Biotechnology

Biotechnology or biotech

• Biotechnology or biotech is the use of living systems and organisms to develop or make useful products, or "any technological application that uses biological systems, living organisms or derivatives thereof, to make or modify products or processes for specific use" (UN Convention on Biological Diversity).[1]

• For thousands of years, humankind has used biotechnology in agriculture, food production and medicine.[2] The term itself is largely believed to have been coined in 1919 by Hungarian engineer Karl Ereky. In the late 20th and early 21st century, biotechnology has expanded to include new and diverse sciences such as genomics, recombinant gene technologies, applied immunology, and development of pharmaceutical therapies and diagnostic tests.[3]

Various definitions of 'biotechnology'

• The concept of 'biotech' or 'biotechnology' encompasses a wide range of procedures (and history) for modifying living organisms according to human purposes — going back to domestication of animals, cultivation of plants, and "improvements" to these through breeding programs that employ artificial selection and hybridization. Modern usage also includes genetic engineering as well as cell and tissue culture technologies. Biotechnology is defined by the American Chemical Society as the application of biological organisms, systems, or processes by various industries to learning about the science of life and the improvement of the value of materials and organisms such as pharmaceuticals, crops, and livestock[4].

• In other words, biotechnology can be defined as the mere application of technical advances in life science to develop commercial products.

• Biotechnology also draws on the pure biological sciences (genetics, microbiology, animal cell culture, molecular biology, biochemistry, embryology, cell biology). And in many instances it is also dependent on knowledge and methods from outside the sphere of biology including:

Insulin crystals

• Conversely, modern biological sciences (including even concepts such as molecular ecology) are intimately entwined and heavily dependent on the methods developed through biotechnology and what is commonly thought of as the life sciences industry. Biotechnology is the research and development in the laboratory using bioinformatics for exploration, extraction, exploitation and production from any living organisms and any source of biomass by means of biochemical engineering where high value-added products could be planned (reproduced by biosynthesis, for example

A rose plant that began as

cells grown in a tissue culture

• ), forecasted, formulated, developed, manufactured and marketed for the purpose of sustainable operations (for the return from bottomless initial investment on R & D) and gaining durable patents rights (for exclusives rights for sales, and prior to this to receive national and international approval from the results on animal experiment and human experiment, especially on the pharmaceutical branch of biotechnology to prevent any undetected side-effects or safety concerns by using the products), for more about the biotechnology industry, see.

• By contrast, bioengineering is generally thought of as a related field with its emphasis more on higher systems approaches (not necessarily altering or using biological materials directly) for interfacing with and utilizing living things. Bioengineering is the application of the principles of engineering and natural sciences to tissues, cells and molecules . This can be considered as the use knowledge from working with and manipulating biology to achieve a result that can improve functions in plants and animals

History of Biotechnology • Brewing was an early application of biotechnology • Although not normally what first comes to mind,

many forms of human-derived agriculture clearly fit the broad definition of "using a biotechnological system to make products". Indeed, the cultivation of plants may be viewed as the earliest biotechnological enterprise.

• Agriculture has been theorized to have become the dominant way of producing food since the Neolithic Revolution. Through early biotechnology, the earliest farmers selected and bred the best suited crops, having the highest yields, to produce enough food to support a growing population.

• As crops and fields became increasingly large and difficult to maintain, it was discovered that specific organisms and their by-products could effectively fertilize, restore nitrogen, and control pests. Throughout the history of agriculture, farmers have inadvertently altered the genetics of their crops through introducing them to new environments and breeding them with other plants — one of the first forms of biotechnology.

• These processes also were included in early fermentation of beer.[12] These processes were introduced in early Mesopotamia, Egypt, China and India, and still use the same basic biological methods. In brewing, malted grains (containing enzymes) convert starch from grains into sugar and then adding specific yeasts to produce beer. In this process, carbohydrates in the grains were broken down into alcohols such as ethanol. Later other cultures produced the process of lactic acid fermentation which allowed the fermentation and preservation of other forms of food, such as soy sauce. Fermentation was also used in this time period to produce leavened bread

Gel electrophoresis

• . Although the process of fermentation was not fully understood until Louis Pasteur's work in 1857, it is still the first use of biotechnology to convert a food source into another form.

