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Partnerships for value-added through bioprospecting

Article  in  Technology in Society · November 1998

DOI: 10.1016/S0160-791X(98)00029-3

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 Technology In Society 20 (1998) 481–498

Partnerships for value-added through

bioprospecting
Charles Weissa,*, Thomas Eisnerb
a
Georgetown University, Science, Technology and International Affairs, Box 571032, Washington, DC
20057-1032, USA
b
Cornell University, USA

Abstract

Bioprospecting in developing countries must be operated on a commercial scale as a biotech-

nology-based business that adds value to a natural resource, if it is to provide incomes to
developing countries and their traditional peoples and incentives for the conservation of biodiv-
ersity resources. For example, the value of extracts of samples derived from plant or animal
species may be increased by processing them into 96-well plates ready for high throughput
screening. More advanced developing countries may wish to aquire their own screening
capacity and thereby to participate directly in the process of new product discovery and to
lay the basis for a local biotechnology industry. Either way, the developing country must
normally enter into a commercial partnership with a company in an advanced country that
can supply, in addition to the technology, the marketing know-how to guide screening efforts
and the capacity to develop the market for the eventual new product and to manufacture and
distribute it. A developing country that wishes a significant share in the intellectual property
deriving from a successful development must be prepared to make a significant financial invest-
ment, to share the risk of failure and to delay the receipt of cash income. A developing country
may seek quicker returns, with fewer risks and delays, by undertaking to develop new phyto-
medicines (herbal extracts sold directly for medicinal purposes), personal care products and
nutriceuticals (food supplements). Alternatively, it may eschew the hope of large financial
gains and devote itself to improving traditional medicines or finding cures for tropical diseases
that affect poor people.  1998 Published by Elsevier Science Ltd. All rights reserved.

Keywords: Bioprospecting; New product development; Developing countries; Natural products; Pharma-
cognosy; Herbal medicines; Pharmaceuticals; Traditional knowledge; Biodiversity; Incentives to conser-
vation; Biotechnology; Screening

* Corresponding author. Tel: ⫹ 1-301-913-9755. Executive Officer, Biotic Exploration Fund, Inter-
national Organization for the Chemical Sciences in Development.

0160-791X/98/$19.00  1998 Published by Elsevier Science Ltd. All rights reserved.

PII: S 0 1 6 0 - 7 9 1 X ( 9 8 ) 0 0 0 2 9 - 3
482 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

Bioprospecting—the systematic search for new applications of hitherto unstudied

biological species—offers a last chance to rescue irreplaceable biological and chemi-
cal information evolved over billions of years before it is forever lost to humanity
[1,2]. This information could some day lead to cures for devastating diseases, natural
ways to grow food crops, or food supplements that really do improve your health.
Bioprospecting can also create economic incentives for the conservation of biodivers-
ity, can serve as the foundation for a modern biotechnology industry in developing
countries and can provide traditional peoples ways to benefit from their unique under-
standing of the environment in which they live [3,4]. A rapid expansion of the world-
wide bioprospecting effort is a critical global environmental priority, and can be
achieved only through partnerships with companies or research institutes in advanced
countries that can contribute essential technology, management, and marketing
know-how [4,5].
The destruction of the world’s biodiversity resources is driven by powerful econ-
omic forces. In the short term, developing countries find it faster and less risky to
destroy biodiverse habitats for quick cash— cutting down tropical forests for timber,
farmland, and firewood, turning wetlands into shrimp farms, and destroying coral
reefs for the benefit of real estate development—than to adopt conservation-oriented
strategies that would serve them better in the long run [6].
Partnerships for bioprospecting are inhibited by lingering resentments in
developing countries over past uncompensated exports of genetic material. Some of
these, like the export of Brazilian rubber seeds that brought a premature end to the
Brazilian rubber boom, date back more than a century [7,8]. Other resentments stem
from philosophical objections to the patenting of life forms, or relate to the patenting
by international pharmaceutical companies of the active principles of traditional
medicines, which are then exported in standardized commercial form back to their
country of origin [9].
Fortunately, institutional models are evolving in different parts of the world that
show the way to a new approach to overcoming previous barriers of distrust born
of centuries of inequity. Of these, the best known is the Biodiversity Institute in
Costa Rica (InBIO), a world-class laboratory dedicated to the systematic inventory
of the hundreds of thousands of unique insects and plants in that tiny Central Amer-
ican country, and the exploration of their possible usefulness to humanity. The world
was first alerted to the economic possibilities of bioprospecting by the pioneering
agreement between InBIO and the Merck Pharmaceutical Company, by which Merck
agreed to pay an up-front fee of 1.3 million dollars for a set of plant samples, plus
royalty arrangements in case of a commercial success [4,10].
Since the founding of InBIO, other institutional models for bioprospecting have
emerged in different parts of the world [11–17]. These varied experiences enable us
to explore alternative pathways to scientifically fruitful, environmentally sustainable,
economically beneficial, commercially profitable and socially equitable bioprospect-
ing. They also illuminate the many practical obstacles facing a developing country
that wishes to undertake such an effort, and provide a fabric of practical experience
to guide the evolution of policy in this field.
A wide variety of broad policy issues shape the debate on bioprospecting: intellec-
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 483

