Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for , and biochemical and genetic information that could be developed into commercially valuable products for the agricultural,
Terrestrial plants, fungi and Actinomycetota have been the focus of many past bioprospecting programs,
When a region's biological resources or indigenous knowledge are unethically appropriated or commercially exploited without providing fair compensation, this is known as biopiracy.
Other risks associated with bioprospecting are the overharvesting of individual species and environmental damage, but legislation has been developed to combat these also. Examples include national laws such as the US Marine Mammal Protection Act and US Endangered Species Act, and international treaties such as the UN Convention on Biological Diversity, the UN Convention on the Law of the Sea, the Biodiversity Beyond National Jurisdictions Treaty, and the Antarctic Treaty.
Bioprospecting-derived resources and products
Agriculture
Bioprospecting-derived resources and products used in agriculture include
,
and veterinary antibiotics.
Rhizobium is a genus of soil bacteria used as biofertilizers,
(also called Bt) and the
(obtained from seeds of the plant
Annona squamosa) are examples of biopesticides,
and
valnemulin and
tiamulin (discovered and developed from the
basidiomycete fungi
Omphalina mutila and
Clitopilus) are examples of veterinary antibiotics.
Bioremediation
Examples of bioprospecting products used in bioremediation include
Coriolopsis gallica- and
Phanerochaete-derived
laccase enzymes, used for treating
brewery wastewater and for dechlorinating and decolorizing
paper mill effluent.
Cosmetics and personal care
Cosmetics and personal care products obtained from bioprospecting include
Porphyridium cruentum-derived
oligosaccharide and oligoelement blends used to treat
erythema (
rosacea, flushing and dark circles),
-derived
zeaxanthin used for skin hydration and UV protection,
-derived
used for
skin regeneration,
and
Microsporum-derived
used for
hair removal.
Nanotechnology and biosensors
Because
microbial have a broad substrate range, they can be used in
biosensor technology to detect a wide range of
. For example, laccase-containing
are used to detect
polyphenol in
wine, and
and
phenols in
wastewater.
Pharmaceuticals
Many of the
antibiotic in current clinical use were discovered through bioprospecting including the
,
,
,
,
and other β-lactam antibiotics,
,
, glycopeptides,
,
,
, and
Phosphonate antibiotics.
The aminoglycoside antibiotic
streptomycin, for example, was discovered from the soil bacterium
Streptomyces griseus, the fusidane antibiotic
fusidic acid was discovered from the soil fungus
Acremonium, and the pleuromutilin antibiotics (eg.
lefamulin) were discovered and developed from the basidiomycete fungi
Omphalina mutila and
Clitopilus passeckerianus.
Other examples of bioprospecting-derived anti-infective drugs include the antifungal drug griseofulvin (discovered from the soil fungus Penicillium griseofulvum),
Bioprospecting-derived pharmaceuticals have been developed for the treatment of non-communicable diseases and conditions too. These include the anticancer drug bleomycin (obtained from the soil bacterium Streptomyces verticillus),
Bioprospecting as a discovery strategy
Bioprospecting has both strengths and weaknesses as a strategy for discovering new genes, molecules, and organisms suitable for development and commercialization.
Strengths
Bioprospecting-derived
(also known as
) are more structurally complex than synthetic chemicals, and therefore show greater specificity towards biological targets. This is a big advantage in
drug discovery and
drug development, especially
pharmacological aspects of drug discovery and development, where off-target effects can cause adverse drug reactions.
Natural products are also more amenable to membrane transport than synthetic compounds. This is advantageous when developing antibiotic drugs, which may need to traverse both an outer membrane and cell membrane to reach their target.
For some biotechnological innovations to work, it is important to have that function at unusually high or low temperatures. An example of this is the polymerase chain reaction (PCR), which is dependent on a DNA polymerase that can operate at 60°C and above.
With the Convention on Biological Diversity (CBD) now ratified by most countries, bioprospecting has the potential to bring biodiversity-rich and technologically advanced nations together, and benefit them both educationally and economically (eg. information sharing, technology transfer, new product development, royalty payment).
