Genetic engineering is the science of manipulating genetic material of an organism. The concept of genetic engineering was first proposed by Nikolay Timofeev-Ressovsky in 1934. The first artificial genetic modification accomplished using biotechnology was transgenesis, the process of transferring genes from one organism to another, first accomplished by Herbert Boyer and Stanley Cohen in 1973. It was the result of a series of advancements in techniques that allowed the direct modification of the genome. Important advances included the discovery of restriction enzymes and DNA ligases, the ability to design plasmids and technologies like polymerase chain reaction and sequencing. Transformation of the DNA into a host organism was accomplished with the invention of biolistics, Agrobacterium-mediated recombination and microinjection. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1976, the technology was commercialised, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. In 1983, an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organisms and induce a range of different effects. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.
Agriculture
Genetic engineering is the direct manipulation of an organism's genome using certain biotechnology techniques that have only existed since the 1970s. Human directed genetic manipulation was occurring much earlier, beginning with the domestication of plants and animals through artificial selection. The dog is believed to be the first animal domesticated, possibly arising from a common ancestor of the grey wolf, with archeological evidence dating to about 12,000 BC. Other carnivores domesticated in prehistoric times include the cat, which cohabited with human 9,500 years ago. Archeological evidence suggests sheep, cattle, pigs and goats were domesticated between 9,000 BC and 8,000 BC in the Fertile Crescent.
The first evidence of plant domestication comes from emmer and einkorn wheat found in pre-Pottery Neolithic A villages in Southwest Asia dated about 10,500 to 10,100 BC. The Fertile Crescent of Western Asia, Egypt, and India were sites of the earliest planned sowing and harvesting of plants that had previously been gathered in the wild. Independent development of agriculture occurred in northern and southern China, Africa's Sahel, New Guinea and several regions of the Americas.the history of maize cultivation in southern Mexico dates back 9,000 years. New York Times, (2010-05-25) The eight Neolithic founder crops (emmer wheat, einkorn wheat, barley, peas, lentils, bitter vetch, chick peas and flax) had all appeared by about 7,000 BC. Horticulture first appears in the Levant during the Chalcolithic period about 6,800 to 6,300 BC. Due to the soft tissues, archeological evidence for early vegetables is scarce. The earliest vegetable remains have been found in Egyptian caves that date back to the 2nd millennium BC.
Selective breeding of domesticated plants was once the main way early farmers shaped organisms to suit their needs. Charles Darwin described three types of selection: methodical selection, wherein humans deliberately select for particular characteristics; unconscious selection, wherein a characteristic is selected simply because it is desirable; and natural selection, wherein a trait that helps an organism survive better is passed on.Kingsbury, Noel (2009). Hybrid: The History and Science of Plant Breeding. University of Chicago Press. . Early breeding relied on unconscious and natural selection. The introduction of methodical selection is unknown. Common characteristics that were bred into domesticated plants include grains that did not shatter to allow easier harvesting, uniform ripening, shorter lifespans that translate to faster growing, loss of toxic compounds, and productivity. Some plants, like the Banana, were able to be propagated by vegetative cloning. Offspring often did not contain seeds, and was therefore sterile. However, these offspring were usually juicier and larger. Propagation through cloning allows these mutant varieties to be cultivated despite their lack of seeds.
Hybridization was another way that rapid changes in plant's makeup were introduced. It often increased vigor in plants, and combined desirable traits together. Hybridization most likely first occurred when humans first grew similar, yet slightly different plants in close proximity. Triticum aestivum, wheat used in baking bread, is an allopolyploid. Its creation is the result of two separate hybridization events.
Grafting can transfer chloroplasts, mitochondrial DNA and the entire cell nucleus containing the genome to potentially make a new species making grafting a form of natural genetic engineering.
X-rays were first used to deliberately mutate plants in 1927. Between 1927 and 2007, more than 2,540 genetically mutated plant varieties had been produced using x-rays.
