2019-2020

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A genetically modified organism (GMO) is any organism
whose genetic material has been altered using genetic
engineering techniques. A wide variety of organisms have been
genetically modified (GM), from animals to plants to small
microorganisms. Genes have been transferred within the same
species, across species (creating transgenic organisms) and
even across kingdoms. New genes can be introduced,
or endogenous genes can be enhanced, altered or knocked
out.
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 number of techniques are available
for inserting the isolated gene into the host genome. Herbert
Boyer and Stanley Cohen made the first genetically modified
organism in 1973, a bacteria resistant to the
antibiotic kanamycin. The first genetically modified animal, a
mouse, was created in 1974 by Rudolf Jaenisch, and the first
plant was produced in 1983. In 1994 the Flavr Savr tomato was
released, the first commercialized genetically modified food.
The first genetically modified animal to be commercialized was
the GloFish (2003) and the first genetically modified animal to
be approved for food use was the AquAdvantage salmon 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. There are proposals to
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remove the virulent 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 are publicly the most
controversial GMOs. The majority are engineered for herbicide
tolerance or insect resistance. Golden rice has been
engineered with three genes that increase its nutritional value.
Other prospects for GM crops are as bioreactors for the
production of biopharmaceuticals, biofuels or medicines.
Animals are generally much harder to transform and the vast
majority are still at the research stage. Mammals are the
best model organisms for humans, making ones genetically
engineered to resemble serious human diseases important to
the discovery and development of treatments. Human proteins
expressed in mammals are more likely to be similar to their
natural counterparts than those expressed in plants or
microorganisms. Livestock are 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 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 for
many deadly diseases. Although human gene therapy is still
relatively new, it has been used to treat genetic disorders such
as severe combined immunodeficiency, and Leber's congenital
amaurosis.
Definition
What constitutes a genetically modified organism (GMO) is not
always clear and can vary widely. At its broadest it 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.
Modern biotechnology is further defined as "In vitro nucleic acid
techniques, including recombinant deoxyribonucleic acid (DNA)

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and direct injection of nucleic acid into cells or organelles, or
fusion of cells beyond the taxonomic family."[12]
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.[13] The term GMO originally was not typically
used by scientists to describe genetically engineered
organisms until after usage of GMO became common in
popular media.[14] The United States Department of
Agriculture (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 techniques,
such as transgenesis.[15]
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.[16][17] 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 institutions and groups looking to ban GMOs. It also
poses problems as new processes are developed. The current
definitions came in before genome editing 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".[23] In contrast the
USDA has ruled that gene edited organisms are not considered
GMOs.[24]
Production

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A gene gun uses biolistics to insert DNA into plant tissue.
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[25] or artificially synthesized.[26] If the chosen gene or the
donor organism's genome has been well studied it may already
be accessible from a genetic library. The gene is then
combined with other genetic elements, including
a promoter and terminator region and a selectable marker.
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 or electroporation. DNA is generally inserted into animal
cells using microinjection, where it can be injected through the
cell's nuclear envelope directly into the nucleus, or through the
use of viral vectors. In plants the DNA is often inserted
using Agrobacterium-mediated recombination, biolistics 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.[33][34] In animals it is
necessary to ensure that the inserted DNA is present in
the embryonic stem cells.[30] Further testing
using PCR, Southern hybridization, and DNA sequencing is
conducted to confirm that an organism contains the new
gene.[35]

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Traditionally the new genetic material was inserted randomly
within the host genome. Gene targeting techniques, which
creates double-stranded breaks and takes advantage on the
cells natural homologous recombination repair systems, have
been developed to target insertion to exact locations. Genome
editing uses artificially engineered nucleases that create breaks
at specific points.
History of genetic engineering

Herbert Boyer (pictured) and Stanley Cohen created the first

genetically modified organism in 1973.
Various advancements in genetics allowed humans to directly
alter the DNA and therefore genes of organisms. In 1972 Paul
Berg created the first recombinant DNA molecule when he
combined DNA from a monkey virus with that of the lambda
virus.
Herbert Boyer 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, inserted it
into a plasmid and then induced other bacteria to incorporate
the plasmid. The bacteria that had successfully incorporated
the plasmid were then able to survive in the presence of
kanamycin.

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In 1974 Rudolf Jaenisch created the first genetically modified
animal.
In 1983 the first genetically engineered plant was developed
by Michael W. Bevan, Richard B. Flavell and Mary-Dell
Chilton.
In 1987 the gene gun was invented which helped in
bombarding recombinant DNA to host cell.
In 2000, Vitamin A-enriched golden rice was the first plant
developed with increased nutrient value.
Genentech announced the production of genetically engineered
human insulin in 1978. The insulin produced by bacteria,
branded humulin, was approved for release by the Food and
Drug Administration in 1982. In 1988 the first human antibodies
were produced in plants.
The first genetically modified crop, 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 attained approval to
commercially release the Flavr Savr tomato, the first genetically
modified food. In 2010, scientists at the J. Craig Venter
Institute announced that they had created the first synthetic
bacterial genome. They named it Synthia and it was the world's
first synthetic life form.
The first genetically modified animal to be commercialized was
the GloFish, a Zebra fish with a fluorescent gene added that
allows it to glow in the dark under ultraviolet light. It was
released to the US market in 2003. In 2015 AquAdvantage

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salmon became the first genetically modified animal to be
approved for food use.
Genetically modified bacteria

Left: Bacteria transformed with pGLO under ambient light

Right: Bacteria transformed with pGLO visualized under
ultraviolet light
Bacteria were the first organisms to be genetically modified in
the laboratory, due to the relative ease of modifying their
chromosomes. Genes and other genetic information from a
wide range of organisms can be added to a plasmid and
inserted into bacteria for storage and modification. 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. The
simplest model organisms come from bacteria, with most of our
early understanding of molecular biology coming from
studying Escherichia coli. 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.
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 enzymes, amino acids, flavourings, and other

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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, and this is where the majority of research into
genetically engineering food-producing bacteria has
gone. Genetically modified bacteria are used to produce large
amounts of proteins for industrial use. Generally the bacteria
are 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 to
treat diabetes. Other medicines produced include clotting
factors to treat haemophilia, human growth hormone to treat
various forms of dwarfism, interferon to treat some
cancers, erythropoietin for anemic patients, and tissue
plasminogen activator which dissolves blood clots.
Outside of medicine they have been used to produce biofuels.
With greater understanding of the role that
the microbiome plays in human health, there is the potential to
treat diseases by genetically altering the bacteria to, them, be
therapeutic agents. Ideas include altering gut bacteria so they
destroy harmful bacteria, or using bacteria to replace or
increase deficient enzymes or proteins.
Application of Bacillus thuringiensis (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

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express the Bt genes responsible for pest
resistance. Pseudomonas strains of bacteria cause frost
damage by nucleating water into ice crystals around
themselves. This led to the development of ice-minus bacteria,
that have the ice-forming genes removed. When applied to
crops they can compete with the non-modified bacteria and
confer some frost resistance.

