Genetic engineering, also calledgenetic modification orgenetic manipulation, is the modification and manipulation of an organism'sgenes usingtechnology. It is a set oftechnologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novelorganisms. NewDNA is obtained by either isolating and copying the genetic material of interest usingrecombinant DNA methods or byartificially synthesising the DNA. Aconstruct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made byPaul Berg in 1972 by combining DNA from the monkey virusSV40 with thelambda virus. As well as insertinggenes, the process can be used to remove, or "knock out", genes. The new DNA can either be inserted randomly ortargeted to a specific part of thegenome.[1]
An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is agenetically modified organism (GMO). The first GMO was abacterium generated byHerbert Boyer andStanley Cohen in 1973.Rudolf Jaenisch created the first GM animal when he inserted foreign DNA into amouse in 1974. The first company to focus on genetic engineering,Genentech, was founded in 1976 and started the production of human proteins. Genetically engineered humaninsulin was produced in 1978 and insulin-producing bacteria were commercialised in 1982.Genetically modified food has been sold since 1994, with the release of theFlavr 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 theUnited States in December 2003. In 2016salmon 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 createanimal model organisms of human diseases. As well as producing hormones, vaccines and other drugs, genetic engineering has the potential to cure genetic diseases throughgene therapy.Chinese hamster ovary (CHO) cells are used in industrial genetic engineering. AdditionallymRNA vaccines are made through genetic engineering to prevent infections by viruses such asCOVID-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 commercialisedgenetically modified crops has provided economic benefit to farmers in many different countries, but has also been the source of most of thecontroversy surrounding the technology. This has been present since its early use; the first field trials were destroyed by anti-GM activists. Although there is ascientific 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 andintellectual 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, theCartagena 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 andEurope.
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.
Comparison of conventional plant breeding withtransgenic andcisgenic genetic modification
Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducingDNA, or modifying existing genetic material in situ. Unlike traditionalanimal andplant breeding, which involves doing multiple crosses and then selecting for the organism with the desiredphenotype, genetic engineering takes thegene 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 differentdomains) and prevents other undesirable genes from also being added.[4]
Genetic engineering could potentially fix severegenetic 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 aidfood security by increasing yield, nutritional value and tolerance to environmental stresses.[8]
The DNA can be introduced directly into thehost organism or into a cell that is thenfused orhybridised with the host.[9] This relies onrecombinant nucleic acid techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through avector system or directly throughmicro-injection, macro-injection ormicro-encapsulation.
Genetic engineering does not normally include traditional breeding,in vitro fertilisation, induction ofpolyploidy,mutagenesis and cell fusion techniques that do not use recombinantnucleic acids or agenetically modified organism in the process.[9] However, some broad definitions of genetic engineering includeselective breeding.[10]Cloning andstem 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 termedgenetically modified organisms or GMOs.[14] If genetic material from another species is added to the host, the resulting organism is calledtransgenic. If genetic material from the same species or a species that can naturally breed with the host is used the resulting organism is calledcisgenic.[15] If genetic engineering is used to remove genetic material from the target organism the resulting organism is termed aknockout organism.[16] In Europe genetic modification issynonymous 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]
Humans have altered the genomes of species for thousands of years throughselective breeding, or artificial selection[20]: 1 [21]: 1 as contrasted withnatural 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 geneticistNikolay 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 novelDragon's Island, published in 1951[23] – one year before DNA's role inheredity was confirmed byAlfred Hershey andMartha Chase,[24] and two years beforeJames Watson andFrancis Crick showed that theDNA molecule has a double-helix structure – though the general concept of direct genetic manipulation was explored in rudimentary form inStanley G. Weinbaum's 1936 science fiction storyProteus Island.[25][26]
In 1983, a biotech company, Advanced Genetic Sciences (AGS) applied for U.S. government authorisation to perform field tests with theice-minus strain ofPseudomonas 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 ofP. syringae became the firstgenetically 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 ofgenetically engineered plants occurred in France and the US in 1986, tobacco plants were engineered to be resistant toherbicides.[39] The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992.[40] In 1994Calgene attained approval to commercially release the firstgenetically modified food, theFlavr Savr, a tomato engineered to have a longer shelf life.[41] In 1994, the European Union approved tobacco engineered to be resistant to the herbicidebromoxynil, making it the first genetically engineered crop commercialised in Europe.[42] In 1995,Bt potato was approved safe by theEnvironmental 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]
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 ofmicroarrays,transcriptomics andgenome sequencing has made it much easier to find suitable genes.[52] Luck also plays its part; theRoundup Ready gene was discovered after scientists noticed a bacterium thriving in the presence of the herbicide.[53]
The next step is to isolate the candidate gene. Thecell containing the gene is opened and the DNA is purified.[54] The gene is separated by usingrestriction enzymes to cut the DNA into fragments[55] orpolymerase chain reaction (PCR) to amplify up the gene segment.[56] These segments can then be extracted throughgel electrophoresis. If the chosen gene or the donor organism'sgenome has been well studied it may already be accessible from agenetic library. If theDNA sequence is known, but no copies of the gene are available, it can also beartificially synthesised.[57] Once isolated the gene isligated into aplasmid that is then inserted into a bacterium. The plasmid is replicated when the bacteria divide, ensuring unlimited copies of the gene are available.[58] TheRK2 plasmid is notable for its ability to replicate in a wide variety ofsingle-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 apromoter andterminator region, which initiate and endtranscription. Aselectable marker gene is added, which in most cases confersantibiotic 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 usingrecombinant DNA techniques, such asrestriction digests, ligations and molecular cloning.[60]
A gene gun usesbiolistics to insert DNA into plant tissue.
