TORTUGUERO NATIONAL PARK, Costa Rica – Carlos Bettancurt cuts the motor and we glide soundlessly toward the bank of the Parismina lagoon, part of the vast network of rivers and canals that crisscross this wildlife sanctuary.
Doused liberally with DEET to ward off mosquitoes and swathed in hats, longsleeved shirts and pants, we step ashore and follow Carlos, a trained Costa Rican naturalist-guide, along the path that he originally hacked out of this steamy jungle six years ago.
We are hunting on this sweltering January afternoon, not for the elusive jaguar or for the huge crocodiles we spotted earlier along the riverbank, but for something both less dangerous and potentially far more valuable – medicinal plants, which grow in abundance in rainforests all over the world.
Most of what Carlos knows about jungle medicine he learned from his grandmother, who is in her 90s now and unable to accompany us. As we alternately take notes and swat bugs, Carlos shows us a platanilla plant, which, when made into a tea, is said to induce abortions. He points out a type of sour cane that, when chewed, is supposed to help with liver and lung problems. And a broom tree, parts of which are said to stop bleeding.
So, why haven’t the big pharmaceutical companies been able to find medicines in the jungle as easily as Carlos? Despite the seeming promise of”bioprospecting” for drugs in rainforests, professional drug hunters have reported no blockbuster drugs after 10 years of looking. Merck & Co. even terminated its landmark bioprospecting contract with Costa Rica in 1999 after producing no commercially viable products – though the company says it’s still analyzing samples.
The difficulties are somewhat ironic, in light of the fact that human beings have always used natural products as medicine, and 80 percent of people in developing countries still do. Chimpanzees and other animals, too, eat certain types of foliage when they’re sick that they wouldn’t ordinarily eat as food, noted tropical ecologist Dan Janzen of the University of Pennsylvania.
Indeed, about 50 percent of all human pharmaceuticals in use today – from simple aspirin to powerful cancer chemotherapy drugs such as vincristine and Taxol – originally came from natural sources.
But modern “bioprospecting” in rainforests, coral reefs, deserts and other exotic locales has been slow going so far. It’s partly because modern drug development is such a costly, plodding process, often taking a decade or more to complete testing and regulatory approvals before the first prescription is written.
But the rainforest fizzle also may reflect unrealistic expectations about companies’ abilities to turn the folk remedies of people such as Carlos’ grandmother into the safe, reliable medicines that Western consumers expect.
Bioprospecting took off in earnest in 1991 amid great hopes when Merck entered into an agreement with Costa Rica’s National Biodiversity Institute, a private, nonprofit group that had been co-founded in the late1980s by Janzen. Under that novel agreement, Merck gained access to some plants, fungi and environmental samples from Costa Rica’s protected rainforests, and the Costa Ricans got the right to royalties if any marketed drugs resulted.
The romantic ideal of bioprospecting gained more steam in 1992, when 177 nations (although not the United States) ratified the Biodiversity Convention, an agreement that outlined ways for rich nations hunting for medicinal gold to share the wealth with cash-poor, plant-rich nations; and just as important, preserve natural habitats and indigenous populations in the process.
The need to protect such habitats was – and still is – acute, said Katy Moran, executive director of The Healing Forest Conservancy, a nonprofit group based in Washington. The equivalent of a football field of rainforest is lost every second to industries such as logging, cattle raising, and oil and mineral extraction, she said.
Bioprospecting has helped to preserve some of the land, said botanist Joshua Rosenthal, who heads the International Cooperative Biodiversity Group program, an effort started in 1993 at the National Institutes of Health to enable American scientists to work with other countries in bioprospecting ventures.
In Surinam, for instance, combined efforts by the US government, Bristol Myers-Squibb, conservationists and scientists from Virginia Polytechnic Institute and the Missouri Botanical Gardens helped the Surinam government set aside 4 million acres as the Central Surinam Reserve a year and a half ago, Rosenthal said.
The disappointing news, however, is that so far – and it really is too soon to judge – bioprospecting has yielded no major new drugs. Some are believed to be in the pipeline, but pharmaceutical companies remain close-mouthed.
“If they get a lead, they won’t tell you,” Janzen said. “They don’t want the competition to know what area they are looking in.
The industry trade group, Pharmaceutical Research and Manufacturers of America, has acknowledged that companies may be reticent to talk about bioprospecting in part because they don’t want to be perceived as stealing the flora or the intellectual property of indigenous people. But the lack of publicized results also reflects the fact that companies are putting more effort into high-tech drug discovery using genomics to design drugs from scratch rather than combing nature for medicine.
