No. 37, Spring/Summer 1995
by Barbara N. Timmermann and Barbara Hutchinson
The International Cooperative Biodiversity Groups (ICBG) program was developed as a result of the United Nations The Convention on Biological Diversity, also known as the Biodiversity Treaty, which was signed in mid-1992 at the Earth Summit in Rio de Janeiro, Brazil. The ICBGs are sponsored by the U.S. National Institutes of Health (NIH), including the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the National Heart, Lung, and Blood Institute; the National Science Foundation (NSF); and the U.S. Agency for International Development (USAID). Administered by the Fogarty International Center, the international arm of the NIH, the ICBG program seeks to involve developing countries in drug discovery from natural sources and in sustainable development by improving infrastructure, developing inventories of native species and indigenous knowledge, training scientists, and assisting with priority health needs.
In September 1993, one of five ICBG projects was awarded to The University of Arizona. The project, titled "Bioactive Agents from Dryland Plants of Latin America," is a five-year collaborative effort and a creative legal and partnership agreement among universities, corporations, and government and nongovernmental nonprofit organizations. The project seeks to discover and develop pharmaceuticals and crop-protection agents from plants of arid and semiarid ecosystems in the participating countries in Latin America and to promote sustainable economic activity while conserving biological resources in fragile environments.(Back to top)
This ICBG involves researchers from The University of Arizona in collaboration with researchers at Pontifícia Universidad Católica de Chile in Santiago, the Instituto de Recursos Biológicos in Buenos Aires, the Universidad Nacional de la Patagonia in Comodoro Rivadavia, Argentina, the Universidad Nacional de Mexico, the Medical (Lederle) and Agricultural (Cyanamid) Divisions of American Cyanamid Company, Purdue University, and the GWL Hansen's Disease Center of the U. S. Department of Health and Human Services (HHS).
The University of Arizona is represented by several academic and research units, including the Office of Arid Lands Studies (its Arid Lands Information Center, Bioresources Research Facility, and Arizona Remote Sensing Center), the Department of Pharmacology/Toxicology (Natural Products Chemistry Laboratory), the School of Renewable Natural Resources, and the Department of Anthropology.
Exploration and Collection. Exploration for new drugs begins by collecting native plants from poorly known floristic areas. Once a plant is located, 1 kg (2.2 lbs) of its leaves, flowers, and stems are collected from areas in which the species occurs in relative abundance and using methods that leave the plant alive and able to reproduce either vegetatively or generatively. The highest priority is given to plant species that have a known history of ethnobotanical uses, which increases the chances for drug discovery and commercialization. Shamans, herbalists, and curanderos in the collection areas are contacted and interviewed about plant remedies from the local flora and herbal remedies are acquired at local markets from reputable sources. Plants also are collected at random because there are many diseases, such as AIDS, that do not have a history of ethnobotanical treatment.
In addition, herbarium specimens are collected for classification by taxonomists and for distribution to the herbaria of the collaborating institutions, as well as to other major herbaria, including the U.S. National Herbarium, the Smithsonian Institution, the New York Botanical Gardens, and the Royal Botanic Gardens at Kew in the United Kingdom.
Noted on specially designed forms is a variety of information, including the longitude, latitude, and elevation of the collection site, the collected plant's phenology and growth, other species that grow in the population, and type of soil. The location of the population is documented using a hand-held electronic device (geopositioning system) that picks up the exact location from Earth's orbiting satellites.
Extraction and Analysis. Plant biomass from Chile is mailed directly to Arizona for extraction; plants from Argentina and Mexico are extracted in their home countries. Fractionation and bioassay-guided isolation and characterization of the active natural products is done both in Arizona and in Mexico, using state of the art techniques for isolation and structure elucidation of the active natural products.