There are a number of techniques used to insert genetic material into the host genome. Some bacteria can naturallytake 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 asextrachromosomal DNA. DNA is generally inserted into animal cells usingmicroinjection, where it can be injected through the cell'snuclear envelope directly into thenucleus, or through the use ofviral vectors.[61]
Plant genomes can be engineered by physical methods or by use ofAgrobacterium for the delivery of sequences hosted inT-DNA binary vectors. In plants the DNA is often inserted usingAgrobacterium-mediated transformation,[62] taking advantage of theAgrobacteriumsT-DNA sequence that allows natural insertion of genetic material into plant cells.[63] Other methods includebiolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells,[64] andelectroporation, 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 beregenerated from that single cell. In plants this is accomplished through the use oftissue culture.[65][66] In animals it is necessary to ensure that the inserted DNA is present in theembryonic stem cells.[62] 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.[67]
Further testing using PCR,Southern hybridization, andDNA sequencing is conducted to confirm that an organism contains the new gene.[68] 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 beexpressed at appropriate levels in the target tissue so methods that look for and measure the gene products (RNA and protein) are also used. These includenorthern hybridisation, quantitativeRT-PCR,Western blot,immunofluorescence,ELISA and phenotypic analysis.[69]
The new genetic material can be inserted randomly within the host genome or targeted to a specific location. The technique ofgene targeting useshomologous recombination to make desired changes to a specificendogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use ofselectable markers. The frequency of gene targeting can be greatly enhanced throughgenome editing. Genome editing uses artificially engineerednucleases that create specificdouble-stranded breaks at desired locations in the genome, and use the cell's endogenous mechanisms to repair the induced break by the natural processes ofhomologous recombination andnonhomologous end-joining. There are four families of engineered nucleases:meganucleases,[70][71]zinc finger nucleases,[72][73]transcription activator-like effector nucleases (TALENs),[74][75] and the Cas9-guideRNA system (adapted fromCRISPR).[76][77] TALEN and CRISPR are the two most commonly used and each has its own advantages.[78] TALENs have greater target specificity, while CRISPR is easier to design and more efficient.[78] In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate agene knockout.[79][80]
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 othersubstrates.[81][82] Plants have been modified for insect protection,herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production ofedible vaccines.[83] Most commercialised GMOs are insect resistant or herbicide tolerant crop plants.[84] Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. The genetically modified animals include animals withgenes knocked out,increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk.[85]
Genetic engineering is also used to create animal models of human diseases.Genetically modified mice are the most common genetically engineered animal model.[90] They have been used to study and model cancer (theoncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease.[91] Potential cures can be tested against these mouse models.
Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community.[99][100] In 2015, CRISPR was used to edit the DNA of non-viablehuman embryos,[101][102] leading scientists of major world academies to call for a moratorium on inheritable human genome edits.[103] 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.[104] The distinction between cure and enhancement can also be difficult to establish.[105] In November 2018,He Jiankui announced that he hadedited the genomes of two human embryos, to attempt to disable theCCR5 gene, which codes for a receptor thatHIV uses to enter cells. The work was widely condemned as unethical, dangerous, and premature.[106] 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.[107]
Researchers are altering the genome of pigs to induce the growth of human organs, with the aim of increasing the success ofpig to human organ transplantation.[108] 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.[109]
Genetic engineering is an important tool fornatural scientists, with the creation of transgenic organisms one of the most important tools for analysis of gene function.[110] Genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creatinggenetically 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.[111]
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.
