Genetically modified foods are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering as opposed to traditional  cross breeding . [ 44 ] [ 45 ]  In the U.S., the  Department of Agriculture  (USDA) and the  Food and Drug Administration  (FDA) favor the use of the term  genetic engineering  over  genetic modification  as being more precise; the USDA defines  genetic modification  to include "genetic engineering or other more traditional methods". [ 46 ] [ 47 ]


According to the  World Health Organization , "Foods produced from or using GM organisms are often referred to as GM foods." [ 44 ]


What constitutes a  genetically modified organism  (GMO) is not clear and varies widely between countries, international bodies and other communities, has changed significantly over time, and was subject to numerous exceptions based on "convention", such as exclusion of  mutation breeding  from the EU definition. [ 48 ]


Even greater inconsistency and confusion is associated with various "Non-GMO" or "GMO-free" labelling schemes in food marketing, where even products such as water or salt, that do not contain any organic substances and genetic material (and thus cannot be genetically modified by definition) are being labelled to create an impression of being "more healthy." [ 49 ] [ 50 ]


Human-directed  genetic  manipulation of food began with the  domestication  of plants and animals through  artificial selection  at about 10,500 to 10,100 BC. [ 51 ] : 1   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 (GM). [ 51 ] : 1  [ 52 ] : 1   With the discovery of  DNA  in the early 1900s and various advancements in genetic techniques through the 1970s [ 2 ]  it became possible to directly alter the DNA and genes within food.


Genetically modified microbial enzymes were the first application of  genetically modified organisms  in food production and were approved in 1988 by the US  Food and Drug Administration . [ 3 ]  In the early 1990s, recombinant  chymosin  was approved for use in several countries. [ 3 ] [ 53 ]  Cheese had typically been made using the enzyme complex  rennet  that had been extracted from cows' stomach lining. Scientists modified  bacteria  to produce chymosin, which was also able to clot milk, resulting in  cheese curds . [ 54 ]


The first genetically modified food approved for release was the  Flavr Savr  tomato in 1994. [ 4 ]  Developed by  Calgene , it was engineered to have a longer shelf life by inserting an  antisense gene  that delayed ripening. [ 55 ]  China was the first country to commercialize a transgenic crop in 1993 with the introduction of virus-resistant tobacco. [ 56 ]  In 1995,  Bacillus thuringiensis  (Bt) Potato was approved for cultivation, making it the first pesticide producing crop to be approved in the US. [ 57 ]  Other genetically modified crops receiving marketing approval in 1995 were:  canola  with modified oil composition,  Bt maize/corn , cotton resistant to the herbicide  bromoxynil ,  Bt cotton ,  glyphosate -tolerant  soybeans , virus-resistant  squash , and another delayed ripening tomato. [ 4 ]


With the creation of  golden rice  in 2000, scientists had genetically modified food to increase its nutrient value for the first time. [ 6 ]


By 2010, 29 countries had planted commercialized biotech crops and a further 31 countries had granted regulatory approval for transgenic crops to be imported. [ 58 ]  The US was the leading country in the production of GM foods in 2011, with twenty-five GM crops having received regulatory approval. [ 59 ]  In 2015, 92% of corn, 94% of soybeans, and 94% of cotton produced in the US were genetically modified varieties. [ 60 ]


The first genetically modified animal to be approved for food use was  AquAdvantage salmon  in 2015. [ 61 ]  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. [ 62 ]


A GM white button mushroom ( Agaricus bisporus ) has been approved in the  United States  since 2016. See  §Mushroom  below.


The most widely planted GMOs are designed to tolerate herbicides. The use of herbicides presents a strong  selection pressure  on treated weeds to gain  resistance to the herbicide . Widespread planting of GM crops resistant to glyphosate has led to the use of glyphosate to control weeds and many weed species, such as  Palmer amaranth , acquiring resistance to the herbicide. [ 63 ] [ 64 ] [ 65 ]


In 2021, the first  CRISPR-edited  food has gone on public sale in Japan. Tomatoes were genetically modified for around five times the normal amount of possibly calming [ 66 ]   GABA . [ 67 ]  CRISPR was first applied in tomatoes in 2014. [ 68 ]  Shortly afterwards, the first CRISPR-gene-edited marine animal/ seafood  and second set of CRISPR-edited food has gone on public sale in Japan: two fish of which one species grows to twice the size of natural specimens due to disruption of  leptin , which controls appetite, and the other grows to 1.2 the natural average size with the same amount of food due to disabled  myostatin , which inhibits  muscle growth . [ 69 ] [ 70 ] [ 71 ]


Creating genetically modified food is a multi-step process. The first step is to identify a useful gene from another organism that you would like to add. The gene can be taken from a  cell [ 72 ]  or  artificially synthesised , [ 73 ]  and then combined with other genetic elements, including a  promoter  and  terminator  region and a  selectable marker . [ 74 ]  Then the genetic elements are  inserted into the targets genome . DNA is generally inserted into animal cells using  microinjection , where it can be injected through the cell's  nuclear envelope  directly into the  nucleus , or through the use of  viral vectors . [ 75 ]  In plants the DNA is often inserted using  Agrobacterium -mediated recombination , [ 76 ] [ 77 ]   biolistics [ 78 ]  or  electroporation . As only a single cell is transformed with genetic material, the organism must be  regenerated  from that single cell. In plants this is accomplished through  tissue culture . [ 79 ] [ 80 ]  In animals it is necessary to ensure that the inserted DNA is present in the  embryonic stem cells . [ 76 ]  Further testing using  PCR ,  Southern hybridization , and  DNA sequencing  is conducted to confirm that an organism contains the new gene. [ 81 ]


Traditionally the new genetic material was inserted randomly within the host genome.  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 , [ 82 ] [ 83 ]   zinc finger nucleases , [ 84 ] [ 85 ]   transcription activator-like effector nucleases  (TALENs), [ 86 ] [ 87 ]  and the Cas9-guideRNA system (adapted from CRISPR). [ 88 ] [ 89 ]  TALEN and CRISPR are the two most commonly used and each has its own advantages. [ 90 ]  TALENs have greater target specificity, while CRISPR is easier to design and more efficient. [ 90 ]


Genetically modified crops (GM crops) are genetically modified plants that are used in  agriculture . The first crops developed were used for animal or human food and provide resistance to certain pests, diseases, environmental conditions, spoilage or chemical treatments (e.g. resistance to a  herbicide ). The second generation of crops aimed to improve the quality, often by altering the  nutrient profile . Third generation genetically modified crops could be used for non-food purposes, including the production of  pharmaceutical agents ,  biofuels , and other industrially useful goods, as well as for  bioremediation . [ 91 ]  GM crops have been produced to improve harvests through reducing insect pressure, increase nutrient value and tolerate different  abiotic stresses . As of 2018, the commercialised crops are limited mostly to  cash crops  like cotton, soybean, maize/corn and canola and the vast majority of the introduced traits provide either herbicide tolerance or insect resistance. [ 91 ]


The majority of GM crops have been modified to be resistant to selected herbicides, usually a  glyphosate  or  glufosinate  based one. Genetically modified crops engineered to resist herbicides are now more available than conventionally bred resistant varieties. [ 92 ]  Most currently available genes used to engineer insect resistance come from the  Bacillus thuringiensis  (Bt) bacterium and code for  delta endotoxins . A few use the genes that encode for  vegetative insecticidal proteins . [ 93 ]  The only gene commercially used to provide insect protection that does not originate from  B. thuringiensis  is the  Cowpea   trypsin inhibitor  (CpTI). CpTI was first approved for use cotton in 1999 and is currently undergoing trials in rice. [ 94 ] [ 95 ]  Less than one percent of GM crops contained other traits, which include providing virus resistance, delaying  senescence  and altering the plants composition. [ 96 ]


Adoption by farmers has been rapid, between 1996 and 2013, the total surface area of land cultivated with GM crops increased by a factor of 100. [ 97 ]  Geographically though the spread has been uneven, with strong growth in the  Americas  and parts of Asia and little in Europe and Africa [ 91 ]  in 2013 only 10% of world cropland was GM, with the US, Canada, Brazil, and Argentina being 90% of that. [ 21 ]  Its  socioeconomic  spread has been more even, with approximately 54% of worldwide GM crops grown in  developing countries  in 2013. [ 97 ]  Although doubts have been raised, [ 98 ]  most studies have found growing GM crops to be beneficial to farmers through decreased pesticide use as well as increased crop yield and farm profit. [ 99 ] [ 100 ] [ 101 ]


Long before humans began using transgenics,  sweet potato  emerged naturally 8000 years ago by embedding of genes from bacteria, that increased its sugar content. Kyndt et al 2015 finds  Agrobacterium tumefaciens  DNA from this natural transgenic event still in the crop's genome today. [ 102 ] [ 103 ] : 141  [ 104 ] [ 105 ]


Papaya  was genetically modified to resist the  ringspot virus  (PSRV). "SunUp" is a transgenic red-fleshed Sunset papaya  cultivar  that is  homozygous  for the coat protein gene PRSV; "Rainbow" is a yellow-fleshed  F1 hybrid  developed by crossing 'SunUp' and nontransgenic yellow-fleshed "Kapoho". [ 106 ]  The GM cultivar was approved in 1998 [ 107 ]  and by 2010 80% of Hawaiian papaya was genetically engineered. [ 108 ]   The New York Times  stated, "without it, the state's papaya industry would have collapsed". [ 108 ]  In China, a transgenic PRSV-resistant papaya was developed by  South China Agricultural University  and was first approved for commercial planting in 2006; as of 2012 95% of the papaya grown in  Guangdong  province and 40% of the papaya grown in  Hainan  province was genetically modified. [ 109 ]  In  Hong Kong , where there is an exemption on growing and releasing any varieties of GM papaya, more than 80% of grown and imported papayas were transgenic. [ 110 ] [ 111 ]


The New Leaf potato, a GM food developed using  Bacillus thuringiensis  (Bt), was made to provide in-plant protection from the yield-robbing  Colorado potato beetle . [ 112 ]  The New Leaf potato, brought to market by  Monsanto  in the late 1990s, was developed for the fast food market. It was withdrawn in 2001 after retailers rejected it and food processors ran into export problems. In 2011,  BASF  requested the  European Food Safety Authority 's approval for cultivation and marketing of its Fortuna potato as feed and food. The potato was made resistant to  late blight  by adding resistant genes blb1 and blb2 that originate from the Mexican wild potato  Solanum bulbocastanum . [ 113 ] [ 114 ]  In February 2013, BASF withdrew its application. [ 115 ] [ 116 ]  In 2014, the USDA approved a  genetically modified potato  developed by  J. R. Simplot Company  that contained ten genetic modifications that prevent bruising and produce less  acrylamide  when fried. The modifications eliminate specific proteins from the potatoes, via  RNA interference , rather than introducing novel proteins. [ 117 ] [ 118 ]


