Genetically modified organism

A genetically modified organism (GMO) is an organism whose genetic material has been altered using genetic engineering techniques. Organisms that have been genetically modified include micro-organisms such as bacteria and yeast, insects, plants, fish, and mammals. GMOs are the source of genetically modified foods, and are also widely used in scientific research and to produce goods other than food. The term GMO is very close to the technical legal term, 'living modified organism' defined in the Cartagena Protocol on Biosafety, which regulates international trade in living GMOs (specifically, "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology").

This article focuses on what organisms have been genetically engineered, and for what purposes. The article on genetic engineering focuses on the history and methods of genetic engineering, and on applications of genetic engineering and of GMOs. Both articles cover much of the same ground but with different organizations (sorted by organism in this article; sorted by application in the other). There are separate articles on genetically modified crops, genetically modified food, regulation of the release of genetic modified organisms, and controversies.

Production
Genetic modification involves the insertion or deletion of genes. When genes are inserted, they usually come from a different species, which is a form of horizontal gene transfer. In nature this can occur when exogenous DNA penetrates the cell membrane for any reason. To do this artificially may require attaching the genes to a virus or just physically inserting the extra DNA into the nucleus of the intended host with a very small syringe, or with very small particles fired from a gene gun. However, other methods exploit natural forms of gene transfer, such as the ability of Agrobacterium to transfer genetic material to plants, or the ability of lentiviruses to transfer genes to animal cells.

History
The general principle of producing a GMO is to add new genetic material into an organism's genome. This is called genetic engineering and was made possible through the discovery of DNA and the creation of the first recombinant DNA molecules by Paul Berg in 1972.

Uses
GMOs are used in biological and medical research, production of pharmaceutical drugs, experimental medicine (e.g. gene therapy), and agriculture (e.g. golden rice, resistance to herbicides). The term "genetically modified organism" does not always imply, but can include, targeted insertions of genes from one species into another. For example, a gene from a jellyfish, encoding a fluorescent protein called GFP, can be physically linked and thus co-expressed with mammalian genes to identify the location of the protein encoded by the GFP-tagged gene in the mammalian cell. Such methods are useful tools for biologists in many areas of research, including those who study the mechanisms of human and other diseases or fundamental biological processes in eukaryotic or prokaryotic cells.

Transgenic plants
Transgenic plants have been engineered for scientific research, to create new colors in plants, and to create different crops.

In research, plants are engineered to help discover the functions of certain genes. One way to do this is to knock out the gene of interest and see what phenotype develops. Another strategy is to attach the gene to a strong promoter and see what happens when it is over expressed. A common technique used to find out where the gene is expressed is to attach it to GUS or a similar reporter gene that allows visualisation of the location. '

After thirteen years of collaborative research by an Australian company – Florigene, and a Japanese company – Suntory, created a blue rose (actually lavender or mauve) in 2004. The genetic engineering involved three alterations – adding two genes, and interfering with another. One of the added genes was for the blue plant pigment delphinidin cloned from the pansy. The researchers then used RNA interference (RNAi) technology to depress all color production by endogenous genes by blocking a crucial protein in color production, called dihydroflavonol 4-reductase) (DFR), and adding a variant of that protein that would not be blocked by the RNAi but that would allow the delphinidin to work. The roses are sold worldwide.   Florigene has also created and sells lavender-colored carnations that are genetically engineered in a similar way.

Simple plants and plant cells have been genetically engineered for production of biopharmaceuticals in bioreactors as opposed to cultivating plants in open fields. Work has been done with duckweed Lemna minor and the moss Physcomitrella patens. An Israeli company, Protalix, has developed a method to produced therapeutics in cultured transgenic carrot and tobacco cells. Protalix and its partner, Pfizer, received FDA approval to market its drug, a treatment for Gaucher's Disease, in 2012.

