Genetic engineering

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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.

Contents

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 made 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 be inserted randomly, or targeted to a specific part of the genome. [1]

An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is a genetically modified organism (GMO). 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 started 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 (CHO) cells are used in industrial genetic engineering. Additionally mRNA vaccines are made through genetic engineering to treat 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, but 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 currently available food derived from GM 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. It has led to an international treaty, the Cartagena Protocol on Biosafety, that was 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.

IUPAC definition

Genetic engineering: Process of inserting new genetic information into existing cells in order to modify a specific organism for the purpose of changing its characteristics.

Note: Adapted from ref. [2] [3]

Overview

Comparison of conventional plant breeding with transgenic and cisgenic genetic modification Breeding transgenesis cisgenesis.svg
Comparison of conventional plant breeding with transgenic and cisgenic genetic modification

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 (even ones from different domains) and prevents other undesirable genes from also being added. [4]

Genetic engineering could potentially fix severe genetic disorders in humans by replacing the defective gene with a functioning one. [5] It is an important tool in research that allows the function of specific genes to be studied. [6] Drugs, vaccines and other products have been harvested from organisms engineered to produce them. [7] Crops have been developed that aid food security by increasing yield, nutritional value and tolerance to environmental stresses. [8]

The DNA can be introduced directly into the host organism or into a cell that is then fused or hybridised with the host. [9] 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. [9] However, some broad definitions of genetic engineering include selective breeding. [10] Cloning and stem cell research, although not considered genetic engineering, [11] are closely related and genetic engineering can be used within them. [12] Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesised material into an organism. [13]

Plants, animals or microorganisms that have been changed through genetic engineering are termed genetically modified organisms or GMOs. [14] 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. [15] If genetic engineering is used to remove genetic material from the target organism the resulting organism is termed a knockout organism. [16] 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. [17] [18] [19]

History

Humans have altered the genomes of species for thousands of years through selective breeding, or artificial selection [20] : 1  [21] : 1  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. [22] Jack Williamson used the term in his science fiction novel Dragon's Island, published in 1951 [23] – one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase, [24] 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. [25] [26]

In 1974 Rudolf Jaenisch created a genetically modified mouse, the first GM animal. Jaenisch 2003 by Sam Ogden.jpg
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. [27] 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. [28] [29] A year later Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal [30] 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. [31] [32]

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 (somatostatin) in E. coli. Genentech announced the production of genetically engineered human insulin in 1978. [33] In 1980, the U.S. Supreme Court in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented. [34] The insulin produced by bacteria was approved for release by the Food and Drug Administration (FDA) in 1982. [35]

In 1983, a biotech company, Advanced Genetic Sciences (AGS) 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. [36] In 1987, the ice-minus strain of P. syringae became the first genetically modified organism (GMO) to be released into the environment [37] when a strawberry field and a potato field in California were sprayed with it. [38] 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". [37]

The first field trials of genetically engineered plants occurred in France and the US in 1986, tobacco plants were engineered to be resistant to herbicides. [39] The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992. [40] In 1994 Calgene attained approval to commercially release the first genetically modified food, the Flavr Savr, a tomato engineered to have a longer shelf life. [41] 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. [42] 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. [43] In 2009 11 transgenic crops were grown commercially in 25 countries, the largest of which by area grown were the US, Brazil, Argentina, India, Canada, China, Paraguay and South Africa. [44]

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. [45] [46] 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. [47] [48] In 2012, Jennifer Doudna and Emmanuelle Charpentier collaborated to develop the CRISPR/Cas9 system, [49] [50] a technique which can be used to easily and specifically alter the genome of almost any organism. [51]

Process

Polymerase chain reaction is a powerful tool used in molecular cloning. Master Mix with Primers form PCR.jpg
Polymerase chain reaction is a powerful tool used in molecular cloning.

Creating a GMO is a multi-step process. Genetic engineers must first choose what gene they wish to insert into the organism. This is driven by what the aim is for the resultant organism and is built on earlier research. Genetic screens can be carried out to determine potential genes and further tests then used to identify the best candidates. The development of microarrays, transcriptomics and genome sequencing has made it much easier to find suitable genes. [52] Luck also plays its part; the Roundup Ready gene was discovered after scientists noticed a bacterium thriving in the presence of the herbicide. [53]

Gene isolation and cloning

The next step is to isolate the candidate gene. The cell containing the gene is opened and the DNA is purified. [54] The gene is separated by using restriction enzymes to cut the DNA into fragments [55] or polymerase chain reaction (PCR) to amplify up the gene segment. [56] These segments can then be extracted through gel electrophoresis. If the chosen gene or the donor organism's genome has been well studied it may already be accessible from a genetic library. If the DNA sequence is known, but no copies of the gene are available, it can also be artificially synthesised. [57] Once isolated the gene is ligated into a plasmid that is then inserted into a bacterium. The plasmid is replicated when the bacteria divide, ensuring unlimited copies of the gene are available. [58] The RK2 plasmid is notable for its ability to replicate in a wide variety of single-celled organisms, which makes it suitable as a genetic engineering tool. [59]

Before the gene is inserted into the target organism it must be combined with other genetic elements. These include a promoter and terminator region, which initiate and end transcription. A selectable marker gene is added, which in most cases confers antibiotic resistance, so researchers can easily determine which cells have been successfully transformed. The gene can also be modified at this stage for better expression or effectiveness. These manipulations are carried out using recombinant DNA techniques, such as restriction digests, ligations and molecular cloning. [60]

Inserting DNA into the host genome

A gene gun uses biolistics to insert DNA into plant tissue. Genegun.jpg
A gene gun uses biolistics to insert DNA into plant tissue.

