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Genetic engineering

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Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesising the DNA. A construct is usually created and used to insert this DNA into the host organism. The first recombinant DNA molecule was made by Paul Berg in 1972 by combining DNA from the monkey virus SV40 with the lambda virus. As well as inserting genes, the process can be used to remove, or "knock out", genes. The new DNA can be inserted randomly, or targeted to a specific part of the genome.[1]

An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is a genetically modified organism (GMO). The first GMO was a bacterium generated by Herbert Boyer and Stanley Cohen in 1973. Rudolf Jaenisch created the first GM animal when he inserted foreign DNA into a mouse in 1974. The first company to focus on genetic engineering, Genentech, was founded in 1976 and started the production of human proteins. Genetically engineered human insulin was produced in 1978 and insulin-producing bacteria were commercialised in 1982. Genetically modified food has been sold since 1994, with the release of the Flavr Savr tomato. The Flavr Savr was engineered to have a longer shelf life, but most current GM crops are modified to increase resistance to insects and herbicides. GloFish, the first GMO designed as a pet, was sold in the United States in December 2003. In 2016 salmon modified with a growth hormone were sold.

Genetic engineering has been applied in numerous fields including research, medicine, industrial biotechnology and agriculture. In research, GMOs are used to study gene function and expression through loss of function, gain of function, tracking and expression experiments. By knocking out genes responsible for certain conditions it is possible to create animal model organisms of human diseases. As well as producing hormones, vaccines and other drugs, genetic engineering has the potential to cure genetic diseases through gene therapy. The same techniques that are used to produce drugs can also have industrial applications such as producing enzymes for laundry detergent, cheeses and other products.

The rise of commercialised genetically modified crops has provided economic benefit to farmers in many different countries, but has also been the source of most of the controversy surrounding the technology. This has been present since its early use; the first field trials were destroyed by anti-GM activists. Although there is a scientific consensus that currently available food derived from GM crops poses no greater risk to human health than conventional food, critics consider GM food safety a leading concern. Gene flow, impact on non-target organisms, control of the food supply and intellectual property rights have also been raised as potential issues. These concerns have led to the development of a regulatory framework, which started in 1975. It has led to an international treaty, the Cartagena Protocol on Biosafety, that was adopted in 2000. Individual countries have developed their own regulatory systems regarding GMOs, with the most marked differences occurring between the US and Europe.

IUPAC definition

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

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

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Gene

Gene

In biology, the word gene can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes.

Genetic engineering techniques

Genetic engineering techniques

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

DNA

DNA

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known 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.

Artificial gene synthesis

Artificial gene synthesis

Artificial gene synthesis, or simply gene synthesis, refers to a group of methods that are used in synthetic biology to construct and assemble genes from nucleotides de novo. Unlike DNA synthesis in living cells, artificial gene synthesis does not require template DNA, allowing virtually any DNA sequence to be synthesized in the laboratory. It comprises two main steps, the first of which is solid-phase DNA synthesis, sometimes known as DNA printing. This produces oligonucleotide fragments that are generally under 200 base pairs. The second step then involves connecting these oligonucleotide fragments using various DNA assembly methods. Because artificial gene synthesis does not require template DNA, it is theoretically possible to make a completely synthetic DNA molecule with no limits on the nucleotide sequence or size.

Gene knockout

Gene knockout

Gene knockouts are a widely used genetic engineering technique that involves the targeted removal or inactivation of a specific gene within an organism's genome. This can be done through a variety of methods, including homologous recombination, CRISPR-Cas9, and TALENs.

Gene targeting

Gene targeting

Gene targeting is a genetic technique that uses homologous recombination to modify an endogenous gene. The method can be used to delete a gene, remove exons, add a gene and modify individual base pairs. The process of gene targeting provides a way to alter specific genes in order to better identify their biological roles. Gene targeting can be permanent or conditional. Conditions can be a specific time during development / life of the organism or limitation to a specific tissue, for example. Gene targeting requires the creation of a specific vector for each gene of interest. However, it can be used for any gene, regardless of transcriptional activity or gene size.

Genentech

Genentech

Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within Roche. Historically, the company is regarded as the world's first biotechnology company.

Flavr Savr

Flavr Savr

Flavr Savr, a genetically modified tomato, was the first commercially grown genetically engineered food to be granted a license for human consumption. It was developed by the Californian company Calgene in the 1980s. The tomato has an improved shelf-life, increased fungal resistance and a slightly increased viscosity compared to its non-modified counterpart. It was meant to be harvested ripe for increased flavor for long-distance shipping. The Flavr Savr contains two genes added by Calgene; a reversed antisense polygalacturonase gene which inhibits the production of the aforementioned rotting enzyme and a gene responsible for the creation of APH(3')II, which confers resistance to certain aminoglycoside antibiotics including kanamycin and neomycin. On May 18, 1994, the FDA completed its evaluation of the Flavr Savr tomato and the use of APH(3')II, concluding that the tomato "is as safe as tomatoes bred by conventional means" and "that the use of aminoglycoside 3'-phosphotransferase II is safe for use as a processing aid in the development of new varieties of tomato, rapeseed oil, and cotton intended for food use." It was first sold in 1994, and was only available for a few years before production ceased in 1997. Calgene made history, but mounting costs prevented the company from becoming profitable, and it was eventually acquired by Monsanto Company.

AquAdvantage salmon

AquAdvantage salmon

AquAdvantage salmon is a genetically engineered (GE) fish, a GE Atlantic salmon developed by AquaBounty Technologies in 1989. The typical growth hormone-regulating gene in the Atlantic salmon was replaced with the growth hormone-regulating gene from Pacific Chinook salmon, with a promoter sequence from ocean pout. This gene enables GM salmon to grow year-round instead of only during spring and summer.

Gene therapy

Gene therapy

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time.

Gene flow

Gene flow

In population genetics, gene flow is the transfer of genetic material from one population to another. If the rate of gene flow is high enough, then two populations will have equivalent allele frequencies and therefore can be considered a single effective population. It has been shown that it takes only "one migrant per generation" to prevent populations from diverging due to drift. Populations can diverge due to selection even when they are exchanging alleles, if the selection pressure is strong enough. Gene flow is an important mechanism for transferring genetic diversity among populations. Migrants change the distribution of genetic diversity among populations, by modifying allele frequencies. High rates of gene flow can reduce the genetic differentiation between the two groups, increasing homogeneity. For this reason, gene flow has been thought to constrain speciation and prevent range expansion by combining the gene pools of the groups, thus preventing the development of differences in genetic variation that would have led to differentiation and adaptation. In some cases dispersal resulting in gene flow may also result in the addition of novel genetic variants under positive selection to the gene pool of a species or population

Cartagena Protocol on Biosafety

Cartagena Protocol on Biosafety

The Cartagena Protocol on Biosafety to the Convention on Biological Diversity is an international agreement on biosafety as a supplement to the Convention on Biological Diversity (CBD) effective since 2003. The Biosafety Protocol seeks to protect biological diversity from the potential risks posed by genetically modified organisms resulting from modern biotechnology.

