ICBG 2002 Program Review Report

I. Executive Summary

The Fogarty International Center (FIC) commissioned this review of the International Cooperative Biodiversity Groups (ICBG) program as it nears the completion of its second award cycle. The objective of the review was to advise FIC and its interagency partners as to whether the ICBG program continues to meet its sponsor's several, interrelated goals and objectives. Initiated in 1993, the ICBG Program is a unique effort that addresses the interdependent issues of drug discovery from natural products, biodiversity conservation, and sustainable economic growth.

The ICBGs are public-private, multi-national consortia funded by cooperative agreement awards from FIC, other components of the National Institutes of Health (NIH,) the US Department of Agriculture, and the National Science Foundation. The NIH institutes participating are the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute on Drug Abuse and the the National Heart, Lung, and Blood Institute.

The reviewers are convinced that the ICBG program should continue and be expanded. The ICBG program concept of combining drug discovery with conservation and economic development represents a critically important approach both for identifying new drugs and other products from natural sources and for assuring fair and equitable distribution of benefits from bioprospecting. The next round of grants must build on the 9 years of experience in the program. Given the information and time available for the review, the reviewers felt that they could not with complete confidence answer the question, 'Does linking conservation, economic development, or drug discovery in the ICBG program or in a given grant improve the probability of success across the spectrum of goals?'. Nonetheless, the reviewers are convinced that the ICBG program shows every indication that it is a successful experiment. There are many examples of achievements including and arising from the processes used to implement the conceptual basis of the ICBGs. For example, the number of species collected and screened in drug discovery efforts since the onset of the program is impressive. Moreover, the ICBGs have done an outstanding job in establishing agreements that define potential benefits and how the benefits from drug discovery will be allocated. Indeed, the ICBG program is leading the effort worldwide to implement the principles of the Convention on Biological Diversity. The ultimate goal of the ICBG program is to assure that when an ICBG grant ends, the scientific, technical, operational, and infrastructure capacities for sustaining drug discovery, related conservation and economic incentives are established in the host countries and remain conceptually linked. If this objective is met it would be, in itself, sufficient justification for the investment of resources by FIC and its partner agencies.

Recommendations for shaping and maturing the ICBG program over the next five to ten years emerged from the review. The reviewers made the following recommendations:

• Drug discovery, conservation and economic development should continue as the core elements of the ICBGs.

• Drug discovery should continue to be the first among three equal goals of the ICBG program, with conservation and creating economic incentives for drug discovery given the emphasis required so that they too will be legacies of the ICBG program.

• ICBG policy should be to fund new grants in two phases: First a planning phase in which grantees establish the fundamental structure and substantive national and local contributions in planning for the ICBG in the host country. Second, an implementation phase to carry out the plans developed in the first phase.

• ICBG grants should include a "business plan" that defines the economic incentives for benefits sharing; agreements, procedures and policies for equitable sharing; and a process whereby the local program will become self-sustaining.

• Given the importance of the ICBG experiment FIC should commission a comprehensive analysis of the 1993-2002 ICBG program to determine what has worked and how, and what has not worked and why.

II. Panel of Experts

III. Introduction and Context

The Fogarty International Center (FIC) initiated the International Cooperative Biodiversity Groups (ICBG) grant program in 1991. The ICBGs seek new drugs and other uses from natural products. The ICBGs are unique in that they also work to integrate conservation and economic growth into their drug discovery efforts. The ICBGs are funded by grants from FIC, other components of the National Institutes of Health (NIH,) the US Department of Agriculture, and the National Science Foundation. The grants are awarded for five years and the second round of grants is expiring. FIC managers are considering whether to continue the ICBG program and assessing the goals and scope of the program should it be continued. The other federal institutes and agencies are also evaluating the ICBG program to assure that it is meeting their missions and priorities in drug discovery, promotion of agriculture, biodiversity conservation, and the advancement of science.

The FIC organized a review of the ICBGs to provide an independent set of observations and recommendations. The primary purpose of the review was to advise as to whether the ICBG program continues to meet its sponsors' several, interrelated goals and objectives.

