Genetic engineering

Image:Glowing tobacco plant.jpg Genetic engineering, genetic modification (GM), and the now-deprecated gene splicing are terms for the process of manipulating genes, usually outside the organism's normal reproductive process.

It often involves the isolation, manipulation and reintroduction of DNAinto cellsor model organisms, usually to expressa protein. The aim is to introduce new characteristics such as making a crop resistant to a herbicide, introducing a novel trait, or producing a new protein or enzyme. Examples include the production of human insulinthrough the use of modified bacteria, the production of erythropoietinin 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 Nathansand Hamilton Smithreceived the 1978Nobel Prize in physiology or medicinefor 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.

Terminology

"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).

Applications

One of the best known applications of genetic engineering is that of the creation of genetically modified organisms(GMOs).

There are potentially momentous biotechnologicalapplications of GM, for example oral vaccinesproduced 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 DNAstrands 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 engineeringand molecular engineeringfor 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).

A radical ambition of some groups is human enhancementvia genetics, eventually by molecular engineering. See also: transhumanism.

DNA sequencingis a technique which is used to identify each base in DNA. Although the costs of DNA sequencing has dropped dramatically, the NIH estimates it costs at least $10 million to sequence 3 billion base pairs [[1]] - the size of the whole human genome.

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, has 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 knockoutexperiment, 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 embryonicstem 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.

Ethics

Proponents of genetic engineering argue that the technology is safe, and that it is necessary in order to maintain foodproduction 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 maizehave 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 Reactionmethod of analysing DNA can often 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". [2] More recent attempts to replicate the original studies have concluded that genetically modified corn is absent from southern Mexico in 2003 and 2004 [3] Also in dispute is the impact on biodiversity of the introgression of transgenes into wild populations [4]. 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. 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 organismswill 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 biodiversityin 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 seedsand/or insects for food resources. The recent (2003) farm scale studies in the UKfound this to be the case with GM sugar beetand 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 worldcountries. 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 riceand 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 eukaryotesand prokaryotes. There have been no known genetic catastrophes as a result of this. They argue that animal husbandryand crop breedingare also forms of genetic engineering that use artificial selectioninstead 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 a power shift in agriculture towards Biotechnology companies gaining excessive control over the production chain of crops and food, and over the farmers that use their products, as well.
• Many proponents of current genetic engineering techniques believe it will lower pesticide usage and has brought higher yields and profitability to many farmers, including those in third world countries. A few GM licenses allow third world farmers to save seeds for next year's planting.
• In August 2002, Zambiacut off the flow of Genetically Modified Food(mostly maize) from UN's World Food Program. Although there were claims that this left a famine-stricken population without food aid, the U.N. program succeeded in replacing the rejected grain with other sources, including some foods purchased locally with European cash donations. In rejecting the maize, Zambians cited the "Precautionary Principle" and also the desire to protect future possibilities of grain exports to Europe.
• In December 2005 the Zambian government changed its mind in the face of further famine and allowed the imporation of GM maize [5]
• In April 2004 Hugo Chávezannounced a total ban on genetically modified seeds in Venezuela.
• In January 2005, the Hungariangovernment announced a ban on importing and planting of genetic modified maize seeds, although these were authorised by the EU. [6]

See also

• List of genetic engineering topics

• Biorobotics
• Cloning
• Gene therapy
• Genetically modified food
• Genetically modified organism
• Genetic engineering in fiction
• Germinal choice technology
• Human genetic engineering
• Human Genome Project
• Plant breeding
• PNA
• Protein engineering
• Reprogenetics
• Substantial equivalence
• Transformation
• Transgenic plant

External links

• Council for Responsible Genetics- Council for Responsible Genetics
• Debate on the genetic modification of plants
• Round table discussion from the Vega Science Trust
• FAO Agriculture Departmentand its SOFA report on Agricultural Biotechnologyaddressing the methods used in genetic engineering
• Genetically Engineered Crops– A summary for non-specialists of the above FAO report by GreenFacts.
• CaMV Promoter is A Recombination Hotspot - No Transgenic Plant Containing CaMV Promoter Should be Released; also [7]as a PDF
• Open Letter from Scientists to All Governments calling for a moratorium on GE technology(825 Names)
• Petition from Scientists In Support Of Agricultural Biotechnology. (3400 names)
• The Fake Persuadersarticle by George Monbiot, published in The Guardian, on Monsanto's use of viral marketingand its role in shaping scientific discourse on native maize contamination.da:Gensplejsning

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It uses material from the http://en.wikipedia.org/wiki/Genetic+engineering Wikipedia article Genetic engineering.