Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for
small molecule
Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...
s,
macromolecule
A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
s and biochemical and genetic information that could be developed into
commercially
Commerce is the large-scale organized system of activities, functions, procedures and institutions directly and indirectly related to the exchange (buying and selling) of goods and services among two or more parties within local, regional, nation ...
valuable products for the
agricultural
Agriculture or farming is the practice of cultivating Plant, plants and livestock. Agriculture was the key development in the rise of Sedentism, sedentary human civilization, whereby farming of Domestication, domesticated species created food ...
,
aquaculture
Aquaculture (less commonly spelled aquiculture), also known as aquafarming, is the controlled cultivation ("farming") of aquatic organisms such as fish, crustaceans, mollusks, algae and other organisms of value such as aquatic plants (e.g. lot ...
,
bioremediation
Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi, and plants), living or dead, is employed for removing environmental pollutants from air, water, soil, flue gasses, industrial effluent ...
,
cosmetics
Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protect ...
,
nanotechnology
Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal o ...
,
or
pharmaceutical
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
industries. In the pharmaceutical industry, for example, almost one third of all small-molecule drugs approved by the
U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) between 1981 and 2014 were either
natural product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...
s or compounds derived from natural products.
Terrestrial
plants
Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...
,
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
and
actinobacteria
The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance to humans because agriculture and forests depend on their contributions to so ...
have been the focus of many past bioprospecting programs,
but interest is growing in less explored ecosystems (e.g. seas and oceans) and organisms (e.g.
myxobacteria
The myxobacteria ("slime bacteria") are a group of bacteria that predominantly live in the soil and feed on insoluble organic substances. The myxobacteria have very large genomes relative to other bacteria, e.g. 9–10 million nucleotides except ...
,
archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
) as a means of identifying new compounds with novel
biological activities.
Species may be randomly screened for bioactivity or rationally selected and screened based on
ecological
Ecology () is the study of the relationships between living organisms, including humans, and their physical environment. Ecology considers organisms at the individual, population, community, ecosystem, and biosphere level. Ecology overlaps wi ...
,
ethnobiological,
ethnomedical
Ethnomedicine is a study or comparison of the traditional medicine based on bioactive compounds in plants and animals and practiced by various ethnic groups, especially those with little access to western medicines, e.g., indigenous peoples. Th ...
,
historical
History (derived ) is the systematic study and the documentation of the human activity. The time period of event before the invention of writing systems is considered prehistory. "History" is an umbrella term comprising past events as well ...
or
genomic
Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
information.
When a region's biological resources or
indigenous knowledge
Traditional knowledge (TK), indigenous knowledge (IK) and local knowledge generally refer to knowledge systems embedded in the cultural traditions of regional, indigenous, or local communities. According to the World Intellectual Property Organ ...
are unethically appropriated or commercially
exploited without providing fair compensation, this is known as biopiracy.
Various international treaties have been negotiated to provide countries legal recourse in the event of biopiracy and to offer commercial actors legal certainty for investment. These include the
UN Convention on Biological Diversity
The Convention on Biological Diversity (CBD), known informally as the Biodiversity Convention, is a multilateral treaty. The Convention has three main goals: the conservation of biological diversity (or biodiversity); the sustainable use of its ...
and the
Nagoya Protocol
The Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity, also known as the Nagoya Protocol on Access and Benefit Sharing (ABS) is a ...
.
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
The Marine Mammal Protection Act (MMPA) was the first act of the United States Congress to call specifically for an ecosystem approach to wildlife management.
Authority
MMPA was signed into law on October 21, 1972, by President Richard Nixon ...
and US
Endangered Species Act
The Endangered Species Act of 1973 (ESA or "The Act"; 16 U.S.C. § 1531 et seq.) is the primary law in the United States for protecting imperiled species. Designed to protect critically imperiled species from extinction as a "consequence of ec ...
, and international treaties such as the UN Convention on Biological Diversity, the UN
Convention on the Law of the Sea
The United Nations Convention on the Law of the Sea (UNCLOS), also called the Law of the Sea Convention or the Law of the Sea Treaty, is an international agreement that establishes a legal framework for all marine and maritime activities. , 167 c ...
, and the
Antarctic Treaty
russian: link=no, Договор об Антарктике es, link=no, Tratado Antártico
, name = Antarctic Treaty System
, image = Flag of the Antarctic Treaty.svgborder
, image_width = 180px
, caption ...