Drugs derived from plants and other natural products continue to make up a major part of the pharmacopoeia of allopathic medicine. Traditional medicine practiced by indigenous peoples in undeveloped areas relies almost exclusively on locally available natural products for use in treating disease and other health conditions. Herbal medicines have an important role across the range of medical practices worldwide and the use of herbal products is growing in the west. Natural products still have a vast potential as a source of medicines. Neither have they been fully explored for broader application in animal health, nutrition, agriculture or other beneficial uses. Thus it would seem that biomedical researchers from academia, pharmaceutical companies, and research entrepreneurs would be rushing to find new drugs in natural products. At the same time their counterparts from veterinary medicine, agriculture sciences, and elsewhere would be evaluating the same resources for their own purposes. In fact this research is progressing at a slower pace than might be expected. There are several intersecting, complicating factors that impede drug discovery and other uses of natural products. Among these are difficult scientific, logistical, economic, social and cultural, and political problems.

There are millions, if not tens of millions, of species among the plants, insects, animals, and microbes on Earth that make up the biological diversity of nature that may yield drug and other beneficial uses. Only a fraction of these have been identified and classified. Very few of the known species have been completely evaluated for beneficial uses. This diverse panorama provides a huge resource base that scientists must select from to screen for potential new drugs. Attractive leads from screening must then be proven to be a practical source of a safe and effective compound for treatment or prevention of disease, an expensive and lengthy process.

The majority of species are found in underdeveloped or undeveloped areas. The application of cutting edge scientific methods and technologies in these remote regions is logistically demanding. Drug discovery requires the application of many specialized scientific disciplines, including medicine and public health, chemistry, several biological sciences, sociology, anthropology, ecology, toxicology and pharmacology, statistics, and informatics. Convening multidisciplinary groups is not easy in modern research institutions and is much more difficult in remote areas where the expertise must be drawn from both local and foreign sources. Maintaining the cutting edge of science in drug discovery from natural products also demands remaining abreast of rapid progress in biomedical research in genetics, genomics and proteomics, combinatorial chemistry, and advances in development of synthetic drugs.

Species, habitats, and genetic biodiversity are being lost at a rapid rate across the globe. The loss is due to resource development, agricultural and industrial practice, and other stresses. At the same time that diversity is being lost, social change and disruption among indigenous people leads to loss of traditional knowledge of the properties and uses of local natural products for medicinal and other purposes. The result is an irrevocable disappearance of species, habitats, and genetic resources that are invaluable in their own right and should be conserved, and the concomitant loss of their potential for improving human health and well being.

Conflict between the desire to conserve habitats rich in biodiversity and development of these areas for commercial, industrial, agricultural, mining, or similar uses creates difficult economic and social equity questions. Drug discovery from natural products is affected by the outcome of the debate addressing these questions and to a limited extent helps frame the questions. Drug discovery is clearly less probable if species are lost to development. But it is not possible to assure that conservation of species to permit drug discovery will bring the level of benefit realized by other developmental uses of the habitat areas. Typically, from the developing country perspective, the economic benefits from commercial or agricultural development of unique habitats would be viewed as a significant benefit to the national economy and perhaps to the local community. Drug discovery and conservation do not compete well by comparison.

There are tensions between who benefits from and who pays for conservation and drug discovery. For example, if the search for a drug used to promote the health of people in the area where the natural product exists is successful, then the local benefit is greater. However, because the diseases that affect indigenous people in remote areas and the populations of developing countries are not the same as those causing greatest morbidity and mortality in the developed world, there are powerful economic incentives to seek drugs for the latter purpose rather than the former. The organization that manages and pays for natural product research expects to benefit both from professional recognition for an important discovery and economically from its sales.

Few developing countries have established a system of rules to govern access to and benefits sharing from development of their biodiversity. Who may enter to collect, and when, and what and how much may be removed on what terms may not be clear. Such practical matters must be resolved to avoid possible misunderstanding and conflict. Equity questions cannot be avoided and are particularly difficult when drug discovery efforts are launched in a developing country by an organization from a country with an advanced economy. While the external group may have modern technical expertise and fiscal resources needed for drug discovery, the natural products are found within the host country. Thus the host country and local population have legitimate arguments for ownership of the species and access to it. In addition, they have a legitimate claim on benefits gained from the products from the species. Benefits claimed are not limited to a portion of the profit from a drug that may be developed and marketed. They may include intellectual property rights to the genome or tangible benefits from some other product unrelated to the medicine or other beneficial use resulting from bioengineering. If local lore or knowledge is used to direct the search for a new drug, the indigenous people have intellectual property claims as their knowledge is shared. Equitable agreements on ownership, access, benefits sharing, etc. can only be established if all of the participants have a full and equal understanding of the issues. These are complex and baffling matters that have not been fully resolved in societies with long histories of scientific inquiry, advanced economies, and a large body of law. Fair agreements based on full knowledge in remote indigenous communities present another, daunting challenge to drug development and conservation.