• For thousands of years, humans have used selective breeding to improve production of crops and livestock to use them for food. In selective breeding, organisms with desirable characteristics are mated to produce offspring with the same characteristics. For example, this technique was used with corn to produce the largest and sweetest crops.[13]

• In the early twentieth century scientists gained a greater understanding of microbiology and explored ways of manufacturing specific products. In 1917, Chaim Weizmann first used a pure microbiological culture in an industrial process, that of manufacturing corn starch using Clostridium acetobutylicum, to produce acetone, which the United Kingdom desperately needed to manufacture explosives during World War I.[14]

• Biotechnology has also led to the development of antibiotics. In 1928, Alexander Fleming discovered the mold Penicillium. His work led to the purification of the antibiotic by Howard Florey, Ernst Boris Chain and Norman Heatley, penicillin. In 1940, penicillin became available for medicinal use to treat bacterial infections in humans.[13]

Brewing was an early application of biotechnology

• The field of modern biotechnology is generally thought of as having been born in 1971 when Paul Berg's (Stanford) experiments in gene splicing had early success. Herbert W. Boyer (Univ. Calif. at San Francisco) and Stanley N. Cohen (Stanford) significantly advanced the new technology in 1972 by transferring genetic material into a bacterium, such that the imported material would be reproduced.

Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues

involved in zinc binding

• The commercial viability of a biotechnology industry was significantly expanded on June 16, 1980, when the United States Supreme Court ruled that a genetically modified microorganism could be patented in the case of Diamond v. Chakrabarty.[15] Indian-born Ananda Chakrabarty, working for General Electric, had modified a bacterium (of the Pseudomonas genus) capable of breaking down crude oil, which he proposed to use in treating oil spills. (Chakrabarty's work did not involve gene manipulation but rather the transfer of entire organelles between strains of the Pseudomonas bacterium.

Gene therapy using an Adenovirus vector. A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a

functional protein

Molecular Breeding

• Molecular breeding is the application of molecular biology tools, often in plant breeding.[1][2]

• The areas of molecular breeding include: • QTL mapping or gene discovery • Marker assisted selection and genomic

selection [3][4] • Genetic engineering • Genetic transformation

Quantitative trait locus

• Quantitative trait loci (QTLs) are stretches of DNA containing or linked to the genes that underlie a quantitative trait. Mapping regions of the genome that contain genes involved in specifying a quantitative trait is done using molecular tags such as AFLP or, more commonly, SNPs. This is an early step in identifying and sequencing the actual genes underlying trait variation. Quantitative traits refer to phenotypes (characteristics) that vary in degree and can be attributed to polygenic effects, i.e., product of two or more genes, and their environment.

Marker-assisted selection

• Marker assisted selection or marker aided selection (MAS) is a process whereby a marker (morphological, biochemical or one based on DNA/RNA variation) is used for indirect selection of a genetic determinant or determinants of a trait of interest (e.g. productivity, disease resistance, abiotic stress tolerance, and quality). This process is used in plant and animal breeding.

Marker types • Markers may be: • Morphological - These markers are often detectable by eye, by simple

visual inspection. Examples of this type of marker include the presence or absence of an awn, leaf sheath coloration, height, grain color, aroma of rice etc. In well-characterized crops like maize, tomato, pea, barley or wheat, tens or hundreds of genes that determine morphological traits have been mapped to specific chromosome locations.

• Biochemical- A protein that can be extracted and observed; for example, isozymes and storage proteins.

• Cytological - The chromosomal banding produced by different stains; for example, G banding.