.
Bioprospecting-derived resources and products
Agriculture
Bioprospecting-derived resources and products used in agriculture include
biofertilizer
A biofertilizer is a substance which contains living micro-organisms which, when applied to seeds, plant surfaces, or soil, colonize the rhizosphere or the interior of the plant and promotes growth by increasing the supply or availability of prim ...
s,
biopesticide
A Biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships.
They are obtained from organisms inclu ...
s and
veterinary antibiotics. ''
Rhizobium
''Rhizobium'' is a genus of Gram-negative soil bacteria that fix nitrogen. ''Rhizobium'' species form an endosymbiotic nitrogen-fixing association with roots of (primarily) legumes and other flowering plants.
The bacteria colonize plant cells ...
'' is a genus of soil bacteria used as biofertilizers,
''
Bacillus thuringiensis
''Bacillus thuringiensis'' (or Bt) is a gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types of moths and butterflie ...
'' (also called Bt) and the
annonin
Annonins are a group of chemical compounds classified as acetogenins. They are found in the extracts of '' Annona'' seeds ('' A. squamosa'' and '' A. muricata''). Annonin-based bioinsecticides are used to control Coleoptera (beetle) pests common ...
s (obtained from seeds of the plant ''
Annona squamosa
''Annona squamosa'' is a small, well-branched tree or shrub from the family Annonaceae that bears edible fruits called sugar-apples or . It tolerates a tropical lowland climate better than its relatives ''Annona reticulata'' and ''Annona cherimo ...
'') are examples of biopesticides,
and
valnemulin
Valnemulin (trade name Econor or Biotilina) is a pleuromutilin antibiotic used to treat swine dysentery, ileitis, colitis and pneumonia. It is also used for the prevention of intestinal
The gastrointestinal tract (GI tract, digestive tract, a ...
and
tiamulin
Tiamulin (previously thiamutilin) is a pleuromutilin antibiotic drug that is used in veterinary medicine particularly for pigs and poultry.
Tiamulin is a diterpene
Diterpenes are a class of chemical compounds composed of four isoprene units, o ...
(discovered and developed from the
basidiomycete
Basidiomycota () is one of two large divisions that, together with the Ascomycota, constitute the subkingdom Dikarya (often referred to as the "higher fungi") within the kingdom Fungi. Members are known as basidiomycetes. More specifically, Basi ...
fungi ''Omphalina mutila'' and ''
Clitopilus passeckerianus
''Clitopilus'' is a genus of fungi in the family Entolomataceae. The genus has a widespread distribution, especially in northern temperate areas. Although a 2008 estimate suggested about 30 species in the genus, a more recent publication (2009) u ...
'') are examples of veterinary antibiotics.
Bioremediation
Examples of bioprospecting products used in bioremediation include ''
Coriolopsis gallica''- and ''
Phanerochaete chrysosporium
''Phanerochaete'' is a genus of crust fungi in the family Phanerochaetaceae.
Taxonomy
The genus was circumscribed by Finnish mycologist Petter Karsten in 1889. Marinus Anton Donk redefined the limits of the genus in two publications in 1957 ...
''-derived
laccase
Laccases () are multicopper oxidases found in plants, fungi, and bacteria. Laccases oxidize a variety of phenolic substrates, performing one-electron oxidations, leading to crosslinking. For example, laccases play a role in the formation of lign ...
enzymes, used for treating
beer factory wastewater
Wastewater is water generated after the use of freshwater, raw water, drinking water or saline water in a variety of deliberate applications or processes. Another definition of wastewater is "Used water from any combination of domestic, industr ...
and for dechlorinating and decolorizing
paper mill
A paper mill is a factory devoted to making paper from vegetable fibres such as wood pulp, old rags, and other ingredients. Prior to the invention and adoption of the Fourdrinier machine and other types of paper machine that use an endless belt, ...
effluent
Effluent is wastewater from sewers or industrial outfalls that flows directly into surface waters either untreated or after being treated at a facility. The term has slightly different meanings in certain contexts, and may contain various pollut ...
.
Cosmetics and personal care
Cosmetics and personal care products obtained from bioprospecting include ''
Porphyridium cruentum
''Porphyridium cruentum'' is a species of red algae in the family Porphyridiophyceae.