Loss of function experiments, such as in agene knockout experiment, in which an organism is engineered to lack the activity of one or more genes. In a simple knockout a copy of the desired gene has been altered to make it non-functional.Embryonic stem cells incorporate the altered gene, which replaces the already present functional copy. These stem cells are injected intoblastocysts, which are implanted into surrogate mothers. This allows the experimenter to analyse the defects caused by thismutation and thereby determine the role of particular genes. It is used especially frequently indevelopmental biology.[112] When this is done by creating a library of genes with point mutations at every position in the area of interest, or even every position in the whole gene, this is called "scanning mutagenesis". The simplest method, and the first to be used, is "alanine scanning", where every position in turn is mutated to the unreactive amino acidalanine.[113]
Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently. Gain of function is used to tell whether or not a protein is sufficient for a function, but does not always mean it is required, especially when dealing with genetic or functional redundancy.[112]
Tracking experiments, which seek to gain information about the localisation and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such asgreen fluorescent protein (GFP) that will allow easy visualisation of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences that will serve as binding motifs to monoclonal antibodies.[112]
Expression studies aim to discover where and when specific proteins are produced. In these experiments, the DNA sequence before the DNA that codes for a protein, known as a gene'spromoter, is reintroduced into an organism with the protein coding region replaced by a reporter gene such as GFP or an enzyme that catalyses the production of a dye. Thus the time and place where a particular protein is produced can be observed. Expression studies can be taken a step further by altering the promoter to find which pieces are crucial for the proper expression of the gene and are actually bound by transcription factor proteins; this process is known aspromoter bashing.[114]
Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they willoverexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism inbioreactor equipment usingindustrial fermentation, and thenpurifying the protein.[115] Some genes do not work well in bacteria, so yeast, insect cells or mammalian cells can also be used.[116] These techniques are used to produce medicines such asinsulin,human growth hormone, andvaccines, supplements such astryptophan, aid in the production of food (chymosin in cheese making) and fuels.[117] Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as makingbiofuels,[118] cleaning up oil spills, carbon and other toxic waste[119] and detecting arsenic in drinking water.[120] Certain genetically modified microbes can also be used inbiomining andbioremediation, due to their ability to extract heavy metals from their environment and incorporate them into compounds that are more easily recoverable.[121]
Inmaterials science, a genetically modified virus has been used in a research laboratory as a scaffold for assembling a more environmentally friendlylithium-ion battery.[122][123] Bacteria have also been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions.[124]
The first crops to be released commercially on a large scale provided protection from insect pests or tolerance toherbicides. Fungal and virus resistant crops have also been developed or are in development.[127][128] This makes the insect and weed management of crops easier and can indirectly increase crop yield.[129][130] 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.[131] In 2016Salmon have been genetically modified with growth hormones to reach normal adult size much faster.[132]
GMOs have been developed that modify the quality of produce by increasing the nutritional value or providing more industrially useful qualities or quantities.[131] TheAmflora potato produces a more industrially useful blend of starches.Soybeans andcanola have been genetically modified to produce more healthy oils.[133][134] The first commercialised GM food was atomato that had delayed ripening, increasing itsshelf life.[135]
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.[136] 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.[137][138]
Genetic engineering has potential applications in conservation and natural area management. Gene transfer throughviral vectors has been proposed as a means of controlling invasive species as well as vaccinating threatened fauna from disease.[139] Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations.[140] With the increasing risks ofmaladaptation in organisms as a result ofclimate change and other perturbations, facilitated adaptation through gene tweaking could be one solution to reducing extinction risks.[141] 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 createmicrobial art.[142] Some bacteria have been genetically engineered to create black and white photographs.[143] Novelty items such as lavender-coloredcarnations,[144]blue roses,[145] andglowing fish,[146][147] have also been produced through genetic engineering.
