Natural capital

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Natural_capital 

 

Mangrove swamp at Iriomote Island, Japan, providing beneficial services of sediment accumulation, coastal protection, nursery and fish-spawning grounds which may in turn support coastal fishing communities. At least 35% of the world's stock of mangrove swamps has been destroyed in just 20 years

 

Remarks from 1937 by FDR on "natural capital" and "balancing the budget of our resources"

 

Honeybee (Apis mellifera) pollinating an Avocado crop. Healthy stocks of wild and cultivated pollinator species are important to support the farming industry and help ensure food security.

 

Aerial view of the Amazon Rainforest. Looked at as a natural capital asset, rainforests provide air and water regulation services, potential sources of new medicines and natural carbon sequestration.

 

Fires along the Rio Xingu, Brazil - NASA Earth Observatory. Loss of natural capital assets may have significant impact on local and global economies, as well as on the climate.

 

The many components of natural capital can be viewed as providing essential goods and ecosystem services which underpin some of our key global issues, such as food and water supply, minimising climate change and meeting energy needs.

Natural capital is the world's stock of natural resources, which includes geology, soils, air, water and all living organisms. Some natural capital assets provide people with free goods and services, often called ecosystem services. Two of these (clean water and fertile soil) underpin our economy and society, and thus make human life possible.

It is an extension of the economic notion of capital (resources which enable the production of more resources) to goods and services provided by the natural environment. For example, a well-maintained forest or river may provide an indefinitely sustainable flow of new trees or fish, whereas over-use of those resources may lead to a permanent decline in timber availability or fish stocks. Natural capital also provides people with essential services, like water catchment, erosion control and crop pollination by insects, which in turn ensure the long-term viability of other natural resources. Since the continuous supply of services from the available natural capital assets is dependent upon a healthy, functioning environment, the structure and diversity of habitats and ecosystems are important components of natural capital. Methods, called 'natural capital asset checks', help decision-makers understand how changes in the current and future performance of natural capital assets will impact human well-being and the economy.

History of the concept

Ecological economics
Humanity's economic system viewed as a subsystem of the global environment

Concepts Carrying capacity Ecological market failure Ecological model of competition Ecosystem services Embodied energy Energy accounting Entropy pessimism Index of Sustainable Economic Welfare Natural capital Spaceship Earth Steady-state economy Sustainability, 'weak' vs 'strong' Uneconomic growth

The term 'natural capital' was first used in 1973 by E.F. Schumacher in his book Small Is Beautiful and was developed further by Herman Daly, Robert Costanza, and other founders of the science of Ecological Economics, as part of a comprehensive critique of the shortcomings of conventional economics. Natural capital is a concept central to economic assessment ecosystem services valuation which revolves around the idea, that non-human life produces goods and services that are essential to life. Thus, natural capital is essential to the sustainability of the economy.

In a traditional economic analysis of the factors of production, natural capital would usually be classified as "land" distinct from traditional "capital." The historical distinction between "land" and "capital" defined “land” as naturally occurring with a fixed supply, whereas “capital,” as originally defined referred only to man-made goods. (e.g., Georgism) It is, however, misleading to view "land" as if its productive capacity is fixed, because natural capital can be improved or degraded by the actions of man over time. Moreover, natural capital yields benefits and goods, such as timber or food, which can be harvested by humans. These benefits are similar to those realized by owners of infrastructural capital which yields more goods, such as a factory that produces automobiles just as an apple tree produces apples.

Ecologists are teaming up with economists to measure and express values of the wealth of ecosystems as a way of finding solutions to the biodiversity crisis. Some researchers have attempted to place a dollar figure on ecosystem services such as the value that the Canadian boreal forest's contribution to global ecosystem services. If ecologically intact, the boreal forest has an estimated value of US$3.7 trillion. The boreal forest ecosystem is one of the planet's great atmospheric regulators and it stores more carbon than any other biome on the planet. The annual value for ecological services of the Boreal Forest is estimated at US$93.2 billion, or 2.5 greater than the annual value of resource extraction.

The economic value of 17 ecosystem services for the entire biosphere (calculated in 1997) has an estimated average value of US$33 trillion per year. These ecological economic values are not currently included in calculations of national income accounts, the GDP and they have no price attributes because they exist mostly outside of the global markets. The loss of natural capital continues to accelerate and goes undetected or ignored by mainstream monetary analysis.

