Bioprospecting - An Overview - ScienceDirect Topics

22/10/21 10:52 Bioprospecting - an overview | ScienceDirect Topics
Bioprospecting
Bioprospecting is defined as a systematic and organized search for
useful products derived from bioresources including plants,
microorganisms, animals, etc., that can be developed further for
commercialization and overall benefits of the society.
From: Medicinal Spices and Vegetables from Africa, 2017
Related terms:
Enzyme, Protein, Biodiversity, Limnology, Bacterium
Bioprospecting
Paul Alan Cox, Steven King, in Encyclopedia of Biodiversity (Second Edition), 2013
Cancer
Bioprospecting has yielded multiple drugs approved by the FDA to treat various
forms of cancer including vincristine and vinblastine isolated from the Madagascar
periwinkle Catharanthus roseus (Apocynaceae). Vincristine and vinblastine are drugs
of choice for the treatment of pediatric leukemia. Taxol, a drug marketed by
Bristol-Meyers Squibb, is used to treat ovarian and breast cancer. Taxol was isolated
from the Pacific yew tree Taxus brevifolia (Taxaceae) during a systematic search by
the National Cancer Institute. Currently, Lars Bohlin at Uppsala University and
Samantha Gerlach at Tulane University are studying cyclotides, small cyclic
peptides from the Violaceae and Rubiaceae, as a new category of biodiversity
derived anticancer compounds.
Some innovative research programs are analyzing complex mixtures of plant and
other naturally occurring substances used in traditional Chinese medicine and
Ayurvedic medicine from India for new anticancer treatments. New Earth Biomed
(NEBM), a not-for-profit cancer research organization, is currently evaluating such
alternative treatments.
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Synthetic Biology and Metabolic Engineering in Plants

and Microbes Part A: Metabolism in Microbes
M.E. Pyne, ... V.J.J. Martin, in Methods in Enzymology, 2016
4.2.3 Bioprospecting of Enzyme Variants

Bioprospecting of orthologous genes from a wide array of plant species offers a
valuable alternative to protein engineering and directed evolution. While enzyme
variants corresponding to any enzymatic step within a target pathway can be
https://www.sciencedirect.com/topics/medicine-and-dentistry/bioprospecting 1/13
screened to enhance catalytic efficiency, pathway bottlenecks present the most
promising opportunities for enzyme bioprospecting. BIA biosynthetic gene variants
can be easily identified by querying genome and transcriptome databases of BIA-
producing plants, including the 1000 Plants Project and the PhytoMetaSyn Project
described briefly in Section 2. Due to the mounting availability of DNA sequence
and transcriptome data available within the public domain, enzyme bioprospecting
offers vast opportunities for enhancing overall BIA pathway efficiency by tapping
into nature's metabolic diversity.
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Marine organisms for bone repair and regeneration

S.A. Clarke, P. Walsh, in Bone Substitute Biomaterials, 2014
Abstract:
Bioprospecting has led to increased interest in potential applications for marine
organisms and their by-products. As a rich source of mineralising porous
organisms, our seas and oceans could provide new directions for bone tissue
engineering, particularly in the supply of biomimetic templates that may enhance
in vivo and ex vivo bone formation. In this chapter we examine the history of marine
organism use in this field; exploring how these organisms could be utilised, given
the problems of sustainability, and reviewing the current evidence to support their
use for bone repair and regeneration.
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African Medicinal Spices of Genus Piper

I.A. Oyemitan, in Medicinal Spices and Vegetables from Africa, 2017
8 Bioprospecting and conservation status of the genus Piper

Bioprospecting is defined as a systematic and organized search for useful products
derived from bioresources including plants, microorganisms, animals, etc., that
can be developed further for commercialization and overall benefits of the society.
The bioprospecting and conservation of the African Piper genus is almost
nonexistent. Available reports from Asian and South American countries indicate
institutional and governmental involvement in prospecting and conservation
program of various species found in those areas (De Britto and Mahesh, 2007;
Landon, 2007). Cultivation and trade in Black Pepper (P. nigrum) has developed to
international scale in South and Central America, India, Pakistan, Malaysia, and
other South Eastern Asian countries. Okafor (1990) has emphasized the imperative
of efficient, economical, standardized nursery procedures, and knowledge of
reliable practices for accelerated seed improvement for a large-scale production of
food trees and shrubs for a conservation program or for commercial scale in
Nigeria. In some West African countries, such as Nigeria and Cameroon, P.
guineense and P. capense are still largely obtained from the forests which are being
threatened by indiscriminate destruction of the forest reserves due to increase in
land usage for diverse purposes. It is therefore suggested that a renewed attention
be focused on the cultivation and preservation of the common species found in
each country as this will protect these species from going into extinction and will
afford the rural populace of economic benefits.
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Protection of Traditional Knowledge Associated with

