If you're prospecting for new drugs in nature--which scientists continue to do, with or without the genome--there's no better place to start than the business end of a good poisonous plant or animal. Modern medicine is filled with drugs derived from deadly poisons, from the muscle relaxant curare (taken from South American vines that are used to poison arrow tips) to the anticoagulant Aggrastat (based on the venom of the saw-scaled viper).
The potency of these compounds is no accident. After all, each is part of an organism's defense and predatory mechanisms, whose specificity has been honed over millions of years of evolution. Animal venoms make particularly good sources of potential drugs because they are designed to kill or immobilize prey. Many contain dozens or even hundreds of potent, fast-acting toxins that home in on the muscles and nervous system. The molecules also tend to be small, which means they can easily slip across the blood-brain barrier, the network of tiny vessels in the brain that blocks larger compounds.
Poisonous snakes, spiders, scorpions and frogs have so far attracted the most scrutiny, but insects and marine creatures are also rich sources of potent compounds. Here's a taste of what's going on in the field.
Thailand (Monocled) Cobra
The Thailand cobra, which can grow to more than 6 ft., is armed with venom that paralyzes nerves and muscles and eventually causes respiratory arrest. For the past 10 years, PhyloMed Corp., of Plantation, Fla., and the Bahamian firm Coral Pharmaceuticals have been conducting clinical trials of Immunokine, a drug derived from Thailand cobra venom, on people with multiple sclerosis. Virtually nontoxic, Immunokine seems to prevent immune cells from attacking and destroying the myelin sheath that protects nerve cells.
So far, the results are encouraging. The drug works best on people with the least nerve damage; its only apparent side effect is that it exacerbates PMS in some women. PhyloMed hopes to launch a more advanced clinical trial on Canadian MS patients early this year. Meanwhile, a British researcher has just begun testing the drug's effectiveness against adrenomyeloneuropathy, another debilitating central-nervous-system disorder.
Phantasmal Poison-Dart Frog
In the early 1990s, John Daly, a biochemist at the National Institutes of Health, discovered that an extract from the skin of a tiny Ecuadorian tree frog was a potent pain killer, some 200 times more effective than morphine--at least in rats. The extract, known as epibatidine, is structurally and functionally similar to nicotine. It seems to prevent the nervous system from processing pain signals by interfering with nicotinic receptors in the brain.
When scientists at Abbott Laboratories heard about Daly's research, they compared epibatidine with several hundred related compounds they had synthesized as experimental treatments for Alzheimer's disease. One of them, ABT-594, turned out to be remarkably similar but much less toxic. Tests on animals indicate that ABT-594 is about 50 times better than morphine in relieving both chronic and acute pain yet seems to be nonaddictive. Phase II tests on humans should be completed by the end of the year.
Southern Copperhead