Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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: protei ...
s using
technology
Technology is the application of Conceptual model, conceptual knowledge to achieve practical goals, especially in a reproducible way. The word ''technology'' can also mean the products resulting from such efforts, including both tangible too ...
. It is a set of
technologies
Technology is the application of Conceptual model, conceptual knowledge to achieve practical goals, especially in a reproducible way. The word ''technology'' can also mean the products resulting from such efforts, including both tangible too ...
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
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
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
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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: protei ...
s, the process can be used to remove, or "
knock out
A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several Contact sports, full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of World Taekwondo Federation#Sparri ...
", genes. The new DNA can either be inserted randomly or
targeted to a specific part of the
genome.
An organism that is generated through genetic engineering is considered to be genetically modified (GM) and the resulting entity is a
genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with ...
(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
A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
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
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
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
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
in December 2003. In 2016
salmon
Salmon (; : salmon) are any of several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the genera ''Salmo'' and ''Oncorhynchus'' of the family (biology), family Salmonidae, native ...
modified with a growth hormone were sold.
Genetic engineering has been applied in numerous fields including research, medicine, industrial biotechnology and agriculture. In research, GMOs are used to study gene function and expression through loss of function, gain of function, tracking and expression experiments. By knocking out genes responsible for certain conditions it is possible to create
animal model organisms of human diseases. As well as producing hormones, vaccines and other drugs, genetic engineering has the potential to cure genetic diseases through
gene therapy.
Chinese hamster ovary (CHO) cells are used in industrial genetic engineering. Additionally
mRNA vaccines are made through genetic engineering to prevent infections by viruses such as
COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic.
The symptoms of COVID‑19 can vary but often include fever ...
. 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
Controversy (, ) is a state of prolonged public dispute or debate, usually concerning a matter of conflicting opinion or point of view. The word was coined from the Latin '' controversia'', as a composite of ''controversus'' – "turned in an op ...
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
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.
Consensus is achieved through scholarly communication at confer ...
that food derived from GMO crops poses no greater risk to human health than conventional food, critics consider GM food safety a leading concern.
Gene flow
In population genetics, gene flow (also known as migration and allele flow) is the transfer of genetic variation, genetic material from one population to another. If the rate of gene flow is high enough, then two populations will have equivalent ...
, impact on non-target organisms, control of the food supply and
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, co ...
rights have also been raised as potential issues. These concerns have led to the development of a regulatory framework, which started in 1975. It has led to an international treaty, the
Cartagena Protocol on Biosafety, that was adopted in 2000. Individual countries have developed their own regulatory systems regarding GMOs, with the most marked differences occurring between the United States and
Europe
Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...
.
Overview

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
Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
and
plant breeding, which involves doing multiple crosses and then selecting for the organism with the desired
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
, genetic engineering takes the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. 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: protei ...
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.
Genetic engineering could potentially fix severe
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 chromosome abnormality. Although polygenic disorders ...
s in humans by replacing the defective gene with a functioning one. It is an important tool in research that allows the function of specific genes to be studied. Drugs, vaccines and other products have been harvested from organisms engineered to produce them.
Crops have been developed that aid
food security
Food security is the state of having reliable access to a sufficient quantity of affordable, healthy Human food, food. The availability of food for people of any class, gender, ethnicity, or religion is another element of food protection. Simila ...
by increasing yield, nutritional value and tolerance to environmental stresses.
The DNA can be introduced directly into the
host organism or into a cell that is then
fused or
hybridised with the host.
This relies on
recombinant nucleic acid techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a
vector system or directly through
micro-injection, macro-injection or
micro-encapsulation.
Genetic engineering does not normally include traditional breeding,
in vitro fertilisation, induction of
polyploidy,
mutagenesis and cell fusion techniques that do not use recombinant
nucleic acids
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic a ...
or a
genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with ...
in the process.
However, some broad definitions of genetic engineering include
selective breeding.
Cloning
Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...
and
stem cell research, although not considered genetic engineering, are closely related and genetic engineering can be used within them.
Synthetic biology
Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms. It applies engineering principles to develop new biological parts, devices, and systems or to redesign existing systems found in nat ...
is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesised material into an organism.
Plants, animals or microorganisms that have been changed through genetic engineering are termed
genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with ...
s or GMOs. 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. If genetic engineering is used to remove genetic material from the target organism the resulting organism is termed a
knockout organism. 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.
History
Humans have altered the genomes of species for thousands of years through
selective breeding, or artificial selection
as contrasted with
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 Heredity, heritable traits characteristic of a population over generation ...
. More recently,
mutation breeding has used exposure to chemicals or radiation to produce a high frequency of random mutations, for selective breeding purposes. Genetic engineering as the direct manipulation of DNA by humans outside breeding and mutations has only existed since the 1970s. The term "genetic engineering" was coined by the Russian-born geneticist
Nikolay Timofeev-Ressovsky in his 1934 paper "The Experimental Production of Mutations", published in the British journal Biological Reviews.
Jack Williamson used the term in his science fiction novel Dragon's Island, published in 1951 – one year before DNA's role in
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 infor ...
was confirmed by
Alfred Hershey and
Martha Chase, 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''.

