muscle contractants and relaxants, and physiological regulators. some of these toxins affect specific organs, such as cardiac glycosides that impinge on the heart, and others interfere with critical life processes, such as molting in insects. Some poisons may have long-term effects and may result in the development of cancerous growths. Virtually all poisons produced or concentrated by plants and many produced or sequestered by animals may be considered passive poisons in that they are delivered only when a target organism (the victim of the poisoner) has contact with or consumes the producer. Active poisoners include all animal species that use their poisons aggressively or have special active mechanisms to deliver them. The subjects of passive and active poisoners are elaborated in following sections. PASSIVE POISONERS Any poisonous species that requires an action by the target organism to dispense its poison is called a passive poisoner. Virtually all plants that produce toxic secondary substances are passive poisoners because they must be ingested in order for their poisons to have an effect. The addictive alkaloid drugs--such as nicotine from tobacco, cocaine from the coca plants, opium from poppies, psilocybin from certain mushrooms, and cannabin from the marijuana plant--belong in this category. Castor beans (Ricinus communis) and oleander foliage (Nerium oleander) are other examples of passive poisons. Some animals are passive poisoners. Puffer fishes in the family Tetrodonidae are considered a delicacy in Japan and southeast Asia, although the viscera of these fish, known as "fugu," contain tetrodoxin, an extremely potent poison. Japanese cooks are specially trained and licensed to prepare this fish; nevertheless, there are more than 150 fatalities each year due to puffer fish poisoning. Other types of passive poisoners that require only animal contact in order to transmit poison include poison oak, poison ivy, and poison sumac, and the skin of bufonid toads, which all exude toxic substances that cause irritation of the epidermal tissues of animals that contact them. Certain Central and South American tree frogs produce a poison from skin glands whose toxicity is so severe that small amounts of the substance are used to tip darts and arrows used in hunting. An additional example of passive poisoning is found in blister beetles in the family Meloidae; when the beetles are molested, they leak their hemolymph (insect blood), which contains the extremely irritating toxin cantharadin, from their leg joints. Cantharidin is used as a skin irritant to remove warts. Some poisonous plants and animals that use passive poisoning both to secure prey and for defense deliver their noxious chemicals when an offending animal punctures itself with sharp spines or triggers an otherwise static delivery mechanism. In nettles tiny spinose hairs inject the plant's poison, as do the urticating (stinging) hairs of certain caterpillars. Lion fish and scorpion fish in the family Scorpaenidae are some of the most venomous fish; if approached in a contentious manner, they present their venomous spines and invite the aggressor to bump them. Coelenterates such as jellyfish, sea anemones, and stinging corals have tiny barbed darts called nematocysts, which inject venoms when triggered by contact. The sting of the large coelenterate known as the Portuguese man-of-war, Physalis, causes intense burning sensations; although the severe pain lasts for hours, the sting is rarely fatal. Active Poisoners The overwhelming majority of venomous animals are active poisoners, with aggressive behavior patterns or mechanisms specifically evolved to dynamically deliver their venoms. Active poisoners employ three basic methods of dispensing their venoms: biting, stinging, and squirting. Biting includes piercing, stabbing, and chewing. Piercing involves highly specialized mouthparts through which sharp stylets pierce the skin of the victim; these parts are found in the insect orders Hemiptera (the true bugs) and Diptera (the flies). Salivary or associated glands produce the venom, and ducts transport it to the tubelike mouthparts through which it is injected into the victim. Stabbers include all hollow-fanged species such as spiders, centipedes, and rattlesnakes. These creatures employ hypodermic injection directly analogous to what is accomplished by a hypodermic needle and syringe. A few species, including the Gila monster and some hind-fang snakes, release their venom into a wound inflicted by their chewing on the victim's flesh. Stinging species that are active poisoners include the sting rays, the scorpions, and the ants, wasps, and bees in the insect order Hymenoptera. The barb at the tip of the scorpion tail injects venom produced in the last tail segment. Ants, wasps, and bees have posterior abdominal stingers that are hollow. These inject venom form special glands and storage sacks in the abdomen. This apparatus is most highly developed in the honeybee Apis melifora, where it is used mainly for defense against vertebrates. The honeybee sting is barbed, and the entire venom delivery system detaches from the bee's body when the stinger is anchored in vertebrate tissue; a bee can sting only once. Venom squirters are a remarkable group that includes whip-scorpions, Uropygi, that spray acetic acid on their antagonists, and the bombardier beetles, Brachinus, that create a small explosion in a specially designed abdominal chamber such that a caustic liquid at a very high temperature blasts from the insect's posterior. Darkling beetles, Eleodes, stand on their heads and squirt a mixture of quinones from a posterior opening when disturbed. The marksmanship of the spitting cobra, Naja nigricollis, is such that it can project its venom up to 3 m (9.8 ft) and hit the eyes of its victim. This feat is surpassed by skunks, Mephitis, which can disable enemies up to 9 m (30 ft) away with a fine spray of butyl mercaptan. Ecology and