Genetic rescue  is seen as a mitigation strategy designed to restore genetic diversity and reduce extinction risks in small, isolated and frequently inbred populations. [ 1 ]  It is largely implemented through translocation, a type of demographic rescue and technical migration that adds individuals to a population to prevent its potential extinction. This demographic rescue may be similar to genetic rescue, as each increase population size and/or fitness. This overlap in meaning has led some researchers to consider a more detailed definition for each type of rescue that details 'assessment and documentation of pre- and post-translocation genetic ancestry'. [ 1 ]  Not every example of genetic rescue is clearly successful and the current definition of genetic rescue does not mandate that the process result in a 'successful' outcome. Despite an ambiguous definition, genetic rescue is viewed positively, with many perceived successes. [ 2 ]


The conceptual foundation of genetic rescue can be traced back to the work of geneticist  Sewall Wright , who studied the effect of immigration among populations linked by gene flow. [ 3 ]  More recently, genetic rescue has been defined by scientific reviews as: "when population fitness, inferred from some demographic vital rate or phenotypic trait, increases by more than can be attributed to the demographic contribution of immigrants." [ 4 ] [ 5 ]  Genetic mixing leading to fitness recovery could be described as "genetic rescue", but perpetuates the unclear differences between genetic rescue and pollution.


When a species' population becomes too small, they are subject to genetic processes such as  inbreeding depression  from a lack of gene flow, allelic fixation from  genetic drift , and loss of diversity. In combination these can lead to a decrease in population fitness, and increase the risk of  extinction. [ 3 ]  Genetic rescue is a conservation tool which tries to address these genetic factors by moving genes from one population to another to increase the overall genetic diversity and minimize inbreeding. [ 6 ]   This conservation technique intended to increase the fitness of a small, imperiled population [ 2 ] [ 3 ]  through the introduction of beneficial alleles through migration. [ 2 ]  It is often used for populations of species that are at a high risk of extinction. A successful genetic rescue occurs when the addition of new genes effectively introduces genetic diversity that leads to increased population size and growth rate, as well as a greater population fitness. [ 2 ]  An unsuccessful genetic rescue may occur if the addition of new genes causes  outbreeding depression , which decreases their population fitness. [ 3 ]  Too much gene flow may lead to genetic swamping through extensive hybridization. [ 2 ]  Genetic rescue can occur through multiple pathways, including  heterosis  and  adaptive evolution . [ 2 ]  It is closely related to, but distinctly different from the concepts of  genetic pollution ,  evolutionary rescue ,  genetic restoration , and assisted gene flow. [ 2 ]


Gene flow (migration) is the introduction of new individuals (and genes) into a target population. [ 7 ]  Predicting the impact of a migrant on a population will depend on combination of complex genetic and non-genetic factors. Whether migration increases population fitness will depend if the genes brought in are adapted to local conditions and if they decrease levels of inbreeding in the target population. An Introduced individuals can also positively or negatively affect genetic rescue through behaviors such as  mate choice , dominance hierarchies, and infanticide. [ 3 ]


Genetic drift is the fixation of  alleles  by chance, hence reducing the overall diversity in the population. Genetic rescue can restore diversity by adding new genes to a population, counteracting fixation. [ 8 ]


Natural selection occurs when variations in heritable traits determines reproductive success of an individual, and thereby determines the persistence of that trait in that population. [ 9 ]  Genetic rescue may introduce traits that are advantageous to the target population or reduced the frequency of disadvantageous traits, increasing the net fitness of a population to ensure the continued survival as a species.


Genetic rescue can be a controversial tool because it is hard to predict how a population will be affected by a migration event. Genetic rescue has the possibility of actually lowering the fitness of a population by swamping the population or increasing rare deleterious alleles. [ 10 ]  This instance may simply be termed genetic pollution instead of being referred to genetic rescue. Rescue may also only be a short-term solution, as shown by the case of the Isle Royale Wolves. In that case, genetic rescue of the wolves resulted in a large initial increase in population fitness followed by a large decline in subsequent years. [ 10 ]  Many conservationists argue that genetic rescue could create unforeseen problems for species at risk, and that it overlooks the underlying problems that push so many species to the brink of extinction, including habitat loss due to human development. [ 11 ]


As with the term genetic pollution, 'genetic rescue' has political connotations. Some of the more controversial  practices which can be considered genetic rescue include


A case of successful genetic rescue can be observed in the  Florida panther  population. Habitat loss and other anthropogenic influences led to  small, inbred population which increased the decline of this population ( Puma concolor  cougar ), . [ 16 ]   Inbreeding depression  resulted in kinked tails and cowlicks, sperm defects, and heart abnormalities. [ 16 ]  The population reached a low of approximately 22 panthers. [ 3 ]  Fearing inevitable extinction, eight panthers from Texas were translocated to Florida in the mid 1990s. [ 16 ]  This effort was deemed successful after analysis showed a 4% annual population growth rate following the immigration event. [ 3 ]  Additionally, researchers found that the resulting hybrid kittens were three times more likely to survive to adulthood than “purebred” kittens. [ 16 ]  The Florida panther population increased from around 25 to over 100 individuals in roughly a decade. [ 4 ]


A case of unsuccessful genetic rescue can be observed in the  Isle Royale  wolf population. In 1997, a single wolf arrived on the island and bred with the wolf population of about 25 individuals. [ 10 ]  Initially, the addition of his genetic variation resulted in a positive effects on the population , shown by a large increase in population fitness. [ 10 ]  However, the addition of genetic variation by this immigrant was only beneficial in the short term. The population swiftly declined, with only two wolves sighted in 2016. [ 10 ]  it is possible that the new immigrant brought a new detrimental allele that increased in frequency as he interbred with the original population or that a single individual was insufficient to overcome the negative impact of genetic load. [ 10 ]


The  greater prairie chicken  is a ground-nesting bird with ecological and evolutionary hurdles that necessitated genetic rescue to avoid extinction. [ 1 ]  It was widely distributed across the North American great plains but now requires population management in small remnant areas. In Illinois, the greater prairie chicken declined from millions of individuals in the mid 19th century to 46 by 1998. This prompted genetic rescue efforts and movement of individuals from neighboring states to increase Illinois greater prairie chicken numbers. This has been considered an early and successful case of genetic rescue. Although the initial genetic rescue actions seem to have led to an increase in fitness, prairie habitat is now limiting recovery. Exclusively genetic efforts to rescue the species are considered insufficient and more focus on habitat protection may be required to save the species. [ 1 ]


Genetically modified agriculture  includes:


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. [ 1 ]


The process of genetically engineering mammals is a slow, tedious, and expensive process. [ 2 ]  As with other genetically modified organisms (GMOs), first genetic engineers must isolate the gene they wish to insert into the host organism. This can be taken from a  cell  containing the gene [ 3 ]  or  artificially synthesised . [ 4 ]  If the chosen gene or the donor organism's  genome  has been well studied it may already be accessible from a  genetic library . The  gene  is then combined with other genetic elements, including a  promoter  and  terminator  region and usually a  selectable marker . [ 5 ]


A number of techniques are available for  inserting the isolated gene into the host genome . With animals  DNA  is generally inserted into using  microinjection , where it can be injected through the cell's  nuclear envelope  directly into the  nucleus , or through the use of  viral vectors . [ 6 ]  The first transgenic animals were produced by injecting viral DNA into embryos and then implanting the embryos in females. [ 7 ]  It is necessary to ensure that the inserted DNA is present in the  embryonic stem cells . [ 8 ]  The embryo would develop and it would be hoped that some of the genetic material would be incorporated into the reproductive cells. Then researchers would have to wait until the animal reached breeding age and then offspring would be screened for presence of the gene in every cell, using  PCR ,  Southern hybridization , and  DNA sequencing . [ 9 ]


New technologies are making genetic modifications easier and more precise. [ 2 ]   Gene targeting  techniques, which creates  double-stranded breaks  and takes advantage on the  cells  natural  homologous recombination  repair systems, have been developed to target insertion to exact  locations .  Genome editing  uses artificially engineered  nucleases  that create breaks at specific points. There are four families of engineered nucleases:  meganucleases , [ 10 ] [ 11 ]   zinc finger nucleases , [ 12 ] [ 13 ]   transcription activator-like effector nucleases  (TALENs), [ 14 ] [ 15 ]  and the Cas9-guideRNA system (adapted from  CRISPR ). [ 16 ] [ 17 ]  TALEN and CRISPR are the two most commonly used and each has its own advantages. [ 18 ]  TALENs have greater target specificity, while CRISPR is easier to design and more efficient. [ 18 ]  The development of the  CRISPR-Cas9 gene editing  system has effectively halved the amount of time needed to develop genetically modified animals. [ 19 ]


Humans have  domesticated  animals since around 12,000 BCE, using  selective breeding  or artificial selection (as contrasted with  natural selection ). The process of  selective breeding , in which organisms with desired  traits  (and thus with the desired  genes ) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification [ 20 ] : 1   Various advancements in  genetics  allowed humans to directly alter the  DNA  and therefore genes of organisms. In 1972,  Paul Berg  created the first  recombinant DNA  molecule when he combined DNA from a  monkey virus  with that of the  lambda virus . [ 21 ] [ 22 ]


In 1974,  Rudolf Jaenisch  created a  transgenic mouse  by introducing foreign DNA into its  embryo , making it the world's first transgenic animal. [ 23 ] [ 24 ]  However it took another eight years before transgenic mice were developed that passed the  transgene  to their offspring. [ 25 ] [ 26 ]  Genetically modified mice were created in 1984 that carried cloned  oncogenes , predisposing them to developing cancer. [ 27 ]  Mice with genes  knocked out  ( knockout mouse ) were created in 1989. The first transgenic livestock were produced in 1985 [ 28 ]  and the first animal to synthesise transgenic proteins in their milk were mice, [ 29 ]  engineered to produce human tissue  plasminogen  activator in 1987. [ 30 ]


The first genetically modified animal to be commercialised was the  GloFish , a  Zebra fish  with a  fluorescent gene  added that allows it to glow in the dark under  ultraviolet light . [ 31 ]  It was released to the US market in 2003. [ 32 ]  The first genetically modified animal to be approved for food use was  AquAdvantage salmon  in 2015. [ 33 ]  The salmon were transformed with a  growth hormone -regulating gene from a  Pacific Chinook salmon  and a promoter from an  ocean pout  enabling it to grow year-round instead of only during spring and summer. [ 34 ]


GM mammals are created for research purposes, production of industrial or therapeutic products, agricultural uses or improving their health. There is also a market for creating genetically modified pets. [ 35 ]