Overview

Comparison of conventional plant breeding with transgenic and cisgenic genetic modification
Comparison of conventional plant breeding with transgenic and cisgenic genetic modification

Genetic engineering is a process that alters the genetic structure of an organism by either removing or introducing DNA, or modifying existing genetic material in situ. Unlike traditional animal and plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired phenotype, genetic engineering takes the gene directly from one organism and delivers it to the other. This is much faster, can be used to insert any genes from any organism (even ones from different domains) and prevents other undesirable genes from also being added.[4]

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

The DNA can be introduced directly into the host organism or into a cell that is then fused or hybridised with the host.[9] This relies on recombinant nucleic acid techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macro-injection or micro-encapsulation.[10]

Genetic engineering does not normally include traditional breeding, in vitro fertilisation, induction of polyploidy, mutagenesis and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process.[9] However, some broad definitions of genetic engineering include selective breeding.[10] Cloning and stem cell research, although not considered genetic engineering,[11] are closely related and genetic engineering can be used within them.[12] Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesised material into an organism.[13]

Plants, animals or microorganisms that have been changed through genetic engineering are termed genetically modified organisms or GMOs.[14] If genetic material from another species is added to the host, the resulting organism is called transgenic. If genetic material from the same species or a species that can naturally breed with the host is used the resulting organism is called cisgenic.[15] If genetic engineering is used to remove genetic material from the target organism the resulting organism is termed a knockout organism.[16] In Europe genetic modification is synonymous with genetic engineering while within the United States of America and Canada genetic modification can also be used to refer to more conventional breeding methods.[17][18][19]

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DNA

DNA

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known 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.

Animal breeding

Animal breeding

Animal breeding is a branch of animal science that addresses the evaluation of the genetic value of livestock. Selecting for breeding animals with superior EBV in growth rate, egg, meat, milk, or wool production, or with other desirable traits has revolutionized livestock production throughout the entire world. The scientific theory of animal breeding incorporates population genetics, quantitative genetics, statistics, and recently molecular genetics and is based on the pioneering work of Sewall Wright, Jay Lush, and Charles Henderson.

Gene

Gene

In biology, the word gene can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes.

Domain (biology)

Domain (biology)

In biological taxonomy, a domain, also dominion, superkingdom, realm, or empire, is the highest taxonomic rank of all organisms taken together. It was introduced in the three-domain system of taxonomy devised by Carl Woese, Otto Kandler and Mark Wheelis in 1990.

Genetic disorder

Genetic disorder

A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.

List of genetically modified crops

List of genetically modified crops

Genetically modified crops are plants used in agriculture, the DNA of which has been modified using genetic engineering techniques. In most cases, the aim is to introduce a new trait to the plant which does not occur naturally in the species. As of 2015, 26 plant species have been genetically modified and approved for commercial release in at least one country. The majority of these species contain genes that make them either tolerant to herbicides or resistant to insects. Other common traits include virus resistance, delayed ripening, modified flower colour or altered composition. In 2014, 28 countries grew GM crops, and 39 countries imported but did not grow them.

Food security

Food security

Food security speaks to the availability of food in a country and the ability of individuals within that country (geography) to access, afford, and source adequate foodstuffs. According to the United Nations Committee on World Food Security, food security is defined as meaning that all people, at all times, have physical, social, and economic access to sufficient, safe, and nutritious food that meets their food preferences and dietary needs for an active and healthy life. The availability of food irrespective of class, gender or region is another element of food security. There is evidence of food security being a concern many thousands of years ago, with central authorities in ancient China and ancient Egypt being known to release food from storage in times of famine. At the 1974 World Food Conference, the term "food security" was defined with an emphasis on supply; food security is defined as the "availability at all times of adequate, nourishing, diverse, balanced and moderate world food supplies of basic foodstuffs to sustain a steady expansion of food consumption and to offset fluctuations in production and prices". Later definitions added demand and access issues to the definition. The first World Food Summit, held in 1996, stated that food security "exists when all people, at all times, have physical and economic access to sufficient, safe and nutritious food to meet their dietary needs and food preferences for an active and healthy life."

Cell fusion

Cell fusion

Cell fusion is an important cellular process in which several uninucleate cells combine to form a multinucleate cell, known as a syncytium. Cell fusion occurs during differentiation of myoblasts, osteoclasts and trophoblasts, during embryogenesis, and morphogenesis. Cell fusion is a necessary event in the maturation of cells so that they maintain their specific functions throughout growth.

Hybrid (biology)

Hybrid (biology)

In biology, a hybrid is the offspring resulting from combining the qualities of two organisms of different breeds, varieties, species or genera through sexual reproduction. Generally, it means that each cell has genetic material from two different organisms, whereas an individual where some cells are derived from a different organism is called a chimera. Hybrids are not always intermediates between their parents, but can show hybrid vigor, sometimes growing larger or taller than either parent. The concept of a hybrid is interpreted differently in animal and plant breeding, where there is interest in the individual parentage. In genetics, attention is focused on the numbers of chromosomes. In taxonomy, a key question is how closely related the parent species are.

Microinjection

Microinjection

Microinjection is the use of a glass micropipette to inject a liquid substance at a microscopic or borderline macroscopic level. The target is often a living cell but may also include intercellular space. Microinjection is a simple mechanical process usually involving an inverted microscope with a magnification power of around 200x.

Micro-encapsulation

Micro-encapsulation

Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, with useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other materials on a micro metric scale. Microencapsulation can also be used to enclose solids, liquids, or gases inside a micrometric wall made of hard or soft soluble film, in order to reduce dosing frequency and prevent the degradation of pharmaceuticals.

In vitro fertilisation

In vitro fertilisation

In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro. The process involves monitoring and stimulating a female's ovulatory process, removing an ovum or ova from their ovaries and letting sperm fertilise them in a culture medium in a laboratory. After the fertilised egg (zygote) undergoes embryo culture for 2–6 days, it is transferred by catheter into the uterus, with the intention of establishing a successful pregnancy.

History

Humans have altered the genomes of species for thousands of years through selective breeding, or artificial selection[20]: 1 [21]: 1  as contrasted with natural selection. More recently, mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations, for selective breeding purposes. Genetic engineering as the direct manipulation of DNA by humans outside breeding and mutations has only existed since the 1970s. The term "genetic engineering" was first coined by Jack Williamson in his science fiction novel Dragon's Island, published in 1951[22] – one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase,[23] and two years before James Watson and Francis Crick showed that the DNA molecule has a double-helix structure – though the general concept of direct genetic manipulation was explored in rudimentary form in Stanley G. Weinbaum's 1936 science fiction story Proteus Island.[24][25]

In 1974 Rudolf Jaenisch created a genetically modified mouse, the first GM animal.
In 1974 Rudolf Jaenisch created a genetically modified mouse, the first GM animal.