This artwork is made with bacteria modified to express 8

different colors of fluorescent proteins.
Other uses for genetically modified bacteria
include bioremediation, 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. Bio art has also been created using genetically
modified bacteria. In the 1980s artist Jon Davis and geneticist
Genetically modified virus
Viruses are often modified so they can be used as vectors for
inserting genetic information into other organisms. 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
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human disease. This is most evident in curing patients
with severe combined immunodeficiency rising from adenosine
deaminase deficiency (ADA-SCID),[107] although the
development of leukemia in some ADA-SCID patients.
The most common virus used for gene delivery come
from adenoviruses 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 viruses, which have lower toxicity and
longer term expression, but can only carry about 4kb of DNA.
Herpes simplex viruses 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 retroviruses, but their
propensity for random integration is
problematic. Lentiviruses 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 alphaviruses, flaviviruses, measles
viruses, rhabdoviruses, Newcastle disease virus, poxviruses,
and picornaviruses.[108]
Most vaccines consist of viruses that have been attenuated,
disabled, weakened or killed in some way so that
their virulent 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, 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 to other
viruses.[111] Another potential approach is to use vectors to
create novel vaccines for diseases that have no vaccines
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available or the vaccines that do not work effectively, such
as AIDS, malaria, and tuberculosis.
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 behaviour of cancer cells
might offer an alternative way of killing tumours. Since then,
several researchers have developed genetically
modified oncolytic viruses that show promise as treatments for
various types of cancer.
Natural viral diseases, such as myxomatosis and rabbit
haemorrhagic disease, 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 have been created in the
laboratory[123] as well as others that target the developmental
stage of the animal.[124] There are concerns with using this
approach regarding virus containment[123] and cross species
infection.[125] Sometimes the same virus can be modified for
contrasting purposes.
Outside of biology scientists have used a genetically modified
virus to construct a lithium-ion battery and
other nanostructured materials. It is possible to
engineer bacteriophages to express modified proteins on their
surface and join them up in specific patterns (a technique
called phage display). These structures have potential uses for
energy storage and generation, biosensing and tissue
regeneration with some new materials currently produced
including quantum dots, liquid
crystals, nanorings and nanofibres. The battery was made by
engineering M13 bacteriaophages so they would coat
themselves in iron phosphate and then assemble themselves
along a carbon nanotube. This created a highly conductive
medium for use in a cathode, allowing energy to be transferred

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quickly. They could be constructed at lower temperatures with
non-toxic chemicals, making them more environmentally
friendly.

Genetically Modified Fungi

Fungi can be used for many of the same processes as bacteria.
For industrial applications, yeasts combines the bacterial
advantages of being a single celled organism that is easy to
manipulate and grow with the advanced protein modifications
found in eukaryotes. 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.
Fungi, being the most common pathogens of insects, make
attractive biopesticides. 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. Genetic engineering can improve virulence, usually
by adding more virulent proteins, increasing infection rate or
enhancing spore persistence. Many of the disease carrying
vectors are susceptible to entomopathogenic fungi. An
attractive target for biological control are mosquitos, vectors for
a range of deadly diseases, including malaria, yellow
fever and dengue fever. Mosquitos can evolve quickly so it
becomes a balancing act of killing them before
the Plasmodium they carry becomes the infectious disease, but
not so fast that they become resistant to the fungi. By
genetically engineering fungi like Metarhizium
anisopliae and Beauveria bassiana to delay the development of
mosquito infectiousness the selection pressure to evolve
resistance is reduced. Another strategy is to add proteins to the
fungi that block transmission of malaria or remove
the Plasmodium altogether.[134]

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A mushroom has been gene edited to resist browning, giving it
a longer shelf life. The process used CRISPR to knock out a
gene that encodes polyphenol oxidase. 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.
Genetically modified plant

Tissue culture used to regenerate Arabidopsis thaliana

Plants have been engineered for scientific research, to display
new flower colours, deliver vaccines and to create enhanced
crops. Many plants are pluripotent, 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.
Much of the advances in the field of genetic engineering have
come from experimentation with tobacco. Major advances in
tissue culture and plant cellular mechanisms for a wide range of
plants has originated from systems developed in tobacco. 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
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tools and procedures are well established making tobacco one
of the easiest plants to transform.
In research, plants are engineered to help discover the
functions of certain genes. The simplest way to do this is to
remove the gene and see what phenotype develops compared
to the wild type form. Any differences are possibly the result of
the missing gene. Unlike mutagenisis, genetic engineering
allows targeted removal without disrupting other genes in the
organism.[138] Some genes are only expressed in certain tissue,
so reporter genes, like GUS, can be attached to the gene of
interest allowing visualization of the location.[144] Other ways to
test a gene is to alter it slightly and then return it to the plant
and see if it still has the same effect on phenotype. Other
strategies include attaching the gene to a strong promoter and
see what happens when it is over expressed, forcing a gene to
be expressed in a different location or at
different developmental stages.[138]

Suntory "blue" rose

Some genetically modified plants are purely ornamental. They
are modified for flower color, fragrance, flower shape and plant
architecture.[145] The first genetically modified ornamentals
commercialized altered color.[146] Carnations were released in
1997, with the most popular genetically modified organism,
a blue rose (actually lavender or mauve) created in 2004. 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.

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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 in 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.
Genetically modified crops

Wild type peanut (left) and transgenic peanut with Bacillus

thuringiensis gene added (right) exposed to cornstalk borer
larva.
Genetically modified crops are genetically modified plants that
are used in agriculture. The first crops developed were used for
animal or human food and provide resistance to certain pests,
diseases, environmental conditions, spoilage or chemical
treatments (e.g. resistance to a herbicide). The second
generation of crops aimed to improve the quality, often by
altering the nutrient profile. Third generation genetically
modified crops could be used for non-food purposes, including
the production of pharmaceutical agents, biofuels, and other
industrially useful goods, as well as for bioremediation.[153]

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Kenyans examining insect-resistant transgenic Bacillus
thuringiensis (Bt) corn
There are three main aims to agricultural advancement;
increased production, improved conditions for agricultural
workers and sustainability. GM crops contribute by improving
harvests through reducing insect pressure, increasing nutrient
value and tolerating different abiotic stresses. Despite this
potential, as of 2018, the commercialized crops are limited
mostly to cash crops like cotton, soybean, maize and canola
and the vast majority of the introduced traits provide either
herbicide tolerance or insect resistance. Soybeans accounted
for half of all genetically modified crops planted in 2014.
The majority of GM crops have been modified to be resistant to
selected herbicides; usually a glyphosate or glufosinate based
one. Most currently available genes used to engineer insect
resistance come from the Bacillus thuringiensis bacterium.