As of 2005, about 13% of the  Zucchini  grown in the US was genetically modified to resist three viruses; that variety is also grown in Canada. [ 119 ] [ 120 ]


In 2013, the USDA approved the import of a GM pineapple that is pink in color and that "overexpresses" a gene derived from  tangerines  and suppress other genes, increasing production of  lycopene . The plant's flowering cycle was changed to provide for more uniform growth and quality. The fruit "does not have the ability to propagate and persist in the environment once they have been harvested", according to USDA APHIS. According to Del Monte's submission, the pineapples are commercially grown in a "monoculture" that prevents seed production, as the plant's flowers aren't exposed to compatible  pollen  sources. Importation into Hawaii is banned for "plant sanitation" reasons. [ 121 ]  Del Monte launched sales of their pink pineapples in October 2020, marketed under the name "Pinkglow". [ 122 ]


In February 2015  Arctic Apples  were approved by the USDA, [ 123 ]  becoming the first genetically modified apple approved for sale in the US. [ 124 ]   Gene silencing  is used to reduce the expression of  polyphenol oxidase (PPO) , thus preventing the fruit from browning. [ 125 ]


Maize/corn  used for food and  ethanol  has been genetically modified to tolerate various  herbicides  and to express a protein from  Bacillus thuringiensis  (Bt) that kills certain insects. [ 126 ]  About 90% of the corn grown in the US was genetically modified in 2010. [ 127 ]  In the US in 2015, 81% of corn acreage contained the Bt trait and 89% of corn acreage contained the glyphosate-tolerant trait. [ 60 ]  Corn can be processed into grits, meal and flour as an ingredient in pancakes, muffins, doughnuts, breadings and batters, as well as baby foods, meat products, cereals and some fermented products. Corn-based masa flour and masa dough are used in the production of taco shells, corn chips and tortillas. [ 128 ]


Soybeans accounted for half of all genetically modified crops planted in 2014. [ 96 ]   Genetically modified soybean  has been modified to tolerate herbicides and produce healthier oils. [ 129 ]  In 2015, 94% of  soybean  acreage in the U.S. was genetically modified to be glyphosate-tolerant. [ 60 ]


Golden rice  is the most well known GM crop that is aimed at increasing nutrient value. It has been engineered with three genes that  biosynthesise   beta-carotene , a precursor of  vitamin A , in the edible parts of rice. [ 130 ]  It is intended to produce a fortified food to be grown and consumed in areas with a  shortage of dietary vitamin A , [ 131 ]  a deficiency which each year is estimated to kill 670,000 children under the age of 5 [ 132 ]  and cause an additional 500,000 cases of irreversible childhood blindness. [ 133 ]   The original golden rice produced 1.6μg/g of the  carotenoids , with further development increasing this 23 times. [ 134 ]  In 2018 it gained its first approvals for use as food. [ 135 ]


As of December 2017,  genetically modified wheat  has been evaluated in field trials, but has not been released commercially. [ 136 ] [ 137 ] [ 138 ]


In April 2016, a white button mushroom ( Agaricus bisporus ) modified using the  CRISPR  technique received  de facto  approval in the United States, after the USDA said it would not have to go through the agency's regulatory process. The agency considers the mushroom exempt because the editing process did not involve the introduction of foreign DNA, rather several  base pairs  were deleted from a duplicated gene coding for an  enzyme  that causes browning causing a 30% reduction in the level of that enzyme. [ 139 ]


Genetically modified livestock are organisms from the group of cattle, sheep, pigs, goats, birds, horses and fish kept for human consumption, whose genetic material ( DNA ) has been altered using  genetic engineering  techniques. In some cases, the aim is to introduce a new  trait  to the animals which does not occur naturally in the species, i.e.  transgenesis .


A 2003 review published on behalf of  Food Standards Australia New Zealand  examined transgenic experimentation on terrestrial livestock species as well as aquatic species such as fish and shellfish. The review examined the molecular techniques used for experimentation as well as techniques for tracing the  transgenes  in animals and products as well as issues regarding transgene stability. [ 140 ]


Some mammals typically used for food production have been modified to produce non-food products, a practice sometimes called  Pharming .


A  GM salmon , awaiting regulatory approval [ 141 ] [ 142 ] [ 8 ]  since 1997, [ 143 ]  was approved for human consumption by the American  FDA  in November 2015, to be raised in specific land-based hatcheries in Canada and Panama. [ 144 ]


Bacteriophages  are an economically significant cause of  culture  failure in  cheese  production. Various culture microbes - especially  Lactococcus lactis  and  Streptococcus thermophilus  - have been studied for genetic analysis and modification to improve  phage resistance . This has especially focused on  plasmid  and  recombinant  chromosomal modifications. [ 145 ] [ 146 ]


Lecithin  is a naturally occurring  lipid . It can be found in egg yolks and oil-producing plants. It is an emulsifier and thus is used in many foods. Corn, soy and safflower oil are sources of  lecithin , though the majority of lecithin commercially available is derived from soy. [ 147 ] [ 148 ] [ 149 ] [ page needed ]  Sufficiently processed lecithin is often undetectable with standard testing practices. [ 150 ] [ failed verification ]  According to the FDA, no evidence shows or suggests hazard to the public when lecithin is used at common levels. Lecithin added to foods amounts to only 2 to 10 percent of the 1 to 5 g of  phosphoglycerides  consumed daily on average. [ 147 ] [ 148 ]  Nonetheless, consumer concerns about GM food extend to such products. [ 151 ] [ better source needed ]  This concern led to policy and regulatory changes in Europe in 2000, [ citation needed ]  when Regulation (EC) 50/2000 was passed [ 152 ]  which required labelling of food containing additives derived from GMOs, including lecithin. [ citation needed ]  Because of the difficulty of detecting the origin of derivatives like lecithin with current testing practices, European regulations require those who wish to sell lecithin in Europe to employ a comprehensive system of  Identity preservation  (IP). [ 153 ] [ verification needed ] [ 154 ] [ page needed ]


The US imports 10% of its sugar, while the remaining 90% is extracted from  sugar beet  and  sugarcane . After deregulation in 2005,  glyphosate-resistant sugar beet  was extensively adopted in the United States. 95% of beet acres in the US were planted with glyphosate-resistant seed in 2011. [ 155 ]  GM sugar beets are approved for cultivation in the US, Canada and Japan; the vast majority are grown in the US. GM beets are approved for import and consumption in Australia, Canada, Colombia, EU, Japan, Korea, Mexico, New Zealand, Philippines, the Russian Federation and Singapore. [ 156 ]  Pulp from the refining process is used as animal feed. The sugar produced from GM sugar beets contains no DNA or protein – it is just sucrose that is chemically indistinguishable from sugar produced from non-GM sugar beets. [ 150 ] [ 157 ]  Independent analyses conducted by internationally recognized laboratories found that sugar from Roundup Ready sugar beets is identical to the sugar from comparably grown conventional (non-Roundup Ready) sugar beets. [ 158 ]


Most  vegetable oil  used in the US is produced from GM crops  canola , [ 159 ]   maize/corn , [ 160 ] [ 161 ]   cotton [ 162 ]  and  soybeans . [ 163 ]  Vegetable oil is sold directly to consumers as  cooking oil ,  shortening  and  margarine [ 164 ]  and is used in prepared foods. There is a vanishingly small amount of protein or DNA from the original crop in vegetable oil. [ 150 ] [ 165 ]  Vegetable oil is made of  triglycerides  extracted from plants or seeds and then refined and may be further processed via  hydrogenation  to turn liquid oils into solids. The refining process removes all, or nearly all non-triglyceride ingredients. [ 166 ]


Livestock and poultry are raised on  animal feed , much of which is composed of the leftovers from processing crops, including GM crops. For example, approximately 43% of a canola seed is oil. What remains after oil extraction is a meal that becomes an ingredient in animal feed and contains canola protein. [ 167 ]  Likewise, the bulk of the soybean crop is grown for oil and meal. The high-protein defatted and toasted soy meal becomes livestock feed and  dog food . 98% of the US soybean crop goes for livestock feed. [ 168 ] [ 169 ]  In 2011, 49% of the US maize/corn harvest was used for livestock feed (including the percentage of waste from  distillers grains ). [ 170 ]  "Despite methods that are becoming more and more sensitive, tests have not yet been able to establish a difference in the meat, milk, or eggs of animals depending on the type of feed they are fed. It is impossible to tell if an animal was fed GM soy just by looking at the resulting meat, dairy, or egg products. The only way to verify the presence of GMOs in animal feed is to analyze the origin of the feed itself." [ 171 ]


A 2012 literature review of studies evaluating the effect of GM feed on the health of animals did not find evidence that animals were adversely affected, although small biological differences were occasionally found. The studies included in the review ranged from 90 days to two years, with several of the longer studies considering reproductive and intergenerational effects. [ 172 ]


Enzymes  produced by genetically modified microorganisms are also integrated into animal feed to enhance availability of nutrients and overall digestion. These enzymes may also provide benefit to the gut  microbiome  of an animal, as well as  hydrolyse   antinutritional factors  present in the feed. [ 173 ]


The foundation of genetic engineering is DNA, which directs the production of proteins. Proteins are also the common source of human allergens. [ 174 ]   When new proteins are introduced they must be assessed for potential allergenicity. [ 175 ]


Rennet  is a mixture of enzymes used to coagulate milk into cheese. Originally it was available only from the fourth stomach of calves, and was scarce and expensive, or was available from microbial sources, which often produced unpleasant tastes. Genetic engineering made it possible to extract rennet-producing genes from animal stomachs and insert them into  bacteria ,  fungi  or  yeasts  to make them produce  chymosin , the key enzyme. [ 176 ] [ 177 ]  The modified microorganism is killed after fermentation. Chymosin is isolated from the fermentation broth, so that the  Fermentation-Produced Chymosin  (FPC) used by cheese producers has an amino acid sequence that is identical to bovine rennet. [ 178 ]  The majority of the applied chymosin is retained in the  whey . Trace quantities of chymosin may remain in cheese. [ 178 ]