• DNA-based or molecular- A unique gene (DNA sequence), occurring in proximity to the gene or locus of interest, can be identified by a range of molecular techniques such as RFLP, RAPD, AFLP, DAF, SCAR, microsatellite, or single-nucleotide polymorphism (SNP) detection.

• The majority of MAS work in the present era uses DNA-based markers.

Genetic Engineering • Genetic engineering, also called genetic modification, is the direct manipulation of an

organism's genome using biotechnology. New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or "knocked out", using a nuclease. Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations.

• An organism that is generated through genetic engineering is considered to be a genetically modified organism (GMO). The first GMOs were bacteria in 1973 and GM mice were generated in 1974. Insulin-producing bacteria were commercialized in 1982 and genetically modified food has been sold since 1994. Glofish, the first GMO designed as a pet, was first sold in the United States December in 2003.[1]

• Genetic engineering techniques have been applied in numerous fields including research, agriculture, industrial biotechnology, and medicine. Enzymes used in laundry detergent and medicines such as insulin and human growth hormone are now manufactured in GM cells, experimental GM cell lines and GM animals such as mice or zebrafish are being used for research purposes, and genetically modified crops have been commercialized.

Transformation • In molecular biology, transformation is the genetic alteration of a cell resulting from

the direct uptake and incorporation of exogenous genetic material (exogenous DNA) from its surroundings and taken up through the cell membrane(s). Transformation occurs naturally in some species of bacteria, but it can also be affected by artificial means in other cells. For transformation to happen, bacteria must be in a state of competence, which might occur as a time-limited response to environmental conditions such as starvation and cell density.

• Transformation is one of three processes by which exogenous genetic material may be introduced into a bacterial cell, the other two being conjugation (transfer of genetic material between two bacterial cells in direct contact) and transduction (injection of foreign DNA by a bacteriophage virus into the host bacterium).

• "Transformation" may also be used to describe the insertion of new genetic material into nonbacterial cells, including animal and plant cells; however, because "transformation" has a special meaning in relation to animal cells, indicating progression to a cancerous state, the term should be avoided for animal cells when describing introduction of exogenous genetic material. Introduction of foreign DNA into eukaryotic cells is often called "transfection".[1]

Plasmid • A plasmid is a small DNA molecule within a cell that is physically

separated from a chromosomal DNA and can replicate independently. They are most commonly found in bacteria as small, circular, double-stranded DNA molecules, however plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids carry genes that may benefit survival of the organism (e.g. antibiotic resistance), and can frequently be transmitted from one bacterium to another (even of another species) via horizontal gene transfer. While the chromosomes are big and contain all the essential information for living (an adequate analogy is the hard-drive of a computer), plasmids usually are very small and contain additional information (in this analogy, plasmids are the USB flash drives). Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms.

Figure 1: Illustration of a bacterium with plasmid enclosed showing chromosomal DNA and plasmids.

Agrobacterium tumefaciens • Agrobacterium tumefaciens (updated scientific name: Rhizobium

radiobacter)[2][3] is the causal agent of crown gall disease (the formation of tumours) in over 140 species of eudicots. It is a rod-shaped, Gram-negative soil bacterium.[1] Symptoms are caused by the insertion of a small segment of DNA (known as the T-DNA, for 'transfer DNA'), from a plasmid, into the plant cell,[4] which is incorporated at a semi.-random location into the plant genome.

• A. tumefaciens is an alphaproteobacterium of the family Rhizobiaceae, which includes the nitrogen-fixing legume symbionts. Unlike the nitrogen-fixing symbionts, tumor-producing Agrobacterium species are pathogenic and do not benefit the plant. The wide variety of plants affected by Agrobacterium makes it of great concern to the agriculture industry.[5]

• Economically, A. tumefaciens is a serious pathogen of walnuts, grape vines, stone fruits, nut trees, sugar beets, horse radish, and rhubarb.

