The Art and Science of Poisons

Beauty is said to be in the eyes of the beholder. Likewise, the deadliness of a poison depends on subjective criteria. Is more weight to be given for quickness of action, stealth, whether an antidote is available, or how little is required? Most accounts declare botulinum A, the toxin produced by a species of anaerobic bacteria, to win the contest based on its LD50 (the amount that kills half of those exposed). Its toxicity, measured this way, is greater than any known substance. I propose a new way of ranking poisons, the LD50*, based on the number of molecules in a deadly dose. This is more equitable because poisons differ greatly in their molecular weights – some are very small and some are very large molecules, and poisons kill molecule-by-molecule. Several snake venoms are deadly and the most toxic is that of the inland taipan, although the coral snake and cobras have very toxic venoms, and rattlesnake, because of the volume injected and the multiplicity of toxic ingredients, deserve mention. Only two species of scorpions (the death stalker and man killer; neither found in the United States) have stings that are life threatening for humans. Spider venoms don’t quite make it to our most deadly list. Radiation exposure is a different kind of “poisoning” and Polonium-210 makes our list because of the small amount required and its intense radiation based on its very short half-life. The most deadly, quick-acting toxins affect the nervous system and cessation of respiration or heart function stops the supply of oxygen to tissues to cause death. It is thought-provoking to consider that all things are poisonous, and that only the dose makes the difference (to paraphrase toxicologists). In this context, life-giving pure water becomes deadly when several liters are consumed rapidly. Why poisons exist has a scientific answer, but perhaps not a satisfactory philosophical answer. “All things are poison and nothing is without poison; only the dose makes a thing not a poison.”1

Poisons, by their nature, conjure up unpleasant thoughts. To the nonscientist, poisons are associated with cowardly acts, sinister motives, painful death, murder, suicide, and deadly plants and animals. To the scientist, poisons are an enigma – how did they come to be – and they are interesting because the study of their mechanism of action can inform us about how the body works and they are a source of medicinals. Poisons also have been the source of historical intrigues, individual and state-sponsored atrocities, and woven into legends and classical stores. In this chapter, three poisons are considered for their horrible and potent effects, as well as their classical and historical importance. Arsenic can be called the “king of poisons” because of its wide use in the 1800s; it was cheap, easily available, did not have a detectable taste when added to food and drink, it could be given surreptitiously in small doses over time with a cumulative effect, its effects mimicked other common illnesses, and until the Marsh test, it was virtually undetectable in the victim. Hemlock is classically known as the poison that killed Socrates and it is biosynthesized by a plant with familiar non-poisonous relatives including the carrot and parsnip. It causes a slow ascending paralysis starting in the feet and ending in death, and was once designated as the “State” poison because of its use as the means of execution in ancient Greece. The asp is a poisonous viper forever associated with Cleopatra. In fact, we do not know what snake caused her death but the story is classical.

More than 1500 species of scorpions are known and they populate every continent except Antarctica. They abound in dry and desert areas of the world. By most accounts, only about 20 species have venom that can kill a human. Mostly, they live secretive lives preferring underground burrows or crevices in rocks by day and come out at night when they hunt for prey that for different species ranges from insects to rats, mice, lizards and other small animals. Scorpions produce complex venoms composed of many chemicals and they possess the ability to control the amount of venom injected by a sting, and even control the quality of that venom. The most toxic venom for humans appears to be that produced by the death stalker, and there are four chemical components. The earliest effect is on the transmission of nerve impulses which creates paralysis, and a subsequent toxicity to the heart. The most significant nerve toxicity is described as an impairment of calcium movement that blocks transmission of impulses across synaptic junctions to cause paralysis.

Many plants contain chemical compounds that are mildly toxic to humans; some plants are overtly poisonous, and a few are deadly. Throughout history, the leaves, roots, stems, and berries of certain plants have been used for murder, often of the vilest sort. Also, people and animals are accidentally poisoned by plants some of which are garden-variety ornamentals. Because there are so many choices, in this chapter, I have elected to describe certain plant toxins because of extreme toxicity, some because of unusual examples of their murderous applications, and a few because they have become the subject of legends. I hope to draw the reader’s interest in the science of toxic plants and their poisons and about the use of these poisons in modern accounts and in tales that are mostly myth. A true story, but one with sensationalized nuances and uncertainties and a modern revisiting, is the murder conviction of Harvey Crippen based on a death from a medicinal chemical derived from the belladonna plant. I will explore what I have chosen to call the art and science of five very poisonous plants: belladonna (deadly nightshade), white snakeroot, castor bean, rosary pea, and monkshood. I will include references rather than extensive descriptions of the plants, details about the signs and symptoms of poisoning, an example of poisonous use (extensive for belladonna), and the biochemistry and biology of the mechanisms of toxicity of the chemicals.