Golden rice compared to white rice

Golden rice is the most well known GM crop that is aimed at
increasing nutrient value. It has been engineered with three
genes that biosynthesise beta-carotene, a precursor of vitamin
A, in the edible parts of rice. 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

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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 carotenoids, with further
development increasing this 23 times. In 2018 it gained its first
approvals for use as food.
Plants and plant cells have been genetically engineered for
production of biopharmaceuticals in bioreactors, a process
known as pharming. Work has been done
with duckweed Lemna minor, the algae Chlamydomonas
reinhardtii and the moss Physcomitrella
patens. Biopharmaceuticals produced
include cytokines, hormones, antibodies, enzymes and
vaccines, most of which are accumulated in the plant seeds.
Many drugs also contain natural plant ingredients and the
pathways that lead to their production have been genetically
altered or transferred to other plant species to produce greater
volume. Other options for bioreactors
are biopolymers and biofuels. Unlike bacteria, plants
can modify the proteins post-translationally, allowing them to
make more complex molecules.They also pose less risk of
being contaminated.
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.[174] 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.
Genetically modified animals
The vast majority of genetically modified animals are at the
research stage with the number close to entering the market

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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 that has increased 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.[183]
Mammals

Some chimeras, like the blotched mouse shown, are created

through genetic modification techniques like gene targeting.
The process of genetically engineering mammals is slow,
tedious, and expensive. However, new technologies are
making genetic modifications easier and more precise.[184] The
first transgenic mammals were produced by injecting viral DNA
into embryos and then implanting the embryos in
females.[185] The embryo would develop and it would be hoped
that some of the genetic material would be incorporated into the
reproductive cells. Then researchers would have to wait until
the animal reached breeding age and then offspring would be
screened for presence of the gene in every cell. The
development of the CRISPR-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.[186]

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A porcine model of hemophilia A.
Mammals are the best models for human disease, making
genetic engineered ones vital to the discovery and
development of cures and treatments for many serious
diseases. Knocking out genes responsible for human genetic
disorders allows researchers to study the mechanism of the
disease and to test possible cures. Genetically modified
mice have been the most common mammals used
in biomedical research, as they are cheap and easy to
manipulate. Pigs are also a good target as they have a similar
body size and anatomical
features, physiology, pathophysiological response and
diet.[187] Nonhuman primates are the most similar model
organisms to humans, but there is less public acceptance
towards using them as research animals.[188] 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.[191]
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.[192] Human alpha-1-antitrypsin is another protein
that has been produced from goats and is used in treating
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humans with this deficiency.[193] Another medicinal area is in
creating pigs with greater capacity for human organ
transplants (xenotransplantation). Pigs have been genetically
modified so that their organs can no longer carry
retroviruses[194] or have modifications to reduce the chance of
rejection.[195][196] Pig lungs from genetically modified pigs are
being considered for transplantation into humans.[197][198] There
is even potential to create chimeric pigs that can carry human
organs.[187][199]
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.

Mice expressing the green fluorescent protein

Scientists have genetically engineered several organisms,
including some mammals, to include green fluorescent

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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[213] as feline immunodeficiency
virus is related to HIV.[214]
There have been suggestions that genetic engineering could be
used to bring animals back from extinction. It involves changing
the genome of a close living relative to resemble the extinct one
and is currently being attempted with the passenger
pigeon.[215] Genes associated with the woolly mammoth have
been added to the genome of an African Elephant, although the
lead researcher says he has no intention of 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.[218]
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 disorders such as severe combined
immunodeficiency. Treatments are also being developed for a
range of other currently incurable diseases, such as cystic
fibrosis, sickle cell anemia, Parkinson's disease, cancer and
diabetes. 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.
Fish
Genetically modified fish are used for scientific research, as
pets and as a food source. Aquaculture is a growing industry,
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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.[239]
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 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.[242]
GM fish are widely used in basic research in genetics and
development. Two species of fish, zebrafish and medaka, are
most commonly modified because they have optically
clear chorions (membranes in the egg), rapidly develop, and
the one-cell embryo is easy to see and microinject with
transgenic DNA.[243] Zebrafish are model organisms for
developmental processes, regeneration, genetics, behaviour,
disease mechanisms and toxicity testing.[244] Their transparency
allows researchers to observe developmental stages, intestinal
functions and tumour growth.[245][246] 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.[247]
GM fish have been developed with promoters driving an over-
production of growth hormone for use in
the aquaculture industry to increase the speed of development
and potentially reduce fishing pressure on wild stocks. This has
resulted in dramatic growth enhancement in several species,
including salmon,[248] trout[249] and tilapia.[250] AquaBounty
Technologies, a biotechnology company, have produced a

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salmon (called AquAdvantage salmon) that can mature in half
the time as wild salmon.[251] It obtained regulatory approval in
2015, the first non-plant GMO food to be commercialized.
Insects

Overexpression of methyl-CpG–binding protein

2 in Drosophila impairs climbing ability (right) compared to the
control group (left).[255]
In biological research, transgenic fruit flies (Drosophila
melanogaster) are model organisms 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 phenotypic analysis
easy.[257] Drosophila have been used to study genetics and
inheritance, embryonic development, learning, behavior, and
aging.[258] The discovery of transposons, in particular the 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.[259]
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

24 | P a g e
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.[267]
Other insect pests that make attractive targets
are moths. Diamondback moths cause US$4 to $5 billion of
damage each year worldwide.[268] 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 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, human collagen
α-chain, mouse monoclonal antibody and N-
glycanase.[273] Silkworms have been created that
produce spider silk, a stronger but extremely difficult to harvest
silk,[274] and even novel silks.[275]
Regulation of genetic engineering
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, California.
The Asilomar meeting recommended a set of guidelines
regarding the cautious use of recombinant technology and any
products resulting from that technology.[301] The Cartagena
Protocol on Biosafety was adopted on 29 January 2000 and

25 | P a g e
entered into force on 11 September 2003.[302] It is an
international treaty that governs the transfer, handling, and use
of genetically modified organisms.[303] One hundred and fifty-
seven countries are members of the Protocol and many use it
as a reference point for their own regulations.[304]
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.[305] 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.[306] 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
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,
26 | P a g e
Russia, Venezuela and Zimbabwe) ban their
importation.[313] Most countries that do not allow GMO
cultivation do permit research using GMOs.[314]