Mammals are the best models for human disease, making genetic engineered ones vital to the discovery and development of cures and treatments for many serious diseases. Knocking out genes responsible for  human genetic disorders  allows researchers to study the mechanism of the disease and to test possible cures.  Genetically modified mice  have been the most common mammals used in  biomedical research , as they are cheap and easy to manipulate. Examples include  humanized mice  created by  xenotransplantation  of human gene products, so as to be utilized as murine  human-animal hybrids  for gaining relevant insights in the  in vivo  context for understanding of human-specific physiology and pathologies. [ 36 ]  Pigs are also a good target, because they have a similar body size, anatomical features,  physiology ,  pathophysiological  response, and diet. [ 37 ]  Nonhuman primates are the most similar model organisms to humans, but there is less public acceptance toward using them as research animals. [ 38 ]  In 2009, scientists announced that they had successfully transferred a gene into a  primate  species ( marmosets ) and produced a stable line of breeding transgenic primates for the first time. [ 39 ] [ 40 ]  Their first research target for these marmosets was  Parkinson's disease , but they were also considering  amyotrophic lateral sclerosis  and  Huntington's disease . [ 41 ]


Human proteins expressed in mammals are more likely to be similar to their natural counterparts than those expressed in plants or microorganisms. Stable expression has been accomplished in sheep, pigs, rats, and other animals. In 2009, the first human biological drug produced from such an animal, a  goat , was approved. The drug,  ATryn , is an  anticoagulant  which reduces the probability of  blood clots  during  surgery  or  childbirth  was extracted from the goat's milk. [ 42 ]  Human  alpha-1-antitrypsin  is another protein that is used in treating humans with this deficiency. [ 43 ]  Another area is in creating pigs with greater capacity for  human organ transplants  ( xenotransplantation ). Pigs have been genetically modified so that their organs can no longer carry retroviruses [ 44 ]  or have modifications to reduce the chance of rejection. [ 45 ] [ 46 ]  Pig lungs from genetically modified pigs are being considered for transplantation into humans. [ 47 ] [ 48 ]  There is even potential to create chimeric pigs that can carry human organs. [ 37 ] [ 49 ]


Livestock are modified with the intention of improving economically important traits such as growth-rate, quality of meat, milk composition, disease resistance and survival. Animals have been engineered to grow faster, be healthier [ 50 ]  and resist diseases. [ 51 ]  Modifications have also improved the wool production of sheep and udder health of cows. [ 1 ]


Goats have been genetically engineered to produce milk with strong spiderweb-like silk proteins. [ 52 ]  The goat gene sequence has been modified, using fresh umbilical cords taken from kids, in order to code for the human enzyme  lysozyme . Researchers wanted to alter the milk produced by the goats, to contain lysozyme in order to fight off bacteria causing  diarrhea  in humans. [ 53 ]


Enviropig was a genetically enhanced line of  Yorkshire pigs  in Canada created with the capability of digesting plant  phosphorus  more efficiently than conventional Yorkshire pigs. [ 54 ] [ 55 ]  The A  transgene  construct consisting of a  promoter  expressed in the  murine   parotid gland  and the  Escherichia coli   phytase  gene was introduced into the pig embryo by pronuclear  microinjection . [ 56 ]  This caused the pigs to produce the enzyme  phytase , which breaks down the indigestible phosphorus, in their saliva. [ 54 ] [ 57 ]  As a result, they excrete 30 to 70% less phosphorus in manure depending upon the age and diet. [ 54 ] [ 57 ]  The lower concentrations of phosphorus in  surface runoff  reduces  algal  growth, because phosphorus is the  limiting nutrient  for algae. [ 54 ]  Because algae consume large amounts of oxygen, excessive growth can result in dead zones for fish. Funding for the Enviropig program ended in April 2012, [ 58 ]  and as no new partners were found the pigs were killed. [ 59 ]  However, the genetic material will be stored at the Canadian Agricultural Genetics Repository Program. In 2006, a pig was engineered to produce  omega-3 fatty acids  through the expression of a  roundworm  gene. [ 60 ]


In 1990, the world's first transgenic  bovine , Herman the Bull, was developed. Herman was genetically engineered by micro-injected embryonic cells with the human gene coding for  lactoferrin . The  Dutch Parliament  changed the law in 1992 to allow Herman to reproduce. Eight calves were born in 1994 and all calves inherited the lactoferrin gene. [ 61 ]  With subsequent sirings, Herman fathered a total of 83 calves. [ 62 ]  Dutch law required Herman to be  slaughtered  at the conclusion of the  experiment . However the Dutch Agriculture Minister at the time,  Jozias van Aartsen , granted him a reprieve provided he did not have more offspring after public and scientists rallied to his defence. [ 62 ]  Together with  cloned  cows named Holly and Belle, he lived out his retirement at  Naturalis , the National Museum of Natural History in Leiden. [ 62 ]  On 2 April 2004, Herman was  euthanised  by  veterinarians  from the  University of Utrecht  because he suffered from  osteoarthritis . [ 63 ] [ 62 ]  At the time of his death Herman was one of the oldest bulls in the Netherlands. [ 63 ]  Herman's hide has been preserved and mounted by  taxidermists  and is permanently on display in Naturalis. They say that he represents the start of a new era in the way man deals with nature, an icon of scientific progress, and the subsequent public discussion of these issues. [ 63 ]


In October 2017, Chinese scientists announced they used  CRISPR gene editing  technology to create of a line of pigs with better body temperature regulation, resulting in about 24% less body fat than typical livestock. [ 64 ]


Researchers have developed GM dairy cattle to grow without horns (sometimes referred to as " polled ") which can cause injuries to farmers and other animals. DNA was taken from the genome of  Red Angus  cattle, which is known to suppress horn growth, and inserted into cells taken from an elite  Holstein  bull called "Randy". Each of the progeny will be a clone of Randy, but without his horns, and their offspring should also be hornless. [ 65 ]  In 2011, Chinese scientists generated  dairy cows  genetically engineered with genes from human beings to produce milk that would be the same as human breast milk. [ 66 ]  This could potentially benefit mothers who cannot produce breast milk but want their children to have breast milk rather than formula. [ 67 ] [ 68 ]  The researchers claim these transgenic cows to be identical to regular cows. [ 69 ]  Two months later, scientists from  Argentina  presented Rosita, a transgenic cow incorporating two human genes, to produce milk with similar properties as human breast milk. [ 70 ]  In 2012, researchers from New Zealand also developed a genetically engineered cow that produced allergy-free milk. [ 71 ]


In 2016  Jayne Raper  and a team announced the first trypanotolerant transgenic cow in the world. This team, spanning the  International Livestock Research Institute ,  Scotland's Rural College , the  Roslin Institute 's Centre for Tropical Livestock Genetics and Health, and the  City University of New York , announced that a  Kenyan Boran  bull had been born and had already successfully had two children. Tumaini - named for the  Swahili  word for "hope" - carries a  trypanolytic factor  from a  baboon  via  CRISPR/Cas9 . [ 72 ] [ 73 ]


Scientists have genetically engineered several organisms, including some mammals, to include  green fluorescent protein  (GFP), for research purposes. [ 74 ]  GFP and other similar reporting genes allow easy visualisation and localisation of the products of the genetic modification. [ 75 ]  Fluorescent pigs have been bred to study human organ transplants, regenerating ocular  photoreceptor cells , and other topics. [ 76 ]  In 2011  green-fluorescent  cats were created to find therapies for  HIV/AIDS  and other diseases [ 77 ]  as  feline immunodeficiency virus  (FIV) is related to HIV. [ 78 ]  Researchers from the University of Wyoming have developed a way to incorporate spiders' silk-spinning genes into goats, allowing the researchers to harvest the silk protein from the goats' milk for a variety of applications. [ 79 ]


Genetic modification of the  myxoma virus  has been proposed to conserve  European wild rabbits  in the  Iberian peninsula  and to help regulate them in Australia. To protect the Iberian species from viral diseases, the myxoma virus was genetically modified to immunize the rabbits, while in Australia the same myxoma virus was genetically modified to lower fertility in the Australian rabbit population. [ 80 ]  There have also been suggestions that genetic engineering could be used to bring animals  back from extinction . It involves changing the genome of a close living relative to resemble the extinct one and is currently being attempted with the  passenger pigeon . [ 81 ]  Genes associated with the  woolly mammoth  have been added to the genome of an  African Elephant , although the lead researcher says he has no intention of using live elephants. [ 82 ]


Gene therapy [ 83 ]  uses genetically modified viruses to deliver genes which can cure disease in humans. Although gene therapy is still relatively new, it has had some successes. It has been used to treat  genetic disorders  such as  severe combined immunodeficiency [ 84 ]  and  Leber's congenital amaurosis . [ 85 ]  Treatments are also being developed for a range of other currently incurable diseases, such as  cystic fibrosis , [ 86 ]   sickle cell anemia , [ 87 ]   Parkinson's disease , [ 88 ] [ 89 ]   cancer , [ 90 ] [ 91 ] [ 92 ]   diabetes , [ 93 ]   heart disease , [ 94 ]  and  muscular dystrophy . [ 95 ]  These treatments only affect  somatic cells , which means that any changes would not be inheritable.  Germline  gene therapy results in any change being inheritable, which has raised concerns within the scientific community. [ 96 ] [ 97 ]  In 2015, CRISPR was used to edit the DNA of non-viable  human embryos . [ 98 ] [ 99 ]  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. He said that twin girls-  Lulu and Nana , had been born a few weeks earlier, and that they carried functional copies of CCR5 along with disabled CCR5 ( mosaicism ), and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature. [ 100 ]


Genetically modified fish are used for scientific research, as pets, and as a food source.  Aquaculture  is a growing industry, currently providing over half of the consumed fish worldwide. [ 101 ]  Through genetic engineering, it is possible to increase growth rates, reduce food intake, remove  allergenic  properties, increase cold tolerance, and provide disease resistance.