tual property rights, regulations governing access to biodiversity resources, the rights
of indigenous peoples, patenting of life forms, and the theoretical treatment of the
likely profitability of bioprospecting as an economic activity [1,18]. These are critical
issues, the more so in view of the dismal history of theft and “biopiracy” that sets
the tone for discussions of the subject [19–21].
On the other hand, none of these issues will be of practical importance if biopros-
pecting does not develop into a viable source of income for developing countries,
an incentive for conservation, and the basis for a local industry based on biotechnol-
ogy. We therefore turn our attention to the practical context of bioprospecting as an
economic activity.

1. Business strategies for bioprospecting in developing countries

If a developing country is to undertake bioprospecting on a scale sufficient to

create economic incentives for the conservation of biodiversity, it must be
approached and managed as a business whose objective is to add value to a natural
resource. It must be competitive with other “high-tech” investments in the country
and (in the case of internationally minded investors) abroad, and specifically with
bioprospecting services in other countries and with synthetic chemicals that may lead
to the development of new medicines, chemicals, foods, or other materials [22].
Developing countries cannot develop this business by themselves. They need to
establish themselves as reliable partners of overseas companies that bring essential
skills in manufacturing, marketing and the management of large-scale research and
development. This partnership must be profitable to both sides. But both sides should
also recognize that the long-run objective of the developing country partner is and
indeed should be to build its own capability to add value to the resource, and to create
opportunities for indigenous peoples and local communities, who are the stewards of
biodiversity and often have special knowledge of its uses.

1.1. The value-added chain

In bioprospecting as in other resource-based businesses, the key to profits is knowl-

edge, not the natural resources themselves. Each link in the “value chain” increases
the sophistication of the scientific, technological and marketing knowledge that is
applied to the resource, and with it the value of the product supplied to the customer,
the price (s)he is willing to pay, and the profitability of the final product. These may
be summarized as follows.
First, samples of biological materials are gathered by collectors in the field. The
samples are then extracted with solvents, and the extracts screened for possible use-
fulness in new products for the pharmaceutical, agri-chemical, personal care, phyto-
medicine (plant extracts marketed directly to the consumer) and nutriceutical (food
supplements) markets.
Promising extracts for pharmaceutical applications are partially purified and given
a rough check for chemical novelty (“dereplicated”). Their active principles are pur-
484 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

ified, dereplicated again, and isolated, and their structures elucidated. These “leads”
are then tested to elucidate the scientific basis for their activity, chemically modified
to improve their effectiveness and reduce toxicity, and finally given an elaborate and
expensive series of tests for effectiveness and safety before they emerge as new
pharmaceutical products tested and ready for world markets. In order to understand
the practical obstacles to an expansion of the world-wide bioprospecting effort, it is
worth reviewing this value added chain in more detail.

1.2. Extract preparation

The raw materials of bioprospecting are extracts, solutions made by soaking dried
plant or animal tissue in suitable solvents under carefully controlled conditions and
removing certain compounds that interfere with subsequent screening tests. (A few
screening programs, like that of the National Cancer Institute, prefer dried samples
[23]). For a sample to be commercially useful, its place of origin (provenance) must
be accurately described, so that additional supplies may be obtained when necessary.
The sample is much more valuable if it is accompanied by ecological or taxonomic
clues to the identity or function of secondary metabolites (chemicals) produced by
the organism, or better yet by ethno-botanical knowledge concerning traditional uses,
preferably those with direct counterparts in Western medicine [24].
The random screening strategy, such as that used by InBIO in its initial collabor-
ation with Merck and other pharmaceutical companies, emphasizes the production
of a large number of samples that are well characterized by taxonomy and ecology,
but are chemically unpurified mixtures. This strategy takes advantage of revolution-
ary technological advances that make initial mass screening for new pharmaceutical
applications easy, quick and cheap.
These “high-throughput screens” use automated, low-cost bioassays that mimic
desirable pharmaceutical properties [25,26]. The results of these bioassays eliminate
the vast majority of samples, allowing researchers to focus on the tiny minority that
have real prospects of commercial success. The flip side of this efficiency is the
disadvantage that these bioassays will eliminate a sample that is active in the parti-
cular application but that works on a principle different from the one embodied in
the bioassay.
A typical screen tests whether anything in a given extract inhibits a specific
enzyme reaction, or else attaches itself to the receptor molecule that serves as a proxy
for the organ or organism the researcher wishes to target. Receptors are proteins that
enable hormones or drugs circulating in the bloodstream to recognize when they
have reached their target organ. A molecule that does not bind to the receptor protein
of a particular organ is unlikely to have a pharmacological effect on that organ.
The choice of these bioassays is made by researchers in the laboratories of pharma-
ceutical or other customers for bioprospecting, consistent with the commercial objec-
tives of the firm as defined by their colleagues in the marketing department. For
example, a laboratory in a large pharmaceutical company will typically employ a
battery of some 10–35 screens, each one corresponding to a different commercial
objective. The composition of this battery may change as often as every 6–18 months
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 485