Evolution Natural poisons, like morphological structures and behavior, allow organisms to manipulate their environments and enable them to better compete, defend, and exploit. The best competitors, defenders, and exploiters among a group of individual organisms are usually the best reproducers, and differential reproduction is the operational definition of natural selection, the principal force driving organic evolution. If an individual organism has a mutation that causes the production of a chemical substance that allows it to survive when other organisms die, then that organism will reproduce more than other individuals who do not possess the mutant gene. As a result, the mutant gene will be more frequently represented in the next generation. After many generations, this process may result in a population that contains only the mutant gene. Assuming that the mutant gene mutates again in such a way that it produces a more powerful chemical that improves its owner's ability to compete, defend, and exploit, this new mutant will be favored by natural selection and again increase in number in the population. So, by favoring small increments of improvement, natural selection results in the evolution of finely tuned sometimes very potent poisons with elaborate delivery systems. Many natural poisons are believed to have begun their evolution as metabolites, mildly toxic intermediate or waste products of essential metabolic processes. This has often been the point of departure in the development of most plant poisons. \Lenzyme\ls, proteins essential to the control of the chemistry of life, were the likely starting compounds for the development of many animal venoms. For example, the digestive enzymes found in animal saliva have been modified to produce venoms in spiders, true bugs, flies, snakes, and shrews. Accessory glands associated with the female reproductive system of wasps, ants, and bees have evolved the secondary function of venom production, and the ovipositor has been modified through evolutionary time to produce the stinger. In the primitive wasps the stinging apparatus functions primarily to secure arthropod prey. Snake fangs have evolved form ordinary teeth that probably went through a grooved stage, as is found in the Gila monster, one of the poisonous lizards. Most animals learn from unpleasant experiences to avoid negative circumstances. Therefore it is not surprising that many animals with particularly punishing chemical defenses have developed bright colors and distinctive behavioral displays that become recognizable to potential victims. some species mimic others to avoid predation (see \Tmimicry\t); for example, the wings of the viceroy butterfly, which is palatable to birds closely resemble those of the monarch butterfly, which contains alkaloids that protect it from predators. Natural Poisons and Humans Although toxins from plants and animals kill only a few people each year, they make life miserable for many thousands. In North America, poisoning by rattlesnakes, Crotalus, coral snakes, Mirurus, widow spiders, Latrodectus, brown spiders, Loxosceles, and scorpions, Centruroides, may be life threatening if untreated. Poisoning, from plants (excluding plant-derived narcotic drugs) amounts to less than 2,000 cases annually, and the number of human deaths attributable to plant poisons is insignificant. The most common plant poisonings of humans are by common ornamental and house plants--such as holly, Ilex pyracantha, Pyracantha, philodendron, Philodendron, and dieffenbachia, Dieffenbachia--consumed by children. Any plant or animal toxin can cause sever allergic reactions in persons who have a tendency to be allergic to various substances. Anaphylaxis (a severe reaction to specific substances such as wasp venom or penicillin) is the life-threatening manifestation of this condition. It is more frequently of caused by bee and wasp stings simply because of the frequency of human exposure. Anaphylactic shock kills far more people than the direct effects of all natural toxins combined. Most U. S. states have poison-control information networks that are operated 24 hours a day. These centers are staffed by well-informed personnel who can provide life-saving information on all kinds of poisoning. The benefits of natural toxins enormously outweigh their negative impact on humans. Natural toxins have evolved varied actions on virtually all species and all physiological processes, including nerve action, water retention, muscle contraction, and reproduction. These compounds, in regulated doses, have great utility as drugs for managing and treating human and domestic animal disease and as research tools to enhance the understanding of life processes. For example, digitalis, a substance obtained from the common foxglove, Digitalis purpurea, is used as a drug to regulate heartbeat rate; quinine, an alkaloid from the bark of the cinchona, Cinchona officinalis, was the first drug to be used successfully to treat malaria. In addition, plants supply commercial insecticides, such as rotenone and pyrethrum. The genes for thousands of compounds may be inserted into the major food and fiber crop plants using \Tgenetic engineering\t to protect them against insects and disease and contribute to global improvements in the standard of living. Robert L. Smith Bibliography: Altmann, Horst, Poisonous Plants and Animals (1981); Frazier, Claude A., and Brown, F. K., Insects and Allergy and What to Do about Them (1980); Gadd, Laurence, Deadly Beautiful: The World's Most Poisonous Animals and Plants (1980); Glass, Thomas G., Management of Poisonous Snakebite, rev. ed. (1986); Harris, John B., ed., Natural Toxins: Animal, Plant and Microbial (1986); Levy, Charles K., Dangerous Animals of North America (1983); Levy, Charles K., and Primack, Richard B., Poisonous Plants and Mushrooms of North America (1984); Minton, Sherman A., Venom Diseases (1974); Smith, Robert L., Venomous Animals of Arizona (1982).