For useful molecules identified through microbial bioprospecting, scale up of production is feasible at reasonable cost because the producing microorganism can be cultured in a bioreactor.
Weaknesses
Although some potentially very useful microorganisms are known to exist in nature (eg.
lignocellulose-metabolizing microbes), difficulties have been encountered cultivating these in a laboratory setting.
This problem may be resolvable by genetically manipulating easier-to-culture organisms such as
Escherichia coli or
Streptomyces coelicolor to express the
gene cluster responsible for the desired activity.
Isolating and identifying the compound(s) responsible for a biological extract's activity can be difficult.
Implementing and enforcing bioprospecting-related treaties and legislation is not always easy.
Whilst the structural complexity of natural products is generally advantageous in drug discovery, it can make the subsequent manufacture of drug candidates difficult. This problem is sometimes resolvable by identifying the part of the natural product structure responsible for activity and developing a simplified synthetic analogue. This was necessary with the natural product halichondrin B, its simplified analogue eribulin now approved and marketed as an chemotherapy.
Bioprospecting pitfalls
Errors and oversights can occur at different steps in the bioprospecting process including collection of source material, screening source material for
bioactivity, testing isolated compounds for
toxicity, and identification of mechanism of action.
Collection of source material
Prior to collecting
Biology material or traditional knowledge, the correct permissions must be obtained from the source country, land owner etc. Failure to do so can result in criminal proceedings and rejection of any subsequent
patent applications. It is also important to collect biological material in adequate quantities, to have biological material formally identified, and to deposit a voucher specimen with a
Biorepository for long-term preservation and storage. This helps ensure any important discoveries are reproducible.
Bioactivity and toxicity testing
When testing extracts and isolated compounds for bioactivity and toxicity, the use of standard protocols (eg. CLSI, ISO, NIH, EURL ECVAM,
OECD) is desirable because this improves test result accuracy and reproducibility. Also, if the source material is likely to contain known (previously discovered) active compounds (eg. streptomycin in the case of actinomycetes), then dereplication is necessary to exclude these extracts and compounds from the discovery pipeline as early as possible. In addition, it is important to consider
solvent effects on the cells or cell lines being tested, to include reference compounds (ie. pure chemical compounds for which accurate bioactivity and toxicity data are available), to set limits on cell line passage number (eg. 10–20 passages), to include all the necessary positive and negative controls, and to be aware of assay limitations. These steps help ensure assay results are accurate, reproducible and interpreted correctly.
Identification of mechanism of action
When attempting to elucidate the mechanism of action of an extract or isolated compound, it is important to use multiple orthogonal assays. Using just a single assay, especially a single
in vitro assay, gives a very incomplete picture of an extract or compound's effect on the human body.
In the case of
Valeriana officinalis root extract, for example, the
Sleep induction effects of this extract are due to multiple compounds and mechanisms including interaction with
and relaxation of
smooth muscle.
The mechanism of action of an isolated compound can also be misidentified if a single assay is used because some compounds interfere with assays. For example, the sulfhydryl-scavenging assay used to detect histone acetyltransferase inhibition can give a false positive result if the test compound reacts covalently with cysteines.
Biopiracy
The term
biopiracy was coined by Pat Mooney,
to describe a practice in which indigenous knowledge of nature, originating with indigenous peoples, is used by others for profit, without authorization or compensation to the indigenous people themselves.
For example, when bioprospectors draw on indigenous knowledge of medicinal plants which is later
by medical companies without recognizing the fact that the knowledge is not new or invented by the patenter, this deprives the indigenous community of their potential rights to the commercial product derived from the technology that they themselves had developed.
Critics of this practice, such as
Greenpeace,
claim these practices contribute to inequality between developing countries rich in
biodiversity, and developed countries hosting
Biotechnology firms.
In the 1990s many large pharmaceutical and drug discovery companies responded to charges of biopiracy by ceasing work on natural products, turning to combinatorial chemistry to develop novel compounds.
