Recombinant Organism
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A genetically modified organism (GMO) is any
organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...
whose
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 ...
tic material has been altered using
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 ...
. The exact definition of a genetically modified organism and what constitutes
genetic engineering 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 Genetic engineering techniques, technologies used to change the genet ...
varies, with the most common being an organism altered in a way that "does not occur naturally by mating and/or natural recombination". A wide variety of organisms have been genetically modified (GM), including animals, plants, and microorganisms. Genetic modification can include the introduction of new genes or enhancing, altering, or
knocking out A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
genes. In some genetic modifications, genes are transferred within the same species, across
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
(creating transgenic organisms), and even across
kingdoms Kingdom commonly refers to: * A monarchic state or realm ruled by a king or queen. ** A monarchic chiefdom, represented or governed by a king or queen. * Kingdom (biology), a category in biological taxonomy Kingdom may also refer to: Arts and me ...
. Creating a genetically modified organism is a multi-step process. Genetic engineers must isolate the gene they wish to insert into the host organism and combine it with other genetic elements, including a promoter and terminator region and often a
selectable marker A selectable marker is a gene introduced into cell (biology), cells, especially bacteria or cells in cell culture, culture, which confers one or more traits suitable for artificial selection. They are a type of reporter gene used in laboratory micr ...
. A number of techniques are available for inserting the isolated gene into the host genome. Recent advancements using
genome editing Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert ge ...
techniques, notably
CRISPR CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is d ...
, have made the production of GMOs much simpler.
Herbert Boyer Herbert Wayne "Herb" Boyer (born July 10, 1936) is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg, he discovered recombinant DNA, a method to coax bacteria into producing for ...
and Stanley Cohen made the first genetically modified organism in 1973, a bacterium resistant to the antibiotic
kanamycin Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamy ...
. The first
genetically modified animal Genetically modified animals are animals that have been genetically modified for a variety of purposes including producing drugs, enhancing yields, increasing resistance to disease, etc. The vast majority of genetically modified animals are at t ...
, a mouse, was created in 1974 by
Rudolf Jaenisch Rudolf Jaenisch (born on April 22, 1942) is a professor of biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisc ...
, and the first plant was produced in 1983. In 1994, the
Flavr Savr Flavr Savr (also known as CGN-89564-2; pronounced "flavor saver"), a genetically modified tomato, was the first commercially grown Genetic engineering, genetically engineered food to be granted a license for human consumption. It was developed by t ...
tomato was released, the first commercialized
genetically modified food Genetically modified foods (GM foods), also known as genetically engineered foods (GE foods), or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using various methods of genetic engineering. G ...
. The first genetically modified animal to be commercialized was the
GloFish The GloFish is a patented and trademarked brand of fluorescently colored genetically modified fish, genetically modified aquarium fish. They have been created from several different species of fish: zebrafish were the first GloFish available in ...
(2003) and the first genetically modified animal to be approved for food use was the
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 gen ...
in 2015. Bacteria are the easiest organisms to engineer and have been used for research, food production, industrial protein purification (including drugs), agriculture, and art. There is potential to use them for environmental purposes or as medicine. Fungi have been engineered with much the same goals. Viruses play an important role as vectors for inserting genetic information into other organisms. This use is especially relevant to human
gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...
. There are proposals to remove the
virulent Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abilit ...
genes from viruses to create vaccines. Plants have been engineered for scientific research, to create new colors in plants, deliver vaccines, and to create enhanced crops.
Genetically modified crops Genetically modified crops (GM crops) are plants used in agriculture, the DNA of which has been modified using genetic engineering methods. Plant genomes can be engineered by physical methods or by use of '' Agrobacterium'' for the delivery of ...
are publicly the most controversial GMOs, in spite of having the most human health and environmental benefits. Animals are generally much harder to transform and the vast majority are still at the research stage. Mammals are the best
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. Mo ...
s for humans. Livestock is modified with the intention of improving economically important traits such as growth rate, quality of meat, milk composition, disease resistance, and survival.
Genetically modified fish Genetically modified fish (GM fish) are genetically modified organism, organisms from the taxonomic clade which includes the classes Agnatha (jawless fish), Chondrichthyes (cartilaginous fish) and Osteichthyes (bony fish) whose genetic material ...
are used for scientific research, as pets, and as a food source. Genetic engineering has been proposed as a way to control mosquitos, a
vector Vector most often refers to: * Euclidean vector, a quantity with a magnitude and a direction * Disease vector, an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematics a ...
for many deadly diseases. Although human gene therapy is still relatively new, it has been used to treat
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 such as
severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...
and
Leber's congenital amaurosis Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life. It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be ...
. Many objections have been raised over the development of GMOs, particularly their commercialization. Many of these involve GM crops and whether food produced from them is safe and what impact growing them will have on the environment. Other concerns are the objectivity and rigor of regulatory authorities, contamination of non-genetically modified food, control of the
food supply Food security is the state of having reliable access to a sufficient quantity of affordable, healthy food. The availability of food for people of any class, gender, ethnicity, or religion is another element of food protection. Similarly, househo ...
, patenting of life, and 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. 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 currently available food derived from GM crops poses no greater risk to human health than conventional food, GM food safety is a leading issue with critics.
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, and escape are the major environmental concerns. Countries have adopted regulatory measures to deal with these concerns. There are differences in the regulation for the release of GMOs between countries, with some of the most marked differences occurring between the US and Europe. Key issues concerning regulators include whether GM food should be labeled and the status of gene-edited organisms.


Definition

The definition of a genetically modified organism (GMO) is not clear and varies widely between countries, international bodies, and other communities. At its broadest, the definition of a GMO can include anything that has had its genes altered, including by nature. Taking a less broad view, it can encompass every organism that has had its genes altered by humans, which would include all crops and livestock. In 1993, the ''
Encyclopedia Britannica An encyclopedia is a reference work or compendium providing summaries of knowledge, either general or special, in a particular field or discipline. Encyclopedias are divided into article (publishing), articles or entries that are arranged Alp ...
'' defined genetic engineering as "any of a wide range of techniques ... among them
artificial insemination Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment ...
, ''in vitro'' fertilization (''e.g.'', 'test-tube' babies),
sperm bank A sperm bank, semen bank, or cryobank is a facility or enterprise which purchases, stores and sells human semen. The semen is produced and sold by men who are known as sperm donation, sperm donors. The sperm is purchased by or for other persons f ...
s,
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 gene manipulation." 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 ...
(EU) included a similarly broad definition in early reviews, specifically mentioning GMOs being produced by "
selective breeding Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
and other means of artificial selection"Staf
Economic Impacts of Genetically Modified Crops on the Agri-Food Sector; p. 42 Glossary – Term and Definitions
The European Commission Directorate-General for Agriculture, "Genetic engineering: The manipulation of an organism's genetic endowment by introducing or eliminating specific genes through modern molecular biology techniques. A broad definition of genetic engineering also includes selective breeding and other means of artificial selection", Retrieved 5 November 2012
These definitions were promptly adjusted with a number of exceptions added as the result of pressure from scientific and farming communities, as well as developments in science. The EU definition later excluded traditional breeding, in vitro fertilization, induction of
polyploidy Polyploidy is a condition in which the cells of an organism have more than two paired sets of ( homologous) chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two complete sets of chromosomes, one fro ...
,
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 mutagen ...
, and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process. Another approach was the definition provided by the
Food and Agriculture Organization The Food and Agriculture Organization of the United Nations; . (FAO) is a specialized agency of the United Nations that leads international efforts to defeat hunger and improve nutrition and food security. Its Latin motto, , translates ...
, the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
, and 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 ...
, stating that the organisms must be altered in a way that does "not occur naturally by mating and/or natural recombination". Progress in science, such as the discovery of
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
being a relatively common natural phenomenon, further added to the confusion on what "occurs naturally", which led to further adjustments and exceptions. There are examples of crops that fit this definition, but are not normally considered GMOs. For example, the grain crop
triticale Triticale (; × ''Triticosecale'') is a hybrid of wheat (''Triticum'') and rye (''Secale'') first bred in laboratories during the late 19th century in Scotland and Germany. Commercially available triticale is almost always a second-generation ...
was fully developed in a laboratory in 1930 using various techniques to alter its genome. Genetically engineered organism (GEO) can be considered a more precise term compared to GMO when describing organisms' genomes that have been directly manipulated with biotechnology. The
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 prot ...
used the synonym ''living modified organism'' (''LMO'') in 2000 and defined it as "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology." Modern biotechnology is further defined as "In vitro nucleic acid techniques, including recombinant deoxyribonucleic acid (DNA) and direct injection of nucleic acid into cells or organelles, or fusion of cells beyond the taxonomic family." Originally, the term GMO was not commonly used by scientists to describe genetically engineered organisms until after usage of GMO became common in popular media. The
United States Department of Agriculture The United States Department of Agriculture (USDA) is an executive department of the United States federal government that aims to meet the needs of commercial farming and livestock food production, promotes agricultural trade and producti ...
(USDA) considers GMOs to be plants or animals with heritable changes introduced by genetic engineering or traditional methods, while GEO specifically refers to organisms with genes introduced, eliminated, or rearranged using molecular biology, particularly
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
transgenesis Gene delivery is the process of introducing foreign genetic material, such as DNA or RNA, into host cells. Gene delivery must reach the genome of the host cell to induce gene expression. Successful gene delivery requires the foreign gene delive ...
. The definitions focus on the process more than the product, which means there could be GMOS and non-GMOs with very similar genotypes and phenotypes. This has led scientists to label it as a scientifically meaningless category, saying that it is impossible to group all the different types of GMOs under one common definition. It has also caused issues for
organic Organic may refer to: * Organic, of or relating to an organism, a living entity * Organic, of or relating to an anatomical organ Chemistry * Organic matter, matter that has come from a once-living organism, is capable of decay or is the product ...
institutions and groups looking to ban GMOs. It also poses problems as new processes are developed. The current definitions came in before
genome editing Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert ge ...
became popular and there is some confusion as to whether they are GMOs. The EU has adjudged that they are changing their GMO definition to include "organisms obtained by
mutagenesis 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 lab ...
", but has excluded those "obtained by means of certain mutagenesis techniques, namely those which have conventionally been used in a number of applications and have a long safety record" from regulation. This refers to traditional random mutagenesis (radiation/chemical
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 mutagen ...
) and would not exclude "new techniques" (especially those that have emerged since the adoption of the GMO directive) like gene editing. In contrast the USDA has ruled that gene edited organisms are not considered GMOs. Even greater inconsistency and confusion is associated with various "Non-GMO" or "GMO-free" labeling schemes in food marketing, where even products such as water or salt, which do not contain any organic substances and genetic material (and thus cannot be genetically modified by definition), are being labeled to create an impression of being "more healthy".