The microalga ''Porphyridium sp''. is a potential source for several products like fatty acids, lipids, cell-wall polysaccharides and pigments . The polysacchar ...
''-derived
oligosaccharide
An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugar ...
and oligoelement blends used to treat
erythema
Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...
(
rosacea
Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarge ...
,
flushing
Flushing may refer to:
Places
* Flushing, Cornwall, a village in the United Kingdom
* Flushing, Queens, New York City
** Flushing Bay, a bay off the north shore of Queens
** Flushing Chinatown (法拉盛華埠), a community in Queens
** Flushing ...
and
dark circles
Periorbital dark circles are dark blemishes around the eyes. There are many causes of this symptom, including heredity and bruising.
Causes
Anatomical factors
Bony structure and prominence of the orbicularis oculi muscle can contribute to infra ...
),
''
Xanthobacter autotrophicus
''Xanthobacter autotrophicus'' is a Gram-negative, aerobic, pleomorphic and nitrogen-fixing bacteria from the family of Xanthobacteraceae which has been isolated from black pool sludge in Germany.Deutsche Sammlung von Mikroorganismen und Zellku ...
''-derived
zeaxanthin
Zeaxanthin is one of the most common carotenoids in nature, and is used in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika (made from bell peppers), corn, saffron, goji ( wolfberries), ...
used for
skin hydration and
UV protection,
''
Clostridium histolyticum
''Hathewaya histolytica'' (formerly ''Clostridium histolyticum'') is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. ''H. histolytica'' is pathogenic in many species, including guinea pigs ...
''-derived
collagenase
Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ga ...
s used for
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
regeneration,
and ''
Microsporum
''Microsporum'' is a genus of fungi that causes tinea capitis, tinea corporis, ringworm, and other dermatophytoses (fungal infections of the skin). ''Microsporum'' forms both macroconidia (large asexual reproductive structures) and microconidia ...
''-derived
keratinase Keratinases are Protease, proteolytic enzymes that digest keratin.
History
They were initially classified as 'proteinases of unknown mechanism' by the Nomenculture Committee on the International Union of Biochemistry in 1978 with Enzyme Commissio ...
s used for
hair removal
Hair removal, also known as epilation or depilation, is the deliberate removal of body hair or head hair.
Hair typically grows all over the human body and can vary in thickness and length across human populations. Hair can become more visible ...
.
Nanotechnology and biosensors
Because
microbial
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
laccase
Laccases () are multicopper oxidases found in plants, fungi, and bacteria. Laccases oxidize a variety of phenolic substrates, performing one-electron oxidations, leading to crosslinking. For example, laccases play a role in the formation of lign ...
s have a broad
substrate range, they can be used in
biosensor
A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector.
The ''sensitive biological element'', e.g. tissue, microorganisms, organelles, cell recep ...
technology to detect a wide range of
organic compounds. For example, laccase-containing
electrodes are used to detect
polyphenolic compounds in
wine, and
lignin
Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidity ...
s and
phenols in
wastewater
Wastewater is water generated after the use of freshwater, raw water, drinking water or saline water in a variety of deliberate applications or processes. Another definition of wastewater is "Used water from any combination of domestic, industr ...
.
Pharmaceuticals
Many of the
antibacterial drugs in current clinical use were discovered through bioprospecting including the
aminoglycosides,
tetracyclines,
amphenicols,
polymyxins,
cephalosporin
The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''.
Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
s and other
β-lactam antibiotics,
macrolides,
pleuromutilins,
glycopeptides,
rifamycin
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium ''Amycolatopsis rifamycinica'' or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective again ...
s,
lincosamides,
streptogramin Streptogramins are a class of antibiotics.
Streptogramins are effective in the treatment of vancomycin-resistant ''Staphylococcus aureus'' (VRSA) and vancomycin-resistant ''Enterococcus'' (VRE), two of the most rapidly growing strains of multidru ...
s, and
phosphonic acid 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 fusidioides
''Acremonium'' is a genus of fungi in the family Hypocreaceae. It used to be known as ''Cephalosporium''.
Description
''Acremonium'' species are usually slow-growing and are initially compact and moist. Their hyphae are fine and hyaline, and pro ...
'', and the pleuromutilin antibiotics (eg.
lefamulin
Lefamulin, sold under the brand name Xenleta, is an antibiotic medication used it to treat adults with community-acquired bacterial pneumonia. It is taken by mouth or by injection into a vein.
