A tobacco plant which has been genetically engineered to express a gene taken from fireflies.

A genetically modified organism (GMO) is an organism whose genetic material has been altered using techniques in genetics generally known as recombinant DNA technology. Recombinant DNA technology is the ability to combine DNA molecules from different sources into the one molecule in a test tube. Thus, the abilities or the phenotype of the organism, or the proteins it produces, can be modified through the modification of its genes.

The term generally does not cover organisms whose genetic makeup have been altered by conventional cross breeding or by "mutagenesis" breeding as these methods predate the discovery of the recombinant DNA techniques.

Examples of GMOs are diverse, and include transgenic experimental animals such as mice, transgenic plants, or various microscopic organisms altered for the purposes of genetic research or for the production of pharmaceuticals.

The term "genetically modified organism" does not necessarily imply, but does include, transgenic substitution of genes from another species, although research is actively being conducted in this field. For example, genes for fluorescent proteins can be co-expressed with complex proteins in cultured cells to facilitate study by biologists, and modified organisms are used in researching the mechanisms of cancer and other diseases.

History

The first GMO was created in 1973 by Stanley N. Cohen and Herbert Boyer [1]. In mid-1974, very soon after the first GMO was created, scientists called for and observed a voluntary moratorium on certain recombinant DNA experiments. One goal of the moratorium was to provide time for a conference that would evaluate the state of the new technology and the risks, if any, associated with it. That conference concluded that recombinant DNA research should proceed but under strict guidelines. Such guidelines were subsequently promulgated by the National Institutes of Health in the United States and by comparable bodies in other countries. These guidelines form the basis upon which GMOs are regulated to this day. [2]

The first transgenic animals were mice created by Rudolf Jaenisch in 1974. Jaenish successfully managed to insert foreign DNA into the early-stage mouse embryos; the resulting mice carried the modified gene in all their tissues. Subsequent experiments, injecting leukemia genes to early mouse embryos using a retrovirus vector, proved the genes integrated not only to the mice themselves, but also to their progeny.

Methods of genetic modification

The double-helix structure of DNA allows modification of plasmids to take place.

Genetic modification involves genetic engineering, also known as gene splicing, a technique to splice together DNA fragments from more than one organism and thus preparing a "recombinant" DNA molecule in a test tube, producing a single piece of genetic material containing the original information from multiple fragments which can then be inserted into another organism. This is achieved by cutting up DNA molecules with restriction enzymes and splicing these fragments together using DNA ligase. A transgenic organism that contains such DNA sequences from a foreign organism integrated into its own genome, the term "transgenic" literally means across gene. An example of a transgenic organism is an animal that is not a jelly fish that expresses the green fluorescence protein, such as mice or fish. The gene coding for the protein originated from jelly fish.

With current technology, transgenic organisms can be produced with only a very small proportion of extraneous DNA. For example, the genome of most mammals contains three billion basepairs of DNA, while it becomes relatively difficult to insert more than 10,000 to 20,000 basepairs of foreign DNA. More sophisticated techniques using yeast artificial chromosomes and bacterial artificial chromosomes allow insertions of up to 320,000 basepairs [3] - approximately 0.01% of the total genome. In concept, multiple rounds of transgenesis or interbreeding of transgenics could lead to organisms with a higher proportion of foreign DNA, but cost and time considerations prevent this.

In order to introduce new DNA into the receiving host, vectors are used. Vectors range from small circular pieces of DNA such as plasmids, to various viruses that can carry and transmit genetic information. Three processes are known by which the genetic composition of bacteria can be altered.

Transformation is a process by which some bacteria are naturally capable of taking up DNA to acquire new genetic traits. This phenomenon was discovered by Frederick Griffith in 1928, although the fact that it was specifically DNA molecules that carried the genetic information was not proven until 1944. Bacteria that are competent to undergo transformation are frequently used in molecular biology. The foreign DNA uptake is facilitated by the presence of certain cations, such as Ca²⁺, or by the use of electric current (electroporation). Transformation does not normally integrate new DNA into the bacterial chromosome. Instead, it remains on a plasmid.