In 1972, Paul Berg created the first recombinant DNA molecules by combining DNA from the monkey virus SV40 with that of the lambda virus.[26] In 1973 Herbert Boyer and Stanley Cohen created the first transgenic organism by inserting antibiotic resistance genes into the plasmid of an Escherichia coli bacterium.[27][28] A year later Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world's first transgenic animal[29] These achievements led to concerns in the scientific community about potential risks from genetic engineering, which were first discussed in depth at the Asilomar Conference in 1975. One of the main recommendations from this meeting was that government oversight of recombinant DNA research should be established until the technology was deemed safe.[30][31]

In 1976 Genentech, the first genetic engineering company, was founded by Herbert Boyer and Robert Swanson and a year later the company produced a human protein (somatostatin) in E. coli. Genentech announced the production of genetically engineered human insulin in 1978.[32] In 1980, the U.S. Supreme Court in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented.[33] The insulin produced by bacteria was approved for release by the Food and Drug Administration (FDA) in 1982.[34]

In 1983, a biotech company, Advanced Genetic Sciences (AGS) applied for U.S. government authorisation to perform field tests with the ice-minus strain of Pseudomonas syringae to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges.[35] In 1987, the ice-minus strain of P. syringae became the first genetically modified organism (GMO) to be released into the environment[36] when a strawberry field and a potato field in California were sprayed with it.[37] Both test fields were attacked by activist groups the night before the tests occurred: "The world's first trial site attracted the world's first field trasher".[36]

The first field trials of genetically engineered plants occurred in France and the US in 1986, tobacco plants were engineered to be resistant to herbicides.[38] The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992.[39] In 1994 Calgene attained approval to commercially release the first genetically modified food, the Flavr Savr, a tomato engineered to have a longer shelf life.[40] In 1994, the European Union approved tobacco engineered to be resistant to the herbicide bromoxynil, making it the first genetically engineered crop commercialised in Europe.[41] In 1995, Bt potato was approved safe by the Environmental Protection Agency, after having been approved by the FDA, making it the first pesticide producing crop to be approved in the US.[42] In 2009 11 transgenic crops were grown commercially in 25 countries, the largest of which by area grown were the US, Brazil, Argentina, India, Canada, China, Paraguay and South Africa.[43]

In 2010, scientists at the J. Craig Venter Institute created the first synthetic genome and inserted it into an empty bacterial cell. The resulting bacterium, named Mycoplasma laboratorium, could replicate and produce proteins.[44][45] Four years later this was taken a step further when a bacterium was developed that replicated a plasmid containing a unique base pair, creating the first organism engineered to use an expanded genetic alphabet.[46][47] In 2012, Jennifer Doudna and Emmanuelle Charpentier collaborated to develop the CRISPR/Cas9 system,[48][49] a technique which can be used to easily and specifically alter the genome of almost any organism.[50]

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History of genetic engineering

History of genetic engineering

Genetic engineering is the science of manipulating genetic material of an organism. The first artificial genetic modification accomplished using biotechnology was transgenesis, the process of transferring genes from one organism to another, first accomplished by Herbert Boyer and Stanley Cohen in 1973. It was the result of a series of advancements in techniques that allowed the direct modification of the genome. Important advances included the discovery of restriction enzymes and DNA ligases, the ability to design plasmids and technologies like polymerase chain reaction and sequencing. Transformation of the DNA into a host organism was accomplished with the invention of biolistics, Agrobacterium-mediated recombination and microinjection. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1976 the technology was commercialised, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. In 1983 an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organisms and induce a range of different effects. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.

Natural selection

Natural selection

Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Charles Darwin popularised the term "natural selection", contrasting it with artificial selection, which is intentional, whereas natural selection is not.

Mutation breeding

Mutation breeding

Mutation breeding, sometimes referred to as "variation breeding", is the process of exposing seeds to chemicals, radiation, or enzymes in order to generate mutants with desirable traits to be bred with other cultivars. Plants created using mutagenesis are sometimes called mutagenic plants or mutagenic seeds.

Jack Williamson

Jack Williamson

John Stewart Williamson, who wrote as Jack Williamson, was an American science fiction writer, often called the "Dean of Science Fiction". He is also credited with one of the first uses of the term genetic engineering. Early in his career he sometimes used the pseudonyms Will Stewart and Nils O. Sonderlund.

Heredity

Heredity

Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic information of their parents. Through heredity, variations between individuals can accumulate and cause species to evolve by natural selection. The study of heredity in biology is genetics.

Alfred Hershey

Alfred Hershey

Alfred Day Hershey was an American Nobel Prize–winning bacteriologist and geneticist.

Martha Chase

Martha Chase

Martha Cowles Chase, also known as Martha C. Epstein, was an American geneticist who in 1952, with Alfred Hershey, experimentally helped to confirm that DNA rather than protein is the genetic material of life.

Francis Crick

Francis Crick

Francis Harry Compton Crick was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical structure of the DNA molecule. Crick and Watson's paper in Nature in 1953 laid the groundwork for understanding DNA structure and functions. Together with Maurice Wilkins, they were jointly awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

DNA

DNA

Deoxyribonucleic acid is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known 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.

Genetically modified mouse

Genetically modified mouse

A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse 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. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics.

Lambda phage

Lambda phage

Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

Herbert Boyer

Herbert Boyer

Herbert Wayne "Herb" Boyer is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg he discovered a method to coax bacteria into producing foreign proteins, thereby jump-starting the field of genetic engineering. By 1969, he performed studies on a couple of restriction enzymes of the E.coli bacterium with especially useful properties. He is recipient of the 1990 National Medal of Science, co-recipient of the 1996 Lemelson–MIT Prize, and a co-founder of Genentech. He was professor at the University of California, San Francisco (UCSF) and later served as vice president of Genentech from 1976 until his retirement in 1991.

Process

Polymerase chain reaction is a powerful tool used in molecular cloning
Polymerase chain reaction is a powerful tool used in molecular cloning

Creating a GMO is a multi-step process. Genetic engineers must first choose what gene they wish to insert into the organism. This is driven by what the aim is for the resultant organism and is built on earlier research. Genetic screens can be carried out to determine potential genes and further tests then used to identify the best candidates. The development of microarrays, transcriptomics and genome sequencing has made it much easier to find suitable genes.[51] Luck also plays its part; the Roundup Ready gene was discovered after scientists noticed a bacterium thriving in the presence of the herbicide.[52]

Gene isolation and cloning

The next step is to isolate the candidate gene. The cell containing the gene is opened and the DNA is purified.[53] The gene is separated by using restriction enzymes to cut the DNA into fragments[54] or polymerase chain reaction (PCR) to amplify up the gene segment.[55] These segments can then be extracted through gel electrophoresis. If the chosen gene or the donor organism's genome has been well studied it may already be accessible from a genetic library. If the DNA sequence is known, but no copies of the gene are available, it can also be artificially synthesised.[56] Once isolated the gene is ligated into a plasmid that is then inserted into a bacterium. The plasmid is replicated when the bacteria divide, ensuring unlimited copies of the gene are available.[57] The RK2 plasmid is notable for its ability to replicate in a wide variety of single-celled organisms, which makes it suitable as a genetic engineering tool.[58]

Before the gene is inserted into the target organism it must be combined with other genetic elements. These include a promoter and terminator region, which initiate and end transcription. A selectable marker gene is added, which in most cases confers antibiotic resistance, so researchers can easily determine which cells have been successfully transformed. The gene can also be modified at this stage for better expression or effectiveness. These manipulations are carried out using recombinant DNA techniques, such as restriction digests, ligations and molecular cloning.[59]

Inserting DNA into the host genome

A gene gun uses biolistics to insert DNA into plant tissue
A gene gun uses biolistics to insert DNA into plant tissue

There are a number of techniques used to insert genetic material into the host genome. Some bacteria can naturally take up foreign DNA. This ability can be induced in other bacteria via stress (e.g. thermal or electric shock), which increases the cell membrane's permeability to DNA; up-taken DNA can either integrate with the genome or exist as extrachromosomal DNA. DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus, or through the use of viral vectors.[60]

Plant genomes can be engineered by physical methods or by use of Agrobacterium for the delivery of sequences hosted in T-DNA binary vectors. In plants the DNA is often inserted using Agrobacterium-mediated transformation,[61] taking advantage of the Agrobacteriums T-DNA sequence that allows natural insertion of genetic material into plant cells.[62] Other methods include biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells,[63] and electroporation, which involves using an electric shock to make the cell membrane permeable to plasmid DNA.

