SAN FRANCISCO, Oct. 16 (UPI) -- In the end, the destiny of the world's dwindling rainforests may depend on drugs, diversity and dividends, conclude researchers who spent five years determining the pragmatics of pinpointing plants with pharmaceutical potential beneath the lush canopy of the Panamanian jungle.
In completing their $3-million survey, the investigators have devised what they see as a practical plan to protect nature's delicate handiwork from decimation. Given proper financial incentives, drug companies can work hand-in-hand with developing nations poor in economy but rich in biodiversity to salvage one of Earth's most valuable, and most threatened, natural resources, the international team of scientists maintains.
Their vision hinges the gateway to success on the pharmaceutical industry establishing scientific laboratories in the Third World and hiring local researchers to extract new medicines from plants that, over the eons, have devised defense mechanisms against insects.
"Until now, efforts to find drugs in the rainforest haven't really led to rainforest conservation," said Tom Kursar, an associate professor and one of the duo of University of Utah biologists who led the collaborative effort, which included 15 U.S. and Panamanian specialists. "But we have developed a novel approach that provides a direct link between looking for drugs and promoting conservation and economic development in biodiversity-rich countries."
Their own experience bespeaks the soundness of their proposal, the scientists state.
"In our research, not only are we finding potential pharmaceuticals, but we are (also) contributing to conservation of the forests," said Phyllis Coley, a biology professor and Kursar's personal and professional partner.
Searching for drugs in the rapidly vanishing rainforests of developing countries might forestall the disappearance of natural treasures that could fill humanity's coffers, she noted.
"(Rainforests) are home to more species of organisms than any other habitat," Coley told United Press International. "The repercussions of losing these habitats are enormous, not only for the species that are lost, but also for global climate, for the livelihood of people living in the tropics and for the goods and services we receive."
The so-called bioprospecting route to rainforest salvation is built on the premise that developing nations will work to preserve their wilderness if nondestructive industries -- among them drug research, ecotourism and watershed protection -- outperform logging and ranching in financial benefits.
The fly in this potential ointment for the ailing economies and disappearing forests of the Third World has been the failure to produce timely, lucrative results. Only a small fraction of compounds derived from plant extracts -- 1 in 10,000 or 1 in 5,000, by some rough estimates -- actually are developed into drugs. Even when they are, it takes years for the rainforests' home country to start earning royalties.
"The challenge, therefore, is to provide immediate and guaranteed benefits even if royalties are not forthcoming," the biologists note in Frontiers in Ecology and the Environment, a journal published by the Ecological Society of America.
Up to one-third of the research carried out by drug companies -- which invest $27 billion to $43 billion worldwide each year in such endeavors -- could be conducted in the Third World, the researchers estimate.
However, those in the business may have other ideas, a spokesman for the Pharmaceutical Research and Manufacturers of America suggested.
"Most companies already have more targets in their research bins than they can handle," said Mark Grayson, PhRMA's deputy vice president for communications. The group represents 34 of the biggest names in an industry that invested more than $30 billion in 2002 in discovering and developing treatments and cures.
"As the National Institutes of Health points out, only 5 percent of research targets are developed, so there's no shortage of targets," Grayson said in a telephone interview. Looking for medicines in plants growing in developing countries "is nowhere near the top of our priority list," he added.
Grayson noted drug discovery and development is an arduous, high-risk and expensive proposition, and called it "suicide" for a company to establish research projects in areas with small potential for investment recovery or profit making.
Nevertheless, proponents do not regard the plan as such a hard sell.
"The advantage of the Panama model is that we are not asking for new funds, simply suggesting that it might be productive to invest current funds in new places," Kursar told UPI, "and, in fact, those research dollars might stretch farther in developing nations."
In a mere five years, for example, the pilot project realized:
-- the establishment of six laboratories in Panama;
-- the employment of home-grown talent, including 10 senior scientists, 57 paid research assistants and 12 student volunteers, and
-- the higher education of dozens of local students, with 20 earning bachelors degrees, 12 receiving or working on master's degrees and one embarking on doctoral studies.
"We don't think there is actual resistance to the idea of collaborating with scientists from developing nations, so if we can make it easy for pharmaceutical companies or granting agencies, we think it will actually happen," Kursar said.
