12.2 The Search for Rain Forest Drugs

I. GREEN MEDICINES

After World War II, the manufacture of synthetic drugs became increasingly important as interest in plant derivatives waned. By 1974, the last cycle of plant-hunting for medicines was ending. The interest in the rain forests was largely left to National Geographic.

Interest in ethnobotany was kept alive by Richard Schultes, a curator, story teller, expert on hallucinogenic drugs . . . and Harvard professor. He has drawn attention to ethnobotany, admittedly a messy, muddy, unpredictable disease ridden work. Ethnobotany may come across as romantic on these pages, but the dropout rate amongst graduate students in the field is high.

Schultes' plea that the botanical knowledge of indigenous peoples should be respected is at last now being heard. During World War II, he became an expert on rubber trees when the Japanese cut off the supply in South East Asia. His definitive work, The Healing Forest is cited at the end of this article. It is in the IUN library.

"A thousand years of practice by the Mayans has got to yield some clues," Schultes notes. The number of plants thoroughly examined for medicinal value range from less than one % to about 10%. Half a percent (that is 0.5%) has given us 25% of all of our drugs. Medicine hunters would do well to look first at traditional folk medicine for new leads. Schulteis' student, Wade Davis (author of Serpent and the Rainbow) have blended anthropology and ethnobotany. He makes an interesting point: cataloging plants is dull business, but studying their cultural use is interesting and productive. Ethnobotany's resurgence has been fueled by a new urgency: the tropical rain forests and aboriginal cultures may soon be gone.

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II. RAINFORESTS AND CONSERVATION

Why are rain forests so diverse? Diversity is greatest where there is the most sunshine, the most climate uniformity, and the largest geographic area. The soils are only two inches thick, yet they support a remarkable ecological system. In the hot, moist environment, the tropical forest lives upon itself with virtually all of its biomass above ground. Stable climate encourages competition amongst the various plants. One of the weapons in that competition is chemical warfare--secondary metabolites.

Unfortunately, the biologically rich countries in the tropics are poor in money. Thus, the rainforests are targeted for exploitation.

One effort at forest preservation is with 'debt-for-nature' swaps. Wealthy First World donors pay off Third World debt in exchange for saving forest acreage. Another tactic is eco-tourism to places such as Iquitos, Peru. There, ACEER-the Amazon Center for Environmental Education and Research is a tax-exempt organization that attains its goals supported by Explorama tours, International Expeditions, and concerned individuals. All royalties revert to the rainforest, via ACEER. (My comment: I did one of those tours in 1995: it was a memorable experience.) Another exciting avenue to save rain forests is to develop their use as a renewable resource.

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III. WORLD WIDE SEARCH FOR PLANT-BASED MEDICINALS

In 1982, the National Cancer Institute began again to look for new drugs from the rain forest. There are good reasons for such renewed interest. One quarter of all prescription drugs contains a useful plant ingredient. One hundred twenty-one prescription drugs are made from higher plants. This does NOT include antibiotics from microorganisms. Half of these plant-based medicines come from the tropics, and 74% of these came from native folklore.

One innovation to aid the search is INBio, the National Institute of Biodiversity in Costa Rica. It has become a cooperative effort between First World donors and Costa Rica. This raises a thorny question: who owns the rights to the genetic resources? It is a continuing debate.

In the decade before INBio, Merck was one of the few companies to keep up its natural products division. It struck pay dirt, literally, with its development of Mevacor© from a soil fungus. (My note: Mevacor is one of the statins now popular for reducing cholesterol.) Another drug marketed by Sandoz is Cyclosporine. It is used to keep transplant patients from rejecting donated organs. Cyclosporine also comes from a fungus.

Bats, ticks, and even creatures from the sea are being screened for phytochemicals. Bloodsuckers like mosquitoes, ticks and hookworms make potent anticoagulants--chemicals that keep the blood from clotting. Drug companies hope that so called natural anticoagulants could be more effective than the present blood thinning agents. A new hookworm protein shows promise as an anticoagulant that in time could replace heparin, a 40-year-old drug. Another promising anticoagulant is hirudin, derived from the saliva from the leech. A drug derived from bats has been used to dissolve artery-clogging blood clots, but it is a protein and humans develop an antibody to it. (My comment: you may find this esoteric, but think of it this way: nature is a testing laboratory with many species competing over a very long period of time.)