The art and history of cyanide as a poison begins innocently with the discovery of Prussian blue as a welcome addition to the palette of artists and dyers of cloth where a vivid blue was difficult to obtain and expensive. It did not take long for the dark and sinister uses of this poison to emerge and continue. A form of cyanide may have been used by the Emperor Nero to murder members of his family. It probably was added to the bayonets of soldiers of Napoleon III in the Franco-Prussian War. In World War II, unspeakable horrors were committed by the Nazis who used Zyklon B (cyanide) to commit mass murders in death camps. Near the end of that war, cyanide was used in mass suicides by the German people, and infamous Nazis, including Hitler, Eva Braun, the Goebbels, and others committed suicide with it. A small quantity of cyanide, taken internally kills almost instantly. Enough cyanide to kill could be placed in a glass capsule that could be conveniently hidden on a person’s body or even secreted in the mouth to be crushed when death by suicide was the chosen option. The mass suicide by more than 900 members of the Jim Jones cult was caused by a drink laced with cyanide.

The sea is a wondrous habitat. Humans, however, venture there at their own peril. Among the perils there are a variety of life forms that biosynthesize poisons administered via bites, stings and other envenomations. A few forms of sea life are poisonous when consumed by humans. Among the poisonous sea life, there are some that harbor other life forms that provide the poison. Several of the toxins described in this chapter are more annoyances than deadly; several are significant threats to human life. Sea snakes are, perhaps, the most feared of poisonous sea creatures. Sea snakes occur in the tropical and subtropical areas of the Indian and Pacific oceans ranging from the east coast of Africa to the Gulf of Panama. Most species of sea snakes, however, inhabit the waters around the Indo-Malayan Archipelago, the seas around China, and waters near Indonesia and Australia. A typical and distinguishing feature of the sea snake is the vertically flattened (paddle like) tail. They are said to be most closely related to terrestrial elapids (which include some of the most poisonous snakes, including the brown snake, taipan, death adder, cobra, krait, and mamba). Isolated but tragic instances of deaths are reported by the stingray, and food poisonings are not uncommon from several fish, due to toxins they produce or which are produced by dinoflagellates they harbor. Tetrodotoxin, produced by dinoflagellates, can be amplified up the food chain. Puffer fish poisoning is a prime example.

Spiders rarely engender neutral feelings in people; many fear them and some find them repugnant. There are a few examples in literature of spiders portrayed in a positive light and they are whimsically described in children’s verses and stories. Scientifically, spiders are interesting biologically for their behavior, especially their webs. Spider silk from which webs are made is noted for its high strength, which exceeds (on a weight-comparison basis) steel and man-made fibers, and its elasticity which allows webs to catch flying insects with impacts of a thousand watts of power. Spider venoms have a wide variety of chemical structures and biological activities. Some, including venom of the black widow spider, have neurotoxic components and the complete venom of this spider is similar in toxicity to that of rattlesnake venom. The Brazilian wandering spider and the Australian funnel web spider vie for the title of most venomous spider. The brown recluse is feared over large regions of the central United States because of the large necrotic wound that can result from their bite and their reclusive nature coupled with their tendency to occupy human residences. The tarantula is widespread around the world and has unusual ability to shoot poisonous hairs from its body in addition to a venomous bite which, fortunately, is not usually medically serious for humans. Venoms from many spider species are useful for scientific studies because some interfere with the mechanisms used for communication between and within cells for various physiologically essential functions. Spider venoms are being investigated as tools for studying nerve cell functions including impulse transmission. They also are being explored as pain killers and used as tools in the search for causation and cures for several devastating neurological conditions.

Snakes, from historical times to the present, have had a bad reputation. The story of the fall in the Garden of Eden has a snake as the betrayer and inducer of original sin. Much of their current reputation is well earned. They are an example of a bearer of poisons that congers up all that we fear about poisoning, and more. As examples of a life form snakes have many unusual features. They lack arms and legs, hands and feet, but they manage to move about, to mate, and to find prey as food. This last function is one where venoms come in handy, given the other deficiencies. There are an amazing variety of poisonous molecules that have been discovered in snake venom. Undoubtedly there are many more to be discovered, and based on what we already know, some of these may be excellent therapeutics for a variety of pathologies. The poison side of these molecules is fascinating with intricate complexities. The toxins are exquisitely specific in the manner in which each can bind and disrupt an essential function – as do the neurotoxins – in a species so far removed from their own lineage as is the mouse or the human. This speaks, at least to me, of the design seen throughout nature.

In creating this book, most poisons of interest naturally fall into reasonably discreet groups. However, there are many other interesting poisonous substances that do not deserve a full chapter and also are disparate in nature. Selecting poisons from this group of chemicals is fraught with risks – being too inclusive or too exclusive. In the end I made choices based on several factors: my interests (I admit it); the extent to which the substance actually has poisoned people; its appearance in literature, including murder mysteries; extensive public awareness of the agent; and its potency. Medicines are a great boon to humankind and I hesitated to include them in a list of poisons. In the end, I justified their inclusion because awareness is useful knowledge and because I sense there is curiosity about this aspect of many highly-prescribed medicines. Several toxic chemicals are included because they are deserving but not a good fit elsewhere. A host of chemicals are sufficiently toxic to be included in a compendium, which this book is not. Environmental pollution raises concern for toxins in our air, water and food. These poisons are present as trace amounts and may be involved in chronic health effects but do not belong in this account. Some chemicals have, unfortunately by my thinking, been unfairly accused and even damned by popular media and lawsuits. I will simply leave these out of my list.