Production

Creating a genetically modified organism (GMO) is a multi-step process. Genetic engineers must isolate the gene they wish to insert into the host organism. This gene can be taken from a
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
or artificially synthesized. If the chosen gene or the donor organism's
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
has been well studied it may already be accessible from a genetic library. The gene is then combined with other genetic elements, including a promoter and terminator region and a
selectable marker A selectable marker is a gene introduced into cell (biology), cells, especially bacteria or cells in cell culture, culture, which confers one or more traits suitable for artificial selection. They are a type of reporter gene used in laboratory micr ...
. A number of techniques are available for inserting the isolated gene into the host genome. Bacteria can be induced to take up foreign DNA, usually by exposed
heat shock The heat shock response (HSR) is a cell stress response that increases the number of molecular chaperones to combat the negative effects on proteins caused by stressors such as increased temperatures, oxidative stress, and heavy metals. In a norm ...
or
electroporation Electroporation, also known as electropermeabilization, is a microbiological and biotechnological technique in which an electric field is applied to cells to briefly increase the permeability of the cell membrane. The application of a high-vo ...
. DNA is generally inserted into animal cells using
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 pro ...
, where it can be injected through the cell's
nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membran ...
directly into the
nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...
, or through the use of
viral vectors A viral vector is a modified virus designed to deliver genetic material into cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, agriculture, and medicine. V ...
. In plants the DNA is often inserted using ''Agrobacterium''-mediated recombination,
biolistics In genetic engineering, a gene gun or biolistic particle delivery system is a device used to deliver exogenous DNA (transgenes), RNA, or protein to cells. By coating particles of a heavy metal with a gene of interest and firing these micro-projec ...
or electroporation. As only a single cell is transformed with genetic material, the organism must be regenerated from that single cell. In plants this is accomplished through
tissue culture Tissue culture is the growth of tissue (biology), tissues or cell (biology), cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-s ...
. In animals it is necessary to ensure that the inserted DNA is present in the
embryonic stem cells Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4†...
. 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. Traditionally the new genetic material was inserted randomly within the host genome.
Gene targeting Gene targeting is a biotechnological tool used to change the DNA sequence of an organism (hence it is a form of Genome Editing). It is based on the natural DNA-repair mechanism of Homology Directed Repair (HDR), including Homologous Recombinat ...
techniques, which creates double-stranded breaks and takes advantage on the cells natural
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 ...
repair systems, have been developed to target insertion to exact
locations In geography, location or place is used to denote a region (point, line, or area) on Earth's surface. The term ''location'' generally implies a higher degree of certainty than ''place'', the latter often indicating an entity with an ambiguous bou ...
.
Genome editing Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly insert ge ...
uses artificially engineered
nuclease In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds that link nucleotides together to form nucleic acids. Nucleases variously affect single and ...
s that create breaks at specific points. There are four families of engineered nucleases:
meganuclease Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence ...
s,
zinc finger nuclease Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a nuclease, DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enab ...
s,
transcription activator-like effector nuclease Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain (a nuclease which cuts DN ...
s (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.


History

Humans have
domesticated Domestication is a multi-generational mutualistic relationship in which an animal species, such as humans or leafcutter ants, takes over control and care of another species, such as sheep or fungi, to obtain from them a steady supply of reso ...
plants and animals since around 12,000 BCE, using
selective breeding Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
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 ...
). The process of
selective breeding Selective breeding (also called artificial selection) is the process by which humans use animal breeding and plant breeding to selectively develop particular phenotypic traits (characteristics) by choosing which typically animal or plant m ...
, in which organisms with desired
traits Trait may refer to: * Phenotypic trait in biology, which involve genes and characteristics of organisms * Genotypic trait, sometimes but not always presenting as a phenotypic trait * Personality, traits that predict an individual's behavior. ** ...
(and thus with the desired
genes 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 ...
) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification. Various advancements in
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
allowed humans to directly alter the DNA and therefore genes of organisms. In 1972,
Paul Berg Paul Berg (June 30, 1926 – February 15, 2023) was an American biochemist and professor at Stanford University. He was the recipient of the Nobel Prize in Chemistry in 1980, along with Walter Gilbert and Frederick Sanger. The award recogniz ...
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 ...
molecule when he combined DNA from a monkey virus with that of the lambda virus.
Herbert Boyer Herbert Wayne "Herb" Boyer (born July 10, 1936) is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg, he discovered recombinant DNA, a method to coax bacteria into producing for ...
and Stanley Cohen made the first genetically modified organism in 1973. They took a gene from a bacterium that provided resistance to the antibiotic
kanamycin Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamy ...
, inserted it 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 ...
and then induced other bacteria to incorporate the plasmid. The bacteria that had successfully incorporated the plasmid was then able to survive in the presence of kanamycin. Boyer and Cohen expressed other genes in bacteria. This included genes from the toad ''
Xenopus laevis The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black ...
'' in 1974, creating the first GMO expressing a gene from an organism of a different kingdom. In 1974,
Rudolf Jaenisch Rudolf Jaenisch (born on April 22, 1942) is a professor of biology at MIT and a founding member of the Whitehead Institute for Biomedical Research. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisc ...
created a
transgenic mouse A genetically modified mouse, genetically engineered mouse model (GEMM) or transgenic mouse is a mouse (''Mus musculus'') that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly use ...
by introducing foreign DNA into its embryo, making it the world's first transgenic animal. However it took another eight years before transgenic mice were developed that passed the
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
to their offspring. Genetically modified mice were created in 1984 that carried cloned
oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
, predisposing them to developing cancer. Mice with genes removed (termed a
knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
) were created in 1989. The first transgenic livestock were produced in 1985 and the first animal to synthesize transgenic proteins in their milk were mice in 1987. The mice were engineered to produce human
tissue plasminogen activator Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots. It acts as an enzyme to convert plasminogen into its active form plasmin, the major enzyme responsible for clot breakdown. It is a s ...
, a protein involved in breaking down
blood clots A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...
. In 1983, the first genetically engineered plant was developed by Michael W. Bevan,
Richard B. Flavell Richard Bailey Flavell CBE, FRS (born 11 October 1943) is a British molecular biologist, Chief Scientific Officer of Ceres, Inc., and was director of John Innes Centre from 1987 to 1998.'FLAVELL, Dr Richard Bailey', Who's Who 2014, A & C Bla ...
and Mary-Dell Chilton. They infected tobacco with ''
Agrobacterium ''Agrobacterium'' is a genus of Gram-negative bacteria established by Harold J. Conn, H. J. Conn that uses horizontal gene transfer to cause tumors in plants. ''Agrobacterium tumefaciens'' is the most commonly studied species in this genus. ''Agr ...
'' transformed with an antibiotic resistance gene and through
tissue culture Tissue culture is the growth of tissue (biology), tissues or cell (biology), cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-s ...
techniques were able to grow a new plant containing the resistance gene. The
gene gun In genetic engineering, a gene gun or biolistic particle delivery system is a device used to deliver exogenous DNA (transgenes), RNA, or protein to cells. By coating particles of a heavy metal with a gene of interest and firing these micro-projec ...
was invented in 1987, allowing transformation of plants not susceptible to ''Agrobacterium'' infection. In 2000,
Vitamin A Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most not ...
-enriched
golden rice Golden rice is a variety of rice ('' Oryza sativa'') produced through genetic engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of the rice. It is intended to produce a fortified food to be grown and ...
was the first plant developed with increased nutrient value. In 1976,
Genentech Genentech, Inc. is an American biotechnology corporation headquartered in South San Francisco, California. It operates as an independent subsidiary of holding company Roche. Genentech Research and Early Development operates as an independent cent ...
, the first genetic engineering company was founded by Herbert Boyer and Robert Swanson; 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 ''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 foun ...
''. 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. The insulin produced by bacteria, branded
Humulin As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes ...
, 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 ...
in 1982. In 1988, the first human antibodies were produced in plants. In 1987, a 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 ...
'' became the first genetically modified organism to be released into the environmentBBC News 14 June 200
GM crops: A bitter harvest?
/ref> when a strawberry and potato field in California were sprayed with it. The first
genetically modified crop Genetically modified crops (GM crops) are plants used in agriculture, the DNA of which has been modified using genetic engineering methods. Plant genomes can be engineered by physical methods or by use of ''Agrobacterium'' for the delivery of se ...
, an antibiotic-resistant tobacco plant, was produced in 1982. China was the first country to commercialize transgenic plants, introducing a virus-resistant tobacco in 1992. In 1994,
Calgene The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best-known product is Roundup, a glyphosate-based herbicide, developed i ...
attained approval to commercially release the
Flavr Savr Flavr Savr (also known as CGN-89564-2; pronounced "flavor saver"), a genetically modified tomato, was the first commercially grown Genetic engineering, genetically engineered food to be granted a license for human consumption. It was developed by t ...
tomato, the first
genetically modified food Genetically modified foods (GM foods), also known as genetically engineered foods (GE foods), or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using various methods of genetic engineering. G ...
. Also in 1994, the European Union approved tobacco engineered to be resistant to the herbicide
bromoxynil Bromoxynil is an organic compound with the formula HOBr2C6H2CN. It is classified as a nitrile herbicide, and as such sold under many trade names. It is a white solid. It works by inhibiting photosynthesis. It is moderately toxic to mammals. It ...
, making it the first genetically engineered crop commercialized in Europe. An insect resistant Potato was approved for release in the US in 1995, and by 1996 approval had been granted to commercially grow 8 transgenic crops and one flower crop (carnation) in 6 countries plus the EU. In 2010, scientists at the
J. Craig Venter Institute The J. Craig Venter Institute (JCVI) is a non-profit genomics research institute founded by J. Craig Venter, Ph.D. in October 2006. The institute was the result of consolidating four organizations: the Center for the Advancement of Ge ...
announced that they had created the first synthetic bacterial
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
. They named it Synthia and it was the world's first
synthetic life 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 ...
form. The first genetically modified animal to be commercialized was the
GloFish The GloFish is a patented and trademarked brand of fluorescently colored genetically modified fish, genetically modified aquarium fish. They have been created from several different species of fish: zebrafish were the first GloFish available in ...
, a
Zebra fish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and ...
with a fluorescent gene added that allows it to glow in the dark under
ultraviolet light Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of th ...
. It was released to the US market in 2003. In 2015,
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 gen ...
became the first genetically modified animal to be approved for food use. Approval is for fish raised in Panama and sold in the US. The salmon were transformed with a
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) 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 ...
-regulating gene from a Pacific Chinook salmon and a promoter from an
ocean pout The ocean pout (''Zoarces americanus'') is an eelpout in the family Zoarcidae. It is found in the Northwest Atlantic Ocean, off the coast of New England and eastern Canada. The fish has antifreeze proteins in its blood, giving it the ability to ...
enabling it to grow year-round instead of only during spring and summer.