Famous cases of biopiracy
The rosy periwinkle
The
rosy periwinkle case dates from the 1950s. The rosy periwinkle, while native to
Madagascar, had been widely introduced into other tropical countries around the world well before the discovery of
vincristine. Different countries are reported as having acquired different beliefs about the medical properties of the plant.
This meant that researchers could obtain local knowledge from one country and plant samples from another. The use of the plant for
diabetes was the original stimulus for research. Effectiveness in the treatment of both
Hodgkin lymphoma and
leukemia were discovered instead.
The Hodgkin lymphoma chemotherapeutic drug
vinblastine is derivable from the rosy periwinkle.
The Maya ICBG controversy
The Maya ICBG bioprospecting controversy took place in 1999–2000, when the International Cooperative Biodiversity Group led by
ethnobiologist Brent Berlin was accused of being engaged in unethical forms of bioprospecting by several
and indigenous organizations. The ICBG aimed to document the biodiversity of
Chiapas,
Mexico, and the
ethnobotanical knowledge of the indigenous
Maya people – in order to ascertain whether there were possibilities of developing medical products based on any of the plants used by the indigenous groups.
The Maya ICBG case was among the first to draw attention to the problems of distinguishing between benign forms of bioprospecting and unethical biopiracy, and to the difficulties of securing community participation and prior informed consent for would-be bioprospectors.
The neem tree
In 1994, the U.S. Department of Agriculture and W. R. Grace and Company received a European patent on methods of controlling fungal infections in plants using a composition that included extracts from the
neem tree (
Azadirachta indica), which grows throughout
India and
Nepal.
[Karen Hoggan for the BBC. May 11, 2000 Neem tree patent revoked ] In 2000 the patent was successfully opposed by several groups from the EU and India including the EU Green Party,
Vandana Shiva, and the International Federation of Organic Agriculture Movements (IFOAM) on the basis that the fungicidal activity of neem extract had long been known in
Ayurveda.
WR Grace appealed and lost in 2005.
[BBC News, March 9, 2005 India wins landmark patent battle ]
Basmati rice
In 1997, the US corporation
RiceTec (a subsidiary of RiceTec AG of Liechtenstein) attempted to patent certain hybrids of
basmati rice and semidwarf long-grain rice.
The Indian government challenged this patent and, in 2002, fifteen of the patent's twenty claims were invalidated.
The Enola bean
The Enola bean is a variety of Mexican yellow bean, so called after the wife of the man who patented it in 1999.
The allegedly distinguishing feature of the variety is seeds of a specific shade of yellow. The patent-holder subsequently sued a large number of importers of Mexican yellow beans with the following result: "...export sales immediately dropped over 90% among importers that had been selling these beans for years, causing economic damage to more than 22,000 farmers in northern Mexico who depended on sales of this bean."
A lawsuit was filed on behalf of the farmers and, in 2005, the US-PTO ruled in favor of the farmers. In 2008, the patent was revoked.
Hoodia gordonii
Hoodia gordonii, a
succulent plant, originates from the
Kalahari Desert of
South Africa. For generations it has been known to the traditionally living
San people as an appetite suppressant. In 1996 South Africa's Council for Scientific and Industrial Research began working with companies, including
Unilever, to develop dietary supplements based on
Hoodia.
Originally the San people were not scheduled to receive any benefits from the commercialization of their traditional knowledge, but in 2003 the South African San Council made an agreement with CSIR in which they would receive from 6 to 8% of the revenue from the sale of
Hoodia products.
In 2008 after having invested €20 million in R&D on Hoodia as a potential ingredient in dietary supplements for weight loss, Unilever terminated the project because their clinical studies did not show that Hoodia was safe and effective enough to bring to market.
Further cases
The following is a selection of further recent cases of biopiracy. Most of them do not relate to traditional medicines.
-
Thirty-six cases of biopiracy in Africa.
-
The case of the Maya people's pozol drink.
-
The case of the Maya and other people's use of Mimosa tenuiflora and many other cases.
-
The case of the Andean Lepidium meyenii radish.