FPC was the first artificially produced enzyme to be approved by the  US Food and Drug Administration . [ 3 ] [ 53 ]  FPC products have been on the market since 1990 and as of 2015 had yet to be surpassed in commercial markets. [ 179 ]  In 1999, about 60% of US  hard cheese  was made with FPC. [ 180 ]  Its global market share approached 80%. [ 181 ]  By 2008, approximately 80% to 90% of commercially made cheeses in the US and Britain were made using FPC. [ 178 ]


In some countries, recombinant (GM)  bovine somatotropin  (also called rBST, or bovine growth hormone or BGH) is approved for administration to increase milk production. rBST may be present in milk from rBST treated cows, but it is destroyed in the digestive system and even if directly injected into the human bloodstream, has no observable effect on humans. [ 182 ] [ 183 ] [ 184 ]  The FDA,  World Health Organization ,  American Medical Association ,  American Dietetic Association  and the  National Institutes of Health  have independently stated that dairy products and meat from rBST-treated cows are safe for human consumption. [ 185 ]  On 30 September 2010, the  United States Court of Appeals, Sixth Circuit , analyzing submitted evidence, found a "compositional difference" between milk from rBGH-treated cows and milk from untreated cows. [ 186 ] [ 187 ]  The court stated that milk from rBGH-treated cows has: increased levels of the hormone  Insulin-like growth factor 1  (IGF-1); higher fat content and lower protein content when produced at certain points in the cow's lactation cycle; and more somatic cell counts, which may "make the milk turn sour more quickly". [ 187 ]


Genetically modified foods are usually edited to have some desired characteristics, including certain benefits for surviving extreme environments, an enhanced level to nutrition, the access of therapeutic substances, and the resistance genes to pesticide and herbicides. These characteristics could be beneficial to humans and the environment in certain ways.


Plants that have undergone genetic modification are capable of surviving  extreme weather . [ 10 ]  Genetically modified (GM) food crops can be cultivated in locations with unfavorable climatic conditions on occasion. [ 11 ]  The quality and yield of genetically modified foods are often improved. [ 10 ]  These foods tend to grow more quickly than conventionally cultivated ones. Furthermore, the application of genetically modified food could be beneficial in resisting drought and poor soil. [ 11 ]


Increased levels of specific nutrients in food crops can be achieved by genetic engineering. The study of this technique, sometimes known as nutritional improvement, is already well advanced. [ 10 ]  Foods are well monitored to gain specific qualities that became practical, for example, concentrated nutraceutical levels and health-promoting chemicals, making them a desirable component of a varied diet. [ 188 ]  Among the notable breakthroughs of genetic modification is Golden Rice, whose genome is altered by the injection of the vitamin A gene from a daffodil plant conditioning provitamin A production. [ 10 ] [ 188 ]  This increases the activity of phytoene synthase, which therefore synthesizes a higher amount of beta-carotene, followed by modification and improvement of the level of iron and  bioavailability . [ 13 ] [ 15 ]  This affects the rice’s color and vitamin content, which is beneficial in places where vitamin A shortage is common. [ 10 ]  In addition, increased mineral, vitamin A, and protein content has played a critical role in preventing childhood blindness and iron deficiency anemia. [ 13 ]


Lipid composition could also be manipulated to produce desirable traits and essential nutrients. [ 15 ]   Scientific evidence  has shown that inadequate consumption of omega-3  polyunsaturated fatty acids  is generally associated with the development of chronic diseases and developmental aberrations. [ 12 ] [ 14 ]  Alimentary lipids can be modified to gain an increased saturated fatty acid together with a decreased polyunsaturated fatty acid component. Genes coded for the synthesis of unsaturated fatty acids are therefore introduced into plant cells, increasing the synthesis of polyunsaturated omega-3 acids. [ 15 ]  This omega-3 polyunsaturated fatty acid is responsible to lower the level of LDL cholesterol and triglyceride level as well as the incidence rate of cardiovascular diseases. [ 12 ] [ 14 ] [ 15 ]


The genetically modified organisms, including potato, tomato, and spinach are applied in the production of substances that stimulate the immune system to respond to specific pathogens. [ 15 ]  With the help of recombinant DNA techniques, the genes encoded for viral or bacterial antigens could be genetically transcribed and translated into plant cells. [ 15 ] [ 16 ]  Antibodies are often produced in response to the introduction of antigens, in which the pathological microflora obtains the immune response towards specific antigens. The transgenic organisms are usually applied to use as oral vaccines, which allows the active substances to enter the human digestive system, targeting the alimentary tract in which stimulate a mucosal immune response. This technique has been widely used in vaccine production including rice, maize, and soybeans. [ 15 ]  Additionally, transgenic plants are widely used as bioreactors in the production of pharmaceutical proteins and peptides, including vaccines, hormones, human serum albumin (HSA), etc. The suitability of transgenic plants can helps meet the demand for the rapid growth of therapeutic antibodies. [ 14 ]  All this has given new impetus to the development of medicine. [ 14 ] [ 15 ] [ 16 ]


There is a  scientific consensus [ 17 ] [ 18 ] [ 19 ] [ 20 ]  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 ]


Opponents claim that long-term health risks have not been adequately assessed and propose various combinations of additional testing, labeling [ 189 ]  or removal from the market. [ 190 ] [ 191 ] [ 192 ] [ 193 ]


There are no  certifications  for foods that have been verified to both be genetically modified – in particular in a way that is ensured to be well-understood,  safe  and  environmentally friendly  – as well as otherwise  organic  (i.e. produced without the use of chemical  pesticides ) in the U.S. and possibly the world, giving consumers the binary choice of either genetically modified food or organic food. [ 194 ] [ 195 ] [ 196 ]


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 ]  Countries such as the United States, Canada, Lebanon and Egypt use  substantial equivalence  to determine if further testing is required, while many countries such as those in the European Union, Brazil and China only authorize GMO cultivation on a case-by-case basis. In the U.S. the FDA determined that GMOs are " generally recognized as safe " (GRAS) and therefore do not require additional testing if the GMO product is substantially equivalent to the non-modified product. [ 197 ]  If new substances are found, further testing may be required to satisfy concerns over potential toxicity, allergenicity, possible gene transfer to humans or genetic outcrossing to other organisms. [ 44 ]


Some studies purporting to show harm have been discredited, in some cases leading to academic condemnation against the researchers such as the  Pusztai affair  and the  Séralini affair . [ 21 ]


Government regulation of GMO development and release varies widely between countries. Marked differences separate  GMO regulation in the U.S.  and  GMO regulation in the European Union . [ 39 ]  Regulation also varies depending on the intended product's use. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety. [ 198 ]  European and EU regulation has been far more restrictive than anywhere else in the world: In 2013 only 1 cultivar of maize/corn and 1 cultivar of potato were approved, and eight EU member states did not allow even those. [ 21 ]


In the U.S., three government organizations regulate GMOs. The  FDA  checks the chemical composition of organisms for potential  allergens . The  United States Department of Agriculture  (USDA) supervises field testing and monitors the distribution of GM seeds. The  United States Environmental Protection Agency  (EPA) is responsible for monitoring pesticide usage, including plants modified to contain proteins  toxic to insects . Like USDA, EPA also oversees field testing and the distribution of crops that have had contact with pesticides to ensure environmental safety. [ 199 ] [ better source needed ]  In 2015 the Obama administration announced that it would update the way the government regulated GM crops. [ 200 ]


In 1992 FDA published "Statement of Policy: Foods derived from New Plant Varieties". This statement is a clarification of FDA's interpretation of the Food, Drug, and Cosmetic Act with respect to foods produced from new plant varieties developed using  recombinant deoxyribonucleic acid (rDNA) technology . FDA encouraged developers to consult with the FDA regarding any bioengineered foods in development. The FDA says developers routinely do reach out for consultations. In 1996 FDA updated consultation procedures. [ 201 ] [ 202 ]


The StarLink corn recalls occurred in the autumn of 2000, when over 300 food products were found to contain a  genetically modified maize/corn  that had not been approved for human consumption. [ 203 ]  It was the first-ever recall of a genetically modified food.


The European Union's control of genetically modified organisms is a particular part of an image of the promise and limitations of debate as a framework for supranational regulation. [ 42 ]  The issues posed by the EU’s GMO regulation have caused major problems in agriculture, politics, societies, status, and other fields. [ 41 ] [ 42 ]  12 The EU law regulates the development and use of GMOs by allocating responsibilities to different authorities, public and private, accompanied by limited recognition of public information, consultation, and participation rights. [ 42 ]  The European Convention on Human Rights (ECHR) provided certain rights and protection for GM biotechnology in the EU. However, the value of human dignity, liberty, equality, and solidarity, as well as the status of democracy and law, as emphasized in the European Charter of Fundamental Rights, are considered the ethical framework governing the employment of scientific and technological research and development. [ 41 ]


Due to the political, religious, and social differences in EU countries, the EU’s position on GM has been divided geographically, including more than 100 “GM-free” regions. Different regional attitudes to GM foods make it nearly impossible to reach a common agreement on GM foods. [ 42 ]  In recent years, however, the sense of crisis that this has generated for the European Union has intensified. [ 43 ]  Some member states, including Germany, France, Austria, Italy, and Luxembourg, have even banned the planting of certain GM food in their countries in response to public resistance to GM foods. [ 42 ] [ 43 ]  The whole thing is set against a backdrop of consumers holding the attitude that GM foods are harmful to both the environment and human health, revolting against GM foods in an anti-biotech coalition. [ 40 ]  The current political deadlock over GM foods is also a consequence of the ban and has yet to be resolved by scientific methods and processes. [ 43 ]  Public opinion tends to politicize the GM issue, which is the main obstacle to an agreement in the EU. [ 42 ]


In the United Kingdom, the  Food Standards Agency  assesses GM foods for their toxicity, nutritional value, and potential to cause allergic reactions. GM foods can be authorised for sale where they present no risk to health, do not mislead consumers, and have nutritional value at least equivalent to non-modified counterparts. [ 204 ]  The Genetic Technology (Precision Breeding) Act passed into law on 23 March 2023. The UK government said it would allow farmers to "grow crops which are drought and disease resistant, reduce use of fertilisers and pesticides, and help breed animals that are protected from catching harmful diseases". [ 205 ]


As of 2015, 64 countries require labeling of GMO products in the marketplace.