There are a number of techniques used to insert genetic material into the host genome. Some bacteria can naturally take up foreign DNA. This ability can be induced in other bacteria via stress (e.g. thermal or electric shock), which increases the cell membrane's permeability to DNA; up-taken DNA can either integrate with the genome or exist as extrachromosomal DNA. DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus, or through the use of viral vectors. [61]

Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. In plants the DNA is often inserted using Agrobacterium-mediated transformation, [62] taking advantage of the Agrobacteriums T-DNA sequence that allows natural insertion of genetic material into plant cells. [63] Other methods include biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells, [64] and electroporation, which involves using an electric shock to make the cell membrane permeable to plasmid DNA.

As only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through the use of tissue culture. [65] [66] In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells. [67] Bacteria consist of a single cell and reproduce clonally so regeneration is not necessary. Selectable markers are used to easily differentiate transformed from untransformed cells. These markers are usually present in the transgenic organism, although a number of strategies have been developed that can remove the selectable marker from the mature transgenic plant. [68]

A. tumefaciens attaching itself to a carrot cell Agrobacterium-tumefaciens.png
A. tumefaciens attaching itself to a carrot cell

Further testing using PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene. [69] These tests can also confirm the chromosomal location and copy number of the inserted gene. The presence of the gene does not guarantee it will be expressed at appropriate levels in the target tissue so methods that look for and measure the gene products (RNA and protein) are also used. These include northern hybridisation, quantitative RT-PCR, Western blot, immunofluorescence, ELISA and phenotypic analysis. [70]

The new genetic material can be inserted randomly within the host genome or targeted to a specific location. The technique of gene targeting uses homologous recombination to make desired changes to a specific endogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use of selectable markers. The frequency of gene targeting can be greatly enhanced through genome editing. Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome, and use the cell's endogenous mechanisms to repair the induced break by the natural processes of homologous recombination and nonhomologous end-joining. There are four families of engineered nucleases: meganucleases, [71] [72] zinc finger nucleases, [73] [74] transcription activator-like effector nucleases (TALENs), [75] [76] and the Cas9-guideRNA system (adapted from CRISPR). [77] [78] TALEN and CRISPR are the two most commonly used and each has its own advantages. [79] TALENs have greater target specificity, while CRISPR is easier to design and more efficient. [79] In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate a gene knockout. [80] [81]

Applications

Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and microorganisms. Bacteria, the first organisms to be genetically modified, can have plasmid DNA inserted containing new genes that code for medicines or enzymes that process food and other substrates. [82] [83] Plants have been modified for insect protection, herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of edible vaccines. [84] Most commercialised GMOs are insect resistant or herbicide tolerant crop plants. [85] Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. The genetically modified animals include animals with genes knocked out, increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk. [86]

Medicine

Genetic engineering has many applications to medicine that include the manufacturing of drugs, creation of model animals that mimic human conditions and gene therapy. One of the earliest uses of genetic engineering was to mass-produce human insulin in bacteria. [33] This application has now been applied to human growth hormones, follicle stimulating hormones (for treating infertility), human albumin, monoclonal antibodies, antihemophilic factors, vaccines and many other drugs. [87] [88] Mouse hybridomas, cells fused together to create monoclonal antibodies, have been adapted through genetic engineering to create human monoclonal antibodies. [89] Genetically engineered viruses are being developed that can still confer immunity, but lack the infectious sequences. [90]

Genetic engineering is also used to create animal models of human diseases. Genetically modified mice are the most common genetically engineered animal model. [91] They have been used to study and model cancer (the oncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. [92] Potential cures can be tested against these mouse models.