-
The cases of turmeric (India),
-
The case of captopril (developed from a Brazilian tribe's Arrow poison).
Legal and political aspects
Patent law
One common misunderstanding is that pharmaceutical companies
patent the plants they collect. While obtaining a patent on a naturally occurring organism as previously known or used is not possible, patents may be taken out on specific chemicals isolated or developed from plants. Often these patents are obtained with a stated and researched use of those chemicals. Generally the existence, structure and synthesis of those compounds is not a part of the indigenous medical knowledge that led researchers to analyze the plant in the first place. As a result, even if the indigenous medical knowledge is taken as prior art, that knowledge does not by itself make the active chemical compound "obvious," which is the standard applied under patent law.
In the United States, patent law can be used to protect "isolated and purified" compounds – even, in one instance, a new chemical element (see USP 3,156,523). In 1873, Louis Pasteur patented a "yeast" which was "free from disease" (patent #141072). Patents covering biological inventions have been treated similarly. In the 1980 case of Diamond v. Chakrabarty, the Supreme Court upheld a patent on a bacterium that had been genetically modified to consume petroleum, reasoning that U.S. law permits patents on "anything under the sun that is made by man." The United States Patent and Trademark Office (USPTO) has observed that "a patent on a gene covers the isolated and purified gene but does not cover the gene as it occurs in nature".
Also possible under US law is patenting a cultivar, a new variety of an existing organism. The patent on the Enola bean (now revoked)
Convention on Biological Diversity
[[File:Convention on Biological Diversity2.svg|thumb|upright=1.3|
]]
The Convention on Biological Diversity (CBD) came into force in 1993. It secured rights to control access to genetic resources for the countries in which those resources are located. One objective of the CBD is to enable lesser-developed countries to better benefit from their resources and traditional knowledge. Under the rules of the CBD, bioprospectors are required to obtain informed consent to access such resources, and must share any benefits with the biodiversity-rich country.
Bioprospecting contracts
The requirements for bioprospecting as set by CBD has created a new branch of international
patent law and trade law, bioprospecting contracts.
Bioprospecting contracts lay down the rules of benefit sharing between researchers and countries, and can bring royalties to lesser-developed countries. However, although these contracts are based on prior informed consent and compensation (unlike biopiracy), every owner or carrier of an indigenous knowledge and resources are not always consulted or compensated,
as it would be difficult to ensure every individual is included.
Because of this, some have proposed that the indigenous or other communities form a type of representative micro-government that would negotiate with researchers to form contracts in such a way that the community benefits from the arrangements.
Unethical bioprospecting contracts (as distinct from ethical ones) can be viewed as a new form of biopiracy.
An example of a bioprospecting contract is the agreement between Merck and INBio of Costa Rica.
Traditional knowledge database
Due to previous cases of biopiracy and to prevent further cases, the Government of India has converted
Ayurveda information from ancient manuscripts and other resources into an electronic resource; this resulted in the Traditional Knowledge Digital Library in 2001.
The texts are being recorded from
Tamil language,
Sanskrit,
Urdu,
Persian language and
Arabic; made available to patent offices in English, German, French, Japanese and Spanish. The aim is to protect India's heritage from being exploited by foreign companies.
Hundreds of
asana are also kept in the collection.
The library has also signed agreements with leading international
such as European Patent Office (EPO), United Kingdom Trademark & Patent Office (UKTPO) and the United States Patent and Trademark Office to protect traditional knowledge from biopiracy as it allows
at International Patent Offices to access TKDL databases for patent search and examination purposes.
See also
-
Intellectual capital/Intellectual property
-
Natural capital
-
Biological patent
-
Traditional knowledge/Indigenous knowledge
-
Pharmacognosy
-
Plant breeders' rights
-
Bioethics
-
Maya ICBG bioprospecting controversy
-
International Cooperative Biodiversity Group
-
Biological Diversity Act, 2002
-
Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) (1994)
-
International Treaty on Plant Genetic Resources for Food and Agriculture (2001)
Bibliography and resources
External links