In 1972,
Paul Berg created the first
recombinant DNA
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
molecules by combining DNA from the monkey virus
SV40 with that of the
lambda virus. In 1973
Herbert Boyer and
Stanley Cohen created the first
transgenic organism by inserting
antibiotic resistance genes into the
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 and ...
of an ''
Escherichia coli
''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'' bacterium. A year later
Rudolf Jaenisch created a
transgenic mouse by introducing foreign DNA into its embryo, making it the world's first
transgenic animal 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.
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
Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by #Nomenclature, several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G ...
) in ''E. coli''. Genentech announced the production of genetically engineered human
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
in 1978.
In 1980, the
U.S. Supreme Court in the ''
Diamond v. Chakrabarty'' case ruled that genetically altered life could be patented. The
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
produced by bacteria was approved for release by the
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) in 1982.
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
''Pseudomonas syringae'' is a rod-shaped, Gram-negative bacterium with polar flagella. As a plant pathology, plant pathogen, it can infect a wide range of species, and exists as over 50 different pathovars, all of which are available to research ...
'' to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges. In 1987, the ice-minus strain of ''P. syringae'' became the first
genetically modified organism
A genetically modified organism (GMO) is any organism whose genetic material has been altered using genetic engineering techniques. The exact definition of a genetically modified organism and what constitutes genetic engineering varies, with ...
(GMO) to be released into the environment
when a strawberry field and a potato field in California were sprayed with it. 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".
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. The People's Republic of China was the first country to commercialise transgenic plants, introducing a virus-resistant tobacco in 1992.
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. 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. 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. 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.
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. Four years later this was taken a step further when a bacterium was developed that replicated a
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 and ...
containing a unique
base pair
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
, creating the first organism engineered to use an expanded genetic alphabet. In 2012,
Jennifer Doudna and
Emmanuelle Charpentier collaborated to develop the
CRISPR/Cas9 system, a technique which can be used to easily and specifically alter the genome of almost any organism.
Process

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. Luck also plays its part; the
Roundup Ready gene was discovered after scientists noticed a bacterium thriving in the presence of the herbicide.
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. The gene is separated by using
restriction enzymes to cut the DNA into fragments or
polymerase chain reaction (PCR) to amplify up the gene segment. 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. Once isolated the gene is
ligated into a
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 and ...
that is then inserted into a bacterium. The plasmid is replicated when the bacteria divide, ensuring unlimited copies of the gene are available. 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.
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
Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
, 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
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
techniques, such as
restriction digests, ligations and molecular cloning.
Inserting DNA into the host genome

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.
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, taking advantage of the ''Agrobacterium''s
T-DNA sequence that allows natural insertion of genetic material into plant cells. Other methods include
biolistics, where particles of gold or tungsten are coated with DNA and then shot into young plant cells, 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. In animals it is necessary to ensure that the inserted DNA is present in the
embryonic stem cells. 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.

Further testing using PCR,
Southern hybridization, and
DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, thymine, cytosine, and guanine. The ...
is conducted to confirm that an organism contains the new gene. 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
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
and phenotypic analysis.
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
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
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
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
and
nonhomologous end-joining. There are four families of engineered nucleases:
meganucleases,
zinc finger nucleases,
transcription activator-like effector nucleases (TALENs), and the Cas9-guideRNA system (adapted from
CRISPR). TALEN and CRISPR are the two most commonly used and each has its own advantages.
TALENs have greater target specificity, while CRISPR is easier to design and more efficient.
In addition to enhancing gene targeting, engineered nucleases can be used to introduce mutations at endogenous genes that generate a
gene knockout
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
.
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
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, 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. Plants have been modified for insect protection,
herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of
edible vaccines. Most commercialised GMOs are insect resistant or herbicide tolerant crop plants. 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.
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.
This application has now been applied to human
growth hormones,
follicle stimulating hormones (for treating infertility),
human albumin,
monoclonal antibodies,
antihemophilic factors,
vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
s and many other drugs. Mouse
hybridomas, cells fused together to create
monoclonal antibodies, have been adapted through genetic engineering to create human monoclonal antibodies.
Genetically engineered viruses are being developed that can still confer immunity, but lack the
infectious sequences.
Genetic engineering is also used to create animal models of human diseases.
Genetically modified mice are the most common genetically engineered animal model. They have been used to study and model cancer (the
oncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. 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
Clinical research is a branch of medical research that involves people and aims to determine the effectiveness (efficacy) and safety of medications, devices, diagnostic products, and treatment regimens intended for improving human health. The ...
using
somatic gene therapy has been conducted with several diseases, including
X-linked SCID,
chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...
(CLL),
and
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
. In 2012,
Alipogene tiparvovec became the first gene therapy treatment to be approved for clinical use.
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.
Germline gene therapy would result in any change being inheritable, which has raised concerns within the scientific community. In 2015, CRISPR was used to edit the DNA of non-viable
human embryos,
leading scientists of major world academies to call for a moratorium on inheritable human genome edits.
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. The distinction between cure and enhancement can also be difficult to establish. 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. 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.
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.
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.
Research

