Genetically modified organism
A genetically modified organism is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified, including animals, plants, and microorganisms.
Genetic modification can include the introduction of new genes or enhancing, altering, or knocking out endogenous genes. In some genetic modifications, genes are transferred within the same species, across species, and even across kingdoms. Creating a genetically modified organism is a multi-step process. Genetic engineers must isolate the gene they wish to insert into the host organism and combine it with other genetic elements, including a promoter and terminator region and often a selectable marker. A number of techniques are available for inserting the isolated gene into the host genome. Recent advancements using genome editing techniques, notably CRISPR, have made the production of GMOs much simpler. Herbert Boyer and Stanley Cohen made the first genetically modified organism in 1973, a bacterium resistant to the antibiotic kanamycin. The first genetically modified animal, a mouse, was created in 1974 by Rudolf Jaenisch, and the first plant was produced in 1983. In 1994, the Flavr Savr tomato was released, the first commercialized genetically modified food. The first genetically modified animal to be commercialized was the GloFish and the first genetically modified animal to be approved for food use was the AquAdvantage salmon in 2015.
Bacteria are the easiest organisms to engineer and have been used for research, food production, industrial protein purification, agriculture, and art. There is potential to use them for environmental purposes or as medicine. Fungi have been engineered with much the same goals. Viruses play an important role as vectors for inserting genetic information into other organisms. This use is especially relevant to human gene therapy. There are proposals to remove the virulent genes from viruses to create vaccines. Plants have been engineered for scientific research, to create new colors in plants, deliver vaccines, and to create enhanced crops. Genetically modified crops are publicly the most controversial GMOs, in spite of having the most human health and environmental benefits. Animals are generally much harder to transform and the vast majority are still at the research stage. Mammals are the best model organisms for humans. Livestock is modified with the intention of improving economically important traits such as growth rate, quality of meat, milk composition, disease resistance, and survival. Genetically modified fish are used for scientific research, as pets, and as a food source. Genetic engineering has been proposed as a way to control mosquitos, a vector for many deadly diseases. Although human gene therapy is still relatively new, it has been used to treat genetic disorders such as severe combined immunodeficiency and Leber's congenital amaurosis.
Concerns
Many objections have been raised over the development of GMOs, particularly their commercialization. Many of these involve GM crops and whether food produced from them is safe and what impact growing them will have on the environment. Other concerns are the objectivity and rigor of regulatory authorities, contamination of non-genetically modified food, control of the food supply, patenting of life, and the use of intellectual property rights. Although there is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, GM food safety is a leading issue with critics. Gene flow, impact on non-target organisms, and escape are the major environmental concerns. Countries have adopted regulatory measures to deal with these concerns. There are differences in the regulation for the release of GMOs between countries, with some of the most marked differences occurring between the US and Europe. Key issues concerning regulators include whether GM food should be labeled and the status of gene-edited organisms.Definition
The definition of a genetically modified organism is not clear and varies widely between countries, international bodies, and other communities. At its broadest, the definition of a GMO can include anything that has had its genes altered, including by nature. Taking a less broad view, it can encompass every organism that has had its genes altered by humans, which would include all crops and livestock. In 1993, the Encyclopedia Britannica defined genetic engineering as "any of a wide range of techniques ... among them artificial insemination, in vitro fertilization, sperm banks, cloning, and gene manipulation." The European Union included a similarly broad definition in early reviews, specifically mentioning GMOs being produced by "selective breeding and other means of artificial selection" These definitions were promptly adjusted with a number of exceptions added as the result of pressure from scientific and farming communities, as well as developments in science. The EU definition later excluded traditional breeding, in vitro fertilization, induction of polyploidy, mutation breeding, and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process.Another approach was the definition provided by the Food and Agriculture Organization, the World Health Organization, and the European Commission, stating that the organisms must be altered in a way that does "not occur naturally by mating and/or natural recombination". Progress in science, such as the discovery of horizontal gene transfer being a relatively common natural phenomenon, further added to the confusion on what "occurs naturally", which led to further adjustments and exceptions. There are examples of crops that fit this definition, but are not normally considered GMOs. For example, the grain crop triticale was fully developed in a laboratory in 1930 using various techniques to alter its genome.
Genetically engineered organism can be considered a more precise term compared to GMO when describing organisms' genomes that have been directly manipulated with biotechnology. The Cartagena Protocol on Biosafety used the synonym living modified organism in 2000 and defined it as "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology." Modern biotechnology is further defined as "In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid and direct injection of nucleic acid into cells or organelles, or fusion of cells beyond the taxonomic family."
Originally, the term GMO was not commonly used by scientists to describe genetically engineered organisms until after usage of GMO became common in popular media. The United States Department of Agriculture considers GMOs to be plants or animals with heritable changes introduced by genetic engineering or traditional methods, while GEO specifically refers to organisms with genes introduced, eliminated, or rearranged using molecular biology, particularly recombinant DNA techniques, such as transgenesis.
The definitions focus on the process more than the product, which means there could be GMOS and non-GMOs with very similar genotypes and phenotypes. This has led scientists to label it as a scientifically meaningless category, saying that it is impossible to group all the different types of GMOs under one common definition. It has also caused issues for organic institutions and groups looking to ban GMOs. It also poses problems as new processes are developed. The current definitions came in before genome editing became popular and there is some confusion as to whether they are GMOs. The EU has adjudged that they are changing their GMO definition to include "organisms obtained by mutagenesis", but has excluded those "obtained by means of certain mutagenesis techniques, namely those which have conventionally been used in a number of applications and have a long safety record" from regulation. This refers to traditional random mutagenesis and would not exclude "new techniques" like gene editing. In contrast the USDA has ruled that gene edited organisms are not considered GMOs.
Even greater inconsistency and confusion is associated with various "Non-GMO" or "GMO-free" labeling schemes in food marketing, where even products such as water or salt, which do not contain any organic substances and genetic material, are being labeled to create an impression of being "more healthy".
Production
Creating a genetically modified organism is a multi-step process. Genetic engineers must isolate the gene they wish to insert into the host organism. This gene can be taken from a cell or artificially synthesized. If the chosen gene or the donor organism's genome has been well studied it may already be accessible from a genetic library. The gene is then combined with other genetic elements, including a promoter and terminator region and a selectable marker.A number of techniques are available for inserting the isolated gene into the host genome. Bacteria can be induced to take up foreign DNA, usually by exposed heat shock or electroporation. DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus, or through the use of viral vectors. In plants the DNA is often inserted using Agrobacterium-mediated recombination, biolistics or electroporation.
As only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through tissue culture. In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells. Further testing using PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene.
Traditionally the new genetic material was inserted randomly within the host genome. Gene targeting techniques, which creates double-stranded breaks and takes advantage on the cells natural homologous recombination repair systems, have been developed to target insertion to exact locations. Genome editing uses artificially engineered nucleases that create breaks at specific points. There are four families of engineered nucleases: meganucleases, zinc finger nucleases, transcription activator-like effector nucleases, and the Cas9-guideRNA system. TALEN and CRISPR are the two most commonly used and each has its own advantages. TALENs have greater target specificity, while CRISPR is easier to design and more efficient.