As only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through the use of tissue culture.[64][65] In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells.[66] Bacteria consist of a single cell and reproduce clonally so regeneration is not necessary. Selectable markers are used to easily differentiate transformed from untransformed cells. These markers are usually present in the transgenic organism, although a number of strategies have been developed that can remove the selectable marker from the mature transgenic plant.[67]

A. tumefaciens attaching itself to a carrot cell
A. tumefaciens attaching itself to a carrot cell

Further testing using PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene.[68] These tests can also confirm the chromosomal location and copy number of the inserted gene. The presence of the gene does not guarantee it will be expressed at appropriate levels in the target tissue so methods that look for and measure the gene products (RNA and protein) are also used. These include northern hybridisation, quantitative RT-PCR, Western blot, immunofluorescence, ELISA and phenotypic analysis.[69]

The new genetic material can be inserted randomly within the host genome or targeted to a specific location. The technique of gene targeting uses homologous recombination to make desired changes to a specific endogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use of selectable markers. The frequency of gene targeting can be greatly enhanced through genome editing. Genome editing uses artificially engineered nucleases that create specific double-stranded breaks at desired locations in the genome, and use the cell's endogenous mechanisms to repair the induced break by the natural processes of homologous recombination and nonhomologous end-joining. There are four families of engineered nucleases: meganucleases,[70][71] zinc finger nucleases,[72][73] transcription activator-like effector nucleases (TALENs),[74][75] and the Cas9-guideRNA system (adapted from CRISPR).[76][77] TALEN and CRISPR are the two most commonly used and each has its own advantages.[78] TALENs have greater target specificity, while CRISPR is easier to design and more efficient.[78] In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate a gene knockout.[79][80]

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Genetic engineering techniques

Genetic engineering techniques

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

Polymerase chain reaction

Polymerase chain reaction

The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail. PCR was invented in 1983 by the American biochemist Kary Mullis at Cetus Corporation; Mullis and biochemist Michael Smith, who had developed other essential ways of manipulating DNA, were jointly awarded the Nobel Prize in Chemistry in 1993.

Molecular cloning

Molecular cloning

Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word cloning refers to the fact that the method involves the replication of one molecule to produce a population of cells with identical DNA molecules. Molecular cloning generally uses DNA sequences from two different organisms: the species that is the source of the DNA to be cloned, and the species that will serve as the living host for replication of the recombinant DNA. Molecular cloning methods are central to many contemporary areas of modern biology and medicine.

Genetic screen

Genetic screen

A genetic screen or mutagenesis screen is an experimental technique used to identify and select individuals who possess a phenotype of interest in a mutagenized population. Hence a genetic screen is a type of phenotypic screen. Genetic screens can provide important information on gene function as well as the molecular events that underlie a biological process or pathway. While genome projects have identified an extensive inventory of genes in many different organisms, genetic screens can provide valuable insight as to how those genes function.

DNA microarray

DNA microarray

A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome. Each DNA spot contains picomoles of a specific DNA sequence, known as probes. These can be a short section of a gene or other DNA element that are used to hybridize a cDNA or cRNA sample under high-stringency conditions. Probe-target hybridization is usually detected and quantified by detection of fluorophore-, silver-, or chemiluminescence-labeled targets to determine relative abundance of nucleic acid sequences in the target. The original nucleic acid arrays were macro arrays approximately 9 cm × 12 cm and the first computerized image based analysis was published in 1981. It was invented by Patrick O. Brown. An example of its application is in SNPs arrays for polymorphisms in cardiovascular diseases, cancer, pathogens and GWAS analysis. It is also used for the identification of structural variations and the measurement of gene expression.

Cell (biology)

Cell (biology)

The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a membrane, and contains many biomolecules such as proteins, DNA and RNA, as well as many small molecules of nutrients and metabolites. The term comes from the Latin word cellula meaning 'small room'.

Gel electrophoresis

Gel electrophoresis

Gel electrophoresis is a method for separation and analysis of biomacromolecules and their fragments, based on their size and charge. It is used in clinical chemistry to separate proteins by charge or size and in biochemistry and molecular biology to separate a mixed population of DNA and RNA fragments by length, to estimate the size of DNA and RNA fragments or to separate proteins by charge.

Genome

Genome

In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA. The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences, and often a substantial fraction of 'junk' DNA with no evident function. Almost all eukaryotes have mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplasts with a chloroplast genome.

Library (biology)

Library (biology)

In molecular biology, a library is a collection of DNA fragments that is stored and propagated in a population of micro-organisms through the process of molecular cloning. There are different types of DNA libraries, including cDNA libraries, genomic libraries and randomized mutant libraries. DNA library technology is a mainstay of current molecular biology, genetic engineering, and protein engineering, and the applications of these libraries depend on the source of the original DNA fragments. There are differences in the cloning vectors and techniques used in library preparation, but in general each DNA fragment is uniquely inserted into a cloning vector and the pool of recombinant DNA molecules is then transferred into a population of bacteria or yeast such that each organism contains on average one construct. As the population of organisms is grown in culture, the DNA molecules contained within them are copied and propagated.

Ligation (molecular biology)

Ligation (molecular biology)

Ligation is the joining of two nucleic acid fragments through the action of an enzyme. It is an essential laboratory procedure in the molecular cloning of DNA, whereby DNA fragments are joined to create recombinant DNA molecules (such as when a foreign DNA fragment is inserted into a plasmid). The ends of DNA fragments are joined by the formation of phosphodiester bonds between the 3'-hydroxyl of one DNA terminus with the 5'-phosphoryl of another. RNA may also be ligated similarly. A co-factor is generally involved in the reaction, and this is usually ATP or NAD+. Eukaryotic cells ligases belong to ATP type, and NAD+ - dependent are found in bacteria (e.g. E. coli).

Plasmid

Plasmid

A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; however, plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids often carry genes that benefit the survival of the organism and confer selective advantage such as antibiotic resistance. While chromosomes are large and contain all the essential genetic information for living under normal conditions, plasmids are usually very small and contain only additional genes that may be useful in certain situations or conditions. Artificial plasmids are widely used as vectors in molecular cloning, serving to drive the replication of recombinant DNA sequences within host organisms. In the laboratory, plasmids may be introduced into a cell via transformation. Synthetic plasmids are available for procurement over the internet.

RK2 plasmid

RK2 plasmid

The RK2 Plasmid is a broad-host-range plasmid belonging to the incP incompatibility group It is notable for its ability to replicate in a wide variety of single-celled organisms, which makes it suitable as a genetic engineering tool. It is capable of transfer, replication, and maintenance in most genera of Gram-negative bacteria. RK2 may sometimes be referred to as pRK2, which is also the name of another, unrelated plasmid. The IncP-1 plasmid group of which RK2 is a part has been described as "highly potent, self-transmissible, selfish DNA molecules with a complicated regulatory circuit"

Applications

Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and microorganisms. Bacteria, the first organisms to be genetically modified, can have plasmid DNA inserted containing new genes that code for medicines or enzymes that process food and other substrates.[81][82] Plants have been modified for insect protection, herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of edible vaccines.[83] Most commercialised GMOs are insect resistant or herbicide tolerant crop plants.[84] Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. The genetically modified animals include animals with genes knocked out, increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk.[85]

Medicine

Genetic engineering has many applications to medicine that include the manufacturing of drugs, creation of model animals that mimic human conditions and gene therapy. One of the earliest uses of genetic engineering was to mass-produce human insulin in bacteria.[32] This application has now been applied to human growth hormones, follicle stimulating hormones (for treating infertility), human albumin, monoclonal antibodies, antihemophilic factors, vaccines and many other drugs.[86][87] Mouse hybridomas, cells fused together to create monoclonal antibodies, have been adapted through genetic engineering to create human monoclonal antibodies.[88] Genetically engineered viruses are being developed that can still confer immunity, but lack the infectious sequences.[89]

Genetic engineering is also used to create animal models of human diseases. Genetically modified mice are the most common genetically engineered animal model.[90] They have been used to study and model cancer (the oncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease.[91] Potential cures can be tested against these mouse models.