Genetic Resources
Padma Nambisan, in An Introduction to Ethical, Safety and Intellectual Property
Rights Issues in Biotechnology, 2017
16.2.2 The World Intellectual Property Organization and Traditional

Knowledge
Bioprospecting, especially for discovering new medicinal products from biological
resources, has relied heavily on the knowledge of local healers of the unique
properties of various organisms (particularly herbs) in their medicine chest. With
many new products and applications based on TK being patented by innovators,
often without the knowledge of the TK holders, and many of these patents being
subsequently challenged (see Box 16.1), policy makers are increasingly aware of a
need for an IP system suitable for protecting TK and associated GR. Some of the
salient issues are as below: (paraphrased from WIPO Booklet No. 2, n.d.):
Box 16.1
Some Examples of “Biopiracy”
Biopiracy of Traditional Knowledge. Retrieved from
http://www.tkdl.res.in/tkdl/langdefault/common/Biopiracy.asp?GL=Eng.
By definition biopiracy is the use of indigenous knowledge of natural resources
for commercial applications without the consent and with little or no
compensation or recognition to the community from which it originates. There
are numerous examples in recent literature, some well-known examples are
discussed here:
1. Turmeric patent (Curcuma longa L.):
Turmeric is a spice with numerous medicinal properties popular in India and
South-East Asian countries. It forms an important part of traditional
medicine in India and is part of every household’s medicinal chest used for
curing a variety of ailments. Turmeric became the center of a patent storm
when two expatriate Indians, Suman K. Das and HariHar P. Kohly, at the
University of Mississippi Medical Centre were granted a U.S. patent in 1995
for the use of turmeric for wound healing. In the ensuing furore, the Council
of Scientific and Industrial Research (CSIR) filed a re-examination case with
the USPTO challenging the patent on the grounds that it was not “novel”
and known to Indians for centuries. Documentary evidence was provided
from ancient Sanskrit texts and a 1953 paper published by the Indian
Medical Association. The U.S. patent was revoked in 1997.
2. Neem patent (Azadirachta indica A. Juss):
The neem tree, common in India and South-East Asia, is considered as the
“Village Pharmacy” as every part of the tree can be used as medicine, and
the leaves and seed-oil as insecticide and fungicide for storing grain and
protecting crop plants. In 1994, the European Patent Office granted a patent
to W.R. Grace and Company and the United States Department of
Agriculture for the use of a hydrophobic substance extracted from neem oil
for controlling fungi on plants. Legal opposition to the patent was mounted
by a group of NGOs and farmers from India in 1995. Based on the evidence
presented, the patent was revoked in May 2000.
3. Hoodia (Hoodia gordonii):
Hoodia is a cactus that has been used for thousands of years by African
bushmen of the San tribe for suppressing hunger and thirst on long hunting
trips. In 1995, the South African Council of Scientific and Industrial Research
(CSIR) patented Hoodia’s appetite suppressing element, and in 1997
licensed it to a Phytopharm, a British biotech company. Pfizer in 1998
acquired the rights from Phytopharm for $32 million to develop and market
the ingredient as a potential cure for obesity, a market worth several billions.
The San soon got to know of it and in June 2001, launched legal action
against the South African CSIR and pharma industry. Phytopharm
conducted extensive enquiries but were unable to identify the knowledge
holders. The San are a nomadic tribe spread over four countries. In trying to
enter into negotiations with the tribe, it was unclear as to who should be
benefited: the person who shared the information, his family, the tribe, or
the entire country. In 2002 the issue had been resolved with the San tribe to
receive a share of future royalties from the patent holder, the South African
CSIR. This would be a fraction of the royalties paid by Pfizer to Phytopharm
and the South African CSIR.
4. Ayahuasca (Banisteriopsis caapi Mort.):
Ayahuasca is a ceremonial drink made from the processed bark of a liana of
the same name, used by the Shamans (medicine men) of indigenous tribes
throughout the Amazon valley to diagnose and treat diseases, as well as
meet with spirits and divine the future. In 1986, Loren Miller obtained a U.S.
Patent for a variety of ayahuasca which he had collected from a domestic
garden in Amazon which had flowers of a different color qualifying it as a
new and distinct variety. The Coordinating Body of Indigenous
Organizations of the Amazon Basin (COICA) which represents more than
400 indigenous tribes in the Amazon region protested as the ayahuasca was