as new screens emerge from research, and as new commercial objectives become
feasible and attractive. “Hits” are confirmed by repeating the bioassay on a second
portion of the same sample.

1.3. Fractionation and rough dereplication

Only the confirmed “hits” emerging from high-throughput screening are partially
purified (“fractionated”), and are subjected to further tests in whole cells and whole
animals. The pattern of their responses to the battery of assays is compared to the
responses of a library of known compounds. This “rough dereplication” process helps
researchers to avoid the trouble and expense of isolating and characterizing an active
principle that they can be reasonably certain will turn out to closely resemble mol-
ecules that are already well known.

1.4. Purification and characterization

The “dereplicated hits” that survive are still not chemically fully characterized or
even chemically pure. The pharmaceutical company must decide whether they are
worthy of the significant investment required for purification and detailed chemical
characterization of the molecule that constitutes the active principle. Purified, derepli-
cated, and chemically characterized hits are termed “leads”, and are frequently
deemed worthy of a first “milestone” payment to the source of the original sample—
assuming that the source has been protected by appropriate contractual arrangements.
This payment should probably be kept modest, lest it put the lead at a disadvantage
in the competition within the company with other, cheaper leads in its develop-
ment portfolio.

1.5. Product development

The mechanism of the pharmacological effects observed in the screening process

is now identified, along with any toxicological characteristics. Extensive animal tests
are undertaken to establish safety and effectiveness in the intended application. A
variety of chemical modifications are assessed to increase the effectiveness and con-
venience of the molecule in the desired application and to minimize its toxicity and
side effects. (This discipline is known as medicinal chemistry.) Efforts are made to
assure a reliable supply of the natural product, or else to synthesize the active prin-
ciple so as to minimize dependence on possibly unreliable natural sources. Those
molecules that survive this multi-step process are dubbed “candidate products,” and
are ready for human testing. If the drugs are intended for the US market, these tests
must be carried out in accordance with detailed regulations laid down by the US
Food and Drug Administration.
The daunting arithmetic of the path from sample to pharmaceutical or other pro-
duct constitutes the essential financial background to business negotiations between
bioprospectors and multinational companies, and the reason why nearly all major
drugs are brought to market by multi-national companies with the huge financial and
486 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

marketing resources needed to finance product and market development [27] The
overall success rate from a screen for a particular application to a final product is
about one in four million. A vigorous bioprospecting operation can generate some
30,000–300,000 such screens a year or even more. So the odds for any one biopros-
pecting operation hitting a large jackpot in any given year, or even in a given decade,
are unfavorable.
The calculation behind this assertion goes as follows. A randomly chosen sample
(of plant, insect, microbiological, marine biological or whatever origin) has about a
chance in 1000 of surviving the first, cheap affinity screens for a given application.
(A smart supplier of extracts will raise the odds by aiming for 35 screens or more
for different potential applications per sample.) Of these “hits”, fewer than 3% will
pass the set of more sophisticated, but still relatively inexpensive tests for effective-
ness and uniqueness and thus graduate to the status of a “lead”. Of these leads,
perhaps 10% become candidate products (and thus subject to detailed and expensive
FDA test protocols in the US), and of these 15% become actual commercial products.
It takes some six years for a sample to beat the odds and gain candidate status, and
another 4–8 years to become a commercial product [28].

1.6. Bioprospecting in developing countries

Traditionally, bioprospecting in developing countries has been the preserve of field