Access, fairness and equity issues cannot be resolved effectively on an ad hoc basis by scientists with good intentions but limited knowledge of law and policy as they implement a project of drug discovery and conservation. Experts in international commercial and intellectual property law and economics with experience in developing countries must be involved from the outset. This expertise is expensive and not widely available. Thus its application adds significant costs to bioprospecting and conservation projects.

The architects of the ICBG program had a good grasp of the scientific, environmental and conservation, economic, social and procedural issues that impact on and detract from successful drug discovery from natural products. They recognized these factors when the program was conceived over a decade ago. Indeed, the ICBG program was originally modeled on a concept that emerged from a conference sponsored by FIC in 1991. The concept proposed combining drug discovery, conservation of biological diversity and economic growth into a unified effort. The ICBG program is intended to test the hypothesis that including conservation and economic development in drug discovery projects will help these programs gain acceptance and be successful in developing countries. The FIC program manager and the grantees continue to stress that the ICBG program is an experiment that tests the hypothesis that a multi-dimensional project that gives balanced emphasis to conservation, economic development and drug discovery will assure that progress made toward any one of these goals will support the progress toward the other two. This conceptual approach contrasts with the popular notion that conservation and economic gain are driven by major commercial success in drug discovery.

The ICBG program is at a critical point as the second consecutive five year grant cycle comes to an end. Substantial commitments of intellectual capital, fiscal resources, and innovation have been focused by the grantees to implement the conceptual basis for the ICBG program. As these grants were implemented and work progressed, they were expected to both test the conceptual basis of the ICBG program and to produce advancements in drug discovery, conservation, and economic development in the regions where they worked.

The reviewers were not specifically asked to discuss whether the fundamental conceptual basis for the ICBG program has been validated. But this concept of linking conservation and economic development to drug discovery and whether this linkage improves the probability of success in the individual grants or the entire program was central to the reviewer's deliberations. Given the information provided in the briefings at the review meeting, the format of the written materials distributed, and the time available for the review, the question could not be answered with complete confidence. Recommendations for shaping and maturing the ICBG program over the next five to ten years emerged from the information provided and discussions among the reviewers and the participants. Nonetheless, the reviewers are convinced that the ICBG program shows every indication that it is a successful experiment. There are many examples of achievements including and arising from the processes used to implement the conceptual basis of the ICBGs. The reviewers earnestly hope that the ICBG program will be continued and expanded. The next round of grants must build on the 10 years of experience in the program to advance and sustain drug discovery, biodiversity conservation, and incentives for economic development. And the FIC should find the resources to commission a thorough, independent analysis aimed at determining whether the conceptual basis of the ICBG program is valid and, as importantly, to collect systematically from the grantee's efforts those achievements and tools that were created from their hard work on and innovative approach to an exceedingly difficult challenge.

This report is based on materials provided by the FIC staff describing program progress to date and presentations by current ICBG grantees and FIC and other federal agency staff at the review meeting. In addition, the reviewers met in closed session following the open meeting.

IV. Consensus Observations and Recommendations Regarding the Core Conceptual Basis of the ICBGs

The reviewers believe that a programmatic focus on the search for new drugs and other beneficial uses derived from natural products is entirely appropriate and has great potential for improving human health and welfare. The effort is particularly important in areas rich with diverse biota that are threatened. The ICBG program concept combining drug discovery with conservation and economic development represents the best conceptual approach both for identifying new drugs and other products and for assuring fair and equitable distribution of benefits from bioprospecting.