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, atAsilomar, California.[148] TheAsilomar meeting recommended a set of voluntary guidelines regarding the use of recombinant technology.[31] As the technology improved the US established a committee at theOffice of Science and Technology,[149] which assigned regulatory approval of GM food to the USDA, FDA and EPA.[150] TheCartagena Protocol on Biosafety, an international treaty that governs the transfer, handling, and use of GMOs,[151] was adopted on 29 January 2000.[152] One hundred and fifty-seven countries are members of the Protocol, and many use it as a reference point for their own regulations.[153]
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.[154][155][156][157] 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.[158] 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 ofsubstantial equivalence.[159] TheEuropean Union by contrast has possibly the most stringent GMO regulations in the world.[160] All GMOs, along withirradiated food, are considered "new food" and subject to extensive, case-by-case, science-based food evaluation by theEuropean Food Safety Authority. The criteria for authorisation fall in four broad categories: "safety", "freedom of choice", "labelling", and "traceability".[161] The level of regulation in other countries that cultivate GMOs lie in between Europe and the United States.
Final decision lies with each individual country.[166]
China
Office of Agricultural Genetic Engineering Biosafety Administration[167]
India
Institutional Biosafety Committee, Review Committee on Genetic Manipulation and Genetic Engineering Approval Committee[168]
Argentina
National Agricultural Biotechnology Advisory Committee (environmental impact), the National Service of Health and Agrifood Quality (food safety) and the National Agribusiness Direction (effect on trade)[169]
Final decision made by the Secretariat of Agriculture, Livestock, Fishery and Food.[169]
Brazil
National Biosafety Technical Commission (environmental and food safety) and the Council of Ministers (commercial and economical issues)[169]
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.[171]
One of the key issues concerning regulators is whether GM products should be labeled. TheEuropean Commission says that mandatory labeling and traceability are needed to allow for informed choice, avoid potentialfalse advertising[172] and facilitate the withdrawal of products if adverse effects on health or the environment are discovered.[173] TheAmerican Medical Association[174] and theAmerican Association for the Advancement of Science[175] say that absent scientific evidence of harm even voluntary labeling ismisleading and will falsely alarm consumers. Labeling of GMO products in the marketplace is required in 64 countries.[176] 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,[177] while in Europe all food (includingprocessed food) orfeed which contains greater than 0.9% of approved GMOs must be labelled.[160]
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.[178]
Accusations that scientists are "playing God" and otherreligious issues have been ascribed to the technology from the beginning.[179] Other ethical issues raised include thepatenting of life,[180] the use ofintellectual property rights,[181] the level of labeling on products,[182][183] control of the food supply[184] and the objectivity of the regulatory process.[185] Although doubts have been raised,[186] economically most studies have found growing GM crops to be beneficial to farmers.[187][188][189]
Gene flow between GM crops and compatible plants, along with increased use of selectiveherbicides, can increase the risk of "superweeds" developing.[190] Other environmental concerns involve potential impacts on non-target organisms, includingsoil microbes,[191] and an increase in secondary and resistant insect pests.[192][193] Many of the environmental impacts regarding GM crops may take many years to be understood and are also evident in conventional agriculture practices.[191][194] With the commercialisation ofgenetically modified fish there are concerns over what the environmental consequences will be if they escape.[195]
There are three main concerns over the safety of genetically modified food: whether they may provoke anallergic reaction; whether the genes could transfer from the food into human cells; and whether the genes not approved for human consumption couldoutcross to other crops.[196] There is ascientific consensus[197][198][199][200] that currently available food derived from GM crops poses no greater risk to human health than conventional food,[201][202][203][204][205] but that each GM food needs to be tested on a case-by-case basis before introduction.[206][207][208] Nonetheless, members of the public are less likely than scientists to perceive GM foods as safe.[209][210][211][212]
Genetic engineering features in manyscience fiction stories.[25]Frank Herbert's novelThe White Plague describes the deliberate use of genetic engineering to create apathogen which specifically kills women.[25] Another of Herbert's creations, theDune series of novels, uses genetic engineering to create the powerfulTleilaxu.[213] Few films have informed audiences about genetic engineering, with the exception of the 1978The Boys from Brazil and the 1993Jurassic Park, both of which make use of a lesson, a demonstration, and a clip of scientific film.[214][215] Genetic engineering methods are weakly represented in film; Michael Clark, writing for theWellcome Trust, calls the portrayal of genetic engineering and biotechnology "seriously distorted"[215] in films such asThe 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.[215]
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^Forsberg, Cecil W. (23 April 2013)."Genetically Modified Foods".The Canadian Encyclopedia. Archived fromthe original on 18 September 2013. Retrieved4 October 2017.