biologists in universities and botanical gardens. Indeed, until recently, most biopros-
pectors in developing countries have been individual professors or collectors, who
collected samples on contract with foreign companies or sold samples left over from
research expeditions. These small-scale activities added little value to the biodiversity
resource and in any case, are now likely to be discouraged by national legislation
implementing the Biodiversity Convention. What is more, samples from these
sources had major disadvantages from the point of view of the purchaser, in that
they were often poorly characterized and poorly extracted, and resupply tended to
be unreliable at best.
A second source of bioprospecting in developing countries has been natural pro-
ducts chemists, many of them highly skilled, working in university laboratories that
are reasonably well equipped for the isolation and structural determination of phar-
macologically active chemical species. These chemists often disdain the commer-
cially oriented, random screening strategy outlined in the previous section, often
preferring to pursue scientifically interesting questions of chemical ecology or ethno-
botany. They might, for example, isolate and characterize the chemical species
responsible for the effectiveness of a traditional medicine, the toxicity of a local
plant, or some other interesting ecological or ethnobotanical effect, without concern-
ing themselves as to whether that molecule was a member of a novel or a well
known chemical family. The product of this research would therefore be a fully
characterized chemical molecule of known physiological activity. If this molecule
embodies a novel chemical principle worthy of extensive screening, it is likely to
be worth far more than a crude extract from a randomly selected plant.
This more research-intensive approach has the advantage that it maximizes the
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 487

involvement of ethnobotanists, anthropologists, and natural products and medicinal

chemists in the developing countries. It fits well with the rhythms of academic
research, and provides many opportunities for training graduate students and post-
doctoral fellows. From the commercial point of view, moreover, it has the substantial
advantage that it enables “hits” to advance rapidly through the subsequent develop-
ment processes, since the difficult and time-consuming processes of chemical iso-
lation and characterization have already been accomplished before screening begins.
It also frees chemical researchers in developing countries to investigate the properties
of active principles that may constitute major advances in pharmaceutical chemistry
but are not on the “wish lists” of pharmaceutical companies.
On the other hand, from the purely commercial point of view, this strategy has
important practical disadvantages. It requires substantial initial investments in
research and development that may result in the rediscovery of a well-known mol-
ecule in a scientifically interesting but commercially useless context. It is difficult
to expand, since it depends on a limited supply of graduate students and financial
support to scientific research. Moreover, most universities in developing countries
place institutional obstacles in the way of professors who wish to spin off start-up
businesses to take advantage of commercial opportunities opened up by the results
of their academic research. Finally, the academic focus on open communication and
quick publication may ironically cut off the opportunity for commercial exploitation
of a discovery as a mainstream pharmaceutical, since publication precludes patenting,
and no commercial company will invest in the development of a drug if it cannot
gain exclusive rights. It is thus important for individual chemists in a developing
country to delay publication until they have availed themselves of legal advice, if
they wish their discoveries eventually to result in royalty income from newly disco-
vered commercial pharmaceuticals or other products.

2. Climbing the value-added chain

Climbing the value chain of a natural resource based industry adds more than
knowledge and profit. It also adds to operational complexity, to the lead time until
income begins to arrive, to the financial commitment, to the costs and to the risks.
In the particular case of bioprospecting, developing countries face a difficult strategic
choice between seeking immediate income from collecting and selling samples and
preparing simple chemical extracts, on the one hand, and the riskier, longer-term but
potentially more profitable path of building a value-added biotechnology industry,
on the other. The choice will depend on both scientific and economic factors.
To launch a bioprospecting effort, a developing country must invest seed capital
in order to expand its facilities for collection, extraction and simple screening, if for
no other reason than to demonstrate its capabilities to potential investors. Since in
the absence of donor support, a bioprospecting effort in a developing country must
usually at least pay its own way more or less from the beginning, its promoters may
be forced to adopt the more commercially oriented, less technologically sophisticated
strategy of providing a large number of samples to overseas pharmaceutical compa-
488 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

nies in exchange for cash, including a substantial up-front payment to cover initial
capital expenses, leaving to their overseas partner the technically and financially
demanding work of screening, research and development.
In principle, any cash-generating commercial activity could provide this initial
cash flow, whether or not it involved new product development. Bioprospecting
could, for example, be established as the research arm of a business in commercial
biologicals (such as snake venom), biochemicals (such as natural hormones), non-
timber forest products (nuts, fruits, oils, fibers, wildlife products, etc.), traditional
medicines, imported pharmaceuticals, or indeed any commercial product or service.
The bioprospectors can then use the income from these less demanding services to
build up cash flow to sustain the operation while they are gaining experience and
building up their own scientific and managerial capacity to move into increasingly
profitable and technically sophisticated activities.
If, on the other hand, the developing country can afford to defer receipt of cash
income and can instead make a longer term investment in building the basis for a
biotechnology industry, it is probably best advised to gain access to screening tech-
nology and marketing capability through a strategic alliance with a foreign company
that is willing to transfer this technology and know-how in exchange for access to
that country’s biodiversity resources. In such a bargain, the developing country is
likely to have to forego any large initial cash payment in return for the transfer of
technology and a share in the rights to any intellectual property that results from the
joint research. It may even find it advantageous to provide samples free of charge
in exchange for equipment and training. If no cash changes hands, the share in these
rights may approach 50:50, so that the risks are shared and the potential rewards
maximized to both parties. The stronger the scientific and technological capability
in the developing country, the more likely this strategy is to be successful.
Such an alliance is in effect an implementation of Articles 16–18 of the Biodivers-
ity Convention, which encourages developing countries to use their biodiversity
resources as a vehicle with which to gain access to advanced biotechnology through
commercial means [29]. Even if it requires no direct expenditure, however, the trans-
fer of technology will be ineffective if it is not accompanied by major investments
of both money and personnel on the part of the developing country.
The partner in such a strategic alliance may be a major pharmaceutical company,
or a relatively small company specializing in screening or in drug discovery and
development, but lacking its own marketing and manufacturing capability. Once a
lead is discovered, the decision regarding whether or not to pursue it depends on
the business strategies of the parties. If the partner is a small company, the partners
are likely to make a joint decision as to whether to develop the lead jointly, to allow
the drug development company to pursue it in exchange for a cash payment to the
developing country partner, or to sell it off to a pharmaceutical company for immedi-
ate income to be split between the parties. A large multi-national pharmaceutical
company, on the other hand, is unlikely to pursue this type of joint development.
Such a company normally invests its own resources in pursuit of any lead that meets
its business strategy and criteria, and may even elect to return all rights to the supplier
of a lead that it elects not to pursue.
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 489

