Apr. 6, 1998 Blacksburg, Va., -- Almost five years ago, a consortium of chemists, conservationists, and botanists began to work in Suriname to discover new drugs to treat human ills and to give the country reasons to preserve the diversity of its forests -- combining the ancient knowledge of shamans with modern chemical screening techniques and biotechnology. So far, the researchers have identified one novel compound with anticancer activity that has made it through several stages of tests at Bristol-Myers Squibb, identified another novel active compound with a structure that can be enhanced as an as analog, begun to develop new assays for the plants shamans use, identified a new species of plant, and saved some of the tropical forest from wood harvesting.
Virginia Tech Chemistry Professor David Kingston, principal investigator and group leader for the Suriname biodiversity utilization and conservation project, talked about "Biodiversity Conservation and Drug Discovery: Explorations in Suriname's Tropical Rainforests" at the American Chemical Society's 215th National Meeting in Dallas, Texas, March 29-April 2. His invited talk was part of the Ernest Guenther Award in the Chemistry of Natural Products Symposium. (The award is being presented to G. Robert Pettit of Arizona State University.)
After conducting some 14,000 assays of more than 3,300 extracts, Virginia Tech has identified 30 different, unique extracts that have activity and has isolated 20 chemical compounds that have bioactivity. "You've got to kiss a lot of frogs before you find a prince," says Kingston.
The most interesting compounds Virginia Tech has discovered are a group of alkaloids from Eclipta alba that have good antifungal activity, better in some cases than the clinically used drug amphotericin B. However, they also had weak cytotoxicity, and the decision was thus made not to develop them as antifungal agents. In another example, graduate student John Berger has been able to enhance the anticancer activity of a new compound by synthesizing analogs, reports Kingston. "Now we're looking for others with more activity from which we can make analogs."
Meanwhile, Bristol-Myers Squibb has put more than 3,000 extracts through 32 screens each in six different therapeutic areas, with the result that one promising compound is continuing to be tested.
While looking for potential pharmaceutical products, project scientists conduct ethnobotanical and random botanical collections. Conservation International (CI) researchers collect plants that the shamans use to treat disease and injury. Such ethnobotanical collection is time consuming. The scientists must gain the shamans' trust to be able to go with them to collect plants. Meanwhile, researchers from the Missouri Botanical Garden (MBG) collect plants of interest at random and end up collecting more plants.
"So which collection strategy is the most productive?" the group wondered. The best way to test plants' activity, says Kingston, is to test it against its intended application. "If you have a plant that the shamans say promotes wound healing, you test it for that benefit. But we have not done that because we don't have tests that mimic whole-body responses."
Pharmaceutical companies are interested in the fundamental biochemistry of disease and have highly specific biochemical assays that they believe provide targets for novel compounds.
"We said to ourselves, 'These plants have been picked out over centuries by the shamans, so one would expect them to be more active than plants collected at random.' So we decided to compare the activity of extracts from plants collected by CI and the Missouri Botanical Garden," Kingston says.
Using yeast-based assays, the Virginia Tech researchers found there was a slight benefit to the ethnobotanical approach: 2.8 percent of the plants collected at random were active in the yeast assay while 3.8 percent of the shamans' plants were bioactive.
"That's all you can expect because the assay we are using isn't specific to how the shamans use the plants."
Bristol-Myers Squibb is now trying to identify assays that will correlate better with the diseases identified by the shamans. "Then we will retest the extracts we've collected with the new assays," says Kingston.
The MBG biodiversity survey has also resulted in the discovery of five rare plants and one plant not previously found in Suriname. Suriname is in the top 50 countries in the world in the richness of its biodiversity.
Tropical forests have been the source of 60 percent of the anticancer drugs discovered in the last 10 years and offer a potentially huge economic reason for preserving the forest, based on the $200 billion market for plant-derived drugs. But the pace of discovery and development may be too slow compared to the certain, immediate payoffs from lumber sales.
"The Surinamese government was planning a large-scale timber concession," Kingston reports, "but the people from Conservation International emphasized that by selling the forest, the country would lose its benefits down the road." A working group within the government is now drafting a national biodiversity strategy using a biodiversity database developed by CI; and Suriname became a part to the Convention on Biodiversity and the Climate Change Convention, which results in some small grants.
Drugs developed from Surinamese plants will result in revenue for the country. And CI has been identifying non-timber forest products to determine their viability as sustainable products. But there need to be short-term incentives to reduce destruction of rainforests -- to counter the poverty that contributes to the loss of biodiversity, the researchers pointed out in their progress report.
Loss of biodiversity through deforestation not only removes materials that could be used to create pharmaceuticals, but eliminates herbal remedies -- a primary source of health care in many countries -- and accelerates the loss of traditional knowledge. One of the contributions of the Suriname project has been preservation of shamans' knowledge, not only in modern databases, but through a shaman's apprentice program.
The Suriname project did provide economic development incentives, in the form of employment in the country, improvements to the National Herbarium of Suriname, and formal training in curation and botanical research. Contributions were also made by Bristol-Myers Squibb to the Forest Peoples Fund, that supported a transport project, agricultural project, leadership and equipment use training, the first meeting ever of all the tribal leaders, and even the purchase of sports equipment.
The five-year research project is supported by a grant from the National Institutes of Health and the National Science Foundation. In addition to Kingston, team members are Jim Miller of the Missouri Botanical Garden, Russell Mittermeier of CI, Jan Wisse of Bedrijf Geneesmiddelen Voorziening Suriname, which is carrying out plant extraction and data management, and Dinesh Vyas of Bristol-Myers Squibb Pharmaceutical Research Institute. The team hopes to continue the work in Suriname with a new contract, and to extend the project to Madagascar, where there is more diversity than in Suriname and many plants that exist nowhere else in the world.
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