Fish can also be used to detect aquatic pollution or function as bioreactors. [ 102 ]  Several groups have been developing  zebrafish  to detect  pollution  by attaching fluorescent proteins to genes activated by the presence of pollutants. The fish will then glow and can be used as environmental sensors. [ 103 ] [ 104 ]


The  GloFish  is a brand of genetically modified fluorescent  zebrafish  with bright red, green, and orange fluorescent color. It was originally developed by one of the groups to detect pollution, but is now part of the ornamental fish trade, becoming the first genetically modified animal to become publicly available as a pet when it was introduced for sale in 2003. [ 105 ]


GM fish are widely used in basic research in genetics and development. Two species of fish- zebrafish and  medaka , are most commonly modified, because they have optically clear  chorions  (membranes in the egg), rapidly develop, and the 1-cell embryo is easy to see and microinject with transgenic DNA. [ 106 ]  Zebrafish are model organisms for developmental processes,  regeneration , genetics, behaviour, disease mechanisms, and toxicity testing. [ 107 ]  Their transparency allows researchers to observe developmental stages, intestinal functions, and tumour growth. [ 108 ] [ 109 ]  The generation of transgenic protocols (whole organism, cell or tissue specific, tagged with reporter genes) has increased the level of information gained by studying these fish. [ 110 ]


GM fish have been developed with promoters driving an over-production of "all fish"  growth hormone  for use in the  aquaculture  industry, to increase the speed of development and potentially reduce fishing pressure on wild stocks. This has resulted in dramatic growth enhancement in several species, including  salmon , [ 111 ]   trout , [ 112 ]  and  tilapia . [ 113 ]


AquaBounty Technologies  have produced a salmon that can mature in half the time as wild salmon. [ 114 ]  The fish is an Atlantic salmon with a  Chinook salmon  ( Oncorhynchus tshawytscha ) gene inserted. This allows the fish to produce growth hormones all year round compared to the wild-type fish that produces the hormone for only part of the year. [ 115 ]  The fish also has a second gene inserted from the eel-like  ocean pout  that acts like an "on" switch for the hormone. [ 115 ]  Pout also have  antifreeze proteins  in their blood, which allow the GM salmon to survive near-freezing waters and continue their development. [ 116 ]  A wild-type salmon takes 24 to 30 months to reach market size (4–6 kg), whereas the producers of the GM salmon say that it requires only 18 months for the GM fish to reach that size. [ 116 ] [ 117 ] [ 118 ]  In November 2015, the FDA of the USA approved the  AquAdvantage salmon  for commercial production, sale, and consumption, [ 119 ]  the first non-plant GMO food to be commercialized. [ 120 ]


AquaBounty  says that to prevent the genetically modified fish from inadvertently breeding with wild salmon, all of the fish will be female and reproductively sterile, [ 118 ]  although a small percentage of the females may remain fertile. [ 115 ]  Some opponents of the GM salmon have dubbed it the "Frankenfish". [ 115 ] [ 121 ]


In biological research, transgenic fruit flies ( Drosophila melanogaster ) are  model organisms  used to study the effects of genetic changes on development. [ 122 ]  Fruit flies are often preferred over other animals due to their short life cycle and low maintenance requirements. It also has a relatively simple genome compared to many  vertebrates , with typically only one copy of each gene, making phenotypic analysis easy. [ 123 ]   Drosophila  have been used to study genetics and inheritance, embryonic development, learning, behavior, and aging. [ 124 ]   Transposons  (particularly P elements) are well developed in  Drosophila  and provided an early method to add transgenes to their genome, although this has been taken over by more modern gene-editing techniques. [ 125 ]


Due to their significance to human health, scientists are looking at ways to control mosquitoes through genetic engineering. Malaria-resistant mosquitoes have been developed in the laboratory. [ 126 ]  by inserting a gene that reduces the development of the malaria parasite [ 127 ]  and then use  homing endonucleases  to rapidly spread that gene throughout the male population (known as a  gene drive ). [ 128 ]  This has been taken further by swapping it for a lethal gene. [ 129 ] [ 130 ]  In trials the populations of  Aedes aegypti  mosquitoes, the single most important carrier of dengue fever and Zika virus, were reduced by between 80% and by 90%. [ 131 ] [ 132 ] [ 130 ]  Another approach is to use the  sterile insect technique , whereby males genetically engineered to be sterile out compete viable males, to reduce population numbers. [ 133 ]


Other  insect  pests that make attractive targets are  moths .  Diamondback moths  cause US$4 to $5 billion of damage a year worldwide. [ 134 ]  The approach is similar to the mosquitoes, where males transformed with a gene that prevents females from reaching maturity will be released. [ 135 ]  They underwent field trials in 2017. [ 134 ]  Genetically modified moths have previously been released in field trials. [ 136 ]  A strain of  pink bollworm  that were sterilised with radiation were genetically engineered to express a  red fluorescent protein  making it easier for researchers to monitor them. [ 137 ]


Silkworm, the larvae stage of  Bombyx mori ,  is an economically important insect in  sericulture . Scientists are developing strategies to enhance silk quality and quantity. There is also potential to use the silk producing machinery to make other valuable proteins. [ 138 ]  Proteins expressed by silkworms include;  human serum albumin ,  human collagen α-chain , mouse  monoclonal antibody  and  N-glycanase . [ 139 ]  Silkworms have been created that produce  spider silk , a stronger but extremely difficult to harvest silk, [ 140 ]  and even novel silks. [ 141 ]


Attempts to produce genetically modified birds began before 1980. [ 142 ]  Chickens have been genetically modified for a variety of purposes. This includes studying  embryo development , [ 143 ]  preventing the transmission of  bird flu [ 144 ]  and providing evolutionary insights using  reverse engineering  to recreate dinosaur-like phenotypes. [ 145 ]  A GM chicken that produces the drug  Kanuma , an enzyme that treats a rare condition, in its egg passed regulatory approval in 2015. [ 146 ]


One potential use of GM birds could be to reduce the spread of avian disease. Researchers at  Roslin Institute  have produced a strain of GM chickens ( Gallus gallus domesticus ) that does not transmit  avian flu  to other birds; however, these birds are still susceptible to contracting it. The genetic modification is an  RNA  molecule that prevents the virus reproduction by mimicking the region of the flu virus genome that controls replication. It is referred to as a "decoy" because it diverts the flu virus enzyme, the  polymerase , from functions that are required for virus replication. [ 147 ]


A team of geneticists led by  University of Montana  paleontologist  Jack Horner  is seeking to modify a chicken to express several features present in ancestral  maniraptorans  but absent in modern birds, such as teeth and a long tail, [ 148 ]  creating what has been dubbed a 'chickenosaurus'. [ 149 ]  Parallel projects have produced chicken embryos expressing dinosaur-like skull, [ 150 ]  leg, [ 145 ]  and foot [ 151 ]  anatomy.


Gene editing is one possible tool in the laying hen breeding industry to provide an alternative to  Chick culling . With this technology, breeding hens are given a genetic marker that is only passed down to male offspring. These males can then be identified during incubation and removed from the egg supply, so that only females hatch. For example, the Israeli startup eggXYt uses  CRISPR  to give male eggs a biomarker that makes then glow under certain conditions. [ 152 ]  Importantly, the resulting laying hen and the eggs it producers are not themselves genetically edited. The European Union's Director General for Health and Food Safety has confirmed that made in this way eggs can be marketed, [ 153 ]  although none are commercially available as of June 2023. [ 154 ]


The first experiments that successfully developed  transgenic  amphibians into embryos began in the 1980s with  Xenopus laevis . [ 155 ]  Later, germline transgenic axolotls in  Ambystoma mexicanum  were produced in 2006 using a technique called I-SceI-mediated transgenesis which utilizes the I-SceI endonuclease  enzyme  that can break DNA at specific sites and allow for foreign DNA to be inserted into the genome. [ 156 ]  Both  Xenopus laevis  and Ambystoma mexicanum are model organisms used to study  regeneration . In addition, transgenic lines have been produced in other  salamanders  including the Japanese newt Pyrrhogaster and  Pleurodeles watl . [ 157 ]  Genetically modified frogs, in particular  Xenopus laevis  and  Xenopus tropicalis , are used in  development biology . GM frogs can also be used as pollution sensors, especially for  endocrine disrupting chemicals . [ 158 ]  There are proposals to use genetic engineering to control  cane toads in Australia . [ 159 ] [ 160 ]  Many lines of transgenic X. laevis are used to study immunology to address how bacteria and viruses cause infectious disease at the University of Rochester Medical Center's X. laevis Research Resource for Immunobiology (XLRRI). [ 161 ]  Amphibians can also be used to study and validate regenerative  signaling pathways  such as the  Wnt pathway . [ 162 ] [ 161 ]  The wound-healing abilities of amphibians have many practical applications and can potentially provide a foundation for scar-free repair in human plastic surgery, such as treating the skin of burn patients. [ 163 ]


Amphibians like X. laevis are suitable for experimental  embryology  because they have large embryos that can be easily manipulated and observed during development. [ 164 ]  In experiments with axolotls, mutants with white pigmented skin are often used because their semi-transparent skin provides an efficient visualization and tracking method for  fluorescently tagged proteins  like  GFP . [ 165 ]  Amphibians are not always ideal when it comes to the resources required to produce genetically modified animals; along with the one to two-year generation time,  Xenopus laevis  can be considered less than ideal for transgenic experiments because of its  pseudotetraploid  genome. [ 164 ]  Due to the same genes appearing in the genome multiple times, the chance of  mutagenesis  experiments working is lower. [ 166 ]  Current methods of freezing and thawing axolotl sperm render them nonfunctional, meaning transgenic lines must be maintained in a facility and this can get quite costly. [ 167 ] [ 168 ]  Producing transgenic axolotls has many challenges due to their large genome size. [ 168 ]  Current methods of generating transgenic axolotls are limited to random integration of the transgene  cassette  into the genome, which can lead to uneven expression or silencing. [ 169 ]  Gene duplicates also complicate efforts to generate efficient  gene knockouts . [ 168 ]


Despite the costs, axolotls have unique regenerative abilities and ultimately provide useful information in understanding tissue regeneration because they can regenerate their limbs, spinal cord, skin, heart, lungs, and other organs. [ 168 ] [ 170 ]  Naturally occurring mutant axolotls like the white strain that are often used in research have a transcriptional mutation at the Edn3 gene locus. [ 171 ]  Unlike other model organisms, the first fluorescently labeled cells in axolotls were differentiated muscle cells instead of embryos. In these initial experiments in the early 2000s, scientists were able to visualize muscle cell regeneration in the axolotl tail using a microinjecting technique, but cells could not be traced for the entire course of regeneration due to too harsh conditions that caused early cell death in labeled cells. [ 172 ] [ 173 ]  Though the process of producing transgenic axolotls was a challenge, scientists were able to label cells for longer durations using a plasmid transfection technique, which involves injecting DNA into cells using an electrical pulse in a process called  electroporation .  Transfecting  axolotl cells is thought to be more difficult because of the composition of the  extracellular matrix  (ECM). This technique allows spinal cord cells to be labeled and is very important in studying limb regeneration in many other cells; it has been used to study the role of the immune system in regeneration. Using  gene knockout  approaches, scientists can target specific regions of DNA using techniques like  CRISPR/Cas9  to understand the function of certain genes based on the absence of the gene of interest. For example, gene knockouts of the  Sox2  gene confirm this region's role in neural stem cell amplification in the axolotl. The technology to do more complex conditional gene knockouts, or conditional knockouts that give the scientist spatiotemporal control of the gene is not yet suitable for axolotls. [ 168 ]  However, research in this field continues to develop and is made easier by recent sequencing of the genome and resources created for scientists, including data portals that contain axolotl genome and transcriptome reference assemblies to identify  orthologs . [ 174 ] [ 175 ]


