Nature's Drugs; Scientists tend to prefer the lab to the mess and complication of living beings. Now they realize that forests and oceans hold a bounty of useful chemicals.

Byline: William Underhill

Swimmers in the coral reefs of the Philippines know to stay away from Conus magus. The sea snail may be small--just a few inches long--but it's deadly mean. One dose of its venom can paralyze the passing fish that make up its diet. To drugmakers, though, the potency of its toxin is sheer poetry. Scientists who recently broke down the poison discovered--and copied exactly--a chemical compound that blocked nerve cells from sending signals to the brain. Result: Prialt, a new painkilling drug 1,000 times more powerful than morphine, the most potent analgesic now available to medicine.

That marks one more triumph for mankind's ingenuity, and a comeback for Nature as well. The development of Prialt, which reached the market earlier this year, neatly demonstrates the latest twist in our relationship with the global ecosystem. As the flow of new drugs down the research pipeline slows to a trickle, pharmaceutical companies are turning again to the natural world for inspiration. Researchers now talk of promising new drugs derived from a vast range of living organisms--everything from Brazilian snakes to Hawaiian mollusks. "The industry is in crisis," says Graham Dutfield, an authority on the bioprospecting business at Queen Mary College in London. "The companies are throwing masses of money at research but just not getting the returns. That's why they are looking at different options."

Blame the vanity of science. Back in the 1980s, the industry's smartest brains reckoned that a purely technological approach--so-called combinatorial chemistry--could replace trial-and-error or the well-informed hunch as the primary source of new products. Machines would mechanically mix and match the basic building blocks of chemistry, throwing up tens of thousands of variations that could be tested automatically for their therapeutic potential. "The big companies just plugged away at screening large libraries of compounds," says Ian Paterson, a chemistry professor at Cambridge University who recently coauthored a new paper on the renaissance of natural products. "The idea was that if you bought enough lottery tickets one would give you a billion-dollar drug." Not so. Even today, it's tough to predict how a wholly artificial product will react with the real flesh-and-blood world. The number of new drugs approved by the U.S. Food and Drug Administration fell from 53 in 1996 to just 23 last year.

Nature, aided by evolution, may often be just as efficient in turning up leads. Living organisms have spent eternity learning to cope and compete with one another, developing structures that are often hugely complex and potent. "Nature has done about 3 billion years of work for you," says Chris Molloy, business-development manager at Singapore-based MerLion, a leading company in the field, which maintains a "library" of 100,000 strains of microorganisms and 38,000 plant samples. "The genome of natural products doesn't waste time in producing molecules that don't interact with biological systems." Big business now takes the point. MerLion has struck partnership deals with several of the world's biggest pharmaceutical companies, including Merck and Schering-Plough.

For older researchers, of course, it's a return to familiar territory. About half of the products in today's medicine chest originated in nature, including some of the top performers. Aspirin was originally synthesized from willow bark, known to reduce fever for more than 2,000 years. The breast-cancer drug Taxol was cribbed from the bark of the Pacific yew. But in ...