GM crops
In agriculture, genetically engineered crops are created to possess several desirable traits, such as resistance to pests, herbicides, or harsh environmental conditions, improved product shelf life, increased nutritional value, or production of valuable goods such as drugs (pharming). Since the first commercial cultivation of genetically modified plants in 1996, they have been modified to be tolerant to the herbicides glufosinate and glyphosate, to be resistant to virus damage as in Ringspot virus-resistant GM papaya, grown in Hawaii, and to produce the Bt toxin, an insecticide that is documented as non-toxic to mammals.

Plants, including algae, jatropha, maize, and other plants have been genetically modified for use in producing fuel, known as biofuel.

Critics have objected to GM crops per se on several grounds, including ecological concerns, and economic concerns raised by the fact these organisms are subject to intellectual property law. GM crops also are involved in controversies over GM food with respect to whether food produced from GM crops is safe and whether GM crops are needed to address the world's food needs. See the genetically modified food controversies article for discussion of issues about GM crops and GM food.

Cisgenic plants
Cisgenesis, sometimes also called intragenesis, is a product designation for a category of genetically engineered plants. A variety of classification schemes have been proposed that order genetically modified organisms based on the nature of introduced genotypical changes rather than the process of genetic engineering.

While some genetically modified plants are developed by the introduction of a gene originating from distant, sexually incompatible species into the host genome, cisgenic plants contain genes that have been isolated either directly from the host species or from sexually compatible species. The new genes are introduced using recombinant DNA methods and gene transfer. Some scientists hope that the approval process of cisgenic plants might be simpler than that of proper transgenics, but it remains to be seen.

Microbes
Bacteria were the first organisms to be modified in the laboratory, due to their simple genetics. These organisms are now used for several purposes, and are particularly important in producing large amounts of pure human proteins for use in medicine.

Genetically modified bacteria are used to produce the protein insulin to treat diabetes. Similar bacteria have been used to produce clotting factors to treat haemophilia, and human growth hormone to treat various forms of dwarfism.

In addition, various genetically engineered micro-organisms are routinely used as sources of enzymes for the manufacture of a variety of processed foods. These include alpha-amylase from bacteria, which converts starch to simple sugars, chymosin from bacteria or fungi that clots milk protein for cheese making, and pectinesterase from fungi which improves fruit juice clarity.

Mammals


Genetically modified mammals are an important category of genetically modified organisms. Ralph L. Brinster and Richard Palmiter developed the techniques responsible for transgenic mice, rats, rabbits, sheep, and pigs in the early 1980s, and established many of the first transgenic models of human disease, including the first carcinoma caused by a transgene. The process of genetically engineering animals is a slow, tedious, and expensive process. However, new technologies are making genetic modifications easier and more precise.

The first transgenic (genetically modified) animal was produced by injecting DNA into mouse embryos then implanting the embryos in female mice.

Genetically modified animals currently being developed can be placed into six different broad classes based on the intended purpose of the genetic modification:
 * 1) to research human diseases (for example, to develop animal models for these diseases);
 * 2) to produce industrial or consumer products (fibres for multiple uses;
 * 3) to produce products intended for human therapeutic use (pharmacutical products or tissue for implantation);
 * 4) to enrich or enhance the animals' interactions with humans (hypo-allergenic pets);
 * 5) to enhance production or food quality traits (faster growing fish, pigs that digest food more efficiently);
 * 6) to improve animal health (disease resistance)

Research use
Transgenic animals are used as experimental models to perform phenotypic and for testing in biomedical research.

Genetically modified (genetically engineered) animals are becoming more vital to the discovery and development of cures and treatments for many serious diseases. By altering the DNA or transferring DNA to an animal, we can develop certain proteins that may be used in medical treatment. Stable expressions of human proteins have been developed in many animals, including sheep, pigs, and rats. Human-alpha-1-antitrypsin, which has been tested in sheep and is used in treating humans with this deficency and transgenic pigs with human-histo-compatibility have been studied in the hopes that the organs will be suitable for transplant with less chances of rejection.