Gene therapy is the genetic engineering of humans, generally by replacing defective genes with effective ones. Clinical research using somatic gene therapy has been conducted with several diseases, including X-linked SCID, [93] chronic lymphocytic leukemia (CLL), [94] [95] and Parkinson's disease. [96] In 2012, Alipogene tiparvovec became the first gene therapy treatment to be approved for clinical use. [97] [98] In 2015 a virus was used to insert a healthy gene into the skin cells of a boy suffering from a rare skin disease, epidermolysis bullosa, in order to grow, and then graft healthy skin onto 80 percent of the boy's body which was affected by the illness. [99]

Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community. [100] [101] In 2015, CRISPR was used to edit the DNA of non-viable human embryos, [102] [103] leading scientists of major world academies to call for a moratorium on inheritable human genome edits. [104] There are also concerns that the technology could be used not just for treatment, but for enhancement, modification or alteration of a human beings' appearance, adaptability, intelligence, character or behavior. [105] The distinction between cure and enhancement can also be difficult to establish. [106] In November 2018, He Jiankui announced that he had edited the genomes of two human embryos, to attempt to disable the CCR5 gene, which codes for a receptor that HIV uses to enter cells. The work was widely condemned as unethical, dangerous, and premature. [107] Currently, germline modification is banned in 40 countries. Scientists that do this type of research will often let embryos grow for a few days without allowing it to develop into a baby. [108]

Researchers are altering the genome of pigs to induce the growth of human organs, with the aim of increasing the success of pig to human organ transplantation. [109] Scientists are creating "gene drives", changing the genomes of mosquitoes to make them immune to malaria, and then looking to spread the genetically altered mosquitoes throughout the mosquito population in the hopes of eliminating the disease. [110]

Research

Knockout mice PCWmice1.jpg
Knockout mice
Human cells in which some proteins are fused with green fluorescent protein to allow them to be visualised Expression of Human Wild-Type and P239S Mutant Palladin.png
Human cells in which some proteins are fused with green fluorescent protein to allow them to be visualised

Genetic engineering is an important tool for natural scientists, with the creation of transgenic organisms one of the most important tools for analysis of gene function. [111] Genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research. [112]

Organisms are genetically engineered to discover the functions of certain genes. This could be the effect on the phenotype of the organism, where the gene is expressed or what other genes it interacts with. These experiments generally involve loss of function, gain of function, tracking and expression.

Industrial

Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they will overexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism in bioreactor equipment using industrial fermentation, and then purifying the protein. [116] Some genes do not work well in bacteria, so yeast, insect cells or mammalian cells can also be used. [117] These techniques are used to produce medicines such as insulin, human growth hormone, and vaccines, supplements such as tryptophan, aid in the production of food (chymosin in cheese making) and fuels. [118] Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as making biofuels, [119] cleaning up oil spills, carbon and other toxic waste [120] and detecting arsenic in drinking water. [121] Certain genetically modified microbes can also be used in biomining and bioremediation, due to their ability to extract heavy metals from their environment and incorporate them into compounds that are more easily recoverable. [122]

In materials science, a genetically modified virus has been used in a research laboratory as a scaffold for assembling a more environmentally friendly lithium-ion battery. [123] [124] Bacteria have also been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions. [125]

Agriculture

Bt-toxins present in peanut leaves (bottom image) protect it from extensive damage caused by lesser cornstalk borer larvae (top image). Bt plants.png
Bt-toxins present in peanut leaves (bottom image) protect it from extensive damage caused by lesser cornstalk borer larvae (top image).

One of the best-known and controversial applications of genetic engineering is the creation and use of genetically modified crops or genetically modified livestock to produce genetically modified food. Crops have been developed to increase production, increase tolerance to abiotic stresses, alter the composition of the food, or to produce novel products. [127]

The first crops to be released commercially on a large scale provided protection from insect pests or tolerance to herbicides. Fungal and virus resistant crops have also been developed or are in development. [128] [129] This makes the insect and weed management of crops easier and can indirectly increase crop yield. [130] [131] GM crops that directly improve yield by accelerating growth or making the plant more hardy (by improving salt, cold or drought tolerance) are also under development. [132] In 2016 Salmon have been genetically modified with growth hormones to reach normal adult size much faster. [133]

GMOs have been developed that modify the quality of produce by increasing the nutritional value or providing more industrially useful qualities or quantities. [132] The Amflora potato produces a more industrially useful blend of starches. Soybeans and canola have been genetically modified to produce more healthy oils. [134] [135] The first commercialised GM food was a tomato that had delayed ripening, increasing its shelf life. [136]

Plants and animals have been engineered to produce materials they do not normally make. Pharming uses crops and animals as bioreactors to produce vaccines, drug intermediates, or the drugs themselves; the useful product is purified from the harvest and then used in the standard pharmaceutical production process. [137] Cows and goats have been engineered to express drugs and other proteins in their milk, and in 2009 the FDA approved a drug produced in goat milk. [138] [139]

Other applications

Genetic engineering has potential applications in conservation and natural area management. Gene transfer through viral vectors has been proposed as a means of controlling invasive species as well as vaccinating threatened fauna from disease. [140] Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations. [141] With the increasing risks of maladaptation in organisms as a result of climate change and other perturbations, facilitated adaptation through gene tweaking could be one solution to reducing extinction risks. [142] Applications of genetic engineering in conservation are thus far mostly theoretical and have yet to be put into practice.

Genetic engineering is also being used to create microbial art. [143] Some bacteria have been genetically engineered to create black and white photographs. [144] Novelty items such as lavender-colored carnations, [145] blue roses, [146] and glowing fish, [147] [148] have also been produced through genetic engineering.