Gene therapy is the genetic engineering of humans, generally by replacing defective genes with effective ones. Clinical research using somatic gene therapy has been conducted with several diseases, including X-linked SCID,[92] chronic lymphocytic leukemia (CLL),[93][94] and Parkinson's disease.[95] In 2012, Alipogene tiparvovec became the first gene therapy treatment to be approved for clinical use.[96][97] In 2015 a virus was used to insert a healthy gene into the skin cells of a boy suffering from a rare skin disease, epidermolysis bullosa, in order to grow, and then graft healthy skin onto 80 percent of the boy's body which was affected by the illness.[98]

Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community.[99][100] In 2015, CRISPR was used to edit the DNA of non-viable human embryos,[101][102] leading scientists of major world academies to call for a moratorium on inheritable human genome edits.[103] There are also concerns that the technology could be used not just for treatment, but for enhancement, modification or alteration of a human beings' appearance, adaptability, intelligence, character or behavior.[104] The distinction between cure and enhancement can also be difficult to establish.[105] In November 2018, He Jiankui announced that he had edited the genomes of two human embryos, to attempt to disable the CCR5 gene, which codes for a receptor that HIV uses to enter cells. The work was widely condemned as unethical, dangerous, and premature.[106] Currently, germline modification is banned in 40 countries. Scientists that do this type of research will often let embryos grow for a few days without allowing it to develop into a baby.[107]

Researchers are altering the genome of pigs to induce the growth of human organs, with the aim of increasing the success of pig to human organ transplantation.[108] Scientists are creating "gene drives", changing the genomes of mosquitoes to make them immune to malaria, and then looking to spread the genetically altered mosquitoes throughout the mosquito population in the hopes of eliminating the disease.[109]

Research

Human cells in which some proteins are fused with green fluorescent protein to allow them to be visualised
Human cells in which some proteins are fused with green fluorescent protein to allow them to be visualised

Genetic engineering is an important tool for natural scientists, with the creation of transgenic organisms one of the most important tools for analysis of gene function.[110] Genes and other genetic information from a wide range of organisms can be inserted into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research.[111]

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

  • Loss of function experiments, such as in a gene knockout experiment, in which an organism is engineered to lack the activity of one or more genes. In a simple knockout a copy of the desired gene has been altered to make it non-functional. Embryonic stem cells incorporate the altered gene, which replaces the already present functional copy. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. This allows the experimenter to analyse the defects caused by this mutation and thereby determine the role of particular genes. It is used especially frequently in developmental biology.[112] When this is done by creating a library of genes with point mutations at every position in the area of interest, or even every position in the whole gene, this is called "scanning mutagenesis". The simplest method, and the first to be used, is "alanine scanning", where every position in turn is mutated to the unreactive amino acid alanine.[113]
  • Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently. Gain of function is used to tell whether or not a protein is sufficient for a function, but does not always mean it is required, especially when dealing with genetic or functional redundancy.[112]
  • Tracking experiments, which seek to gain information about the localisation and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as green fluorescent protein (GFP) that will allow easy visualisation of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences that will serve as binding motifs to monoclonal antibodies.[112]
  • Expression studies aim to discover where and when specific proteins are produced. In these experiments, the DNA sequence before the DNA that codes for a protein, known as a gene's promoter, is reintroduced into an organism with the protein coding region replaced by a reporter gene such as GFP or an enzyme that catalyses the production of a dye. Thus the time and place where a particular protein is produced can be observed. Expression studies can be taken a step further by altering the promoter to find which pieces are crucial for the proper expression of the gene and are actually bound by transcription factor proteins; this process is known as promoter bashing.[114]

Industrial

Products of genetic engineering
Products of genetic engineering

Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they will overexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism in bioreactor equipment using industrial fermentation, and then purifying the protein.[115] Some genes do not work well in bacteria, so yeast, insect cells or mammalian cells can also be used.[116] These techniques are used to produce medicines such as insulin, human growth hormone, and vaccines, supplements such as tryptophan, aid in the production of food (chymosin in cheese making) and fuels.[117] Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as making biofuels,[118] cleaning up oil spills, carbon and other toxic waste[119] and detecting arsenic in drinking water.[120] Certain genetically modified microbes can also be used in biomining and bioremediation, due to their ability to extract heavy metals from their environment and incorporate them into compounds that are more easily recoverable.[121]

In materials science, a genetically modified virus has been used in a research laboratory as a scaffold for assembling a more environmentally friendly lithium-ion battery.[122][123] Bacteria have also been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions.[124]

Agriculture

Bt-toxins present in peanut leaves (bottom image) protect it from extensive damage caused by lesser cornstalk borer larvae (top image).[125]
Bt-toxins present in peanut leaves (bottom image) protect it from extensive damage caused by lesser cornstalk borer larvae (top image).[125]

One of the best-known and controversial applications of genetic engineering is the creation and use of genetically modified crops or genetically modified livestock to produce genetically modified food. Crops have been developed to increase production, increase tolerance to abiotic stresses, alter the composition of the food, or to produce novel products.[126]

The first crops to be released commercially on a large scale provided protection from insect pests or tolerance to herbicides. Fungal and virus resistant crops have also been developed or are in development.[127][128] This makes the insect and weed management of crops easier and can indirectly increase crop yield.[129][130] GM crops that directly improve yield by accelerating growth or making the plant more hardy (by improving salt, cold or drought tolerance) are also under development.[131] In 2016 Salmon have been genetically modified with growth hormones to reach normal adult size much faster.[132]

GMOs have been developed that modify the quality of produce by increasing the nutritional value or providing more industrially useful qualities or quantities.[131] The Amflora potato produces a more industrially useful blend of starches. Soybeans and canola have been genetically modified to produce more healthy oils.[133][134] The first commercialised GM food was a tomato that had delayed ripening, increasing its shelf life.[135]

Plants and animals have been engineered to produce materials they do not normally make. Pharming uses crops and animals as bioreactors to produce vaccines, drug intermediates, or the drugs themselves; the useful product is purified from the harvest and then used in the standard pharmaceutical production process.[136] Cows and goats have been engineered to express drugs and other proteins in their milk, and in 2009 the FDA approved a drug produced in goat milk.[137][138]

Other applications

Genetic engineering has potential applications in conservation and natural area management. Gene transfer through viral vectors has been proposed as a means of controlling invasive species as well as vaccinating threatened fauna from disease.[139] Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations.[140] With the increasing risks of maladaptation in organisms as a result of climate change and other perturbations, facilitated adaptation through gene tweaking could be one solution to reducing extinction risks.[141] Applications of genetic engineering in conservation are thus far mostly theoretical and have yet to be put into practice.

Genetic engineering is also being used to create microbial art.[142] Some bacteria have been genetically engineered to create black and white photographs.[143] Novelty items such as lavender-colored carnations,[144] blue roses,[145] and glowing fish[146][147] have also been produced through genetic engineering.