Scientists have genetically engineered several organisms, including some mammals, to include green fluorescent protein (GFP) for medical research purposes (Chalfie, Shimoura, and Tsien were awarded the Nobel prize in 2008 for GFP ). For example fluorescent pigs have been bred in the US in 2000, in Korea in 2002, in Taiwan in 2006, in China in 2008 and Japan in 2009. These pigs were bred to study human organ transplants, regenerating ocular photoreceptor cells, neuronal cells in the brain, regenerative medicine via stem cells, tissue engineering, and other diseases. In 2011 a Japanese-American Team created green-fluorescent cats in order to find therapies for HIV/AIDS and other diseases as Feline immunodeficiency virus (FIV) is related to HIV.

In 2009, scientists in Japan announced that they had successfully transferred a gene into a primate species (marmosets) and produced a stable line of breeding transgenic primates for the first time. Their first research target for these marmosets was Parkinson's disease, but they were also considering Amyotrophic lateral sclerosis and Huntington's disease.

Producing human therapeutics
Within the field known as pharming, intensive research has been conducted to develop transgenic animals that produce biotherapeutics. On 6 February 2009, the U.S. Food and Drug Administration approved the first human biological drug produced from such an animal, a goat. The drug, ATryn, is an anticoagulant which reduces the probability of blood clots during surgery or childbirth. It is extracted from the goat's milk.

Production or food quality traits
Enviropig is a genetically enhanced line of Yorkshire pigs created with the capability of digesting plant phosphorus more efficiently than conventional Yorkshire pigs and dubbed them Enviropig. These pigs produce the enzyme phytase, which breaks down the indigestible phosphorus, in their saliva. The enzyme was introduced into the pig chromosome by pronuclear microinjection. With this enzyme, Enviropig is able to digest cereal grain phosphorus, so there is then no need to supplement the pigs' diet with either phosphate minerals or commercially produced phytase, and less phosphorus is lost in the manure. Enviropig would reduce feed costs because farmers would not need to purchase feed including the phytase, and it also would reduce the potential of water pollution since the Enviropig excretes from 30 to 70.7% less phosphorus in manure depending upon the age and diet. The lower concentrations of phosphorus in surface runoff reduces algal growth, because phosphorus is the limiting nutrient for algae. Because algae consume large amounts of oxygen, it can result in dead zones for fish. This would not only be advantageous for the waters surrounding the pigs, but also for the water neighboring the areas which use the manure for fertilizers. There are no current regulations or pending approvals on the Enviropig for human consumption in the United States. In February 2010, Environment Canada determined that Enviropigs are in compliance with the Canadian Environmental Protection Act and can be produced outside of the research context in controlled facilities where they are segregated from other animals.

In 2011, Chinese scientists generated dairy cows genetically engineered with genes for human beings to produce milk that would be the same as human breast milk. This could potentially benefit mothers who cannot produce breast milk but want their children to have breast milk rather than formula. Aside from milk production, the researchers claim these transgenic cows to be identical to regular cows. Two months later scientists from Argentina presented Rosita, a transgenic cow incorporating two human genes, to produce milk with similar properties as human breast milk. In 2012, researchers from New Zealand also developed a genetically engineered cow that produced allergy-free milk.

In 2006, a pig was engineered to produce omega-3 fatty acids through the expression of a roundworm gene.

Goats have been genetically engineered to produce milk with strong spiderweb-like silk proteins in their milk.

Genetically modified fish have been developed with promoters driving an over-production of growth hormone for use in the aquaculture industry to increase the speed of development and potentially reduce fishing pressure on wild stocks. AquaBounty, a biotechnology company working on bringing a GM salmon to market, claims that their GM AquAdvantage salmon can mature in half the time it takes non-GM salmon and achieves twice the size. AquaBounty has applied for regulatory approval to market their GM salmon in the US. As of May 2012 the application was still pending.

