Ethics, Biodiversity, and New Natural Products Development

This report was written by A.B.Cunningham as part of the WWF/UNESCO/Kew «People and Plants» Initiative. The report has been endorsed by the International Society of Ethnobiology. Any inaccuracies in the report remain the responsibility of the author. The opinions expressed are the author’s and do not necessarily reflect the views of WWF.

Author's address:

A B Cunningham
84 Watkins St, White Gum Valley, Freemantle,
6162, AUSTRALIA

Edited by Baxter Lindsay

Desktop publishing by Madlen Tschopp

Produced by the WWF International Publications Unit

Published April 1993 (under the title of Ethics, Ethnobiological Research, and Biodiversity), reprinted September 1996 by WWF-World Wide Fund For Nature (formerly World Wildlife Fund), Gland, Switzerland.

Any reproduction in full or in part of this publication must mention the title, and credit the above-mentioned publisher as the copyright owner.

Contents

Executive Summary

1. Introduction

2. Objectives

3. Procedures and Key Players in Chemical prospecting

4. The Issues Involved

4.1 Ethical and Legal Approaches

4.2 Conservation and Biodiversity

5. Wild Harvesting, Herbal Preparations, and Extracts

6. Expectations and Economic Benefits

7. Changes and Linkages

7.1 Researchers as Expert Advisors

7.2 Researchers as Brokers

7.3 Fitting Research Objectives to National and Local Priorities

8. Regional Returns

9. Policy and Principles for Equitable Partnerships

10. Checks and Balances

11. Conclusion

Appendix

List of Acronyms

Glossary

References

Personal Communications

Acknowledgements

Ethics, Biodiversity, and New Natural Products Development: Guidelines for the Equitable Use and Development of Indigenous Knowledge and Biological Resources

Executive Summary

In an ideal world, biological diversity would be protected for ethical, aesthetic, or spiritual reasons. Forests, coral reefs, or wetlands, for example, would be conserved out of respect for other forms of life, for their natural beauty, or for the spiritual link provided between the human species and the natural world. Unfortunately, this is not the case. Forests, coral reefs, and wetlands are not being adequately conserved. They are being replaced at an alarming rate by monocultures of crops, pasture, algae, or by construction projects.

Fortunately, utilitarian values (monetary and non-monetary) are playing an important role in justifying the conservation of biodiversity as a form of land use. «Chemical prospecting» is a useful argument in favour of conservation.

In an ideal academic world, there would be a free flow of knowledge for the good of all. But once again, this is not the case. In the development of natural products and in «chemical prospecting», research knowledge is often patented before it is made public ensuring a flow of benefits only to the patenting country or company.

Biodiversity will only be relevant to national governments or local people if a fair share of benefits from new natural products is returned to the region of origin. Until recently, however, chemical resources - whether derived from plants, corals or micro-organisms - were considered global common property. The fact is that biodiversity is being destroyed because it is undervalued, and chemical compounds that are the precursors of new natural products are no exception. To consider chemical compounds of the wild habitat as a global commons, freely available to all, reduces their value to national governments and to the local people who are best placed to conserve them. For this reason, clear guidelines are required for the development of new natural products.

National sovereignty is recognized wherever oil, minerals, timber, rattan, and several other resources are found. Why should. it not also apply to the chemical compounds that come from species with limited distribution? They are the starting points for the development of new natural products.

And what about the indigenous knowledge that provides a key to the active ingredients in plants or fungi? Why shouldn't this be recognized as the valuable product of an intellectual and experimental process? Why shouldn't local rights be attached to this knowledge as well as the natural compounds from biodiversity, before they are made public?

These questions cannot be resolved by ethnobiologists alone, but only through a wider awareness of the issues and actions required by governments, chemists, industrial companies, and the indigenous peoples involved. For this reason, these guidelines have been developed. They:

• outline the ethical and conservation issues that require the creation of equitable partnerships in the development of new natural products; partnerships that recognize and compensate for the use of indigenous knowledge and natural resources.
• facilitate international cooperation in the collection, conservation, use, and development of new natural products
• ensure that any collecting for export and use outside a country has the full approval of the competent authorities, and is carried out with the cooperation of the host country and representatives of the local communities involved. They also ensure that these collections comply with conservation and quarantine regulations in the countries of origin and destination
• outline the general principles that will facilitate the development of national regulations by governments or agreements between organizations.

This is not a futuristic issue. In 1991, the American National Cancer Institute (NCI) awarded three five-year collecting contracts worth $3.8 million to two US botanical gardens and the University of Illinois. A similar five-year contract worth $2.9 million was awarded to the Coral Reef Foundation for collecting marine organisms for screening. Kew Gardens has a contract from Glaxo to screen its living plant collection for active ingredients. In this way, scientific activities are directly linked to commercial interests. Understandably, national governments in the tropical countries concerned are asking "What right do these organizations have to 'privatize' our resources?"