known for several generations and they felt this was an appropriation of
their traditional knowledge. The patent was revoked in 1999, but as the
inventor was able to convince the USPTO of its novelty, the patent was
restored in 2001 with the original claims.
1. Whether the existing IP system which privilege individual rights over collective
interests of the community is compatible with the values and interests of the
community.
2. Whether an IP system could give a community greater recognition for their TK
and control the use and management of their TK.
3. Whether an IP system could help communities safeguard their interests, and
ensure a fair and equitable share in the profits.
The WIPO began work on TK in 1998 and at its twenty-sixth session held in Geneva
in 2000 established the Intergovernmental Committee on Intellectual Property and
Genetic Resources, Traditional Knowledge and Folklore (IGC) to primarily look into IP
issues that arise in the context of:
1. Access to GRs and benefit sharing
2. Protection of TK, whether or not associated with those resources
3. The protection of folklore, including handicrafts (WIPO, 2001)
International cooperation and coordination in the protection of TK is necessary as
utilization of TK is not confined to nations and international partnerships are often
crucial to research and development efforts in the utilization of the TK. The IGC
currently provides the main forum in WIPO for an international discussion on
various aspects of protection of TK and has since its formation generated
considerable information toward understanding and resolving the issues
associated with access to GRs and benefit sharing as well as protection of TK
(available at http://www.wipo.int/tk/en/tk/). Participants in the IGC include Member
States, indigenous and local communities, representatives from business and civil
societies, and Non-Governmental Organizations (NGOs). Since 2009, the IGC has
concentrated on text-based negotiations with the objective of reaching an
agreement on a text of an international legal instrument(s) which will ensure
effective protection of TK and GRs. A “Draft objectives and principles relating to
intellectual property and genetic resources” was discussed in the twentieth session of
the IGC in Geneva in February 2012. By 2014, three revisions of the text had been
made, but the recommendations could not be agreed upon to transmit to the
Assembly (Saez, 2014). At the General Assembly, no decision could be reached on
the draft of the IGC, and with the mandate of the IGC coming to an end in 2015, it
needed to be renewed if work on policy solutions to provide international
protection for TK, GR and TCE was to be continued (Saez, 2015). The United States
attributed the collapse of the discussions to lack of consensus on fundamental
issues, such as what should be protected, who should be the beneficiaries of the
protection, and the exceptions to the proposal. The United States suggested that
the IGC should be replaced by an ad-hoc expert working group which by seminars
and studies would be able to better understand the issues at stake. However, other
countries, Switzerland, Norway, New Zealand, Holy See, Kenya, and Mozambique,
proposed that the mandate be renewed to continue negotiations on text-based
solution (Saez, 2015). The fifty-fifth session of the Assemblies of Member States of
WIPO held in October 2015, extended the mandate of the IGC during the next
budgetary biennium 2016/2017 to continue to expedite its work (WIPO, 2015).
16.2.2.1 Traditional knowledge
Two types of IP protection are being sought (WIPO, n.d.):
• Positive protection: granting of rights that empower communities to promote
their TK, control its uses and benefit from its commercial exploitation.
• Defensive protection: aims to stop people outside the community from acquiring
IP rights over TK
16.2.2.2 Genetic resources
GRs themselves are not IP as they are not creations of the human mind, hence
cannot be protected as IP. However, inventions based on GR may be patentable, or
capable of protection under plant breeder’s rights. Issues being discussed at WIPO
include:
• Disclosure requirements: Several countries have enacted domestic legislation
putting into effect the CBD obligations that necessitate access to the country’s
GR to be on the basis of PIC and mutually agreeable understanding of fair and
equitable sharing of the benefits. WIPO is considering whether it should be
incorporated into international legal instruments.
• Defensive protection of genetic resources: prevents patents from being granted
over GR and associated TK, and possible disqualification of patents that do not
comply with CBD obligations of PIC and MAT, and disclosure of origin. Aims to
prevent biopiracy.
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Advances in Applied Microbiology

