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An iconic image of
genetic engineering; this
1986 "autoluminograph" of a
glowing transgenic
tobacco plant bearing
the
luciferase gene of
fireflys strikingly
demonstrates the power and
potential of genetic
manipulation.
Genetic engineering,
genetic modification (GM),
and the now-deprecated gene
splicing are terms for the
process of manipulating
genes in an
organism, usually outside the
organism's normal
reproductive process.
It often involves the
isolation, manipulation and
reintroduction of
DNA into
model organisms, usually to
express a
protein. The aim is to
introduce new characteristics to
an organism in order to increase
its usefulness, such as increasing
the yield of a crop species,
introducing a novel
characteristic, or producing a new
protein or enzyme. Examples are
the production of human insulin
through the use of modified
bacteria and the production of new
types of experimental mice such as
the
OncoMouse (cancer mouse) for
research, through genetic
redesign.
Since a protein is specified by
a segment of DNA called a gene,
future versions of that protein
can be modified by changing the
gene's underlying DNA. One way to
do this is to isolate the piece of
DNA containing the gene, precisely
cut the gene out, and then
reintroduce (splice) the gene into
a different DNA segment.
Daniel Nathans and
Hamilton Smith received the
1978
Nobel Prize in physiology or
medicine for their isolation
of
restriction endonucleases,
which are able to cut DNA at
specific sites. Together with
ligase, which can join
fragments of DNA together,
restriction enzymes formed the
initial basis of recombinant DNA
technology.
Naming
"Transgenic
organism" is now the preferred
term for genetically modified
organisms with extra-genome
(foreign genetic) information, as
opposed to "genetically
engineered" or "genetically
modified" organisms (which may
refer to changes made within the
genome such as amplification or
deletion of genes).
Applications
One of the best known
applications of genetic
engineering is that of the
creation of
genetically modified organisms
(GMOs).
There are potentially momentous
biotechnology applications of
GM, for example oral
vaccines produced naturally in
fruit, at very low cost. This
represents, however, a spread of
genetic modification to medical
purposes and opens an ethical door
to other uses of the technology to
directly modify human genomes.
These effects are often not
traceable back to direct causes in
the
genome, but rather in the
environment or interaction of
proteins. The means by which
'genes' (in fact
DNA strands that are assumed
to have discrete effects) are
detected and inserted are inexact,
including such means as coating
gold particles with DNA to be
inserted and literally firing it
at strands of target DNA (see
gene gun), which is guaranteed
to cause insertions in at least
some random locations, which can
on rare occasion cause unplanned
characteristics.
Similar objections apply to
protein engineering and
molecular engineering for use
as drugs. However, a single
protein or a molecule is easier to
examine for 'quality
control' than a complete
genome, and there are more limited
claims made for the reliability of
proteins and molecules, than for
the genomes of whole organisms.
While protein and molecule
engineers often times acknowledge
the requirement to test their
products in a wide variety of
environments to determine if they
pose dangers to life, the position
of many genetic engineers is that
they do not need to do so, since
the outputs of their work are
'substantially the same as' the
original organism which was
produced by the original genome(s).
A radical ambition of some
groups is
human enhancement via
genetics, eventually by
molecular engineering. See
also:
transhumanism.
Genetic sequencing which is
used to identify each base in DNA
is exceedingly cheap. As of
mid-2005, it cost 1/10 of 1 cent
to sequence a single base. At the
current rate of price decrease,
the entire human genome could have
been sequenced for less than 100
U.S. dollars.
Genetic engineering and
research
Although there has been a
tremendous revolution in the
biological sciences in the past
twenty years, there is still a
great deal that remains to be
discovered. The completion of the
sequencing of the human genome, as
well as the genomes of most
agriculturally and scientifically
important plants and animals, have
increased the possibilities of
genetic research immeasurably.
Expedient and inexpensive access
to comprehensive genetic data has
become a reality, with billions of
sequenced nucleotides already
online and annotated. Now that the
rapid sequencing of arbitrarily
large genomes has become a simple,
if not trivial affair, a much
greater challenge will be
elucidating function of the
extraordinarily complex web of
interacting proteins, dubbed the
proteome, that constitutes and
powers all living things. Genetic
engineering has become the gold
standard in protein research, and
major research progress has been
made using a wide variety of
techniques, including:
- loss of function, such as in
a
knockout experiment, in
which an organism is engineered
to lack the activity of one or
more genes. This allows the
experimenter to analyze the
defects caused by this mutation,
and can be considerably useful
in unearthing the function of a
gene. It is used especially
frequently in
developmental biology. A
knockout experiment involves the
creation and manipulation of a
DNA construct in vitro, which,
in a simple knockout, consists
of a copy of the desired gene
which has been slightly altered
such as to cripple its function.
The construct is then taken up
by
embryonic
stem cells, where the
engineered copy of the gene
replaces the organism's own
gene. These stem cells are
injected into blastocysts, which
are implanted into surrogate
mothers. Another method, useful
in organisms such as Drosophila
(fruit fly), is to induce
mutations in a large population
and then screen the progeny for
the desired mutation. A similar
process can be used in both
plants and prokaryotes.
