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Impact of the Convention on Biological Diversity: The Lessons of Ten Years of
Experience with Models for Equitable Sharing of Benefits
James S. Miller
Missouri Botanical Garden
P.O. Box 299, St. Louis, Missouri 63166-0299, U.S.A.
james.miller@mobot.org
Natural products discovery programs expanded tremendously during the last two
decades of the twentieth century because of a series of technological advances. The
ability to develop molecular bioassay targets, the introduction of mechanisms to
robotically control much of the screening process, and the incorporation of information
systems to analyze results have given rise to the capacity for screening very large
numbers of samples in short periods of time. This coupled with concern that available
biological resources will be diminished (e.g. Wilson, 1988) helped fuel tremendous
interest in natural products screening in the 1980s and 1990s. Plants were the major
focus of screening and numerous efforts to collect large sets of plant samples were
established during this period for several reasons. Plants have always been an important
source of chemical compounds useful in medicine and agriculture, they are quite diverse
with more than 250,000 species (Thorne, 2002), they are easier to collect than many other
groups of organisms, and they are easily cultivated to produce raw material for
production.
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The same time period that saw the introduction of new technology that facilitated
natural products work was also an era of intense discussion and examination of national
and international laws that governed ownership of and access to biological resources and
the property rights that controlled how benefits that arose from this type of work were
distributed. The most important of these was the Convention on Biological Diversity,
which entered into force in December of 1993 with the three specified aims of
conservation of biological diversity, sustainable use of its components, and fair and
equitable sharing of benefits (Glowka et al., 1994).
The research community has been an active partner in many collaborative natural
products discovery efforts, particularly the research groups of botanical gardens and
museums that often house strong collecting programs. These institutions conduct two
types of research. Most activities at research institutions involve basic or academic
research that extends knowledge, but do not seek to produce patentable products and do
not expected to generate monetary benefits. Commercial research is aimed at the
development of new marketable products, often through partnerships. Commercial
research has included discovery efforts looking for new pharmaceutical, agricultural, or
nutritional products from a wide variety of organisms with governmental, corporate, and
academic research partners. Access to large numbers of species for screening is a critical
component of all of these programs and the period of time from the mid-1980s through
the present time has been a period of great evolution in thinking about ownership of
biological resources and legal instruments to ensure equity in the distribution of benefits
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that arise from their development. Access to the biological resources that are the raw
materials for natural products discovery is one of the elements covered by the
Convention.
The present paper reviews issues associated with access to genetic resources and
equitable distribution of resulting benefits accruing from both basic and commercial
research, based on the experience of the Missouri Botanical Garden and other members
of the botanical research community. While natural products discovery efforts have been
conducted with many types of organisms, this paper will discuss only examples based on
plants as the issues surrounding access are parallel with other groups of organisms.
Specifically, the paper addresses three questions:
1. What kinds of benefits may be expected to result from natural products discovery
programs?
2. Has the Convention on Biological Diversity helped achieve more equitable
distribution of benefits?
3. What has been the impact of the Convention on Biological Diversity on
international botanical research?
What kinds of benefits may be expected to result from natural products discovery
programs?
One of the principal tenets of the Convention is equitable sharing of any benefits
derived from the development of biological resources. In general, drug development
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from natural products is expensive, time consuming, and the time between discovery and
marketing of new products is often well in excess of ten years (Farnsworth, 1984). As a
result, recent examples are limited and the value of access to biological diversity is
therefore open to great interpretation. Estimates of value vary greatly, no system for
assigning value has been universally accepted, and there are no recently discovered
products that could serve as auditable examples. Because of the lack of clear examples
that define value, the issue of equity remains open to question.
Benefits may be thought of as comprising three categories: public, long-term, and
short-term, each of which may be either monetary or non-monetary and direct and/or
indirect (Table 1). Direct benefits may be monetary or non-monetary and are those that
accrue to participants in the research programs, such as royalties for discoveries or
opportunities to participate in research. Indirect benefits are largely those elements that
arise from infrastructure supported by discovery programs, such as improvement in