Relatively common side effects include diarrhea, ...
) were discovered and developed from the basidiomycete fungi ''Omphalina mutila'' and ''Clitopilus passeckerianus''.
Other examples of bioprospecting-derived anti-infective drugs include the
antifungal
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...
drug
griseofulvin (discovered from the soil fungus ''
Penicillium griseofulvum''),
the antifungal and
antileishmanial
Leishmaniasis is a wide array of clinical manifestations caused by parasites of the trypanosome genus '' Leishmania''. It is generally spread through the bite of phlebotomine sandflies, ''Phlebotomus'' and ''Lutzomyia'', and occurs most fre ...
drug
amphotericin B (discovered from the soil bacterium ''
Streptomyces nodosus
''Streptomyces nodosus'' is a bacterial species in the genus ''Streptomyces''.
Uses
''Streptomyces nodosus'' is used to produce amphotericin B.
Saquayamycins ( saquayamycins A, B, C and D) are antibiotics of the aquayamycin
Aquayamycin ...
''),
the
antimalarial drug
artemisinin (discovered from the plant ''
Artemisia annua''),
and the
antihelminthic drug
ivermectin (developed from the soil bacterium ''
Streptomyces avermitilis'').
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''), the
immunosuppressant drug
ciclosporin used to treat autoimmune diseases such as
rheumatoid arthritis and
psoriasis (obtained from the soil fungus ''
Tolypocladium inflatum''),
the anti-inflammatory drug
colchicine used to treat and prevent
gout flares (obtained from the plant ''
Colchicum autumnale''),
the
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
drug
ziconotide (developed from the
cone snail ''
Conus magus''),
and the
acetylcholinesterase inhibitor galantamine used to treat
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(obtained from plants in the ''
Galanthus
''Galanthus'' (from Ancient Greek , (, "milk") + (, "flower")), or snowdrop, is a small genus of approximately 20 species of bulbous perennial herbaceous plants in the family Amaryllidaceae. The plants have two linear leaves and a single ...
'' genus).
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
small molecule
Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...
s (also known as
natural product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...
s) are more structurally complex than synthetic chemicals, and therefore show greater
specificity towards
biological targets. This is a big advantage in
drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.
Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...
and
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
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them. Th ...
than synthetic compounds. This is advantageous when developing
antibacterial drugs, which may need to traverse both an
outer membrane and
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
to reach their target.
For some
biotechnological innovations to work, it is important to have
enzymes 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.
In other situations, for example
dephosphorylation, it can be desirable to run the reaction at low temperature.
Extremophile bioprospecting is an important source of such enzymes, yielding thermostable enzymes such as
''Taq'' polymerase (from ''
Thermus aquaticus''),
and cold-adapted enzymes such as shrimp
alkaline phosphatase
The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...
(from ''
Pandalus borealis'').
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
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
bioprospecting, scale up of production is feasible at reasonable cost because the producing microorganism can be
cultured
Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tylor ...
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.
Also, subsequent elucidation of the
mechanism of action of the isolated compound can be time-consuming.
Technological advancements in
liquid chromatography,
mass spectrometry
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...
and other techniques are helping to overcome these challenges.
Implementing and enforcing bioprospecting-related treaties and legislation is not always easy.
Drug development is an inherently expensive and time-consuming process with low success rates, and this makes it difficult to quantify the value of potential products when drafting bioprospecting agreements.
Intellectual property rights may be difficult to award too. For example, legal rights to a
medicinal plant may be disputable if it has been discovered by different people in different parts of the world at different times.
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
anticancer drug.
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
biological
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary in ...
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
''Identified'' is the second studio album by Vanessa Hudgens, released on July 1, 2008 in the U.S. June 24, 2008 in Japan, February 13, 2009 in most European countries and February 16, 2009 in the United Kingdom. The album re ...
, and to deposit a voucher specimen with a
repository 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
The Clinical and Laboratory Standards Institute (CLSI) is a volunteer-driven, membership-supported, not-for-profit, standards development organization. CLSI promotes the development and use of voluntary laboratory consensus standards and guidelin ...
,
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
Valerian (''Valeriana officinalis'', Caprifoliaceae) is a perennial flowering plant native to Europe and Asia. In the summer when the mature plant may have a height of , it bears sweetly scented pink or white flowers that attract many fly specie ...