A label marking this peanut butter as being non-GMO

The European Union (EU) differentiates between approval for
cultivation within the EU and approval for import and
processing.[315] While only a few GMOs have been approved for
cultivation in the EU a number of GMOs have been approved
for import and processing.[316] The cultivation of GMOs has
triggered a debate about the market for GMOs in
Europe.[317] 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. 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 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. Labeling can be mandatory up to

27 | P a g e
a threshold GM content level (which varies between countries)
or voluntary.
Genetically modified food controversies
The dispute involves consumers, producers, biotechnology
companies, governmental regulators, nongovernmental
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 outcross into
the food supply.[329] Before food is released it is tested for
animal toxicity and allergenicity.[330]

There is a scientific consensus 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.
Gene flow between GM crops and compatible plants, along
with increased use of broad-spectrum herbicides,[352] can
increase the risk of herbicide resistant weed
populations.[353] 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 crops 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
28 | P a g e
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.[364] 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.[365]
Accusations that scientists are "playing God" and
other religious issues have been ascribed to the technology
from the beginning.[366] 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, 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. Other issues raised include
the patenting of life and the use of intellectual property rights.
There are large differences in consumer acceptance of GMOs,
with Europeans more likely to view GM food negatively than
29 | P a g e
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.[379] 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.
Disadvantages of Genetically Modified or GM Crops
1. The production imposes high risks to the disruption of
ecosystem and biodiversity because the “better” traits produced
from engineering genes can result in the favouring of one
organism. Hence, it can eventually disrupt the natural process
of gene flow.

2. It increases the cost of cultivation and more inclined towards

marketization of farming that work on immoral profits.

3. The transgenic crops endanger not only farmers but also the
trade, and the environment as well.

4. It is biologically altered. Hence, biotech foods may pose a

human health risk.

5. The excessive production of genetically modified foods will

be rendered ineffective over time because the pests that these
toxins used to deter might eventually develop resistance
towards them.

What Are the Disadvantages of GMOs?

1. It can be dangerous to other insects that are important to our

ecosystem.
GMOs are believed to be dangerous to some insects because

30 | P a g e
new crop genes can be deadly to them. This is worth noting
when it comes to certain insects, such as butterflies, that are
not actually dangerous to crops.
2. It sparks concerns on changing the field of agriculture.
The process of making GMOs includes adding new genetic
material into an organism’s genome. In agricultural ecology,
this means introducing new genes in the genome of crops like
corn. Research on the effects of cultivation of GM crops in a
large scale has sparked various concerns, specifically those
ideas on ecosystems with GMO strains. As proven by certain
studies, GMO strains have the potential to change agriculture.
3. It can damage the environment.
Genetically modified crops can cause a threat to the
environment due to the fact that they are not a natural way to
plant and cultivate plants.
4. It causes unwanted residual effects.
A genetically modified plant can leave unwanted residual
substances that can remain in the soil for extended periods of
time. Agricultural regulators were alerted by research that
strains from GM crops would remain in the soil for years after
the crops were removed. Its data even reported that despite the
absence of these plants, the strain persisted for up to more
than 5 years.
5. It can create more weeds.
Take note that engineered crops can act as mediators in
transferring genes to wild plants, which can create more weeds.
To keep these new weeds under control, scientists then
invented new herbicides that were not necessary for non-GMO
weeds. These chemicals are also toxic to various mammals
and amphibians, who are feeding on GMO crops. Tests even
show that the uptake of these herbicides also has toxic
consequences on aquatic ecosystems.
6. It threatens crop diversity.
There is opposition to introducing GM genes on genetic
diversity because these genes can spread to other organic farm
crops and threaten crop diversity in agriculture. And if crop
diversity decreases, it will have a direct impact on our entire

31 | P a g e
ecosystem and would affect the population dynamics of other
organisms. The chance that a single genetically modified crop
strain could pollinate an already existing non-GM crop is
unlikely and unpredictable, and there are many conditions that
must be met for cross pollination to occur. However, when a
large scale plantation releases a GM strain during pollination,
this risk increases, where the cross pollination to non-GM
plants could create a hybrid strain. This means there is a
greater possibility of ecological novelty or new artificial strains
that are being introduced into the environment that could
potentially reduce biodiversity through competition.
7. It has trade issues.
In other countries and regions in the world, there may be
problems regarding trade matters, such as tariff and quota.

But What Does Being Genetically Modified Mean?

32 | P a g e
Being genetically modified means that a “Gene of Interest” from
one organism is extracted and is inserted into the genes of the
target organisms.

For example, if researchers want to make a particular organism

produce a nutrient that it naturally isn’t capable of producing,
they will look for another organism that can produce that
specific nutrient.

The “Gene of Interest” may come from bacteria, insects, and

animals that have the specific target trait. Hence, genetically
modified (GM) organisms are also called as “transgenic”
because they involve such transfer of genes.

The primary objectives of genetically modifying food products

are to increase yield and increase resistance to a pest, in
animals and plants respectively. Although some genetically
modified foods have already been approved and passed to be
safe as their traditional counterparts, their continued production
is still very controversial.

Did you know that despite their seemingly wonderful

characteristics, it is believed that several disadvantages may
result from the process of genetic engineering?

This is because the mere process of recombinant DNA

technology is already prone to a mutation that can lead to
unpredictable changes in the DNA and their proteins produced.
The following are just some of these harmful effects.

Disadvantages of Genetically Modified Foods On The

Environment

33 | P a g e
Release of toxins to soil

Toxins on soil

As you can see, the disadvantages of GM crops are much

larger than simply harming our health. Regarding
its environmental effects, toxicity is a huge issue concerning
GM crops. One particular example is the Bt Corn (Bacillus
Thuringensis Corn), which is widely known for its pest
controlling ability.

Bacillus thuringensis is a soil bacterium that has a gene that

produces certain protein toxins that effectively destroy pests
and insects, like larval caterpillars. This gene is then inserted
into the corn to make it more resistant to pests.

While such characteristic is helpful in controlling pests, this may

result to the releasing of the said toxin to the soil. Too much
toxins in the soil can prevent the growth of bacteria essential for
plant growth. As a result, the soil becomes void of all necessary
nutrients.

Resistance of pests to toxins

34 | P a g e
 Resistance of pests to toxins

In addition to that, the long term effects of GMOs are not

certain. Scientists fear that excessive production of genetically
modified foods that have toxin producing property will be
rendered ineffective over time. This is because the pests that
these toxins used to deter might eventually develop resistance
towards them.