Regulation

The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of GMOs. The development of a regulatory framework began in 1975, at Asilomar, California. [149] The Asilomar meeting recommended a set of voluntary guidelines regarding the use of recombinant technology. [31] As the technology improved the US established a committee at the Office of Science and Technology, [150] which assigned regulatory approval of GM food to the USDA, FDA and EPA. [151] The Cartagena Protocol on Biosafety, an international treaty that governs the transfer, handling, and use of GMOs, [152] was adopted on 29 January 2000. [153] One hundred and fifty-seven countries are members of the Protocol, and many use it as a reference point for their own regulations. [154]

The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation. [155] [156] [157] [158] Some countries allow the import of GM food with authorisation, but either do not allow its cultivation (Russia, Norway, Israel) or have provisions for cultivation even though no GM products are yet produced (Japan, South Korea). Most countries that do not allow GMO cultivation do permit research. [159] Some of the most marked differences occur between the US and Europe. The US policy focuses on the product (not the process), only looks at verifiable scientific risks and uses the concept of substantial equivalence. [160] The European Union by contrast has possibly the most stringent GMO regulations in the world. [161] All GMOs, along with irradiated food, are considered "new food" and subject to extensive, case-by-case, science-based food evaluation by the European Food Safety Authority. The criteria for authorisation fall in four broad categories: "safety", "freedom of choice", "labelling", and "traceability". [162] The level of regulation in other countries that cultivate GMOs lie in between Europe and the United States.

Regulatory agencies by geographical region
RegionRegulatorsNotes
US USDA, FDA and EPA [151]
Europe European Food Safety Authority [162]
Canada Health Canada and the Canadian Food Inspection Agency [163] [164] Regulated products with novel features regardless of method of origin [165] [166]
Africa Common Market for Eastern and Southern Africa [167] Final decision lies with each individual country. [167]
ChinaOffice of Agricultural Genetic Engineering Biosafety Administration [168]
IndiaInstitutional Biosafety Committee, Review Committee on Genetic Manipulation and Genetic Engineering Approval Committee [169]
ArgentinaNational Agricultural Biotechnology Advisory Committee (environmental impact), the National Service of Health and Agrifood Quality (food safety) and the National Agribusiness Direction (effect on trade) [170] Final decision made by the Secretariat of Agriculture, Livestock, Fishery and Food. [170]
BrazilNational Biosafety Technical Commission (environmental and food safety) and the Council of Ministers (commercial and economical issues) [170]
Australia Office of the Gene Technology Regulator (oversees all GM products), Therapeutic Goods Administration (GM medicines) and Food Standards Australia New Zealand (GM food). [171] [172] The individual state governments can then assess the impact of release on markets and trade and apply further legislation to control approved genetically modified products. [172]

One of the key issues concerning regulators is whether GM products should be labeled. The European Commission says that mandatory labeling and traceability are needed to allow for informed choice, avoid potential false advertising [173] and facilitate the withdrawal of products if adverse effects on health or the environment are discovered. [174] The American Medical Association [175] and the American Association for the Advancement of Science [176] say that absent scientific evidence of harm even voluntary labeling is misleading and will falsely alarm consumers. Labeling of GMO products in the marketplace is required in 64 countries. [177] Labeling can be mandatory up to a threshold GM content level (which varies between countries) or voluntary. In Canada and the US labeling of GM food is voluntary, [178] while in Europe all food (including processed food) or feed which contains greater than 0.9% of approved GMOs must be labelled. [161]

Controversy

Critics have objected to the use of genetic engineering on several grounds, including ethical, ecological and economic concerns. Many of these concerns involve GM crops and whether food produced from them is safe and what impact growing them will have on the environment. These controversies have led to litigation, international trade disputes, and protests, and to restrictive regulation of commercial products in some countries. [179]

Accusations that scientists are "playing God" and other religious issues have been ascribed to the technology from the beginning. [180] Other ethical issues raised include the patenting of life, [181] the use of intellectual property rights, [182] the level of labeling on products, [183] [184] control of the food supply [185] and the objectivity of the regulatory process. [186] Although doubts have been raised, [187] economically most studies have found growing GM crops to be beneficial to farmers. [188] [189] [190]

Gene flow between GM crops and compatible plants, along with increased use of selective herbicides, can increase the risk of "superweeds" developing. [191] Other environmental concerns involve potential impacts on non-target organisms, including soil microbes, [192] and an increase in secondary and resistant insect pests. [193] [194] Many of the environmental impacts regarding GM crops may take many years to be understood and are also evident in conventional agriculture practices. [192] [195] With the commercialisation of genetically modified fish there are concerns over what the environmental consequences will be if they escape. [196]

There are three main concerns over the safety of genetically modified food: whether they may provoke an allergic reaction; whether the genes could transfer from the food into human cells; and whether the genes not approved for human consumption could outcross to other crops. [197] There is a scientific consensus [198] [199] [200] [201] that currently available food derived from GM crops poses no greater risk to human health than conventional food, [202] [203] [204] [205] [206] but that each GM food needs to be tested on a case-by-case basis before introduction. [207] [208] [209] Nonetheless, members of the public are less likely than scientists to perceive GM foods as safe. [210] [211] [212] [213]