^Evans, Brent and Lupescu, Mihai (15 July 2012)Canada – Agricultural Biotechnology Annual – 2012 GAIN (Global Agricultural Information Network) report CA12029, United States Department of Agriculture, Foreifn Agricultural Service, Retrieved 5 November 2012
^"Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September 2003 On Genetically Modified Food And Feed"(PDF).Official Journal of the European Union. The European Parliament and the Council of the European Union. 2003. Archived fromthe original(PDF) on 20 January 2014.The labeling should include objective information to the effect that a food or feed consists of, contains or is produced from GMOs. Clear labeling, irrespective of the detectability of DNA or protein resulting from the genetic modification in the final product, meets the demands expressed in numerous surveys by a large majority of consumers, facilitates informed choice and precludes potential misleading of consumers as regards methods of manufacture or production.
^Areal FJ, Riesgo L, Rodríguez-Cerezo E (1 February 2013). "Economic and agronomic impact of commercialized GM crops: a meta-analysis".The Journal of Agricultural Science.151 (1):7–33.doi:10.1017/S0021859612000111.S2CID85891950.
^Nicolia A, Manzo A, Veronesi F, Rosellini D (March 2014). "An overview of the last 10 years of genetically engineered crop safety research".Critical Reviews in Biotechnology.34 (1):77–88.doi:10.3109/07388551.2013.823595.PMID24041244.S2CID9836802.We have reviewed the scientific literature on GE crop safety for the last 10 years that catches the scientific consensus matured since GE plants became widely cultivated worldwide, and we can conclude that the scientific research conducted so far has not detected any significant hazard directly connected with the use of GM crops. The literature about Biodiversity and the GE food/feed consumption has sometimes resulted in animated debate regarding the suitability of the experimental designs, the choice of the statistical methods or the public accessibility of data. Such debate, even if positive and part of the natural process of review by the scientific community, has frequently been distorted by the media and often used politically and inappropriately in anti-GE crops campaigns.
^"State of Food and Agriculture 2003–2004. Agricultural Biotechnology: Meeting the Needs of the Poor. Health and environmental impacts of transgenic crops". Food and Agriculture Organization of the United Nations. Retrieved8 February 2016.Currently available transgenic crops and foods derived from them have been judged safe to eat and the methods used to test their safety have been deemed appropriate. These conclusions represent the consensus of the scientific evidence surveyed by the ICSU (2003) and they are consistent with the views of the World Health Organization (WHO, 2002). These foods have been assessed for increased risks to human health by several national regulatory authorities (inter alia, Argentina, Brazil, Canada, China, the United Kingdom and the United States) using their national food safety procedures (ICSU). To date no verifiable untoward toxic or nutritionally deleterious effects resulting from the consumption of foods derived from genetically modified crops have been discovered anywhere in the world (GM Science Review Panel). Many millions of people have consumed foods derived from GM plants – mainly maize, soybean and oilseed rape – without any observed adverse effects (ICSU).
^Ronald P (May 2011)."Plant genetics, sustainable agriculture and global food security".Genetics.188 (1):11–20.doi:10.1534/genetics.111.128553.PMC3120150.PMID21546547.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).
^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.PMID21296423.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.S2CID40855100. Archived fromthe original(PDF) on 7 February 2016. Retrieved30 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.PMID26767435.S2CID11786594.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.andYang 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.PMID26536836.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.
^"Statement by the AAAS Board of Directors on Labeling of Genetically Modified Foods"(PDF). American Association for the Advancement of Science. 20 October 2012. Retrieved8 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. Retrieved8 February 2016.
^"AMA Report on Genetically Modified Crops and Foods (online summary)". American Medical Association. January 2001. Retrieved19 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 byISAAA)" "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 fromthe original(PDF) on 7 September 2012. Retrieved19 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.
^"Restrictions on Genetically Modified Organisms: United States. Public and Scholarly Opinion". Library of Congress. 9 June 2015. Retrieved8 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.
^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.ISBN978-0-309-43738-7.PMID28230933. Retrieved19 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.
^"Frequently asked questions on genetically modified foods". World Health Organization. Retrieved8 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.
^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.PMID12833088.S2CID2533628.These principles dictate a case-by-case premarket assessment that includes an evaluation of both direct and unintended effects.
^Some medical organizations, including theBritish Medical Association, advocate further caution based upon theprecautionary 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. Retrieved21 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.
^Funk C, Rainie L (29 January 2015)."Public and Scientists' Views on Science and Society". Pew Research Center. Archived fromthe original on 9 January 2019. Retrieved24 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.
^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.PMID27217243.S2CID261060.