The ICBGs funded over the past decade have accepted the new conceptual approach to drug discovery and transformed it into practical, functional, productive projects that embraced and tested the concept. The next group of ICBGs should move from a set of independent projects testing approaches to implementing the concept of integrating conservation and economic development into drug discovery to a comprehensive program that advances the proven elements of the concept. This transition must be managed by FIC and its federal funding partners such that innovation and experimental approaches to the science of drug discovery and conservation by individual ICBGs are not threatened.

The reviewers suggest that the ultimate goal of the ICBG program is to assure that when an ICBG grant ends, the scientific, technical, operational, and infrastructure capacity for sustaining drug discovery, related conservation, and economic incentives have been established in the host countries. Meeting this goal will help ensure that bioprospecting and conservation will be sustained and that follow up on the drug development in the pipeline will continue. It will foster and preserve the conceptual approach linking drug development, conservation, and incentives for economic development. And it will create, test and implement mechanisms for equitable sharing of benefits with indigenous peoples and host countries that protect local knowledge and biological resources and offer tangible benefits to all participants. These objectives are in themselves sufficient justification for the investment of resources by FIC and its partner agencies.

The following recommendations and observations are intended by the reviewers to advance the ICBG program and help assure that the ICBGs establish lasting programs of scientific rigor and fundamental fairness in the host countries that offer a paradigm for other, similar efforts.

Drug discovery, conservation, and economic development should continue as the core elements of the ICBGs.

These three goals need to be clarified, tightened and more carefully tied together. To the extent practical, conservation activities supported by the ICGB grants should relate directly to drug discovery activities. Preferably they will be driven by drug discovery needs and protection of traditional medicine practices in the host country site(s).

The term "economic incentives for drug development and for conservation" should be adopted as an alternative to "economic development." Economic incentives should recognize both the short term and long term costs and benefits of drug discovery and conservation and the distinction between who benefits and who pays. Since the goal of the ICBG program is to establish an infrastructure for drug discovery in a developing country, it is the academic institutions and scientists who are most likely to reap immediate benefits. Yet it is local communities with other, competing, and perhaps more immediate goals and incentives for use of biodiversity that make the immediate sacrifice. These communities must forego other short-term economic benefits that could come from uses or exploitation that permanently damages or destroys biodiversity and habitats. This disconnect must be addressed as the ICBG project is planned and implemented. Local governments share a critical role as participants in the planning so that the trade-offs are evaluated and managed equitably as the projects go forward. Achieving balance among the goals will require a broader range of expertise than is likely to exist in the US-based institutions participating as ICBG grantees. Grantees should first attempt to fill such gaps with experts from the host country. If this expertise is not available in the host country, the ICBGs should give priority to developing the expertise locally through training and education. The FIC proposal to support an NIH fellowship program in technology transfer is an example of an opportunity to expand local expertise necessary to the ICBG program.

Drug discovery should continue to be the "first among three equal" goals of the ICBG program with conservation and creating economic incentives for drug discovery given the emphasis required so that they too will be legacies of the ICBG program.

The number of species collected and screened in drug discovery efforts since the onset of the ICBG program is impressive. The quality and output from the species collected and screened by the ICBGs should continue to be used as one marker of productivity in the drug discovery effort.

Although it is appropriate that drug discovery drive the ICBG program, the ICBGs should not be expected to produce a major new drug or be evaluated on this basis. The process of screening natural products for candidates for drug discovery through the many complex steps necessary to bring a major new drug to market takes at least 10 to 15 years. Thus it becomes critical that each ICBG prepare local experts to take responsibility for continuing the project. Local personnel who participate in the ICBG should be able to conduct collaborative research and to attract alternative funding sources. They must be able to manage benefits sharing schemes, write competitive grants, prepare partnership agreements with private industry, and do outreach and education. Each ICBG would leave behind, after 10 years of work, an organization that is fully prepared for finding a breakthrough drug. The local participants should be trained and equipped to assume the role as the source of national expertise and leadership in the science and policy for biodiversity protection and conservation, bioprospecting, drug discovery, and associated matters such as economic incentives and intellectual property rights.

Adopting a stronger program focus on capacity building should not be viewed as limiting the potential benefits from drug discovery. Instead, it should improve the odds for identifying medicines from natural products.