Within the international community the basic principle is not controversial, although much uncertainty exists over how best to value different aspects of ecological health, natural capital and ecosystem services. Full-cost accounting, triple bottom line, measuring well-being and other proposals for accounting reform often include suggestions to measure an "ecological deficit" or "natural deficit" alongside a social and financial deficit. It is difficult to measure such a deficit without some agreement on methods of valuation and auditing of at least the global forms of natural capital (e.g. value of air, water, soil).

All uses of the term currently differentiate natural from man-made or infrastructural capital in some way. Indicators adopted by United Nations Environment Programme's World Conservation Monitoring Centre and the Organisation for Economic Co-operation and Development (OECD) to measure natural biodiversity use the term in a slightly more specific way. According to the OECD, natural capital is “natural assets in their role of providing natural resource inputs and environmental services for economic production” and is “generally considered to comprise three principal categories: natural resources stocks, land, and ecosystems.”

The concept of "natural capital" has also been used by the Biosphere 2 project, and the Natural Capitalism economic model of Paul Hawken, Amory Lovins, and Hunter Lovins. Recently, it has begun to be used by politicians, notably Ralph Nader, Paul Martin Jr., and agencies of the UK government, including its Natural Capital Committee and the London Health Observatory.

In Natural Capitalism: Creating the Next Industrial Revolution the author claims that the "next industrial revolution" depends on the espousal of four central strategies: "the conservation of resources through more effective manufacturing processes, the reuse of materials as found in natural systems, a change in values from quantity to quality, and investing in natural capital, or restoring and sustaining natural resources."

Natural capital declaration

In June 2012 a 'natural capital declaration' (NCD) was launched at the Rio+20 summit held in Brazil. An initiative of the global finance sector, it was signed by 40 CEOs to 'integrate natural capital considerations into loans, equity, fixed income and insurance products, as well as in accounting, disclosure and reporting frameworks.' They worked with supporting organisations to develop tools and metrics to integrate natural capital factors into existing business structures.

In summary, its four key aims are to:

• Increase understanding of business dependency on natural capital assets;
• Support development of tools to integrate natural capital considerations into the decision-making process of all financial products and services;
• Help build a global consensus on integrating natural capital into private sector accounting and decision-making;
• Encourage a consensus on integrated reporting to include natural capital as one of the key components of an organisation's success.

Natural Capital Protocol

In July 2016, the Natural Capital Coalition released the Natural Capital Protocol. The Protocol provides a standardised framework for organisations to identify, measure and value their direct and indirect impacts and dependencies on natural capital. The Protocol harmonises existing tools and methodologies, and guides organisations towards the information they need to make strategic and operational decisions that include impacts and dependencies on natural capital.

The Protocol was developed in a unique collaboration between 38 organisations who signed voluntary, pre-competitive contracts.

The Protocol is available on a creative commons license and is free for organisations to apply.

Internationally agreed standard

Environmental-economic accounts provide the conceptual framework for integrated statistics on the environment and its relationship with the economy, including the impacts of the economy on the environment and the contribution of the environment to the economy. A coherent set of indicators and descriptive statistics can be derived from the accounts that inform a wide range of policies.

These include, but are not limited to:

• Green economy/green growth
• Natural resource management
• Sustainable development

The System of Integrated Environmental and Economic Accounting (SEEA) contains the internationally agreed standard concepts, definitions, classifications, accounting rules and tables for producing internationally comparable statistics on the environment and its relationship with the economy. The SEEA is a flexible system in the sense that its implementation can be adapted to countries' specific situations and priorities. Coordination of the implementation of the SEEA and on-going work on new methodological developments is managed and supervised by the UN Committee of Experts on Environmental-Economic Accounting (UNCEEA). The final, official version of the SEEA Central Framework was published in February 2014.

Private sector approaches

Some studies envisage a private sector natural capital 'ecosystem', including investors, assets and regulators.

Criticism

Whilst measuring the components of natural capital in any region is a relatively straightforward process, both the task and the rationale of putting a monetary valuation on them, or on the value of the goods and services they freely give us, has proved more contentious. Within the UK, Guardian columnist, George Monbiot, has been critical of the work of the government's Natural Capital Committee and of other attempts to place any sort of monetary value on natural capital assets, or on the free ecosystem services they provide us with. In a speech referring to a report to government which suggested that better protection of the UK's freshwater ecosystems would yield an enhancement in aesthetic value of £700m, he derided attempts 'to compare things which cannot be directly compared'. He went on to say:

These figures, ladies and gentlemen, are marmalade. They are finely shredded, boiled to a pulp, heavily sweetened ... and still indigestible. In other words they are total gibberish.