• A: Agrobacterium tumefaciens B: Agrobacterium genome C: Ti Plasmid : a: T-DNA ,

• b: Vir genes , c: Replication origin , d: Opines catabolism genes D: Plant cell E: Mitochondria F: Chloroplast G: Nucleus

T-DNA • The transfer DNA (abbreviated T-DNA) is the transferred DNA of the

tumor-inducing (Ti) plasmid of some species of bacteria such as Agrobacterium tumefaciens and Agrobacterium rhizogenes. It derives its name from the fact that the bacterium transfers this DNA fragment into the host plant's nuclear DNA genome. The T-DNA is bordered by 25-base-pair repeats on each end. Transfer is initiated at the right border and terminated at the left border and requires the vir genes of the Ti plasmid.

• The bacterial T-DNA is about 24,000 base pairs long[1][2] and contains genes that code for enzymes synthesizing opines and phytohormones. By transferring the T-DNA into the plant genome, the bacterium essentially reprograms the plant cells to grow into a tumor and produce a unique food source for the bacteria. The synthesis of the plant hormones auxin and cytokinin enables the plant cell to grow uncontrollably, thus forming the crown gall tumors typically induced by Agrobacterium infection. The opines are amino acid derivatives used by the bacterium as a source of carbon and energy.

Transfer DNA

• Plants that have undergone transformation with Agrobacterium

Gene gun PSD-1000/He Particle Delivery System

• A gene gun or a biolistic particle delivery system, originally designed for plant transformation, is a device for injecting cells with genetic information. The payload is an elemental particle of a heavy metal coated with plasmid DNA. This technique is often simply referred to as bioballistics or biolistics.

• This device is able to transform almost any type of cell, including plants, and is not limited to genetic material of the nucleus: it can also transform organelles, including plastids.

Application • Gene guns are so far mostly applied for plant cells. However, there is much potential

use in humans and other animals as well. • Plants • The target of a gene gun is often a callus of undifferentiated plant cells growing on gel

medium in a petri dish. After the gold particles have impacted the dish, the gel and callus are largely disrupted. However, some cells were not obliterated in the impact, and have successfully enveloped a DNA coated gold particle, whose DNA eventually migrates to and integrates into a plant chromosome.

• Cells from the entire petri dish can be re-collected and selected for successful integration and expression of new DNA using modern biochemical techniques, such as a using a tandem selectable gene and northern blots.

• Selected single cells from the callus can be treated with a series of plant hormones, such as auxins and gibberellins, and each may divide and differentiate into the organized, specialized, tissue cells of an entire plant. This capability of total re-generation is called totipotency. The new plant that originated from a successfully shot cell may have new genetic (heritable) traits.

• The use of the gene gun may be contrasted with the use of Agrobacterium tumefaciens and its Ti plasmid to insert genetic information into plant cells. See transformation for different methods of transformation in different species.

• Revenue in the industry is expected to grow by 12.9% in 2008. Another factor influencing the biotechnology sector's success is improved intellectual property rights legislation—and enforcement—worldwide, as well as strengthened demand for medical and pharmaceutical products to cope with an ageing, and ailing, U.S. population.[16]

• Rising demand for biofuels is expected to be good news for the biotechnology sector, with the Department of Energy estimating ethanol usage could reduce U.S. petroleum-derived fuel consumption by up to 30% by 2030.

DNA microarray chip – some can do as many as a million blood tests at once

• The biotechnology sector has allowed the U.S. farming industry to rapidly increase its supply of corn and soybeans—the main inputs into biofuels—by developing genetically modified seeds which are resistant to pests and drought. By boosting farm productivity, biotechnology plays a crucial role in ensuring that biofuel production targets are met.[17]

Applications • Biotechnology has applications in four major industrial

areas, including health care (medical), crop production and agriculture, non food (industrial) uses of crops and other products (e.g. biodegradable plastics, vegetable oil, biofuels), and environmental uses.

• For example, one application of biotechnology is the directed use of organisms for the manufacture of organic products (examples include beer and milk products). Another example is using naturally present bacteria by the mining industry in bioleaching. Biotechnology is also used to recycle, treat waste, cleanup sites contaminated by industrial activities (bioremediation), and also to produce biological weapons.