In conjugation, DNA is transferred from one bacterium to another via a temporary connecting tube of protein called a pilus (a process analogous to but biologically distinct from mating). A plasmid is transferred through the pilus. Conjugation is not widely used for the artificial genetic modification of bacteria, but happens often in nature.

Transduction refers to the introduction of new DNA into a bacterial cell by a bacteriophage, a virus that infects bacteria.

In order to gain knowledge about a particular gene's function, researchers often use knock out organisms. These organisms have a specific gene that has been functionally destroyed or "knocked out." They are used extensively in disease research with model organisms. For example, when investigating the cause of cystic fibrosis, researchers identified the CFTR gene as a likely candidate for the disease, found the mouse equivalent, bred a mouse with this gene "knocked out", and noted that the knockout mouse also had cystic fibrosis.

Genetic modification of plants

Main article: Transgenic plants

The principal technique for the genetic modification of plants is based on a natural ability of the bacterium Agrobacterium tumefaciens. This bacterium infects plants and causes a tumor-like growth termed a crown gall. A. tumefaciens contains a plasmid (a circular piece of DNA) that transfers from the bacteria into the infected plant and integrates into the plant's genome. The transferred genes cause the plant to form the gall, which houses the bacteria and produces nutrients that support the bacteria's growth. A number of scientists contributed to this discovery throughout the late 1960s and the 1970s, with key discoveries by Jeff Schell, Marc Van Montagu, Georges Morel, Mary-Dell Chilton and Jacques Tempé. By 1983 biotechnology had reached the point where it was possible to insert additional genes of interest into A. tumefaciens and thus transfer those genes into plants. This process is commonly used to create transgenic crop plants for agricultural purposes. Another widely used process to create transgenic crops is the biolistic method (gene gun), a method used for the creation of the two most common transgenic crops - RoundUp ready soybean and Bt-corn. Biolistic techniques are generally more suited to monocots, whereas agrobacteria are used primarily with dicots. However, newer techniques and strains of A. tumefaciens have also found utility in the transformation of monocots.

Genetic modification of animals

Like bacteria and plants, animals can be genetically modified by viral infection. However, the genetic modification occurs only in those cells that become infected, and in most cases these cells are eventually eliminated by the immune system. In some cases it is possible to use the gene-transferring ability of viruses for gene therapy, i.e. to correct diseases caused by a defective gene by supplying a normal copy of the gene. Permanent genetic modification of entire animals can be accomplished in mice. The process begins by first genetically modifying a mouse embryonic stem cell. This is normally done by physically introducing into the cell a plasmid that can integrate into the genome by a process known as transfection [4]. During transfection the DNA integrates into the animal genome via non-homologous recombination. This altered cell is implanted into a blastocyst (an early embryo), which is then implanted into the uterus of a female mouse. A pup born from this blastocyst will be a chimera containing some cells derived from the unmodified cells of the blastocyst and some derived from the modified stem cell. By selecting mice whose germ cells (sperm- or egg-producing cells) developed from the modified cell and interbreeding them, pups that contain the genetic modification in all of their cells will be born.

There has also been the genetically manipulated bull Herman with 55 offspring. A human gene was built into his genetic code while in an early embryonic stage in 1990. As a result, milk from his female descendants contained the human protein lactoferrine, that can be used as medicine, but it was present at such low levels that it was not profitable to extract them.

Insects can be genetically modified by injecting them with artificial transposons and a source of the enzyme transposase. The transposon, which can include new genes, is then integrated into the genome. Such insertions are unstable and can 'jump-out' in the presence of transposase.

Controversies over genetic modification

See also Genetically modified food and Transgenic plants

Genetic modification (GM) is the subject of controversy in its own right [5]. Some see the science itself as intolerable meddling with "natural" order, despite known examples of natural genetic crossings occurring throughout history. While some would like to see it banned, others push simply for required labeling of genetically modified food. Other controversies include the definition of patent and property pertaining to products of genetic engineering and the possibility of unforeseen global side effects as a result of modified organisms proliferating. The basic ethical issues involved in genetic research are discussed in the article on genetic engineering.