— G. Monbiot

Others have defended efforts to integrate the valuation of natural capital into local and national economic decision-making, arguing that it puts the environment on a more balanced footing when weighed against other commercial pressures, and that 'valuation' of those assets is not the same as monetisation.

Global biogeochemical cycles critical for life

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  Nitrogen cycle

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  Water cycle

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  Carbon cycle

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  Oxygen cycle

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  Phosphorus cycle

 

Bioprospecting

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Bioprospecting 

Many important medications have been discovered by bioprospecting including the diabetes drug metformin (developed from a natural product found in Galega officinalis).

Intellectual property
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Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for small molecules, macromolecules and biochemical and genetic information that could be developed into commercially valuable products for the agricultural, aquaculture, bioremediation, cosmetics, nanotechnology, or pharmaceutical industries. In the pharmaceutical industry, for example, almost one third of all small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) between 1981 and 2014 were either natural products or compounds derived from natural products.

Terrestrial plants, fungi and actinobacteria 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, archaea) 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, ethnobiological, ethnomedical, historical or genomic information.

When a region’s biological resources or indigenous knowledge 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 and the Nagoya Protocol.

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, and the UN Antarctic Treaty.

Bioprospecting-derived resources and products

Agriculture

Annonin-based biopesticides, used to protect crops from beetles and other pests, were developed from the plant Annona squamosa.

Bioprospecting-derived resources and products used in agriculture include biofertilizers, biopesticides and veterinary antibiotics. Rhizobium is a genus of soil bacteria used as biofertilizers, Bacillus thuringiensis (also called Bt) and the annonins (obtained from seeds of the plant Annona squamosa) are examples of biopesticides, and valnemulin and tiamulin (discovered and developed from the basidiomycete fungus Clitopilus passeckerianus) are examples of veterinary antibiotics.

Bioremediation

Examples of bioprospecting products used in bioremediation include Coriolopsis gallica- and Phanerochaete chrysosporium-derived laccase enzymes, used for treating beer factory 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), Xanthobacter autotrophicus-derived zeaxanthin used for skin hydration and UV protection, Clostridium histolyticum-derived collagenases used for skin regeneration, and Microsporum-derived keratinases used for hair removal.

Nanotechnology and biosensors

Because microbial laccases have a broad substrate range, they can be used in biosensor technology to detect a wide range of organic compounds. For example, laccase-containing electrodes are used to detect polyphenolic compounds in wine, and lignins and phenols in wastewater.

Pharmaceuticals

The tuberculosis drug streptomycin was discovered from the actinomycete Streptomyces griseus.

Many of the antibacterial drugs in current clinical use were discovered through bioprospecting including the β-lactam antibiotics, aminoglycosides, tetracyclines, amphenicols, polymyxins, macrolides, pleuromutilins, glycopeptides, rifamycins, lincosamides, streptogramins 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, and the pleuromutilin antibiotics (eg. lefamulin) were discovered and developed from the basidiomycete fungus Clitopilus passeckerianus.

Other examples of bioprospecting-derived anti-infective drugs include the antifungal drug griseofulvin (discovered from the soil fungus Penicillium griseofulvum), the antifungal and antileishmanial drug amphotericin B (discovered from the soil bacterium Streptomyces nodosus), 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 drug ziconotide (developed from the cone snail Conus magus), and the acetylcholinesterase inhibitor galantamine used to treat Alzheimer's disease (obtained from plants in the Galanthus genus).

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

Voucher deposition allows species identity to be re-evaluated if there are problems re-isolating an active constituent from a biological source.

Prior to collecting biological 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 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, 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-inducing effects of this extract are due to multiple compounds and mechanisms including interaction with GABA receptors 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 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, 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

A white rosy periwinkle

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's Disease and leukemia were discovered instead. The Hodgkin's 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 NGOs 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

A 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. 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.^[45] WR Grace appealed and lost in 2005.

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

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

The succulent 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 maca radish.
• The cases of turmeric (India), karela (India), quinoa (Bolivia), oubli berries (Gabon), and others.
• The case of captopril (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 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) 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, 7 U.S.C. §§ 2321–2582.

Convention on Biological Diversity (CBD)

  Parties to the CBD

  Signed, but not ratified

  Non-signatory

The 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. 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 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 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 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 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.

Medicinal chemistry

From Wikipedia, the free encyclopedia

 

Medicinal chemistry seeks to develop therapeutic agents. Pharmacophore model of the benzodiazepine binding site on the GABAA receptor

Medicinal chemistry and pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where they are involved with design, chemical synthesis and development for market of pharmaceutical agents, or bio-active molecules (drugs).

