Surprising Allies
The yew tree, Taxus, has a legendary connection to death. Its seeds, leaves, and bark are highly poisonous to humans. In recent decades, however, this long-lived plant genus has earned a different reputation: as a potential preserver of life.
In the 1960s, researchers working for the U.S. National Cancer Institute discovered that the bark of Taxus brevifolia, the Pacific yew, contained a toxic ingredient that could be harnessed on a cellular level to inhibit the progress of some cancers.
A derived compound known as paclitaxel, produced in the laboratory and available commercially since the late 1990s, has been found to be effective in the treatment of breast, lung, and other cancers, as well as AIDS-related Kaposi’s sarcoma. It has also been found useful in preventing a re-narrowing of coronary arteries in stent recipients.
The drug is a prime example of the use of poisons in the service of medicine, a challenge to the modern view of poison as an instrument of death, whether by accident, suicide, or murder most foul. Of course, nature’s poisons have been used for medicinal purposes for millennia. Small doses of opium, mandrake, henbane, and hemlock numbed the pain of surgery for more than 1,000 years.
In William Shakespeare’s time, 400 years ago, poisonous extracts were combined into cough medicine. Well into the 20th century, mercury was an ingredient in popular remedies, from purgatives to infants’ teething powder.
But modern scientific techniques have allowed researchers to better understand, and then take advantage of, the underlying mechanisms by which plant toxins and animal venoms attack normal metabolic processes. For example, some neurotoxins block the release of chemical messengers called neurotransmitters; some stop neurotransmitter messages from being received; some send false signals; and still others disrupt nerve cell activity by opening channels in cell walls. If muscles in the heart or lungs fail to get the proper signal to function, the results are fatal. But applying the same effect in nonlethal doses can stem tremors or the registering of pain.
“What is a poison?” asks Mark Siddall, curator of the special exhibition The Power of Poison. “It’s a substance that interferes with normal physiological processes, that alters or stops them, or makes things happen. That is essentially what medicines are, too.”
Natural Resources
The potential for tapping nature is staggering. By conservative estimates, some 100,000 animals, from lizards and snakes to sea anemones and jellyfish, produce venom, which in turn can contain hundreds of different toxins. So far, only about 10,000 animal toxins have been identified, and 1,000 of these have been studied in depth, with a view to developing drugs. The anticoagulants tyrofabin and hirudin were derived from animal sources, respectively, the blood-thinning venom of the African saw-scaled viper and a substance secreted by leeches.
The diabetes drug Exenatide, which lowers blood sugar and increases the body’s production of insulin, is a synthetic version of a component in the saliva of Gila monsters, large venomous lizards found in the southwestern U.S. and northwestern Mexico.
The development of the first oral ACE (angiotensin-converting enzyme) inhibitor, which treats hypertension, was based on an understanding of how the venom of the Brazilian pit viper, Bothrops jararaca, causes a drastic drop in blood pressure in its prey.
Plants are an even richer mine, with more than 400,000 identified species and many of them toxic to one degree or another. Fixed in place, plants are especially adept at producing chemical defenses against insects, larger plant-eaters, and even other plants—a process that has allowed land plants to flourish for about 450 million years.
Caffeine and nicotine are both plant-based products with well-known pleasurable effects on the body until taken in excess, revealing their essentially poisonous nature. But just as with animal toxins and venoms, plant compounds that affect the human body can be employed for medicinal purposes. Salicylic acid, the active ingredient in aspirin, for example, is found in a number of plants, including the willow tree Salix, from which it takes its name.
Similarly, the antimalarial drug artemisinin is derived from the herb sweet wormword, Artemisia annua.
“Plants and animals are doing complex biochemistry all the time, creating things we couldn’t imagine making without the temperature of the Sun and the pressure of the center of the Earth,” says Dr. Siddall.
Urgent Quest
In many ways, nature is one huge laboratory, making and testing countless plant and animal substances in each species’ efforts to prevail. In what has been called an evolutionary arms race, as predators up the potency of their poisons, prey strengthen their resistance. This is especially apparent at the microscopic level, where microbes compete endlessly by developing their own antibiotics to fight off other microbes, teaching us in turn what works and what doesn’t. Bacteria, algae, and fungi, including molds, that produce toxins could all potentially yield medicines.
Whether at the microscopic level or the level of plants and animals, researchers are in a race against time as they seek to unlock the potential of poisons. “Habitat loss from overpopulation, climate change, and other factors have put more species of plants and animals at risk,” says Siddall.
Consider those toxin-rich snakes: by conservative estimates, one in five reptiles are now threatened with extinction, losses that could radically diminish a promising source for healing.
“If the world was populated by only pine trees and pandas,” says Siddall, “we wouldn’t have this rich diversity of resources to help us understand the physiology of diseases and find out what’s out there that might target them.”
Stay tuned for more on poisons in animals (from cone snails to spiders) that are today used in powerful medicines.
A version of this story appears in the Fall 2013 issue of Rotunda, the Member magazine.