The  nematode   Caenorhabditis elegans  is one of the major model organisms for researching  molecular biology . [ 176 ]   RNA interference  (RNAi) was discovered in  C. elegans [ 177 ]  and could be induced by simply feeding them bacteria modified to express  double stranded RNA . [ 178 ]  It is also relatively easy to produce stable transgenic nematodes and this along with RNAi are the major tools used in studying their genes. [ 179 ]  The most common use of transgenic nematodes has been studying gene expression and localisation by attaching reporter genes. Transgenes can also be combined with RNAi to rescue phenotypes, altered to study gene function, imaged in real time as the cells develop or used to control expression for different tissues or developmental stages. [ 179 ]  Transgenic nematodes have been used to study viruses, [ 180 ]  toxicology, [ 181 ]  and diseases [ 182 ] [ 183 ]  and to detect environmental pollutants. [ 184 ]


Systems have been developed to create transgenic organisms in a wide variety of other animals. The gene responsible for  albinism  in  sea cucumbers  has been found, and used to engineer  white sea cucumbers , a rare delicacy. The technology also opens the way to investigate the genes responsible for some of the cucumbers more unusual traits, including  hibernating  in summer,  eviscerating  their intestines, and dissolving their bodies upon death. [ 185 ]   Flatworms  have the ability to regenerate themselves from a single cell. [ 186 ] [ 187 ]  Until 2017 there was no effective way to transform them, which hampered research. By using microinjection and radiation, scientists have now created the first genetically modified flatworms. [ 188 ]  The  bristle worm , a marine  annelid , has been modified. It is of interest due to its reproductive cycle being synchronized with lunar phases, regeneration capacity and slow evolution rate. [ 189 ]   Cnidaria  such as  Hydra  and the sea anemone  Nematostella vectensis  are attractive model organisms to study the  evolution  of  immunity  and certain developmental processes. [ 190 ]  Other organisms that have been genetically modified include  snails , [ 191 ]   geckos ,  turtles , [ 192 ]   crayfish ,  oysters ,  shrimp ,  clams ,  abalone , [ 193 ]  and  sponges . [ 194 ]


Food products derived from genetically modified (GM) animals have not yet entered the European market. Nonetheless, the on-going discussion about GM crops [1], and the developing debate about the safety and ethics of foods and pharmaceutical products produced by both GM animals and plants, have provoked varying views across different sectors of society [ 195 ]


Genetic modification  and  genome editing  hold potential for the future, but decisions regarding the use of these technologies must be based not only on what is possible, but also on what is ethically reasonable. Principles such as animal integrity, naturalness, risk identification and animal welfare are examples of ethically important factors that must be taken into consideration, and they also influence public perception and regulatory decisions by authorities. [ 196 ]


The utility of extrapolating animal data to humans has been questioned. This has led ethical committees to adopt the principles of the four Rs (Reduction, Refinement, Replacement, and Responsibility) as a guide for decision-making regarding  animal experimentation . However, complete abandonment of  laboratory animals  has not yet been possible, and further research is needed to develop a roadmap for robust alternatives before their use can be fully discontinued. [ 197 ]


Genetically modified crops  ( GM 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 (e.g. resistance to a  herbicide ), 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 . [ 1 ]


Farmers have widely adopted GM technology. Acreage increased from 1.7 million hectares in 1996 to 185.1 million hectares in 2016, some 12% of global cropland. As of 2016, major crop ( soybean ,  maize ,  canola  and  cotton ) traits consist of herbicide tolerance (95.9 million hectares) insect resistance (25.2 million hectares), or both (58.5 million hectares). In 2015, 53.6 million ha of  Genetically modified maize  were under cultivation (almost 1/3 of the maize crop). GM maize outperformed its predecessors: yield was 5.6 to 24.5% higher with less  mycotoxins  (−28.8%),  fumonisin  (−30.6%) and thricotecens (−36.5%). Non-target organisms were unaffected, except for lower populations some  parasitoid  wasps due to decreased populations of their pest host  European corn borer ; European corn borer is a target of  Lepidoptera  active Bt maize. Biogeochemical parameters such as lignin content did not vary, while biomass decomposition was higher. [ 2 ]


A 2014 meta-analysis concluded that GM technology adoption had reduced chemical  pesticide  use by 37%, increased  crop yields  by 22%, and increased farmer profits by 68%. [ 3 ]  This reduction in pesticide use has been ecologically beneficial, but benefits may be reduced by overuse. [ 4 ]  Yield gains and pesticide reductions are larger for insect-resistant crops than for herbicide-tolerant crops. [ 5 ]  Yield and profit gains are higher in  developing countries  than in  developed countries . [ 3 ]   Pesticide poisonings  were reduced by 2.4 to 9  million cases per year in India alone. [ 6 ]  A 2011 review of the relationship between  Bt cotton adoption and farmer suicides in India  found that "Available data show no evidence of a 'resurgence' of farmer suicides" and that "Bt cotton technology has been very effective overall in India." [ 7 ]  During the time period of  Bt cotton  introduction in India, farmer suicides instead declined by 25%. [ 6 ]


There is a  scientific consensus [ 8 ] [ 9 ] [ 10 ] [ 11 ]  that currently available food derived from GM crops poses no greater risk to human health than conventional food, [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  but that each GM food needs to be tested on a case-by-case basis before introduction. [ 17 ] [ 18 ] [ 19 ]  Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe. [ 20 ] [ 21 ] [ 22 ] [ 23 ]  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. [ 24 ] [ 25 ] [ 26 ] [ 27 ]


Humans have directly influenced the genetic makeup of plants to increase their value as a crop through  domestication . The first evidence of plant domestication comes from  emmer  and  einkorn wheat  found in  pre-Pottery Neolithic A  villages in Southwest Asia dated about 10,500 to 10,100 BC. [ 28 ]   The  Fertile Crescent  of Western Asia,  Egypt , and  India  were sites of the earliest planned sowing and harvesting of plants that had previously been gathered in the wild. Independent development of agriculture occurred in northern and southern China, Africa's  Sahel ,  New Guinea  and several regions of the Americas. [ 29 ]  The eight  Neolithic founder crops  ( emmer wheat ,  einkorn wheat ,  barley ,  peas ,  lentils ,  bitter vetch ,  chick peas  and  flax ) had all appeared by about 7,000 BC. [ 30 ]  Traditional crop breeders have long introduced foreign  germplasm  into crops by creating novel crosses. A  hybrid   cereal  grain was created in 1875, by crossing  wheat  and  rye . [ 31 ]  Since then traits including  dwarfing genes  and  rust resistance  have been introduced in that manner. [ 32 ]   Plant tissue culture  and deliberate  mutations  have enabled humans to alter the makeup of plant genomes. [ 33 ] [ 34 ]


Modern advances in genetics have allowed humans to more directly alter plants genetics.  In 1970  Hamilton Smith's  lab discovered  restriction enzymes  that allowed DNA to be cut at specific places, enabling scientists to isolate genes from an organism's genome. [ 35 ]   DNA ligases  that join broken DNA together had been discovered earlier in 1967, [ 36 ]  and by combining the two technologies, it was possible to "cut and paste" DNA sequences and create  recombinant DNA .  Plasmids , discovered in 1952, [ 37 ]  became important  tools  for transferring information between cells and  replicating  DNA sequences. In 1907 a bacterium that caused plant tumors,  Agrobacterium tumefaciens , was discovered and in the early 1970s the tumor inducing agent was found to be a DNA plasmid called the  Ti plasmid . [ 38 ]  By removing the genes in the plasmid that caused the tumor and adding in novel genes researchers were able to infect plants with  A. tumefaciens  and let the bacteria insert their chosen DNA sequence into the genomes of the plants. [ 39 ]  As not all plant cells were susceptible to infection by  A. tumefaciens  other methods were developed, including  electroporation ,  micro-injection [ 40 ]  and particle bombardment with a  gene gun  (invented in 1987). [ 41 ] [ 42 ]  In the 1980s techniques were developed to introduce isolated  chloroplasts  back into a plant cell that had its cell wall removed. With the introduction of the gene gun in 1987 it became possible to integrate foreign genes into a  chloroplast . [ 43 ]  Genetic transformation has become very efficient in some model organisms. In 2008 genetically modified seeds were produced in  Arabidopsis thaliana  by dipping the flowers in an  Agrobacterium  solution. [ 44 ]  In 2013  CRISPR  was first used to target modification of plant genomes. [ 45 ]


The first genetically engineered crop plant was tobacco, reported in 1983. [ 46 ]  It was developed creating a  chimeric gene  that joined an antibiotic resistant gene to the T1 plasmid from  Agrobacterium . The tobacco was infected with  Agrobacterium  transformed with this plasmid resulting in the chimeric gene being inserted into the plant. Through  tissue culture  techniques a single tobacco cell was selected that contained the gene and a new plant grown from it. [ 47 ]   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 . [ 48 ]  In 1987  Plant Genetic Systems , founded by  Marc Van Montagu  and  Jeff Schell , was the first company to genetically engineer insect-resistant plants by incorporating genes that produced insecticidal proteins from  Bacillus thuringiensis  (Bt) into  tobacco . [ 49 ]  The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992. [ 50 ]  In 1994  Calgene  attained approval to commercially release the  Flavr Savr  tomato, a tomato engineered to have a longer shelf life. [ 51 ]  Also 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. [ 52 ]  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. [ 53 ]  In 1996 a total of 35 approvals had been granted to commercially grow 8 transgenic crops and one flower crop (carnation), with 8 different traits in 6 countries plus the EU. [ 48 ]  By 2010, 29 countries had planted commercialised genetically modified crops and a further 31 countries had granted regulatory approval for transgenic crops to be imported. [ 54 ]


GM banana cultivar QCAV-4 was approved by Australia and New Zealand in 2024. The banana resists the fungus that is fatal to the  Cavendish banana , the dominant cultivar. [ 55 ]


Genetically engineered crops have genes added or removed using  genetic engineering  techniques, [ 56 ]  originally including  gene guns ,  electroporation ,  microinjection  and  agrobacterium . More recently,  CRISPR  and  TALEN  offered much more precise and convenient editing techniques.


