Programs
and Initiatives | Research
Grants
International
Cooperative Biodiversity Groups (ICBG)
2002
Program Review Report
October 2002
Table of Contents
Executive
Summary
Panel of Experts
Program Review Report
January
14-16, 2002
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.
The reviewers also
provided some answers to focus questions posed by the program
officials regarding specific decisions for management of the
program.
Panel
of Experts
Raymond
J. Andersen, Ph.D., Chair
Department
of Chemistry and
Department
of Earth and Ocean Science
University
of British Columbia
Vancouver,
CANADA
|
David
Downes
Office
of the Secretary
US
Department of the Interior
Washington,
DC
|
Nina
Etkin, Ph.D.
Department
of Anthropology
University
of Hawaii
Honolulu,
HA
|
Victoria
Hale, Ph.D.
Institute
for One World Health
San
Francisco, CA
|
John
Kilama, Ph.D.
Global
BioDiversity Group
Wilmington,
DE
|
Antonio
LaVina, Ph.D.
World
Resources Institute
Washington,
DC
|
James
McChesney, Ph.D.
NaPro
BioTherapeutics, Inc.
Boulder,
CO
|
Charles
Peters, Ph.D.
New
York Botanical Gardens
Bronx,
NY
|
Jose
Carlos Fernandez-Ugalde
Federal
Institute for the Environment
Government
of Mexico
Mexico
City, MEXICO
|
Ignacio
Chapela, Ph.D.
Department
of Environmental Science
University
of California at Berkeley
Berkeley,
CA
|
Dan
C. VanderMeer, Executive Secretary
Environmental
Health Consultant
Chapel
Hill, NC
|
|
January
14-16, 2002
Program
Review Report
I.
Introduction and Context
II.
Consensus Observations and Recommendations Regarding
the Core Conceptual Basis of the ICBGs
III.
Response to Focus Questions and Other Questions Posed
to the Reviewers
IV.
Reviewer Comment on International Convention on
Biological Diversity (CBD)
I.
Introduction and Context of the ICBG Program Review
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, climate change,
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.
II.
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 strengthes 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.
III.
Focus Questions
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?
The reviewers
believe that phytomedicines development generally offers one
of the best initial targets for drug discovery screening.
Local ethno-medical practices help focus the initial
search. Screens
of phytomedicines for other uses, including veterinary
medicines and control of plant pests may also be productive. Additional possible uses as nutritional supplements, dyes,
fragrances, and/or cosmetics may enhance the local acceptance
of the ICBG program but these should not detract from the
medical and public health goals of the program.
These may also promote the program’s conservation and
economic incentive goals.
A
focus on drug development to meet local needs and interests
provides a base for drug development for diseases and
conditions of broader interest.
In addition it would serve as the foundation for a more
ambitious program in drug discovery.
Compounds derived from
natural products should be sought for treatment of cancer and
other chronic diseases as the local program matures in
expertise and as procedures to identify high-priority
candidates are implemented.
Expansion of
discovery efforts to microorganisms or marine species should
be considered as individual ICBGs mature and as opportunities
arise. It may be
more difficult to tie discovery to conservation in these
areas. However a
link between drug discovery from screening marine organisms in
and around coral reefs presents an attractive opportunity to
tie drug discovery with conservation.
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?
ICBG grantees should
be strongly encouraged but not mandated to solicit
partnerships with small biotech companies.
The same kind of encouragement should be given to
inviting not-for-profit drug discovery groups to participate.
The diseases of most concern in developing countries,
namely TB, malaria and other parasitic diseases, etc. are most
often not of interest to big pharma because the potential
financial return is too low. Therefore, the ICBGs should work
with academic groups and government agencies that have
expertise in these diseases. They should also explore the
possibility that drug companies in the source countries might
be interested in participating in the discovery, development
and marketing of drugs for these diseases. There should also
be thought given to how the decisions are made about whether a
particular chemical entity has drug potential or not. If this
is left only to big pharma partners, some promising compounds
might get missed. In a big company, the criteria for moving a
compound ahead are extremely demanding. For example, the
compound of interest has to compete with other leads generated
in-house by the company for the same disease indication. Often
the second best compound is not advanced, but that doesn’t
necessarily mean it has no value. In addition, big companies
often make a business decision about a compound independent of
its ability to treat a disease. Thus a compound that might
have promising drug potential may get dropped because the
anticipated sales don’t meet the requirements of a big
company.
These are all
legitimate reasons for the big pharma to not pursue a
compound. However, some of these compounds might be of
interest to smaller companies, companies in the source country
where the business requirements are very different, or NIH.
The natural product resources of the source countries are an
important resource of chemical diversity and it is important
to treat them as such to make sure that all the interesting
compounds realize their true drug potential. As part of this,
there has to be a clear recognition of the importance of
getting effective patent protection on promising compounds
before the structures are published in the open literature.
Often publishing a structure before a patent has been filed
destroys the compound’s drug potential for companies. This
creates an obvious tension for the ICBG grantees between the
need/desire to publish versus drug discovery, particularly if
the success of an ICBG and its ultimate renewal is partially
measured by publications coming out of the project. The above
is not meant to discount the potential role of big pharma,
which has had and will continue to have a very important role
to play in these programs. More than one partner, large or
small, is likely to be needed.