Carl J. Yeoman, ... Isaac K.O. Cann, in Advances in Applied Microbiology, 2010
V Improving Thermostability and Biotechnological Applicability

In addition to bioprospecting, many groups are moving forward through the
manipulation of enzymes already available to researchers. Single or successive
rounds of random mutagenesis using methods such as error-prone PCR or DNA
shuffling, followed by selection for improvements in desired traits, such as catalytic
activity, thermostability, or pH tolerance is becoming a commonly employed tool
for optimizing an enzyme's characteristics (Stephens et al., 2009, Wang and Xia,
2008). This process, known as directed evolution, is not new but allows researchers
a route forward in the absence of knowledge regarding the features underpinning
these traits. These methods have successfully led to significant increases in catalytic
activity, thermostability, and pH stability of a number of xylanases (Chen et al.,
2001; Stephens et al., 2009; Stephens et al., 2007; Wang and Xia, 2008). Methods
are continuing to be developed to expedite and simplify the selection procedures
(Liu et al., 2009). Other more calculated approaches include the structure-guided
recombination process, SCHEMA (Meyer et al., 2006). The SCHEMA process
produces chimeric proteins by interchanging contiguous blocks of amino acids.
SCHEMA is more directed than a random process, using the parental proteins’
structural data to define the boundaries of these amino acid blocks so as to
minimize the average number of amino acid sidechain contacts that are broken in
the library. SCHEMA was recently employed to develop a library of CBHs with
improved thermal stability. Chimeric CBHs were produced through recombination
of CBH genes from the fungi Chaetomium thermophilum, Humicola insolens, and
Hypocrea jecorina (Heinzelman et al., 2009). Although the authors only studied a
small fraction of the library of chimeras (48 from 6561 total chimeras), a number of
novel enzymes with improved traits were identified, including HJPlus, which gave a
high specific activity across a broad pH range and exhibited a 7–15 °C increase in
temperature optimum over the parental enzymes. Given the sampling size, it is
predicted that many more enzymes with improved thermal stability, along with
other biotechnological attributes, may reside within this chimeric library, and
consequently this appears a very valuable approach.
Similarly, the exchange of identifiable modules can lead to commensurate
increases in thermostability and hydrolytic activity. An obvious example is the
addition of CBMs to enzymes lacking this module, which has regularly been shown
to improve performance, particularly against crystalline substrate (Kang et al., 2007;
Kittur et al., 2003; Szijarto et al., 2008). Module shuffling between two GH 10
family xylanases with different thermostabilities, Cex (optimum temperature: 40 °C)
from Cellulomonas fimi and XylA (optimum temperature: 80 °C) from
Thermomonospora alba, led to a recombinant enzyme that exhibited significantly
improved thermal profiles (optimum temperature: 65 °C) compared to one of the
parental proteins, Cex (Ahsan et al., 2001). Studies such as these suggest that in
some proteins, specific protein domains may exist that confer or enhance
thermostability. Consistent with this hypothesis the deletion of particular domains
resident in some cellulases and hemicellulases has resulted in decreases in
thermostability (Hayashi et al., 1997; Riedel et al., 1998). One such domain, the A-
domain, has been identified in the N-terminal regions of xylanases from
organisms such as T. maritima, C. thermocellum, and T. saccharolyticum (Fontes et
al., 1995; Lee et al., 1993) and has been shown to improve its cognate enzyme's
thermostability and substrate-binding capacity (He et al., 2009). This may suggest
that a major source of thermoinstability derives from the binding module. It is
evident from these studies that modest changes in an enzymes primary structure
can lead to significant improvements in biotechnologically important traits
(Stephens et al., 2009), although such changes may also lead to undesirable
properties.
The extracellular cellulolytic enzymes of several bacteria, particularly Clostridia,
assemble as protein complexes or aggregates known as cellulosomes.
Cellulosomes have often been attributed with having improved catalytic activities,
particularly on crystalline substrate, as compared to the free form (individually
acting) enzymes due to the improved synergy afforded by colocalization of
complementary enzymatic activities (Fierobe et al., 2005). Consequently significant
research has been invested in developing thermostable cellulosomes and
optimizing their enzymatic constituents. The rozettazyme, for instance, is a group
II chaperonin that derives from the hyperthermo-acidophilic archaeon Sulfolobus
shibatae, which has been retrofitted with cohesin modules from the C. thermocellum
CipA protein. This synthetic scaffoldin self-assembles in the presence of ATP and
Mg2+ ions into a thermostable double-ringed structure capable of aggregating 18
complementary enzymatic activities through interactions between their dockerin
domains and the cohesins (Mitsuzawa et al., 2009). In native systems, cellulosome-
associated activities are wide ranging and can include cellulases, hemicellulases,
pectinases, chitinases, glycosidases, and esterases (Zverlov et al., 2002, 2005a,b,c)
demonstrating the heterogeneous and highly associative nature of the substrates
that these systems have evolved to degrade (Zverlov et al., 2005a,c). The
development of synthetic cellulosomes that are effective in biotechnological
applications will require optimization of the enzyme constituents. Recently derived
methods such as cohesin-dockerin microarrays will undoubtedly simplify this
process (Haimovitz et al., 2008).
An alternative approach for colocalizing synergistic lignocellulase activities is the
construction of gene fusions (Hong et al., 2006). Both approaches have shown
promising results; however, issues have occasionally emerged with the latter
regarding enzyme folding and stability.
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Ethnomedicine and Drug Discovery