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. 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.
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
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
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
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
and thereby determine the role of particular genes. It is used especially frequently in
developmental biology
Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
.
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.
* 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.
* 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.
* 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.
Industrial
Organisms can have their cells transformed with a gene coding for a useful protein, such as an enzyme, so that they will
overexpress the desired protein. Mass quantities of the protein can then be manufactured by growing the transformed organism in
bioreactor equipment using
industrial fermentation, and then
purifying the protein. Some genes do not work well in bacteria, so yeast, insect cells or mammalian cells can also be used. These techniques are used to produce medicines such as
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
,
human growth hormone, and
vaccine
A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
s, supplements such as
tryptophan, aid in the production of food (
chymosin in cheese making) and fuels. Other applications with genetically engineered bacteria could involve making them perform tasks outside their natural cycle, such as making
biofuel
Biofuel is a fuel that is produced over a short time span from Biomass (energy), biomass, rather than by the very slow natural processes involved in the formation of fossil fuels such as oil. Biofuel can be produced from plants or from agricu ...
s, cleaning up oil spills, carbon and other toxic waste and detecting arsenic in drinking water. 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.
In
materials science
Materials science is an interdisciplinary field of researching and discovering materials. Materials engineering is an engineering field of finding uses for materials in other fields and industries.
The intellectual origins of materials sci ...
, a genetically modified virus has been used in a research laboratory as a scaffold for assembling a more environmentally friendly
lithium-ion battery. Bacteria have also been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions.
Agriculture