3. Seeking profit all along the value-added chain

Developing countries naturally wish to begin their bioprospecting activities at as

high a technological level as possible, so as to maximize their value-added and to
avoid relegating themselves to their traditional roles as suppliers of raw materials to
industries in more advanced countries. There is every reason why they should do
this, especially given the rapid pace of scientific development.
Developing countries need to keep abreast of scientific developments in basic
science if they wish to launch a biotechnology industry based on biodiversity
resources. First, many developing countries are likely to develop capability to provide
samples of plant and animal material, resulting in depressed prices for samples with
little or no value-added [22]. Second, the price of plant and animal extracts is cur-
rently being depressed by the availability of convenient, man-made sources of whole-
sale lead compounds from “combinatorial” chemistry: a sophisticated technique of
chemical synthesis that results in the random synthesis of huge numbers of different
polymers from a given set of monomers (“pharmacophores”) [30–34]. Refinements
of this technique provide built-in “locators” to enable “hits” to be easily extracted
from a heterogeneous screening mixture. Third, advances in microbiology have rev-
olutionized our notion of the tree of life, uncovering a whole new world of
“extremophiles” and possibly relegating the plant and animal kingdoms to relative
insignificance as sources of biodiversity [35–37]. At the same time, new techniques
of “shotgun cloning” now allow researchers to retrieve DNA from microbial species
directly from soil or seawater, making it possible to capture and express microbial
genes that were previously inaccessible because their parent microbe could not be
cultured in the laboratory. Finally, new techniques may soon make it possible to
obtain the natural products corresponding to genes that are present in the DNA of
a plant but that were not being expressed when the plant specimen was collected in
the field—for example, a natural pesticide that is produced only when the plant is
under attack by a particular kind of insect.
However, as we have seen, the technical, managerial and especially the financial
costs increase geometrically at each stage of the value chain, as do the technical,
regulatory and market risks. Despite its low standing in the value-added chain, pro-
viding samples is a reliable source of cash flow, especially in the early stages of a
bioprospecting undertaking, and can provide some of the resources needed to build
more sophisticated scientific and managerial capability. For all these reasons, it may
not make business or practical sense to invest in the human and financial resources
to create the necessary capability all at once. Besides, there are many ways to add
knowledge to samples and extracts, and in this way to increase their value, without
acquiring screening or other chemical capabilities. For example, income from plant
samples can be increased if extracts are derived with different solvents (polar, non-
polar) and from different parts of the same plant (stem, leaves, roots, fruits). More-
over, the same sample can be supplied to several drug companies, each with an
exclusive right for a different set of applications.
The value of samples can be further increased by application of chemical, biologi-
cal and business information and know-how, taking advantage of a developing coun-
490 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