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Bacteria

Bacteria

Bacteria are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep biosphere of Earth's crust. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of dead bodies; bacteria are responsible for the putrefaction stage in this process. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised and there are many species that cannot be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.

Oncomouse

Oncomouse

The OncoMouse or Harvard mouse is a type of laboratory mouse that has been genetically modified using modifications designed by Philip Leder and Timothy A Stewart of Harvard University to carry a specific gene called an activated oncogene. The activated oncogene significantly increases the mouse's susceptibility to cancer, and thus makes the mouse a suitable model for cancer research.

Model organism

Model organism

A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are widely used to research human disease when human experimentation would be unfeasible or unethical. This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution.

Gene therapy

Gene therapy

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time.

Growth hormone

Growth hormone

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

Follicle-stimulating hormone

Follicle-stimulating hormone

Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) work together in the reproductive system.

Vaccine

Vaccine

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.

Hybridoma technology

Hybridoma technology

Hybridoma technology is a method for producing large numbers of identical antibodies. This process starts by injecting a mouse with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal B cell cancer cells, a myeloma, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma. The hybridomas can be grown in culture, each culture starting with one viable hybridoma cell, producing cultures each of which consists of genetically identical hybridomas which produce one antibody per culture (monoclonal) rather than mixtures of different antibodies (polyclonal). The myeloma cell line that is used in this process is selected for its ability to grow in tissue culture and for an absence of antibody synthesis. In contrast to polyclonal antibodies, which are mixtures of many different antibody molecules, the monoclonal antibodies produced by each hybridoma line are all chemically identical.

Genetically modified mouse

Genetically modified mouse

A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse 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. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics.

Regulation

The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of GMOs. The development of a regulatory framework began in 1975, at Asilomar, California.[148] The Asilomar meeting recommended a set of voluntary guidelines regarding the use of recombinant technology.[30] As the technology improved the US established a committee at the Office of Science and Technology,[149] which assigned regulatory approval of GM food to the USDA, FDA and EPA.[150] The Cartagena Protocol on Biosafety, an international treaty that governs the transfer, handling, and use of GMOs,[151] was adopted on 29 January 2000.[152] One hundred and fifty-seven countries are members of the Protocol, and many use it as a reference point for their own regulations.[153]

The legal and regulatory status of GM foods varies by country, with some nations banning or restricting them, and others permitting them with widely differing degrees of regulation.[154][155][156][157] Some countries allow the import of GM food with authorisation, but either do not allow its cultivation (Russia, Norway, Israel) or have provisions for cultivation even though no GM products are yet produced (Japan, South Korea). Most countries that do not allow GMO cultivation do permit research.[158] Some of the most marked differences occur between the US and Europe. The US policy focuses on the product (not the process), only looks at verifiable scientific risks and uses the concept of substantial equivalence.[159] The European Union by contrast has possibly the most stringent GMO regulations in the world.[160] All GMOs, along with irradiated food, are considered "new food" and subject to extensive, case-by-case, science-based food evaluation by the European Food Safety Authority. The criteria for authorisation fall in four broad categories: "safety", "freedom of choice", "labelling", and "traceability".[161] The level of regulation in other countries that cultivate GMOs lie in between Europe and the United States.

Regulatory agencies by geographical region
Region Regulators Notes
US USDA, FDA and EPA[150]
Europe European Food Safety Authority[161]
Canada Health Canada and the Canadian Food Inspection Agency[162][163] Regulated products with novel features regardless of method of origin[164][165]
Africa Common Market for Eastern and Southern Africa[166] Final decision lies with each individual country.[166]
China Office of Agricultural Genetic Engineering Biosafety Administration[167]
India Institutional Biosafety Committee, Review Committee on Genetic Manipulation and Genetic Engineering Approval Committee[168]
Argentina National Agricultural Biotechnology Advisory Committee (environmental impact), the National Service of Health and Agrifood Quality (food safety) and the National Agribusiness Direction (effect on trade)[169] Final decision made by the Secretariat of Agriculture, Livestock, Fishery and Food.[169]
Brazil National Biosafety Technical Commission (environmental and food safety) and the Council of Ministers (commercial and economical issues)[169]
Australia Office of the Gene Technology Regulator (oversees all GM products), Therapeutic Goods Administration (GM medicines) and Food Standards Australia New Zealand (GM food).[170][171] The individual state governments can then assess the impact of release on markets and trade and apply further legislation to control approved genetically modified products.[171]

One of the key issues concerning regulators is whether GM products should be labeled. The European Commission says that mandatory labeling and traceability are needed to allow for informed choice, avoid potential false advertising[172] and facilitate the withdrawal of products if adverse effects on health or the environment are discovered.[173] The American Medical Association[174] and the American Association for the Advancement of Science[175] say that absent scientific evidence of harm even voluntary labeling is misleading and will falsely alarm consumers. Labeling of GMO products in the marketplace is required in 64 countries.[176] Labeling can be mandatory up to a threshold GM content level (which varies between countries) or voluntary. In Canada and the US labeling of GM food is voluntary,[177] while in Europe all food (including processed food) or feed which contains greater than 0.9% of approved GMOs must be labelled.[160]

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Asilomar Conference Grounds

Asilomar Conference Grounds

Asilomar Conference Grounds is a conference center built for the Young Women's Christian Association (YWCA). It is located east of what was known as Moss Beach on the western tip of the Monterey Peninsula in Pacific Grove, California. Between 1913 and 1929 architect Julia Morgan designed and built 16 of the buildings on the property, of which 11 are still standing. In 1956 it became part of the State Division of Beaches and Parks of California's Department of Natural Resources, and Moss Beach was renamed Asilomar State Beach. Asilomar is a derivation of the Spanish phrase asilo al mar, meaning asylum or refuge by the sea. It is the native homeland of the Rumsen Ohlone people.

Office of Science and Technology Policy

Office of Science and Technology Policy

The Office of Science and Technology Policy (OSTP) is a department of the United States government, part of the Executive Office of the President (EOP), established by United States Congress on May 11, 1976, with a broad mandate to advise the President on the effects of science and technology on domestic and international affairs.

Cartagena Protocol on Biosafety

Cartagena Protocol on Biosafety

The Cartagena Protocol on Biosafety to the Convention on Biological Diversity is an international agreement on biosafety as a supplement to the Convention on Biological Diversity (CBD) effective since 2003. The Biosafety Protocol seeks to protect biological diversity from the potential risks posed by genetically modified organisms resulting from modern biotechnology.

European Union

European Union

The European Union (EU) is a supranational political and economic union of 27 member states that are located primarily in Europe. The union has a total area of 4,233,255.3 km2 (1,634,469.0 sq mi) and an estimated total population of nearly 447 million. The EU has often been described as a sui generis political entity combining the characteristics of both a federation and a confederation.

European Food Safety Authority

European Food Safety Authority

The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, is based in Parma, Italy, and for 2021 it has a budget of €118.6 million, and a total staff of 542.

Food and Drug Administration

Food and Drug Administration

The United States Food and Drug Administration is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products.

Health Canada

Health Canada

Health Canada is the department of the Government of Canada responsible for national health policy. The department itself is also responsible for numerous federal health-related agencies, including the Canadian Food Inspection Agency (CFIA) and the Public Health Agency of Canada (PHAC), among others. These organizations help to ensure compliance with federal law in a variety of healthcare, agricultural, and pharmaceutical activities. This responsibility also involves extensive collaboration with various other federal- and provincial-level organizations in order to ensure the safety of food, health, and pharmaceutical products—including the regulation of health research and pharmaceutical manufacturing/testing facilities.