Bacteria

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 ...
were the first organisms to be genetically modified in the laboratory, due to the relative ease of modifying their chromosomes. This ease made them important tools for the creation of other GMOs. Genes and other genetic information from a wide range of organisms can be added to 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 ...
and inserted into bacteria for storage and modification. Bacteria are cheap, easy to grow, clonal, multiply quickly and can be stored at −80 Â°C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria, providing an unlimited supply for research. A large number of custom plasmids make manipulating DNA extracted from bacteria relatively easy. Their ease of use has made them great tools for scientists looking to study gene function and
evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
. The simplest
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. Mo ...
s come from bacteria, with most of our early understanding of
molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
coming from studying ''
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 ...
''. Scientists can easily manipulate and combine genes within the bacteria to create novel or disrupted proteins and observe the effect this has on various molecular systems. Researchers have combined the genes from bacteria and
archaea Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...
, leading to insights on how these two diverged in the past. In the field of
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 ...
, they have been used to test various synthetic approaches, from synthesizing genomes to creating novel
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
. Bacteria have been used in the production of food for a long time, and specific strains have been developed and selected for that work on an industrial scale. They can be used to produce
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s,
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s,
flavoring A flavoring (or flavouring), also known as flavor (or flavour) or flavorant, is a food additive that is used to improve the taste or smell of food. It changes the perceptual impression of food as determined primarily by the chemoreceptors of ...
s, and other compounds used in food production. With the advent of genetic engineering, new genetic changes can easily be introduced into these bacteria. Most food-producing bacteria are
lactic acid bacteria Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped (bacilli) or spherical ( cocci) bacteria that share common metabolic and physiological characteristics. These bact ...
, and this is where the majority of research into genetically engineering food-producing bacteria has gone. The bacteria can be modified to operate more efficiently, reduce toxic byproduct production, increase output, create improved compounds, and remove unnecessary pathways. Food products from genetically modified bacteria include alpha-amylase, which converts starch to simple sugars,
chymosin Chymosin or rennin is a protease found in rennet. It is an aspartic endopeptidase belonging to MEROPS A1 family. It is produced by newborn ruminant animals in the lining of the abomasum to curdle the milk they ingest, allowing a longer reside ...
, which clots milk protein for cheese making, and
pectinesterase Pectinesterase (EC 3.1.1.11; systematic name pectin pectylhydrolase) is a ubiquitous cell-wall-associated enzyme that presents several isoforms that facilitate plant cell wall modification and subsequent breakdown. It catalyzes the following rea ...
, which improves fruit juice clarity. The majority are produced in the US and even though regulations are in place to allow production in Europe, as of 2015 no food products derived from bacteria are currently available there. Genetically modified bacteria are used to produce large amounts of proteins for industrial use. The bacteria are generally grown to a large volume before the gene encoding the protein is activated. The bacteria are then harvested and the desired protein purified from them. The high cost of extraction and purification has meant that only high value products have been produced at an industrial scale. The majority of these products are human proteins for use in medicine. Many of these proteins are impossible or difficult to obtain via natural methods and they are less likely to be contaminated with pathogens, making them safer. The first medicinal use of GM bacteria was to produce the protein
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 ...
to treat
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
. Other medicines produced include
clotting factors Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulatio ...
to treat
hemophilia Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
,
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) 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 ...
to treat various forms of
dwarfism Dwarfism is a condition of people and animals marked by unusually small size or short stature. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dwarfism is . '' ...
,
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
to treat some cancers,
erythropoietin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
for anemic patients, and
tissue plasminogen activator Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots. It acts as an enzyme to convert plasminogen into its active form plasmin, the major enzyme responsible for clot breakdown. It is a s ...
which dissolves blood clots. Outside of medicine they have been used to produce
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. There is interest in developing an extracellular expression system within the bacteria to reduce costs and make the production of more products economical. With a greater understanding of the role that the
microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...
plays in human health, there is a potential to treat diseases by genetically altering the bacteria to, themselves, be therapeutic agents. Ideas include altering gut bacteria so they destroy harmful bacteria, or using bacteria to replace or increase deficient
enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
or proteins. One research focus is to modify ''
Lactobacillus ''Lactobacillus'' is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically div ...
'', bacteria that naturally provide some protection against
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
, with genes that will further enhance this protection. If the bacteria do not form
colonies A colony is a territory subject to a form of foreign rule, which rules the territory and its indigenous peoples separated from the foreign rulers, the colonizer, and their '' metropole'' (or "mother country"). This separated rule was often or ...
inside the patient, the person must repeatedly ingest the modified bacteria in order to get the required doses. Enabling the bacteria to form a colony could provide a more long-term solution, but could also raise safety concerns as interactions between bacteria and the human body are less well understood than with traditional drugs. There are concerns that
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
to other bacteria could have unknown effects. As of 2018 there are clinical trials underway testing the
efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
and safety of these treatments. For over a century, bacteria have been used in agriculture. Crops have been inoculated with
Rhizobia Rhizobia are diazotrophic bacteria that fix nitrogen after becoming established inside the root nodules of legumes (Fabaceae). To express genes for nitrogen fixation, rhizobia require a plant host; they cannot independently fix nitrogen. I ...
(and more recently ''
Azospirillum ''Azospirillum'' is a Gram-negative, microaerophilic, non-fermentative and nitrogen-fixing bacterial genus from the family of Rhodospirillaceae. ''Azospirillum'' bacteria can promote plant growth. Characteristics The genus ''Azospirillum'' bel ...
'') to increase their production or to allow them to be grown outside their original
habitat In ecology, habitat refers to the array of resources, biotic factors that are present in an area, such as to support the survival and reproduction of a particular species. A species' habitat can be seen as the physical manifestation of its ...
. Application of ''
Bacillus thuringiensis ''Bacillus thuringiensis'' (or Bt) is a gram-positive bacteria, gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types ...
'' (Bt) and other bacteria can help protect crops from insect infestation and plant diseases. With advances in genetic engineering, these bacteria have been manipulated for increased efficiency and expanded host range. Markers have also been added to aid in tracing the spread of the bacteria. The bacteria that naturally colonize certain crops have also been modified, in some cases to express the Bt genes responsible for pest resistance. ''
Pseudomonas ''Pseudomonas'' is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...
'' strains of bacteria cause frost damage by nucleating water into
ice crystals Ice crystals are solid water (known as ice) in crystal structure, symmetrical shapes including hexagonal crystal family, hexagonal columns, hexagonal plates, and dendrite (crystal), dendritic crystals. Ice crystals are responsible for various at ...
around themselves. This led to the development of
ice-minus bacteria Ice-minus bacteria is a common name given to a variant of the common bacterium ''Pseudomonas syringae'' (''P. syringae''). This strain of ''P. syringae'' lacks the ability to produce a certain surface protein, usually found on wild-type ''P. syri ...
, which have the ice-forming genes removed. When applied to crops they can compete with the non-modified bacteria and confer some frost resistance. Other uses for genetically modified bacteria include
bioremediation Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi in mycoremediation, and plants in phytoremediation), living or dead, is employed for removing environmental pollutants from air, wate ...
, where the bacteria are used to convert pollutants into a less toxic form. Genetic engineering can increase the levels of the enzymes used to degrade a toxin or to make the bacteria more stable under environmental conditions. Bioart has also been created using genetically modified bacteria. In the 1980s artist Jon Davis and geneticist Dana Boyd converted the Germanic symbol for femininity (ᛉ) into binary code and then into a DNA sequence, which was then expressed in ''
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 ...
''. This was taken a step further in 2012, when a whole book was encoded onto DNA. Paintings have also been produced using bacteria transformed with fluorescent proteins.