A code of practice is suggested (see Appendix) that requires:

• Legislation to be enacted at a regional or national level to control the collection and export of biological material, with advice from appropriate professional organizations.
• A strict code of professional ethics to ensure that:

• research participants (e.g. traditional specialists) and members of relevant local organizations (e.g. herbaria) are fully informed of the objectives, commercial aspects, and possible results of research
• confidential information and research participants’, requests for anonymity are respected.
• equitable compensation is made for assistance by individuals
• the relevant national or regional organization receives fair royalty payments
• national requirements for plant collecting, including collection with local counterparts, are observed.

• Maximum use of local expertise within developing countries, or at regional level, to undertake extraction and screening of important compounds. This should apply equally to compounds of regional significance (e.g. anti-fungus, or anti-parasite) and global significance (e.g. anti-inflammation, anti-virus, anti-cancer). This will involve a commitment to training, technology transfer, and the development of practical, initial screening techniques. It will also require government support for local scientists and research organizations.
• Supply agreements should only be made with reputable organizations, not with individuals whose primary interest may be personal gain.

1. Introduction

This document is a research paper concerned with the ethical issues that arise when new commercial products are developed from biological materials. The main part of the paper is a discussion of the issues, and a recommended code of practice is given in the Appendix. Although the discussion concentrates on plants, similar principles apply to other organisms. Comments on this paper should be sent to the Biodiversity Unit, WWF International.

The bulk of the world’s biological and cultural diversity occurs in developing countries. These are rich sources of potential new natural products, and contain much indigenous knowledge about plant and animal uses. Although some developing countries, such as India and Brazil, have expanding pharmaceutical industries, much of the technology and expertise required to develop new industrial products from biological materials is centered in the industrialized countries of the temperate zone. For many researchers who are involved in recording indigenous knowledge and identifying potentially valuable biological resources, this raises ethical, legal, and political issues.

The need for socially and environmentally responsible action also applies to industrial companies, corporations and government agencies. Technological developments in genetic engineering and biotechnology, and new screening procedures for active ingredients have all stimulated interest amongst large companies which see new industrial products arising from plants, micro-organisms and marine organisms (Weislow et al., 1989; Hamburger et al., 1991).^69,33 At the same time, there is the realization that both indigenous knowledge and biological diversity are disappearing with cultural and environmental change.

Three main issues have been the focus of parallel debates relating to professional ethics, traditional knowledge and plant conservation. First, international debate since the early 1980s has focused on local knowledge, farmers' rights, and equity in the distribution and control of genetic resources from crop plants (Mooney, 1983; Kloppenberg, 1988).^50,42 This issue has drawn heated opposition from some prominent botanists (Arnold et al., 1986),⁶ but was partially resolved when the Commission on Plant Genetic Resources (PGR) revised the FAO Undertaking for PGR to recognize both plant-breeders’ and farmers’ rights (WRI, 1992).⁷⁰

Second and more recently, there has been debate relating to the development of new natural products from plants. There has been focus on new pharmaceuticals, but the issues are similar in the case of development of new waxes, oils, perfumes, and other products. (The issues are also similar in the case of other types of organisms, such as soil fungi, marine organisms, and terrestrial animals.)

The third area of debate has been the distribution of economic benefits from plant species with horticultural potential, such as the African violet (Saintpaulia) (Lovett, 1988).⁴⁵

These debates hinge on:

• the recognition of the intellectual contribution made by farmers or specialist plant users, such as herbalists, beekeepers, and master fishermen, to the development or identification of crop land races and new natural products
• the equitable distribution of benefits from the use of these crops, ornamentals, wild plants, or their genetic or chemical structures, to assist people and the conservation of biodiversity in their regions of origin
• commitment to technology transfer, infrastructure development, training programmes, and local government support to enable the development of crop varieties, new natural products and horticultural exports in the regions of origin.

Debate on these issues has also pointed to the linked interests of multinational companies such as Ciba-Geigy, Pfizer, and Monsanto in the seeds, fertilizer and pharmaceuticals industries (see Table 1 and Mooney, 1983).^35,50 It has also called into question the historic international view that indigenous knowledge, as well as chemical and genetic resources, is a freely available global commons i.e. the property of everyone. An unfortunate result of regarding indigenous knowledge, chemical structures, or genes as common property is that these resources are seen as belonging to nobody, and there is little incentive to conserve either species or habitats. This view has recently changed.

Table 1. The world's top ten pharmaceutical, seed and pesticide companies showing dominance of major companies in these fields and their global sales values.