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.
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. This makes the insect and weed management of crops easier and can indirectly increase crop yield.
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.
In 2016
Salmon
Salmon (; : salmon) are any of several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the genera ''Salmo'' and ''Oncorhynchus'' of the family (biology), family Salmonidae, native ...
have been genetically modified with growth hormones to reach normal adult size much faster.
GMOs have been developed that modify the quality of produce by increasing the nutritional value or providing more industrially useful qualities or quantities.
The
Amflora potato produces a more industrially useful blend of starches.
Soybeans
The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean. Soy is a staple crop, the world's most grown legume, and an important animal feed.
Soy is a key source of f ...
and
canola
file:CanolaBlooms.JPG, Close-up of canola blooms
file:Canola Flower.jpg, Canola flower
Rapeseed oil is one of the oldest known vegetable oils. There are both Edible oil, edible and industrial forms produced from rapeseed, the seed of several ...
have been genetically modified to produce more healthy oils. The first commercialised GM food was a
tomato
The tomato (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible Berry (botany), berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originate ...
that had delayed ripening, increasing its
shelf life.
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. 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.
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. Transgenic trees have been suggested as a way to confer resistance to pathogens in wild populations. With the increasing risks of
maladaptation in organisms as a result of
climate change
Present-day climate change includes both global warming—the ongoing increase in Global surface temperature, global average temperature—and its wider effects on Earth's climate system. Climate variability and change, Climate change in ...
and other perturbations, facilitated adaptation through gene tweaking could be one solution to reducing extinction risks. 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. Some bacteria have been genetically engineered to create black and white photographs. Novelty items such as lavender-colored
carnations,
blue roses, and
glowing fish, have also been produced through genetic engineering.
Regulation
The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of GMOs. The development of a regulatory framework began in 1975, at
Asilomar, California. The
Asilomar meeting recommended a set of voluntary guidelines regarding the use of recombinant technology.
As the technology improved the US established a committee at the
Office of Science and Technology,
which assigned regulatory approval of GM food to the USDA, FDA and EPA.
The
Cartagena Protocol on Biosafety, an international treaty that governs the transfer, handling, and use of GMOs, was adopted on 29 January 2000. One hundred and fifty-seven countries are members of the Protocol, and many use it as a reference point for their own regulations.
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. 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. 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.
The
European Union
The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...
by contrast has possibly the most stringent GMO regulations in the world.
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".
[GMO Compass: The European Regulatory System.](_blank)
Retrieved 28 July 2012. The level of regulation in other countries that cultivate GMOs lie in between Europe and the United States.
One of the key issues concerning regulators is whether GM products should be labeled. The
European Commission
The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...
says that mandatory labeling and traceability are needed to allow for informed choice, avoid potential
false advertising and facilitate the withdrawal of products if adverse effects on health or the environment are discovered.
The
American Medical Association and the
American Association for the Advancement of Science
The American Association for the Advancement of Science (AAAS) is a United States–based international nonprofit with the stated mission of promoting cooperation among scientists, defending scientific freedom, encouraging scientific responsib ...
[American Association for the Advancement of Science (AAAS), Board of Directors (2012)]
Statement by the AAAS Board of Directors On Labeling of Genetically Modified Foods
and associate
Press release: Legally Mandating GM Food Labels Could Mislead and Falsely Alarm Consumers
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.
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,
while in Europe all food (including
processed food) or
feed which contains greater than 0.9% of approved GMOs must be labelled.
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.
Accusations that scientists are "
playing God" and other
religious issues have been ascribed to the technology from the beginning. Other ethical issues raised include the
patenting of life, the use of
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, co ...
rights, the level of labeling on products, control of the food supply and the objectivity of the regulatory process. Although doubts have been raised, economically most studies have found growing GM crops to be beneficial to farmers.
Gene flow
In population genetics, gene flow (also known as migration and allele flow) is the transfer of genetic variation, genetic material from one population to another. If the rate of gene flow is high enough, then two populations will have equivalent ...
between GM crops and compatible plants, along with increased use of selective
herbicides, can increase the risk of "
superweeds" developing. Other environmental concerns involve potential impacts on non-target organisms, including
soil microbes,
and an increase in secondary and resistant insect pests. Many of the environmental impacts regarding GM crops may take many years to be understood and are also evident in conventional agriculture practices.
With the commercialisation of
genetically modified fish there are concerns over what the environmental consequences will be if they escape.
There are three main concerns over the safety of genetically modified food: whether they may provoke an
allergic reaction
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
; 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. There is a
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.
Consensus is achieved through scholarly communication at confer ...
that currently available food derived from GM crops poses no greater risk to human health than conventional food, but that each GM food needs to be tested on a case-by-case basis before introduction. Nonetheless, members of the public are less likely than scientists to perceive GM foods as safe.
In popular culture
Genetic engineering features in many
science fiction
Science fiction (often shortened to sci-fi or abbreviated SF) is a genre of speculative fiction that deals with imaginative and futuristic concepts. These concepts may include information technology and robotics, biological manipulations, space ...
stories.
Frank Herbert
Franklin Patrick Herbert Jr. (October 8, 1920February 11, 1986) was an American science-fiction author, best known for his 1965 novel Dune (novel), ''Dune'' and its five sequels. He also wrote short stories and worked as a newspaper journalist, ...
's novel ''
The White Plague'' describes the deliberate use of genetic engineering to create a
pathogen
In biology, a pathogen (, "suffering", "passion" and , "producer of"), 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 theory of d ...
which specifically kills women.
Another of Herbert's creations, the ''
Dune'' series of novels, uses genetic engineering to create the powerful
Tleilaxu.
Few films have informed audiences about genetic engineering, with the exception of the 1978 ''
The Boys from Brazil'' and the 1993 ''
Jurassic Park
''Jurassic Park'', later referred to as ''Jurassic World'', is an American science fiction media franchise created by Michael Crichton, centered on a disastrous attempt to create a theme park of De-extinction#Cloning, cloned dinosaurs. It bega ...
'', both of which make use of a lesson, a demonstration, and a clip of scientific film.
Genetic engineering methods are weakly represented in film; Michael Clark, writing for the
Wellcome Trust
The Wellcome Trust is a charitable foundation focused on health research based in London, United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome (founder of Burroughs Wellcome, one of the predec ...
, calls the portrayal of genetic engineering and biotechnology "seriously distorted"
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.
See also
*
Biological engineering
*
Computational genomics
*
Modifications (genetics)
*
Mutagenesis (molecular biology technique)
Mutagenesis () is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using labo ...
References
Further reading
*
*
*
*
*
*
*
External links
GMO Safety - Information about research projects on the biological safety of genetically modified plants.GMO-compass, news on GMO en EU
{{Authority control
1950s neologisms
1972 introductions
Biological engineering
Biotechnology
Molecular biology
Molecular genetics
Engineering disciplines