Placing an initial focus on phytomedicines in drug discovery would also help document, evaluate, and preserve local medical practices, particularly if a social sciences perspective were added to these projects. Many indigenous peoples are going to remain where the ICBG work is conducted and their local medical practices will continue to be important to their health status. Employing additional, specialized social sciences expertise in the ICBG drug discovery effort would help preserve traditional medical practices and assist in gaining local acceptance for western medicine as an adjunct to indigenous practice. An approach that recognizes the importance of local diseases and local practices will highlight the importance of conservation and incentives for economic development at the local level. Another advantage of this approach is that it provides a role for smaller pharmaceutical firms in the host country in developing and marketing phytomedicines.

The ICBG program has demonstrated the technical difficulty involved in elucidating the chemical structures of novel bioactive compounds in natural products. Intense collaboration between US-based institutions and local scientists is necessary to establish core chemistry activities. New ICBG grant applicants (including those competing for renewal of existing grants) must demonstrate a thorough understanding of the complexities of the drug discovery process and must describe resource conservation goals that are directly linked to drug discovery. The best evidence of such understanding is a plan for drug discovery and related conservation activities that describes the processes to be followed in the proposed ICBG grant. The application should describe drug discovery from bioprospecting through in-vivo testing and how collaborations will be established in the host country site. Local expertise and institutions should be used where these exist in the host country and roles and responsibilities must be spelled out.

Technical and scientific methods for screening, chemistry, and testing must be standardized, state-of-the-art, and reproducible. Where capacity for screening does not exist, it should be sought from outside either from private industry or from government agencies. The plan must recognize and be consistent with host country legal, social, and political practices.

FIC policy should be to fund new ICBG grants in two phases: First, a planning phase in which grantees establish the fundamental structure and substantive national and substantive local contributions in planning for the ICBG in the host country. Second, an implementation phase to carry out the plans developed in the first phase.

As the ICBG program enters its second decade, it should reach its potential to set or model the paradigm for similar efforts to promote partnerships for public health, natural resource conservation, and incentives for economic development between developing and developed nations. Grant applicants should submit proposals that describe the entire ICBG from its onset to completion. These grants should then be funded in two phases. The first phase, proposed to last two years, would establish the basis for the full ICBG. The second phase would fund the full operation of the ICBG only if the start-up planning yields good evidence that the ICBG will succeed.

The ICBG should include host country participants as active colleagues in the planning effort wherever possible. The ICBG grantee should propose broad goals, objectives and guidelines for the project. The specific program should be designed in partnership with the host country at both the national and local levels.

In addition to activities supported in the current ICBG grants the planning phase would include:

• Identifying key individuals and local practices in the ICBG program site.

• Identifying policy makers, policies and regulations at the national level.

• Identifying the media and other institutions that are targets for outreach and education.

• Developing culturally appropriate prior informed consent agreements.

• Completing agreements for access, export, and intellectual property and benefits sharing.

• Identifying applicable expertise needed to fill gaps missing in the host country.

• Creating data management systems that are integrated with other grants and centrally with FIC.

• Establishing stronger partnerships for drug development in the grantee institution, in federal health laboratories at NIH and elsewhere to increase drug discovery opportunities.

• Establishing collaborative scientific research relationships and communications links with other ICBGs and the FIC and its funding partners.

The second phase of an ICBG grant should be awarded when FIC staff determines that the foundation for a full program is in place and there is good probability that the full program will produce the intended purpose. It is anticipated that second phase work can begin in the third year and continue through the five-year term of the grant.

New ICBGs should plan to be renewed for a second five-year term. After ten years, the ICBG should have attained its goals. Some current grantees have participated in the program since its inception ten years ago. These grantees should not be prohibited from reapplying nor should they necessarily abandon established partnerships in the US or in host countries. However all grant applications should compete equally and adhere to any new, applicable guidelines set by FIC and its funding partners for the third round of competition.

ICBG grants should include a "business plan" that defines the economic incentives for benefits sharing; agreements, procedures and policies for equitable sharing; and a process whereby the local program will become self-sustaining.

The ICBGs have done an outstanding job in establishing agreements that define potential benefits and how the benefits from drug discovery will be allocated. However, financial rewards from drug discovery are possible but they are not assured. Moreover, any profits will accrue late in the tenure of the ICBG. Thus, the ICBGs have provided education, training, equipment, infrastructure, and technical advice and consultation as compensation benefits to host countries as an immediate benefit. In addition, some ICBGs have supported eco-tourism and other similar activities to generate financial benefits from conservation. This approach is admirable and should continue to be supported by FIC. It should, however, be supplemented by a business plan for sustaining the local program beyond the term of the ICBG project.