Genetic engineering features in many science fiction stories. [214] Frank Herbert's novel The White Plague describes the deliberate use of genetic engineering to create a pathogen which specifically kills women. [214] Another of Herbert's creations, the Dune series of novels, uses genetic engineering to create the powerful Tleilaxu. [215] Few films have informed audiences about genetic engineering, with the exception of the 1978 The Boys from Brazil and the 1993 Jurassic Park , both of which make use of a lesson, a demonstration, and a clip of scientific film. [216] [217] Genetic engineering methods are weakly represented in film; Michael Clark, writing for the Wellcome Trust, calls the portrayal of genetic engineering and biotechnology "seriously distorted" [217] in films such as The 6th Day . In Clark's view, the biotechnology is typically "given fantastic but visually arresting forms" while the science is either relegated to the background or fictionalised to suit a young audience. [217]

See also

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The term modifications in genetics refers to both naturally occurring and engineered changes in DNA. Incidental, or natural mutations occur through errors during replication and repair, either spontaneously or due to environmental stressors. Intentional modifications are done in a laboratory for various purposes, developing hardier seeds and plants, and increasingly to treat human disease. The use of gene editing technology remains controversial.

<span class="mw-page-title-main">Genetically modified crops</span> Plants used in agriculture

Genetically modified crops are plants used in agriculture, the DNA of which has been modified using genetic engineering methods. Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. In most cases, the aim is to introduce a new trait to the plant which does not occur naturally in the species. Examples in food crops include resistance to certain pests, diseases, environmental conditions, reduction of spoilage, resistance to chemical treatments, or improving the nutrient profile of the crop. Examples in non-food crops include production of pharmaceutical agents, biofuels, and other industrially useful goods, as well as for bioremediation.

A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the phenotype of an organism. Transgene describes a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. This non-native segment of DNA may either retain the ability to produce RNA or protein in the transgenic organism or alter the normal function of the transgenic organism's genetic code. In general, the DNA is incorporated into the organism's germ line. For example, in higher vertebrates this can be accomplished by injecting the foreign DNA into the nucleus of a fertilized ovum. This technique is routinely used to introduce human disease genes or other genes of interest into strains of laboratory mice to study the function or pathology involved with that particular gene.

<span class="mw-page-title-main">Genetically modified food controversies</span>

Genetically modified food controversies are disputes over the use of foods and other goods derived from genetically modified crops instead of conventional crops, and other uses of genetic engineering in food production. The disputes involve consumers, farmers, biotechnology companies, governmental regulators, non-governmental organizations, and scientists. The key areas of controversy related to genetically modified food are whether such food should be labeled, the role of government regulators, the objectivity of scientific research and publication, the effect of genetically modified crops on health and the environment, the effect on pesticide resistance, the impact of such crops for farmers, and the role of the crops in feeding the world population. In addition, products derived from GMO organisms play a role in the production of ethanol fuels and pharmaceuticals.

<span class="mw-page-title-main">Gene targeting</span> Genetic technique that uses homologous recombination to change an endogenous gene

Gene targeting is a biotechnological tool used to change the DNA sequence of an organism. It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombination. Gene targeting can be used to make a range of sizes of DNA edits, from larger DNA edits such as inserting entire new genes into an organism, through to much smaller changes to the existing DNA such as a single base-pair change. Gene targeting relies on the presence of a repair template to introduce the user-defined edits to the DNA. The user will design the repair template to contain the desired edit, flanked by DNA sequence corresponding (homologous) to the region of DNA that the user wants to edit; hence the edit is targeted to a particular genomic region. In this way Gene Targeting is distinct from natural homology-directed repair, during which the ‘natural’ DNA repair template of the sister chromatid is used to repair broken DNA. The alteration of DNA sequence in an organism can be useful in both a research context – for example to understand the biological role of a gene – and in biotechnology, for example to alter the traits of an organism.

<span class="mw-page-title-main">Genetically modified plant</span> Plants with human-introduced genes from other organisms

Genetically modified plants have been engineered for scientific research, to create new colours in plants, deliver vaccines, and to create enhanced crops. Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. Many plant cells are pluripotent, meaning that a single cell from a mature plant can be harvested and then under the right conditions form a new plant. This ability is most often taken advantage by genetic engineers through selecting cells that can successfully be transformed into an adult plant which can then be grown into multiple new plants containing transgene in every cell through a process known as tissue culture.

<span class="mw-page-title-main">Plant genetics</span> Study of genes and heredity in plants

Plant genetics is the study of genes, genetic variation, and heredity specifically in plants. It is generally considered a field of biology and botany, but intersects frequently with many other life sciences and is strongly linked with the study of information systems. Plant genetics is similar in many ways to animal genetics but differs in a few key areas.

<span class="mw-page-title-main">Genetically modified animal</span> Animal that has been genetically modified

Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at the research stage while the number close to entering the market remains small.

