Plant-based research among the International Cooperative Biodiversity Groups

Abstract

The International Cooperative Biodiversity Groups (ICBG), administered by the Fogarty International Center, was created in 1992. By 2007, the program had completed three cycles of funding. In the last cycle (2003-2008), seven ICBGs were operating in biodiversity hotspots around the world with support from nine Institutes and Centers of the National Institutes of Health and from the National Science Foundation and the US Department of Agriculture. Accomplishments over the history of the program include discovery of numerous bioactive compounds, training of thousands of young scientists in the US and abroad, and the creation and enhancement of biodiversity protected areas around the world. Over the history of the ICBG program plant-based research has been a significant component of many projects. Over 10,000 species of tropical, temperate and arid lands plants from 350 plant families have been analyzed. While some of the research has been guided by ethnobotanical science, particularly science oriented toward botanical medicines, much has been focused around diversity-oriented collections, and some have used ecological principles to identify active compounds. While marine and microbial organisms have grown in importance among the natural products research community, plants will continue to play important roles for the foreseeable future.

Keywords::

• ICBG
• plant research
• biodiversity conservation
• drug discovery
• economic growth

Introduction

The International Cooperative Biodiversity Groups (ICBG) is one of the longest running programs (1993-present) of the Fogarty International Center (FIC) of the National Institutes of Health (NIH). This past year, FIC celebrated its 40th anniversary (Fogarty International Center, 2009). Since its founding in 1968, FIC has been dedicated to advancing the mission of the NIH by supporting and facilitating global health research through international partnerships. Consistent with a focus on population health in low and middle income countries, Fogarty has long viewed environmental quality as an integral aspect of human health.

Significant advances have been made during the past decade in understanding the relationship between human health, economic welfare and ecosystem quality, and many of these are recognized in the voluminous Global Assessment Reports of the Millennium Ecosystem Assessment program, “Ecosystems and Human Well-being” (MEA, 2005). A general understanding has emerged that improvements in human health may be impeded by the destruction of the natural resources that provide important ecosystem services such as purifying water and air. Similarly, we understand that biodiversity has provided a diversity of modern products to society (Chivian & Bernstein, 2008). For instance, biodiversity has provided and continues to provide foodstuffs, cosmetics, industrial oils, and medicines (Beattie et al., 2005). Among the latter, it is estimated that 40-50% of currently used drugs have an origin in natural products (Newman et al., 2003). Today, there are dozens of new natural product-based drugs in clinical trials, and some of these will likely emerge as important treatments in the future (Newman & Cragg, 2007).

Unfortunately, a combination of factors have led to a decline in the relative investment dedicated directly to natural products discovery research from both industrial and government sources over the past decade. The emergence of high throughput screening and the associated speed of analysis have placed the more complex natural product molecules, especially in unpurified extracts, at a competitive disadvantage relative to synthetics in large discovery programs. The availability of the complete sequence of the human genome has led to a growing focus on rational design of therapeutics and a consequent de-emphasis on molecular diversity screening for new drugs. Finally, the political and legal challenges posed by the access and benefit-sharing regimes for international collections-based research have discouraged many from conducting or investing in natural products research. In this context, it is worth noting that it is likely that less than 1% of the world’s probable 14 million taxa have been scientifically investigated for potential pharmaceutical utility. Accelerating habitat destruction and the resulting loss of biodiversity through extinction elevates the urgency of our need to explore biodiversity and find ways to support conservation efforts.

The ICBG is a unique effort to address the interdependent issues of drug discovery, biodiversity conservation, and sustainable benefits to countries who provide genetic resources for research. The conceptual basis for the ICBG program was developed during a conference in 1991 (Schweitzer et al., 1991) sponsored by the NIH, the National Science Foundation (NSF) and the US Agency for International Development (USAID). The conference focused on the potential relationships between drug development, biological diversity and economic growth. As an outcome of this conference, the ICBG program was initiated in 1992 in a collaborative effort of NIH, NSF and USAID to advance these three interrelated goals. Interagency cooperation was required to cover the broad mandate of the ICBG and, as the program evolved, the drug discovery component was expanded to encompass more areas of biodiscovery. Over the history of this program, funding has been provided by four agencies of the US government: nine components of the National Institutes of Health (NIH); both the Biological and Geological Sciences Directorates of the NSF; USAID; and both the Foreign Agriculture Service and the Forest Service of the US Department of Agriculture (USDA). More recently, the Office of Biological and Environmental Research of the Department of Energy and the Cooperative State Research, Education and Extension Service of the USDA have joined the program. The cooperating NIH components are FIC, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, National Center for Complementary and Alternative Medicine, Office of Dietary Supplements, and National Institute of General Medical Sciences.