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?
FIC cannot enforce a
mandate for information sharing but should make every effort
to encourage it. The
RFA should include a plan for collaboration and information
sharing with other ICBGs.
FIC staff should strongly consider devoting one of two
annual program meetings for technical collaboration in drug
discovery (there is currently only a single joint annual
meeting). The meeting would be closed and confidentiality
agreements would be necessary.
FIC
staff should put additional resources into their central data
repository. It
should be expanded to include program conservation data in
addition to natural products.
Grantees should be encouraged to participate in the
design of the database and in determining rules for access to
and uses of shared data.
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?
Experience from the
ICBG program and from research in ethno-pharmacology and
ethno-medicine suggests that careful assessments of local
medical practice provide productive leads for drug discovery-
an observation that needs further evaluation. The ICBGs would
benefit from substantially increased application of the
expertise of sociologists with specialized training and
experience in these fields to increase the constructive
involvement of indigenous peoples. ICBGs
should be urged to focus drug discovery initially on screening
and development of phytomedicines and herbal products for
treatment for diseases and conditions affecting local
populations such as malaria and other parasitic diseases,
HIV-AIDS, or other sexually transmitted diseases. Such focus should make the ICBG more meaningful and
acceptable to the local population. Similarly,
the local indigenous community must participate in identifying
the options for use of the local biodiversity and in setting
priorities for its use. And
compensation mechanisms must be created with the knowledge,
understanding and consent of the local community.
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?
This
question indicates that FIC staff is taking the proper
attitude in response to the position of groups that oppose
globalization of trade and development and who directed this
opposition to the ICBG grant in Mexico.
The
controversy and events surrounding the project received wide
publication in the science media and was the subject of a
briefing session during the open session of the review
meeting. The
reviewers discussed the demise of the ICBG project in the
State of Chiapas in Mexico in the closed session.
No specific conclusions or recommendations regarding
the circumstances were drawn, however some general guidance
was offered. The
loss of a project that was part of related activities in
Chiapas that predated the ICBG grant and that was managed by
scientists with outstanding reputations is troubling.
It is likely that similar controversy will arise at
another place in the world where an ICBG is operating.
The program analysis recommended in the Consensus
Observations above should investigate the circumstances in
Chiapas to identify how such events can be avoided or better
managed. The idea
is to learn from the Chiapas incident, not to find fault with
the program or its managers. Early signs of problems, strategies for coaching those
involved, things to be avoided, and lessons learned are a few
of the issues to be investigated. Clearly the situation in
Mexico would benefit from careful analysis.
There are many questions to be answered.
How might problems have been prevented if given the
benefit of hindsight? How should this experience shape the implementation of the
third cycle of grants? What
additional efforts might be made by FIC staff and by the US
Department of State to assist the grantees and the ICBG
program in advancing its goals?
What are the arguments needed to either gain the
support of the program opponents or that are effective in
offsetting their opposition?
Who should make these arguments, to whom and in what
settings?
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?
The
reviewers did not rule out a greater role for economic
analysis, but assign a far greater priority to the need for
business development expertise that would help ICBGs with
preparing “business plans” for long-term viability of
in-country development of natural products based on locally
available natural sources.
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?
In many cases, it
was not clear from the presentations and background materials
how the conservation efforts reported were linked to drug
discovery at the local project level.
Many appeared to be done to meet the requirement to
include a conservation component in the grant.
In some instances reports of successful conservation
efforts appeared both unrelated and overstated.
Conservation must be defined by local needs rather than
by macro goals. Applicants
for new ICBG grants and for competing renewals should
demonstrate an understanding of local needs and the need to
include local participants in the planning phase. Conservation does not necessarily mean protection from
development. In
fact, careful harvesting and cultivation may preserve species
that are endangered. Use of plants and other natural product
sources for drug development should not preclude the
development of their use for other purposes.
8.
What
should be the appropriate balance of training in the ICBGs to
ensure maximum contribution to health, conservation, and
economic sustainability?
If resources are
limited, training should only be at the graduate student,
post-doctoral fellow, and visiting scientist level.
Such individuals can return to the source countries and
train additional students and technicians. Training
technicians from source countries does not have the same
long-term propagation effect.
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?
The reviewers are in complete support of the ICBG conceptual
approach that integrates drug discovery, natural resource
conservation and incentives for economic development.
Their discussion at review meeting kept returning to
the importance of continuing the ICBG program and concentrated
on suggestions to both strengthen the approach and to maximize
the potential for successful and sustained programs in
developing countries.
In fact, the reviewers all agreed that this question
could have been the only question addressed during the review.
In discussing the ICBG program, the reviewers
considered not so much what would be lost if the ICBG program
were not to continue but rather how great a potential the ICBG
program has.
Based on its performance to date it is clear that it
continues to have a tremendous potential. Bioprospecting will
continue whether the ICBG program does or does not.
However termination of the program would leave a huge
void in the leadership of how bioprospecting should be done in
a responsible and equitable manner.
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.
IV.
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.
|