It often involves the isolation, manipulation and reintroduction of DNA into cells or model organisms, usually to express a protein. The aim is to introduce new characteristics such as increasing the yield of a crop species, introducing a novel trait, or producing a new protein or enzyme. Examples include the production of human insulin through the use of modified bacteria, the production of erythropoietin in Chinese Hamster Ovary cells, and the production of new types of experimental mice such as the OncoMouse (cancer mouse) for research, through genetic redesign.
Since a protein is specified by a segment of DNA called a gene, future versions of that protein can be modified by changing the gene's underlying DNA. One way to do this is to isolate the piece of DNA containing the gene, precisely cut the gene out, and then reintroduce (splice) the gene into a different DNA segment. Daniel Nathans and Hamilton Smith received the 1978 Nobel Prize in physiology or medicine for their isolation of restriction endonucleases, which are able to cut DNA at specific sites. Together with ligase, which can join fragments of DNA together, restriction enzymes formed the initial basis of recombinant DNA technology.
"Transgenic organism" is now the preferred term for genetically modified organisms with extra-genome (foreign genetic) information, as opposed to "genetically engineered" or "genetically modified" organisms (which may refer to changes made within the genome such as amplification or deletion of genes).
One of the best known applications of genetic engineering is that of the creation of genetically modified organisms (GMOs).
There are potentially momentous biotechnological applications of GM, for example oral vaccines produced naturally in fruit, at very low cost. This represents, however, a spread of genetic modification to medical purposes and opens an ethical door to other uses of the technology to directly modify human genomes.
These effects are often not traceable back to direct causes in the genome, but rather in the environment or interaction of proteins. The means by which 'genes' (in fact DNA strands that are assumed to have discrete effects) are detected and inserted are inexact, including such means as coating gold particles with DNA to be inserted and literally firing it at strands of target DNA (see gene gun), which is guaranteed to cause insertions in at least some random locations, which can on rare occasion cause unplanned characteristics.
Similar objections apply to protein engineering and molecular engineering for use as drugs. However, a single protein or a molecule is easier to examine for 'quality control' than a complete genome, and there are more limited claims made for the reliability of proteins and molecules, than for the genomes of whole organisms. While protein and molecule engineers often times acknowledge the requirement to test their products in a wide variety of environments to determine if they pose dangers to life, the position of many genetic engineers is that they do not need to do so, since the outputs of their work are 'substantially the same as' the original organism which was produced by the original genome(s).
Genetic sequencing which is used to identify each base in DNA is exceedingly cheap. As of mid-2005, it cost 1/10 of 1 cent to sequence a single base.
Genetic engineering and research
Although there has been a tremendous revolution in the biological sciences in the past twenty years, there is still a great deal that remains to be discovered. The completion of the sequencing of the human genome, as well as the genomes of most agriculturally and scientifically important plants and animals, have increased the possibilities of genetic research immeasurably. Expedient and inexpensive access to comprehensive genetic data has become a reality, with billions of sequenced nucleotides already online and annotated. Now that the rapid sequencing of arbitrarily large genomes has become a simple, if not trivial affair, a much greater challenge will be elucidating function of the extraordinarily complex web of interacting proteins, dubbed the proteome, that constitutes and powers all living things. Genetic engineering has become the gold standard in protein research, and major research progress has been made using a wide variety of techniques, including:
- loss of function, such as in a knockout experiment, in which an organism is engineered to lack the activity of one or more genes. This allows the experimenter to analyze the defects caused by this mutation, and can be considerably useful in unearthing the function of a gene. It is used especially frequently in developmental biology. A knockout experiment involves the creation and manipulation of a DNA construct in vitro, which, in a simple knockout, consists of a copy of the desired gene which has been slightly altered such as to cripple its function. The construct is then taken up by embryonic stem cells, where the engineered copy of the gene replaces the organism's own gene. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. Another method, useful in organisms such as Drosophila (fruit fly), is to induce mutations in a large population and then screen the progeny for the desired mutation. A similar process can be used in both plants and prokaryotes.
- gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or attracting more frequent transcription.
- 'tracking' experiments, which seek to gain information about the localization and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as Green Fluorescent Protein (GFP)that will allow easy visualization of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences which will serve as binding motifs to monoclonal antibodies.
Proponents of genetic engineering argue that the technology is safe, and that it is necessary in order to maintain food production that will continue to match population growth and help feed millions in the third world more effectively. Others argue that there is more than enough food in the world and that the problem is food distribution, not production, so people should not be forced to eat food that may carry some degree of risk.