research capacity of participating institutions where equipment provided to directly
support product development may also be used for educational or other research projects.
Public benefits include the direct contribution that new pharmaceutical,
agricultural, or nutritional products may provide by improving human health and
nutrition. The benefit of new drugs not only affects those directly involved with research
and marketing but also the general public, which benefits from the drug’s availability.
Research and conservation efforts also benefit indirectly from the support that
bioprospecting provides to the communities involved in these activities, such as improved
ability to conduct botanical inventory using vehicles and collecting supplies provided to
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the University of Ghana by a program that supplied plant samples for pharmaceutical
evaluation by the Monsanto Company.
Long-term benefits are associated with the primary goals that are central to
bioprospecting (discovery, marketing) and do not generally accrue until many years into
a research program or even afterwards. The accrual of long-term benefits is usually
dependent on successful discovery and product development, so they have a low
likelihood of accruing and thus can be considered high risk. Long-term benefits include
mechanisms for sharing monetary gains from developed products, means to ensure that
the products themselves will be available and affordable to the source counties that
contribute to their development, and mechanisms to guarantee that source countries will
play appropriate roles in the development and manufacture of new products, ensuring
another form of financial equity.
Short-term benefits are associated with the actual implementation of a research
program and are thus inherent and certain results of its operation. They are low risk and
it is almost certain they will be realized. Most short-term benefits are indirect, such as
support that arises through training and institutional capacity improvement, although they
can be direct when specifically funded as activities of individual programs. Short-term
benefits may be monetary, as in the case of up-front payments, but perhaps more
importantly they include activities that improve research capacity through institutional
support, training, and technology transfer, which can have significant impact in
developing countries.
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Post-Convention discussions have focused more on long-term, monetary benefits,
but it may be in the best immediate interest of developing countries with pressing
environmental problems to leverage acceptance of a smaller share of long-term benefits
that have a low probability of accruing to obtain a greater share of short-term benefits
that are more certain and will have more immediate impact. Large monetary benefits,
such as royalties on marketed drugs, generally accrue only after many years and the
chances of receiving such benefits are small. Short-term benefits, such as improving incountry technical capacity to advise on environmental issues, may be more beneficial in
the near term than pursuing the slim possibility that pharmaceutical royalties might arise
in the distant future.
Access to developed medicines is of great important in countries where health
care options are limited and the majority cannot afford the cost of drugs. This type of
benefit, which is often overlooked, may have a broader positive impact for the population
of a country than direct, monetary payments, which are likely to be more restricted in
distribution. As an example, the United States National Cancer Institute’s discovered
Michellamine B, a compound with potent in-vitro anti-HIV activity, from a sample of
Ancistrocladus korupensis collected in Cameroon. The compound later proved too toxic
to be used directly as a medicine, but had it progressed, it could have had wide impact in
a country with a serious AIDS epidemic. A drug of this sort made available at a cost
affordable in Cameroon through licensing of production technology or direct donation of
the medicine, might have affected more people than a direct monetary payment.
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Has the Convention on Biological Diversity helped achieve more equitable
distribution of benefits from botanical bioprospecting?
Using the definitions for the three kinds of benefits outlined above, it is possible
to examine several programs as case studies and review how effective they have been at
generating benefits as intended by the Convention. Since the Convention entered into
force, a variety of mechanisms have been developed to share benefits equitably and in
ways that support conservation and economic development. Achieving a successful
framework for sharing benefits that arise from both basic and commercial research has in
many countries become a pre-requisite for obtaining prior informed consent and ensuring
that permission to operate will be granted. There are many examples of programs that
have achieved interesting models for benefit sharing relationships with source countries
(e.g. Gamez et al., 1993; King, 1994; Carlson et al. 1997), two of which are reviewed
below.
The National Cancer Institute has been involved in natural products discovery
since its inception in 1937 (Shepartz, 1976). Its formal plant-collecting program, which
began in 1960, has been conducted in two phases. The first phase ran from 1960 through
1982 (Cragg et al., 1994b), and evaluated a large number of plants from many parts of the
world (Shepartz, 1976), collected largely by the USDA. The second phase, which began
in 1986 and continues to the present (Cragg et al., 1993), has been accomplished through