In comparison to lab-based genetic research, bioprospecting is a hit-or-miss proposition fraught with obstacles, as biologist Steven King, chief operating officer of Shaman Pharmaceuticals in South San Francisco, can attest.
Shaman Pharmaceuticals started up in 1989, armed with a short list of a dozen promising medical plants that company officials knew grew in specific regions, such as the northwest Amazon basin in South America. One plant in particular, which contained a molecule the Shaman scientists dubbed SP303, seemed to be highly effective against diarrhea, just as indigenous healers had said it was.
Encouraged by the US Food and Drug Administration to do the research that could get this extract approved quickly as a prescription drug, the company launched human studies, including one on 400 patients at 25 US medical centers. The results were encouraging, King said, but apparently not quite good enough. The FDA demanded another study, but Shaman didn’t have the $15 million to $20 million to do it.
The result? Shaman is now reorganizing in the face of bankruptcy and has decided to market its once-promising prescription drug as a dietary supplement, for which prior FDA approval is not necessary. The product is now sold in health food stores, under the rather drab name, NSF, for normal stool formula. The good news for Shaman, King said, is that the food supplement seems to combat not just traveler’s diarrhea, but irritable bowel syndrome as well.
Despite such bumps in the road, there is still considerable optimism that bioprospecting will yield new pharmaceuticals because of the sheer numbers of plant species in the world, many of which are as genetically complex as humans.
“Plants contain enormous numbers of genes and, if you multiply the number of species times the genes, the number is huge,” said biochemist Malcolm Morville, who runs Worcester-based Phytera Inc., a biotech company.
“Plants can’t move,” he said, which means the only way plants can adapt to threatening changes in their environment is by turning on or off certain genes. “That’s why plants are of interest because, genetically and chemically, they’re some of the most sophisticated species on Earth.” Sponges and some other marine organisms use the same defenses.
“Nature produces many wonderful molecules for various reasons as a form of chemical defense,” said Gordon Cragg, chief of the natural products branch at the National Cancer Institute, which has been testing extracts from nature as potential cancer-killing agents for 45 years.
“You comb through nature, collect a whole range of plants, marine organisms and microorganisms, and then test extracts of these substances to see if they kill cancer cells in the test tube. The extracts often are mixtures of hundreds or thousands of chemicals. You have to try to isolate the one or two chemicals that are responsible for killing cancer cells.”
This, not surprisingly, can be a long and tedious process, and one that may seem far removed from the muggy, buggy reality of a Costa Rican rainforest.
But it is a path well worth pursuing, said Mark Plotkin, a Tufts University-trained ethnobotanist who now heads the Amazon Conservation Team, a Virginia-based group dedicated to protecting biological and cultural diversity.
“Western medicine is the most successful, sophisticated method of healing ever devised, but it doesn’t have all the answers,” he said. “Rainforest shamans claim they can cure – not just treat, but cure – some of the things we can’t. Doesn’t it make sense to go ask these guys what they have?”
SIDEBAR: Some Drugs From Nature Show Promise
Although drug researchers haven’t hit the jackpot, they are developing some promising medicines from plants, insects, marine organisms, soil bacteria and other natural products.
Researchers from Abbott Laboratories are now conducting trials in human volunteers of a painkiller called ABT-594, which the company believes is about 50 times better than morphine in relieving both chronic and acute pain, yet is not addictive. Abbott scientists had already synthesized ABT-594 for other uses when they learned that John Daly of the National Institutes of Health already had discovered the powerful painkiller in the skin of a tiny Ecuadoran tree frog.
An Argentine soil microorganism has already been turned into an approved drug that fights antibiotic-resistant bacteria, Syncercid. And Neurex Corp. is working on a painkiller made from cone snails that live in tropical oceans.
Meanwhile, esearchers at Arizona State University have begun human testing for a cancer-fighting drug, bryostatin, made from a marine weed that grows off the California coast. The researchers also see anti-cancer promise in a blue-green algae found near Guam, and have begun safety testing of a drug derived from it.
Finally, a Malaysian plant may produce a potential drug to combat AIDS, called calanolide A, which is now in human testing.
For more information, a good source is “Medicine Quest” by Mark J. Plotkin (Penguin Putnam Inc. New York) or check out www.amazonteam.org.