Compounds used as medicines are most often organic compounds, which are often divided into the broad classes of small organic molecules (e.g., atorvastatin, fluticasone, clopidogrel) and "biologics" (infliximab, erythropoietin, insulin glargine), the latter of which are most often medicinal preparations of proteins (natural and recombinant antibodies, hormones etc.). Inorganic and organometallic compounds are also useful as drugs (e.g., lithium and platinum-based agents such as lithium carbonate and cisplatin as well as gallium).

In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses synthetic organic chemistry and aspects of natural products and computational chemistry in close combination with chemical biology, enzymology and structural biology, together aiming at the discovery and development of new therapeutic agents. Practically speaking, it involves chemical aspects of identification, and then systematic, thorough synthetic alteration of new chemical entities to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their structure–activity relationships (SAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for purpose of medicinal products.

At the biological interface, medicinal chemistry combines to form a set of highly interdisciplinary sciences, setting its organic, physical, and computational emphases alongside biological areas such as biochemistry, molecular biology, pharmacognosy and pharmacology, toxicology and veterinary and human medicine; these, with project management, statistics, and pharmaceutical business practices, systematically oversee altering identified chemical agents such that after pharmaceutical formulation, they are safe and efficacious, and therefore suitable for use in treatment of disease.

In the path of drug discovery

Discovery

Discovery is the identification of novel active chemical compounds, often called "hits", which are typically found by assay of compounds for a desired biological activity. Initial hits can come from repurposing existing agents toward a new pathologic processes, and from observations of biologic effects of new or existing natural products from bacteria, fungi, plants, etc. In addition, hits also routinely originate from structural observations of small molecule "fragments" bound to therapeutic targets (enzymes, receptors, etc.), where the fragments serve as starting points to develop more chemically complex forms by synthesis. Finally, hits also regularly originate from en-masse testing of chemical compounds against biological targets, where the compounds may be from novel synthetic chemical libraries known to have particular properties (kinase inhibitory activity, diversity or drug-likeness, etc.), or from historic chemical compound collections or libraries created through combinatorial chemistry. While a number of approaches toward the identification and development of hits exist, the most successful techniques are based on chemical and biological intuition developed in team environments through years of rigorous practice aimed solely at discovering new therapeutic agents.

Hit to lead and lead optimization

Further chemistry and analysis is necessary, first to identify the "triage" compounds that do not provide series displaying suitable SAR and chemical characteristics associated with long-term potential for development, then to improve remaining hit series with regard to the desired primary activity, as well as secondary activities and physiochemical properties such that the agent will be useful when administered in real patients. In this regard, chemical modifications can improve the recognition and binding geometries (pharmacophores) of the candidate compounds, and so their affinities for their targets, as well as improving the physicochemical properties of the molecule that underlie necessary pharmacokinetic/pharmacodynamic (PK/PD), and toxicologic profiles (stability toward metabolic degradation, lack of geno-, hepatic, and cardiac toxicities, etc.) such that the chemical compound or biologic is suitable for introduction into animal and human studies.

Process chemistry and development

The final synthetic chemistry stages involve the production of a lead compound in suitable quantity and quality to allow large scale animal testing, and then human clinical trials. This involves the optimization of the synthetic route for bulk industrial production, and discovery of the most suitable drug formulation. The former of these is still the bailiwick of medicinal chemistry, the latter brings in the specialization of formulation science (with its components of physical and polymer chemistry and materials science). The synthetic chemistry specialization in medicinal chemistry aimed at adaptation and optimization of the synthetic route for industrial scale syntheses of hundreds of kilograms or more is termed process synthesis, and involves thorough knowledge of acceptable synthetic practice in the context of large scale reactions (reaction thermodynamics, economics, safety, etc.). Critical at this stage is the transition to more stringent GMP requirements for material sourcing, handling, and chemistry.

Synthetic analysis

The synthetic methodology employed in medicinal chemistry is subject to constraints that do not apply to traditional organic synthesis. Owing to the prospect of scaling the preparation, safety is of paramount importance. The potential toxicity of reagents affects methodology.

Structural analysis

The structures of pharmaceuticals are assessed in many ways, in part as a means to predict efficacy, stability, and accessibility. Lipinski's rule of five focus on the number of hydrogen bond donors and acceptors, number of rotatable bonds, surface area, and lipophilicity. Other parameters by which medicinal chemists assess or classify their compounds are: synthetic complexity, chirality, flatness, and aromatic ring count.