five-year contracts with outside organizations. The first and second five-year contract
periods of the second phase (1986-1996) included contracts to obtain material from South
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America, Africa and Madagascar, and tropical Asia. The third and fourth periods
included contracts for collections from North America, Africa and Madagascar, and
tropical Asia. The NCI program has frequently been cited as a model for appropriate
mechanisms to ensure equitable distribution of a wide range of benefits with source
countries (Cragg et al., 1994a). The NCI’s source country agreement, originally called
the Letter of Intent (LOI) and later the Letter of Collection (LOC), originated in
Madagascar in 1990 (Miller et al., this volume), a full year before the Merck-INBio
agreement (Reid et al., 1994). The LOC makes provisions for a range of potential
benefits, including royalties from sales of developed products, income from cultivation of
plant material for production, training and direct institutional support, and transfer of
technology.
The origins of several currently used anticancer drugs can be traced to the first
phase of plant screening from 1960 to 1982, including camptothecin (Potmeisel and
Pinedo, 1995) and taxol (Wall and Wani, 1994). However, the discovery and marketing
of both of these drugs predate the Convention on Biological Diversity, the NCI’s LOC,
and the evolution of modern ideas about equitable sharing of benefits. In the eighteenyear history of the second phase of NCI’s program, many novel bioactive compounds
have been discovered and characterized (e.g. Gustafson et al., 1992; Hallock et al., 1995),
several of which show promise for development (Cragg et al., 1994b). However, to date
no drugs have been approved and marketed as a result of NCI’s program so the complete
range of benefits anticipated in the LOC remains to be fully realized.
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One plant-derived compound identified during the currenct phase of NCI’s
program, calanolide A, is in human clinical trials (Cragg and Newman, 2002). This
compound, originally isolated from the latex of Calophyllum lanigerum but
semisynthetically produced from the more abundant C. teysmanii, shows significant
activity against HIV-1. Calanolide A has been developed through Sarawak Medichem
Pharmaceuticals Incorporated, a joint venture of the Sarawak State Government and
Medichem Research. Terms of the partnership ensure that research related to the
development of calanolide A takes place in Sarawak and helps build institutional capacity
there. If calanolide A progresses successfully through clinical trials and is approved as a
drug, it will be the first test of the NCI’s LOC as a legal instrument for generating longterm monetary benefits, such as royalties.
To date the NCI program has generated only limited long-term benefits, and no
direct financial royalties have accrued to participating countries. However, there are
numerous examples of short-term benefits that have provided very significant aid,
including training of scientific personnel, direct support for improvement of research
capacity and facilities in source countries, and opportunities for joint collaborative
research. The NCI program has provided opportunities for scientists from the United
States to partner in research with colleagues from source countries and has generated
support to ensure that facilities are adequate and technology is transferred through
equipment and training.
Another natural products discovery program that has developed interesting
models for access and benefit sharing is the International Cooperative Biodiversity
Groups (ICBG) sponsored by the National Institutes of Health (NIH), National Science
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Foundation (NSF), and the Department of Agriculture (USDA) and administered by the
Fogarty International Center at NIH. These programs aim to discovery novel natural
products through programs that support economic development and conservation in the
developing countries where they take place. The program began in 1993 (Rosenthal et
al., 1999), so it has less history than the NCI efforts and is thus further from marketing
drugs. However, the ICBG program has placed substantial emplasis on providing shortterm benefits. All eight ICBG projects have been built on strong partnerships with source
country institutions and several have been very successful at catalyzing an improvement
in the science conducted within those institutions.
The NCI and ICBG programs both demonstrate an obvious trend in
bioprospecting, namely that marketable discoveries are rare and, despite screening more
than 50,000 plant samples, none have yet yielded a new drug. The experience of these
two programs is consistent with other discovery efforts, all of which suggest that the
realization of marketable products requires many years. Not enough time has elapsed
since the Convention was ratified a decade ago to evaluate the potential of discovery
programs to deliver direct, monetary benefits such as royalties. During this period,
however, most bioprospecting programs have provided significant indirect, short-term
benefits such as increased scientific cooperation, training, and capacity building, which
have had a tremendous impact on capacity to conduct scientific research in source
countries. While discussions on equitable distribution of benefits have focused on
royalties and other long-term benefits, the examples presented here stress the importance
of short-term benefits that are more immediate and have a greater likelihood of accruing.
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What has been the impact of the Convention on Biological Diversity on