Marianne Guerin-McManus, ... Sarah A Laird, in Advances in Phytomedicine, 2002
IX.A. The Panama ICBG Trust Fund: The National Environment Fund
of the Fundación NATURA, Todd Capson, Smithsonian Tropical
Institute, Panama
To couple biodiversity conservation with bioprospecting, we chose to establish a
fund that works through a Panama-based foundation that promotes the study,
conservation, and sustainable use of biological diversity. The foundation we work
with, Fundación NATURA, has supported projects throughout Panama. The fund
we established, the National Environment Fund, will provide financing that will be
available for conservation and development projects, including biodiversity
prospecting, accessible through Fundación NATURA's existing competitive grants
program. The National Environment Fund will receive a portion of all access fees,
milestones and royalties that are generated by ICBG bioprospecting activities in
Panama.
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DIVERSA INC.: ETHICAL ISSUES IN

BIOPROSPECTING PARTNERSHIPS1
David L. Finegold, ... Peter A. Singer, in BioIndustry Ethics, 2005
ETHICAL DECISION MAKING

Diversa's approach to biodiversity and to ethical issues associated with their
business begins with the top leadership. ”Jay [Short] is very important,” said
Mathur. ”He's a very ethical man. Basically most of the issues are dealt with by Jay,
myself, and Leif…If we didn't care about diversity, we wouldn't be here.” In addition
to these three key individuals, Diversa involves a number of other departments
when ethical issues arise: the IP group, finance and accounting, the R&D team, and
public relations (PR).
Diversa ”tries to be proactive and not reactive” in dealing with ethical issues,
according to Christoffersen. He believes that the company has not faced any
significant ethical problems to date because it continues to find ways ”to make sure
that we are not reacting to problems or criticisms, but are ahead of the curve.”
Despite this proactive stance, Diversa cites three types of issues it has had to
confront. The first involves general ethical objections to bioprospecting and genetic
engineering; the second focuses on opposition to a for-profit company that is seen
to be exploiting natural resources that are public, and the confidentiality of the
benefit-sharing terms; the third concerns publication of the results of its research
and what information should be in the public domain.
The general objections to bioprospecting are part of a wider ethical debate on
whether it should be permissible to patent any life forms. This debate reached a
crescendo in the late 1990s with the sequencing of the human genome, when
some companies, such as Human Genome Sciences and Celera, filed patents
covering thousands of segments of the genome that were thought to have
potential medical uses. In the case of patenting genes that encode proteins
discovered through bioprospecting, Christoffersen describes the characteristics of
the typical critics:
There are some environmental organizations that are against genetic research and
associated patents. If they can prevent a company from collecting samples, then
they believe that they can prevent them from engaging in genetic research and
securing patents for their work. No one has approached us about such issues, but
they may tackle bioprospecting to get at it… Others are just totally against genetic
research. No matter how great the package is and how happy the collaborator is,
anti-genetic-research environmental organizations won't be happy.
The counter-argument that Diversa and the many countries and environmental
groups that supported the CBD make is that the best way to preserve biodiversity is
to show the direct health and economic benefits to humans that can be derived
from these natural habitats without disturbing the ecosystem. By operating under
the principles of the CBD, even in countries that have not ratified it, Diversa feels it
is on safe legal and ethical grounds. In addition, Diversa notes that it is not
patenting natural life-forms, but rather genes that encode proteins from the
artificially generated, enhanced modifications of these microorganisms produced
through its Directed Evolution technology, and that along with patenting comes
the obligation to publicly disclose the results of this research. Because its
biodiversity agreements are all non-exclusive, other firms or scientists who want to
negotiate similar access to these natural resources can do so. ”I've been offered
exclusive agreements a few times, including one place just a few months ago,” said
Short. ”I do not want us to be in that position and I believe it is a questionable
stance for any company to take.”
The other, related criticism of Diversa and other companies engaged in
bioprospecting is that they are exploiting public resources for private gain. In part,
this may be a result of public misunderstanding associated with the term
bioprospecting and its association with the Gold Rush and other pioneers who were
not sensitive to the environment, according to Yellowstone's Varley:
Everything is an education problem. Partly this is because of when you use the
name ‘bioprospecting’ in the Western US, people see mining and logging. They see
big stacks of spoiled land and toxic water. I didn't pick the term. There's a lot of
concern out there that this will turn into a case like the Pacific yew tree, where the
drug Taxol was found in its bark, and every tree was seen to be at risk. None of that
would be allowable here [in Yellowstone].
In Diversa's case, because the size of the samples required for microorganisms is so