try’s traditional understanding of its own resources and of the comparative advantage
that it enjoys in technically demanding but labor intensive tasks. For example, a
sample is worth much more if it is “garnished” with information about previous
screens (even if negative), with taxonomic or ecological information indicating likely
pharmacological activity (related to plants with known activity, or not attacked by
omnivorous plant-eaters, for example). A sample is especially valuable if it is
accompanied by information about long-standing ethno-botanical usage. In extreme
cases—for example, evidence of long-standing traditional use to treat a syndrome
that is likely be recognized as such by a traditional healer and yet is directly transfer-
able to modern life, such as a contraceptive or a cure for athlete’s foot, diabetes, or
congestive heart failure—such information can increase the value of a sample 10–
20 times. On the other hand, the automated screens used in large pharmaceutical
laboratories are so fast and efficient that all samples may be run through all screens
regardless of their origin, reducing the value of ethnobotanical or ecological infor-
mation. Moreover, ethno-botanical information may be a less valuable aid to the
search for cures for diseases not typically diagnosed by traditional healers, such as
AIDS and many kinds of cancer.
Developing countries can also add value to samples by taking on labor-intensive
technical work that their lower salary structure allows them to do much more cheaply
than their customers in advanced countries. For examples, they can “beneficiate” the
samples by purifying them of tannins and other high molecular weight compounds
that interfere with screens and are unlikely to have pharmacological value. Moreover,
depending on the requirements of their customers, they may be able to multiply the
value of each sample many-fold by fractionating it by solvent extraction or by high
performance liquid chromatography, thus selling fractions instead of samples. Still
higher value-added can be created by marketing samples or fractions as ready-made
96-well plates that can be introduced directly into high-throughput screening systems.
Another source of early cash flow for the fledgling bioprospecting service is the
resupply of material from samples that have achieved “hit” or more advanced status.
Capability for resupply requires efficient information management: a well-maintained
geographical information system, covering where each sample was gathered and what
grows where in the country and under what conditions.
Once the likelihood for extensive resupply of a particular species is clearly estab-
lished, the bioprospecting service should make arrangements with the national agri-
cultural research laboratory or other organization to begin work on the development
of a sustainable technology for production of the plant by plantation or small-holder
agriculture. Such a technology creates the possibility of a profitable agricultural crop
if agricultural production can compete with chemical synthesis, and reduces the prob-
ability that resupply requirements will endanger the viability of the wild population
of the plant, which is the source of genetic variability of the species. The latter
danger is real [38]. Business arrangements with the purchaser of the sample should
provide the country of origin with first right of refusal of the opportunity for agricul-
tural production of successful plant species in commercial quantities.
If business arrangements have been properly drawn up, a “lead” compound may
become a continuing source of income from “milestone” payments as the sample
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 491

passes successive tests and advances towards commercialization. (See Table 1.) A
“candidate product” selected to undergo clinical testing may net hundreds of thou-
sands of dollars in milestone payments, depending on the value of the application
and the degree of chemical modification that was necessary to make a promising
drug out of the active principle of the original sample. Successful passage of phase
II (effectiveness) clinical testing warrants another, somewhat larger payment.
The real money comes with successful passage of phase III (safety) testing and
filing of a so-called “new drug application”. This “victory” money may exceed a
million dollars, even before marketing begins. Royalties on gross sales of an ethical
drug paid to sample providers may range from 0.5–2.5%, again depending on the
amount of information provided with the sample and the level of investment that
was necessary to bring the drug to market. Given that an anticipated $200 million
annual market is necessary to justify the research and development expenditures on
a new drug, this level of royalty is a major contribution to the income stream of a
developing country laboratory.
The returns from discovery of new pharmaceuticals, while lucrative, are risky and
long in coming. Quicker although lesser rewards may be sought in other markets,
such as phytomedicines and personal care products. Phytomedicines, for example,
are plant extracts sold for medicinal purposes, especially in Europe, often without
detailed chemical characterization and subject to much less stringent regulation than
“ethical” pharmaceuticals. A developing country laboratory may speed up its cash
flow by identifying and characterizing the active principle of a well established folk
medicine used to treat ailments recognizable in western countries, proving the effi-
cacy of the active ingredient through clinical tests, and commercializing the resulting
standardized plant extract with documented claims of effectiveness for the indications
for which its usefulness has been established. Alternatively, it may sell the extract
without specific therapeutic claims on the less regulated but less lucrative market
for traditional herbal medicines or personal care products. Such commercialization
would normally take place in collaboration with overseas firms that are well estab-
lished in markets for herbal medicines in Europe, Japan or the United States. The
same is true for cosmetics and other personal care products, except that safety and
availability of large quantities of raw material is likely to be more important than
proven efficacy.

4. Encouraging biotechnology-based business

The business of bioprospecting is thus quite different from the relatively low-
tech manufacturing businesses typical of developing countries. It requires a different
mentality on the part of local scientists, business people, and investors, and a corre-
spondingly different set of government policies for its encouragement. Because of
the potential importance of bioprospecting to the global environment, this change in
mentality is of substantial importance, not only to the developing countries, but to
the entire world.
Most businesses in developing countries produce standard, well-known products
 492

Table 1
The value added chain for pharmaceutical products

Typical
Link in value-added Time milestone Survivors are
chain Screening process Supply required required % Surviving payment called