international botanical research?
While the Convention encourages source countries to promote access to their
biological resources in a regulated manner in exchange for an equitable share of the
benefits, article 15.1 states that the authority to regulate access rests with national
governments and is subject to national legislation. Article 15.5 explicitly requires that
prior informed consent be obtained from the party providing access to genetic resources,
yet many countries have been slow to develop transparent systems for regulating access
and to designate authority to regulate access to a specific government office. The
responses to this mandate have been quite varied but only a few countries, most notably
Costa Rica and the Philippines (ten Kate and Laird, 1999), have passed enabling
legislation specifically intended to regulate access. Glowka (1998) asserts that the
variety of national responses to implementation can be grouped into five categories
(Table 2), but in fact clear designation of which government office has the authority to
regulate access has been difficult to determine. The Convention Secretariat has recently
developed a guide to national focal points (http://www.biodiv.org/world/map.asp), which
should help facilitate negotiations in the future. In the absence of a transparent system
for obtaining prior informed consent, usually through a permitting process, negotiating
permission to operate and a system for sharing benefits can be complex and difficult.
Another problem with current regulatory systems is that they frequently have
been designed with the primary aim of controlling access to wild relatives of crop plants
or landraces that may be used in plant breeding programs or to material for use in
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bioprospecting efforts, the natural resources assumed to have the largest economic
potential. While controlling activities with obvious commercial goals is important,
regulatory systems have often not accommodated the differences between commercial
and basic or academic research. As a result, the expectations placed on basic researchers
are often similar to those of a commercially oriented program. Up-front payments,
expensive permit fees, and/or significant commitments to training or capacity building
may be reasonable expectations of research efforts conducted by large corporate entities,
but they may be prohibitive impediments for individual non-commercial researchers or
small commercial programs. Moreover, most basic research programs now face far more
complex procedures when applying for permission to collect and export material
necessary for study. The time needed to obtain approval has grown significantly longer
and application fees have generally increased. These procedures discourage small
research programs, both basic and commercial, that are unable to meet financial
expectations for benefit sharing, or which lack the resources necessary to complete long,
complex permitting processes.
Despite the weaknesses in the regulatory mechanisms of specific countries, the
Convention has been successful at catalyzing methods to achieve reasonable benefits
from commercial programs for pharmaceutical discovery or crop improvement. It has
become accepted practice to negotiate agreements (contracts) with source countries that
specify commitments and arrangements for distribution of benefits. Thus access to
genetic resources for most post-Convention commercial research programs now requires
structured plans for benefit sharing.
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Another success of the Convention has been to promote a re-examination of the
basic elements of scientific collaboration within the academic research community.
Examples of positive elements that have been at least implicitly expected by the drafters
of the Convention include research goals that more closely meet the expectations of both
parties, more equitable sharing of credit for research through joint authorship, fair
distribution of collected specimens, and full access to collected data. While basic
research programs should not be expected to yield large monetary benefits for source
countries, their indirect contributions to development of a scientific community with
greater capacity can be very significant, especially in countries where scientific expertise
is inadequate.
Ten years after the Convention entered into force, it is now apparent that the
initial expectations for large monetary benefits from new drugs or improved crop plants
were unrealistic. Since the Convention was originally conceptualized with these
elements in mind, the regulatory systems developed to date, have mostly aimed to capture
the kinds of benefits that were anticipated from large-scale commercial research. The
resulting regulatory structure is difficult and expensive for academic researchers to
penetrate as they attempt to obtain prior informed consent and permission to operate.
However, this same system has also led to a very positive re-examination of collaborative
research, which has fostered short-term benefits that have greatly supported the
development of biological research capacity in source countries. While large monetary,
long-term benefits remain an unfulfilled goal of commercial research programs, the shortterm, indirect benefits realized through the impact of the Convention have had a
tremendous positive influence on the growth of science in the developing world.
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Acknowledgements
Gordon Cragg and David Newman from the National Cancer Institute, Joshua
Rosenthal of the Fogarty International Center at NIH, Charles McManis from the