Canadian Food Inspection Agency

Canadian Food Inspection Agency

The Canadian Food Inspection Agency is a regulatory agency that is dedicated to the safeguarding of food, plants, and animals (FPA) in Canada, thus enhancing the health and well-being of Canada's people, environment and economy. The agency is governed by the Minister of Agriculture and Agri-Food and Minister of Health.

Common Market for Eastern and Southern Africa

Common Market for Eastern and Southern Africa

The Common Market for Eastern and Southern Africa (COMESA) is a regional economic community in Africa with twenty-one member states stretching from Tunisia to Eswatini. COMESA was formed in December 1994, replacing a Preferential Trade Area which had existed since 1981. Nine of the member states formed a free trade area in 2000, with Rwanda and Burundi joining the FTA in 2004, the Comoros and Libya in 2006, Seychelles in 2009 and Tunisia and Somalia in 2018.

Office of the Gene Technology Regulator

Office of the Gene Technology Regulator

The Office of the Gene Technology Regulator, supports the Gene Technology Regulator, and is a part of the Australian Government Department of Health and Ageing. The Office was established under the Commonwealth Gene Technology Act 2000. This legislation sets forth a nationally consistent regulatory system for gene technology in Australia.

Food Standards Australia New Zealand

Food Standards Australia New Zealand

Food Standards Australia New Zealand (FSANZ), formerly Australia New Zealand Food Authority (ANZFA), is the statutory authority in the Australian Government Health portfolio that is responsible for developing food standards for Australia and New Zealand.

European Commission

European Commission

The European Commission (EC) is part of the executive of the European Union (EU), together with the European Council. It operates as a cabinet government, with 27 members of the Commission headed by a President. It includes an administrative body of about 32,000 European civil servants. The Commission is divided into departments known as Directorates-General (DGs) that can be likened to departments or ministries each headed by a Director-General who is responsible to a Commissioner.

Controversy

Critics have objected to the use of genetic engineering on several grounds, including ethical, ecological and economic concerns. Many of these concerns involve GM crops and whether food produced from them is safe and what impact growing them will have on the environment. These controversies have led to litigation, international trade disputes, and protests, and to restrictive regulation of commercial products in some countries.[178]

Accusations that scientists are "playing God" and other religious issues have been ascribed to the technology from the beginning.[179] Other ethical issues raised include the patenting of life,[180] the use of intellectual property rights,[181] the level of labeling on products,[182][183] control of the food supply[184] and the objectivity of the regulatory process.[185] Although doubts have been raised,[186] economically most studies have found growing GM crops to be beneficial to farmers.[187][188][189]

Gene flow between GM crops and compatible plants, along with increased use of selective herbicides, can increase the risk of "superweeds" developing.[190] Other environmental concerns involve potential impacts on non-target organisms, including soil microbes,[191] and an increase in secondary and resistant insect pests.[192][193] Many of the environmental impacts regarding GM crops may take many years to be understood and are also evident in conventional agriculture practices.[191][194] With the commercialisation of genetically modified fish there are concerns over what the environmental consequences will be if they escape.[195]

There are three main concerns over the safety of genetically modified food: whether they may provoke an allergic reaction; whether the genes could transfer from the food into human cells; and whether the genes not approved for human consumption could outcross to other crops.[196] There is a scientific consensus[197][198][199][200] that currently available food derived from GM crops poses no greater risk to human health than conventional food,[201][202][203][204][205] but that each GM food needs to be tested on a case-by-case basis before introduction.[206][207][208] Nonetheless, members of the public are less likely than scientists to perceive GM foods as safe.[209][210][211][212]

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Genetically modified food controversies

Genetically modified food controversies

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

Playing God (ethics)

Playing God (ethics)

Playing God refers to assuming powers of decision, intervention or control metaphorically reserved to God. Acts described as playing God may include, for example, deciding who should live or die in a situation where not everyone can be saved, the use and development of biotechnologies such as synthetic biology, and in vitro fertilisation. Usually the expression is used pejoratively and to criticize or argue against the supposedly God-like actions.

Religious views on genetically modified foods

Religious views on genetically modified foods

Religious views on genetically modified foods have been mixed, although as yet, no genetically modified foods have been designated as unacceptable by religious authorities.

Biological patent

Biological patent

A biological patent is a patent on an invention in the field of biology that by law allows the patent holder to exclude others from making, using, selling, or importing the protected invention for a limited period of time. The scope and reach of biological patents vary among jurisdictions, and may include biological technology and products, genetically modified organisms and genetic material. The applicability of patents to substances and processes wholly or partially natural in origin is a subject of debate.

Intellectual property

Intellectual property

Intellectual property (IP) is a category of property that includes intangible creations of the human intellect. There are many types of intellectual property, and some countries recognize more than others. The best-known types are patents, copyrights, trademarks, and trade secrets. The modern concept of intellectual property developed in England in the 17th and 18th centuries. The term "intellectual property" began to be used in the 19th century, though it was not until the late 20th century that intellectual property became commonplace in the majority of the world's legal systems.

Gene flow

Gene flow

In population genetics, gene flow is the transfer of genetic material from one population to another. If the rate of gene flow is high enough, then two populations will have equivalent allele frequencies and therefore can be considered a single effective population. It has been shown that it takes only "one migrant per generation" to prevent populations from diverging due to drift. Populations can diverge due to selection even when they are exchanging alleles, if the selection pressure is strong enough. Gene flow is an important mechanism for transferring genetic diversity among populations. Migrants change the distribution of genetic diversity among populations, by modifying allele frequencies. High rates of gene flow can reduce the genetic differentiation between the two groups, increasing homogeneity. For this reason, gene flow has been thought to constrain speciation and prevent range expansion by combining the gene pools of the groups, thus preventing the development of differences in genetic variation that would have led to differentiation and adaptation. In some cases dispersal resulting in gene flow may also result in the addition of novel genetic variants under positive selection to the gene pool of a species or population

Herbicide

Herbicide

Herbicides, also commonly known as weed killers, are substances used to control undesired plants, also known as weeds. Selective herbicides control specific weed species while leaving the desired crop relatively unharmed, while non-selective herbicides can be used to clear waste ground, industrial and construction sites, railways and railway embankments as they kill all plant material with which they come into contact. Apart from selective/non-selective, other important distinctions include persistence, means of uptake, and mechanism of action. Historically, products such as common salt and other metal salts were used as herbicides, however, these have gradually fallen out of favor, and in some countries, a number of these are banned due to their persistence in soil, and toxicity and groundwater contamination concerns. Herbicides have also been used in warfare and conflict.

Genetically modified fish

Genetically modified fish

Genetically modified fish are organisms from the taxonomic clade which includes the classes Agnatha, Chondrichthyes and Osteichthyes whose genetic material (DNA) has been altered using genetic engineering techniques. In most cases, the aim is to introduce a new trait to the fish which does not occur naturally in the species, i.e. transgenesis.

Outcrossing

Outcrossing

Out-crossing or out-breeding is the technique of crossing between different breeds. This is the practice of introducing distantly related genetic material into a breeding line, thereby increasing genetic diversity.

Scientific consensus

Scientific consensus

Scientific consensus is the generally held judgment, position, and opinion of the majority or the supermajority of scientists in a particular field of study at any particular time.