The impetus must come from institutions such as the National Institutes of Health, the National Science Foundation, the European Union, non-governmental organizations, conservation groups, the United Nations and non-profit foundations, researchers told UPI. Already, there is some progressive movement afoot, they noted.
For example, the International Cooperative Biodiversity Groups program, conceived in 1991 by the NIH, NSF and the U.S. Agency for International Development to focus on the interrelationship among drug development, biological diversity and economic growth, has just entered its third round of funding projects.
"In part because of the success of the Panama model, (the ICBG) made it a requirement to have a significant portion of the project based in the (plant) source countries," Kursar said.
About half of all new drugs come from natural products derived from plants, microbes and, to some extent, animals such as corals and other marine lifeforms, poison arrow frogs and insects, the ICBG notes.
Of the 868 treatments developed between 1981 and 2002, 55 percent had such beginnings, David Newman, Gordon Cragg and Kenneth Snader, all of the National Cancer Institute in Bethesda, Md., noted in an analysis published in the July issue of the Journal of Natural Products. From 2000 to 2002, they traced 50 of 83 new drugs -- or 60 percent -- to similarly natural roots.
"To stay competitive, companies must find unstudied organisms that may provide novel medicines, the tropics being a very attractive target," Coley said.
As a bonus, the Panama project yielded the first test of a compound's effect on malaria -- a plague that kills a child somewhere in the world every 20 seconds -- that does not require radioactivity, thereby making its use plausible in developing countries. Already, scientists from Madagascar have arrived in Panama, eager to learn the technique.
In addition, the Smithsonian Tropical Research Institute in Balboa, Panama -- where Coley and Kursar also hold appointments -- and Panamanian scientists have obtained a provisional patent for four alkaloid chemicals extracted from local plants.
Laboratory tests by Luis Cubilla Rios of the University of Panama and Luz Romero of Florida State University in Panama revealed the compounds' toxic effect on the parasite that causes leishmaniasis, a disfiguring and potentially fatal disease transmitted by the bite of any of 30 species of sand flies.
Endemic in 88 countries on five continents -- Africa, Asia, Europe, North and South America -- the infection threatens some 350 million people, according to the World Health Organization. The disease affects an estimated 12 million people worldwide, with 2.4 million new cases and 59,000 deaths reported in 2002 alone.
Most often attacking the skin or internal organs, the disease brings on a variety of symptoms, ranging from self-healing but unsightly ulcers to life-threatening infections. Currently, no vaccines or drugs are available to prevent the infection.
The researchers are establishing mice colonies in Panama to test the safety and effectiveness of the newfound compounds against leishmaniasis. They hope to expand the research to other tropical diseases. Their work -- funded by the NIH, NSF and U.S. Department of Agriculture -- won praise from Jeffrey McNeeley, chief scientist of the World Conservation Union in Switzerland.
"(The new project) shows how to conduct more of the value-added bioprospecting research in the source country and build the technical capacity of local people while doing so," McNeeley said.
The study brought to light ways to boost the effectiveness of drug discovery by focusing on the chemical arsenal plants have assembled against insects. The scientists tested extracts from leaves carpeting Panama's protected wild lands on breast, lung and nervous system cancer cells; the AIDS virus, and organisms causing malaria, leishmaniasis and Chagas' disease, a parasitic infection with an annual death toll of 50,000. They found younger leaves, not yet toughened in their anti-pest defenses, showed greater chemical activity and higher number of potentially useful compounds than did older ones, even on the same plant.
They also discovered shade-tolerant flora offer a more plentiful source of active substances than the sun worshippers, which can replace insect-ravaged leaves more quickly and, therefore, have less need to develop stronger chemical defenses.
"Probably the most important, from a drug-discovery point of view, is that young leaves are defended by both greater amounts and by unique compounds not found in mature leaves," Coley said. "Thus, conventional collections, which have focused on mature leaves, may have missed much of the chemical promise in plants."
In the next phase, the scientists will work to improve techniques to purify and test promising compounds in mice, continue training Panamanian students and serve as a model for other countries.
"Personally, we have seen the destruction of tropical forests worldwide, and it is very painful," Coley told UPI. "Although drug companies have done little to safeguard this resource, our project agrees that drug discovery could play a key role in saving the rainforest."
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