DRUGS FROM PLANTS

Many drugs in use today have their basis in wild plants. A small selection of these are shown here:

Drugs derived from wild plants

Plant	Location	Drug	Use
Willow	Worldwide	Aspirin	Fever and pain
Cinchone	Tropics	Quinine	Malaria
Rosy Periwinkle	Madagascar	Vincristine	Leukemia
Rosy Periwinkle	Madagascar	Vinblastine	Hodgkin's disease
Pacific Yew	Pacific Northwest	Taxol	Ovarian cancer
Opium Poppy	Eurasia, Africa	Morphine	Pain
Curare	Amazon	Tubocurarine	Muscle relaxant
Snakeroot	India	Reserpine	Hypertension
Foxglove	Eurasia, Africa	Digoxin	Cardiac arrhythmia

Of course, targeting a promising compound is only the first step. Before developing a drug from it, a renewable resource for the compound has to be established. This task poses an enormous barrier. Because these compounds often come from rare or slow-growing organisms, or are produced in minute quantities, harvesting the source organisms in sufficient amounts may be unrealistic.

     To address this problem, researchers usually try to make synthetic derivatives. But sometimes synthesis proves impossible, or uneconomical, as in the case of Ecteinascidin-743, an anticancer compound currently in clinical trials that comes from a creature called a sea squirt. Scientists from CalBioMarine Technologies in Carlsbad, Calif., have developed a method of culturing the animal, going so far as creating an artificial version of the mangrove roots it settles on in the wild. In other cases, simply culturing cells from the source organism is sufficient.

     Once developed, these drugs, as with all proposed pharmaceuticals, must pass a battery of rigorous test that evaluate their safety and efficacy in animals and then humans. This step, too, can take its toll, especially on start-up companies. Take, for example, the case of Shaman Pharmaceuticals, a once-promising company armed with a product poised to treat people suffering from chronic diarrhea. Their drug, Provir — derived from the sap of croton, a common Amazonian tree—did so well in two years of clinical trials that the FDA granted it fast-track status, requiring only one final Phase III trial instead of two. When the FDA later decided to demand a second Phase III trial, though, Shaman couldn't afford it. Today the company sells dietary supplements.

Bioprospecting or Biopiracy?

     In addition to the difficulties posed by the research itself, the scientists and pharmaceutical companies hunting for natural miracle drugs face critical ethical dilemmas. In Brazil, for example, officials have expressed concern over the possibility that the scientific demand for plant samples has led to plant smuggling. And indigenous groups around the world worry that in the race to patent Nature's million-dollar molecules, science is stealing their intellectual property.

     Indeed, according to a report that appeared earlier this year in the Atlanta Journal and Constitution, even a project that aimed to share future profits with the native people — Mayans in Mexico's Chiapas state — has floundered, owing to disagreements over who owns the plants, folk knowledge and commercial rights to whatever drugs might result from the collaboration.

     Other efforts to ensure these often poorer nations benefit from visits from bioprospectors have had happier outcomes. In South America's Suriname, for instance, Bristol Myers-Squibb, scientists and conservationists from the Missouri Botanical Gardens, the Virginia Polytechnic Institute and Conservation International helped to establish a four-million-acre reserve. Conservation International has also been active in helping the governments of Madagascar and Indonesia to develop policies aimed at maintaining national sovereignty over their biological resources.

On the Horizon

     Bioprospecting during the past decade has yet to turn up a blockbuster drug, but a number of naturally derived pharmaceuticals are being evaluated in human trials. These include compounds ranging from Immunokine, derived from the venom of the Thailand cobra, which may effectively combat multiple sclerosis, to calanolide A, an anti-HIV agent retrieved from a Malaysian plant. Ziconotide, a potent pain reliever extracted from the tropical marine cone snail, has come particularly far and is awaiting FDA approval. Once approved, Ziconotide will become the first marine-organism-based pharmaceutical.

     In many cases, though, the environments in which potentially healing organisms live are being destroyed. Estimates place the number of species screened for their medicinal properties at a mere 1 percent, yet each year more than 30 million acres of tropical forest are lost. Human activity is taking its toll on the oceans, too, in the form of pollution and overfishing. Such large-scale destruction of our planet's complex ecosystems will no doubt come back to haunt us — if for no other reason than the fact that with every species lost, Mother Nature is taking potentially lifesaving chemical formulas to the grave.