Viruses

Viruses are often modified so they can be used as vectors for inserting genetic information into other organisms. This process is called transduction and if successful the recipient of the introduced DNA becomes a GMO. Different viruses have different efficiencies and capabilities. Researchers can use this to control for various factors; including the target location, insert size, and duration of gene expression. Any dangerous sequences inherent in the virus must be removed, while those that allow the gene to be delivered effectively are retained. While viral vectors can be used to insert DNA into almost any organism it is especially relevant for its potential in treating human disease. Although primarily still at trial stages, there has been some successes using
gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...
to replace defective genes. This is most evident in curing patients with
severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...
rising from
adenosine deaminase deficiency Adenosine deaminase deficiency (ADA deficiency) is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immun ...
(ADA-SCID), although the development of
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
in some ADA-SCID patients along with the death of
Jesse Gelsinger Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the ...
in a 1999 trial set back the development of this approach for many years. In 2009, another breakthrough was achieved when an eight-year-old boy with
Leber's congenital amaurosis Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life. It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be ...
regained normal eyesight and in 2016
GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...
gained approval to commercialize a gene therapy treatment for ADA-SCID. As of 2018, there are a substantial number of
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s underway, including treatments for
hemophilia Haemophilia (British English), or hemophilia (American English) (), is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a long ...
,
glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
,
chronic granulomatous disease Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the react ...
,
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
and various
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s. The most common virus used for gene delivery comes from
adenoviruses Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
as they can carry up to 7.5 kb of foreign DNA and infect a relatively broad range of host cells, although they have been known to elicit immune responses in the host and only provide short term expression. Other common vectors are
adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus '' Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in ...
es, which have lower toxicity and longer-term expression, but can only carry about 4kb of DNA.
Herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are two members of the Herpesviridae#Human herpesvirus types, human ''Herpesviridae'' family, a set of viruses that produce Viral disease, viral infections in the majority of humans. Both HSV-1 a ...
es make promising vectors, having a carrying capacity of over 30kb and providing long term expression, although they are less efficient at gene delivery than other vectors. The best vectors for long term integration of the gene into the host genome are
retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase e ...
es, but their propensity for random integration is problematic.
Lentivirus ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...
es are a part of the same family as retroviruses with the advantage of infecting both dividing and non-dividing cells, whereas retroviruses only target dividing cells. Other viruses that have been used as vectors include
alphavirus ''Alphavirus'' is a genus of RNA viruses, the sole genus in the ''Togaviridae'' family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphavirus spe ...
es,
flavivirus ''Flavivirus'', renamed ''Orthoflavivirus'' in 2023, is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika viru ...
es,
measles virus The measles virus (MV), with scientific name ''Morbillivirus hominis'', is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus ''Morbillivirus'' within the family ''Paramyxoviridae''. It is the cause of measles. H ...
es,
rhabdovirus ''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order ''Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member virus ...
es,
Newcastle disease virus Newcastle usually refers to: *Newcastle upon Tyne, a city and metropolitan borough in Tyne and Wear, England, United Kingdom *Newcastle-under-Lyme, a town in Staffordshire, England, United Kingdom *Newcastle, New South Wales, a metropolitan area ...
,
poxviruses ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...
, and
picornavirus Picornaviruses are a group of related Viral envelope, nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, Positive-sense single-stranded RNA virus, positi ...
es. Most
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 consist of viruses that have been attenuated, disabled, weakened or killed in some way so that their
virulent Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abilit ...
properties are no longer effective. Genetic engineering could theoretically be used to create viruses with the virulent genes removed. This does not affect the viruses
infectivity In epidemiology, infectivity is the ability of 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 refer ...
, invokes a natural immune response and there is no chance that they will regain their virulence function, which can occur with some other vaccines. As such they are generally considered safer and more efficient than conventional vaccines, although concerns remain over non-target infection, potential side effects and
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
to other viruses. Another potential approach is to use vectors to create novel vaccines for diseases that have no vaccines available or the vaccines that do not work effectively, such as
AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
,
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
, and
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
. The most effective vaccine against Tuberculosis, the Bacillus Calmette–Guérin (BCG) vaccine, only provides partial protection. A modified vaccine expressing ''a M tuberculosis'' antigen is able to enhance BCG protection. It has been shown to be safe to use at
phase II trials The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
, although not as effective as initially hoped. Other vector-based vaccines have already been approved and many more are being developed. Another potential use of genetically modified viruses is to alter them so they can directly treat diseases. This can be through expression of protective proteins or by directly targeting infected cells. In 2004, researchers reported that a genetically modified virus that exploits the selfish behavior of cancer cells might offer an alternative way of killing tumours. Since then, several researchers have developed genetically modified
oncolytic virus An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic vi ...
es that show promise as treatments for various types of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. In 2017, researchers genetically modified a virus to express spinach
defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct Antimicrobial, antimicrobial activit ...
proteins. The virus was injected into orange trees to combat
citrus greening disease Citrus greening disease ( abbr. HLB) is a disease of citrus caused by a vector-transmitted pathogen. The causative agents are motile bacteria, '' Liberibacter'' spp. The disease is transmitted by the Asian citrus psyllid, '' Diaphorina citri'', ...
that had reduced orange production by 70% since 2005. Natural viral diseases, such as
myxomatosis Myxomatosis is a disease caused by '' Myxoma virus'', a poxvirus in the genus '' Leporipoxvirus''. The natural hosts are tapeti (''Sylvilagus brasiliensis'') in South and Central America, and brush rabbits (''Sylvilagus bachmani'') in North ...
and
rabbit hemorrhagic disease Rabbit hemorrhagic disease (RHD), also known as viral hemorrhagic disease (VHD), is a highly infectious and lethal form of viral hepatitis that affects European rabbits. Some viral strains also affect hares and cottontail rabbits. Mortality rat ...
, have been used to help control pest populations. Over time the surviving pests become resistant, leading researchers to look at alternative methods. Genetically modified viruses that make the target animals infertile through
immunocontraception Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently approved for human use. Typically immunocontraception involves the administration of a vaccine tha ...
have been created in the laboratory as well as others that target the developmental stage of the animal. There are concerns with using this approach regarding virus containment and cross species infection. Sometimes the same virus can be modified for contrasting purposes. Genetic modification of the
myxoma virus Myxoma virus is a poxvirus in the genus '' Leporipoxvirus''. The two broad geographic types of Myxoma virus are Californian and South American. Californian myxoma virus is found on the West Coast of the United States, the Baja Peninsula of Mexi ...
has been proposed to conserve European wild rabbits in the
Iberian peninsula The Iberian Peninsula ( ), also known as Iberia, is a peninsula in south-western Europe. Mostly separated from the rest of the European landmass by the Pyrenees, it includes the territories of peninsular Spain and Continental Portugal, comprisin ...
and to help regulate them in Australia. To protect the Iberian species from viral diseases, the myxoma virus was genetically modified to immunize the rabbits, while in Australia the same myxoma virus was genetically modified to lower fertility in the Australian rabbit population. Outside of biology scientists have used a genetically modified virus to construct a
lithium-ion battery A lithium-ion or Li-ion battery is a type of rechargeable battery that uses the reversible intercalation of Li+ ions into electronically conducting solids to store energy. Li-ion batteries are characterized by higher specific energy, energ ...
and other
nanostructure A nanostructure is a structure of intermediate size between microscopic and molecular structures. Nanostructural detail is microstructure at nanoscale. In describing nanostructures, it is necessary to differentiate between the number of dimen ...
d materials. It is possible to engineer
bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
s to express modified proteins on their surface and join them up in specific patterns (a technique called
phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein–DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...
). These structures have potential uses for energy storage and generation,
biosensing A biosensor is an analytical device, used for the detection of a chemical substance, that combines a biological component with a physicochemical detector. The ''sensitive biological element'', e.g. tissue, microorganisms, organelles, cell recep ...
and tissue regeneration with some new materials currently produced including
quantum dot Quantum dots (QDs) or semiconductor nanocrystals are semiconductor particles a few nanometres in size with optical and electronic properties that differ from those of larger particles via quantum mechanical effects. They are a central topic i ...
s,
liquid crystal Liquid crystal (LC) is a state of matter whose properties are between those of conventional liquids and those of solid crystals. For example, a liquid crystal can flow like a liquid, but its molecules may be oriented in a common direction as i ...
s, nanorings and nanofibres. The battery was made by engineering M13 bacteriaophages so they would coat themselves in
iron phosphate Iron phosphate may refer to: * Iron(II) phosphate * Iron(III) phosphate See also * Strengite Strengite is a relatively rare iron phosphate mineral with the formula: FePO4·2H2O. The mineral is named after the German mineralogist (1830–1 ...
and then assemble themselves along a
carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with a diameter in the nanometre range ( nanoscale). They are one of the allotropes of carbon. Two broad classes of carbon nanotubes are recognized: * ''Single-walled carbon nanotubes'' (''S ...
. This created a highly conductive medium for use in a cathode, allowing energy to be transferred quickly. They could be constructed at lower temperatures with non-toxic chemicals, making them more environmentally friendly.