(USA = United States of America; UK = United Kingdom: F = France: G = Germany: NL = Netherlands: CH = Switzerland)

From Hobbelinh 1991³⁵

* Elanco was formed by the merger between Eli Lilley and Dow Chemicals

In 1989, UNESCO (see List of Acronyms) adopted a resultion on the Safeguarding of Traditional Culture and Folklore (UNESCO, 1989).⁶⁶ In 1991, the FAO Commission on Plant Genetic Resources produced a draft International Code of Conduct for Plant Germplasm Collecting and Transfer (FAO, 1991).²⁷ This was a voluntary code of conduct recognizing farmers’ rights and setting guidelines for the exchange of germplasm. It was addressed to FAO, UNEP, UNESCO, IBPGR, CGIAR, and other international and national agricultural research institutions. In 1992, these issues were highlighted at the UNCED meeting in Rio de Janeiro, and through the Global Biodiversity Strategy (World Resources Institute, 1992).⁷⁰

These developments have emphasized the need for researchers, collectors, and sponsoring organizations to clarify their codes of ethics. They have also focused attention on the importance of developing equitable partnerships for «capturing» and effectively dispersing benefits from these resources, rather than considering them global commodities. Three features highlight this issue:

• First, countries rich in biodiversity generally have low per-capita income, while most countries in the North are wealthy (see Table 2).
• Second, most companies involved in the development of new drugs from plants, micro-organisms, and marine organisms are based in the industrialized countries of the North.
• Third, there is wide recognition of the role that economics can play in justifying conservation as a form of land use (McNeely, 1988)⁴⁹ and the need to maximize "value-adding" from resource harvesting, including the use of genes and chemical structures.

Table 2. Wild plant diversity and financial income.

From Davis et al., 1986; WRI, 1992 ^22,70

2.Objectives

This paper is intended for policy makers in governments, research institutes, botanical gardens, herbaria, universities, and industry. It outlines some of the dilemmas facing ethnobotanists, anthropologists, and phytochemists in developing new natural products from biological materials, and suggests solutions. Recommendations for a code of practice are made in the Appendix.

The specific objectives of this paper are:

• to present the background to the ethical and conservation issues that arise in the development of new natural products; in particular, to outline the need to create equitable partnerships and recognize the value of indigenous knowledge which will lead to the payment of fair compensation to source regions
• to facilitate international cooperation in the collection, conservation, use, and development of new natural products
• to ensure that any collecting for export and use outside a country has the full approval of the competent authorities, and is carried out with the cooperation of the host country and representatives of the local communities involved; also to ensure that these collections comply with conservation and quarantine regulations in the countries of origin and destination
• to outline the general principles that will facilitate development of national regulations by governments or agreements between organizations.
•  

3. Procedures and Key Players in Chemical Prospecting

The interest in new biological compounds has stimulated a search for sample material from almost the entire range of life forms, and in every corner of the globe. Typical examples include parasitologists working with Antibody Systems, Inc. searching for parasites on Tasmanian devils (Bowie, 1992),¹² marine biologists screening Gorgonian corals from tropical reefs for anti-inflammatory compounds, botanists collecting medicinal plants for anti-cancer or anti-HIV activity, and mycologists collecting soil from tropical rainforests to find new antibiotics.

The search for new natural products is widely recognized as an interdisciplinary process with the following steps (Hamburger et al., 1991):³³

§ collection, scientific identification and preservation of the biological material

§ preparation of appropriate extracts and preliminary chromatographic analysis

§ biological and pharmacological screening of crude extracts

• consecutive steps of chromatographic separation, with bioassays for each fraction (activity- guided fractionation)

§ verification of the purity of isolated compounds

§ elucidation of structure by chemical and physico-chemical methods

§ partial or total synthesis

§ preparation of derivatives/analogues and investigation of structure-activity relationships

§ large-scale isolation for further pharmacological and toxicological tests.

What may be forgotten in the laboratory is the role that indigenous knowledge often plays in new drug discovery (Figure 1). Collectors of plants for screening take three basic approaches to obtaining samples (Figure 2).

First, with random sampling, material is collected from the largest possible number of identifiable plant species within a habitat, with the emphasis on plants that are flowering or fruiting, so that good voucher specimens are obtained. A second approach is to focus collecting on certain plant families that are known to be rich sources of interesting, biologically active compounds such as the Apocynaceae, Euphorbiaceae, Menispermaceae , and Solanaceae . Third, collecting is guided by a knowledge of traditional uses of plants; this has been termed «ethnodirected» sampling (Balick, 1990).⁸

Figure 1. As experts on «underground botany» and the symbolic and active ingredients of local plants, traditional healers such as this diviner (isangoma) in southern Africa can play an important role in «ethno-directed» sampling. Photo: A B Cunningham