<span class="mw-page-title-main">Genetically modified bacteria</span> First organisms to be modified in the laboratory

Genetically modified bacteria were the first organisms to be modified in the laboratory, due to their simple genetics. These organisms are now used for several purposes, and are particularly important in producing large amounts of pure human proteins for use in medicine.

<span class="mw-page-title-main">Genetically modified soybean</span> Soybean that has had DNA introduced into it using genetic engineering techniques

A genetically modified soybean is a soybean that has had DNA introduced into it using genetic engineering techniques. In 1996, the first genetically modified soybean was introduced to the U.S. by Monsanto. In 2014, 90.7 million hectares of GM soybeans were planted worldwide, making up 82% of the total soybeans cultivation area.

Genetically modified canola is a genetically modified crop. The first strain, Roundup Ready canola, was developed by Monsanto for tolerance to glyphosate, the active ingredient in the commonly used herbicide Roundup.

<span class="mw-page-title-main">Genetically modified tomato</span> Tomato with modified genes

A genetically modified tomato, or transgenic tomato, is a tomato that has had its genes modified, using genetic engineering. The first trial genetically modified food was a tomato engineered to have a longer shelf life, which was on the market briefly beginning on May 21, 1994. The first direct consumption tomato was approved in Japan in 2021. Primary work is focused on developing tomatoes with new traits like increased resistance to pests or environmental stresses. Other projects aim to enrich tomatoes with substances that may offer health benefits or be more nutritious. As well as aiming to produce novel crops, scientists produce genetically modified tomatoes to understand the function of genes naturally present in tomatoes.

<span class="mw-page-title-main">Regulation of genetic engineering</span>

The regulation of genetic engineering varies widely by country. Countries such as the United States, Canada, Lebanon and Egypt use substantial equivalence as the starting point when assessing safety, while many countries such as those in the European Union, Brazil and China authorize GMO cultivation on a case-by-case basis. Many countries allow the import of GM food with authorization, but either do not allow its cultivation or have provisions for cultivation, but no GM products are yet produced. Most countries that do not allow for GMO cultivation do permit research. Most (85%) of the world's GMO crops are grown in the Americas. One of the key issues concerning regulators is whether GM products should be labeled. Labeling of GMO products in the marketplace is required in 64 countries. Labeling can be mandatory up to a threshold GM content level or voluntary. A study investigating voluntary labeling in South Africa found that 31% of products labeled as GMO-free had a GM content above 1.0%. In Canada and the US labeling of GM food is voluntary, while in Europe all food or feed which contains greater than 0.9% of approved GMOs must be labelled.

<span class="mw-page-title-main">History of genetic engineering</span>

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.

<span class="mw-page-title-main">Genetic engineering techniques</span> Methods used to change the DNA of organisms

Genetic engineering techniques allow the modification of animal and plant genomes. Techniques have been devised to insert, delete, and modify DNA at multiple levels, ranging from a specific base pair in a specific gene to entire genes. There are a number of steps that are followed before a genetically modified organism (GMO) is created. Genetic engineers must first choose what gene they wish to insert, modify, or delete. The gene must then be isolated and incorporated, along with other genetic elements, into a suitable vector. This vector is then used to insert the gene into the host genome, creating a transgenic or edited organism.