The implementation of this program is based on the belief that the discovery and development of pharmaceutical and other useful agents from the world’s biodiversity can, under appropriate circumstances, promote scientific capacity development and economic incentives to conserve the biological resources from which these products are derived. The individual projects are undertaken in such a way that local communities and other source country organizations can derive direct benefits from the activities of the projects and ultimately from the diverse biological resources of their countries. In this way benefit-sharing may provide clear incentives for preservation and sustainable use of biodiversity (Rosenthal, 1999; Rosenthal et al., 1999; Rosenthal & Katz, 2004). To date there have been three competition cycles (1993, 1998 and 2003/2005), which provided 4- to 5-year cooperative agreement awards to support collaborations between the USA and low- and middle-income country institutions and scientists. Reflecting the wide range of goals and activities in the projects, the research teams represent a diversity of scientific expertise and often involve public–private partnerships, including pharmaceutical and agrochemical companies. A complete review of the first two cycles of the ICBG Program has been published (Rosenthal et al., 1999).

Progress to date

Given the multiple goals and complexity of the ICBG program, there have also been achievements in multiple areas including chemistry, ecology, biodiversity, and policy development, which have been documented in over 500 publications in the academic literature. In the area of biodiscovery, the ICBG projects have employed a diversity of approaches to access biological and chemical diversity, including collections based on taxonomy, ecology, and ethnobotany, and the use of metagenomics and metabolic engineering for isolation of small molecule new chemical entities and botanicals. To date, over 11,500 species of macroorganisms have been collected, including terrestrial plant species (11,000+), marine algae/invertebrates (200+), and lichens (200+). Several thousand microorganisms including endophytic fungi (2,000 isolates) and bacteria (2,000 isolates) have also been examined. These species have been analyzed in bioassays across 26 therapeutic areas and several agrochemical areas, and more than 1,300 bioactive compounds have been isolated, many of them new to science. Many of these compounds and their activities have been published. Examples of plant extracts and compounds with diverse activities of current interest include the cytotoxic ipomoeassins from Suriname (Cao et al., 2005, 2007); the anti-Mycobacterium tuberculosis (TB) micromolides from Vietnam (Ma et al., 2005); anti-TB tetrahydroxysqualene from Papua New Guinea (Noro et al., 2008), anti-Leishmania aporphine alkaloids from Panama (Montenegro et al., 2003; Correa et al., 2006), and anti-inflammatory plant extracts from Central Asia (Dey et al., 2008).

In addition, new species and genera have been identified, although most of these are not yet published. Between 75 and 100 new species of plants have been described or are in the process of identification. Among others, these include two new genera and species of orchids (Averyanov & Averyanova, 2003; Soejarto et al., 2006) and a new species of Begonia (Nguyen & Tebbitt, 2005) from Vietnam, and two new species of Olax from Madagascar (Ravintsara, 2006).

Short-term benefits to host countries have been diverse. On the conservation front, the projects have directly initiated new biodiversity reserves and/or strengthened existing reserves in eight countries. A recent example is a cooperative effort in Panama initiated by the Panama ICBG that resulted in the designation of Coiba National Park as a new World Heritage Site (UNESCO, 2009). Importantly, over 4,000 people have been trained in drug discovery and biodiversity sciences, 90% of whom were from the collaborating low- and middle-income countries. Among these there were 350 long-term trainees, including 125 Master’s and Doctoral students. Of these degree students, 70% were from the host countries. Furthermore, the program has increased laboratory, museum and field research capacity in over 50 institutions across 21 countries.

Finally, the program as a whole and the projects individually have informed multiple United Nations proceedings regarding access and benefit sharing policies in development under the Convention on Biological Diversity (CBD, 1992), and have influenced relevant national policies in at least 12 countries. Our principal policy message is that well-constructed projects can and should return multiple benefits to both users and providers of biodiversity, whether or not a strict legal regime is in place. The ICBG philosophical approach identifies equitable partnerships as an explicit and necessary objective of any high quality international research project that is working in low income nations. The short- and medium-term products of the FIC-managed Biodiversity Program reflect this approach and illustrate how local communities and other host country organizations can derive direct benefits from collaborative research on their diverse biological resources. At least one important benefit is incentive and knowledge to enhance preservation and sustainable use of that biodiversity.

Current ICBG awards

At the completion of the third cycle of awards, there were seven active ICBGs working in ten countries in Latin America, Africa, Southeast and Central Asia, and the Pacific Islands, building research capacity in more than 20 different institutions and training hundreds of individuals (Appendix 1). Total inter-agency funding for the program in the fiscal year 2007 was $6 million, with approximately $800,000 per project in total costs per year.

These projects include discovery and analysis of natural products derived from biological diversity as potential therapeutic agents for diseases of concern to both developed and developing countries. Diseases of concern include AIDS, malaria, tuberculosis and other infectious diseases, cancers, heart disease, metabolic syndrome, drug addiction and central nervous system disorders, including Alzheimer’s disease. Other important components include discovery of safe new agents for crop protection and veterinary medicines. In the most recent (fourth) round of awards, ICBGs have begun to incorporate study of microorganisms that may yield enhanced technologies for the breakdown of complex plant biomass to facilitate cellulosic ethanol production and the discovery of alternative biofuels.