Plant extracts, fractions, and pure compounds are submitted to a battery of bioassays using several automated, high throughput enzyme assays developed by Lederle and American Cyanamid. An assortment of mechanism-based, whole organism, and enzyme-induction assays are employed in the primary screening program. An extensive battery of organisms resistant to a wide variety of clinically used antimicrobial agents are employed for secondary testing of active leads.
Both mechanism-based and whole virus-infected tissue culture assays for RNA and DNA viruses, including HIV, are part of the anti-infective program. Molecular targets, such as unique virus-encoded enzymes and regulatory proteins, are emphasized. Therapeutic areas of potential target application include the central nervous system, the cardiovascular system, intermediary metabolism, allergy/inflammation, the gastrointestinal system, cancer, anti-viral, anti-bacterial, and agricultural applications in crop protection and animal health. Bioassays against tuberculosis, leprosy and opportunistic infections using the BACTEC system are conducted at the GWL Hansen's Disease Center.
Biodiversity Conservation and Economic Development. One of the project's central goals is to address biodiversity conservation and sustainable economic activity, including development of strategies for minimizing negative environmental impacts and assuring that economic and social benefits accrue to the local community.
In this connection, the project concerns itself with the potential for commercial production of biological compounds that ultimately could result in development of specialty cash crops for the country in which the compound originated. If a valuable chemical is discovered, for example, the source plant could be cultivated to provide local jobs or could be sustainably collected from the wild by people from nearby communities.
Intellectual property agreements were negotiated among all participating institutions before the project began, to ensure that economic benefits from any discovery are equitably shared. If new drugs are developed and marketed, a percentage of royalties from sales will go back to the communities that supplied the plant and to those individuals who provided information about the plant. A substantial share of any royalty proceeds also will go to trust funds for conservation projects in the country where a drug was discovered.
Information Management. One of the unique features of the project is an information management and dissemination component. It was designed to promote the sharing of resources and knowledge and to create the necessary framework for achieving the project's long-term conservation and public health goals.
Specific plans include building an arid lands plant database, including bibliographic and geographic information systems (GIS) functions, and helping to build information-handling capabilities at all project sites to facilitate collaboration among the cooperating institutions.
The primary tool for communication at this time is a newsletter, Bio-D Prospects , which is produced quarterly at The University of Arizona with input from information counterparts at each participating institution. Issues contain updates on all project components, as well as news items, publications announcements, and columns on Internet information resources.(Back to top)
About 500 plant species were collected and classified during the project's first year; bioassays and isolation of active natural products are underway for some specimens and completed for others. Information and data obtained during the collection phase are being entered into the BIOD-Database, a custom-designed graphical user interface based on Microsoft's MS Access relational database management (RDBM) package. Concurrently, database searches for bibliographic citations are being performed on arid lands plants selected for study by project personnel. BIOSIS, Chemical Abstracts, CAB ABSTRACTS, Napralert, and Medline databases are the primary focus for the searches and selected results are being compiled as a companion to the BIOD-Database.
Another important part of the project is training and infrastructure support for host-country institutions and the training of both Latin American and North American graduate students and postdoctoral fellows. Several U.S. graduate students are conducting ethnobotanical field research in South America as part of their Master's theses and Ph.D. dissertations. One microbiologist from Argentina is learning anti-tuberculosis assays in the U.S. and soon will be joined by a colleague from Buenos Aires. Laboratory equipment, computers, collecting gear, and other items have been purchased with ICBG funds to improve the technological capabilities of collaborating countries.
In the area of biodiversity conservation and sustainable development, the first year of the project focused on establishing cooperative relationships among academic, governmental, and nongovernmental agencies. Team members gathered background materials on biodiversity, sustainability, and traditional uses of plants. They also briefed the research team on the principles of the Biodiversity Treaty and its implications for this project.
Finally, a background paper covering treaties, intellectual property rights, and conservation strategies was prepared to provide the framework for workshops planned for Latin America in early 1996. The purpose of these workshops is to insure that biodiversity and cultural issues are considered in the process of prospecting for plant resources.
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