A business plan should emphasize the roles of the various host country participants at the local level and the activities that will create a local and national infrastructure for drug discovery and development. Elements of the business plan should contain country-specific activities in negotiating, grant-writing, acquisition of private capital, and business development.

The business plan must define how new drug leads will be pursued and researched and then developed. This element should describe both the specific roles in science-and-technology and benefits sharing. Collaborative arrangements for following attractive drug leads involving large and small pharmaceutical firms, government, and academic laboratories should improve prospects for discovery. However such arrangements pose difficult administrative, confidentiality, and benefits sharing issues that should be addressed in the business plan.

FIC should commission an analysis of the 1992-2001 ICBG Program to determine what has worked and how- and what has not worked and why.

FIC staff and ICBG project investigators describe the ICBG program as an experiment designed to test the conceptual approach that links drug discovery with conservation and economic development. The ICBG grantees took the concept to the field. With innovation, flexibility, and determination, they tested the concept. The reviewers believe that this experimental phase of the ICBGs should be ended. The key is to learn from successes and failures so that future ICBGs and other similar development programs benefit from the combined experience of the ICBG program.

FIC should conduct analysis of the program to assure that the knowledge gained by the ICBGs to date is collected, analyzed, reported and disseminated. This is so important FIC should consider withholding a portion of funds available for grant activities should that be necessary. The analysis should address the kinds of scientific, economic, social and cultural, and political questions posed in this review. For example, it should compare the productivity of high through-put collection and screening against targeted screening based on leads from ethnopharmacological and ethnomedical knowledge; the relative contribution to conservation from a linkage to conservation; balance of screening for drugs for morbidity and mortality in local populations or in developed nations; and the potential for organisms other than plant species to yield medicines and other beneficial uses.

The individual agreements for benefits sharing, for protection of rights to intellectual property, and for prior informed consent appear to be excellent and progressive adjuncts to the ICBG program. The analysis should review these tools and evaluate them for strengths and weaknesses. A "tool kit" or guidelines for these kinds of agreements would be of great general interest beyond the ICBG program. A review of the agreements with an eye toward gaps or limitations that might be exploited when a local ICBG project policy or benefits sharing agreement is challenged, or when an important new drug is discovered, would also be of great use inside the ICGB program.

FIC staff are limited in the technical resources needed to conduct an analysis of the ICBG program and should not be expected to conduct the review. Rather they should look for a foundation with the broad interdisciplinary interests and expertise to analyze the ICBG program and provide advice and guidance to the FIC and the ICBG grantees. A foundation may find the project of sufficient interest to underwrite the costs. An evaluation contract would be the least attractive option. In any event, FIC staff (along with their funding partners) and ICBG grantees must be deeply involved in the analysis, from defining its scope through its report and recommendations.

V. Response to Focus Questions and Other Questions Posed to the Reviewers

The FIC posed some "Focus Questions" in the materials sent to the reviewers. At the meeting, FIC staff, members of the Technical Advisory Group representing the federal institutes and agencies that co-fund the ICBGs, and scientists who received ICBG grants briefed the reviewers. The following responses to the Focus Questions have been constructed from the background materials, the briefings and individual, informal discussions between the reviewers and others participating in the meeting.

1. Does it appear that broadening of the original scope of the program is productive in the context of the integrated goals of the program?
2. Should future applicants be explicitly encouraged to consider small biotech companies and non-profit drug discovery groups as alternatives or additional partners? How significant are the likely tradeoffs in technical and financial resources for ICBGs?
3. Are there some guidelines or trust-building activities that will facilitate maximum flow of data for research and a sense of confidence among participants and stakeholders regarding the destiny of data and samples?
4. Is there evidence that either the involvement of indigenous communities and their traditional knowledge in drug discovery or in conservation/ development opportunities offer merit and should be given continued encouragement in the new application?
5. What lessons should be drawn from these events (the controversy surrounding the ICBG in Chiapas State in Mexico) and how might similar situations be avoided?
6. Would progress toward the goal of economic development be substantially enhanced by including more formal economic research or expertise within the projects? Are there other types of activities compatible with the basic ICBG model that might enhance economic development?
7. As conservation is one of the principal goals of the program, what types of dissemination are most likely to produce conservation benefits today? How can this be encouraged?
8. What should be the appropriate balance of training in the ICBGs to ensure maximum contribution to health, conservation, and economic sustainability?
9. Have there been significant changes since 1997 in the science or the economic and political context in which these projects operate that would lessen enthusiasm for the ICBG approach? Are there significant concerns regarding the overall merit of renewing the ICBG program? What would be lost if this program were not to continue?