Gene guns (also known as biolistics) "shoot" (direct high energy particles or radiations against [ 57 ] ) target genes into plant cells. It is the most common method.  DNA  is bound to tiny particles of gold or tungsten which are subsequently shot into plant tissue or single plant cells under high pressure. The accelerated particles penetrate both the  cell wall  and  membranes . The DNA separates from the metal and is integrated into plant DNA inside the  nucleus . This method has been applied successfully for many cultivated crops, especially  monocots  like wheat or maize, for which  transformation  using  Agrobacterium tumefaciens  has been less successful. [ 58 ]  The major disadvantage of this procedure is that serious damage can be done to the cellular tissue.


Agrobacterium tumefaciens - mediated transformation is another common technique. Agrobacteria are natural plant  parasites . [ 59 ]  Their natural ability to transfer genes provides another engineering method. To create a suitable environment for themselves, these Agrobacteria insert their genes into plant hosts, resulting in a proliferation of modified plant cells near the soil level ( crown gall ). The genetic information for tumor growth is encoded on a mobile, circular DNA fragment ( plasmid ). When  Agrobacterium  infects a plant, it transfers this  T-DNA  to a random site in the plant genome. When used in genetic engineering the bacterial T-DNA is removed from the bacterial plasmid and replaced with the desired foreign gene. The bacterium is a  vector , enabling transportation of foreign genes into plants. This method works especially well for  dicotyledonous  plants like potatoes, tomatoes, and tobacco. Agrobacteria infection is less successful in crops like wheat and maize.


Electroporation is used when the plant tissue does not contain cell walls. In this technique, "DNA enters the plant cells through miniature pores which are temporarily caused by electric pulses."


Microinjection is used to directly inject foreign DNA into cells. [ 60 ]


Plant scientists, backed by results of modern comprehensive profiling of crop composition, point out that crops modified using GM techniques are less likely to have unintended changes than are conventionally bred crops. [ 61 ] [ 62 ]


In research  tobacco  and  Arabidopsis thaliana  are the most frequently modified plants, due to well-developed transformation methods, easy propagation and well studied genomes. [ 63 ] [ 64 ]  They serve as model organisms for other plant species.


Introducing new genes into plants requires a  promoter  specific to the area where the gene is to be expressed. For instance, to express a gene only in rice grains and not in leaves, an  endosperm -specific promoter is used. The  codons  of the gene must be optimized for the organism due to  codon usage bias .


Transgenic  plants have genes inserted into them that are derived from another species. The inserted genes can come from species within the same  kingdom  (plant to plant), or between kingdoms (for example, bacteria to plant). In many cases the inserted DNA has to be modified slightly in order to be correctly and efficiently  expressed  in the host organism. Transgenic plants are used to express  proteins , like the  cry toxins  from  B. thuringiensis ,  herbicide -resistant genes,  antibodies , [ 65 ]  and  antigens  for  vaccinations . [ 66 ]  A study led by the European Food Safety Authority (EFSA) also found viral genes in transgenic plants. [ 67 ]


Transgenic carrots have been used to produce the drug  Taliglucerase alfa  which is used to treat  Gaucher's disease . [ 68 ]  In the laboratory, transgenic plants have been modified to increase  photosynthesis  (currently about 2% at most plants versus the theoretic potential of 9–10%). [ 69 ]  This is possible by changing the  rubisco  enzyme (i.e. changing  C 3  plants into  C 4  plants [ 70 ] ), by placing the rubisco in a  carboxysome , by adding CO 2  pumps in the cell wall, [ 71 ]  or by changing the leaf form or size. [ 72 ] [ 73 ] [ 74 ]  Plants have been engineered to exhibit  bioluminescence  that may become a sustainable alternative to electric lighting. [ 75 ]


Cisgenic  plants are made using genes found within the same species or a sexually-compatible closely related one, where conventional  plant breeding  can occur. [ 76 ]  Some breeders and scientists argue that cisgenic modification is useful for plants that are difficult to  crossbreed  by conventional means (such as  potatoes ), and that plants in the cisgenic category should not require the same regulatory scrutiny as transgenics. [ 77 ]


Genetically modified plants can also be developed using  gene knockdown  or  gene knockout  to alter the genetic makeup of a plant without incorporating genes from other plants. In 2014, Chinese researcher Gao Caixia filed patents on the creation of a strain of  wheat  that is resistant to  powdery mildew . The strain lacks genes that encode proteins that repress defenses against the mildew. The researchers deleted all three copies of the genes from wheat's  hexaploid  genome. Gao used the  TALENs  and  CRISPR   gene editing  tools without adding or changing any other genes. No field trials were immediately planned. [ 78 ] [ 79 ]  The CRISPR technique has also been used by Penn State researcher Yinong Yang to modify white button mushrooms ( Agaricus bisporus ) to be non-browning, [ 80 ]  and by  DuPont Pioneer  to make a new variety of corn. [ 81 ]


With multiple trait integration, several new traits may be integrated into a new crop. [ 82 ]


GM food's economic value to farmers is one of its major benefits, including in developing nations. [ 83 ] [ 84 ] [ 85 ]  A 2010 study found that Bt corn provided economic benefits of $6.9 billion over the previous 14 years in five Midwestern states. The majority ($4.3 billion) accrued to farmers producing non-Bt corn. This was attributed to European corn borer populations reduced by exposure to Bt corn, leaving fewer to attack conventional corn nearby. [ 86 ] [ 87 ]  Agriculture economists calculated that "world surplus [increased by] $240.3 million for 1996. Of this total, the largest share (59%) went to U.S. farmers. Seed company Monsanto received the next largest share (21%), followed by US consumers (9%), the rest of the world (6%), and the germplasm supplier,  Delta & Pine Land Company of Mississippi  (5%)." [ 88 ]


According to the  International Service for the Acquisition of Agri-biotech Applications  (ISAAA), in 2014 approximately 18 million farmers grew biotech crops in 28 countries; about 94% of the farmers were resource-poor in developing countries. 53% of the global biotech crop area of 181.5 million hectares was grown in 20 developing countries. [ 89 ]  PG Economics comprehensive 2012 study concluded that GM crops increased farm incomes worldwide by $14 billion in 2010, with over half this total going to farmers in developing countries. [ 90 ]


Forgoing these benefits is costly. [ 91 ] [ 92 ]  Wesseler  et al. , 2017 estimate the cost of delay for several crops including GM banana in  Uganda ,  GM cowpea  in  west Africa , and  GM maize/corn  in  Kenya . [ 91 ]  They estimate Nigeria alone loses $33–46m annually. [ 91 ]  The potential and alleged harms of GM crops must then be compared to these costs of delay. [ 91 ] [ 92 ]


Critics challenged the claimed benefits to farmers over the prevalence of biased observers and by the absence of  randomized controlled trials . [ citation needed ]  The main Bt crop grown by small farmers in developing countries is cotton. A 2006 review of Bt cotton findings by agricultural economists concluded, "the overall balance sheet, though promising, is mixed. Economic returns are highly variable over years, farm type, and geographical location". [ 93 ]


In 2013 the European Academies Science Advisory Council (EASAC) asked the EU to allow the development of agricultural GM technologies to enable more sustainable agriculture, by employing fewer land, water, and nutrient resources. EASAC also criticizes the EU's "time-consuming and expensive regulatory framework" and said that the EU had fallen behind in the adoption of GM technologies. [ 94 ]


Participants in agriculture business markets include seed companies, agrochemical companies, distributors, farmers, grain elevators and universities that develop new crops/traits and whose agricultural extensions advise farmers on best practices. [ citation needed ]  According to a 2012 review based on data from the late 1990s and early 2000s, much of the GM crop grown each year is used for livestock feed and increased demand for meat leads to increased demand for GM feed crops. [ 95 ]  Feed grain usage as a percentage of total crop production is 70% for corn and more than 90% of oil seed meals such as soybeans. About 65 million metric tons of GM corn grains and about 70 million metric tons of soybean meals derived from GM soybean become feed. [ 95 ]


In 2014 the global value of biotech seed was US$15.7 billion; US$11.3 billion (72%) was in industrial countries and US$4.4 billion (28%) was in the developing countries. [ 89 ]  In 2009,  Monsanto  had $7.3 billion in sales of seeds and from licensing its technology; DuPont, through its  Pioneer  subsidiary, was the next biggest company in that market. [ 96 ]  As of 2009, the overall Roundup line of products including the GM seeds represented about 50% of Monsanto's business. [ 97 ]


Some patents on GM traits have expired, allowing the legal development of generic strains that include these traits. For example, generic glyphosate-tolerant GM soybean is now available. Another impact is that traits developed by one vendor can be added to another vendor's proprietary strains, potentially increasing product choice and competition. [ 98 ]  The patent on the first type of  Roundup Ready  crop that Monsanto produced (soybeans) expired in 2014 [ 99 ]  and the first harvest of off-patent soybeans occurs in the spring of 2015. [ 100 ]  Monsanto has broadly licensed the patent to other seed companies that include the glyphosate resistance trait in their seed products. [ 101 ]  About 150 companies have licensed the technology, [ 102 ]  including Syngenta [ 103 ]  and  DuPont Pioneer . [ 104 ]


In 2014, the largest review yet concluded that GM crops' effects on farming were positive. The  meta-analysis  considered all published English-language examinations of the agronomic and economic impacts between 1995 and March 2014 for three major GM crops: soybean, maize, and cotton. The study found that herbicide-tolerant crops have lower production costs, while for insect-resistant crops the reduced pesticide use was offset by higher seed prices, leaving overall production costs about the same. [ 3 ] [ 105 ]


Yields increased 9% for herbicide tolerance and 25% for insect resistant varieties. Farmers who adopted GM crops made 69% higher profits than those who did not. The review found that GM crops help farmers in developing countries, increasing yields by 14 percentage points. [ 105 ]


The researchers considered some studies that were not peer-reviewed and a few that did not report sample sizes. They attempted to correct for  publication bias , by considering sources beyond  academic journals . The large data set allowed the study to control for potentially confounding variables such as fertilizer use. Separately, they concluded that the funding source did not influence study results. [ 105 ]


Under special conditions meant to reveal only genetic yield factors, many GM crops are known to actually have  lower  yields. This is variously due to one or both of: Yield drag, wherein the trait itself lowers yield, either by competing for synthesis  feedstock  or by being inserted slightly inaccurately, into the middle of a yield-relevant gene; and/or  yield lag , wherein it takes some time to breed the newest yield genetics into the GM lines. This does not reflect realistic field conditions however, especially leaving out  pest pressure  which is often the point of the GM trait. [ 106 ]  See for example  Roundup Ready § Productivity claims .