Genetics
Various genetic discoveries have been essential in the development of genetic engineering. Genetic inheritance was first discovered by Gregor Mendel in 1865 following experiments crossing peas. Although largely ignored for 34 years he provided the first evidence of hereditary segregation and independent assortment. In 1889 Hugo de Vries came up with the name "(pan)gene" after postulating that particles are responsible for inheritance of characteristicsVries, H. de (1889) Intracellular Pangenesis ("pan-gene" definition on page 7 and 40 of this 1910 translation in English) and the term "genetics" was coined by William Bateson in 1905. In 1928 Frederick Griffith proved the existence of a "transforming principle" involved in inheritance, which Avery, MacLeod and McCarty later (1944) identified as DNA. Edward Lawrie Tatum and George Wells Beadle developed the central dogma that genes code for proteins in 1941. The double helix structure of DNA was identified by James Watson and Francis Crick in 1953.As well as discovering how DNA works, tools had to be developed that allowed it to be manipulated. In 1970 Hamilton Smith's lab discovered restriction enzymes that allowed DNA to be cut at specific places and separated out on an electrophoresis gel. This enabled scientists to isolate genes from an organism's genome. DNA ligases, that join broken DNA together, had been discovered earlier in 1967 and by combining the two enzymes it was possible to "cut and paste" DNA sequences to create recombinant DNA. Plasmids, discovered in 1952, became important tools for transferring information between cells and replicating DNA sequences. Frederick Sanger developed a method for sequencing DNA in 1977, greatly increasing the genetic information available to researchers. Polymerase chain reaction (PCR), developed by Kary Mullis in 1983, allowed small sections of DNA to be amplified and aided identification and isolation of genetic material.
As well as manipulating the DNA, techniques had to be developed for its insertion (known as transformation) into an organism's genome. Griffiths experiment had already shown that some bacteria had the ability to naturally take up and express foreign DNA. Artificial competence was induced in Escherichia coli in 1970 when Morton Mandel and Akiko Higa showed that it could take up bacteriophage λ after treatment with calcium chloride solution (CaCl2). Two years later, Stanley Cohen showed that CaCl2 treatment was also effective for uptake of plasmid DNA. Transformation using electroporation was developed in the late 1980s, increasing the efficiency and bacterial range. In 1907 a bacterium that caused plant tumors, Agrobacterium tumefaciens, was discovered and in the early 1970s the tumor inducing agent was found to be a DNA plasmid called the Ti plasmid. By removing the genes in the plasmid that caused the tumor and adding in novel genes researchers were able to infect plants with A. tumefaciens and let the bacteria insert their chosen DNA into the genomes of the plants.
Early genetically modified organisms
In 1971 Paul Berg used restriction enzymes and DNA ligases to create the first recombinant DNA molecules. He combined DNA from the monkey virus SV40 with that of the lambda virus. Herbert Boyer and Stanley Norman Cohen took Berg's work a step further and introduced recombinant DNA into a bacterial cell. Cohen was researching plasmids, while Boyers work involved restriction enzymes. They recognised the complementary nature of their work and teamed up in 1972. Together they found a restriction enzyme that cut the pSC101 plasmid at a single point and were able to insert and ligate a gene that conferred resistance to the kanamycin antibiotic into the gap. Cohen had previously devised a method where bacteria could be induced to take up a plasmid and using this they were able to create a bacterium that survived in the presence of the kanamycin. This represented the first genetically modified organism. They repeated experiments showing that other genes could be expressed in bacteria, including one from the toad Xenopus laevis, the first cross kingdom transformation.
In 1974 Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal. Jaenisch was studying mammalian cells infected with simian virus 40 (SV40) when he happened to read a paper from Beatrice Mintz describing the generation of chimera mice. He took his SV40 samples to Mintz's lab and injected them into early mouse embryos expecting tumours to develop. The mice appeared normal, but after using radioactive probes he discovered that the virus had integrated itself into the mice genome. However the mice did not pass the transgene to their offspring. In 1981 the laboratories of Frank Ruddle, Frank Constantini and Elizabeth Lacy injected purified DNA into a single-cell mouse embryo and showed transmission of the genetic material to subsequent generations.
The first genetically engineered plant was tobacco, reported in 1983. It was developed by Michael W. Bevan, Richard B. Flavell and Mary-Dell Chilton by creating a chimeric gene that joined an antibiotic resistant gene to the T1 plasmid from Agrobacterium. The tobacco was infected with Agrobacterium transformed with this plasmid resulting in the chimeric gene being inserted into the plant. Through tissue culture techniques a single tobacco cell was selected that contained the gene and a new plant grown from it.
Regulation
The development of genetic engineering technology led to concerns in the scientific community about potential risks. The development of a regulatory framework concerning genetic engineering began in 1975, at Asilomar, California. The Asilomar meeting recommended a set of guidelines regarding the cautious use of recombinant technology and any products resulting from that technology. The Asilomar recommendations were voluntary, but in 1976 the US National Institute of Health (NIH) formed a recombinant DNA advisory committee. This was followed by other regulatory offices (the United States Department of Agriculture (USDA), Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), effectively making all recombinant DNA research tightly regulated in the US.