Washington University School of Law, and my colleages Pete Lowry, W.D. Stevens, and
D.K. Harder from the Missouri Botanical Garden have all been instrumental in helping
formulate my thoughts on access and benefit sharing issues. Support from the National
Institutes of Health through National Cancer Institute contract NO2-CM-17108 and one
of the ICBG projects through the Fogarty International Center have supported programs
that have encouraged our thought with these issues.
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Literature Cited
Carlson, T.J., M.M. Iwu, S.R. King, C. Obialor, and A. Ozioko. 1997. Medicinal plant
research in Nigeria: An approach for compliance with the Convention on Biological
Diversity. Diversity 13: 29-33.
Cragg, G., M. R. Boyd, J. H. Cardellina II, M. R. Grever, S. A. Shepartz, K. M. Snader,
and M. Suffness. 1993. Role of plants in the National Cancer Institute drug discovery
and development program. Pp. 80-95. In: A. D. Kinghorn and M. F. Balandrin (eds.)
Human Medicinal Agents from Plants. Amer. Chem. Soc. Symposium Series 534,
American Chemical Society, Washington, D.C.
Cragg, G. M., M. R. Boyd, M. R. Grever, T. D. Mays, D. J. Newman, and S. A. Shepartz.
1994a. Natural product drug discovery and development at the National Cancer Institute.
Policies for international collaboration and compensation. In: R. P. Adams, J. S. Miller,
E. M. Golenberg, and J. E. Adams (eds.) Conservation of Plant Genes II: Utilization of
Ancient and Modern DNA. Monogr. Syst. Bot. Missouri Bot. Gard. 48: 221-232.
Cragg, G. M., M. R. Boyd, J. H. Cardellina II, D. J. Newman, K. M. Snader, and T. G.
McCloud. 1994b. Ethnobotany and drug discovery: the experience of the US National
Cancer Institute. Pp. 178-196 In: D. J. Chadwick and J. Marsh (eds.) Ethnobotany and
Miller - 16
the Search for New Drugs. Ciba Foundation Symposium 154. Wiley and Sons,
Chichester, U.K.
Cragg, G. M. and D. J. Newman. 2002. Drugs from nature: past achievements, future
prospects. Pp. 23-37 In: M. M. Iwu and J. C. Wooten (eds.) Ethnomedicine and Drug
Discovery. Elsevier, Amsterdam.
Farnsworth, N. R. 1984. How can the well be dry when it is filled with water?
Economic Botany 38: 4-13.
Gámez, R., A. Piva, A. Sittenfeld, E. Leon, J. Jimenez, and G. Mirabelli. 1993. Pp. 5368 In: W. Reid, S.A. Laird, C.A. Meyer, R. Gámez, A. Sittenfeld, D.H. Janzen, M.A.
Gollin, and C. Juma (eds.) Biodiversity Prospecting: Using Genetic Resources for
Sustainable Development. World Resources Institute, Washington, DC.
Glowka, L. F. 1998. A guide to designing legal frameworks to determine access to
genetic resources. Environmental Policy and Law Paper no 34, IUCN Environmental
Law Centre, Bonn.
Glowka, L, F. Burhenne-Guilmin, and H. Synge. 1994. A Guide to the Convention on
Biological Diversity. Environmental Policy and Law Paper No. 30, IUCN – The World
Conservation Union, Gland, Switzerland and Cambridge, U.K.
Miller - 17
Gustafson, K.R., J.W. Blunt, M.H.G. Munro, R.W. Fuller, T.C. McKee, J.H. Cardellina
II, J.B. McMahon, G.M. Cragg, and M.R. Boyd. 1992. The Guttiferones, HIV-inhibitory
benzophenones from Symphonia globulifera, Garcinia livingstonei, Garcinia ovalifolia,
and Clusia rosea. Tetrahedron 48: 10093-10102.
Hallock, Y.F., J.H. Cardellina II, T. Kornek, K.P. Gulden, G. Bringmann, and M.R.
Boyd. 1995. Gentrymine B, the first quaternary isoquinoline alkaloid from
Ancistrocladus korupensis. Tetrahedron Letters 36: 4753-4756.
King, S. R. 1994. Establishing reciprocity: Biodiversity, Conservation, and New Models
for cooperation between forest-dwelling peoples and the pharmaceutical industry. Pp.
69-82 In: T. Greaves (ed) Intellectual Property Rights for Indigenous Peoples: A Source
Book. Society for Applied Anthropology, Oklahoma City, OK.
Potmeisel, M. and H. Pinedo. 1995. Camptothecins. New anticancer agents. CRC
Press, Boca Raton, FL.
Reid, W. V., S. A. Laird, R. Gámez, A. Sittenfeld, D. H. Janzen, M. A. Gollin, and C.
Juma. 1994. A new lease on life. Pp. 1-52 In: W. V. Reid, S. A. Laird, C. A. Meyer, R.
Gámez, A. Sittenfeld, D. H. Janzen, M. A. Gollin, C. Juma (eds.) Biodiversity
Prospecting: Using Genetic Resources for Sustainable Development. World Resources
Institute, Washington, D.C.
Miller - 18
Rosenthal, J., D. Beck, A. Bhat, J. Biswas, L. Brady, K. Bridbord, S. Collins, G. Cragg, J.
Edwards, A. Fairfield, M. Gottleib, L.A. Gschwind, Y. Hallock, R. Hawks, R. Hegyeli,
G. Johnson, G.T. Keusch, E.E. Lyons, R. Miller, J. Rodman, J. Roskoski, and D. SiegelCausey. 1999. Combining high risk science with ambitious social and economic goals.
Pharmaceutical Biology, 37, suppl. 6-21.
Schepartz, S. 1976. History of the National Cancer Institute and the plant screening
program. Cancer Treatment Reports 60: 975-978.
ten Kate, K. and S. Laird. 1999. The commercial use of biodiversity: access to genetic
resources and benefit-sharing. London: Earthscan.
Thorne, R. F. 2002. How many species of seed plants are there? Taxon 51: 511-512.
Wall, M. E. and M. C. Wani. 1994. Taxol: discovery to clinic. Pp. 299-322 In: H.
Wagner and N. R. Farnsworth (eds.) Economic and Medicinal Plant Research.
Academic Press, London.
Wilson, E. O. 1988. The current state of biological diversity. Pp. 3-18 In: E. O. Wilson
and F. M. Peter (eds.), Biodiversity, National Academy Press, Washington, D.C.
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_______________________________________________________________________
Table 1. Types of benefits that may arise from bioprospecting programs. Royalties,
milestone payments, and income from cultivation and supply of plant material are
monetary. All other benefits are non-monetary.
_______________________________________________________________________
Public Benefits