Gene editing may also increase yields non-specific to the use of any biocides/pesticides. In March 2022, field test results showed  CRISPR -based  gene knockout  of KRN2 in maize and OsKRN2 in rice increased grain yields by ~10% and ~8% without any detected negative effects. [ 107 ] [ 108 ]


GM crops grown today, or under development, have been modified with various  traits . These traits include improved  shelf life ,  disease resistance , stress resistance,  herbicide resistance ,  pest resistance , production of useful goods such as biofuel or drugs, and ability to absorb toxins and for use in  bioremediation  of pollution.


Recently,  research and development  has been targeted to  enhancement of crops  that are locally important in  developing countries , such as insect-resistant  cowpea  for Africa [ 109 ]  and insect-resistant  brinjal  (eggplant). [ 110 ]


The first genetically modified crop approved for sale in the U.S. was the  FlavrSavr  tomato, which had a longer shelf life. [ 51 ]  First sold in 1994, FlavrSavr tomato production ceased in 1997. [ 111 ]  It is no longer on the market.


In November 2014, the USDA approved a  GM potato  that prevents bruising. [ 112 ] [ 113 ]


In February 2015  Arctic Apples  were approved by the USDA, [ 114 ]  becoming the first genetically modified apple approved for US sale. [ 115 ]   Gene silencing  was used to reduce the expression of  polyphenol oxidase (PPO) , thus preventing enzymatic browning of the fruit after it has been sliced open. The trait was added to  Granny Smith  and  Golden Delicious  varieties. [ 114 ] [ 116 ]  The trait includes a bacterial  antibiotic resistance  gene that provides resistance to the antibiotic  kanamycin . The genetic engineering involved cultivation in the presence of kanamycin, which allowed only resistant cultivars to survive. Humans consuming apples do not acquire kanamycin resistance, per arcticapple.com. [ 117 ]  The FDA approved the apples in March 2015. [ 118 ]


Plants use  non-photochemical quenching  to protect them from excessive amounts of sunlight. Plants can switch on the quenching mechanism almost instantaneously, but it takes much longer for it to switch off again. During the time that it is switched on, the amount of energy that is wasted increases. [ 119 ]  A genetic modification in three genes allows to correct this (in a trial with tobacco plants). As a result, yields were 14-20% higher, in terms of the weight of the dry leaves harvested. The plants had larger leaves, were taller and had more vigorous roots. [ 119 ] [ 120 ]


Another improvement that can be made on the photosynthesis process (with  C3 pathway plants ) is on  photorespiration . By inserting the C4 pathway into C3 plants, productivity may increase by as much as 50% for  cereal crops , such as rice. [ 121 ] [ 122 ] [ 123 ] [ 124 ] [ 125 ]


The  Harnessing Plants Initiative  focuses on creating GM plants that have increased root mass, root depth and suberin content.


Some GM soybeans offer improved oil profiles for processing. [ 126 ]   Camelina sativa  has been modified to produce plants that accumulate high levels of oils similar to  fish oils . [ 127 ] [ 128 ]


Golden rice , developed by the  International Rice Research Institute  (IRRI), provides greater amounts of  vitamin A  targeted at reducing  vitamin A deficiency . [ 129 ] [ 130 ]  As of January 2016, golden rice has not yet been grown commercially in any country. [ 131 ]


A genetically modified  cassava  under development offers lower  cyanogen   glucosides  and enhanced protein and other nutrients (called BioCassava). [ 132 ]


In November 2014, the USDA approved a potato that prevents bruising and produces less  acrylamide  when fried. [ 112 ] [ 113 ]  They do not employ genes from non-potato species. The trait was added to the  Russet Burbank ,  Ranger Russet  and Atlantic varieties. [ 112 ]


Plants have been engineered to tolerate non-biological  stressors , such as  drought , [ 112 ] [ 113 ] [ 133 ] [ 134 ]   frost , [ 135 ]  and high  soil salinity . [ 64 ]  In 2011, Monsanto's DroughtGard maize became the first drought-resistant GM crop to receive US marketing approval. [ 136 ]


Drought resistance occurs by modifying the plant's genes responsible for the mechanism known as the  crassulacean acid metabolism  (CAM), which allows the plants to survive despite low water levels. This holds promise for water-heavy crops such as rice, wheat, soybeans and poplar to accelerate their adaptation to water-limited environments. [ 137 ] [ 138 ]  Several salinity tolerance mechanisms have been identified in salt-tolerant crops. For example, rice, canola and tomato crops have been genetically modified to increase their tolerance to salt stress. [ 139 ] [ 140 ]


The most prevalent GM trait is herbicide tolerance, [ 141 ]  where  glyphosate -tolerance is the most common. [ 142 ]  Glyphosate (the active ingredient in Roundup and other herbicide products) kills plants by interfering with the  shikimate  pathway in plants, which is essential for the synthesis of the  aromatic amino acids   phenylalanine ,  tyrosine , and  tryptophan . The shikimate pathway is not present in animals, which instead obtain aromatic amino acids from their diet. More specifically, glyphosate inhibits the enzyme  5-enolpyruvylshikimate-3-phosphate synthase  (EPSPS).


This trait was developed because the herbicides used on grain and grass crops at the time were highly toxic and not effective against narrow-leaved weeds. Thus, developing crops that could withstand spraying with glyphosate would both reduce environmental and health risks, and give an agricultural edge to the farmer. [ 143 ]


Some micro-organisms have a version of EPSPS that is resistant to glyphosate inhibition. One of these was isolated from an  Agrobacterium  strain CP4 (CP4 EPSPS) that was resistant to glyphosate. [ 144 ] [ 145 ]  The CP4 EPSPS gene was engineered for plant  expression  by  fusing  the 5' end of the gene to a  chloroplast   transit peptide  derived from the  petunia  EPSPS. This transit peptide was used because it had shown previously an ability to deliver bacterial EPSPS to the chloroplasts of other plants. This CP4 EPSPS gene was  cloned  and  transfected  into  soybeans .


The  plasmid  used to move the gene into soybeans was PV-GMGTO4. It contained three bacterial genes, two CP4 EPSPS genes, and a gene  encoding   beta-glucuronidase  (GUS) from  Escherichia coli  as a marker. The DNA was injected into the soybeans using the  particle acceleration method . Soybean cultivar A54O3 was used for the  transformation .


Tobacco plants have been engineered to be resistant to the herbicide  bromoxynil . [ 146 ]


Crops have been commercialized that are resistant to the herbicide  glufosinate , as well. [ 147 ]  Crops engineered for resistance to multiple herbicides to allow farmers to use a mixed group of two, three, or four different chemicals are under development to combat growing herbicide resistance. [ 148 ] [ 149 ]


In October 2014 the US EPA registered  Dow 's  Enlist Duo  maize, which is genetically modified to be resistant to both  glyphosate  and  2,4-D , in six states. [ 150 ] [ 151 ] [ 152 ]  Inserting a bacterial aryloxyalkanoate dioxygenase gene,  aad1  makes the corn resistant to 2,4-D. [ 150 ] [ 153 ]  The USDA had approved maize and soybeans with the mutation in September 2014. [ 154 ]


Monsanto has requested approval for a stacked strain that is tolerant of both glyphosate and  dicamba . The request includes plans for avoiding  herbicide drift  to other crops. [ 155 ]  Significant damage to other non-resistant crops occurred from dicamba formulations intended to reduce  volatilization  drifting when sprayed on resistant soybeans in 2017. [ 156 ]  The newer dicamba formulation labels specify to not spray when average wind speeds are above 10–15 miles per hour (16–24 km/h) to avoid particle drift, average wind speeds below 3 miles per hour (4.8 km/h) to avoid  temperature inversions , and rain or high temperatures are in the next day forecast. However, these conditions typically only occur during June and July for a few hours at a time. [ 157 ] [ 158 ]


Tobacco, corn, rice and some other crops have been engineered to express genes encoding for insecticidal proteins from  Bacillus thuringiensis  (Bt). [ 159 ] [ 160 ]  The introduction of Bt crops during the period between 1996 and 2005 has been estimated to have reduced the total volume of insecticide active ingredient use in the United States by over 100 thousand tons. This represents a 19.4% reduction in insecticide use. [ 161 ]


In the late 1990s, a  genetically modified potato  that was resistant to the  Colorado potato beetle  was withdrawn because major buyers rejected it, fearing consumer opposition. [ 112 ]


Plant viruses are a cause of around half of the plant diseases emerging worldwide, and an estimated 10–15% of losses in crop yields. [ 162 ]  Papaya, potatoes, and squash have been engineered to resist viral pathogens such as  cucumber mosaic virus  which, despite its name, infects a wide variety of plants. [ 163 ] [ 162 ]
Virus resistant papaya were developed in response to a  papaya ringspot virus  (PRV) outbreak in Hawaii in the late 1990s. They incorporate PRV DNA. [ 164 ] [ 165 ]  By 2010, 80% of Hawaiian papaya plants were genetically modified. [ 166 ] [ 167 ]


Potatoes were engineered for resistance to  potato leaf roll virus  and  Potato virus Y  in 1998. Poor sales led to their market withdrawal after three years. [ 168 ]


Yellow squash that were resistant to at first two, then three viruses were developed, beginning in the 1990s. The viruses are watermelon, cucumber and zucchini/courgette yellow mosaic. Squash was the second GM crop to be approved by US regulators. The trait was later added to zucchini. [ 169 ]


Many strains of corn have been developed in recent years to combat the spread of  Maize dwarf mosaic virus , a costly virus that causes stunted growth which is carried in  Johnson grass  and spread by aphid insect vectors. These strands are commercially available although the resistance is not standard among GM corn variants. [ 170 ]


In 2012, the FDA approved the first  plant-produced pharmaceutical , a treatment for  Gaucher's Disease . [ 171 ]  Tobacco plants have been modified to produce therapeutic antibodies. [ 172 ]


Algae  is under development for use in  biofuels . [ 173 ]  The focus of Microalgae for mass production for biofuels modifying the algae to produce more lipid has become a focus yet will take years to see results due to the cost of this process to extract lipids. [ 174 ]  Researchers in Singapore were working on GM  jatropha  for biofuel production. [ 175 ]   Syngenta  has USDA approval to market a maize trademarked Enogen that has been genetically modified to convert its starch to sugar for  ethanol . [ 176 ]  Some trees have been  genetically modified  to either have less  lignin , or to express lignin with chemically labile bonds. Lignin is the critical limiting factor when using wood to make  bio-ethanol  because lignin limits the accessibility of  cellulose   microfibrils  to  depolymerization  by  enzymes . [ 177 ]  Besides with trees, the chemically labile lignin bonds are also very useful for cereal crops such as maize, [ 178 ] [ 179 ]


Companies and labs are working on plants that can be used to make  bioplastics . [ 180 ]  Potatoes that produce industrially useful starches have been developed as well. [ 181 ]   Oilseed  can be modified to produce fatty acids for  detergents , substitute  fuels  and  petrochemicals .