Fungi

Fungi can be used for many of the same processes as bacteria. For industrial applications, yeasts combine the bacterial advantages of being a single-celled organism that is easy to manipulate and grow with the advanced protein modifications found in
eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s. They can be used to produce large complex molecules for use in food, pharmaceuticals, hormones, and steroids. Yeast is important for wine production and as of 2016 two genetically modified yeasts involved in the fermentation of wine have been commercialized in the United States and Canada. One has increased
malolactic fermentation Malolactic conversion (also known as malolactic fermentation or MLF) is a process in winemaking in which Tart (flavor), tart-tasting malic acid, naturally present in grape must, is converted to softer-tasting lactic acid. Malolactic fermentation ...
efficiency, while the other prevents the production of dangerous
ethyl carbamate Ethyl carbamate (also called urethane) is an organic compound with the formula CH3CH2OC(O)NH2. It is an ester of carbamic acid and a white solid. Despite its name, it is not a component of polyurethanes. Because it is a carcinogen, it is rarely use ...
compounds during fermentation. There have also been advances in the production of
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 ...
from genetically modified fungi. Fungi, being the most common
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 ...
s of insects, make attractive
biopesticide A biopesticide is a biological substance or organism that damages, kills, or repels organisms seens as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships. They are obtained from organisms incl ...
s. Unlike bacteria and viruses they have the advantage of infecting the insects by contact alone, although they are out competed in efficiency by
chemical pesticides Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for approximately 50% of all pesti ...
. Genetic engineering can improve virulence, usually by adding more virulent proteins, * increasing infection rate or enhancing
spore In biology, a spore is a unit of sexual reproduction, sexual (in fungi) or asexual reproduction that may be adapted for biological dispersal, dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores fo ...
persistence. Many of the disease carrying vectors are susceptible to
entomopathogenic fungi Entomopathogenic fungi are parasitic unicellular or multicellular microorganisms belonging to the kingdom of Fungi, that can infect and seriously disable or kill insects. Pathogenicity for insects is widely distributed in the kingdom of fungi and ...
. An attractive target for
biological control Biological control or biocontrol is a method of controlling pests, whether pest animals such as insects and mites, weeds, or pathogens affecting animals or plants by using other organisms. It relies on predation, parasitism, herbivory, or o ...
are
mosquito Mosquitoes, the Culicidae, are a Family (biology), family of small Diptera, flies consisting of 3,600 species. The word ''mosquito'' (formed by ''Musca (fly), mosca'' and diminutive ''-ito'') is Spanish and Portuguese for ''little fly''. Mos ...
s, vectors for a range of deadly diseases, including
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
, yellow fever and
dengue fever Dengue fever is a mosquito-borne disease caused by dengue virus, prevalent in tropical and subtropical areas. Asymptomatic infections are uncommon, mild cases happen frequently; if symptoms appear, they typically begin 3 to 14 days after i ...
. Mosquitos can evolve quickly so it becomes a balancing act of killing them before the ''
Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a Hematophagy, blood-feeding insect host (biology), host which then inj ...
'' they carry becomes the infectious disease, but not so fast that they become resistant to the fungi. By genetically engineering fungi like ''
Metarhizium anisopliae ''Metarhizium anisopliae'' is a fungus, the type species in the ''Metarhizium'' genus. It grows naturally in soils throughout the world and causes disease in various insects by acting as a parasitoid. Ilya Ilyich Mechnikov, Ilya I. Mechnikov nam ...
'' and ''
Beauveria bassiana ''Beauveria bassiana'' is a fungus that grows naturally in soils throughout the world and acts as a parasite on various arthropod species, causing white muscardine disease; it thus belongs to the group of entomopathogenic fungi. It is used as a ...
'' to delay the development of mosquito infectiousness the
selection pressure Evolutionary pressure, selective pressure or selection pressure is exerted by factors that reduce or increase reproductive success in a portion of a population, driving natural selection. It is a quantitative description of the amount of change oc ...
to evolve resistance is reduced. Another strategy is to add proteins to the fungi that block transmission of malaria or remove the ''Plasmodium'' altogether. ''
Agaricus bisporus ''Agaricus bisporus'', commonly known as the cultivated mushroom, is a basidiomycete mushroom native to grasslands in Eurasia and North America. It is cultivated in more than 70 countries and is one of the most commonly and widely consumed ...
'' the common white button mushroom, has been gene edited to resist browning, giving it a longer
shelf life Shelf life is the length of time that a commodity may be stored without becoming unfit for use, consumption, or sale. In other words, it might refer to whether a commodity should no longer be on a pantry shelf (unfit for use), or no longer on a s ...
. The process used
CRISPR CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is d ...
to
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 ...
a gene that encodes
polyphenol oxidase Polyphenol oxidase (PPO; also polyphenol oxidase i, chloroplastic), an enzyme involved in fruit browning, is a tetramer that contains four atoms of copper per molecule. PPO may accept monophenols and/or ''o''-diphenols as substrates. The ...
. As it didn't introduce any foreign DNA into the organism it was not deemed to be regulated under existing GMO frameworks and as such is the first CRISPR-edited organism to be approved for release. This has intensified debates as to whether gene-edited organisms should be considered genetically modified organisms and how they should be regulated.


Plants

Plants have been engineered for scientific research, to display new flower colors, deliver vaccines, and to create enhanced crops. Many plants are
pluripotent Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
, meaning that a single cell from a mature plant can be harvested and under the right conditions can develop into a new plant. This ability can be taken advantage of by genetic engineers; by selecting for cells that have been successfully transformed in an adult plant a new plant can then be grown that contains the transgene in every cell through a process known as
tissue culture Tissue culture is the growth of tissue (biology), tissues or cell (biology), cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-s ...
. Much of the advances in the field of genetic engineering has come from experimentation with
tobacco Tobacco is the common name of several plants in the genus '' Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the ...
. Major advances in tissue culture and
plant cell Plant cells are the cells present in Viridiplantae, green plants, photosynthetic eukaryotes of the kingdom Plantae. Their distinctive features include primary cell walls containing cellulose, hemicelluloses and pectin, the presence of plastids ...
ular mechanisms for a wide range of plants has originated from systems developed in tobacco. It was the first plant to be altered using genetic engineering and is considered a model organism for not only genetic engineering, but a range of other fields. As such the transgenic tools and procedures are well established making tobacco one of the easiest plants to transform. Another major model organism relevant to genetic engineering is ''
Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally ...
''. Its small genome and short life cycle makes it easy to manipulate and it contains many
homologs Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same loci, where they provide points along each chromosome th ...
to important crop species. It was the first plant
sequenced In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succi ...
, has a host of online resources available and can be transformed by simply dipping a flower in a transformed ''Agrobacterium'' solution. In research, plants are engineered to help discover the functions of certain genes. The simplest way to do this is to remove the gene and see what
phenotype 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 ...
develops compared to the
wild type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, " ...
form. Any differences are possibly the result of the missing gene. Unlike mutagenisis, genetic engineering allows targeted removal without disrupting other genes in the organism. Some genes are only expressed in certain tissues, so reporter genes, like
GUS Gus is a masculine name, often a diminutive for Angus, August, Augustine, Gustave, Constantine, Konstantinos, Augusten, Gustavo, Gusten, Augustus, Aengus, Argus, Fergus, Gustav, Gustafson, Ferguson, and Gussie). It can also be used as t ...
, can be attached to the gene of interest allowing visualization of the location. Other ways to test a gene is to alter it slightly and then return it to the plant and see if it still has the same effect on phenotype. Other strategies include attaching the gene to a strong promoter and see what happens when it is overexpressed, forcing a gene to be expressed in a different location or at different
developmental stages Stages of development may refer to: Biology *Developmental biology, the study of the process by which animals and plants grow and develop *Prenatal development, also called fetal development, or embryology *Human development (biology), the proc ...
. Some genetically modified plants are purely
ornamental Ornamental may refer to: *Ornamental grass, a type of grass grown as a decoration *Ornamental iron, mild steel that has been formed into decorative shapes, similar to wrought iron work *Ornamental plant, a plant that is grown for its ornamental qua ...
. They are modified for flower color, fragrance, flower shape and plant architecture. The first genetically modified ornamentals commercialized altered color.
Carnations ''Dianthus caryophyllus'' ( ), commonly known as carnation or clove pink, is a species of ''Dianthus'' native to the Mediterranean region. Its exact natural range is uncertain due to extensive cultivation over the last 2,000 years. Carnations ...
were released in 1997, with the most popular genetically modified organism, a
blue rose A blue rose is a flower of the genus ''Rosa'' (family Rosaceae) that presents blue-to-violet pigmentation instead of the more common red, white, or yellow, through use of artificial means such as dyes. Blue roses are often used to symbolize myst ...
(actually
lavender ''Lavandula'' (common name lavender) is a genus of 47 known species of perennial flowering plants in the sage family, Lamiaceae. It is native plant, native to the Old World, primarily found across the drier, warmer regions of the Mediterranean ...
or
mauve Mauve ( ; ) is a pale purple color named after the mallow flower (French: ). The first use of the word ''mauve'' as a color was in 1796–1798 according to the ''Oxford English Dictionary'', but its use seems to have been rare before 1859. ...
) created in 2004. The roses are sold in Japan, the United States, and Canada. Other genetically modified ornamentals include ''
Chrysanthemum Chrysanthemums ( ), sometimes called mums or chrysanths, are flowering plants in the Asteraceae family. They are native to East Asia and northeastern Europe. Most species originate from East Asia, and the center of diversity is in China. Co ...
'' and ''
Petunia ''Petunia'' is a genus of 20 species of flowering plants of South American origin. The popular flower of the same name derived its epithet from the French, which took the word , 'tobacco', from a Tupi–Guarani language. A tender perennial plan ...
''. As well as increasing aesthetic value there are plans to develop ornamentals that use less water or are resistant to the cold, which would allow them to be grown outside their natural environments. It has been proposed to genetically modify some plant species threatened by extinction to be resistant to invasive plants and diseases, such as the
emerald ash borer The emerald ash borer (''Agrilus planipennis''), also known by the abbreviation EAB, is a green buprestid or jewel beetle native to north-eastern Asia that feeds on ash trees, ash species (''Fraxinus'' spp.). Females lay eggs in bark crevices o ...
in North American and the fungal disease, ''
Ceratocystis platani ''Ceratocystis platani'' is a fungus that causes a disease on Platanus, plane trees in the genus ''Platanus'', mostly in North America and Southern Europe. Description ''Ceratocystis platani'' is believed to be native to southeastern USA. The fu ...
'', in European
plane trees ''Platanus'' ( ) is a genus consisting of a small number of tree species native to the Northern Hemisphere. They are the sole living members of the family Platanaceae. All mature members of ''Platanus'' are tall, reaching in height. The type ...
. The
papaya ringspot virus ''Papaya ringspot virus'' (PRSV) is a pathogenic plant virus in the genus ''Potyvirus'' and the virus family ''Potyviridae'' which primarily infects the papaya tree. The virus is a non-enveloped, flexuous rod-shaped particle that is between 760& ...
devastated papaya trees in Hawaii in the twentieth century until transgenic
papaya The papaya (, ), papaw, () or pawpaw () is the plant species ''Carica papaya'', one of the 21 accepted species in the genus '' Carica'' of the family Caricaceae, and also the name of its fruit. It was first domesticated in Mesoamerica, within ...
plants were given pathogen-derived resistance. However, genetic modification for conservation in plants remains mainly speculative. A unique concern is that a transgenic species may no longer bear enough resemblance to the original species to truly claim that the original species is being conserved. Instead, the transgenic species may be genetically different enough to be considered a new species, thus diminishing the conservation worth of genetic modification.