In popular culture

Genetic engineering features in many science fiction stories.[213] Frank Herbert's novel The White Plague describes the deliberate use of genetic engineering to create a pathogen which specifically kills women.[213] Another of Herbert's creations, the Dune series of novels, uses genetic engineering to create the powerful Tleilaxu.[214] Few films have informed audiences about genetic engineering, with the exception of the 1978 The Boys from Brazil and the 1993 Jurassic Park, both of which make use of a lesson, a demonstration, and a clip of scientific film.[215][216] Genetic engineering methods are weakly represented in film; Michael Clark, writing for the Wellcome Trust, calls the portrayal of genetic engineering and biotechnology "seriously distorted"[216] in films such as The 6th Day. In Clark's view, the biotechnology is typically "given fantastic but visually arresting forms" while the science is either relegated to the background or fictionalised to suit a young audience.[216]

In the 2007 video game, BioShock, genetic engineering plays an important role in the central storyline and universe. The game takes place in the fictional underwater dystopia Rapture, in which its inhabitants possess genetic superhuman abilities after injecting themselves with “plasmids”, a serum which grants such powers. Also in the city of Rapture are “Little Sisters”, little girls who are generically engineered, as well as a side-plot in which a cabaret singer sells her foetus to genetic scientists who implant false memories into the newborn and genetically engineer it to grow into an adult.

Discover more about In popular culture related topics

Science fiction

Science fiction

Science fiction is a genre of speculative fiction, which typically deals with imaginative and futuristic concepts such as advanced science and technology, space exploration, time travel, parallel universes, and extraterrestrial life. Science fiction can trace its roots to ancient mythology. It is related to fantasy, horror, and superhero fiction and contains many subgenres. Its exact definition has long been disputed among authors, critics, scholars, and readers.

Frank Herbert

Frank Herbert

Franklin Patrick Herbert Jr. was an American science fiction author best known for the 1965 novel Dune and its five sequels. Though he became famous for his novels, he also wrote short stories and worked as a newspaper journalist, photographer, book reviewer, ecological consultant, and lecturer.

The White Plague

The White Plague

The White Plague is a 1982 science fiction novel by American author, Frank Herbert that explores madness and revenge on a global scale.

Pathogen

Pathogen

In biology, a pathogen in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Dune (franchise)

Dune (franchise)

Dune, also known as the Dune Chronicles, is an American science fiction media franchise that originated with the 1965 novel Dune by Frank Herbert and has continued to add new publications. Dune is frequently described as the best selling science fiction novel in history. It won the inaugural Nebula Award for Best Novel and the Hugo Award in 1966, and was later adapted into a 1984 film, a 2000 television miniseries, and a 2021 film. The latter will be followed by a 2023 direct sequel. Herbert wrote five sequels, the first two of which were concomitantly adapted as a 2003 miniseries. Dune has also inspired some traditional games and a series of video games. Since 2009, the names of planets from the Dune novels have been adopted for the real-world nomenclature of plains and other features on Saturn's moon Titan.

The Boys from Brazil (film)

The Boys from Brazil (film)

The Boys from Brazil is a 1978 thriller film directed by Franklin J. Schaffner. It stars Gregory Peck and Laurence Olivier, and features James Mason, Lilli Palmer, Uta Hagen, Anne Meara, Denholm Elliott, and Steve Guttenberg in supporting roles. The film is a British-American co-production and is based on the 1976 novel of the same title by Ira Levin. It was nominated for three Academy Awards.

Jurassic Park (film)

Jurassic Park (film)

Jurassic Park is a 1993 American science fiction action film directed by Steven Spielberg, produced by Kathleen Kennedy and Gerald R. Molen, and starring Sam Neill, Laura Dern, Jeff Goldblum, and Richard Attenborough. It is the first installment in the Jurassic Park franchise, and the first film in the Jurassic Park original trilogy, and is based on the 1990 novel of the same name by Michael Crichton and a screenplay by Crichton and David Koepp. The film is set on the fictional island of Isla Nublar, located off Central America's Pacific Coast near Costa Rica, where a wealthy businessman named John Hammond (Attenborough) and a team of genetic scientists have created a wildlife park of de-extinct dinosaurs. But, when industrial sabotage leads to a catastrophic shutdown of the park's power facilities and security precautions, a small group of visitors, including Hammond's grandchildren, struggle to survive and escape the now perilous island.

Wellcome Trust

Wellcome Trust

The Wellcome Trust is a charitable foundation focused on health research based in London, in the United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome to fund research to improve human and animal health. The aim of the Trust is to "support science to solve the urgent health challenges facing everyone." It had a financial endowment of £29.1 billion in 2020, making it the fourth wealthiest charitable foundation in the world. In 2012, the Wellcome Trust was described by the Financial Times as the United Kingdom's largest provider of non-governmental funding for scientific research, and one of the largest providers in the world. According to their annual report, the Wellcome Trust spent GBP £1.1Bn on charitable activities across their 2019/2020 financial year. According to the OECD, the Wellcome Trust's financing for 2019 development increased by 22% to US$327 million.

The 6th Day

The 6th Day

The 6th Day is a 2000 American science fiction action film directed by Roger Spottiswoode and starring Arnold Schwarzenegger, Tony Goldwyn, Michael Rapaport, and Robert Duvall. In the film, a family man of the future is illegally cloned by accident as part of a vast conspiracy involving a shady billionaire businessman, and is thrust into a struggle to clear his name and protect his family from the conspirators who seek to keep the cloning a secret. The title refers to the Judeo-Christian Genesis creation narrative, where God created mankind on the sixth day. The film was Terry Crews' acting debut.

BioShock

BioShock

BioShock is a 2007 first-person shooter game developed by 2K Boston and 2K Australia, and published by 2K Games. The first game in the BioShock series, it was released for Microsoft Windows and Xbox 360 platforms in August 2007; a PlayStation 3 port by Irrational, 2K Marin, 2K Australia and Digital Extremes was released in October 2008. The game is set in 1960, and follows Jack who discovers the underwater city of Rapture. Built by business magnate Andrew Ryan to be an isolated utopia, the discovery of ADAM, a genetic material which grants superhuman powers, initiated the city's turbulent decline. Jack attempts to escape, fighting ADAM-obsessed enemies and Big Daddies, while engaging with the few sane humans that remain and learning of Rapture's past. The player, as Jack, can defeat foes in several ways by using weapons, utilizing plasmids that give unique powers, and by turning Rapture's defenses against them.

Rapture (BioShock)

Rapture (BioShock)

Rapture is a fictional city in the BioShock series published by 2K Games. It is an underwater city that is the main setting for the games BioShock and BioShock 2. The city also briefly appears in BioShock Infinite, and is featured in its downloadable content, Burial at Sea. The game's back-story describes the city as envisioned by business tycoon Andrew Ryan in the mid-1940s as a means to create a utopia for mankind's greatest artists and thinkers to prosper in a laissez-faire environment outside of increasing oppression by the world's governments and religion. However, the lack of government made many people uneasy, and the masses turned toward political activists like Atlas who advocated stability under a government, turning the city into a dystopia; and on the eve of 1959, a civil war broke out, leaving much of Rapture's population dead. The remaining citizens either became psychotic "Splicers" due to the effects of ADAM, a substance that can alter genetic material, or have barricaded themselves from the Splicers to protect themselves, leaving the city to fail and fall apart around them.

Source: "Genetic engineering", Wikipedia, Wikimedia Foundation, (2023, March 11th), https://en.wikipedia.org/wiki/Genetic_engineering.

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