small and there is no need to harvest particular microorganisms on an ongoing
basis, there is no measurable negative impact on the environment. Even without a
risk of physical exploitation, some critics are concerned that the company may be
financially exploiting its non-profit counterparts by not fairly sharing benefits. ”The
other problem is not trusting that our partners know enough to effectively
negotiate a deal,” observed Christoffersen, adding that NGOs have ”concerns about
companies cutting corners and taking advantage of the situation.” Christoffersen
argues that it would not be in Diversa's own interests to negotiate a one-sided deal,
even if they were in a position to take advantage of a partner less experienced in
such negotiations:
We feel that to have a good and productive collaboration, we have to be fair. In
order to better conserve the biodiversity of interest to us, we want to empower our
partners as much as possible to reinforce their knowledge of their resources so they
can more effectively manage and protect the natural resources under their care.
The success of our company is based on the biodiversity, so we have an interest in
maintaining or amplifying it by empowering our partners… For example, we have
at times offered milestone payments, even though some of our partners didn't ask
for them. We focus in each agreement on their needs and capacities to collaborate
with us. Those that can only provide samples get different packages from those
who process the DNA and save us a step.
Because of these variations among its partnerships and the central role that these
agreements play in its business model, Diversa has kept the specific financial terms
of each agreement confidential. This decision, however, has raised concerns among
the critics of bioprospecting about the lack of transparency. Christoffersen
explained, ”Ethics also comes up through outside parties who try to evaluate and
assess the collaboration. Some interest groups, such as journalists searching for a
story, or environmental groups in need of controversy to help boost fundraising
efforts, may find the mere fact that these benefit-sharing terms are confidential is
unethical.” He noted that the bulk of the agreement is made public, with only the
precise level of payments for services, milestones, and royalties kept confidential,
and described Diversa's rationale:
We're proud of being the world leader in this area. Other competing companies
may be working with biodiversity, but for them it is only a small percentage of their
activity [while it is core for Diversa]… You can look at it in several different ways:
from our point of view it's important to keep some things confidential because it
[the agreement] is based on our determination jointly with our partner of the value
of the services provided and their financial needs. We don't want one biodiversity
collaboration to bias another one. We could justify and explain how we came to
each arrangement. But it is easier if we can avoid getting into that discussion. We
would rather focus on what they need and the value of what they can provide. In
cases where you're talking about a small area, for example, the Meadowlands where
we had a small partnership with Rutgers, it is not the same as dealing with all of
Alaska or Kenya… For us it is important not to have outside parties who have no
direct stake in the matter assess the terms of our agreements. We don't want to be
caught up in discussions of why these terms vary from partner to partner. You
could spend the rest of your life debating what is equitable. Ultimately, what is
most important is that the parties to the agreement are pleased with the terms.
Though not wanting to involve outside parties in these negotiations, Diversa has
sought to explain its approach to biodiversity access and benefit sharing to
stakeholder groups, but has had some difficulty engaging in a constructive
dialogue. Christoffersen cited the example of Diversa's efforts to join the World
Conservation Union:
They are a powerful and important environmental organization, whose members
are governments and NGOs. They have no private firms as members. I've
approached them to ask if they would allow corporate members. I was told that
there is no way they can do it; the non-profits would refuse. How do they ever hope
to have major impact if they shut out companies? The point of mentioning this
example is to reinforce the problem we face with a significant portion of the
environmental community that believes that companies should not be involved in
any aspect of the conservation of nature. What many of these environmental
organizations fail to recognize is that biotech companies are made up of scientists
primarily from the field of biology. Hence, these are biologists that love life, the
diversity of life, and nature. Their aim is not to destroy the environment, but rather
more often than not to figure out ways to protect it.
In addition to biodiversity issues, the other ethical question that Diversa faces, like
most life-science firms, is how to balance the need to protect its intellectual
property and their shareholders' interests with the scientific norms around public
disclosure of research findings. Mathur admitted:
As a company, you don't want to publish. But as a scientist, you do, particularly if
you're going to have a scientific paper, and readers are going to want to have
access to the underlying sequence. We decided to abide by the guidelines set down
in the Bermuda meetings on genome policy, which allow for a 6-month window [to
conduct research and file patents] prior to publication.
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Ethnomedicine and Drug Discovery