'' root extract, for example, the
sleep-inducing effects of this extract are due to multiple compounds and mechanisms including interaction with
GABA receptors and
relaxation of
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
.
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
Pat Roy Mooney, for more than thirty years, has worked with civil society organizations on international trade and development issues related to agriculture, biodiversity and emerging technologies.
He was born and lived on the Canadian prairies f ...
,
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
patented 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
Greenpeace is an independent global campaigning network, founded in Canada in 1971 by Irving Stowe and Dorothy Stowe, immigrant environmental activists from the United States. Greenpeace states its goal is to "ensure the ability of the Earth t ...
, claim these practices contribute to inequality between developing countries rich in
biodiversity, and developed countries hosting
biotech 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
The Maya ICBG bioprospecting controversy took place in 1999–2000, when the International Cooperative Biodiversity Group led by ethnobiologist Dr. Brent Berlin was accused of engaging in unethical forms of bioprospecting (biopiracy) by several N ...
took place in 1999–2000, when the
International Cooperative Biodiversity Group International Cooperative Biodiversity Groups (or ICBG) is a program under National Institutes of Health, National Science Foundation and USAID established in 1993 to promote collaborative research between American universities and research institut ...
led by
ethnobiologist ]
Ethnobiology is the scientific study of the way living things are treated or used by different human cultures. It studies the dynamic relationships between people, biota, and environments, from the distant past to the immediate present.culture ...
Brent Berlin was accused of being engaged in unethical forms of bioprospecting by several
NGOs and indigenous organizations. The ICBG aimed to document the biodiversity of
Chiapas
Chiapas (; Tzotzil language, Tzotzil and Tzeltal language, Tzeltal: ''Chyapas'' ), officially the Free and Sovereign State of Chiapas ( es, Estado Libre y Soberano de Chiapas), is one of the states that make up the Political divisions of Mexico, ...
,
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, 200]
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
Indian traditional medicine.
WR Grace appealed and lost in 2005.
[BBC News, March 9, 200]
India wins landmark patent battle
Basmati rice
In 1997, the US corporation
RiceTec
RiceTec Inc. is a private American company based and headquartered in Alvin, Texas, that develops and produces hybrid (biology), hybrid rice seed for the American and various international markets. RiceTec previously owned the consumer brand name ...
(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
In botany, succulent plants, also known as succulents, are plants with parts that are thickened, fleshy, and engorged, usually to retain water in arid climates or soil conditions. The word ''succulent'' comes from the Latin word ''sucus'', meani ...
, 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
The Council for Scientific and Industrial Research (CSIR) is South Africa's central and premier scientific research and development organisation. It was established by an act of parliament in 1945 and is situated on its own campus in the cit ...
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
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients either extr ...
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 ''
maca'' radish.
* The cases of ''
turmeric'' (India),
''
karela
''Momordica charantia'' (commonly called bitter melon; Goya; bitter apple; bitter gourd; bitter squash; balsam-pear; with many more names listed below) is a tropical and subtropical vine of the family Cucurbitaceae, widely grown in Asia, Afri ...
'' (India), ''
quinoa'' (Bolivia), ''
oubli'' berries (Gabon), and others.
* The case of
captopril
Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...
(developed from a Brazilian tribe's
arrowhead 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
Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...
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
A supreme court is the highest court within the hierarchy of courts in most legal jurisdictions. Other descriptions for such courts include court of last resort, apex court, and high (or final) court of appeal. Broadly speaking, the decisions of ...
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) was an example of this sort of patent. The
intellectual property laws of the US also recognize
plant breeders' rights under the
Plant Variety Protection Act
The Plant Variety Protection Act of 1970 (PVPA), 7 U.S.C. §§ 2321-2582, is an intellectual property statute in the United States. The PVPA gives breeders up to 25 years of exclusive control over new, distinct, uniform, and stable sexually reprod ...
, 7 U.S.C. §§ 2321–2582.
Convention on Biological Diversity
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
Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
to access such resources, and must share any benefits with the biodiversity-rich country. However, some critics believe that the CBD has failed to establish appropriate regulations to prevent biopiracy.