Crops

Genetically modified crops are genetically modified plants that are used in
agriculture Agriculture encompasses crop and livestock production, aquaculture, and forestry for food and non-food products. Agriculture was a key factor in the rise of sedentary human civilization, whereby farming of domesticated species created ...
. The first crops developed were used for animal or human food and provide resistance to certain pests, diseases, environmental conditions, spoilage or chemical treatments (e.g. resistance to a
herbicide Herbicides (, ), also commonly known as weed killers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page f ...
). The second generation of crops aimed to improve the quality, often by altering the nutrient profile. Third generation genetically modified crops could be used for non-food purposes, including the production of
pharmaceutical agents Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the m ...
,
biofuels Biofuel is a fuel that is produced over a short time span from 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 agricultural, domestic ...
, and other industrially useful goods, as well as for
bioremediation Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi in mycoremediation, and plants in phytoremediation), living or dead, is employed for removing environmental pollutants from air, wate ...
. There are three main aims to agricultural advancement; increased production, improved conditions for agricultural workers and
sustainability Sustainability is a social goal for people to co-exist on Earth over a long period of time. Definitions of this term are disputed and have varied with literature, context, and time. Sustainability usually has three dimensions (or pillars): env ...
. GM crops contribute by improving harvests through reducing insect pressure, increasing nutrient value and tolerating different
abiotic stress Abiotic stress is the negative impact of non-living factors on the living organisms in a specific environment. The non-living variable must influence the environment beyond its normal range of variation to adversely affect the population performan ...
es. Despite this potential, as of 2018, the commercialized crops are limited mostly to
cash crop A cash crop, also called profit crop, is an Agriculture, agricultural crop which is grown to sell for profit. It is typically purchased by parties separate from a farm. The term is used to differentiate a marketed crop from a staple crop ("subsi ...
s like cotton, soybean, maize and canola and the vast majority of the introduced traits provide either herbicide tolerance or insect resistance. Soybeans accounted for half of all genetically modified crops planted in 2014. Adoption by farmers has been rapid, between 1996 and 2013, the total surface area of land cultivated with GM crops increased by a factor of 100.ISAAA 2013 Annual Repor
Executive Summary, Global Status of Commercialized Biotech/GM Crops: 2013
ISAAA Brief 46-2013, Retrieved 6 August 2014
Geographically though the spread has been uneven, with strong growth in the
Americas The Americas, sometimes collectively called America, are a landmass comprising the totality of North America and South America.''Webster's New World College Dictionary'', 2010 by Wiley Publishing, Inc., Cleveland, Ohio. When viewed as a sing ...
and parts of Asia and little in Europe and Africa. Its
socioeconomic Economics () is a behavioral science that studies the Production (economics), production, distribution (economics), distribution, and Consumption (economics), consumption of goods and services. Economics focuses on the behaviour and interac ...
spread has been more even, with approximately 54% of worldwide GM crops grown in
developing countries A developing country is a sovereign state with a less-developed Secondary sector of the economy, industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. ...
in 2013. Although doubts have been raised, most studies have found growing GM crops to be beneficial to farmers through decreased pesticide use as well as increased crop yield and farm profit. The majority of GM crops have been modified to be resistant to selected herbicides, usually a
glyphosate Glyphosate (IUPAC name: ''N''-(phosphonomethyl)glycine) is a broad-spectrum systemic herbicide and crop desiccant. It is an organophosphorus compound, specifically a phosphonate, which acts by EPSP inhibitor, inhibiting the plant enzyme 5-en ...
or
glufosinate Glufosinate (also known as phosphinothricin and often sold as an ammonium salt) is a naturally occurring broad-spectrum herbicide produced by several species of ''Streptomyces'' soil bacteria. Glufosinate is a non-selective, contact herbicide, w ...
based one. Genetically modified crops engineered to resist herbicides are now more available than conventionally bred resistant varieties; in the USA 93% of soybeans and most of the GM maize grown is glyphosate tolerant. Most currently available genes used to engineer insect resistance come from the ''
Bacillus thuringiensis ''Bacillus thuringiensis'' (or Bt) is a gram-positive bacteria, gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types ...
'' bacterium and code for
delta endotoxin Delta endotoxins (δ-endotoxins) are a family of pore-forming toxins produced by '' Bacillus thuringiensis'' species of bacteria. They are useful for their insecticidal action and are the primary toxin produced by the genetically modified ...
s. A few use the genes that encode for
vegetative insecticidal protein Vegetative describes vegetation. Vegetative may also refer to: *Vegetative reproduction, a type of asexual reproduction for plants *Persistent vegetative state, a condition of people with severe brain damage *Plant community A plant community is ...
s. The only gene commercially used to provide insect protection that does not originate from ''B. thuringiensis'' is the
Cowpea The cowpea (''Vigna unguiculata'') is an annual herbaceous legume from the genus '' Vigna''. Its tolerance for sandy soil and low rainfall have made it an important crop in the semiarid regions across Africa and Asia. It requires very few inpu ...
trypsin inhibitor A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor ( serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins. Trypsin is an enzyme involved in the breakdow ...
(CpTI). CpTI was first approved for use cotton in 1999 and is currently undergoing trials in rice. Less than one percent of GM crops contained other traits, which include providing virus resistance, delaying senescence and altering the plants composition.
Golden rice Golden rice is a variety of rice ('' Oryza sativa'') produced through genetic engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of the rice. It is intended to produce a fortified food to be grown and ...
is the most well known GM crop that is aimed at increasing nutrient value. It has been engineered with three genes that
biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
e beta-carotene, a precursor of
vitamin A Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most not ...
, in the edible parts of rice. It is intended to produce a fortified food to be grown and consumed in areas with a shortage of dietary vitamin A, a deficiency which each year is estimated to kill 670,000 children under the age of 5 and cause an additional 500,000 cases of irreversible childhood blindness. The original golden rice produced 1.6μg/g of the
carotenoid Carotenoids () are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, archaea, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, cana ...
s, with further development increasing this 23 times. It gained its first approvals for use as food in 2018. Plants and plant cells have been genetically engineered for production of
biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...
s in
bioreactors A bioreactor is any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derive ...
, a process known as
pharming Pharming is a cyberattack intended to redirect a website's traffic to another, fake site by installing a malicious program on the victim's computer in order to gain access to it. Pharming can be conducted either by changing the hosts file on a vi ...
. Work has been done with
duckweed Lemnoideae is a subfamily of flowering aquatic plants, known as duckweeds, water lentils, or water lenses. They float on or just beneath the surface of still or slow-moving bodies of fresh water and wetlands. Also known as bayroot, they arose fr ...
''
Lemna minor ''Lemna minor'', the common duckweed or lesser duckweed, is a species of aquatic freshwater plant in the subfamily Lemnoideae of the arum family Araceae. ''L. minor'' is used as animal fodder, bioremediator, for wastewater nutrient recovery, and ...
'', the
algae Algae ( , ; : alga ) is an informal term for any organisms of a large and diverse group of photosynthesis, photosynthetic organisms that are not plants, and includes species from multiple distinct clades. Such organisms range from unicellular ...
''
Chlamydomonas reinhardtii ''Chlamydomonas reinhardtii'' is a single-cell green alga about 10 micrometres in diameter that swims with two flagella. It has a cell wall made of hydroxyproline-rich glycoproteins, a large cup-shaped chloroplast, a large pyrenoid, and a ...
'' and the
moss Mosses are small, non-vascular plant, non-vascular flowerless plants in the taxonomic phylum, division Bryophyta (, ) ''sensu stricto''. Bryophyta (''sensu lato'', Wilhelm Philippe Schimper, Schimp. 1879) may also refer to the parent group bryo ...
''
Physcomitrella patens ''Physcomitrella patens'' is a synonym of ''Physcomitrium patens'', the spreading earthmoss. It is a moss, a bryophyte used as a model organism for studies on plant evolution, development, and physiology. Distribution and ecology ''Physcomitr ...
''. Biopharmaceuticals produced include
cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s,
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s,
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
,
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s and vaccines, most of which are accumulated in the plant seeds. Many drugs also contain natural plant ingredients and the pathways that lead to their production have been genetically altered or transferred to other plant species to produce greater volume. Other options for bioreactors are
biopolymer Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, ...
s and
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. Unlike bacteria, plants can modify the proteins post-translationally, allowing them to make more complex molecules. They also pose less risk of being contaminated. Therapeutics have been cultured in transgenic carrot and tobacco cells, including a drug treatment for Gaucher's disease. Vaccine production and storage has great potential in transgenic plants. Vaccines are expensive to produce, transport, and administer, so having a system that could produce them locally would allow greater access to poorer and developing areas. As well as purifying vaccines expressed in plants it is also possible to produce edible vaccines in plants. Edible vaccines stimulate the immune system when ingested to protect against certain diseases. Being stored in plants reduces the long-term cost as they can be disseminated without the need for cold storage, don't need to be purified, and have long term stability. Also being housed within plant cells provides some protection from the gut acids upon digestion. However the cost of developing, regulating, and containing transgenic plants is high, leading to most current plant-based vaccine development being applied to veterinary medicine, where the controls are not as strict. Genetically modified crops have been proposed as one of the ways to reduce farming-related emissions due to higher yield, reduced use of pesticides, reduced use of tractor fuel and no tillage. According to a 2021 study, in EU alone widespread adoption of GE crops would reduce greenhouse gas emissions by 33 million tons of equivalent or 7.5% of total farming-related emissions.