Structural analysis of lead compounds is often performed through computational methods prior to actual synthesis of the ligand(s). This is done for a number of reasons, including but not limited to: time and financial considerations (expenditure, etc.). Once the ligand of interest has been synthesized in the laboratory, analysis is then performed by traditional methods (TLC, NMR, GC/MS, and others). 

Training

Medicinal chemistry is by nature an interdisciplinary science, and practitioners have a strong background in organic chemistry, which must eventually be coupled with a broad understanding of biological concepts related to cellular drug targets. Scientists in medicinal chemistry work are principally industrial scientists (but see following), working as part of an interdisciplinary team that uses their chemistry abilities, especially, their synthetic abilities, to use chemical principles to design effective therapeutic agents. The length of training is intense, with practitioners often required to attain a 4-year bachelor's degree followed by a 4-6 year Ph.D. in organic chemistry. Most training regimens also include a postdoctoral fellowship period of 2 or more years after receiving a Ph.D. in chemistry, making the total length of training range from 10–12 years of college education. However, employment opportunities at the Master's level also exist in the pharmaceutical industry, and at that and the Ph.D. level there are further opportunities for employment in academia and government. Many medicinal chemists, particularly in academia and research, also earn a Pharm.D. (doctor of pharmacy). Some of these PharmD/PhD researchers are RPhs (Registered Pharmacists).

Graduate level programs in medicinal chemistry can be found in traditional medicinal chemistry or pharmaceutical sciences departments, both of which are traditionally associated with schools of pharmacy, and in some chemistry departments. However, the majority of working medicinal chemists have graduate degrees (MS, but especially Ph.D.) in organic chemistry, rather than medicinal chemistry, and the preponderance of positions are in discovery, where the net is necessarily cast widest, and most broad synthetic activity occurs.

In discovery of small molecule therapeutics, an emphasis on training that provides for breadth of synthetic experience and "pace" of bench operations is clearly present (e.g., for individuals with pure synthetic organic and natural products synthesis in Ph.D. and post-doctoral positions, ibid.). In the medicinal chemistry specialty areas associated with the design and synthesis of chemical libraries or the execution of process chemistry aimed at viable commercial syntheses (areas generally with fewer opportunities), training paths are often much more varied (e.g., including focused training in physical organic chemistry, library-related syntheses, etc.).

As such, most entry-level workers in medicinal chemistry, especially in the U.S., do not have formal training in medicinal chemistry but receive the necessary medicinal chemistry and pharmacologic background after employment—at entry into their work in a pharmaceutical company, where the company provides its particular understanding or model of "medichem" training through active involvement in practical synthesis on therapeutic projects. (The same is somewhat true of computational medicinal chemistry specialties, but not to the same degree as in synthetic areas.)

 

Biomedicine

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Biomedicine

Biomedicine (also referred to as Western medicine, mainstream medicine or conventional medicine) is a branch of medical science that applies biological and physiological principles to clinical practice. Biomedicine stresses standardized, evidence-based treatment validated through biological research, with treatment administered via formally trained doctors, nurses, and other such licensed practitioners.

Biomedicine also can relate to many other categories in health and biological related fields. It has been the dominant system of medicine in the Western world for more than a century.

It includes many biomedical disciplines and areas of specialty that typically contain the "bio-" prefix such as molecular biology, biochemistry, biotechnology, cell biology, embryology, nanobiotechnology, biological engineering, laboratory medical biology, cytogenetics, genetics, gene therapy, bioinformatics, biostatistics, systems biology, neuroscience, microbiology, virology, immunology, parasitology, physiology, pathology, anatomy, toxicology, and many others that generally concern life sciences as applied to medicine.

Overview

Biomedicine is the cornerstone of modern health care and laboratory diagnostics. It concerns a wide range of scientific and technological approaches: from in vitro diagnostics to in vitro fertilisation, from the molecular mechanisms of cystic fibrosis to the population dynamics of the HIV virus, from the understanding of molecular interactions to the study of carcinogenesis, from a single-nucleotide polymorphism (SNP) to gene therapy.

Biomedicine is based on molecular biology and combines all issues of developing molecular medicine into large-scale structural and functional relationships of the human genome, transcriptome, proteome, physiome and metabolome with the particular point of view of devising new technologies for prediction, diagnosis and therapy 

Biomedicine involves the study of (patho-) physiological processes with methods from biology and physiology. Approaches range from understanding molecular interactions to the study of the consequences at the in vivo level. These processes are studied with the particular point of view of devising new strategies for diagnosis and therapy.