In vitro affinity assay Test for affinity for receptors that 10–1000 Mg unpurified 1 week 1:1000 None Hits*
indicate affinity for target organ, material
enzyme, or cell
In vivo or whole cell Fractionate, verify activity in animal 10 g of Semi purified 6 months 1:30 $10,000 Leads
assay tests material
Research and Purify, elucidate structure and modify 50–200 Kg of crude 6 years 1:10 $100,000 Candidate
preliminary chemically: understand mechanism of material products
development action: synthesize active principle of
assure natural supply: test on animals:
study toxicology, pharmacokinetics,
formulation; continue animal tests
Clinical testing (under Test on human patients to determine 50–5000 Kg of crude 4–8 years 1:6 $100,000– Commercial
FDA regulations for dosage, side effects, and formulations, material, plus assurance $1M products
investigational new and to prove safety, efficacy, and defined of resupply on
drugs) application. commercial scale if
needed
Commercial success Major practical advance in major 1:100 $1M–$10M Blockbusters
C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

($300 million/year pharmaceutical market: post-market

market is minimum) studies

*
In Vitro Screening is repeated with material taken from the same sample. Survivors of the repeated screen are called “confirmed hits”.
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 493

aimed at well established domestic or export markets. They use well proven, rela-
tively stable technologies transferred from the advanced countries. Investors and fin-
ancial institutions are accustomed to relatively quick return of invested capital—say
3–4 years—and are unaccustomed to technological risk. The recent liberalization of
the economic policies of many developing countries, along with the sale of publicly
owned infrastructure to private investors, have created large numbers of relatively
low-risk investments promising high returns in fast-growing “emerging markets” in
developing countries.
To be sure, globalized markets have increasingly forced developing country manu-
facturers to keep up with world trends in markets and technology. This in turn has
given rise to increasing requirements for information management and communi-
cations infrastructure, and sometimes for proprietary technology that can be imported
only into countries offering adequate protection to intellectual property. Even so, the
typical developing country business has little connection with local universities and
research laboratories and no need at all to keep up with developments in sophisticated
basic science. Its major requirement from the government is a stable macro-economic
environment, a climate favorable to business and foreign investment, and freedom
from excessive regulation and corruption. Consumers, for their part, benefit from
policies that encourage competition and protect the environment.
Science-based businesses, on the other hand, like those based on bioprospecting,
depend on constant investment in research, development, and training, and close
relations with universities and research laboratories at home and abroad. This in turn
requires a quite different set of government policies. For such business, efficient
communication, connectivity via Internet, and strict protection of intellectual pro-
perty are absolute requirements, along with “patient” capital willing to accept the
risks and long time horizon of the research based business and customs officials
willing to expedite delivery of perishable supplies. In this way, biotechnology-based
firms in developing countries have characteristics in common with software and other
information- and science-based businesses.
The development of such attitudes and policies has usually been considered a
hallmark of the most advanced stages of the transition from developing to newly
industrialized country. If a developing country wishes to build a biotechnology indus-
try on the basis of its biodiversity resources, however, it needs to address these
issues at a relatively early stage. Given the importance of bioprospecting to the world
environment, assisting developing countries with these policies should be a major
objective for development assistance agencies.

5. Fairness towards traditional peoples

In many cases, successful bioprospecting requires not only a partnership between

researchers in developing and advanced countries, but also between the two scien-
tifically advanced partners and the traditional healers and traditional peoples who in
many cases are the stewards of biodiversity and of biocultural knowledge [39]. At
a minimum, the latter should be compensated for the time they spend in passing
494 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

their knowledge on to inquiring western scientists, and their intellectual contribution

acknowledged in professional publications and (when this is consistent with patent
laws) patent applications.
More fundamentally, equity demands that the contribution of traditional peoples
to bioprospecting deserves equitable financial compensation, whether or not this con-
tribution is recognized by prevailing concepts of the protection of intellectual pro-
perty [40–42]. Only in this way will traditional peoples have an incentive to preserve
this valuable and irreplaceable traditional knowledge and to pass it on to future
generations. This consideration may present practical problems in cultures that are
not monetized. The Healing Forest Foundation, an off-shoot of the Shaman Pharma-
ceutical Company, has sometimes found it advisable to finance development projects
requested by a particular village rather than to provide cash rewards [43–45]. In
other cases, substantial discussion and negotiation may be necessary to identify
recognized tribal authorities through whom monetary rewards may be channeled.
These techniques are still developing, and a substantial period of experimentation is
likely to be necessary before the best practice is clear.
Equity demands that traditional peoples receive full disclosure of the intentions
of bioprospectors, including the possibility of practical application and commercial
use and profit, as well as frank disclosure of the uncertainties inherent in bioprospect-
ing and more generally in pharmaceutical and other forms of technological research.
The cultural value of traditional knowledge deserves the full respect of bioprospec-
tors. Specifically, the secrecy of certain forms of traditional knowledge must be
respected. If a traditional healer or a traditional culture does not wish to disclose
the use of a particular species, this wish must be respected [46,47].
Ultimately, the best way to assure equitable treatment for traditional peoples is to
provide them not only with a basic understanding of the legal principles concerning
access to biodiversity resources, but also of the practical considerations surrounding
bioprospecting. After all, biodiversity resources will not be an economic asset to
traditional peoples or to anyone else if the regulations controlling access are so strin-
gent as to scare off all potential investors or to drive them back to the “bad old”
days when genetic materials were removed from developing countries with little or
no compensation to anyone. It is in everyone’s interest that indigenous peoples have
a basic understanding of the workings of the markets for pharmaceuticals and other
products of bioprospecting, so that they can defend their own interests on the basis
of their own sophisticated technical understanding. Ideally, scientists in both
developed and developing countries should some day be working as full collaborators
with counterparts from indigenous peoples, or even be employed by them as contrac-
tors.