US and Canadian national policy is to require a label only given significant composition differences or documented health impacts, although some individual US states (Vermont, Connecticut and Maine) enacted laws requiring them. [ 206 ] [ 207 ] [ 208 ] [ 209 ]  In July 2016,  Public Law 114-214  was enacted to regulate labeling of GMO food on a national basis.


In some jurisdictions, the labeling requirement depends on the relative quantity of GMO in the product. A study that investigated voluntary labeling in South Africa found that 31% of products labeled as GMO-free had a GM content above 1.0%. [ 210 ]


In the European Union all food (including  processed food ) or  feed  that contains greater than 0.9% GMOs must be labelled. [ 211 ]


At the same time, due to lack of  single, clear definition of GMO , a number of foods created using genetic engineering techniques (such as  mutation breeding ) are excluded from labelling and regulation based on "convention" and traditional usage. [ 48 ]


The Non-GMO Project is the sole U.S. organization that does verifiable testing and places seals on labels for presence of GMO in products. The "Non-GMO Project Seal" indicates that the product contains 0.9% or less GMO ingredients, which is the European Union's standard for labeling. [ 212 ]


Efforts across the world that are being made to help restrict and label GMO's in food involve anti-genetic engineering campaigns and in America the "Just Label It" movement is joining organizations together to call for mandatory labeling. [ 212 ]


Testing on GMOs in food and feed is routinely done using molecular techniques such as  PCR  and  bioinformatics . [ 213 ]


In a January 2010 paper, the extraction and detection of DNA along a complete industrial soybean oil processing chain was described to monitor the presence of  Roundup Ready  (RR) soybean: "The amplification of soybean lectin gene by end-point polymerase chain reaction (PCR) was successfully achieved in all the steps of extraction and refining processes, until the fully refined soybean oil. The amplification of RR soybean by PCR assays using event-specific primers was also achieved for all the extraction and refining steps, except for the intermediate steps of refining (neutralisation, washing and bleaching) possibly due to sample instability. The real-time PCR assays using specific probes confirmed all the results and proved that it is possible to detect and quantify genetically modified organisms in the fully refined soybean oil. To our knowledge, this has never been reported before and represents an important accomplishment regarding the traceability of genetically modified organisms in refined oils." [ 214 ]


According to Thomas Redick, detection and prevention of cross-pollination is possible through the suggestions offered by the  Farm Service Agency  (FSA) and  Natural Resources Conservation Service  (NRCS). Suggestions include educating farmers on the importance of coexistence, providing farmers with tools and incentives to promote coexistence, conducting research to understand and monitor gene flow, providing assurance of quality and diversity in crops, and providing compensation for actual economic losses for farmers. [ 215 ]


The genetically modified foods controversy consists of a set of disputes over the use of food made from genetically modified crops. The disputes involve consumers, farmers, biotechnology companies, governmental regulators, non-governmental organizations, environmental and political activists and scientists. The major disagreements include whether GM foods can be safely consumed, harm the human body and the environment and/or are adequately tested and regulated. [ 191 ] [ 217 ]  The objectivity of scientific research and publications has been challenged. [ 190 ]  Farming-related disputes include the use and impact of pesticides, seed production and use, side effects on non-GMO crops/farms, [ 218 ]  and potential control of the GM food supply by seed companies. [ 190 ]


The conflicts have continued since GM foods were invented. They have occupied the media, the courts, [ 219 ]  local, regional, national governments, and international organizations. [ citation needed ]


"GMO-free" labelling schemes are causing controversies in farming community due to  lack of clear definition , inconsistency of their application and are described as "deceptive". [ 220 ] [ 221 ]


New allergies could be introduced inadvertently, according to scientists, community groups, and members of the public concerned about the genetic variation of foods. [ 10 ]  An example involves the methionine rich soybean production. [ 15 ]  Methionine is an amino acid obtained by synthesizing substances derived from Brazil nuts, which could be an allergen. [ 15 ] [ 222 ]  A gene from the Brazil nut was inserted into soybeans during laboratory trials. [ 11 ] [ 222 ]  Because it was discovered that those who were allergic to Brazil nuts could also be allergic to genetically modified soybeans, the experiment was stopped. [ 10 ] [ 223 ]  In vitro assays such as RAST or serum from people allergic to the original crop could be applied to test the allergenicity of GM goods with known source of the gene. [ 10 ]  This was established in GM soybeans that expressed Brazil nut 2S proteins and GM potatoes that expressed cod protein genes. [ 11 ]  The expression and synthesis of new proteins that were previously unavailable in parental cells were achieved by gene transfer from the cells of one organism to the nuclei of another organism. The potential risks of allergy that may develop with the intake of transgenic food come from the amino acid sequence in protein formation. [ 188 ]  However, there have been no reports of allergic reactions to currently approved GM foods for human consumption, and experiments showed no measurable difference in allergenicity between GM and non-GM soybeans. [ 10 ] [ 188 ] [ 224 ] [ 225 ]


Scientists suggest that consumers should also pay attention to the health issues associated with the utilizations of pesticide-resistant and herbicide-resistant plants. [ 11 ]  The ‘Bt’ genes cause insect resistance in today's GM crops; however, other methods to confer insect resistance are in the works. [ 226 ]  The Bt genes are usually obtained from the soil bacteria Bacillus thuringiensis, and they can generate a protein that breaks down in the insect’s gut, releasing a toxin called delta-endotoxin, which causes paralysis and death. [ 43 ]  Concerns about resistance and off-target effects of crops expressing Bt toxins, consequences of transgenic herbicide-tolerant plants caused by the use of herbicide, and the transfer of gene expression from GM crops via vertical and horizontal gene transfer are all related to the expression of transgenic material. [ 41 ]


Another concern raised by ecologists is the possible spread of the pest-resistant genes to wildlife. [ 10 ] [ 43 ]  This is an example of gene pollution, which is often associated with a decrease in biodiversity, proliferation resistant weeds, and the formation of new pests and pathogens. [ 227 ] [ 226 ]


Studies have proven that herbicide resistant pollen from transgenic rapeseed could spread up to 3 km, while the average gene spread of transgenic crops is 2 km and even reach to maximum 21 kilometers. [ 227 ]  The high aggressiveness of these GM crops could cause certain disasters by competing with traditional crops for water, light, and nutrients. [ 222 ]  Crossbreeding of spreading pollens with the surrounding organisms has led to the introduction of the modified resistant genes. [ 11 ]  An international database that demonstrated genetic contaminations with undesired seeds has been a major problem due to the expansion of field trials and commercially viable cultivation of GM crops around the world. [ 227 ] [ 222 ]   Even a decrease in the number of one pest under the impact of a pest-resistant weed could increase the population of other pests that compete with it. [ 11 ]  Beneficial insects, so named because they prey on crop pests, were also exposed to dangerous doses of Bt. [ 10 ]


The introduction of GM crops in place of more locally adapted varieties could lead to long-term negative effects on the entire agricultural system. [ 16 ]  Much of the concern with GM technology involves encoding genes that increase or decrease biochemicals. Alternatively, the newly programmed enzyme might result in the consumption of the substrate, forming and accumulating the products. [ 10 ]


In terms of socioeconomics, GM crops are usually dependent on high levels of external products, for example, pesticides and herbicides, which limit GM crops to high-input agriculture. This, coupled with the widespread patents held on GM crops, limited farmers’ trading rights over the harvested seeds without paying royalties. Other arguments against GM crops held by some opponents are based on the high costs of isolating and distributing GM crops over non-GM crops. [ 16 ]


Consumers could be categorized based on their attitudes regarding genetically modified foods. [ 40 ]  The ‘attitudinal’ sector of US consumers could be explained in part by cognitive characteristics that are not always observable. Individual characteristics and values, for example, can play a role in shaping consumer acceptance of biotechnology. The concept of transplanting animal DNA into plants is unsettling for many people. [ 11 ]  Studies have shown that consumers' attitudes towards GM technology are positively correlated to their knowledge about it. [ 228 ]  It was found that elevated acceptance of genetic modification is usually associated with a high education level, whereas high levels of perceived risks are associated with the opposite. [ 40 ] [ 228 ]  People tend to worry about unpredictable dangers due to the lack of sufficient knowledge to predict or avoid negative impacts. [ 228 ]


Another crucial link of the change in consumer attitudes towards genetically modified foods has been shown to be closely related to their interaction with socioeconomic and demographic characteristics, for example, age, ethnicity, residence, and level of consumption. [ 40 ] [ 222 ]  Opposition to genetically modified foods could also include religious and cultural groups, because the nature of GM foods goes against what they believe are natural products. [ 11 ] [ 222 ] [ 229 ]  On the one hand, it was found that consumers in most European countries, especially in northern Europe, the UK and Germany, believe that the benefits of GM foods do not outweigh the potential risks. On the other hand, consumers in the United States and other European countries generally hold to view that the risks of GM foods could be far less than the benefits it brought. [ 188 ]  GM foods are then expected to be supported by more appropriate policies and clearer regulations. [ 222 ]


Domingo, José L.; Bordonaba, Jordi Giné (2011).  "A literature review on the safety assessment of genetically modified plants"   (PDF) .  Environment International .  37  (4):  734– 742.  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, Sheldon (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.


Panchin, Alexander Y.; Tuzhikov, Alexander I. (January 14, 2016). "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 .  ISSN   0738-8551 .  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.