Animals

The vast majority of genetically modified animals are at the research stage with the number close to entering the market remaining small. As of 2018 only three genetically modified animals have been approved, all in the USA. A goat and a chicken have been engineered to produce medicines and a salmon has increased its own growth. Despite the differences and difficulties in modifying them, the end aims are much the same as for plants. GM animals are created for research purposes, production of industrial or therapeutic products, agricultural uses, or improving their health. There is also a market for creating genetically modified pets.Rudinko, Larisa (20). Guidance for industry. USA: Center for veterinary medicin
Link.
/ref>


Mammals

The process of genetically engineering mammals is slow, tedious, and expensive. However, new technologies are making genetic modifications easier and more precise.Murray, Joo (20)
Genetically modified animals
. Canada: Brainwaving
The first transgenic mammals were produced by injecting viral DNA into embryos and then implanting the embryos in females. The embryo would develop and it would be hoped that some of the genetic material would be incorporated into the reproductive cells. Then researchers would have to wait until the animal reached breeding age and then offspring would be screened for the presence of the gene in every cell. The development of the
CRISPR CRISPR (; acronym of clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. Each sequence within an individual prokaryotic CRISPR is d ...
-Cas9 gene editing system as a cheap and fast way of directly modifying germ cells, effectively halving the amount of time needed to develop genetically modified mammals. Mammals are the best models for human disease, making genetic engineered ones vital to the discovery and development of cures and treatments for many serious diseases. Knocking out genes responsible for human genetic disorders allows researchers to study the mechanism of the disease and to test possible cures. Genetically modified mouse, Genetically modified mice have been the most common mammals used in biomedical research, as they are cheap and easy to manipulate. Pigs are also a good target as they have a similar body size and anatomical features, physiology, Pathophysiology, pathophysiological response and diet. Nonhuman primates are the most similar model organisms to humans, but there is less public acceptance towards using them as research animals. In 2009, scientists announced that they had successfully transferred a gene into a primate species (marmosets) for the first time. Their first research target for these marmosets was Parkinson's disease, but they were also considering amyotrophic lateral sclerosis and Huntington's disease. Human proteins expressed in mammals are more likely to be similar to their natural counterparts than those expressed in plants or microorganisms. Stable expression has been accomplished in sheep, pigs, rats and other animals. In 2009, the first human biological drug produced from such an animal, a goat, was approved. The drug, ATryn, is an anticoagulant which reduces the probability of blood clots during surgery or childbirth and is extracted from the goat's milk. Human Alpha-1 antitrypsin, alpha-1-antitrypsin is another protein that has been produced from goats and is used in treating humans with this deficiency. Another medicinal area is in creating pigs with greater capacity for Organ transplantation, human organ transplants (xenotransplantation). Pigs have been genetically modified so that their organs can no longer carry retroviruses or have modifications to reduce the chance of rejection. Chimeric pigs could carry fully human organs. The first human transplant of a genetically modified pig heart occurred in 2023, and kidney in 2024. Livestock are modified with the intention of improving economically important traits such as growth-rate, quality of meat, milk composition, disease resistance and survival. Animals have been engineered to grow faster, be healthier and resist diseases. Modifications have also improved the wool production of sheep and udder health of cows. Goats have been genetically engineered to produce milk with strong spiderweb-like silk proteins in their milk. A GM pig called Enviropig was created with the capability of digesting plant phosphorus more efficiently than conventional pigs. They could reduce water pollution since they excrete 30 to 70% less phosphorus in manure. Dairy cows have been genetically engineered to produce milk that would be the same as human breast milk. This could potentially benefit mothers who cannot produce breast milk but want their children to have breast milk rather than formula. Researchers have also developed a genetically engineered cow that produces allergy-free milk. Scientists have genetically engineered several organisms, including some mammals, to include green fluorescent protein (GFP), for research purposes. GFP and other similar reporting genes allow easy visualization and localization of the products of the genetic modification. Fluorescent pigs have been bred to study human organ transplants, regenerating ocular photoreceptor cells, and other topics. In 2011, green-fluorescent cats were created to help find therapies for HIV/AIDS and other diseases as feline immunodeficiency virus is related to
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
. There have been suggestions that genetic engineering could be used to bring animals De-extinction, back from extinction. It involves changing the genome of a close living relative to resemble the extinct one and is currently being attempted with the passenger pigeon. Genes associated with the woolly mammoth have been added to the genome of an African elephant, African Elephant, although the lead researcher says he has no intention of creating live elephants and transferring all the genes and reversing years of genetic evolution is a long way from being feasible. It is more likely that scientists could use this technology to conserve endangered animals by bringing back lost diversity or transferring evolved genetic advantages from adapted organisms to those that are struggling.


Humans

Gene therapy uses genetically modified viruses to deliver genes which can cure disease in humans. Although gene therapy is still relatively new, it has had some successes. It has been used to treat
genetic 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 such as
severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...
, and
Leber's congenital amaurosis Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life. It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be ...
. Treatments are also being developed for a range of other currently incurable diseases, such as
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
, sickle cell anemia, Parkinson's disease,
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
,
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
, heart disease and muscular dystrophy. These treatments only effect somatic cells, meaning any changes would not be inheritable. Germline gene therapy results 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. In November 2018, He Jiankui announced that he had Genome editing, edited the genomes of two human embryos, in an attempt to disable the ''CCR5'' gene, which codes for a receptor that HIV uses to enter cells. He said that twin girls, Lulu and Nana, had been born a few weeks earlier and that they carried functional copies of CCR5 along with disabled CCR5 (mosaicism) and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature.


Fish

Genetically modified fish are used for scientific research, as pets and as a food source. Aquaculture is a growing industry, currently providing over half the consumed fish worldwide. Through genetic engineering it is possible to increase growth rates, reduce food intake, remove allergenic properties, increase cold tolerance and provide disease resistance. Fish can also be used to detect aquatic pollution or function as bioreactors. Several groups have been developing zebrafish to detect pollution by attaching fluorescent proteins to genes activated by the presence of pollutants. The fish will then glow and can be used as environmental sensors. The
GloFish The GloFish is a patented and trademarked brand of fluorescently colored genetically modified fish, genetically modified aquarium fish. They have been created from several different species of fish: zebrafish were the first GloFish available in ...
is a brand of genetically modified fluorescent zebrafish with bright red, green, and orange fluorescent color. It was originally developed by one of the groups to detect pollution, but is now part of the ornamental fish trade, becoming the first genetically modified animal to become publicly available as a pet when in 2003 it was introduced for sale in the USA. GM fish are widely used in basic research in genetics and development. Two species of fish, zebrafish and Oryzias latipes, medaka, are most commonly modified because they have optically clear Chorion (egg), chorions (membranes in the egg), rapidly develop, and the one-cell embryo is easy to see and microinject with transgenic DNA. Zebrafish are model organisms for developmental processes, Regeneration (biology), regeneration, genetics, behavior, disease mechanisms and toxicity testing. Their transparency allows researchers to observe developmental stages, intestinal functions and tumour growth. The generation of transgenic protocols (whole organism, cell or tissue specific, tagged with reporter genes) has increased the level of information gained by studying these fish. GM fish have been developed with promoters driving an over-production of
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) 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 ...
for use in the aquaculture industry to increase the speed of development and potentially reduce fishing pressure on wild stocks. This has resulted in dramatic growth enhancement in several species, including salmon, trout and tilapia. AquaBounty Technologies, a biotechnology company, have produced a salmon (called
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 gen ...
) that can mature in half the time as wild salmon. It obtained regulatory approval in 2015, the first non-plant GMO food to be commercialized. As of August 2017, GMO salmon is being sold in Canada. Sales in the US started in May 2021.


Insects

In biological research, transgenic fruit flies (''Drosophila melanogaster'') are
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. Mo ...
s used to study the effects of genetic changes on development. Fruit flies are often preferred over other animals due to their short life cycle and low maintenance requirements. They also have a relatively simple genome compared to many vertebrates, with typically only one copy of each gene, making Phenotype, phenotypic analysis easy. ''Drosophila'' have been used to study genetics and inheritance, embryonic development, learning, behavior, and aging. The discovery of Transposable element, transposons, in particular the P element, p-element, in ''Drosophila'' provided an early method to add transgenes to their genome, although this has been taken over by more modern gene-editing techniques. Due to their significance to human health, scientists are looking at ways to control mosquitoes through genetic engineering. Malaria-resistant mosquitoes have been developed in the laboratory by inserting a gene that reduces the development of the malaria parasite and then use homing endonucleases to rapidly spread that gene throughout the male population (known as a gene drive). This approach has been taken further by using the gene drive to spread a lethal gene. In trials the populations of ''Aedes aegypti'' mosquitoes, the single most important carrier of dengue fever and Zika virus, were reduced by between 80% and by 90%. Another approach is to use a sterile insect technique, whereby males genetically engineered to be sterile out compete viable males, to reduce population numbers. Other insect pests that make attractive targets are moths. Diamondback moths cause US$4 to $5 billion of damage each year worldwide. The approach is similar to the sterile technique tested on mosquitoes, where males are transformed with a gene that prevents any females born from reaching maturity. They underwent field trials in 2017. Genetically modified moths have previously been released in field trials. In this case a strain of pink bollworm that were sterilized with radiation were genetically engineered to express a Green fluorescent protein, red fluorescent protein making it easier for researchers to monitor them. Silkworm, the larvae stage of ''Bombyx mori'', is an economically important insect in sericulture. Scientists are developing strategies to enhance silk quality and quantity. There is also potential to use the silk producing machinery to make other valuable proteins. Proteins currently developed to be expressed by silkworms include; human serum albumin, Collagen alpha-1(IV) chain, human collagen α-chain, mouse monoclonal antibody and NGLY1, N-glycanase. Silkworms have been created that produce spider silk, a stronger but extremely difficult to harvest silk, and even novel silks.