Besides the modified oilcrop above,  Camelina sativa  has also been modified to produce  Helicoverpa armigera   pheromones  and is in progress with a  Spodoptera frugiperda  version. The  H. armigera  pheromones have been tested and are effective. [ 182 ]


Scientists at the University of York developed a weed ( Arabidopsis thaliana ) that contains genes from bacteria that could clean  TNT  and  RDX -explosive soil contaminants in 2011. [ 183 ]  16 million hectares in the US (1.5% of the total surface) are estimated to be contaminated with TNT and RDX. However  A. thaliana  was not tough enough for use on military test grounds. [ 184 ]  Modifications in 2016 included  switchgrass  and  bentgrass . [ 185 ]


Genetically modified plants have been used for  bioremediation  of contaminated soils.  Mercury ,  selenium  and organic pollutants such as  polychlorinated biphenyls  (PCBs). [ 184 ] [ 186 ]


Marine environments are especially vulnerable since pollution such as  oil spills  are not containable. In addition to anthropogenic pollution, millions of tons of  petroleum  annually enter the marine environment from natural seepages. Despite its toxicity, a considerable fraction of petroleum oil entering marine systems is eliminated by the hydrocarbon-degrading activities of microbial communities. Particularly successful is a recently discovered group of specialists, the so-called  hydrocarbonoclastic bacteria  (HCCB) that may offer useful genes. [ 187 ]


Crops such as  maize  reproduce sexually each year. This randomizes which genes get propagated to the next generation, meaning that desirable traits can be lost. To maintain a high-quality crop, some farmers purchase seeds every year. Typically, the seed company maintains two  inbred  varieties and crosses them into a  hybrid  strain that is then sold. Related plants like  sorghum  and gamma grass are able to perform  apomixis , a form of asexual reproduction that keeps the plant's DNA intact. This trait is apparently controlled by a single dominant gene, but traditional breeding has been unsuccessful in creating asexually-reproducing maize. Genetic engineering offers another route to this goal. Successful modification would allow farmers to replant harvested seeds that retain desirable traits, rather than relying on purchased seed. [ 188 ]


Genetic modifications to some crops also exist, which make it easier to process the crop, i.e. by growing it in a more compact form. [ 189 ]  Crops such as tomatoes have been modified to be seedless. [ 190 ]  Tobacco has been modified to produce  chlorophyll c  in addition to  a  and  b , increasing growth rates. The transgene was discovered in  marine algae , which uses it to gain energy from the blue light that is able to penetrate seawater more effectively than longer wavelengths. [ 191 ] [ 192 ]


Margarine


Emulsifiers in packaged foods [ 194 ]


high-fructose corn syrup


corn starch [ 194 ]


Soybean oil [ 194 ]


Several modifications of  Camelina sativa  have been done, see  §Edible oils  and  §Non-pesticide pest management products  above.


The number of USDA-approved field releases for testing grew from 4 in 1985 to 1,194 in 2002 and averaged around 800 per year thereafter. The number of sites per release and the number of gene constructs (ways that the gene of interest is packaged together with other elements) – have rapidly increased since 2005. Releases with agronomic properties (such as drought resistance) jumped from 1,043 in 2005 to 5,190 in 2013. As of September 2013, about 7,800 releases had been approved for corn, more than 2,200 for soybeans, more than 1,100 for cotton, and about 900 for potatoes. Releases were approved for herbicide tolerance (6,772 releases), insect resistance (4,809), product quality such as flavor or nutrition (4,896), agronomic properties like drought resistance (5,190), and virus/fungal resistance (2,616). The institutions with the most authorized field releases include Monsanto with 6,782, Pioneer/DuPont with 1,405, Syngenta with 565, and USDA's Agricultural Research Service with 370. As of September 2013 USDA had received proposals for releasing GM rice, squash, plum, rose, tobacco, flax, and chicory. [ 207 ]


Researchers at  North Carolina State University  are designing genetically modified plants or  seeds  to ship to  Mars , that can live in  habitable   greenhouses  or  bio-domes  to help build  plant life  on the planet. NASA's  NIAC  is sponsoring this work on designer plants/trees or  genetically modified   vegetation  that could better survive on Mars.  CRISPR gene editing  from  extremophiles  on Earth is used to help withstand the harsh  Martian regolith  and  atmosphere , including such challenges as  ultraviolet radiation , extreme cold, low  atmospheric pressure ,  perchlorates , and  drought tolerance . [ 208 ]  The plants and seeds could then be tested outdoors to try and start an  ecosystem  for the full  terraforming of Mars . [ 209 ] [ 210 ] [ 211 ] [ 212 ]


Constant exposure to a toxin creates  evolutionary pressure  for pests resistant to that toxin. [ 213 ]  Over-reliance on  glyphosate  and a reduction in the diversity of weed management practices allowed the spread of glyphosate resistance in 14 weed species in the US, [ 207 ]  and in soybeans. [ 5 ]


To reduce resistance to  Bacillus thuringiensis  (Bt) crops, the 1996 commercialization of transgenic cotton and maize came with a management strategy to prevent insects from becoming resistant. Insect resistance management plans are mandatory for Bt crops. The aim is to encourage a large population of pests so that any (recessive) resistance genes are diluted within the population. Resistance lowers evolutionary fitness in the absence of the stressor, Bt. In refuges, non-resistant strains outcompete resistant ones. [ 214 ]


With sufficiently high levels of transgene expression, nearly all of the heterozygotes (S/s), i.e., the largest segment of the pest population carrying a resistance allele, will be killed before maturation, thus preventing transmission of the resistance gene to their progeny. [ 215 ]  Refuges (i. e., fields of nontransgenic plants) adjacent to transgenic fields increases the likelihood that homozygous resistant (s/s) individuals and any surviving heterozygotes will mate with susceptible (S/S) individuals from the refuge, instead of with other individuals carrying the resistance allele. As a result, the resistance gene frequency in the population remains lower.


Complicating factors can affect the success of the high-dose/refuge strategy. For example, if the temperature is not ideal, thermal stress can lower Bt toxin production and leave the plant more susceptible. More importantly, reduced late-season expression has been documented, possibly resulting from  DNA methylation  of the  promoter . [ 216 ]  The success of the high-dose/refuge strategy has successfully maintained the value of Bt crops. This success has depended on factors independent of management strategy, including low initial resistance allele frequencies, fitness costs associated with resistance, and the abundance of non-Bt host plants outside the refuges. [ 217 ]


Companies that produce Bt seed are introducing strains with multiple Bt proteins. Monsanto did this with Bt cotton in India, where the product was rapidly adopted. [ 218 ]  Monsanto has also; in an attempt to simplify the process of implementing refuges in fields to comply with Insect Resistance Management(IRM) policies and prevent irresponsible planting practices; begun marketing seed bags with a set proportion of refuge (non-transgenic) seeds mixed in with the Bt seeds being sold. Coined "Refuge-In-a-Bag" (RIB), this practice is intended to increase farmer compliance with refuge requirements and reduce additional labor needed at planting from having separate Bt and refuge seed bags on hand. [ 219 ]  This strategy is likely to reduce the likelihood of Bt-resistance occurring for  corn rootworm , but may increase the risk of resistance for  lepidopteran  corn pests, such as  European corn borer . Increased concerns for resistance with seed mixtures include partially resistant larvae on a Bt plant being able to move to a susceptible plant to survive or cross pollination of refuge pollen on to Bt plants that can lower the amount of Bt expressed in kernels for ear feeding insects. [ 220 ] [ 221 ]


Best management practices  (BMPs) to control weeds may help delay resistance. BMPs include applying multiple herbicides with different modes of action, rotating crops, planting weed-free seed, scouting fields routinely, cleaning equipment to reduce the transmission of weeds to other fields, and maintaining field borders. [ 207 ]  The most widely planted GM crops are designed to tolerate herbicides. By 2006 some weed populations had evolved to tolerate some of the same herbicides.  Palmer amaranth  is a weed that competes with cotton. A native of the southwestern US, it traveled east and was first found resistant to glyphosate in 2006, less than 10 years after GM cotton was introduced. [ 222 ] [ 223 ]


Farmers generally use less insecticide when they plant Bt-resistant crops. Insecticide use on corn farms declined from 0.21 pound per planted acre in 1995 to 0.02 pound in 2010. This is consistent with the decline in  European corn borer  populations as a direct result of Bt corn and cotton. The establishment of minimum refuge requirements helped delay the evolution of Bt resistance. However, resistance appears to be developing to some Bt traits in some areas. [ 207 ]  In Columbia, GM cotton has reduced insecticide usage by 25% and herbicide usage by 5%, and GM corn has reduced insecticide and herbicide usage by 66% and 13%, respectively. [ 224 ]


By leaving at least 30% of crop residue on the soil surface from harvest through planting,  conservation tillage  reduces soil erosion from wind and water, increases water retention, and reduces  soil degradation  as well as water and chemical runoff. In addition, conservation tillage reduces the carbon footprint of agriculture. [ 225 ]  A 2014 review covering 12 states from 1996 to 2006, found that a 1% increase in herbicde-tolerant (HT) soybean adoption leads to a 0.21% increase in conservation tillage and a 0.3% decrease in quality-adjusted herbicide use. [ 225 ]


Combined features of increased yield, decreased land use, reduced use of fertilizer and reduced farming machinery use create a feedback loop that reduces carbon emissions related to farming. These reductions have been estimated at 7.5% of total agricultural emissions in the EU or 33 millions tons of CO 2 [ 226 ]  and an estimated 8.76 million tons of CO 2  in Columbia. [ 224 ]


The use of drought tolerant crops can increase yield in water-scarce locations, making farming possible in new areas. The adoption of drought tolerant maize in Ghana was shown to increase yield by more than 150% and boost commercialization intensity, although it did not significantly affect farm income. [ 227 ]


The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of genetically modified crops. There are differences in the regulation of GM crops between countries, with some of the most marked differences occurring between the US and Europe. Regulation varies in a given country depending on the intended use of each product. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety. [ 228 ] [ 229 ]


In 2013, GM crops were planted in 27 countries; 19 were developing countries and 8 were developed countries. 2013 was the second year in which developing countries grew a majority (54%) of the total GM harvest. 18 million farmers grew GM crops; around 90% were small-holding farmers in developing countries. [ 1 ]


The  United States Department of Agriculture  (USDA) reports every year on the total area of GM crop varieties planted in the United States. [ 231 ] [ 232 ]  According to  National Agricultural Statistics Service , the states published in these tables represent 81–86 percent of all corn planted area, 88–90 percent of all soybean planted area, and 81–93 percent of all upland cotton planted area (depending on the year).