6. Partnerships for the global environment

A major expansion in bioprospecting is required if humanity’s endowment of

information concerning the economic value of biodiversity is to be rescued from the
threat posed by the extinction crisis. Such an expansion will require partnerships
 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498 495

between developing countries and the multi-national pharmaceutical, phytomedicine,

personal care, and agri-chemical industries—in some cases, intermediated by smaller,
high-tech companies specializing in new product discovery.
To these partnerships, the multi-national company brings major capital, human,
scientific and organizational resources for testing, marketing, and manufacturing of
the ultimate product, plus the full range of scientific and managerial resources needed
for screening, research and development. The developing country partner brings to
the partnership legitimate access to biodiversity resources, plus a variety of signifi-
cant but usually fragmented scientific skills: sample collection, taxonomic classi-
fication, extract preparation and fractionation, natural products chemistry, clinical
testing, and screening. It naturally wishes to use the partnership to improve its skills,
acquire technology and equipment, and learn how to operate in the world of high
technology business. It is likely to need to balance its need for short-term income
with the higher but longer-term and riskier rewards of drug discovery.
Any such partnership depends on mutual respect and mutual advantage. Biopros-
pecting requires cooperation among a variety of disparate stakeholders, all of which
must benefit if bioprospecting is ever to be carried out on a scale sufficient to make
a difference in the world-wide conservation effort.
The multi-national (and the smaller intermediary) needs to respect the sovereign
rights of the developing countries to control access to their biodiversity resources.
The Biodiversity Convention confirms these rights.
The developing country partner must recognize that in most cases only large multi-
national corporations command the resources to manufacture products based on
newly discovered uses of novel species, to market them around the world, and in
many cases to manage the research and development. Developing countries must
therefore learn to operate as a business rather than an academic operation—with a
much quicker pace, a larger scope and a greater respect for deadlines. They need
also to recognize that technology transfer requires a substantial investment of time,
personnel and money, and proceeds from a relationship built on mutual respect and
trust, and that this takes time to cement.
Both partners need to be careful to share the benefits of their efforts with indigen-
ous peoples and traditional healers who are stewards of the biodiversity and biocultu-
ral resources and who have unique and irreplaceable knowledge of how to use local
plants and animals. It is desirable to integrate biosprospecting strategy with a conser-
vation strategy that insures the sustainability of the overall effort. The involvement
of local communities and businesspeople is essential if developing countries are to
see their biodiversity resources as economic assets worth saving and if biodiverse
habitats are not to be destroyed for conversion to other uses.
In this way, a global environmental imperative, that of conserving knowledge of
biodiversity, has become closely linked with the intensely practical issues surround-
ing the launching of biotechnology industry in developing countries: development
of local scientific capacity, links between research laboratories and business, govern-
ment policies friendly to high-tech business, protection of intellectual property, a
private sector attuned to the special problems of science-based industry, and investors
496 C. Weiss, T. Eisner / Technology In Society 20 (1998) 481–498

and financial institutions willing to accept the risks and long time horizons associated
with investments in new technology.
To achieve the global goal of conservation of knowledge concerning biodiversity
thus requires a multi-dimensional partnership between the public and private sectors,
with careful attention both to practical considerations of business profitability and
to ethical principles of sustainability and equity. This new paradigm is already fam-
iliar from such environmental issues as depletion of the ozone layer and climate
change, and is likely to be applicable to many other global environmental goals in
the future.

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Charles Weiss is Distinguished Professor and Director of the Program on Science, Technology and International
Affairs at the School of Foreign Service at Georgetown University. He is the former Science and Technology
Advisor to the World Bank.

Thomas Eisner is Schurman Professor of Chemical Ecology in the Section on Neurobiology and Behavior at
Cornell University and Director of the Cornell Institute for Research in Chemical Ecology. He is a Member
of the National Academy of Sciences and recipient of the National Medal of Science and many other awards.

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