A  genetically modified mouse ,  genetically engineered mouse model  ( GEMM ) [ 1 ]  or  transgenic mouse  is a  mouse  ( Mus musculus ) that has had its  genome  altered through the use of  genetic engineering  techniques. Genetically modified mice are commonly used for research or as animal models of human diseases and are also used for research on genes. Together with  patient-derived xenografts  (PDXs), GEMMs are the most common  in vivo  models in  cancer research . Both approaches are considered complementary and may be used to recapitulate different aspects of disease. [ 2 ]  GEMMs are also of great interest for  drug development , as they facilitate target validation and the study of response, resistance, toxicity and  pharmacodynamics . [ 3 ]


In 1974  Beatrice Mintz  and  Rudolf Jaenisch  created the first genetically modified animal by inserting a DNA virus into an early-stage mouse  embryo  and showing that the inserted genes were present in every cell. [ 4 ]  However, the mice did not pass the  transgene  to their offspring, and the impact and applicability of this experiment were, therefore, limited. In 1981 the laboratories of  Frank Ruddle [ 5 ]  from  Yale University , Frank Costantini and Elizabeth Lacy from  Oxford , and  Ralph L. Brinster  and Richard Palmiter in collaboration from the  University of Pennsylvania  and the  University of Washington  injected purified DNA into a  single-cell mouse embryo  utilizing techniques developed by Brinster in the 1960s and 1970s, showing transmission of the genetic material to subsequent generations for the first time. [ 6 ] [ 7 ] [ 8 ]  During the 1980s, Palmiter and Brinster developed and led the field of transgenesis, refining methods of  germline  modification and using these techniques to elucidate the activity and function of genes in a way not possible before their unique approach. [ 9 ]


There are two basic technical approaches to produce genetically modified mice. The first involves  pronuclear injection , a technique developed and refined by  Ralph L. Brinster  in the 1960s and 1970s, into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. [ 10 ]  This method creates a  transgenic  mouse and is used to insert new genetic information into the mouse genome or to over-express  endogenous  genes. The second approach, pioneered by  Oliver Smithies  and  Mario Capecchi , involves modifying  embryonic stem cells  with a  DNA construct  containing DNA sequences  homologous  to the target gene. Embryonic stem cells that  recombine  with the genomic DNA are selected for and they are then injected into the mice  blastocysts . [ 11 ]  This method is used to manipulate a single gene, in most cases  "knocking out"  the target gene, although increasingly more subtle and complex genetic manipulation can occur (e.g. humanisation of a specific protein, or only changing single  nucleotides ). A  humanised mouse  can also be created by direct addition of human genes, thereby creating a  murine  form of  human–animal hybrid . For example, genetically modified mice may be born with  human leukocyte antigen  genes in order to provide a more realistic environment when introducing human  white blood cells  into them in order to study  immune system  responses. [ 12 ]  One such application is the identification of  hepatitis C virus  (HCV) peptides that bind to HLA, and that can be recognized by the human immune system, thereby potentially being targets for future vaccines against HCV. [ 13 ]


Genetically modified mice are used extensively in research as models of human disease. [ 14 ]  Mice are a useful model for genetic manipulation and research, as their  tissues  and  organs  are similar to that of a human and they carry virtually all the same genes that operate in humans. [ 15 ]  They also have advantages over other mammals, in regards to research, in that they are available in hundreds of genetically homogeneous strains. [ 15 ]  Also, due to their size, they can be kept and housed in large numbers, reducing the cost of research and experiments. [ 15 ]  The most common type is the  knockout mouse , where the activity of a single (or in some cases multiple) genes are removed. They have been used to study and model obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging, temperature and pain reception, and Parkinson disease. [ 16 ] [ 17 ]  Transgenic mice generated to carry cloned  oncogenes  and knockout mice lacking  tumor suppressing genes  have provided good models for human  cancer . Hundreds of these  oncomice  have been developed covering a wide range of cancers affecting most organs of the body and they are being refined to become more representative of human cancer. [ 9 ]  The disease symptoms and potential drugs or treatments can be tested against these mouse models.


A mouse has been genetically engineered to have increased muscle growth and strength by overexpressing the  insulin-like growth factor I  (IGF-I) in differentiated  muscle fibers . [ 18 ] [ 19 ]  Another mouse has had a gene altered that is involved in  glucose metabolism  and runs faster, lives longer, is more sexually active and eats more without getting fatter than the average mouse (see  Metabolic supermice ). [ 20 ] [ 21 ]  Another mouse had the  TRPM8 receptor  blocked or removed in a study involving  capsaicin  and  menthol . [ 17 ]  With the TRPM8 receptor removed, the mouse was unable to detect small changes in temperature and the pain associated with it. [ 17 ]


Great care should be taken when deciding how to use genetically modified mice in research. [ 22 ]  Even basic issues like choosing the correct "wild-type" control mouse to use for comparison are sometimes overlooked. [ 23 ]


Genetically modified plants  have been engineered for scientific research, to create new colours in plants, deliver vaccines,  and to create enhanced crops. Plant genomes can be engineered by physical methods or by use of  Agrobacterium  for the delivery of sequences hosted in  T-DNA binary vectors . Many plant cells are  pluripotent , meaning that a single cell from a mature plant can be harvested and then under the right conditions form a new plant. This ability is most often taken advantage by genetic engineers through selecting cells that can successfully be transformed into an adult plant which can then be grown into multiple new plants containing transgene in every cell through a process known as  tissue culture . [ 1 ]


Much of the advances in the field genetic engineering has come from experimentation with  tobacco . Major advances in tissue culture and  plant cellular  mechanisms for a wide range of plants has originated from systems developed in tobacco. [ 2 ]  It was the first plant to be genetically engineered and is considered a model organism for not only genetic engineering, but a range of other fields. [ 3 ]  As such the transgenic tools and procedures are well established making it one of the easiest plants to transform. [ 4 ]  Another major model organism relevant to genetic engineering is  Arabidopsis thaliana .  Its small genome and short life cycle makes it easy to manipulate and it contains many  homologs  to important crop species. [ 5 ]  It was the first plant  sequenced , has abundant  bioinformatic  resources and can be transformed by simply dipping a flower in a transformed  Agrobacterium  solution. [ 6 ]


In research, plants are engineered to help discover the functions of certain genes. The simplest way to do this is to remove the gene and see what  phenotype  develops compared to the  wild type  form. Any differences are possibly the result of the missing gene. Unlike  mutagenisis , genetic engineering allows targeted removal without disrupting other genes in the organism. [ 1 ]  Some genes are only expressed in certain tissue, so reporter genes, like  GUS , can be attached to the gene of interest allowing visualisation of the location. [ 7 ]  Other ways to test a gene is to alter it slightly and then return it to the plant and see if it still has the same effect on phenotype. Other strategies include attaching the gene to a strong  promoter  and see what happens when it is over expressed, forcing a gene to be expressed in a different location or at different  developmental stages . [ 1 ]


Some genetically modified plants are purely  ornamental . They are modified for flower color, fragrance, flower shape and plant architecture. [ 8 ]  The first genetically modified ornamentals commercialised altered colour. [ 9 ]   Carnations  were released in 1997, with the most popular genetically modified organism, a  blue rose  (actually lavender or mauve) created in 2004. [ 10 ]  The roses are sold in Japan, the United States, and Canada. [ 11 ] [ 12 ]  Other genetically modified ornamentals include  Chrysanthemum  and  Petunia . [ 8 ]  As well as increasing aesthetic value there are plans to develop ornamentals that use less water or are resistant to the cold, which would allow them to be grown outside their natural environments. [ 13 ]


It has been proposed to genetically modify some plant species threatened by extinction to be resistant invasive plants and diseases, such as the  emerald ash borer  in North American and the fungal disease,  Ceratocystis platani , in European  plane trees . [ 14 ]  The  papaya ringspot virus  (PRSV) devastated papaya trees in Hawaii in the twentieth century until transgenic  papaya  plants were given pathogen-derived resistance. [ 15 ]  However, genetic modification for conservation in plants remains mainly speculative. A unique concern is that a transgenic species may no longer bear enough resemblance to the original species to truly claim that the original species is being conserved. Instead, the transgenic species may be genetically different enough to be considered a new species, thus diminishing the conservation worth of genetic modification. [ 14 ]


Genetically modified crops are genetically modified plants that are used in  agriculture . The first crops provided are used for animal or human food and provide resistance to certain pests, diseases, environmental conditions, spoilage or chemical treatments (e.g. resistance to a  herbicide ). [ 16 ]  The second generation of crops aimed to improve the quality, often by altering the  nutrient profile . Third generation genetically modified crops can be used for non-food purposes, including the production of  pharmaceutical agents ,  biofuels , and other industrially useful goods, as well as for  bioremediation . [ 17 ]


There are three main aims to agricultural advancement; increased production, improved conditions for agricultural workers and  sustainability . GM crops contribute by improving harvests through reducing insect pressure, increasing nutrient value and tolerating different  abiotic stresses . Despite this potential, as of 2018, the commercialised crops are limited mostly to  cash crops  like cotton, soybean, maize and canola and the vast majority of the introduced traits provide either herbicide tolerance or insect resistance. [ 17 ]  Soybeans accounted for half of all genetically modified crops planted in 2014. [ 18 ]  Adoption by farmers has been rapid, 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). [ 19 ]  Geographically though the spread has been very uneven, with strong growth in the  Americas  and parts of Asia and little in Europe and Africa. [ 17 ]  Its  socioeconomic  spread has been more even, with approximately 54% of worldwide GM crops grown in  developing countries  in 2013. [ 19 ]


The majority of GM crops have been modified to be resistant to selected herbicides, usually a  glyphosate  or  glufosinate  based one. Genetically modified crops engineered to resist herbicides are now more available than conventionally bred resistant varieties; [ 20 ]  in the USA 93% of soybeans and most of the  GM maize  grown is glyphosate tolerant. [ 21 ]  Most currently available genes used to engineer insect resistance come from the  Bacillus thuringiensis  bacterium. Most are in the form of  delta endotoxin  genes known as cry proteins, while a few use the genes that encode for  vegetative insecticidal proteins . [ 22 ]  The only gene commercially used to provide insect protection that does not originate from  B. thuringiensis  is the  Cowpea   trypsin inhibitor  (CpTI). CpTI was first approved for use cotton in 1999 and is currently undergoing trials in rice. [ 23 ] [ 24 ]  Less than one percent of GM crops contained other traits, which include providing virus resistance, delaying senescence, modifying flower colour and altering the plants composition. [ 18 ]
 Golden rice  is the most well known GM crop that is aimed at increasing nutrient value. It has been engineered with three genes that  biosynthesise   beta-carotene , a precursor of  vitamin A , in the edible parts of rice. [ 25 ]  It is intended to produce a fortified food to be grown and consumed in areas with a  shortage of dietary vitamin A . [ 26 ]  a deficiency which each year is estimated to kill 670,000 children under the age of 5 [ 27 ]  and cause an additional 500,000 cases of irreversible childhood blindness. [ 28 ]   The original golden rice produced 1.6μg/g of the  carotenoids , with further development increasing this 23 times. [ 29 ]  In 2018 it gained its first approvals for use as food. [ 30 ]