Disruption of biodiversity

Biodiversity

The production of GM foods imposes high risks to

the disruption of biodiversity. This is because the “better” traits
produced from engineering genes can result in the favoring of
one organism. Furthermore, the introduction of genetically

35 | P a g e
modified organisms can eventually disrupt the natural process
of gene flow.

So what does this mean? Disrupted gene flow can also lead to
these genetically modified crops to become weeds because
they breed so rapidly and out-compete other crops.

How to avoid GMO foods?

36 | P a g e
37 | P a g e
Source: Pinterest

Social and Ethical Concerns

In addition to health and environmental issues, the production

of GM crops and animals has become the center of social and
ethical debates. And at present, it is still very difficult to
decipher their long term effects, hence, leaving consumers the
fear for safety.

Arguably, every food carries along with its associated health

benefits and risks. Upon knowing all the
mentioned disadvantages of genetically modified foods and
crops not only to human health but in the environment as well,
the decision is all up to you.

BUT ARE YOU STILL WILLING TO TAKE THE RISK?

Genetically modified foods: A critical review of their promise

and problems

Abstract

The term “genetic modified organisms (GMO)” has become a

controversial topic as its benefits for both food producers and
consumers are companied by potential biomedical risks and
environmental side effects. Increasing concerns from the public
about GMO, particularly in the form of genetic modified (GM)
foods, are aimed at the short- and long-lasting health problems
that may result from this advanced biotechnology. Complex
studies are being carried out around the world independently to
evaluate the advantages and disadvantages of GM foods. In

38 | P a g e
this paper, we attempt to summarize up-to-date knowledge
about the benefits and potential problems of GM food. We also
introduce some recent technological developments in GM foods
and their impact in the field.

Keywords

Genetic modified (GM) food

Transgenic
Safety
DNA
CRISPR-Cas9

1. Introduction

In July 2011, a group of protesters from Greenpeace, a non-

governmental, environmental organization, broke into an
experimental farm of the Commonwealth Scientific and
Industrial Research Organization (CSIRO), an Australian
federal government agency for scientific research, and
destroyed the entire crop of genetically modified wheat. In
August 2013, a research field of Golden Rice managed by the
Philippine Government's International Rice Research Institute
(IRRI), and other public sector partners was attacked by anti-
GMO (Genetically-Modified Organisms) activists. “Golden Rice”
expresses high levels of beta-carotene (a precursor of vitamin
A) thanks to its modified genetic properties. After 25 years’
bench work in the laboratory, Golden Rice, designed as a
cheap and effective way to deliver dietary source of vitamin A
for developing areas of the world, had finally reached the point
where field trials were practical [1]. Although different in many
ways from the 2011 CSIRO break-in, the 2013 incident
triggered strong condemnation by the scientific community,
though that reaction failed to achieve consensus among public

39 | P a g e
voices. The fundamental reason for the failure is the continuing
lack of comprehensive understanding of current agricultural
problems and the nature of GMO. In this review, starting with
the history of GMO, we address the motivation for GMO
(including GM foods), their benefits and risks, as well as the
impact of recent technology developments on GMO/GM foods.

2. What are GMOs and GM foods?

Genetic modification is a biological technique that effects

alterations in the genetic machinery of all kinds of living
organisms. GMO is defined as follows by WHO (World Health
Organization): “Organisms (i.e. plants, animals or
microorganisms) in which the genetic material (DNA) has been
altered in a way that does not occur naturally by mating and/or
natural recombination” [2]. The definition seeks to distinguish
the direct manipulation of genetic material from the millennial-
old practice of improvement in the genetic stock of plants and
animals by selective breeding. With DNA recombinant
technology, genes from one organism can be transferred into
another, usually unrelated, organism.
Similarly, the FAO (Food and Agriculture Organization of the
United Nations) and the European Commission define a GMO
as a product “not occur naturally by mating and/or natural
recombination” [3]. “GM foods” refer to foods produced
from genetically modified plants or animals.
However, Oliver [1] pointed out the aforementioned definitions
are somewhat imperfect, giving Triticale as an example.
Triticale is a grain widely used in bread and pasta. It was
developed the 19th century by crossing wheat with rye (a
conventional, selective breeding approach). However, the
resulting hybrid is sterile, and in the 1930s, the
chemical colchicine was used to generate polyploid embryo
cells, which are fertile. Triticale would seem unambiguously to
fit the definition of a GMO, even if the genetic modification is
somewhat primitive by current molecularly biological standards.
40 | P a g e
Thus, Oliver suggests “biotechnologically modified organism”
as a closer definition for GMO [1].

3. History of GM foods

The genesis of DNA modification technology can be traced

back to 1944, when scientists discovered that genetic material
can be transferred between different species [4]. Several
hallmark papers paved the way to the modern science of
molecular biology. In 1954, Watson and Crick discovered the
double helix structure of DNA, and the “central dogma” – DNA
transcribed to messenger RNA, translated to protein – was
established. Nobel Laureate Marshall Nirenberg [5] and others
had deciphered the genetic code by 1963. In 1973, Cohen et
al. [6] developed DNA recombination technology, showing that
genetically engineered DNA molecules can be transferred
among different species.
The history really begins with Charles Darwin's notions of
species variation and selection. Table 1 presents a sort of time-
capsule of the seminal discoveries that are crucial to modern
genomics.

Table 1. Crucial steps in the history of genetic

modification.
Time Event Time Event

Charles Darwin
published the first Jon W. Gordon et al. made
1859 1980
edition of “On the first transgenic mice
Origin of Species”

1865 Gregor Mendel 1983 Kary Mullis invented PCR

discovered that (polymerase chain

41 | P a g e
Time Event Time Event

heredity transmitted in reaction)

units

Generate the first

Frederick Miescher
1869 1985 transgenic domestic
isolated DNA
animal, a pig

Walter Sutton
developed First human genetic map
1902 1987
chromosome theory of was discovered
inheritance

Thomas Hunt Morgan

showed Human genome project
1911 1990
chromosomes carry was launched
genes

George Beadle and

Edward Tatum
First gene therapy trials on
1941 Hypothesized one 1991
humans
gene one enzyme
theory

Oswald Avery et al.