Others claim that the main problem is the failure of national governments to pass appropriate laws implementing the provisions of the CBD. The
Nagoya Protocol
The Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity, also known as the Nagoya Protocol on Access and Benefit Sharing (ABS) is a ...
to the CBD, which came into force in 2014, provides further regulations. The CBD has been ratified, acceded or accepted by 196 countries and jurisdictions globally, with exceptions including the
Holy See and
United States.
Bioprospecting contracts
The requirements for bioprospecting as set by CBD has created a new branch of international
patent 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
Merck refers primarily to the German Merck family and three companies founded by the family, including:
* the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668
** Merck Serono (known as EMD Serono in the Unite ...
and
INBio
The Instituto Nacional de Biodiversidad (INBio) is the national institute for biodiversity and conservation in Costa Rica. Created at the end of the 1980s, and despite having national status, it is a privately run institution that works closely ...
of
Costa Rica
Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...
.
Traditional knowledge database
Due to previous cases of biopiracy and to prevent further cases, the Government of India has converted
traditional Indian medicinal 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,
Sanskrit,
Urdu,
Persian 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
yoga poses
An asana is a body posture, originally and still a general term for a sitting meditation pose,Verse 46, chapter II, "Patanjali Yoga sutras" by Swami Prabhavananda, published by the Sri Ramakrishna Math p. 111 and later extended in hatha yoga ...
are also kept in the collection.
The library has also signed agreements with leading international
patent offices 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
patent examiners at International Patent Offices to access TKDL databases for patent search and examination purposes.
See also
*
Intellectual capital/
Intellectual property
*
Natural capital
*
Biological patent
A biological patent is a patent on an invention in the field of biology that by law allows the patent holder to exclude others from making, using, selling, or importing the protected invention for a limited period of time. The scope and reach of ...
*
Traditional knowledge/
Indigenous knowledge
*
Pharmacognosy
Pharmacognosy is the study of medicinal plants and other natural substances as sources of drugs. The American Society of Pharmacognosy defines pharmacognosy as "the study of the physical, chemical, biochemical, and biological properties of drug ...
*
Plant breeders' rights
*
Bioethics
*
Maya ICBG bioprospecting controversy
The Maya ICBG bioprospecting controversy took place in 1999–2000, when the International Cooperative Biodiversity Group led by ethnobiologist Dr. Brent Berlin was accused of engaging in unethical forms of bioprospecting (biopiracy) by several N ...
*
International Cooperative Biodiversity Group International Cooperative Biodiversity Groups (or ICBG) is a program under National Institutes of Health, National Science Foundation and USAID established in 1993 to promote collaborative research between American universities and research institut ...
*
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)
References
Bibliography and resources
* The Secretariat of the Convention on Biological Diversity (United Nations Environment Programme) maintains a
information centrewhich as of April 2006 lists some 3000 "monographs, reports and serials".
* Secretariat of the Convention on Biological Diversity (United Nations Environment Programme)
Bibliography of Journal Articles on the Convention on Biological Diversity(March 2006). Contains references to almost 200 articles. Some of these are available in full text from th
CBD information centre
*
*
External links
Out of Africa: Mysteries of Access and Benefit-Sharing– a 2006 report on biopiracy in Africa b
The Edmonds InstituteCape Town Declaration– Biowatch South Africa
Genetic Resources Action International (GRAIN)Indian scientist denies accusation of biopiracy–
SciDev.Net
SciDev.Net is a not-for-profit organisation that produces news, views and analysis about science and technology in the context of global development. It primarily engages with development professionals, policymakers, researchers, the media and the ...
African 'biopiracy' debate heats up–
SciDev.Net
SciDev.Net is a not-for-profit organisation that produces news, views and analysis about science and technology in the context of global development. It primarily engages with development professionals, policymakers, researchers, the media and the ...
Bioprospecting: legitimate research or 'biopiracy'?–
SciDev.Net
SciDev.Net is a not-for-profit organisation that produces news, views and analysis about science and technology in the context of global development. It primarily engages with development professionals, policymakers, researchers, the media and the ...
* ETC Group papers on Biopiracy
Topics include: Monsanto's species-wide patent on all genetically modified soybeans (EP0301749); Synthetic Biology Patents (artificial, unique life forms); Terminator Seed Technology; etc...Who Owns Biodiversity, and How Should the Owners Be Compensated? ''Plant Physiology'', April 2004, Vol. 134, pp. 1295–1307
*
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