The search for medicinals from insects has begun in a big way. Have you seen the Sean Connery film Medicine Man? Researchers have explained that chemical communication is one of the oldest and most basic ways of getting a message across. Our sense of smell is based on it. So are neurotransmitters and hormones inside our bodies. Ants make chemical trails to guide members of their colonies.

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INBio has become a vehicle for the search. How is it done? Plants and insects are ground up and compounds extracted. The assay techniques, a trade secret, are designed to target a specific 'working part' of a bacterium, virus, or cancer cell at the biochemical level. If a chemical shows promise, the real challenge begins, making the discovery work for humans.

If an extract 'rings all of the bells,' that is reacts with most or all of the assays, it is normally discarded. If the extract 'rings just a few bells,' then it is broken down into its individual components and each one is researched. It is a tedious process.

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IV. COMMERCIAL EXPLOITATION AND GENETIC RIGHTS

INBio has brought up the issue of ownership, namely: who owns the planet's diversity? It is a big stakes game with hundreds of millions of dollars as the lure. The drug industry argues that biodiversity can be bought and sold. What are the rights of indigenous peoples? They have often been exploited by their home governments and they are dubious of foreigners. Ownership of resources is a contentious issue. Madagascar didn't make a dime off of its periwinkle.

Wall Street came up with a creative wrinkle. Shaman Pharmaceuticals, Inc. was founded in 1989 on the premise that native healers' knowledge of medicinal plants could help unearth curative compounds. (My note: note the approach here: Instead of blindly gathering, grinding, and testing rain forest plants, indigenous healers are approached first for their knowledge. They used the shaman's extensive arsenal of medicinal knowledge plus centuries of clinical trials to narrow their search.)

Shaman, Inc. devoted some 20% of its plant prospecting budget to help finance water, school and social welfare projects in exchange for knowledge about medicinal flora. Shaman Inc. hoped for major successes in finding antiviral and antifungal compounds. (My note: Shaman Pharmaceutical is on the NASDAQ; its price in March, 1998, was about $5. per share. This compares to about $6. two years ago. As of July, 1999 Shaman had not brought a single product to market. It is no longer listed on the NASDAQ.)

Others have used a less focused search technique. In the field, crude assays are done just to determine if harvested plants contain any of the major bioactive compounds such as alkaloids. Rain forest drugs are the long shot, and many identified bioactive compounds end up with no human use. There are a lot of plants to examine. The Shuar, for example, use a phenomenal 245 different plants as medicines. They use 103 plant species just for gastrointestinal ailments.

First World intrusion into the rain forest is accelerating the disappearance of native knowledge. Potent manufactured drugs easily replace local medicinals, leading to the discredit of indigenous healers. Formal schooling which replaces apprenticeship learning tends to be on the Western model, another blow to local medicine men.

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V. THE END OF THE PIPELINE

At Fort Dietrick in Maryland is the end of the pipeline from such places as Ecuador, Belize, the Cameroon and many other places. This is the National Cancer Institutes' Natural Products Repository, where plants. fungi, protozoa and microorganisms come from all over the earth. The NCI's plant discovery program was restarted in 1986. Back in 1982, the NCI had quit its phytochemical search. An early search of 100,000 plants and 200,000 microorganisms had yielded nothing. For a brief period, synthetic chemicals alone were used by researchers. One idea that fuels future research comes from aboriginal people themselves: almost every plant has a purpose. Furthermore, they can be used sustainably.

Not everyone agrees on a random 'find, grind, and test.' Michael Boyd argues that the methods used in the search are wrong. The endeavor had been for a 'magic bullet'--against tumors in mice. Humans aren't mice! Cancer, for example, is not just one disease, but is a family of diseases. There is another way to test besides the 'find them and grind them' approach.

Boyd suggested and developed a more delicate approach. It involves tissue culture. Tissue culture is the technique of growing small colonies of cells in the laboratory. (My note: tissue culture is NOT easy; I did it for my PhD thesis and the problems are many. Among them are contamination, refusal of the cells to grow in vitro, infection, and other pitfalls.)