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  200. ↑ Ronald P (May 2011). "Plant genetics, sustainable agriculture and global food security". Genetics. 188 (1): 11–20. doi:10.1534/genetics.111.128553. PMC   3120150 . PMID   21546547. There is broad scientific consensus that genetically engineered crops currently on the market are safe to eat. After 14 years of cultivation and a cumulative total of 2 billion acres planted, no adverse health or environmental effects have resulted from commercialization of genetically engineered crops (Board on Agriculture and Natural Resources, Committee on Environmental Impacts Associated with Commercialization of Transgenic Plants, National Research Council and Division on Earth and Life Studies 2002). Both the U.S. National Research Council and the Joint Research Centre (the European Union's scientific and technical research laboratory and an integral part of the European Commission) have concluded that there is a comprehensive body of knowledge that adequately addresses the food safety issue of genetically engineered crops (Committee on Identifying and Assessing Unintended Effects of Genetically Engineered Foods on Human Health and National Research Council 2004; European Commission Joint Research Centre 2008). These and other recent reports conclude that the processes of genetic engineering and conventional breeding are no different in terms of unintended consequences to human health and the environment (European Commission Directorate-General for Research and Innovation 2010).
  201. ↑ But see also: Domingo JL, Giné Bordonaba J (May 2011). "A literature review on the safety assessment of genetically modified plants". Environment International. 37 (4): 734–42. Bibcode:2011EnInt..37..734D. doi:10.1016/j.envint.2011.01.003. PMID   21296423. In spite of this, the number of studies specifically focused on safety assessment of GM plants is still limited. However, it is important to remark that for the first time, a certain equilibrium in the number of research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was observed. Moreover, it is worth mentioning that most of the studies demonstrating that GM foods are as nutritional and safe as those obtained by conventional breeding, have been performed by biotechnology companies or associates, which are also responsible of commercializing these GM plants. Anyhow, this represents a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies.Krimsky S (2015). "An Illusory Consensus behind GMO Health Assessment" (PDF). Science, Technology, & Human Values. 40 (6): 883–914. doi:10.1177/0162243915598381. S2CID   40855100. Archived from the original (PDF) on 7 February 2016. Retrieved 30 October 2016. I began this article with the testimonials from respected scientists that there is literally no scientific controversy over the health effects of GMOs. My investigation into the scientific literature tells another story. And contrast: Panchin AY, Tuzhikov AI (March 2017). "Published GMO studies find no evidence of harm when corrected for multiple comparisons". Critical Reviews in Biotechnology. 37 (2): 213–217. doi:10.3109/07388551.2015.1130684. PMID   26767435. S2CID   11786594. Here, we show that a number of articles some of which have strongly and negatively influenced the public opinion on GM crops and even provoked political actions, such as GMO embargo, share common flaws in the statistical evaluation of the data. Having accounted for these flaws, we conclude that the data presented in these articles does not provide any substantial evidence of GMO harm. The presented articles suggesting possible harm of GMOs received high public attention. However, despite their claims, they actually weaken the evidence for the harm and lack of substantial equivalency of studied GMOs. We emphasize that with over 1783 published articles on GMOs over the last 10 years it is expected that some of them should have reported undesired differences between GMOs and conventional crops even if no such differences exist in reality. and Yang YT, Chen B (April 2016). "Governing GMOs in the USA: science, law and public health". Journal of the Science of Food and Agriculture. 96 (6): 1851–5. Bibcode:2016JSFA...96.1851Y. doi:10.1002/jsfa.7523. PMID   26536836. It is therefore not surprising that efforts to require labeling and to ban GMOs have been a growing political issue in the USA (citing Domingo and Bordonaba, 2011). Overall, a broad scientific consensus holds that currently marketed GM food poses no greater risk than conventional food... Major national and international science and medical associations have stated that no adverse human health effects related to GMO food have been reported or substantiated in peer-reviewed literature to date. Despite various concerns, today, the American Association for the Advancement of Science, the World Health Organization, and many independent international science organizations agree that GMOs are just as safe as other foods. Compared with conventional breeding techniques, genetic engineering is far more precise and, in most cases, less likely to create an unexpected outcome.
  202. ↑ "Statement by the AAAS Board of Directors on Labeling of Genetically Modified Foods" (PDF). American Association for the Advancement of Science. 20 October 2012. Retrieved 8 February 2016. The EU, for example, has invested more than €300 million in research on the biosafety of GMOs. Its recent report states: "The main conclusion to be drawn from the efforts of more than 130 research projects, covering a period of more than 25 years of research and involving more than 500 independent research groups, is that biotechnology, and in particular GMOs, are not per se more risky than e.g. conventional plant breeding technologies." The World Health Organization, the American Medical Association, the U.S. National Academy of Sciences, the British Royal Society, and every other respected organization that has examined the evidence has come to the same conclusion: consuming foods containing ingredients derived from GM crops is no riskier than consuming the same foods containing ingredients from crop plants modified by conventional plant improvement techniques.Pinholster G (25 October 2012). "AAAS Board of Directors: Legally Mandating GM Food Labels Could "Mislead and Falsely Alarm Consumers"". American Association for the Advancement of Science. Retrieved 8 February 2016.
  203. ↑ European Commission. Directorate-General for Research (2010). A decade of EU-funded GMO research (2001–2010) (PDF). Directorate-General for Research and Innovation. Biotechnologies, Agriculture, Food. European Commission, European Union. doi:10.2777/97784. ISBN   978-92-79-16344-9. Archived (PDF) from the original on 24 December 2010. Retrieved 8 February 2016.