Nigel Gericke, in Advances in Phytomedicine, 2002
I. Introduction
Southern Africa's remarkable diversity of climate, geology and soil is reflected in the
region's biodiversity, and, combined with the rich cultural diversity, it is not
surprising to find that about 3500 species of higher plants are used as medicines.
The sale of traditionally used minimally processed medicines is generally ignored
by the authorities, but the lack of regulatory clarity for manufactured products has
inhibited investment in this sector and delayed the development of a vibrant
natural products industry.
Some medicinal plants have been selected to highlight recent developments,
including Harpagophytum procumbens – Devil's Claw, Pelargonium sidoides –
Umckaloabo, Sutherlandia microphylla – Cancer Bush, and Sceletium tortuosum –
Kougoed.
Commercial opportunities in South Africa include:
• bioprospecting
• novel products
• new crop development
• raw material production
• extracts for clinical studies
• clinical studies.
Southern Africa's remarkable diversity of climate, rainfall, geology and soil types is
reflected in the region's biodiversity. There are some 30,000 species of higher
plants and a high degree of endemism, particularly in Cape Floral Kingdom and
the succulent karroo vegetation types. The region also has a rich cultural diversity,
so it is not surprising to find that about 3500 species of higher plants are used as
medicines.
There are presently an estimated 200,000 indigenous healers in South Africa alone.
About two-thirds of these practise full-time, and the remainder work as healers in
their spare time, often working full time as subsistence farmers, domestic workers,
and laborers. Healers rarely have a tertiary education such as a nursing
qualification. Mr. Isaac Mayeng, a Tswana healer, is an exception indeed, since he
has a B.Sc. degree in medicinal chemistry from New York State University in
Buffalo, and is assisting the Ministry of Health develop regulations for the
registration of indigenous medicines.
Plants are the main materia medica of local healers, and although there is no hard
scientific evidence, I am quite convinced that many southern African medicinal
plants have a history of use that dates back to the earliest ancestors of man. South
Africa has a wealth of Australopithicene fossils dating back to some three million
years, and is increasingly gaining recognition as a possible cradle of mankind.
More recently, Homo erectus used hand-axes and other stone tools that are found
throughout the region, and are between 1.2 million years to 200,000 years old, and
these archaic hominids were likely to have been self-medicating with the local flora.
Somewhere in the region of 80% of people in southern Africa consume
unprocessed or minimally processed indigenous medicines, usually in addition to
using modern healthcare facilities and over-the-counter health products. In South
Africa, some 20,000 tons of wild-harvested medicinal plants are traded in a year,
worth approximately US$60 million. These figures are from a recent
comprehensive study undertaken by Myles Mander on behalf of the Food and
Agricultural Organization.1
Unfortunately there is still a great deal of regulatory uncertainty in South Africa,
and it is not yet clear how the regulatory authority intends to deal with health
products manufactured from indigenous plants. The sale of traditionally used
minimally processed medicines is presently ignored by the authorities, but the lack
of regulatory clarity for manufactured products has inhibited investment in this
sector and delayed the development of a vibrant natural products industry in the
country. Local pharmaceutical companies and natural products companies are
largely importing products from Europe and the USA. It is presently easier to
register products made from well-known European, North American, Indian and
Chinese medicinal plants. This is a great tragedy from a cultural as well as an
economic perspective, and I hope that a pragmatic regulatory framework can be
developed to facilitate this fledgling industry.
The Medical Research Council of South Africa (MRC) is presently involved in
supporting university programs that are collaborating with indigenous healers to
find effective phytomedicines or new chemical entities for the major infective
diseases in the region. Ongoing research into novel antimalarial drugs is taking
place, which will most likely be extended to TB and HIV/AIDs, and AIDS-related
opportunistic infections. One of the researchers at the Pharmacology Department
of the University of Cape Town, Mr Gilbert Matsibisa (personal communication),
has confirmed the antimalarial activity of a South African plant traditionally used to
treat malaria, and has further isolated the pure compound responsible for this
activity. It is highly active in vitro in exceedingly low doses against both
chloroquine-sensitive and chloroquin-resistant malaria. The identity of the plant is
being kept confidential as intellectual property is still being generated.
Unfortunately, many of these positive research results simply earn the researcher a
post-graduate degree, and do not end up being studied clinically. Partnerships that
may be forged with the WHO Tropical Diseases Research Program and improved
culture of university-industry collaboration could change this.
One of the major flaws in research being done to validate traditional uses is that
this validation is primarily being done using a limited range of in vitro bioassays. I
am struggling to convince research organizations of the value of direct observation
of traditional treatments and outcomes in the field by MDs, and the need to
develop ethical guidelines and formal ethics-committee approval for this type of
activity. On a recent visit to an area on the Zimbabwe border, where endemic
malaria is a major problem, I found that a highly respected Venda healer, Mr
Joseph Tshikovha, has been successfully treating malaria in adults and children for
many years with a decoction of two plants: Sclerocarya birrea and Siphonochilus
aethiopicus. Knowing the healer, and the context in which he practices, I think that
his information is highly credible, and should be thoroughly researched. An added
advantage is that the two plants are widely used for other medicinal purposes, and
are regarded by southern African healers as being entirely safe.
The following descriptions of a few indigenous South African medicinal plants
highlight some recent developments and issues.
Read full chapter