Plants and plant cells have been genetically engineered for production of  biopharmaceuticals  in  bioreactors , a process known as  Pharming . Work has been done with  duckweed   Lemna minor , [ 31 ]  the  algae   Chlamydomonas reinhardtii [ 32 ]  and the  moss   Physcomitrella patens . [ 33 ] [ 34 ]  Biopharmaceuticals produced include  cytokines ,  hormones ,  antibodies ,  enzymes  and vaccines, most of which are accumulated in the plant seeds. Many drugs also contain natural plant ingredients and the pathways that lead to their production have been genetically altered or transferred to other plant species to produce greater volume and better products. [ 35 ]  Other options for bioreactors are  biopolymers [ 36 ]  and  biofuels . [ 37 ]  Unlike bacteria, plants can modify the proteins post- translationally , allowing them to make more complex molecules. They also pose less risk of being contaminated. [ 38 ]  Therapeutics have been cultured in transgenic carrot and tobacco cells, [ 39 ]  including a drug treatment for  Gaucher's disease . [ 40 ]


Vaccine production and storage has great potential in transgenic plants. Vaccines are expensive to produce, transport and administer, so having a system that could produce them locally would allow greater access to poorer and developing areas. [ 35 ]  As well as purifying vaccines expressed in plants, it is also possible to produce edible vaccines in plants. Edible vaccines stimulate the  immune system  when ingested to protect against certain diseases. Being stored in plants reduces the long-term cost as they can be disseminated without the need for cold storage, do not need to be purified, and have long term stability. Also being housed within plant cells provides some protection from the gut acids upon digestion; the cost of developing, regulating and containing transgenic plants is high, leading to most current plant-based vaccine development being applied to  veterinary medicine , where the controls are not as strict. [ 41 ]


A  genetically engineered   fluorescent protein  that changes its  fluorescence  when bound to the neurotransmitter  glutamate . [ 1 ]  Glutamate-sensitive fluorescent reporters (iGluSnFR, colloquially pronounced ' glue sniffer ') are used to monitor the activity of  presynaptic terminals  by  fluorescence microscopy . GluSnFRs are a class of  optogenetic  sensors used in  neuroscience  research. [ 2 ]  In brain tissue,  two-photon microscopy  is typically used to monitor GluSnFR fluorescence.


The widely used iGluSnFR consists of a  circularly permuted   enhanced green fluorescent protein (cpEGFP)  fused to a glutamate binding protein (GluBP) from a  bacterium . [ 3 ]  When GluBP binds a  glutamate  molecule, it changes its shape, pulling the EGFP  barrel  together, increasing fluorescence. A specific peptide segment ( PDGFR ) is included to bring the sensor to the outside of the  cell membrane . [ 4 ]  In the more recent version by Aggarwal  et al.  (2022), [ 1 ]  researchers introduced iGluSnFR to two additional anchoring domains, a glycosylphostidylinositol (GPI) anchor, and a modified form of the cytosolic -cterminal domain of Stargazin with a PDZ ligand.


The first genetically encoded fluorescent glutamate sensors (FLIPE, GluSnFR and SuperGluSnFR) were constructed by attaching cyan-fluorescent protein (CFP) and yellow-fluorescent protein (YFP) to a bacterial glutamate  binding protein  (GluBP). [ 5 ] [ 6 ]   Glutamate  binding changed the distance between CFP and YFP, changing the efficiency of energy transfer ( FRET ) between the two  fluorophores . [ 7 ] [ 8 ]  A breakthrough in visualizing glutamate release was achieved with iGluSnFR, a single-fluorophore glutamate sensor based on  EGFP  producing a ~5‑fold increase in fluorescence. [ 3 ]  To measure synaptic transmission at high frequencies, novel iGluSnFR variants with accelerated kinetics have recently been developed. [ 9 ] [ 10 ]


Hachimoji DNA  (from  Japanese   八文字   hachimoji , "eight letters") is a synthetic  nucleic acid analog  that uses four synthetic  nucleotides  in addition to the four present in the natural  nucleic acids , DNA and RNA.  This leads to four allowed  base pairs : two  unnatural base pairs  formed by the synthetic  nucleobases  in addition to the two normal pairs.  Hachimoji bases have been demonstrated in both DNA and RNA analogs, using  deoxyribose  and  ribose  respectively as the backbone sugar. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]


Benefits of such a nucleic acid system may include an enhanced ability to  store data , as well as insights into what may be possible in the search for  extraterrestrial life . [ 5 ] [ 6 ]


The hachimoji DNA system produced one type of catalytic RNA ( ribozyme  or  aptamer )  in vitro .


Natural  DNA  is a molecule carrying the  genetic  instructions used in the growth, development, functioning, and  reproduction  of all known living  organisms  and many  viruses . DNA and  ribonucleic acid  (RNA) are  nucleic acids ; alongside  proteins ,  lipids  and complex carbohydrates ( polysaccharides ), nucleic acids are one of the four major types of  macromolecules  that are essential for all known forms of  life . DNA is a  polynucleotide  as it is composed of simpler  monomeric  units called  nucleotides ; when double-stranded, the two chains coil around each other to form a  double helix . [ 7 ] [ 8 ]


In natural DNA, each nucleotide is composed of one of four  nucleobases  ( cytosine  [C],  guanine  [G],  adenine  [A] or  thymine  [T]), a  sugar  called  deoxyribose , and a  phosphate group . The nucleotides are joined to one another in a chain by  covalent bonds  between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating  sugar-phosphate backbone . The nitrogenous bases of the two separate polynucleotide strands are bound to each other with  hydrogen bonds , according to  base pairing  rules (A with T and C with G), to make double-stranded DNA.


Hachimoji DNA is similar to natural DNA but differs in the number, and type, of nucleobases. [ 1 ] [ 5 ]  Unnatural nucleobases, more  hydrophobic  than  natural bases , [ 9 ] [ 10 ]  are used in successful hachimoji DNA. Such a DNA always formed the  standard double helix , no matter what sequence of bases were used. An  enzyme  ( T7 polymerase ) was adapted by the researchers to be used  in vitro  to   transcribe  hachimoji DNA into hachimoji RNA, which, in turn, produced chemical activity in the form of a glowing green  fluorophore . [ 4 ] [ 5 ]


DNA and RNA are naturally composed of four nucleotide bases that form hydrogen bonds in order to pair. Hachimoji DNA uses an additional four synthetic nucleotides to form four types of base pairs, two of which are unnatural:  P  binds with  Z  and  B  binds with  S  ( dS  in  DNA ,  rS  in  RNA ). [ 1 ]


2-amino-8-(1′-b-D-2′-deoxyribofuranosyl)-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one [ 1 ]


6-amino-3-(1′-b-D-2′-deoxyribofuranosyl)-5-nitro-1H-pyridin-2-one [ 1 ]


6-amino-9[(1′-b-D-2′-deoxyribofuranosyl)-4-hydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1H-purin-2-one [ 1 ]


3-methyl-6-amino-5-(1′-b-D-2′-deoxyribofuranosyl)-pyrimidin-2-one [ 1 ]


Earlier, the research group responsible for the hachimoji DNA system, headed by  Harvard University  chemist  Steven Benner , had studied a  synthetic DNA analog  system, named  Artificially Expanded Genetic Information System  (AEGIS), that used twelve different nucleotides, including the four found in DNA. [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]


Scripps Research  chemist  Floyd Romesberg , noted for creating the first  Unnatural Base Pair (UBP) , and expanding the genetic alphabet of four letters to six in 2012, [ 16 ]  stated that the invention of the hachimoji DNA system is an example of the fact that the natural bases (G, C, A and T) "are not unique". [ 17 ] [ 18 ]  Creating new life forms may be possible, at least theoretically, [ 9 ]  with the new DNA system. [ 18 ]  For now, however, the hachimoji DNA system is not self-sustaining; the system needs a steady supply of unique building blocks and proteins found only in the laboratory. As a result, "Hachimoji DNA can go nowhere if it escapes the laboratory." [ 4 ]


NASA  funded this research to "expand[s] the scope of the structures that we might encounter as we search for life in the cosmos". [ 1 ]  According to  Lori Glaze  of the  Planetary Science Division  of NASA, "Life detection is an increasingly important goal of NASA's planetary science missions, and this new work [with hachimoji DNA] will help us to develop effective instruments and experiments that will expand the scope of what we look for." [ 3 ] [ 19 ]  Research team leader  Steven Benner  notes, "By carefully analyzing the roles of shape, size and structure in hachimoji DNA, this work expands our understanding of the types of  molecules  that might store information in extraterrestrial life on alien worlds." [ 20 ]


According to researchers, [ 1 ]  hachimoji DNA could also be used "to develop clean  diagnostics  for  human diseases , in  DNA digital data storage ,  DNA barcoding , self-assembling  nanostructures , and to make  proteins  with unusual  amino acids . Parts of this hachimoji DNA are already being commercially produced by Firebird Biomolecular Sciences LLC". [ 1 ] [ 4 ]


A  human–animal hybrid  and  animal–human hybrid  is an organism that incorporates elements from both  humans  and non-human  animals . Technically, in a  human–animal  hybrid , each cell has both human and non-human genetic material. It is in contrast to an individual where some cells are human and some are derived from a different organism, called a  human-animal chimera . [ 1 ]   (A  human chimera , on the other hand, consists only of human cells, from different zygotes.)


Examples of human–animal hybrids mainly include  humanized mice  that have been  genetically modified  by  xenotransplantation  of human genes. [ 2 ]   Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics.