The second-generation
demonstrated DNA
1944 1992 genetic map of human
can transform the
genome was developed
properties of cells

Alfred Hershey and FDA approved the use of

1952 Martha Chase 1993 Bovine somatotropin (bST)
showed that genes to increase milk production

42 | P a g e
Time Event Time Event

are made of DNA in dairy cows

Francis H. Crick and

FDA approved the sale of
James D. Watson
1953 1994 the first GM food, the
described the double
FLAVR SAVR tomato
helix structure of DNA

Matthew Meselson
and Franklin Stahl The birth of Dolly the
1958 discovered the 1996 sheep, the first cloned
semiconservative animal
replication of DNA

Sydney Brenner et al.

reported that mRNA The E. coli genome was
1961 1997
ferries information sequenced
from DNA

Marshall Nirenberg et M. tuberculosis Bacterium

1966 al. cracked genetic 1998 and Roundworm C.
codes elegans were sequenced

Steward Linn and

The first human
Werner Arber
1968 1999 chromosome, chromosome
described first
22 was decoded
restriction enzyme

Stanley Cohen and

Mouse genome working
1973 Herbert Boyer 2002
draft was assembled
invented DNA cloning

43 | P a g e
Time Event Time Event

Richard Roberts and

The human genome
1977 Phil Sharp discovered 2003
sequencing was completed
introns

This table is modified based

on http://www.gmeducation.org/faqs/p149248-
20brief%20history%20of%20genetic%20modification.html and
https://www.genome.gov/Pages/Education/GeneticTimeline.pdf
.
The first genetically modified plants – antibiotic resistant
tobacco and petunias – were produced by three independent
research groups in 1983 [7], [8], [9]. Scientists in China first
commercialized genetically modified tobacco in early 1990s. In
1994 the US market saw the first genetically modified species
of tomato with the property of delayed ripening approved by
the Food and Drug Administration (FDA). Since then,
several transgenic crops have received FDA approvals,
including “Canola” with modified oil composition, cotton
and soybeans resistant to herbicides, etc. GM foods that are
available in the market include
potatoes, eggplants, strawberries, carrots, and many more are
in pipeline [10].

4. Do we need GM foods?

Before starting discussing the merits and demerits of GM foods,

it is important to set forth why there is such great effort to
develop them. There are three major challenges we are facing
that motivate our resort to the new technology for help.

4.1. Expansion of population

The current global human population is approximately 7.35

billion (United Nations Department of Economic and Social

44 | P a g e
Affairs/Population Division World Population Prospects: The
2015 Revision, Key Findings and Advance Tables). Fig.
1A shows the distribution of population around the world (upper
panel). Although growth rate of the world population has slowed
in recent years (1.24% per year 10 years ago versus 1.18% per
year in recent years), an annual addition of 83 million people is
expected. The estimated global population will be 8.5 billion in
2030, and 9.7 billion in 2050 (Fig. 1B). The expansion of
population is one of the major contributors
to undernourishment around the world. In 2016, the U.N. Food
and Agricultural Organization (FAO) reported that 795 million
people in the world were undernourished, among which 780
million people in developing regions [11]. Therefore the
eradication of hunger should be a priority of policy-making.

45 | P a g e
1. Download : Download high-res image (352KB)
2. Download : Download full-size image
Fig. 1. Distribution and projected growth of world's
population. (A) Distribution of the world's population by
age and sex, 2015 Source: United Nations, Department of
Economic and Social Affairs, Population Division (2015).
World Population Prospects: The 2015 Revision. New
York: United Nations. (B) Population of the world:
estimates, 1950–2015, medium-variant projection and
80% and 95% confidence intervals, 2015–2100.
(Charts are adopted
from http://esa.un.org/unpd/wpp/publications/files/key_findings_
wpp_2015.pdf).
Arguably the most realistic solution for matching increased
global demand for crops is to boost the crop yields on currently
cultivated land. Currently, the rate of increase in crop-yield is
less than 1.7% whereas the annual increase in yield needs to
be 2.4% to meet the demands of population growth, improved
nutritional standards and decreasing arability (see below) [12].
This is a daunting task, which seems only achievable by means
of optimization of crop genetics coupled with quantitative
improvements in management of the agricultural system.

4.2. Decrease in arable land

FAO predicted that the finite amount of arable land available for
food production per person will decrease from the current
0.242 ha to 0.18 ha by 2050 [13]. This problem confounds
those of population growth and malnutrition. Yet our ability to
bring additional acreage under cultivation seems limited. The
alternative is greater yield per acre, which in turn must come
from greater agriculture inputs, such as fertilizer, water, pest
and weed control – and/or genetic improvement [1]. This
scenario is compounded by several complicating factors: (1)
the increased demand for biofuel and feedstock production; (2)
accelerated urbanization; (3) land desertification, salinization,
46 | P a g e
and degradation; (4) altered land use from staple foods
to pasture, driven by socioeconomic considerations; (5) climate
change; (6) water resource limitation.

4.3. Bottleneck of conventional and modern breeding

Conventional breeding relies on sexual crossing of one parental

line with another parental line, in hopes of expressing some
desired property (e.g. disease resistance) [1]. To select for the
desired trait and to dilute irrelevant or undesired traits, breeders
choose the best progeny and back-cross it to one of its parents
(plant or animal). The process usually takes several years
(depending on generational time, e.g. 10–15 years for wheat)
before actual expression of the desired trait that can be
assessed, and further expanded by conventional breeding to
commercially useful numbers. Besides the inherently long
generation times, the following facts limit the development of
conventional breeding: Prerequisite to breeding strategies is
the existence of genetic variation that is, existence of an
available gene-pool manifesting the desired traits, and sexual
compatibility of organisms with those traits. In fact, nowadays
genetic variety has dwindled (probably as a result of past
efforts at optimization), thus we operate in a restricted space for
improvement. Modern methodologies can increase this space
by utilizing chemicals or radiation to introduce new mutational
variation. However, these are blunt instruments that result in
improved traits only by random chance and sparse luck.
Indeed, the non-selectivity of these methods probably extend
the breeding timeline [1].
Taking these facts into account, the emergence of biological
technologies and the development of GM foods promise to
reduce dramatically production timelines to new strains, and to
provide us with optional strategies to achieve sustainable global
food security.

5. Generation of GM crops

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In order to generate GM foods, researchers need to introduce
the gene(s) coding for certain traits into a plant cell, and then
regenerate a plant through tissue culture. When and where the
transferred gene is expressed is usually inherent in the scheme
to optimize the property of the product. Generally speaking,
there are three ways to modify genes in the cells.

5.1. Directly transfer DNA

The most widely used technique for delivering exogenous DNA

is microparticle bombardment. The technique was developed in
the late 1980s by Sanford [14]. Naked, engineered DNA is
coated on gold or tungsten microparticles, which, in turn, are
delivered at high velocity into targeted tissues, such as
embryonic tissues from the seed or meristems, propelled by
pressurized helium. There are other ways to deliver DNA into
plant cells, including electroporation (letting the negatively
charged DNA move down an electric potential gradient)
into protoplasts, microinjection, chloroplast transformation, silic
on-carbide slivers, mesoporous silica nanoparticles, etc. [15].
However, particle bombardment remains more effective at
transferring large DNA fragments – even whole chromosomes
– simultaneously [16].