- gain of function
experiments, the logical
counterpart of knockouts. These
are sometimes performed in
conjunction with knockout
experiments to more finely
establish the function of the
desired gene. The process is
much the same as that in
knockout engineering, except
that the construct is designed
to increase the function of the
gene, usually by providing extra
copies of the gene or attracting
more frequent transcription.
- 'tracking' experiments,
which seek to gain information
about the localization and
interaction of the desired
protein. One way to do this is
to replace the wild-type gene
with a 'fusion' gene, which is a
juxtaposition of the wild-type
gene with a reporting element
such as Green Fluorescent
Protein (GFP)that
will allow easy visualization of
the products of the genetic
modification. While this is a
useful technique, the
manipulation can destroy the
function of the gene, creating
secondary effects and possibly
calling into question the
results of the experiment. More
sophisticated techniques are now
in development that can track
protein products without
mitigating their function, such
as the addition of small
sequences which will serve as
binding motifs to monoclonal
antibodies.
Ethics
Proponents of genetic
engineering argue that the
technology is safe, and that it is
necessary in order to maintain
food production that will
continue to match population
growth and help feed millions in
the third world more effectively.
Others argue that there is more
than enough food in the world and
that the problem is food
distribution, not production, so
people should not be forced to eat
food that may carry some degree of
risk.
Others oppose genetic
engineering on the grounds that
genetic modifications might have
unforeseen consequences, both in
the initially modified organisms
and their environments. For
example, certain strains of
maize have been developed that
are toxic to plant eating insects
(see
Bt corn). However, when those
strains cross-pollinated with
other varieties of wild and
domestic maize, the relevant genes
were passed on. This introduced a
new gene into the
gene pool of the maize
population outside of the crop
field. The ecological and
environmental effects of
transgenic plants are
continually being investigated.
Activists opposed to genetic
engineering say that with current
recombinant technology there is no
way to ensure that
genetically modified organisms
will remain under control, and the
use of this technology outside of
secure laboratory environments
carries unacceptable risks for the
future.
Some fear that certain types of
genetically engineered crops will
further reduce
biodiversity in the cropland;
herbicide-tolerant crops will
for example be treated with the
relevant herbicide to the extent
that there are no wild
plants ('weeds') able to
survive, and plants toxic to
insects will mean
insect-free crops. This could
result in declines in other
wildlife (e.g.
birds) which depend on weed
seeds and/or insects for food
resources. The recent (2003) farm
scale studies in the
UK found this to be the case
with GM
sugar beet and GM
rapeseed, but not with GM
maize (though in the last
instance, the non-GM comparison
maize crop had also been treated
with environmentally-damaging
pesticides subsequently (2004)
withdrawn from use in the
EU).
Proponents of current genetic
techniques as applied to food
plants cite the benefits that the
technology can have, for example,
in the harsh agricultural
conditions of
third world countries. They
say that with modifications,
existing crops would be able to
thrive under the relatively
hostile conditions providing much
needed food to their people.
Proponents also cite
golden rice and golden rice 2,
genetically engineered rice
varieties (still under
development) that contain elevated
vitamin A levels. There is hope
that this rice may alleviate
vitamin A deficiency that
contributes to the death of
millions and permanent blindness
of 500,000 annually.
Proponents say that
genetically-engineered crops are
not significantly different from
those modified by nature or humans
in the past, and are as safe or
even safer than such methods.
There is gene transfer between
unicellular
eukaryotes and
prokaryotes. There have been
no known genetic catastrophes as a
result of this. They argue that
animal husbandry and
crop breeding are also forms
of genetic engineering that use
artificial selection instead
of modern genetic modification
techniques. It is politics, they
argue, not economics or science,
that causes their work to be
closely investigated, and for
different standards to apply to it
than those applied to other forms
of agricultural technology.
Proponents also note that
Mother Nature has crossed species
and genera barriers in the past.
An oft-cited example is today's
modern red wheat variety, which is
the result of two natural
crossings made long ago. It is
made up of three groups of seven
chromosomes. Each of those three
groups came from a different wild
wheat grass. First, Mother Nature
crossed two of the grasses,
creating the
durum wheats, which were the
commercial grains of the first
civilizations up through the
Roman Republic. Then Mother
Nature crossed that 14-chromosome
durum wheat with another wild
grass to create what became modern
red wheat at the time of the
Roman Empire.
Economic and political effects
- Many opponents of current
genetic engineering believe the
increasing use of GM in major
crops has caused a power shift
in agriculture towards
Biotechnology companies gaining
excessive control over the
production chain of crops and
food, and over the farmers that
use their products, as well.
- Many proponents of current
genetic engineering techniques
believe it will lower pesticide
usage and has brought higher
yields and profitability to many
farmers, including those in
third world countries. A few GM
licenses allow third world
farmers to save seeds for next
year's planting.
- In January 2005, the
Hungarian government
announced a ban on importing and
planting of genetic modified
maize seeds, although these were
authorised by the EU.
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See also