Collectors initially take samples ranging from 50g for soils to a few kilograms in the case of plants or coral. Extracts are prepared and screened for activity against diseases such as cancer and AIDS. In many cases, additional collections are required, to obtain sufficient material for isolation and identification of the active compound(s). In this case, large quantities of material may be collected by professional contract plant collectors on short collecting trips, gathering large bulk samples for screening. In some cases, this swift bulk collection is made possible because of reference to herbarium material and ethnobotanical information previously collected by other researchers. In the 1970s for example, in only 17 days in Tanzania, a USA-based professional collector gathered 150-kg samples of each of 14 plant species, including 150-kg samples of bark from Garcinia smeathmannii and Podocarpus milanjianus trees. Other examples are his collections of 10-15 tonnes of Maytenus buchanani in East Africa and 5 tonnes of Bouvardia ternifolia plants in Mexico. This collector still operates under contract for the American NCI and has formed an organization which specializes in bulk collecting. The sustainability of this scale of collecting is questionable. In Kenya, local overexploitation of the widespread shrub Maytenus buchanani certainly took place in a conservation area in the Shimba hulls so that NCI could screen for its value as an anticancer agent. When additional material was required four years after the first harvesting in 1972, regeneration was found to have been so poor that collectors reportedly struggled to obtain additional material (Juma, 1989).40 Fortunately, the recent surge of interest in screening for new compounds has increased awareness of the conservation implications of destructive harvesting and the need for equitable partnerships.

	Figure 2. The three main collection methods used in sampling plant material for biologically active compounds (Balick, 1990).7 A: Random sampling. B: Taxonomically directed sampling. C: «pre-screening» based on indigenous knowledge of plant uses. This has been termed «ethno-directed» sampling.

Figure 3. Fruits and seeds of Castanospermum australe (Fabaceae). This Australian tree is the source of the anti-viral compound, castanospermine, which has been used in treating the HIV virus which causes AIDS. Photo A.B. Cunningham

Table 3. Pharmaceutical companies and research organizations involved in screening plants for new natural products, showing sources of supply.

From Findeisen, 1991²⁹ and other sources

Recent advances in molecular and biochemical pharmacology have made it easier to carry out new assays for the development of drugs from plants, micro-organisms, and marine corals. As a result, new screening programmes have been started in a wide range of developing countries. These programmes focus on identifying active compounds with anti-cancer, anti-HIV, anti-inflammatory, antibiotic, or anti-parasitic activity. Endemic species are of particular interest. There is also a resurgence of interest in soil fungi, particularly non-streptomycetous actinomycetes, due to increasing resistance in humans to commonly used antibiotics.

The value of contracts awarded by the US Developmental Therapeutics Programme (DTP) of the NCI indicates how much interest there is in discovering new natural-product drugs. In 1986 three five-year contracts worth $2.7 million were awarded. In 1991 these were renewed, with the three contracts valued at $3.8 million (NCI, 1992).⁵¹ The three contractors are all based in the USA: Missouri Botanical Garden, Bishop Museum, Honolulu, and New York Botanical Garden together with the University of Illinois at Chicago, which subcontracts to the Arnold Arboretum (Harvard University). Collections are focused respectively on Africa and Madagascar, Central and South America, and Southeast Asia. These collaborative programmes have resulted in the discovery of several interesting new compounds, including some with anti-HIV properties, from the Ancistrocladaceae, Combretaceae, Euphorbiaceae, and Piperaceae (Kashman et al., 1992;⁴¹ Table 4). A similar five-year contract, valued at $2.9 million, was awarded to the Coral Reef Foundation for collection of marine organisms to determine their potential as the source of valuable new compounds.

In the past, collecting has been largely uncontrolled, with sample material usually being taken for analysis to Europe, Japan, or North America. Drug development and patenting has taken place without the knowledge of people in the country of origin, with no recompense for use of regional natural resources, and often without any contractual obligation. When permit applications have been made, this has been done without indicating the commercial intent of the collectors. Local professionals such as botanists or foresters are paid privately to collect samples for industrial companies or other sponsoring organizations. These people often do not understand the full implications of their work and their payment bears little relation to the potential value of the resource. As many developing countries pay them relatively little, and hard currency is hard to get, it is understandable that this occurs. Nevertheless, it has important implications for regional development and conservation. From the point of view of national and local interests, why should these sponsoring organizations be allowed to treat a county's natural resources as global common property, especially considering that the natural resources may later be privatized by the same organization?

Table 4. Examples of drugs and new therapeutic agents discovered by screening plants for biologically active substances.

(Also indicated: species’ region of origin, potential clinical use, and use in traditional medicine)

From Hamburger et al., 1991;³³ Manfredi et al., 1991;⁴⁷ Kashman et al., 1992;⁴¹ Gustafson et al., 1992.³²

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