In addition to the Focus Questions, FIC staff sought advice from the reviewers on suggested levels of funding and technical support from FIC to the grantees and the proper role of FIC in the US and abroad in outreach, education, and program advocacy to policy makers, the general public, and the scientific community:

Level of Support - ICBG grants operate on about $500,000 to $750,000 per year from FIC and its co-funders. A portion of these funds are retained by the ICBG's parent institution to cover research overhead costs. FIC has taken every possible measure to assure that overhead costs are kept to a minimum. ICBGs have been unusually successful in obtaining funds from public and private sources and using FIC funds to leverage other grants. These funding arrangements reflect the innovation, successes, and deep commitment of the ICBG principal investigators. The reviewers believe that about $750,000 per year is an adequate base. The aim is to provide adequate funding to assure that the ICBG project can operate, but not so much as to obviate the need to leverage funds from other sources.

Outreach and Advocacy - FIC should take a limited but active role in outreach, education, and public relations in support of the goals and methods of the ICBG program. There will surely be continued local and international debate about the ICBG program and similar activities, in particular fomented by groups and individuals who oppose economic globalization. FIC should implement efforts to reduce its impact on individual ICBG grant activities. ICBG project directors must be encouraged to pursue local efforts to create broad support for their projects at the local and national level. Local involvement in planning grants will be helpful as will outreach to the local media. As the ICBG's progress, the impact and benefits should be tracked and routinely reported locally and to FIC. Local or national workshops provide a good venue for such outreach and could be a part of the planning phase of new grants.

FIC staff can provide guidelines for local outreach and education but it is probably not necessary or appropriate that they be directly involved. FIC should continue to promote the ICBG's within the US. A major announcement of the next group of ICBG grants might set the stage for additional positive outreach. It is anticipated that the program analysis will produce findings that might be the subject of a meeting of grantees, the policy makers, industry, NGO's, foundations, and the science press. Such a meeting would advocate the ICBG program. As importantly, it should help assure that grantees fine tune their programs to follow the recommendations evolving from the analysis. Outreach education requires a fundamental understanding of the dynamics in the host country, thus it would be wise to involve an institution that specializes in outreach education to undertake or assist in such training.

VI. Reviewer Comment on International Convention on Biological Diversity (CBD)

Lessons learned from the ICBG program will gain greater international acceptance and credibility if the US is viewed as supporting rather than opposing the principles contained in the CBD. Because the ICBG's operate in countries that have ratified the CBD, they must operate within its framework. It is the sense of the reviewers that current ICBG grantees may be limited in their efforts to establish local partnerships and programs linking drug discovery to conservation in the developing countries where they work. Local officials may mistakenly believe that as American scientists they must embrace the policies of the government of United States and that they oppose the CBD. The US is isolated by virtue of the fact that it has not ratified the CBD.

While the ICBG program is leading the effort worldwide to implement the principles of the CBD, the US does not receive enough credit for its leadership. The failure to ratify the CBD overshadows the contributions of the ICBG program. The ICBGs and the benefit sharing, development, and cooperation they promote are in the long-term interests of the US and would be promoted further if the US did ratify the CBD. The FIC should use its influence on policy makers in the National Institutes of Health, the Department of Health and Human Services, and the Department of State to encourage the US to ratify the Convention. The reviewers understand that such influence must be exercised with tact and confined to opportunities for internal discussion with the Department of State and US elected officials. The reviewers believe that the practical experiences gained from the ICBG program lends credibility to the FIC staff views on the CBD as it applies to drug development and conservation and could be persuasive in changing current US policy regarding the CBD.