In 2004, Mendocino County, California became the first county in the United States to ban the production of GMOs. The measure passed with a 57% majority. In 2005, a standing committee of the government of Prince Edward Island in Canada began work to assess a proposal to ban the production of GMOs in the province. This is a largely symbolic and empty gesture as PEI has already banned GMO potatoes, which account for most of its crop. The Californian counties of Trinity and Marin counties have also imposed bans on GM crops, while ordinances to do so were unsuccessful in Butte, San Luis Obispo, Humboldt and Sonoma counties. Supervisors in the ag-rich counties of Fresno, Kern, Kings, Solano, Sutter and Tulare have passed resolutions supporting the practice [6].

Currently, there is little international consensus regarding the acceptability and effective role of modified "complete" organisms such as plants or animals. A great deal of the modern research that is illuminating complex biochemical processes and disease mechanisms makes vast use of genetic engineering.

The practice of genetic modification as a scientific technique is not restricted in the United States. Individual genetically modified crops (such as soybeans) are subject to intense study before being brought to market and are common in the United States, but estimates of their market saturation vary widely. Some countries in Europe have taken the opposite position, stating that genetic modification has not been proven safe, and therefore that they will not accept genetically modified food from the United States or any other country. This issue has been brought before the World Trade Organization, which determined that not allowing modified food into the country creates an unnecessary obstacle to international trade. Consequently, genetic modification within agriculture is an issue of some strong debate in the United States, the European Union, and some other countries.

Some critics have raised the concern that conventionally bred crop plants can be cross-pollinated (bred) from the pollen of modified plants. Pollen can be dispersed over large areas by wind, animals, and insects. Recent research with creeping bentgrass has lent support to the concern when modified genes were found in normal grass up to 21 km (13 miles) away from the source, and also within close relatives of the same genus Agrostis [7]. GM proponents point out that outcrossing, as this process is known as, is not new. The same thing happens with any new open-pollinated crop variety - newly introduced traits can potentially cross out into neighbouring crop plants of the same species and in same cases to closely related wild relatives. Defenders of GM technology point out that each GM crop is assessed on a case by case basis to determine if there is any risk associated with the outcrossing of the GM trait into wild plant populations. The fact that a GM plant may outcross with a related wild relative is not, in itself, a risk unless such an occurrence has consequences. If, for example, a herbicide resistance trait was to cross into a wild relative of a crop plant it can be predicted that this would not have any concequences except in areas where herbicides are sprayed - eg. a farm. In such a setting the farmer can manage this risk by rotating herbicides. If patented genes are outcrossed, even accidentally, to other commercial fields and a person deliberately selects the outcrossed plants for subsquent planting then the patent holder has the right to control the use of those crops. This was supported in Canadian law in the case of Monsanto vs. Percy Schmeiser Monsanto Canada Inc. v. Schmeiser#Aftermath .

There was much fervor generated when Monsanto submitted a patent for a hypothetical Technology Protection technology (dubbed terminator by NGOs) to produce first generation crops that would not generate seeds in the second generation because the plants yielded sterile seeds. The so-called "terminator" gene technology was developed by Delta and Pine Land and the USDA, who co-owned the patent. In addition to the commercial protection of proprietary technology in selfpollinating crops such as soybean (a generally contentious issue) another purpose of the terminator gene is to prevent the escape of genetically modified traits from crosspollinating crops into wild-type species by sterilizing any resultant hybrids. The terminator gene technology created a backlash amongst those who felt the technology would prevent re-use of seed by farmers growing such terminator varieties in the developing world and was ostensibly a means to protect intellectual property rights. Use of the terminator technology would also prevent "volunteers", or crops that grow from unharvested seed, a major concern that arose during the Starlink debacle.

Transgenics featured in fiction

Genetically modified characters, whether as heroes, villains, or backdrop, feature prominently in many works of fiction, in particular science fiction and cyberpunk, where it is used as a plot device to explain differences in a character or setting, such as explaining increased longevity or eradication of disease in a non fictional civilization.