Global estimates are produced by the  International Service for the Acquisition of Agri-biotech Applications  (ISAAA) and can be found in their annual reports, "Global Status of Commercialized Transgenic Crops". [ 1 ] [ 233 ]


Farmers have widely adopted GM technology (see figure). Between 1996 and 2013, the total surface area of land cultivated with GM crops increased by a factor of 100, from 17,000 square kilometers (4,200,000 acres) to 1,750,000 km 2  (432 million acres). [ 1 ]  10% of the world's  arable land  was planted with GM crops in 2010. [ 54 ]  As of 2011, 11 different transgenic crops were grown commercially on 395 million acres (160 million hectares) in 29 countries such as the US, Brazil, Argentina, India, Canada, China, Paraguay, Pakistan, South Africa, Uruguay, Bolivia, Australia, Philippines, Myanmar, Burkina Faso, Mexico and Spain. [ 54 ]  One of the key reasons for this widespread adoption is the perceived economic benefit the technology brings to farmers. For example, the system of planting glyphosate-resistant seed and then applying glyphosate once plants emerged provided farmers with the opportunity to dramatically increase the yield from a given plot of land, since this allowed them to plant rows closer together. Without it, farmers had to plant rows far enough apart to control post-emergent weeds with mechanical tillage. [ 234 ]  Likewise, using Bt seeds means that farmers do not have to purchase insecticides, and then invest time, fuel, and equipment in applying them. However critics have disputed whether yields are higher and whether chemical use is less, with GM crops. See  Genetically modified food controversies  article for information.


In the US, by 2014, 94% of the planted area of soybeans, 96% of cotton and 93% of corn were genetically modified varieties. [ 235 ] [ 236 ] [ 237 ]  Genetically modified soybeans carried herbicide-tolerant traits only, but maize and cotton carried both herbicide tolerance and insect protection traits (the latter largely Bt protein). [ 238 ]  These constitute "input-traits" that are aimed to financially benefit the producers, but may have indirect environmental benefits and cost benefits to consumers. The Grocery Manufacturers of America estimated in 2003 that 70–75% of all processed foods in the U.S. contained a GM ingredient. [ 239 ]


As of 2024, the cultivation of genetically engineered crops is banned in 38 countries, while 9 countries have banned their import. [ 240 ]  Europe grows relatively few genetically engineered crops [ 241 ]  with the exception of Spain, where one fifth of maize is genetically engineered, [ 242 ]  and smaller amounts in five other countries. [ 243 ]  The  EU  had a 'de facto' ban on the approval of new GM crops, from 1999 until 2004. [ 244 ] [ 245 ]  GM crops are now regulated by the EU. [ 246 ]   Developing countries grew 54 percent of genetically engineered crops in 2013. [ 1 ]


In recent years GM crops expanded rapidly in  developing countries . In 2013 approximately 18 million farmers grew 54% of worldwide GM crops in developing countries. [ 1 ]  2013's largest increase was in Brazil (403,000 km 2  versus 368,000 km 2  in 2012). GM cotton began growing in India in 2002, reaching 110,000 km 2  in 2013. [ 1 ]


According to the 2013 ISAAA brief: "a total of 36 countries (35 + EU-28) have granted regulatory approvals for biotech crops for food and/or feed use and for environmental release or planting since 1994 ... a total of 2,833 regulatory approvals involving 27 GM crops and 336 GM events (NB: an "event" is a specific genetic modification in a specific species) have been issued by authorities, of which 1,321 are for food use (direct use or processing), 918 for feed use (direct use or processing) and 599 for environmental release or planting. Japan has the largest number (198), followed by the U.S.A. (165, not including "stacked" events), Canada (146), Mexico (131), South Korea (103), Australia (93), New Zealand (83), European Union (71 including approvals that have expired or under renewal process), Philippines (68), Taiwan (65), Colombia (59), China (55) and South Africa (52). Maize has the largest number (130 events in 27 countries), followed by cotton (49 events in 22 countries), potato (31 events in 10 countries), canola (30 events in 12 countries) and soybean (27 events in 26 countries). [ 1 ]


Direct genetic engineering has been controversial since its introduction. Most, but not all of the controversies are over GM foods rather than crops per se. GM foods are the subject of protests, vandalism, referendums, legislation, court action [ 247 ]  and scientific disputes. The controversies involve consumers, biotechnology companies, governmental regulators, non-governmental organizations and scientists.


Opponents have objected to GM crops on multiple grounds including environmental impacts, food safety, whether GM crops are needed to address food needs, whether they are sufficiently accessible to farmers in developing countries, [ 248 ]  concerns over subjecting crops to  intellectual property  law, and on religious grounds. [ 249 ]  Secondary issues include labeling, the behavior of government regulators, the effects of pesticide use and pesticide tolerance.


A significant environmental concern about using genetically modified crops is possible cross-breeding with related crops, giving them advantages over naturally occurring varieties. One example is a glyphosate-resistant rice crop that crossbreeds with a weedy relative, giving the weed a competitive advantage. The transgenic hybrid had higher rates of photosynthesis, more shoots and flowers, and more seeds than the non-transgenic hybrids. [ 250 ]  This demonstrates the possibility of ecosystem damage by GM crop usage.


The role of  biopiracy  in the development of GM crops is also potentially problematic, as developed countries have gotten economic gain by using the genetic resources of developing countries. In the twentieth century, the International Rice Research Institute catalogued the genomes of almost 80,000 varieties of rice from Asian farms, which has since been used to create new higher yielding varieties of rice. These new varieties create almost 655 million dollars of economic gain for Australia, USA, Canada, and New Zealand every year. [ 251 ]


No reports of ill effects from GM food have been documented in the human population. [ 252 ] [ 253 ] [ 254 ]  GM crop labeling is required in many countries, although the United States  Food and Drug Administration  does not, nor does it distinguish between approved GM and non-GM foods. [ 255 ]  The United States enacted a law that requires labeling regulations to be issued by July 2018. It allows indirect disclosure such as with a phone number, bar code, or web site. [ 256 ]


Advocacy groups such as  Center for Food Safety ,  Union of Concerned Scientists , and  Greenpeace  claim that risks related to GM food have not been adequately examined and managed, that GM crops are not sufficiently tested and should be labelled, and that regulatory authorities and scientific bodies are too closely tied to industry.  [ citation needed ]  Some studies have claimed that genetically modified crops can cause harm; [ 257 ] [ 258 ]  a 2016 review that reanalyzed the data from six of these studies found that their statistical methodologies were flawed and did not demonstrate harm, and said that conclusions about GM crop safety should be drawn from "the totality of the evidence ... instead of far-fetched evidence from single studies". [ 259 ]


But see also:


Domingo JL, Giné Bordonaba J (May 2011).  "A literature review on the safety assessment of genetically modified plants"   (PDF) .  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".  Science, Technology, & Human Values .  40  (6):  883– 914.  doi : 10.1177/0162243915598381 .  S2CID   40855100 .  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.


Genetically modified foods  ( GM foods ), also known as  genetically engineered foods  ( GE foods ), or  bioengineered foods  are foods produced from  organisms  that have had changes introduced into their  DNA  using various methods of  genetic engineering . Genetic engineering techniques allow for the introduction of new traits as well as greater control over traits when compared to previous methods, such as  selective breeding  and  mutation breeding . [ 1 ]


The discovery of DNA and the improvement of genetic technology in the 20th century played a crucial role in the development of transgenic technology. [ 2 ]  In 1988, genetically modified microbial enzymes were first approved for use in food manufacture. Recombinant rennet was used in few countries in the 1990s. [ 3 ]  Commercial sale of genetically modified foods began in 1994, when  Calgene  first marketed its unsuccessful  Flavr Savr  delayed-ripening tomato. [ 4 ] [ 5 ]  Most food modifications have primarily focused on  cash crops  in high demand by farmers such as  soybean ,  maize/corn ,  canola , and  cotton .  Genetically modified crops  have been engineered for resistance to  pathogens  and  herbicides  and for better nutrient profiles. The production of golden rice in 2000 marked a further improvement in the nutritional value of genetically modified food. [ 6 ]   GM livestock  have been developed, although, as of 2015 [update] , none were on the market. [ 7 ]  As of 2015, the   AquAdvantage  salmon was the only animal approved for commercial production, sale and consumption by the FDA. [ 8 ] [ 9 ]   It is the first genetically modified animal to be approved for human consumption.


Genes encoded for desired features, for instance an improved nutrient level, pesticide and  herbicide resistances , and the possession of therapeutic substances, are often extracted and transferred to the target organisms, providing them with superior survival and production capacity. [ 10 ] [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ]  The improved utilization value usually gave consumers benefit in specific aspects. [ 10 ] [ 11 ] [ 15 ]


There is a  scientific consensus [ 17 ] [ 18 ] [ 19 ] [ 20 ] [ 21 ]  that currently available food derived from GM crops poses no greater risk to human health than conventional food, [ 22 ] [ 23 ] [ 24 ] [ 25 ] [ 26 ] [ 27 ] [ 28 ]  but that each GM food needs to be tested on a case-by-case basis before introduction. [ 29 ] [ 30 ] [ 31 ]  Nonetheless, members of the public are much less likely than scientists to perceive GM foods as safe. [ 32 ] [ 33 ] [ 34 ] [ 35 ]  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, [ 36 ] [ 37 ] [ 38 ] [ 39 ]  which varied due to geographical, religious, social, and other factors. [ 10 ] [ 40 ] [ 41 ] [ 42 ] [ 43 ]