• A series of derived terms have been coined to identify several branches of biotechnology; for example:

Cloning • Cloning involves the removal of the nucleus from one cell and its

placement in an unfertilized egg cell whose nucleus has either been deactivated or removed.

• There are two types of cloning: • Reproductive cloning. After a few divisions, the egg cell is placed into a

uterus where it is allowed to develop into a fetus that is genetically identical to the donor of the original nucleus.

• Therapeutic cloning.[26] The egg is placed into a Petri dish where it develops into embryonic stem cells, which have shown potentials for treating several ailments.[27]

• In February 1997, cloning became the focus of media attention when Ian Wilmut and his colleagues at the Roslin Institute announced the successful cloning of a sheep, named Dolly, from the mammary glands of an adult female. The cloning of Dolly made it apparent to many that the techniques used to produce her could someday be used to clone human beings.[28] This stirred a lot of controversy because of its ethical implications.

• Agriculture • Genetically modified food

Crop yield • Using the techniques of modern biotechnology, one or two

genes (Smartstax from Monsanto in collaboration with Dow AgroSciences will use eight, starting in 2010) may be transferred to a highly-developed crop variety to impart a new character that would increase its yield.[29] However, while increases in crop yield are the most obvious applications of modern biotechnology in agriculture, they are also the most difficult ones. Current genetic engineering techniques work best for effects that are controlled by a single gene. Many of the genetic characteristics associated with yield (e.g., enhanced growth) are controlled by a large number of genes, each of which has a minimal effect on the overall yield.[30] There is, therefore, much scientific work to be done in this area.

Reduced vulnerability of crops to environmental stresses

• Crops containing genes that will enable them to withstand biotic and abiotic stresses may be developed. For example, drought and excessively salty soil are two important limiting factors in crop productivity. Biotechnologists work to find genes that enable some plants to cope with these extreme conditions and eventually to transfer these genes to the more productive crops. One of the latest developments is the identification of a plant gene, At-DBF2, from Arabidopsis thaliana. Arabidopsis thaliana is a tiny weed often used for plant research because it is very easy to grow. Its genetic code, approximately 115 Mb of the 125 Mb genome [31], which has been sequenced and interpreted which can be manipulated in many ways.

Biotechnology regulations The National Institutes of Health (NIH) was the first

federal agency to assume regulatory responsibility in the United States. The Recombinant DNA Advisory Committee of the NIH published guidelines for working with recombinant DNA and recombinant organisms in the laboratory. Nowadays, the agencies that are responsible for the biotechnology regulation are: US Department of Agriculture (USDA) that regulates plant pests and medical preparation from living organisms, Environmental Protection Agency (EPA) that regulates pesticides and herbicides, and the Food and Drug Administration (FDA) which ensures that the food and drug products are safe and effective [13]

• chemical engineering, • bioprocess engineering, • bioinformatics, a new brand of

information technology, and • biorobotics.

• See also • Biotechnology portal • Outline of biotechnology • Bioeconomics (biophysical) • Bioengineering • Biomimetics • Bioculture • Pharmaceutical companies

• Pharmaceutical chemistry • Bionic architecture • Biotechnology industrial park • Competitions and prizes in

biotechnology • Genetic Engineering • Green Revolution • History of Biotechnology • List of biotechnology articles • List of biotechnology companies • List of emerging biotechnologies • Metabolic engineering • NASDAQ Biotechnology Index • SWORD-financing

Kinds of Biotechnology

• Plant Biotechnology • Tree Biotechnology • Forest Biotechnology

• Animal Biotechnology

Bioreactor

• 원예과학과 백기엽 교수가 영어전문서적 “Production of Biomass and Bioactive Compounds Using Bioreactor Technology” (2014, 709 p. 212 illus., 96 illus. in color)를 출판했다.