All ICBG projects include biodiversity inventories and surveys, and several examine and document traditional medical practices and the biochemical basis of plant-based medicines. Efforts to develop long-term strategies to ensure sustainable harvesting, to promote training and infrastructure support for host-country institutions and long-term funding for biodiversity conservation in the host countries are significant components of several projects (Fogarty International Center, 2009).

Future of plants and pharmaceutical research

Examining recent trends in publications, clinical trials, and investments by government and industry leads us to believe that marine and microbial organisms are starting to dominate natural products-based drug discovery. We believe that plants will continue to have an important role in bioprospecting in several ways. Ethnomedical investigations of plants should continue to help us uncover new biological mechanisms for therapeutics. Consumer health concerns and interests in botanicals will continue to stimulate research and training opportunities. Finally, plants will continue to play a major role in the pharmacopeia of traditional societies, and will continue to make plant-based research important for conservation and development planning.

Appendix 1. International Cooperative Biodiversity Groups (2003-2008).

Biodiversity conservation and drug discovery in Madagascar

Dr. David G.I. Kingston of the Virginia Polytechnic Institute and State University in Blacksburg, Virginia, is collaborating in a fourth five-year ICBG to study tropical plants, marine organisms and microorganisms in Madagascar. The group includes Missouri Botanical Garden, Conservation International, the Madagascar National Centers for Pharmaceutical Research, for Environmental Research, and for Oceanographic Research as well as Eisai Research Institute and Dow Agrosciences.

ICBG: Training, conservation and drug discovery using Panamanian microorganisms

Dr. William H. Gerwick, in collaboration with colleagues at the Smithsonian Tropical Research Institute, building on two previous five-year ICBG awards, continue a biodiscovery program in Panama for discovery of both pharmaceutical and agricultural products from endophytic fungi, cyanobacteria and heterotrophic bacteria from both terrestrial and marine sources. Partners include the University of Panama, Panama’s National Secretariat for Science, Technology, and Innovation (INDICASAT), Smithsonian Tropical Research Institute, University of California San Diego, University of Utah, University of California Santa Cruz, Oregon State University, Scripps Institution of Oceanography, University of Arizona, Eisai Research Institute and Dow Agrosciences.

Biodiversity of Vietnam and Laos

Dr. Djaja (Doel) Soejarto and colleagues from the University of Illinois at Chicago are leading a second five-year ICBG to integrate studies on biodiversity and the discovery of pharmacological agents for AIDS, cancer, malaria and tuberculosis from tropical forest plants of Laos and Vietnam. Collaborating institutions include the National Center for Natural Sciences and Technology and Cuc-Phuong National Park in Vietnam, the Research Institute for Medicinal Plants in Laos, Purdue University, and Bristol Myers-Squibb Pharmaceutical Research Institute.

Building new pharmaceutical capabilities in central Asia

Dr. Ilya Raskin and colleagues from Rutgers University lead a project focused on the plant, fungal and microbial biodiversity of Uzbekistan, Kyrgyzstan, Tajikistan, and Khazakhstan. Other partners include the University of Illinois at Champaign-Urbana, Tashkent State Agrarian University and Kyrgyz Agricultural Research Institute, Eisai Research Institute, Wyeth Pharmaceuticals, Phytomedics Inc., and WellGen.

Conservation and sustainable use of biodiversity in Papua New Guinea

Dr. Louis R. Barrows and colleagues from the University of Utah are collaborating with several organizations of Papua New Guinea as sources of pharmaceutical and botanical therapies for local and global health needs. Partners in this project include the University of Papua New Guinea, National Forest Research Institute, and PNG Bionet of Papua New Guinea, the Smithsonian Institution, University of Miami, Nature Conservancy, and Wyeth Pharmaceuticals.

Ecological leads: Drugs from reefs and microbes in Fiji

Dr. Mark Hay and colleagues of the Georgia Institute of Technology are collaborating with Scripps Institution of Oceanography, the University of the South Pacific, and the South Pacific Applied Geoscience Commission of Fiji to examine plant, freshwater and marine coral reef organisms of Fiji to assess conservation priorities and discover new therapeutic agents.

Potential drugs from poorly understood Costa Rican biota

Dr. Jon Clardy of Harvard University is collaborating with the National Biodiversity Institute of Costa Rica (INBio) to explore poorly understood endophytic fungi and uncultured soil microbes of Costa Rica. Bioassays cover a wide diversity of therapeutic areas.

Acknowledgements

This paper was first presented at the symposium “Plants in the service of human health: Continuing search for plant-based therapies” as part of the 48th annual meeting of the Society for Economic Botany at Lake Forest College in Chicago, June 4, 2007.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.