The plan devised by Boyd was this: To grow sixty variations of cancer cells in tiny wells punched into plastic sheets. Into each well would go extracts from nature, up to 300 a week in a continuous production. Boyd signed on three organizations for the job: The New York Botanical Garden, the Missouri Botanical Garden, and the University of Illinois at Chicago.

Growing human cancer cells in the laboratory is a tricky business, but the technique has led to new prospects for further investigation. In 1990, a wonder drug materialized, not from some exotic tropical island, but from here in the United States. The substance was taxol, derived from the Pacific yew.

Why test the bark of a tree for phytochemicals? Bark extracts have a long history with Native Americans, and alkaloids from yew bark were known prior to the identification of taxol. Once refined, it proved stunningly successful against ovarian cancer. In 1993, taxol was approved by the FDA. In its development, a conservation dilemma appeared: should the Pacific yew trees be harvested to extinction for its bark, or should cancer victims die to save the trees? Bristol Myer solved the problem by developing a semi-synthetic process that could use common forms of yew instead of the scarce wild growing Pacific yew.

Renewed plant-hunting on a global scale has raised the question of intellectual property rights, corporate profits, and proprietary drugs. Third World governments are in principle dead set against turning over what they consider to be their genetic treasure. To appease the countries where plant hunters roam, the NCI has offered a 'letter of intent' to assure that there will be no rip-and-run exploitation. This assures an NCI effort to share profits. By accident, one of the most powerful HIV-killers from plants was found in Australia back in 1989. It was conocurvone. It was found in the Outback. Australia, a country with its own sophisticated drug industry considers the NCI letter to be 'toilet paper' and won't submit it to NCI. It remains in preliminary trials. The search continues with ongoing pleas to save the rain forest so it will be there for the future.

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VI. RECENT EVENTS

In 1999, Brazil spoke out against 'jungle plunder' by biotech firms. They want a portion of the money make from rainforest products to be returned to them.

A California company already has patented the active ingredient in the forest vine ayahuasca, which indigenous Brazilians use to brew an ancient purgative and hallucinogenic drink used in religious ceremonies. Furious Indians charge that this is tantamount to them patenting the Roman Catholic host. The Brazilians charge that flood collected from Brazilian Indians is being marketed on the Internet.

Brazil wishes to have anyone collecting indigenous genes or knowledge is required to specify what financial return would go back to local communities. Brazil has a painful memory of plant theft: Latex rubber tree seeds were smuggled out of the country nearly a century ago.

The United States refused to sign a biodiversity treaty with foreign countries, wishing instead to preserve the strength of patent laws.

Source:

Goering, L. "Brazil wants cut of biotech firms' jungle plunder" Chicago Tribuen July 6, 1999.

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A program at the University of Illinois at Chicago has, for the last six years, been collecting plants world wide. They test about 200 plants a year collected from 30 countries. The greenhouses and storage areas in Downers Grove are where the plants are dried, pulverized, and then tested in UIC facilities on Chicago's Near West Side. Of any 100 plants tested, only about three may have a chemical worthy of further investigation in fighting cancer,

Source:

Christian, S. "UIC attacks cancer's root" Chicago Tribune September 5, 1999.

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..... CJ '99

Resources

Duke and Vasquez Amazonian Ethnobotanical Dictionary Boca Raton: CRC Press, 1994.

Goering, L. "Tiny frog offers major new painkiller, drug research finds) Chicago Tribune August 30, 1998

Gould, P. "Prairie Pharm" Kankakee Journal January 24, 1999.

Gregory, T. "Summer Harvest of Hope" Chicago Tribune September 8, 1999.

Haapoja, M. "Tropical Medicine: An Interview with Sadie Brorson" Hemispheres March, 1997.

Joyce, C. Earthly Goods Medicine Hunting in the Rainforest New York: Little Brown & Company, 1994.

Plotkin, M. Tales of a Shaman's Apprentice New York: Penguin Group, 1994.

Stevens, D. "Lab grows on potential for health' Chicago Tribune June 18, 1997.