Depending on the severity of the disease, biomedicine pinpoints a problem within a patient and fixes the problem through medical intervention. Medicine focuses on curing diseases rather than improving one's health.

In social sciences biomedicine is described somewhat differently. Through an anthropological lens biomedicine extends beyond the realm of biology and scientific facts; it is a socio-cultural system which collectively represents reality. While biomedicine is traditionally thought to have no bias due to the evidence-based practices, Gaines & Davis-Floyd (2004) highlight that biomedicine itself has a cultural basis and this is because biomedicine reflects the norms and values of its creators.

Molecular biology

Molecular biology is the process of synthesis and regulation of a cell's DNA, RNA, and protein. Molecular biology consists of different techniques including Polymerase chain reaction, Gel electrophoresis, and macromolecule blotting to manipulate DNA.

Polymerase chain reaction is done by placing a mixture of the desired DNA, DNA polymerase, primers, and nucleotide bases into a machine. The machine heats up and cools down at various temperatures to break the hydrogen bonds binding the DNA and allows the nucleotide bases to be added onto the two DNA templates after it has been separated.

Gel electrophoresis is a technique used to identify similar DNA between two unknown samples of DNA. This process is done by first preparing an agarose gel. This jelly-like sheet will have wells for DNA to be poured into. An electric current is applied so that the DNA, which is negatively charged due to its phosphate groups is attracted to the positive electrode. Different rows of DNA will move at different speeds because some DNA pieces are larger than others. Thus if two DNA samples show a similar pattern on the gel electrophoresis, one can tell that these DNA samples match.

Macromolecule blotting is a process performed after gel electrophoresis. An alkaline solution is prepared in a container. A sponge is placed into the solution and an agaros gel is placed on top of the sponge. Next, nitrocellulose paper is placed on top of the agarose gel and a paper towels are added on top of the nitrocellulose paper to apply pressure. The alkaline solution is drawn upwards towards the paper towel. During this process, the DNA denatures in the alkaline solution and is carried upwards to the nitrocellulose paper. The paper is then placed into a plastic bag and filled with a solution full of the DNA fragments, called the probe, found in the desired sample of DNA. The probes anneal to the complementary DNA of the bands already found on the nitrocellulose sample. Afterwards, probes are washed off and the only ones present are the ones that have annealed to complementary DNA on the paper. Next the paper is stuck onto an x ray film. The radioactivity of the probes creates black bands on the film, called an autoradiograph. As a result, only similar patterns of DNA to that of the probe are present on the film. This allows us the compare similar DNA sequences of multiple DNA samples. The overall process results in a precise reading of similarities in both similar and different DNA sample.

Biochemistry

Biochemistry is the science of the chemical processes which takes place within living organisms. Living organisms need essential elements to survive, among which are carbon, hydrogen, nitrogen, oxygen, calcium, and phosphorus. These elements make up the four macromolecules that living organisms need to survive: carbohydrates, lipids, proteins, and nucleic acids.

Carbohydrates, made up of carbon, hydrogen, and oxygen, are energy-storing molecules. The simplest carbohydrate is glucose,

C₆H₁₂O₆, is used in cellular respiration to produce ATP, adenosine triphosphate, which supplies cells with energy.

Proteins are chains of amino acids that function, among other things, to contract skeletal muscle, as catalysts, as transport molecules, and as storage molecules. Protein catalysts can facilitate biochemical processes by lowering the activation energy of a reaction. Hemoglobins are also proteins, carrying oxygen to an organism's cells.

Lipids, also known as fats, are small molecules derived from biochemical subunits from either the ketoacyl or isoprene groups. Creating eight distinct categories: fatty acids, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, and polyketides (derived from condensation of ketoacyl subunits); and sterol lipids and prenol lipids (derived from condensation of isoprene subunits). Their primary purpose is to store energy over the long term. Due to their unique structure, lipids provide more than twice the amount of energy that carbohydrates do. Lipids can also be used as insulation. Moreover, lipids can be used in hormone production to maintain a healthy hormonal balance and provide structure to cell membranes.

Nucleic acids are a key component of DNA, the main genetic information-storing substance, found oftentimes in the cell nucleus, and controls the metabolic processes of the cell. DNA consists of two complementary antiparallel strands consisting of varying patterns of nucleotides. RNA is a single strand of DNA, which is transcribed from DNA and used for DNA translation, which is the process for making proteins out of RNA sequences.