Human gene therapy
Gene therapy, uses genetically modified viruses to deliver genes that can cure disease into humans. Although gene therapy is still relatively new, it has had some successes. It has been used to treat genetic disorders such as severe combined immunodeficiency, and treatments are being developed for a range of other currently incurable diseases, such as cystic fibrosis, sickle cell anemia, Parkinson's disease, cancer,  diabetes and muscular dystrophy. Current gene therapy technology only targets the non-reproductive cells meaning that any changes introduced by the treatment can not be transmitted to the next generation. Gene therapy targeting the reproductive cells—so-called "Germ line Gene Therapy"—is very controversial and is unlikely to be developed in the near future.

Fruit flies
In biological research, transgenic fruit flies (Drosophila melanogaster) are model organisms used to study the effects of genetic changes on development. Fruit flies are often preferred over other animals due to their short life cycle, low maintenance requirements, and relatively simple genome compared to many vertebrates.

Mosquitoes
In 2010, scientists created "malaria-resistant mosquitoes" in the laboratory. The World Health Organisation estimated that Malaria killed almost one million people in 2008. Genetically modified male mosquitoes containing a lethal gene have been developed in order to combat the spread of Dengue fever. Aedes aegypti mosquitoes, the single most important carrier of dengue fever, were reduced by 80% in a 2010 trial of these GM mosquitoes in the Cayman Islands. Between 50 and 100 million people are affected by Dengue fever every year and 40,000 people die from it.

Bollworms
A strain of Pectinophora gossypiella (Pink bollworm) has been developed that contains a fluorescent marker in their DNA. This allows researchers to monitor bollworms that have been sterilized by radiation and released in order to reduce bollworm infestation.

Cnidarians
Cnidarians such as Hydra and the sea anemone Nematostella vectensis have become attractive model organisms to study the evolution of immunity and certain developmental processes. An important technical breakthrough was the development of procedures for generation of stably transgenic hydras and sea anemones by embryo microinjection.

Fish
GM fish are used for scientific research and as pets, and are being considered for use as food and as aquatic pollution sensors.

Genetically engineered fish are widely used in basic research in genetics and development. Two species of fish, zebrafish and medaka, are most commonly modified because they have optically clear chorions (shells), rapidly develop, and the 1-cell embryo is easy to see and microinject with transgenic DNA.

The GloFish is a patented brand of genetically modified (GM) fluorescent zebrafish with bright red, green, and orange fluorescent color. Although not originally developed for the ornamental fish trade, it became the first genetically modified animal to become publicly available as a pet when it was introduced for sale in 2003. They were quickly banned for sale in California.

Genetically modified fish have been developed with promoters driving an over-production of "all fish" growth hormone for use in the aquaculture industry to increase the speed of development and potentially reduce fishing pressure on wild stocks. This has resulted in dramatic growth enhancement in several species, including salmon, trout and tilapia. AquaBounty, a biotechnology company working on bringing a GM salmon to market, claims that their GM AquAdvantage salmon can mature in half the time it takes non-GM salmon and achieves twice the size. AquaBounty has applied for regulatory approval to market their GM salmon in the US. As of December 2012 the application was still pending.

Several academic groups have been developing GM zebrafish to detect aquatic pollution. The lab that originated the GloFish discussed above originally developed them to change color in the presence of pollutants, to be used as environmental sensors. A lab at University of Cincinnati has been developing GM zebrafish for the same purpose, as has a lab at Tulane University.

Regulation
The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the use of genetic engineering technology and the development and release of genetically modified organisms (GMO), including genetically modified crops and genetically modified fish. There are differences in the regulation of GMOs between countries, with some of the most marked differences occurring between the USA and Europe. Regulation varies in a given country depending on the intended use of the products of the genetic engineering. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety.

Controversy
There are controversies around GMOs on several levels, including whether making them is ethical, whether food produced with them is safe, whether such food should be labeled and if so how, whether agricultural biotech is needed to address world hunger now or in the future, and more specifically to GM crops—intellectual property and market dynamics; environmental effects of GM crops; and GM crops' role in industrial agricultural more generally.