5.2. Indirectly using bacterial vehicle

The use of Agrobacterium tumefaciens opened a new era for

inserting exogenous genes into plant cells. The soil
bacterium A. tumefaciens infects plants, forming a gall at the
crown. The bacteria actually alter the genome of the plant, not
only causing proliferation of the plant cells, but also enabling
the plant to produce modified amino acids as a specialized food
source for themselves. The bacteria possess a tumor-
inducing plasmid (“Ti-plasmid”), which enable them to
accomplish gene-insertion; researchers hijack the plasmid by

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inserting “designer gene's” into the T-DNA (transfer DNA)
section of the Ti-plasmid.

5.3. Direct editing of genomic DNA

In 2012, the “CRISPR-Cas9” system was developed. It

constitutes a revolutionary genome editing tool, and provides
another method to alter genes in various type of cells [17], [18].
This technique dramatically increases the efficiency of genetic
engineering, making the work with plants much easier [19].
Cas9 is a DNA endonuclease originally found in bacteria,
where it protects the host bacteria from invading DNA
molecules (e.g. viruses). The endonuclease is guided to the
invading/targeting DNA by a special “guide RNA” (gRNA),
whose sequence is complementary to the invading sequence to
be expunged. Thus guided by the offensive, Cas9 utilizes its
two active sites to cleave both strands of the double-stranded
DNA. The newly formed DNA double-stranded breaks (DSBs)
are then repaired by two different mechanisms inside cells: The
“non-homologous end joining” (NHEJ) mechanism can cause a
small deletion or random DNA insertion, leading to a truncated
gene or knockout, while the “homologous recombination” (HR)
mechanism allows the addition of a donor DNA into the
endogenous gene at the break site (Fig. 2).
The rapid development of these cutting-edge biotechnologies
has also challenged the food regulation law. The US
Department of Agriculture (USDA) has determined that the
current regulations are not suitable for several genome-edited
crops, therefore, on November 18th, 2015, the USDA released
provisional plans to revise its guidelines for GM crops. GM
foods produced in the U.S. are listed in Table 2.

6. Benefits of GM foods

6.1. Agronomic benefits

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1996–2012 saw an increase of more than 370 million tons of
food crops. One-seventh of the increased yield is attributed to
GM crops in the U.S. To achieve an equal increase in yield as
delivered by GM crops, it is estimated that an addition of more
than 300 million acres of conventional crops would have been
needed [20], [21]. These additional 300 million acres would
necessarily be lands requiring more fertilizer or irrigation, or
carved out tropical forests. Such conversion of land would
generate serious ecological and environmental stress to the
world. A report from Graham Brookes and Peter Barfoot (17)
arrived as similar conclusions: for the period 1996–2013 they
estimate that biotechnology was responsible for additional
global production of 138 million tons of soybeans, 274 million
tons of corn, 21.7 million tons of cotton lint, and 8 million tons
of canola. If those biotechnologies had not been available, to
maintain equivalent production levels would have required an
increment of 11% of the arable land in the US, or 32% of
the cereal area in the EU.

6.2. Economic benefits

From 2006 to 2012, the global increase in farm income

from GM food had reached $116 billion, almost triple that of
previous 10 years [20], [21]. According to the estimation from
James and Brookes, about 42% of the economic gain was from
the increased yield due to advanced genetics and resistance to
pests and weeds. The decreased costs of production (e.g. from
reduced pesticide and herbicide usage) contributed the
remaining 58%.

6.3. Modification of the chemical composition in food

Some genetic modification is specifically targeted to enrich

certain nutrients or substances having high therapeutic and
pro-health value, including vitamins A, C, E, unsaturated fatty
acids, alimentary cellulose and probiotics [22]. The

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aforementioned “Golden Rice” is a significant example. It
ameliorates malnutrition in an effective and economic way.
Similarly, using this biotechnology, researchers can also alter
the amino acid composition of proteins as well as the content of
carbohydrates. The former is exemplified by sweet lupine, of
which the content of methionine is enriched [23], [24]. The
generation of Amflora, a modified potato variety, is a good
example for the latter scenario.
Enhanced nutritional value in transgenic products has been
obtained by manipulating their composition of carbohydrates.
Let us consider further the example of Amflora. The bulk
of polysaccharides in the potato-bulb is formed by two types of
starch: amylose and amylopectin. Amylose is useful only as
food starch, while amylopectin is widely used in the production
of non-food starch, paper, and in textile processing. The
synthesis of starch requires various enzymes, which include a
granule-bound starch synthase (GSBB), the primary function of
which involves the production of amylose. In the absence of
GSBB, amylopectin is produced exclusively. Exploiting this
knowledge has led to methods to modify the composition
of potato starch. The transgenic process involves the
introduction into potato bulbs of an additional copy of the
GSBB-coding gene. Counter intuitively, the extra gene in fact
suppressed expression of GSBB, by a process know as “co-
suppression”, a.k.a. “gene silencing”. The resultant Amflora
potato is with decreased amylose, but rich in amylopectin [25].

6.4. Improvement in food processing

The GM technology can also be employed to facilitate food

processing. A notable achievement is “Flavr Savr” tomatoes.
They were produced by the California company, Calgene, in
1992. The genetic alteration consists of introduction of an
antisense gene, which suppresses the
enzyme polygalacturonase; the consequence is to slow down
the ripening of tomatoes and thus allow longer shelf life for the
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fruits. The composition in potato bulbs has also been altered
by gene editing. For instance, using
a cyclodextrin glycosyltransferases gene from bacteria,
potatoes exhibit greater stability of brightness factors and, thus,
a more attractive appearance [26].
Genetic modification is not limited to plants, but is also applied
to animal products. Some researchers are exploring transgenic
fish with a view to enhancing the generation of growth
hormones to accelerate growth and body mass [27], [28], [29].
Very recently the FDA (the US Food and Drug Administration)
has approved the first genetically engineered animal,
“AquAdvantagea” salmon – a fast-growing salmon – for human
consumption in the United States. The decision was made after
two decades of regulatory limbo. Because the fish grow to full
size in 18 months, rather than 3 years, and with less demand
for food resources per kilogram of harvested fish,
farming “AquaAdvantagea” may ease pressure caused by
heavy fishing of wild populations. Meanwhile, quite a few
attempts have been made to generate milk with decreased
content of lactose or humanized bovine milk [29], [30].