Positive Impact on Human Health (Direct)

Promotion of Research (Indirect)

Promotion of Conservation (Indirect)
Long-Term Benefits

Royalties (Direct)

Milestone Payments (Direct)

Income from Cultivation and Supply of Plant Material (Direct)

Access to Developed Technology (Direct)
Short-Term Benefits

Up-front payments (Direct)

Shared Research Opportunities (Direct & Indirect)

Exchange and Repatriation of Biological Data (Direct & Indirect)

Training (Direct & Indirect)

Institutional Capacity Improvement (Direct & Indirect)

Technology Transfer (Direct & Indirect)
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Table 2. Types of biodiversity access legislation (following Glowka, 1998)
Type of Law
Mechanism for Access
Example Countries
Environmental
Framework Laws
designate a national authority
to develop regulations for access
Kenya, Uganda
Sustainable
detailed laws that use principle of
Costa Rica, Mexico
Development; Nature prior informed consent to implement
Conservation, or
convention to regulate access
Biodiversity Laws
Dedicated Laws on
Access to Genetic
Resources
laws that specifically design
system for regulating access
Philippines
Modification of
Existing Laws
Amendments to existing law
to establish requirements for
Access
Nigeria
Regional Treaties
Multilateral agreements that
create a system for regulating
access
Andean Pact Countries:
Venezuela, Colombia,
Ecuador, Peru, Bolivia