URL: https://www.sciencedirect.com/science/article/pii/S1572557X02800228
Mining Chemodiversity From Biodiversity:

Pharmacophylogeny of Ranunculaceae Medicinal Plants
Da-Cheng Hao, in Ranunculales Medicinal Plants, 2019
2.7 Conclusion
Biodiversity and its compositional chemical diversity have served as one of the
richest sources of bioprospecting, resulting in the discovery of some of the most
important clinical drugs. Ranunculaceae plants have a huge reservoir of chemical
constituents, which are not distributed randomly and thus have taxonomic
implication. Alkaloids, saponin, and ranunculin are the main chemical features and
could be useful in chemotaxonomy. The new chemical profile data, based on the
more sensitive analytical technology, show that the distribution of ranunculin and
magnoflorine are not mutually exclusive. This book agrees with Wang et al.’s
system (2009) that divides Ranunculaceae into 5 subfamilies and the subfamily
Ranunculeae into 10 tribes. More species could be discovered in biodiversity hot
spots, and there is a lack of chemical data in many Ranunculaceae genera, for
example, Dichocarpum, Paraquilegia, Urophysa, Hepatica, Naravelia, Oxygraphis, and
Halerpestes, implying that the biological and chemical space for exploration is still
wide open. Pharmacophylogeny, as a fascinating approach of mining
chemodiversity from biodiversity, could be further developed and used in the
future to accelerate the pace of drug discovery.
Read full chapter

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Enzyme, Protein, Biodiversity, Limnology, Bacterium

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