  204. ↑ "AMA Report on Genetically Modified Crops and Foods (online summary)". American Medical Association. January 2001. Retrieved 19 March 2016. A report issued by the scientific council of the American Medical Association (AMA) says that no long-term health effects have been detected from the use of transgenic crops and genetically modified foods, and that these foods are substantially equivalent to their conventional counterparts. (from online summary prepared by ISAAA)" "Crops and foods produced using recombinant DNA techniques have been available for fewer than 10 years and no long-term effects have been detected to date. These foods are substantially equivalent to their conventional counterparts. "Report 2 of the Council on Science and Public Health (A-12): Labeling of Bioengineered Foods" (PDF). American Medical Association. 2012. Archived from the original on 7 September 2012. Retrieved 19 March 2016. Bioengineered foods have been consumed for close to 20 years, and during that time, no overt consequences on human health have been reported and/or substantiated in the peer-reviewed literature.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  205. ↑ "Restrictions on Genetically Modified Organisms: United States. Public and Scholarly Opinion". Library of Congress. 9 June 2015. Retrieved 8 February 2016. Several scientific organizations in the US have issued studies or statements regarding the safety of GMOs indicating that there is no evidence that GMOs present unique safety risks compared to conventionally bred products. These include the National Research Council, the American Association for the Advancement of Science, and the American Medical Association. Groups in the US opposed to GMOs include some environmental organizations, organic farming organizations, and consumer organizations. A substantial number of legal academics have criticized the US's approach to regulating GMOs.
  206. ↑ National Academies of Sciences, Engineering; Division on Earth Life Studies; Board on Agriculture Natural Resources; Committee on Genetically Engineered Crops: Past Experience Future Prospects (2016). Genetically Engineered Crops: Experiences and Prospects. The National Academies of Sciences, Engineering, and Medicine (US). p. 149. doi:10.17226/23395. ISBN   978-0-309-43738-7. PMID   28230933 . Retrieved 19 May 2016. Overall finding on purported adverse effects on human health of foods derived from GE crops: On the basis of detailed examination of comparisons of currently commercialized GE with non-GE foods in compositional analysis, acute and chronic animal toxicity tests, long-term data on health of livestock fed GE foods, and human epidemiological data, the committee found no differences that implicate a higher risk to human health from GE foods than from their non-GE counterparts.
  207. ↑ "Frequently asked questions on genetically modified foods". World Health Organization. Retrieved 8 February 2016. Different GM organisms include different genes inserted in different ways. This means that individual GM foods and their safety should be assessed on a case-by-case basis and that it is not possible to make general statements on the safety of all GM foods. GM foods currently available on the international market have passed safety assessments and are not likely to present risks for human health. In addition, no effects on human health have been shown as a result of the consumption of such foods by the general population in the countries where they have been approved. Continuous application of safety assessments based on the Codex Alimentarius principles and, where appropriate, adequate post market monitoring, should form the basis for ensuring the safety of GM foods.
  208. ↑ Haslberger AG (July 2003). "Codex guidelines for GM foods include the analysis of unintended effects". Nature Biotechnology. 21 (7): 739–41. doi:10.1038/nbt0703-739. PMID   12833088. S2CID   2533628. These principles dictate a case-by-case premarket assessment that includes an evaluation of both direct and unintended effects.
  209. ↑ Some medical organizations, including the British Medical Association, advocate further caution based upon the precautionary principle: "Genetically modified foods and health: a second interim statement" (PDF). British Medical Association. March 2004. Archived (PDF) from the original on 22 March 2014. Retrieved 21 March 2016. In our view, the potential for GM foods to cause harmful health effects is very small and many of the concerns expressed apply with equal vigour to conventionally derived foods. However, safety concerns cannot, as yet, be dismissed completely on the basis of information currently available. When seeking to optimise the balance between benefits and risks, it is prudent to err on the side of caution and, above all, learn from accumulating knowledge and experience. Any new technology such as genetic modification must be examined for possible benefits and risks to human health and the environment. As with all novel foods, safety assessments in relation to GM foods must be made on a case-by-case basis. Members of the GM jury project were briefed on various aspects of genetic modification by a diverse group of acknowledged experts in the relevant subjects. The GM jury reached the conclusion that the sale of GM foods currently available should be halted and the moratorium on commercial growth of GM crops should be continued. These conclusions were based on the precautionary principle and lack of evidence of any benefit. The Jury expressed concern over the impact of GM crops on farming, the environment, food safety and other potential health effects. The Royal Society review (2002) concluded that the risks to human health associated with the use of specific viral DNA sequences in GM plants are negligible, and while calling for caution in the introduction of potential allergens into food crops, stressed the absence of evidence that commercially available GM foods cause clinical allergic manifestations. The BMA shares the view that there is no robust evidence to prove that GM foods are unsafe but we endorse the call for further research and surveillance to provide convincing evidence of safety and benefit.
  210. ↑ Funk C, Rainie L (29 January 2015). "Public and Scientists' Views on Science and Society". Pew Research Center. Archived from the original on 9 January 2019. Retrieved 24 February 2016. The largest differences between the public and the AAAS scientists are found in beliefs about the safety of eating genetically modified (GM) foods. Nearly nine-in-ten (88%) scientists say it is generally safe to eat GM foods compared with 37% of the general public, a difference of 51 percentage points.
  211. ↑ Marris C (July 2001). "Public views on GMOs: deconstructing the myths. Stakeholders in the GMO debate often describe public opinion as irrational. But do they really understand the public?". EMBO Reports. 2 (7): 545–8. doi:10.1093/embo-reports/kve142. PMC   1083956 . PMID   11463731.
  212. ↑ Final Report of the PABE research project (December 2001). "Public Perceptions of Agricultural Biotechnologies in Europe". Commission of European Communities. Retrieved 24 February 2016.
  213. ↑ Scott SE, Inbar Y, Rozin P (May 2016). "Evidence for Absolute Moral Opposition to Genetically Modified Food in the United States". Perspectives on Psychological Science. 11 (3): 315–324. doi:10.1177/1745691615621275. PMID   27217243. S2CID   261060.
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