In one of the odd twists of fate that make the topic of medicines derived from animals so fascinating, one of the most fruitful places to look within the animal kingdom is the vast array of poisons and venoms that organisms have evolved to ward off predators or to attack prey. More than 30 years ago, Capoten (captopril)—copied from a pit viper venom peptide—became the first approved venom-derived drug (in this case for hypertension). Several venom-derived drugs have since been approved for cardiovascular disease, as has a venom-derived painkiller. Today, thanks to increasing knowledge of the human nervous and immune systems, the pipeline “from fang to pharmacy” (as The Scientist memorably described it in 2013) is growing ever bigger.
Scorpions are proving useful in medicine as well. As reported recently by Christie Wilcox in her book Venomous: How Earth’s Deadliest Creatures Mastered Biochemistry, researchers are at work on a “tumor paint” known as BLZ-100, derived from scorpion venom, which causes rapid paralysis in insects. This targeted contrast agent, which is being used in clinical studies for children’s brain tumors, binds to chloride channels found in tumor cells; thus, by linking this toxin to a fluorescent dye, doctors can see and remove an entire cancerous mass.
Another venom-derived drug comes from the sun anemone Stichodactyla helianthus, which lives on reefs in the Caribbean and uses its soft green tentacles to stun shrimp with a cocktail of toxins. Physiologists have shown that one of these toxins, a peptide called ShK, is a potent inhibitor of a T-lymphocyte potassium channel called Kv1.3, the upregulation of which is implicated in autoimmune diseases. And a poison produced by the cone snail Conus geographus has been shown to be 1,000 times more powerful than morphine in treating certain kinds of chronic pain. For example, the snail-derived drug Prialt® (ziconotide) jams up nerve transmission in the spinal cord and blocks certain pain signals from reaching the brain.
The tropical forests and savannahs of Argentina, Brazil, and Paraguay are the habitats of the feared pit viper Bothrops jararaca (also known as the fer-de-lance). Snakebites from this species often result in the victim’s collapse due to a massive drop in blood pressure. A research effort has worked out how the viper venom causes that blood pressure decrease and exactly what chemical in the venom is responsible. That knowledge led to abatement of morbidity and mortality from the pathological effects of chronic high blood pressure, via the creation of so-called angiotensin-converting enzyme (ACE) inhibitors. As another example, the diabetes drug exenatide, which lowers blood sugar and increases the body’s production of insulin, is a synthetic version of a component exendin-4 in the saliva of Gila monsters, large venomous lizards found in the southwestern U.S. and northwestern Mexico.
Finally, one of the more unlikely inspirations in recent years involves one of the natural world’s least-celebrated liquids: the saliva of the tick Ornithodoros moubata. A new inhibitor of the complement protein C5, a small recombinant compact protein named Coversin, has been derived from a protein in the tick’s saliva. The natural Coversin molecule works by damping down the immune response of the host animal that the tick feeds off of, enabling it to feed repeatedly without damage from host inflammatory substances. Coversin is currently being studied as a potential treatment for rare autoimmune diseases, including paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and Guillain-Barre´ syndrome.
Despite the challenges involved—on average, only one in thousands of natural compounds tested shows pharmaceutical promise and only a handful of those ever make it to market, according to Scientific American—researchers press on. Mother Nature, with millions of years of experience under her belt, continues to be the ultimate drug developer.