6.5. Products for therapeutic purposes

Genetic engineering techniques enable the expression of viral

or bacterial antigens in the edible portion of plant
cells [28], [31], [32]. In theory, thus, transgenic foods could
serve as oral vaccines, capable of stimulating the immune
system, via mucosal immunity, to produce antibodies. A variety
of crops (e.g. rice, maize, soybean and potatoes) are under
study as potential bearers of edible vaccines against different
infections, including Escherichia coli toxins, rabies
virus, Helicobacter pylori bacteria, and type B viral
hepatitis [27], [28], [31], [32], [33], [34].

7. Potential risks of GM foods

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The debates over GM foods focus mostly on uncertainties
concerning the potential adverse effects of GM foods on human
health and environmental safety. The anxiety among
consumers can be attributed to four sources: the difficulty of the
scientific community in explaining concisely to the lay public the
biological techniques involved; concerns about the improper
dissemination of GM foods; and the ethical principles inherent
in traditional food processing; the misgivings with regards to the
adequacy of evaluation of the GM foods.

7.1. Health risks associated with GM foods

Three major health risks potentially associated with GM foods

are: toxicity, allergenicity and genetic hazards. These arise
from three potential sources, the inserted gene and their
expressed proteins per se, secondary or pleiotropic effects of
the products of gene expression, and the possible disruption of
natural genes in the manipulated organism [10].
“Starlink” maize provides an example of a food hazard caused
directly by the expression of the inserted
gene [29], [35], [37], [38], [39]. The modified plant was
engineered with genetic information from Bacillus
thuringinesis in order to endow the plant with resistance to
certain insects. The inserted gene encodes a protein, called
Cry9c, with pesticidal properties, but with an unintended, strong
allergenicity. Several cases have been reported of allergic
reaction in consumers after consuming the “Starlink” maize.
Modification on the expression level of natural components of
the manipulated organism can also exacerbate allergy. One
example is the production of soybeans enriched in the amino
acid methionine. The enhanced synthesis of this amino acid is
the result of a gene isolated from Brazil nuts. As a
consequence, some consumers allergenically sensitized to
these nuts have allergic reactions to the transgenic soybean.
Secondary and pleiotropic effects are much less straightforward
to recognize than direct effects of the gene or its products. The
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modified gene may encode an enzyme involved in otherwise
natural metabolic pathways of the modified organisms. Such
changes might alter the levels of other metabolites, including
toxic ones, at some “metabolic distance” from actual metabolic
perturbation. Connecting the causative dots presupposes an
intimate understanding of the biochemical and regulatory
pathways – which may be beyond current comprehension.
Another scenario of potential risk is that the inserted gene
might disrupt the integrity of existing genomic information in the
plant, leading to inactivation, or other modulation, of
endogenous genes. Again, such a disruption might be
envisioned to activate (or deactivate) metabolic processes
involving product or toxins, or their detoxification – in any case
by events far removed from the known and intended effect of
the inserted gene, and thus confounding our ability to draw a
causal connection between the inserted gene and the alleged
effect.

7.2. Ecological risks associated with GM food

7.2.1. Selection of resistance

Currently, the majority of GM foods are aimed at endowing the

altered plant two desirable properties – pest-
resistance or herbicide-resistance. Insect-resistant crops are
typically designed to express insecticidal crystal proteins
(CRY), naturally produced by the soil bacterium Bacillus
thuringiensis (Bt). Herbicide-tolerant crops are designed to
express enzymes that protect against herbicides (primarily
the glyphosate Roundup™), often by their ability to degrade the
herbicide. The strategy is clever: the human-applied herbicide
kills the weeds, but does not harm the crop-plant.
The use of these two technologies greatly reduces immediate
input costs incurred by farmers – the battle against weeds
becomes much less labor-intensive, and the battle again
insects requires much less expensive and toxic pesticides. But,

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in the long-term, can these strategies really out-fox Nature, in
her ineluctable progress toward selecting better-adapted
species? When heartier weeds and insects evolve, what then?
It seems almost inevitable that, in a few years, insects and
weeds will respond to the human-made pressures in their
habitats by evolving ways to nullify our clever design
of transgenic crops [10].

7.2.2. Disruption of the food web

Another issue is the possibility that the insect-resistant plants

might increase the number of minor pests while reducing the
major type of pest. The scenario here is that the pest
population might shift from those put-off by the engineered
plants to other, undaunted species. This shift, in turn, might
unleash a pervasive disruption of the entire food chain, with
new predators of the new insect species, and so on up to the
top of the chain [10]. Or the disruption might work in the other
direction, whereby residues of herbicide or insect resistant
plants might generate negative effects on organisms (e.g.
bacteria, fungi, etc.) found in surrounding soil [40].

7.2.3. Resistance to antibiotics

Development of resistance to antibiotics is a scourge well

known to medical science, and is traceable to the over-use of
therapeutic antibiotics in medicine and agriculture. In the
processes of genetic modification, antibiotics are also
frequently employed, typically as selection markers, to
distinguish successfully transformed bacteria from those in
which the transfecting genes did not take hold. Thus, the
machinations to genetically modify an organism carries the risk
of transferring the genes of antibiotics resistance into the
benign bacteria comprising the microflora of human and
animal gastrointestinal tracts, or, worse yet, to pathogenic
bacteria harbored by the consumer of GM a food, because
bacteria, good and bad, are quite capable of shuttling useful
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genes – like those that protect them from nasty antibiotics –
around by horizontal transfer between species.

8. Conclusions

The question of whether or not humans should eat food

from genetically modified organisms – and, therefore, if they
should develop and propagate them – is clearly not amenable
to a simple “yes” or “no”. Indeed, a wise answer comprehends
a diverse array of scientific expertise, not only in files of
molecular biology, but also in agricultural economics, animal
and microbial ecology, food technology, and immunology – a
breadth of expertise unlikely to be found in one person.
The arguments, pro and con, reverberate the whole history of
human technological development, pitting the clear advantages
of intended consequence against the mucky possibilities of
unintended consequence. One needs to think only of the fossil-
fueled industrial revolution versus global warming. Or of that
much-heralding replacement for fossil fuel, nuclear
power generation, versus Tokushima. Certainly, many of the
risks of GM crops, noted above, are speculative, but they are
scientifically plausible, and offered in good faith. Ignoring them
in a euphoria of immediate advantage is equally unscientific.
Drawing from past experience it seems unlikely the
technological momentum toward genetically modified foods can
be stopped dead in its tracks. Or should be. The immediate
advantages are too tangible to ignore or set aside out of fear of
the unknown and unintended disadvantages.
With un-Hamlet-like indecisiveness, we suggest evaluating,
gingerly, and always with keen (and collective) circumspection
toward the first signs of problems.

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