Other

Systems have been developed to create transgenic organisms in a wide variety of other animals. Chickens have been genetically modified for a variety of purposes. This includes studying embryo development, preventing the transmission of Bird-flu, bird flu and providing evolutionary insights using reverse engineering to recreate dinosaur-like phenotypes. A GM chicken that produces the drug Kanuma (drug), Kanuma, an enzyme that treats a rare condition, in its egg passed US regulatory approval in 2015. Genetically modified frogs, in particular ''African clawed frog, Xenopus laevis'' and ''Western clawed frog, Xenopus tropicalis'', are used in Development (biology), developmental biology research. GM frogs can also be used as pollution sensors, especially for Endocrine disruptor, endocrine disrupting chemicals. There are proposals to use genetic engineering to control cane toads in Australia. The nematode ''Caenorhabditis elegans'' is one of the major model organisms for researching
molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
. RNA interference (RNAi) was discovered in ''C. elegans'' and could be induced by simply feeding them bacteria modified to express Double-stranded RNA, double stranded RNA. It is also relatively easy to produce stable transgenic nematodes and this along with RNAi are the major tools used in studying their genes. The most common use of transgenic nematodes has been studying gene expression and localization by attaching reporter genes. Transgenes can also be combined with RNAi techniques to rescue phenotypes, study gene function, image cell development in real time or control expression for different tissues or developmental stages. Transgenic nematodes have been used to study viruses, toxicology, diseases, and to detect environmental pollutants. The gene responsible for albinism in sea cucumbers has been found and used to engineer white sea cucumbers, a rare delicacy. The technology also opens the way to investigate the genes responsible for some of the cucumbers more unusual traits, including Hibernation, hibernating in summer, Evisceration (autotomy), eviscerating their intestines, and dissolving their bodies upon death. Flatworms have the ability to regenerate themselves from a single cell. * Until 2017 there was no effective way to transform them, which hampered research. By using microinjection and radiation scientists have now created the first genetically modified flatworms. The bristle worm, a marine annelid, has been modified. It is of interest due to its reproductive cycle being synchronized with lunar phases, regeneration capacity and slow evolution rate. Cnidarians, Cnidaria such as ''Hydra (genus), Hydra'' and the sea anemone ''Starlet sea anemone, Nematostella vectensis'' are attractive model organisms to study the evolution of immunity (medical), immunity and certain developmental processes. Other animals that have been genetically modified include snails, geckos, turtles, crayfish, oysters, shrimp, clams, abalone and sponges.


Regulation

Genetically modified organisms are regulated by government agencies. This applies to research as well as the release of genetically modified organisms, including crops and food. The development of a regulatory framework concerning genetic engineering began in 1975, at Asilomar Conference Grounds, Asilomar, California. The Asilomar conference on recombinant DNA, Asilomar meeting recommended a set of guidelines regarding the cautious use of recombinant technology and any products resulting from that technology. The
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 prot ...
was adopted on 29 January 2000 and entered into force on 11 September 2003. It is an international treaty that governs the transfer, handling, and use of genetically modified organisms. One hundred and fifty-seven countries are members of the Protocol and many use it as a reference point for their own regulations. Universities and research institutes generally have a special committee that is responsible for approving any experiments that involve genetic engineering. Many experiments also need permission from a national regulatory group or legislation. All staff must be trained in the use of GMOs and all laboratories must gain approval from their regulatory agency to work with GMOs. The legislation covering GMOs are often derived from regulations and guidelines in place for the non-GMO version of the organism, although they are more severe. There is a near-universal system for assessing the relative risks associated with GMOs and other agents to laboratory staff and the community. They are assigned to one of four risk categories based on their virulence, the severity of the disease, the mode of transmission, and the availability of preventive measures or treatments. There are four biosafety levels that a laboratory can fall into, ranging from level 1 (which is suitable for working with agents not associated with disease) to level 4 (working with life-threatening agents). Different countries use different nomenclature to describe the levels and can have different requirements for what can be done at each level. There are differences in the regulation for the release of GMOs between countries, with some of the most marked differences occurring between the US and Europe. Regulation varies in a given country depending on the intended use of the products of the genetic engineering. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety. Some nations have banned the release of GMOs or restricted their use, and others permit them with widely differing degrees of regulation. In 2016, thirty eight countries officially ban or prohibit the cultivation of GMOs and nine (Algeria, Bhutan, Kenya, Kyrgyzstan, Madagascar, Peru, Russia, Venezuela and Zimbabwe) ban their importation. Most countries that do not allow GMO cultivation do permit research using GMOs. Despite regulation, illegal releases have sometimes occurred, due to weakness of enforcement. The European Union (EU) differentiates between approval for cultivation within the EU and approval for import and processing. While only a few GMOs have been approved for cultivation in the EU a number of GMOs have been approved for import and processing. The cultivation of GMOs has triggered a debate about the market for GMOs in Europe. Depending on the coexistence regulations, incentives for cultivation of GM crops differ. The US policy does not focus on the process as much as other countries, looks at verifiable scientific risks and uses the concept of substantial equivalence.Emily Marden, Risk and Regulation: U.S. Regulatory Policy on Genetically Modified Food and Agriculture, 44 B.C.L. Rev. 733 (200

/ref> Whether gene edited organisms should be regulated the same as genetically modified organism is debated. USA regulations sees them as separate and does not regulate them under the same conditions, while in Europe a GMO is any organism created using genetic engineering techniques. 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 ScienceAmerican 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 Fear, uncertainty and doubt, 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 the U.S., the National Bioengineered Food Disclosure Standard (Mandatory Compliance Date: January 1, 2022) requires labeling GM foods. In Canada, labeling of GM food is voluntary, while in Europe all food (including processed food) or Compound feed, feed which contains greater than 0.9% of approved GMOs must be labeled. In 2014, sales of products that had been labeled as non-GMO grew 30 percent to $1.1 billion.


Controversy

There is controversy over GMOs, especially with regard to their release outside laboratory environments. The dispute involves consumers, producers, biotechnology companies, governmental regulators, non-governmental organizations, and scientists. 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. Most concerns are around the health and environmental effects of GMOs. These include whether they may provoke an allergic reaction, whether the transgenes could transfer to human cells, and whether genes not approved for human consumption could Outcrossing, outcross into the
food supply Food security is the state of having reliable access to a sufficient quantity of affordable, healthy food. The availability of food for people of any class, gender, ethnicity, or religion is another element of food protection. Similarly, househo ...
. 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 much less likely than scientists to perceive GM foods as safe. 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. As late as the 1990s gene flow into wild populations was thought to be unlikely and rare, and if it were to occur, easily eradicated. It was thought that this would add no additional environmental costs or risks – no effects were expected other than those already caused by pesticide applications. CAB Direct (database), CABD]
20083026795
However, in the decades since, several such examples have been observed. Gene flow between GM crops and compatible plants, along with increased use of broad-spectrum
herbicide Herbicides (, ), also commonly known as weed killers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page f ...
s, can increase the risk of Herbicide#Resistance, herbicide resistant weed populations. Debate over the extent and consequences of gene flow intensified in 2001 when a paper was published showing transgenes had been found in landrace maize in Mexico, the crop's Centre of diversity, center of diversity. Gene flow from GM crops to other organisms has been found to generally be lower than what would occur naturally. In order to address some of these concerns some GMOs have been developed with traits to help control their spread. To prevent the genetically modified salmon inadvertently breeding with wild salmon, all the fish raised for food are females, triploid, 99% are reproductively sterile, and raised in areas where escaped salmon could not survive. Bacteria have also been modified to depend on nutrients that cannot be found in nature, and genetic use restriction technology has been developed, though not yet marketed, that causes the second generation of GM plants to be sterile. Other environmental and agronomic concerns include a decrease in biodiversity, an increase in secondary pests (non-targeted pests) and evolution of resistant insect pests. In the areas of China and the US with Bt crops the overall biodiversity of insects has increased and the impact of secondary pests has been minimal. Resistance was found to be slow to evolve when best practice strategies were followed. The impact of Bt crops on beneficial non-target organisms became a public issue after a 1999 paper suggested they could be toxic to monarch butterflies. Follow up studies have since shown that the toxicity levels encountered in the field were not high enough to harm the larvae. Accusations that scientists are "Playing God (ethics), playing God" and other Religious views on genetically modified foods, religious issues have been ascribed to the technology from the beginning. With the ability to genetically engineer humans now possible there are ethical concerns over how far this technology should go, or if it should be used at all. Much debate revolves around where the line between treatment and enhancement is and whether the modifications should be inheritable. Other concerns include contamination of the non-genetically modified food supply,Chartered Institute of Environmental Health (2006
"Proposals for managing the coexistence of GM, conventional and organic crops Response to the Department for Environment, Food and Rural Affairs consultation paper"
. October 2006
the rigor of the regulatory process, consolidation of control of the food supply in companies that make and sell GMOs, exaggeration of the benefits of genetic modification, or concerns over the use of herbicides with
glyphosate Glyphosate (IUPAC name: ''N''-(phosphonomethyl)glycine) is a broad-spectrum systemic herbicide and crop desiccant. It is an organophosphorus compound, specifically a phosphonate, which acts by EPSP inhibitor, inhibiting the plant enzyme 5-en ...
. Other issues raised include the patenting of life and 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. There are large differences in consumer acceptance of GMOs, with Europeans more likely to view GM food negatively than North Americans. GMOs arrived on the scene as the public confidence in food safety, attributed to recent food scares such as Bovine spongiform encephalopathy and other scandals involving government regulation of products in Europe, was low. This along with campaigns run by various non-governmental organizations (NGO) have been very successful in blocking or limiting the use of GM crops. NGOs like the Organic Consumers Association, the Union of Concerned Scientists, Greenpeace and other groups have said that risks have not been adequately identified and managed and that there are unanswered questions regarding the potential long-term impact on human health from food derived from GMOs. They propose mandatory labeling or a moratorium on such products.Canadian Association of Physicians for the Environment (2013
"Statement on Genetically Modified Organisms in the Environment and the Marketplace"
. October 2013
Irish Doctors' Environmental Associatio
"IDEA Position on Genetically Modified Foods"
. Retrieved 25 March 2014.
PR Newswir

11 November 2013


References


External links


ISAAA database

GMO-Compass: Information on genetically modified organisms
{{Authority control Genetically modified organisms, Molecular biology 1973 introductions Articles containing video clips