Others oppose genetic engineering on the grounds that genetic modifications might have unforeseen consequences, both in the initially modified organisms and their environments. For example, certain strains of maize have been developed that are toxic to plant eating insects (see Bt corn). It has been alleged those strains cross-pollinated with other varieties of wild and domestic maize and passed on these genes with a putative impact on Maize biodiversity (Quist D and Chapela IH Nature 414: 541- 543 2001). Subsequent to the publication of these results, several scientists pointed out that the conclusions were based on experiments with design flaws. It is well known that the results from the Polymerase Chain Reaction method of analysing DNA can ofter be confounded by sample contamination and experimental artifacts. Appropriate controls can be included in experiments to eliminate these as a possible explaination of the results - however these controls were not included in the methods used by Quist and Chapela. (Transgenic Research 11: iii-v, 2002.). After this criticism Nature, the scientific journal where this data was originally published "concluded that the evidence available is not sufficient to justify the publication of the original paper". [] More recent attempts to replicate the original studies have concluded that genetically modified corn is absent from southern Mexico in 2003 and 2004 [] Also in dispute is the impact on biodiversty of the introgression of transgenes into wild populations []. Unless a transgene offers a massive selective advantage in a wild population, a transgene that enters such a population will be maintained at a low gene frequency (See Ecological effects of transgenic plants). In such situations it can be argued that such an introgression actually increases biodiversity rather than lowers it.
Activists opposed to genetic engineering say that with current recombinant technology there is no way to ensure that genetically modified organisms will remain under control, and the use of this technology outside secure laboratory environments carries unacceptable risks for the future.
Some fear that certain types of genetically engineered crops will further reduce biodiversity in the cropland; herbicide-tolerant crops will for example be treated with the relevant herbicide to the extent that there are no wild plants ('weeds') able to survive, and plants toxic to insects will mean insect-free crops. This could result in declines in other wildlife (e.g. birds) which depend on weed seeds and/or insects for food resources. The recent (2003) farm scale studies in the UK found this to be the case with GM sugar beet and GM rapeseed, but not with GM maize (though in the last instance, the non-GM comparison maize crop had also been treated with environmentally-damaging pesticides subsequently (2004) withdrawn from use in the EU).
Proponents of current genetic techniques as applied to food plants cite the benefits that the technology can have, for example, in the harsh agricultural conditions of third world countries. They say that with modifications, existing crops would be able to thrive under the relatively hostile conditions providing much needed food to their people. Proponents also cite golden rice and golden rice 2, genetically engineered rice varieties (still under development) that contain elevated vitamin A levels. There is hope that this rice may alleviate vitamin A deficiency that contributes to the death of millions and permanent blindness of 500,000 annually.
Proponents say that genetically-engineered crops are not significantly different from those modified by nature or humans in the past, and are as safe or even safer than such methods. There is gene transfer between unicellular eukaryotes and prokaryotes. There have been no known genetic catastrophes as a result of this. They argue that animal husbandry and crop breeding are also forms of genetic engineering that use artificial selection instead of modern genetic modification techniques. It is politics, they argue, not economics or science, that causes their work to be closely investigated, and for different standards to apply to it than those applied to other forms of agricultural technology.
Proponents also note that species or genera barriers have been crossed in nature in the past. An oft-cited example is today's modern red wheat variety, which is the result of two natural crossings made long ago. It is made up of three groups of seven chromosomes. Each of those three groups came from a different wild wheat grass. First, a cross between two of the grasses occurred, creating the durum wheats, which were the commercial grains of the first civilizations up through the Roman Republic. Then a cross occurred between that 14-chromosome durum wheat and another wild grass to create what became modern red wheat at the time of the Roman Empire.
Economic and political effects
- Many opponents of current genetic engineering believe the increasing use of GM in major crops has caused amodified seeds in Venezuela.
- In January]] government announced a ban on importing and planting of genetic modified maize seeds, although these were authorised by the EU. 
- Gene therapy
- Genetically modified food
- Genetically modified organism
- Genetic engineering in fiction
- Human Genetic Engineering
- Human Genome Project
- Plant breeding
- Protein engineering
- Substantial equivalence
- Transgenic plant
- Council for Responsible Genetics - Council for Responsible Genetics
- Debate on the genetic modification of plants
- Round table discussion from the Vega Science Trust
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