Genetic engineering
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was designed by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can either be inserted randomly or targeted to a specific part of the genome.
An organism that is generated through genetic engineering is considered to be genetically modified, and the resulting entity is a genetically modified organism. The first GMO was a bacterium generated by Herbert Boyer and Stanley Cohen in 1973. Rudolf Jaenisch created the first GM animal when he inserted foreign DNA into a mouse in 1974. The first company to focus on genetic engineering, Genentech, was founded in 1976 and began the production of human proteins. Genetically engineered human insulin was produced in 1978, and insulin-producing bacteria were commercialised in 1982. Genetically modified food has been sold since 1994, with the release of the Flavr Savr tomato. The Flavr Savr was engineered to have a longer shelf life, but most current GM crops are modified to increase resistance to insects and herbicides. GloFish, the first GMO designed as a pet, was sold in the United States in December 2003. In 2016, salmon modified with a growth hormone were sold.
Genetic engineering has been applied in numerous fields, including research, medicine, industrial biotechnology, and agriculture. In research, GMOs are used to study gene function and expression through loss-of-function, gain-of-function, tracking, and expression experiments. By knocking out genes responsible for certain conditions, it is possible to create animal model organisms of human diseases. As well as producing hormones, vaccines, and other drugs, genetic engineering has the potential to cure genetic diseases through gene therapy. Chinese hamster ovary cells are used in industrial genetic engineering. Additionally, mRNA vaccines are made through genetic engineering to prevent infections by viruses such as COVID-19. The same techniques that are used to produce drugs can also have industrial applications, such as producing enzymes for laundry detergent, cheeses, and other products.
The rise of commercialised genetically modified crops has provided economic benefit to farmers in many different countries; however, it has also been the source of most of the controversy surrounding the technology. This has been present since its early use; the first field trials were destroyed by anti-GM activists. Although there is a scientific consensus that food derived from GMO crops poses no greater risk to human health than conventional food, critics consider GM food safety a leading concern. Gene flow, impact on non-target organisms, control of the food supply, and intellectual property rights have also been raised as potential issues. These concerns have led to the development of a regulatory framework, which started in 1975. Eventually, this has led to a proposal of an international treaty, the Cartagena Protocol on Biosafety, which was officially adopted in 2000. Individual countries have developed their own regulatory systems regarding GMOs, with the most marked differences occurring between the United States and Europe.
Overview
Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducing DNA or modifying existing genetic material in situ. Unlike traditional animal and plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired phenotype, genetic engineering takes the gene directly from one organism and delivers it to the other. This is much faster, can be used to insert any genes from any organism, and prevents other undesirable genes from also being added.Genetic engineering could potentially fix severe genetic disorders in humans by replacing the defective gene with a functioning one. It is an important tool in research that allows the function of specific genes to be studied. Drugs, vaccines, and other products have been harvested from organisms engineered to produce them. Crops have been developed that aid food security by increasing yield, nutritional value, and tolerance to environmental stresses.
The DNA can be introduced directly into the host organism or into a cell that is then fused or hybridised with the host. This relies on recombinant nucleic acid techniques to form new combinations of heritable genetic material, followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macro-injection, or micro-encapsulation.
Genetic engineering does not normally include traditional breeding, in vitro fertilisation, induction of polyploidy, mutagenesis, and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process. However, some broad definitions of genetic engineering include selective breeding. Cloning and stem cell research, although not considered genetic engineering, are closely related, and genetic engineering can be used within them. Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesised material into an organism.
Plants, animals, or microorganisms that have been changed through genetic engineering are termed genetically modified organisms or GMOs. If genetic material from another species is added to the host, the resulting organism is called transgenic. If genetic material from the same species or a species that can naturally breed with the host is used, the resulting organism is called cisgenic. If genetic engineering is used to remove genetic material from the target organism, the resulting organism is termed a knockout organism. In Europe, genetic modification is synonymous with genetic engineering while within the United States of America and Canada, genetic modification can also be used to refer to more conventional breeding methods.
History
Humans have altered the genomes of species for thousands of years through selective breeding, or artificial selection as contrasted with natural selection. More recently, mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations for selective breeding purposes. Genetic engineering, as the direct manipulation of DNA by humans outside breeding and mutations, has only existed since the 1970s. The term "genetic engineering" was coined by the Russian-born geneticist Nikolay Timofeev-Ressovsky in his 1934 paper "The Experimental Production of Mutations", published in the British journal Biological Reviews. Jack Williamson used the term in his science fiction novel Dragon's Island, published in 1951 – one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase, and two years before James Watson and Francis Crick showed that the DNA molecule has a double-helix structure – though the general concept of direct genetic manipulation was explored in rudimentary form in Stanley G. Weinbaum's 1936 science fiction story Proteus Island.File:Jaenisch 2003 by Sam Ogden.jpg|thumb|upright|In 1974, Rudolf Jaenisch created a genetically modified mouse, the first GM animal.
In 1972, Paul Berg created the first recombinant DNA molecules by combining DNA from the monkey virus SV40 with that of the lambda virus. In 1973, Herbert Boyer and Stanley Cohen created the first transgenic organism by inserting antibiotic resistance genes into the plasmid of an Escherichia coli bacterium. A year later Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal These achievements led to concerns in the scientific community about potential risks from genetic engineering, which were first discussed in depth at the Asilomar Conference in 1975. One of the main recommendations from this meeting was that government oversight of recombinant DNA research should be established until the technology was deemed safe.
In 1976, Genentech, the first genetic engineering company, was founded by Herbert Boyer and Robert Swanson and, a year later, the company produced a human protein in E. coli. Genentech announced the production of genetically engineered human insulin in 1978. In 1980, the Supreme Court of the United States in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented. The insulin produced by bacteria was approved for release by the Food and Drug Administration in 1982.
In 1983, a biotech company, Advanced Genetic Sciences, applied for U.S. government authorisation to perform field tests with the ice-minus strain of Pseudomonas syringae to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges. In 1987, the ice-minus strain of P. syringae became the first genetically modified organism to be released into the environment when a strawberry field and a potato field in California were sprayed with it. Both test fields were attacked by activist groups the night before the tests occurred: "The world's first trial site attracted the world's first field trasher".
The first field trials of genetically engineered plants occurred in France and the US in 1986, and tobacco plants were engineered to be resistant to herbicides. The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992. In 1994, Calgene received official approval to commercially release the first genetically modified food, the Flavr Savr, a tomato engineered to have a longer shelf life. In 1994, the European Union approved tobacco engineered to be resistant to the herbicide bromoxynil, making it the first genetically engineered crop commercialised in Europe. In 1995, Bt potato was approved safe by the Environmental Protection Agency, after having been approved by the FDA, making it the first pesticide-producing crop to be approved in the US. In 2009, 11 transgenic crops were grown commercially in 25 countries, the largest of which by area grown were the United States, Brazil, Argentina, India, Canada, People's Republic of China, Paraguay, and South Africa.
In 2010, scientists at the J. Craig Venter Institute created the first synthetic genome and inserted it into an empty bacterial cell. The resulting bacterium, named Mycoplasma laboratorium, could replicate and produce proteins. Four years later, this was taken a step further when a bacterium was developed that replicated a plasmid containing a unique base pair, creating the first organism engineered to use an expanded genetic alphabet. In 2012, Jennifer Doudna and Emmanuelle Charpentier collaborated to develop the CRISPR/Cas9 system, a technique that can be used to easily and specifically alter the genome of almost any organism.