Human–animal hybrids are the subject of legal, moral, and technological debate in the context of recent advances in  genetic engineering . [ 3 ] [ 4 ] [ 5 ]


Human–animal hybrids have existed throughout  social cultures  for a long time (particularly in terms of  mythology ), being a part of  storytelling  across multiple  continents , and have also been incorporated into  comic books ,  films ,  video games , and other related  mass media  in recent decades. [ 6 ] [ 3 ] [ 7 ] [ 4 ] [ 8 ]


Defined by the magazine  H+  as "genetic alterations that are blendings [sic] of animal and human forms", such hybrids may be referred by other names occasionally such as "para-humans". [ 6 ] [ 3 ]  They may additionally may be called "humanized animals". [ 5 ]  Technically speaking, they are also related to "cybrids" ( cytoplasmic hybrids ), with "cybrid" cells featuring foreign human  nuclei  inside of them being a topic of interest. Possibly, a real-world human-animal hybrid may be an entity formed from either a  human egg  fertilized by a nonhuman  sperm  or a nonhuman egg fertilized by a human sperm. [ 3 ]


Artificially created human-animal hybrids include  humanized mice  that have been  xenotransplanted  with human gene products, so as to be utilized for gaining relevant insights in the  in vivo  context for understanding of human-specific physiology and pathologies. [ 2 ]   Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics including infectious diseases and cancer. For example,  genetically modified mice  may be born with  human leukocyte antigen  genes in order to provide a more realistic environment when introducing human  white blood cells  into them in order to study  immune system  responses. [ 9 ]


Advances in  genetic engineering  have generally caused a large number of debates and discussions in the fields related to  bioethics , including research relating to the creation of human-animal hybrids. Although the two topics are not strictly related, the debates involving the creation of human-animal hybrids have paralleled that of the debates around the stem-cell research controversy. [ 3 ]


The question of what line exists between a "human" being and a "non-human" being has been a difficult one for many researchers to answer. While animals having one percent or less of their cells originally coming from humans may clearly appear to be in the same boat as other animals, no consensus exists on how to think about beings in a genetic middle ground that have something like an even mix. "I don't think anyone knows in terms of crude percentages how to differentiate between humans and nonhumans,"  U.S. patent office  official John Doll has stated. [ 5 ]  Critics of increased government restrictions include scientists such as Dr. Douglas Kniss, head of the Laboratory of Perinatal Research at  Ohio State University , who has remarked that formal laws aren't the best option since the "notion of animal-human hybrids is very complex." He's also argued that their creation is inherent "not the kind of thing we support" in his kind of research since scientists should "want to respect human life". [ 3 ]


In contrast, notable socio-economic theorist  Jeremy Rifkin  has expressed opposition to research that creates beings crossing species boundaries, arguing that it interferes with the fundamental 'right to exist' possessed by each animal species. "One doesn't have to be religious or into animal rights to think this doesn't make sense," he has argued when expressing support for anti-chimera and anti-hybrid legislation. As well, William Cheshire, associate professor of neurology at the  Mayo Clinic 's Florida branch, has called the issue "unexplored biologic territory" and advocated for a "moral threshold of human neural development" to restrict the destroying a human embryo to obtain cell material and/or the creation of an organism that's partly human and partly animal." He has said, "We must be cautious not to violate the integrity of humanity or of animal life over which we have a stewardship responsibility". [ 4 ]


While laws against the creation of hybrid beings have been proposed in U.S. states and in the  U.S. Congress , several scientists have argued that legal barriers might go too far and prohibit medically beneficial studies into human modification. [ 3 ] [ 4 ] [ 5 ]


In terms of  scientific ethics , restrictions on the creation of human–animal hybrids have proved a controversial matter in multiple countries. While the state of  Arizona  banned the practice altogether in 2010, a proposal on the subject that sparked some interest in the  United States Senate  from 2011 to 2012 ended up going nowhere. Although the two concepts are not strictly related, discussions of experimentation into blended human and animal creatures has paralleled the discussions around  embryonic stem-cell research  (the ' stem cell controversy '). [ 3 ]  The creation of  genetically modified organisms  for a multitude of purposes has taken place in the modern world for decades, examples being specifically designed foodstuffs made to have features such as higher crop yields through better disease resistance. [ 10 ]


President  George W. Bush  brought up the topic in his  2006 State of the Union Address , in which he called for the prohibition of "human cloning in all its forms", "creating or implanting embryos for experiments", "creating  human-animal hybrids ", and also "buying, selling, or patenting human embryos". He argued, "A hopeful society has institutions of science and medicine that do not cut ethical corners and that recognize the matchless value of every life." He also stated that humanity "should never be discarded, devalued or put up for sale." [ 11 ]


A 2005 appropriations bill passed by the U.S. Congress and signed into law by President Bush contained specific wording forbidding any patents on humans or human embryos. [ 5 ]  In terms of outright bans on hybrid research in the first place, a measure came up in the  110th Congress  entitled the  Human-Animal Hybrid Prohibition Act of 2008 . Congressman  Chris Smith  ( R ,  NJ-4 ) introduced it on April 24, 2008. The text of the proposed act stated that "human dignity and the integrity of the human species are compromised" if such hybrids exist and set up the punishment of imprisonment for up to ten years as well as a fine of over one million dollars. Though attracting support from many co-sponsors such as then  Representatives   Mary Fallin ,  Duncan Hunter ,  Joseph R. Pitts , and  Rick Renzi  among others, the Act failed to get through Congress. [ 12 ]


A related proposal had come up in the  U.S. Senate  the prior year, the  Human-Animal Hybrid Prohibition Act of 2007 , and it also had failed. That effort was proposed by then-Senator  Sam Brownback  ( R ,  KS ) on November 15, 2007. Featuring the same language as the later measure in the House, its bipartisan group of cosponsors included then Senators  Tom Coburn ,  Jim DeMint , and  Mary Landrieu . [ 13 ]


A localized measure designed to ban the creation of hybrid entities came up in the state of  Arizona  in 2010. The proposal was signed into law by then  Governor   Jan Brewer . Its sponsor stated that it was needed to clarify important "ethical boundaries" in research. [ 3 ]


For thousands of years, these  hybrids  have been one of the most common themes in  storytelling  about animals throughout the world. The lack of a strong divide between humanity and animal nature in multiple traditional and ancient cultures has provided the underlying historical context for the popularity of tales where humans and animals have mingling relationships, such as in which one turns into the other or in which some mixed being goes through a journey. [ 14 ]   Interspecies friendships  within the animal kingdom, as well as between humans and their pets, additionally provides an underlying root for the popularity of such beings. [ 6 ]


In various mythologies throughout history, many particularly famous hybrids have existed, including as a part of Egyptian and Indian spirituality. [ 14 ]  The entities have also been characters in fictional media such as in  H. G. Wells ' work  The Island of Doctor Moreau , adapted into the popular  1932 film   Island of Lost Souls . [ 7 ]  In legendary terms, the hybrids have played varying roles from that of trickster and/or villain to serving as divine heroes in very different contexts, depending on the given culture. [ 14 ]


Beings displaying a mixture of human and animal traits while also having a similarly blended appearance have played a vast and varied role in multiple traditions around the world. [ 14 ]  Artist and scholar Pietro Gaietto has written that "representations of human-animal hybrids always have their origins in religion". In "successive traditions they may change in meaning but they still remain within spiritual culture", Gaietto has argued, when looking back in an  evolution -minded point of view. The beings show up in both  Greek  and  Roman mythology , with various elements of  ancient Egyptian  society ebbing and flowing into those cultures in particular. Prominent examples in  ancient Egyptian religion , featuring some of the earliest such hybrid beings, include the  canine -like  god of death  known as  Anubis  and the lion-like  Sphinx . [ 15 ] [ unreliable source? ]  Other instances of these types of characters include figures within both  Chinese  and  Japanese mythology . [ 14 ] [ 16 ]  The observation of  interspecies friendships  within the animal kingdom, as well as the bonds existing between humans and their pets, have been a source of the appeal in such stories. [ 6 ]


A prominent hybrid figure that's internationally known is the  mythological Greek  figure of Pan. A deity that rules over and symbolizes the untamed wild, he helps express the inherent beauty of the natural world as the Greeks saw things. He specifically received reverence by ancient  hunters , fishermen, shepherds, and other groups with a close connection to nature. Pan is a Satyr who possesses the hindquarters, legs, and horns of a goat while otherwise being essentially human in appearance; stories of his encounters with different gods, humans, and others have been  a part of popular culture  in several different cultures for many years. [ 17 ]  The human-animal hybrid has appeared in acclaimed works of art by figures such as  Francis Bacon , [ 8 ]  also being mentioned in  poetic pieces  such as in  John Fletcher's  writings. [ 17 ]  Specifically, the human-animal hybrid has appeared in acclaimed works of art by figures such as  Francis Bacon . [ 8 ]  Additional famous mythological hybrids include the Egyptian  god of death , named  Anubis , and the fox-like Japanese beings that are called  Kitsune . [ 14 ]


In  Chinese mythology , the figure of  Chu Pa-chieh  ( Chinese :  豬八戒 ;  pinyin :  Zhūbājiè ) undergoes a personal journey in which he gives up wickedness for virtue. After causing a disturbance in heaven from his licentious actions, he is exiled to Earth. By mistake, he enters the womb of a sow and ends up being born as a half-man/half-pig entity. With the head and ears of a pig coupled with a human body, his already animal-like sense of selfishness from his past life remains.  Killing and eating his mother  as well as  devouring his brothers , he makes his way to a mountain hideout, spending his days preying on unwary travelers unlucky enough to cross his path. However, the exhortations of the kind  goddess   Kuan Yin , journeying in China, persuade him to seek a nobler path, and his life's journey and the side of goodness proceeds on such that even he is ordained a priest by the goddess herself. [ 18 ]  Remarking on the character's role in the religious novel  Journey to the West , where the being first appears, professor  Victor H. Mair  has commented that "[p]ig-human hybrids represent descent and the grotesque, a capitulation to the basest appetites" rather than "self-improvement". [ 16 ]


Several hybrid entities have long played a major role in Japanese media and in traditional beliefs within the country. For example, a warrior god known as Amida received worship as a part of  Japanese mythology  for many years; he possessed a generally humanoid appearance while having a canine-like head. However, the god's devotional popularity fell in about the middle of the 19th century. [ 15 ] [ unreliable source? ]  A  Tanuki  resembles a  raccoon dog , but its  shape-shifting  talents allow it to turn into humans for the purposes of trickery, such as impersonating  Buddhist   monks . The fox-like creatures known as  Kitsune  also possess similar powers, and stories abound of them tricking human men into marriage by turning into seductive women. [ 14 ]


Other examples include characters in ancient  Anatolia  and  Mesopotamia . The latter region has had the tradition of a malevolent human-animal hybrid deity in  Pazuzu , the  demon  featuring a humanoid shape yet having grotesque features such as sharp  talons . [ 15 ] [ unreliable source? ]  The character picked up revived attention when  an interpretation of it  appeared in  William Peter Blatty 's  1971 novel   The Exorcist  and the  Academy Award  winning  1973 film adaption of the same name , with the demon possessing the body of an innocent young girl. The movie, regarded as  one of the greatest horror films of all time , has a prologue in which co-protagonist  Father Merrin  ( Max von Sydow ) visits an  archaeological dig  in  Iraq  and ominously discovers an old statue of the monstrous being. [ 19 ] [ 20 ]


"Theriocephaly" (from  Greek  θηρίον  therion  'beast' and κεφαλή  kefalí  'head') is the  anthropomorphic  condition or quality of having the head of an animal with a body either mostly or entirely looking human – the term being commonly used to refer the depiction of  deities  or otherwise specially able individuals. An entity with such qualities is said to be "theriomorphous". [ 21 ]  Many of the  gods and goddesses  worshipped by the  ancient Egyptians , for example, were commonly depicted as being theriocephalic. This phenomenon partly represented an intermediate step in a longer process of anthropomorphization of former animal deities (e.g. the goddess  Hathor  in her earliest form was depicted as a cow and in her latest manifestation as a woman with cows ears and sometimes a hairstyle resembling cows horns). But the form of depiction sometimes depended also on the aspects of a deity an artist wanted to accentuate (e.g.  Ba , the aspect of personality of a human soul, was depicted as a bird with a humans head). This can also be seen in the different hieroglyphs that could be used to write the name of a single deity.
Other notable examples include:


Examples from other geographic areas include:


Many prominent pieces of children's literature over the past two centuries have featured humanized animal characters, often as  protagonists  in the stores. In the opinion of popular educator  Lucy Sprague Mitchell , the appeal of such mythical and fantastic beings comes from how children desire "direct" language "told in terms of images— visual, auditory, tactile, muscle images". Another author has remarked that an "animal costume" provides "a way to emphasize or even exaggerate a particular characteristic".


