Genetic resources

The raw material used in biotechnology is the genetic code found within the DNA of living organisms. While not viewed as a natural resource historically, genetic material has, with the advent of modern biotechnology, become a commodity that not only can be manipulated to improve agricultural yield but also can be used as a source by which to produce novel pharmaceutical or chemical products.

Background

Biotechnology can be defined as the use of living organisms to achieve human goals; in this sense, humans have used biotechnology throughout history to provide themselves with such things as food, clothing, shelter, cosmetics, and medicine. Starting around 10,000 B.C.E., humans began to alter the genetic makeup of the plants and animals that they used by artificially selecting certain traits in the crops and livestock that they were breeding. Because farmers lived in different areas around the world with varying environmental conditions, the varieties of domesticated organism that eventually developed initially preserved what is known as “ genetic diversity.” Every organism on Earth has a particular genome, its entire set of DNA, which is specific to that particular living thing. Therefore, genetic diversity is at its greatest when the widest variety of organisms available are in existence in a particular area. The term “ biodiversity” refers to the number of different species (or other taxonomical units) that inhabit a given or geographical area.

Genetic Erosion of Plants and Animals

A process known as “genetic erosion” decreases the of cultivated areas. In this process, local species are lost from an area as they are replaced by less diverse, domesticated varieties. Human activities such as urbanization, the replacement of traditional agriculture with more modern techniques, and the introduction of high-yield varieties of crops have been blamed for such erosion of genetic resources. One example can be seen in the crops that are utilized for food in modern society. Among the 300,000 or so flowering plants that have been characterized to date, estimates indicate that humankind has used around 7,000 of these throughout history to satisfy basic human needs. However, only 30 of these account for 95 percent of the world’s dietary calories, less than 10 account for 75 percent, and a mere 3 (corn, wheat, and rice) make up nearly 50 percent of the caloric intake of humankind. Not only has the number of different crops decreased over time, but also the variety of crop species has declined. Such a narrow genetic base of crops puts the food supply at risk from pests or diseases that affect a specific type of crop. Apparently, humans, in their eagerness to improve crop varieties, have somehow robbed the Earth of a portion of the genetic diversity that has taken millions of years to develop. Traditional subsistence agriculture, although it may have lacked the productivity of modern methods, actually increased the likelihood of a reasonable level of production by preserving the genetic diversity of the crops that were being grown.

This is not to say that using plants as a food source is their only economically viable use. Terrestrial plants have long been used as medicine or for other chemical applications. The recent loss of plant biodiversity is alarming for this reason also. Possibly, some undiscovered cure for a particular disease is at risk from disappearing permanently from the Earth, if it has not done so already. Of the remaining flowering plants on Earth, estimates indicate that one in four could become extinct by 2050. Compounding the problem, most of the world’s biodiversity is located in geographically or politically unstable areas, namely in tropical or subtropical developing countries. A full two-thirds of all plant species known to humankind are located in the tropics; about 60,000 species are found in Latin America alone.

Animals have also served as an important source of food and medicine throughout history and have also been submitted to artificial genetic selection, along with accompanying genetic erosion. Marine invertebrates, in particular, have been investigated as a source of molecular compounds with medicinal properties. It has also been during more recent times that the importance of microorganisms in producing therapeutically relevant products has become known. While the full extent of microbial diversity remains unclear and bacterial diversity in particular appears to follow different biogeographical patterns from those found for plants and animals, it is evident that many natural habitats that may harbor medicinally relevant microbes are disappearing rapidly. The worldwide loss of biodiversity comprises all types of living organisms, including plants, animals, fungi, protists, and bacteria.

Paradigm Shift

In the 1990s, a significant shift occurred in the way that genetic resources were viewed as well as how their ownership was determined. Before this time, genetic resources were considered to be a common heritage of humankind and were to be treated so that they were used to the benefit of all. The only problem with this notion is that it gave host countries little economic incentive for conservation. Another reason for this paradigm shift was a revolution in biology which had taken place in the decade that preceded the change. Biological tools that allowed for genetic engineering had been developed during this time, thereby expanding the number of organisms amenable to biotechnology. These included those that could be artificially selected for particular traits and bred with one another to any organism from which DNA could be extracted. This extracted DNA could then be introduced into a number of living vectors that may have been completely unrelated to the original source of genetic material. This new technology not only ensured that virtually any organism could be used as a source of genetic innovation with a potential for practical application but also decreased the cost of working with genetic material to a level at which many more laboratories could afford to participate in genetic engineering efforts.

The United Nations Convention on Biological Diversity (CBD) was signed at a meeting in Rio de Janeiro, Brazil, in 1992 and went into effect the following year. The CBD affirmed the sovereign right of individual nations to their biodiversity and gave them a means by which to regulate access to their genetic resources, creating the stipulation that entities such as bioengineering firms secure informed written consent before collecting genetic material from any particular country. The export of a seed, microbe, or other plant- or animal-derived sample has been compared to exporting a very small chemical factory, complete with blueprints and its own source of venture capital. While most countries would not allow this to happen using conventional technology, prior to 1992 this had been the norm for biological goods.

Despite the establishment of the CBD, a number of potential problems concerning genetic resources remain. Developing countries are leery of corporations from developed nations that may, given the opportunity, engage in biopiracy. This includes taking advantage of indigenous knowledge and local technologies without providing adequate compensation. Genetic material is similar to electronic media in that it can be reproduced easily and relatively inexpensively, a fact that makes enforcing antipiracy legislation difficult. Conditions of contracts and changes in patent legislation must be followed closely by developing nations to ensure that undue control is not handed to foreign investors.

In addition, just because a country as a whole receives compensation for a particular genetic resource does not mean that a given region of that country will see any economic benefit. Two examples from the United States (which predate the CBD) include the cancer drug Taxol and Taq polymerase, an enzyme used in genetic engineering. These products were discovered respectively in Pacific yew bark from the Pacific Northwest and from hot springs in Yellowstone National Park. Despite the fact that both of these products have produced millions of dollars worth of profits, the regions of the country where they were first discovered ended up receiving little or no financial benefit. This somewhat flawed system of compensation and financial incentive is not expected to work much better in developing countries. Historically, even when indigenous knowledge was used to develop a specific product, indigenous peoples often received little or no benefit from sharing their knowledge.

Conservation Efforts

The same year the CBD was signed, an interdepartmental effort in the U.S. government created the International Conservation of Biodiversity Groups (ICBG) initiative. The objectives of the ICBG were to establish an inventory of species that have been used in traditional medicine, identify lead compounds for the treatment of human disease from this group, conduct economic assessments of species in the host country, establish study plots in developing countries to study changes in rain-forest ecology, and train local scientists in the principles of drug-development and biodiversity conservation. Conservation of genetic resources typically fits into one of two categories, or ex situ: The former is Latin for “in the place,” and the latter means “out of the place.” In situ conservation takes place on farms, for agricultural crops, or in natural reserves, for wild plants. This type of conservation preserves the evolutionary dynamics of the species in question. Ex situ conservation usually involves storing samples, called accessions, of seeds or vegetative material for plants in what are known as gene banks. This type of conservation can also be applied to animals, where embryos or germ cells are stored frozen. This latter conservation technique has the disadvantage of being able to preserve only a small amount of the genetic diversity present in a given population but often plays a critical role in the of many varieties of organisms, particularly those which are endangered or have already become extinct.

Screening for Compounds

Biological organisms of interest to the pharmaceutical or chemical industries are typically those which produce small organic compounds known as secondary metabolites. Some hypothesize that these compounds serve either defensive or signaling roles in the cell: Plants and animals use these compounds to defend themselves from potential predators, and microbes use these to defend themselves from and signal to the other organisms that surround them. Overall, more than one-half of the best-selling pharmaceuticals in use are derived from such natural products. Bioprospecting is the act of systematically searching through given genetic resources for compounds that may have a commercial application. Scientists are thus screening large numbers of extracts from plants, microbes, and marine organisms for secondary metabolites containing antifungal, antiviral, or antitumor activities.

There are a number of hurdles that must be overcome before a specific activity can be gleaned from a particular natural product. Because most natural products consist of mixtures of crude extracts, a certain degree of purification must take place before a lead compound can be tested for a desired application. “Time-to-lead” is a term that refers to the degree of purification and structural characterization that is necessary before a sample can be effectively assayed for a given activity. Another issue is the continued supply of a given natural product. In the past several decades, techniques for the extraction, fractionation, and chemical identification of secondary metabolites have become more routine and less expensive to perform. Before this was the case, it was often necessary to re-collect samples of particular natural products for use in large-scale purifications. Frequently, developers would then discover that it was impossible to reproduce the originally detected activity. Advances in genetic engineering as well as cell culture techniques have largely eliminated the need to re-collect an original sample. These advances actually make it more challenging for a supplier country to adequately charge for the use of a natural resource, because they can no longer rely on the need for re-collection of biological material to take place. This leaves two basic strategies for institutions seeking to benefit from international biotrade: becoming a low-cost supplier or becoming a value-added supplier.

This latter strategy relies on the fact that selection of natural products for testing purposes does not have to occur randomly: Both chemotaxonomic and ethnomedical techniques can be applied to create a value-added product. Chemotaxonomic strategies rely on the selection of organisms from a related taxonomic group that are expected to produce a similar chemical category of substances as the original sample. An example of this can be seen in the soil-derived filamentous fungi as well as in the Actinobacteria. Since the antibiotics penicillin and streptomycin were isolated from the former group in the 1930s and from the latter group a decade later, taxonomically related groups have been successfully screened for secondary metabolites. In contemporary society, such compounds are used to treat cancer, arteriosclerosis, and infectious disease and are even used as immunosuppressive agents. In ethnomedical selection, knowledge of the use of a natural product in traditional medicine is expected to increase the chance of getting positive results with a particular extract. This approach involves sending experts into the field to conduct interviews with traditional healers. While this type of value-added product is more likely to generate a positive “hit,” it is time-consuming and therefore often slow to generate high numbers of potential compounds. Another disadvantage of this type of approach is that it has proven difficult to select with efficacy for agents against complex diseases like cancer, because indigenous traditional healers may be unfamiliar with such maladies.

The most recent approach to the isolation of bioactive natural products eliminates the supply and subsequent screening of live organisms altogether. Because it is actually the genetic data that are of interest to most researchers and not the isolated organism, collecting DNA from environmental samples and directly cloning it into a host vector is becoming more commonplace. While the nature of the organism which contributed its genetic material to any metagenome, the collection of a large number of genomes, may not be determined with any certainty, the end result of having a gene that produces a particular compound of interest has been achieved. This approach is especially adaptable to microorganisms that inhabit soil and water samples in high numbers, the DNA of which can be extracted with relative ease. This approach gained favor when it became evident that a minority of microbial diversity exists in those microbes amenable to being grown under laboratory conditions, and that vast amounts of biodiversity are present in the microorganisms, which resist culturing in the lab for some reason. While activity-based screening of cloned metagenomic libraries is, by definition, a random process, it is believed that new classes of useful compounds are bound to be discovered using this technique.

Bibliography

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