The  anthropomorphic  characters in the seminal works by English writer  Beatrix Potter  in particular live an ambiguous situation, having human dress yet displaying many instinctive animal traits. Writing on the popularity of  Peter Rabbit , a later author commented that in "balancing humanized domesticity against wild rabbit foraging, Potter subverted parental authority and its built in hypocrisy" in Potter's child-centered books. Writer Lisa Fraustino has cited on the subject  R.M. Lockley 's tongue-in-cheek observation: "Rabbits are so human. Or is it the other way around— humans are so rabbit?" [ 22 ]


Writer  H. G. Wells  created his famous work  The Island of Doctor Moreau , featuring a mixture of  horror  and  science fiction  elements, to promote the anti- vivisection  cause as a part of his long-time advocacy for  animal rights . Wells' story describes a man stuck on an island ruled over by the titular Dr. Moreau, a morally depraved scientist who has created several human-animal hybrids referred to as 'Beast Folk' through vivisection and even by combining parts of other animals for some of the 'Beast Folk'. The story has been adapted into film several times, with varying success. The most acclaimed version is the 1932  black-and-white  treatment called  Island of Lost Souls . [ 7 ]  Wells himself wrote that "this story was the response of an imaginative mind to the reminder that humanity is but animal rough-hewn to a reasonable shape and in perpetual internal conflict between instinct and injunction," with the scandals surrounding  Oscar Wilde  being the impetus for the English writer's treatment of themes such as ethics and psychology. Challenging the  Victorian era  viewpoints of its time, the  1896 work  presents a complex situation in which enhancing animals into hybrids involves both terrifying violence and pain as well as appears essentially futile, given the power of raw instinct. A pessimistic view towards the ability of human civilization to live by  law-abiding ,  moral standards  for long thus follows. [ 23 ]


The 1986  horror film   The Fly  features a deformed and monstrous human-animal hybrid, played by actor  Jeff Goldblum . [ 6 ]  His character, scientist Seth Brundle, undergoes a  teleportation  experiment that goes awry and fuses him at a fundamental genetic level with a  common fly  caught besides him. Brundle experiences drastic mutations as a result that horrify him. Movie critic Gerardo Valero has written that the famous horror work, "released at the dawn of the  AIDS epidemic ", "was seen by many as a metaphor for the disease" while also playing on bodily fears about  dismemberment  and coming apart that human beings inherently share. [ 24 ]


The  science fiction film   Splice , released 2009, shows scientists mixing together human and animal  DNA  in the hopes of advancing medical research at the pharmaceutical company that they work at. Calamitous results occur when the hybrid named Dren is born. [ 3 ]


The  H. P. Lovecraft –inspired movie  Dagon , released in 2001, additionally features grotesque hybrid beings. In terms of  comic books , examples of fictional human-animal hybrids include the characters in  Charles Burns '  Black Hole  series. In those comics, a set of teenagers in a 1970s era town become afflicted by a bizarre disease; the  sexually transmitted affliction  mutates them into monstrous forms. [ 6 ]


Multiple video games have featured human-animal hybrids as enemies for the protagonist(s) to defeat, including powerful  boss characters . For instance, the 2014  survival horror  release  The Evil Within  includes grotesque hybrid beings, looking like the  undead , attacking main character Detective Sebastian Castellanos. With partners Joseph Oda and Julie Kidman, the protagonist attempts investigate a multiple homicide at a  mental hospital  yet discovers a mysterious figure who turns the world around them into a living  nightmare , Castellanos having to find the truth about the criminal  psychopath . [ 25 ]


Heroic character  examples of human-animal anthropomorphic characters include the two protagonists of the  2002 movie   The Cat Returns  ( Japanese title : 猫の恩返し), with the  animated film  featuring a young girl (named "Haru") being transformed against her will into a  feline -human hybrid and fighting a villainous  king  of the cats with the help of a dashing male cat companion (known as the "Baron") at her side.


On a more everyday life tone, featuring human-animal hybrids of mythological beings having common human experiences,  A Centaur's Life , known in Japan as  Centaur's Worries  ( Japanese :  セントールの悩み ,  Hepburn :  Sentōru no Nayami ) , is a Japanese  slice of life   comedy   manga  series by Kei Murayama. [ 26 ] [ 27 ]  The series has been serialized in  Tokuma Shoten 's  Monthly Comic Ryū  magazine since February 2011, and is published in English by  Seven Seas Entertainment . [ 28 ] [ 29 ]  An  anime  television series adaptation by  Haoliners Animation League  aired in Japan from July to September 2017. [ 30 ] [ 31 ]


With general  U.S. popular culture  and its various  subcultures , the  furry fandom  consists of individuals interested in a variety of  artistic materials , this often featuring "furry art... [that] depicts a human-animal hybrid in everyday life". Specific people involved in  creative media  will frequently come up with a " fursona " depicting a version or versions of themselves as a hybrid creature. This practice functions as an outlet based on "personal ideas of self-expression" ( self-realization ). [ 32 ]


A  hypervariable region  ( HVR ) is a location within a sequence where  polymorphisms  frequently occur. It is used in two contexts:


Because there already is a separate article for the antibody region, this article will focus on the nucleic acid case.


There are two mitochondrial hypervariable regions used in human mitochondrial  genealogical DNA testing . HVR1 is considered a "low resolution" region and HVR2 is considered a "high resolution" region. Getting HVR1 and HVR2 DNA tests can help determine one's  haplogroup . In the revised  Cambridge Reference Sequence  of the human mitogenome, the most variable sites of HVR1 are numbered 16024-16383 (this subsequence is called HVR-I), and the most variable sites of HVR2 are numbered 57-372 ( i.e.,  HVR-II) and 438-574 ( i.e.,  HVR-III). [ 2 ] [ 3 ]


In some  bony fishes , for example certain  Protacanthopterygii  and  Gadidae , the  mitochondrial control region  evolves remarkably slowly. Even functional mitochondrial  genes  accumulate mutations faster and more freely. It is not known whether such hypovariable control regions are more widespread. In the  Ayu  ( Plecoglossus altivelis ), an  East Asian  protacanthopterygian, control region  mutation  rate is not markedly lowered, but sequence differences between  subspecies  are far lower in the control region than elsewhere. This phenomenon completely defies explanation at present. [ 4 ]


The 16S ribosomal RNA in prokaryotes have nine hypervariable regions where mutation rates are higher than neighboring parts, numbered V1 to V9. V4 one of the most conservative, while V3 is one of the fastest-evolving. These regions offer a way to quickly determine the identity of a prokaryote: because the surrounding regions are relatively conserved, a "universal primer" can be used to selectively amplify one or a stretch of several HV regions using PCR. The resultant amplicon is sequenced, and each unique sequence is termed an amplicon sequence variant (ASV). [ 5 ]   A database such as Greengenes2 can then be used to look up an ASV (often an exact match) in the taxonomic and phylogenetic trees. [ 6 ]


Simple sequence repeats, specifically variable number tandem repeats and  microsatellites , commonly occur in the human genome. Their repeated nature allows a unique form of mutation: the number of copies can increase or decrease when strand slippage occurs during DNA replication. (Regular point mutation still happens and could be more frequent than slippage.) [ 7 ]  Their copy number not only have use in forensics and ancestry testing, [ 8 ]  but are also linked to diseases. [ 9 ]


Institute for Genetic Engineering and Biotechnology  ( INGEB ) is a  Bosnian
public research institute, member of  Sarajevo University (UNSA) , [ 1 ]  and affiliate center of  International Centre for Genetic Engineering and Biotechnology  (ICGEB).


ICGEB was established as a special project of the  United Nations Industrial Development Organization  (UNIDO). [ 2 ] [ 3 ]


INGEB was founded under the name "Center for Genetic Engineering and Biotechnology", in 1988. INGEB's headquarters are located in  Sarajevo .


One of INGEB's most prominent founders was Professor  Rifat Hadžiselimović , [ 4 ] [ 5 ]  with the support of the Government of  Socialist Republic of Bosnia and Herzegovina ,  ANUBiH  and the biggest B&H economic systems. [ 6 ]  After the  establishment document, INGEB was entrusted with the functions maker, institutional creator and carrier of the overall scientific and professional work in the development of  genetic engineering  and  biotechnology  based  molecular biology  in B&H. [ 7 ] [ 8 ]


In 1993, by a legal act, [ citation needed ]  the Assembly of  Republic of Bosnia and Herzegovina , [ 9 ]  assumed the right of the founder of the institution, at the beginning of the  Bosnian War , and later, in 1999, entitled founder of INGEB (as a "public institution that will operate within the University of Sarajevo") took over the  Sarajevo Canton . [ 10 ] [ 11 ] [ clarification needed ]


In INGEB, there are following functional units:


Laboratory for forensic genetics provides scientific approach to analysis of samples of different origin. In this laboratory  DNA profiling  is routinely done for skeletal remains, blood stains (on different materials), hair, semen, controversial traces on cigarette butts, controversial traces under fingernails, in urine etc.


Expert activities perform in laboratory for forensic genetics include: