What is a GMO?

GMOs, or genetically modified organisms are organisms whose genetic material has been altered
using genetic engineering. Genetic engineering is the modification of an organism's phenotype
by altering its genetic make-up. Genetic engineering is primarily performed by simple mating or
gene recombination. A latter section in this module elaborates further on how genetically
modified crops are created. . GMOs range from micro-organisms like yeast and bacteria to
insects, plants, fish and mammals. Genetically modified crops (GM crops) are those engineered
to introduce a new trait into the species. Purposes of GM crops generally include resistance to
certain pests, diseases, or environmental conditions, or resistance to chemical treatments (e.g.
resistance to a herbicide). Other purposed of genetic modification of crops is to enhance its
nutritional value, as seen in the case of golden rice.

The use of GM crops is widely debated. At the moment there is no known harm in consuming
genetically modified foods. GM foods are developed – and marketed – because there is some
perceived advantage either to the producer or consumer of these foods. This is meant to translate
into a product with a lower price, greater benefit (in terms of durability or nutritional value) or
both.

GM foods currently available on the international market have passed risk assessments and are
not likely to present risks for human health. In addition, no effects on human health have been
shown as a result of the consumption of such foods by the general population in the countries
where they have been approved.

History of GMOs

Additionally, with the production of golden rice, scientists have genetically modified food to
increase its nutrient value for the first time.

Risks Related to the Use of Genetically Modified Organisms Ecological Stability of the GMO

The application of genetic modification allows genetic material to be transferred from

any species into plants or other organisms. The introduction of a gene into different cells can
result in different outcomes, and the overall pattern of gene expression can be altered by the
introduction of a single gene. The sequence of the gene and its role in the donor organism may
have a relatively well-characterized function in the organism from which it is isolated. However,
this apparent “precision” in the understanding of a gene does not mean that the consequences of
the transfer are known or can be predicted. Copies of a gene may be integrated, additional
fragments inserted, and gene sequences rearranged and deleted—which may result in lack of
operation of the genes instability or interference with other gene functions possibly cause some
potential risks. Therefore, there could be a number of predictable and unpredictable risks related
to release of GMOs in the open environment. The report prepared by the Law Centre of IUCN,
the World Conservation Union (2004), enlists numerous environmental risks likely to occur by
the use of GMOs in the field. These risks are as follows.

Each gene may control several different traits in a single organism. Even the insertion of a single
gene can impact the entire genome of the host resulting in unintended side effects, all of which
may not be recognizable at the same time. It is difficult to predict this type of risk.

Environmental Risks
Genetic Contamination/Interbreeding

Introduced GMOs may interbreed with the wild-type or sexually compatible relatives.
The novel trait may disappear in wild types unless it confers a selective advantage to the
recipient. However, tolerance abilities of wild types may also develop, thus altering the native
species’ ecological relationship and behaviour.

Competition with Natural Species

Faster growth of GMOs can enable them to have a competitive advantage over the native
organisms. This may allow them to become invasive, to spread into new habitats, and cause
ecological and economic damage.

Increased Selection Pressure on Target and Nontarget Organisms

Pressure may increase on target and non-target species to adapt to the introduced changes as if to
a geological change or a natural selection pressure causing them to evolve distinct resistant
populations.
Ecosystem Impacts

The effects of changes in a single species may extend well beyond to the ecosystem. Single
impacts are always joined by the risk of ecosystem damage and destruction.

Impossibility of Followup

Once the GMOs have been introduced into the environment and some problems arise, it
is impossible to eliminate them. Many of these risks are identical to those incurred with regards
to the introduction of naturally or conventionally bred species. But still this does not suggest that
GMOs are safe or beneficial, nor that they should be less scrutinized.

Horizontal Transfer of Recombinant Genes to Other Microorganisms

One risk of particular concern relating to GMOs is the risk of horizontal gene transfer
(HGT). HGT is the acquisition of foreign genes (via transformation, transduction, and
conjugation) by organisms in a variety of environmental situations. It occurs especially in
response to changing environments and provides organisms, especially prokaryotes, with access
to genes other than those that can be inherited.
HGT of an introduced gene from a GMO may confer a novel trait in another organism,
which could be a source of potential harm to the health of people or the environment. For
example, the transfer of antibiotic resistance genes to a pathogen has the potential to compromise
human or animal therapy. HGT has been observed for many different bacteria, for many genes,
and in many different environments. It would therefore be a mistake to suppose that recombinant
genes would not spread to other bacteria, unless precautions are taken. Recent evidence from the
HGT technology confirms that transgenic DNA in GM crops and products can spread by being
taken up directly by viruses and bacteria as well as plant and animals cells. Very recently,
Yoshida et al. reported that HGT also moved from a nuclear monocot gene into the genome of
the eudicot parasite witchweed, which infects many grass species in Africa.
Some of the important potential impacts of HGT from GMOs include the following .

Adverse Effects on the Health of People or the Environment

These include enhanced pathogenicity, emergence of a new disease, pest or weed,

increased disease burden if the recipient organism is a pathogenic microorganism or virus,
increased weed or pest burden if the recipient organism is a plant or invertebrate, and adverse
effects on species, communities, or ecosystems.

Unpredictable and Unintended Effects

HGT may transfer the introduced genes from a GMO to potential pests or pathogens
and many yet to be identified organisms. This may alter the ecological niche or ecological
potential of the recipient organism and even bring about unexpected changes in structure or
function. Furthermore, the gene transferred may insert at variable sites of the recipient gene, not
only introducing a novel gene but also disrupting an endogenous gene, causing unpredictable and
unintended effects.

Loss of Management Control Measures

Regulatory approvals for field trials of GMOs often require measures to limit and control
the release in space and time. With the spread of the introduced gene(s) to another species by
HGT, a new GMO is created. This new GMO may give rise to adverse effects which are not
controlled by management measures imposed by the original license or permit.

Long-Term Effects
Sometimes the impact of HGT may be more severe in the long term. Even under
relatively strong selection pressure, it may take thousands of generations for a recipient organism
to become the dominant form in the population. In addition, other factors such as timing of
appropriate biotic or abiotic environmental conditions and additional changes in the recipient
organism could delay adverse effects.

Ethical Concerns
Various ethical issues associated with HGT from GMOs have been raised including
perceived threats to the integrity and intrinsic value of the organisms involved, to the concept of
natural order and integrity of species, and to the integrity of the ecosystems in which the
genetically modified organism occurs .
Several scientific evidence that has emerged on GMOs over the last couple of years
shows that there are several clear risks to human health and the environment. When genetic
engineers create GMO or transgenic plants, they have no means of inserting the gene in a
particular position. The gene ends up in a random location in the genetic material, and its
position is not usually identified. There are already several examples of such undesired effects
being identified in the US after approval (e.g., GM cotton with deformed cotton bolls; increased
lignin in GM soya, etc.) . Releasing genetically modified plants or crop into the environment
may have direct effects, including gene transfer to wild relatives or conventional crops,
weediness, trait effects on nontarget species, and other unintended effects.
It is widely accepted that the gene flow from GM crops is possible through pollen, from open-
pollinated varieties crossing with local crops or wild relatives. Because gene flow has happened
for millennia between land races and conventionally bred crops, it is reasonable to expect that it
could also happen with transgenic crops. Transgenic crops vary in their tendency to outcross, and
the ability to outcross depends on the presence of sexually compatible wild relatives or crops,
which varies according to location. However, some lines of evidence suggested that whether or
not gene flow between transgenic crops and wild relatives matters, in and of itself . If a resulting
transgenic/wild hybrid had some competitive advantage over the wild population, it could persist
in the environment and potentially disrupt the ecosystem.
In addition, some indirect effects of GMO were also observed which potentially harm to
the environment. For example, some transgenic traits such as the pesticidal toxins expressed by
Bt genes may affect nontarget species as well as the crop pests. It could happen but still uncertain
how likely it is. The toxicological studies of Monarch butterfly provide excellent examples,
which established the sensitivity of Monarch larvae to consuming Cry1Ab protein from Bacillus
thuringiensis (Bt) expressed in transgenic maize thereby triggering further to assess exposure and
population level effects .It was determined that larval exposure to pollen on a population-wide
basis was low, given the proportion of larvae in maize fields during pollen shed, the proportion
of fields planted in Bt maize, and the levels of pollen within and around maize fields that exceed
the toxicity threshold. However, an acute dose, even if several times higher than would be
expected in the field, is not equivalent to a low natural chronic dose experienced over a longer
period; therefore, a two-year study was undertaken and subsequently demonstrated that the risk
to Monarch butterfly populations is 0.6% of the total of Monarch butterflies breeding in the
North American Corn Belt .These results indicated negligible effects of Bt pollen to Monarch
butterfly larvae from extended exposures in field settings.
Extensive long-term use of herbicides glyphosate and gluphosinate in the Bt crops can promote
the development of resistant insect pests and weeds. The Royal Society in the year 2003 has
published the results of extensive farm-scale evaluations of the impacts of transgenic HT maize,
spring oilseed rape (canola), and sugar beet on biodiversity in the United Kingdom. These
studies found that the main effect of these crops compared with conventional cropping practices
was on weed vegetation, with consequent effects on the herbivores, pollinators, and other
populations that are feed on it. These groups were negatively affected in the case of transgenic
HT sugar beet, were, positive in case of HT Maiza and showed no effect in spring oilseed rape.
However, there is still insufficient evidence to predict what the long-term impacts of transgenic
HT crops will be on weed populations and associated in-crop biodiversity.
Most of the ecologists agree that gene flow is not an environmental problem unless it
leads to undesirable consequences. In the short term, the spread of transgenic herbicide
resistance via gene flow may create logistical and/or economic problems. Over the long term,
transgenes that confirm resistance to pests and environmental stress and/or lead to greater seed
production have the greatest likelihood of aiding weeds or harming nontarget species. However,
these outcomes seem unlikely for most currently grown transgenic crops. Many transgenic traits
are likely to be innocuous from an environmental standpoint, and some could lead to more
sustainable agricultural practices.

RISK FACTORS OF GMOS

There are a number of publications which address this issue. Maclean and Laight (2001) and
Dunham (1999) have produced very useful reviews which discuss many of the points raised in
this paper.

In our view the most important areas of risks which need to be considered in the use of
transgenics are:

1. human health
2. biodiversity
3. animal welfare
4. poor communities

In each of these categories there exists a multiplicity of pathways by which effects could, in
principle, be brought about. Rational and responsible assessment of risk requires that the
following properties are all considered:

1. source of the DNA of the target gene;

2. source of the non target DNA segments of the construct used;
3. site(s) of incorporation of the transgene within the recipient genome;
4. product of the transgene;
5. interaction of the transgenic product with other molecules in host and consumer;
6. possible molecular changes in transgene product during processing;
7. pleiotropic effects of transgene;
8. tissue specificity of transgenic expression; and
9. numbers of transgenic organisms capable of interacting with natural systems).

1.1 Human health

The risks to health will depend upon all of the factors listed above. In practical terms the most
important of these are likely to be the source of the DNA and the nature of the product.

The great majority (98 percent) of dietary DNA is degraded by digestive enzymes relatively
quickly (Royal Society, 2001) but use of viruses (disarmed or otherwise) as vectors, must
increase the risk factor significantly as these are organisms which are adapted to integrating into
host genomes and some represent risk factors for cancer induction. The work of Zhixong Li et
al. (2002) who induced leukaemia by using retroviral vectors in making transgenics for a
commonly used marker gene in mice and a recent report of leukaemia induction in a child
undergoing gene therapy for x-SCID using a retrovirus (Hawkes, 2002) show that this is not a
trivial risk. Arguments about risks and benefits attached to this form of gene therapy are current
(Kaiser, 2003).

At the other extreme the use of autotransgenics must be seen as posing a risk which is orders of
magnitude lower than that for allotransgenics and probably negligible. The major risk from the
production of the transgene will lie in the use of novel proteins or other molecules produced by
the transgenic organisms. Either in the native form or, following modifications in the human
body, such molecules could be inimical to human health (e.g. through allergies). It would seem
sensible to avoid the use of such substances except where strictly necessary and under rigorous
control.

Other potential risks may lie in incorporation of transgenic DNA into the genomes of resident
gut microflora (though this is likely to be very improbable) or a change in the pathogen spectrum
of the transgenic fish leading to it hosting a new pathogen which happens to be also a human
pathogen.

Maclean and Laight (2000) assessed risks to consumers as “very low”.

1.2 Biodiversity

The extent of aquatic diversity is both extremely large and relatively poorly understood
(Beardmore, Mair and Lewis, 1997). This means that the task of estimating the risks to aquatic
biodiversity at all of its levels from the use of GMOs or indeed, any genetically distinctive strain
used in aquaculture is monumentally large. Aquaculture has a further problem in that the (almost
always unintended) escapes of genetically distinct farmed fish are unpredictable and often large
in numbers. Stenquist (1996) in discussing transgenics in open ocean aquaculture, quotes some
relevant figures. Thus, 15 percent escapes for Atlantic salmon, escapes of 150 000 salmon and 50
000 trout in Chile and catch statistics for Atlantic salmon off Norway in which 15?20 percent of
the fish caught were of farmed origin. In Scotland an escape of 100 000 Atlantic salmon was
reported recently. It is clear that escapes of these magnitudes pose considerable problems and it
is not surprising that in some parts of Norway fish of farmed origin represent a majority of the
animals fished (Saegrov et al., 1997)

The major focus of attention in the literature lies, understandably, upon the effects of
escapes upon natural populations of the same species, but we must always bear in mind possible
impacts across an assemblage or ecosystem as a whole. The first general point to make is that
there is, in principle, no difference between the biodiversity risks from escapes of GMOs and
from fish genetically improved in some other way, e.g. by selective breeding or (in some
respects) from exotic species.

The second general principle is that such genetically improved forms including GMOs,
are developed for a specific set of environmental circumstances in which they enjoy an
advantage conferred by human decisions. In nature, however, such genetically distinct forms
may legitimately be regarded as mutant forms of the wild type. A considerable body of genetical
knowledge tells us that the probability of survival of mutant forms is extremely low because they
are disadvantaged in viability and/or fertility under natural conditions. Thus, for example, in the
genetically distinct farmed Atlantic salmon in Norway the males are very much less successful
than wild males in securing mates (Jonssen, 1997).

However, it must be conceded that in species like salmon where the farmed populations
outnumber the wild populations by orders of magnitude, the effects of escapes of any genetically
distinct genotype upon natural populations may be both deleterious and of significant size simply
as a result of “swamping”

An interesting model of the effects on a medaka (Oryzias latipes) population of

transgenic release has been produced by Muir and Howard (2001) using estimates of juvenile
and adult viability, age at sexual maturity, female fecundity, male fertility and mating advantage.
They were able to demonstrate that the transgene would spread in natural populations, despite
low juvenile viability, if transgenes have sufficient high positive effects on other fitness
components. It has been argued that this might lead to extinction but the selective pressure for
recombinant genomes with higher viability would be expected to be immense.

Maclean and Laight (2000) simulated the changes in frequency of a transgene expected
with different scenarios embracing a range of selective values including heterozyote advantage.
They note that “repeated small introductions [of the transgene] can have an effect on ...
frequency ... since the frequency of advantageous alleles rises much more rapidly than if a single
large introduction is considered”.

A major problem in assessing risk to natural populations is that of scale. Even if farmed
fish are at a selective disadvantage in natural conditions, the ratio of wild:farmed numbers may
in some areas, be relatively small. In these situations significant modification of the “native”
population and its role in the ecosystem is inevitable.

Whilst not providing a completely satisfactory answer, there is little doubt that making
farmed fish sterile would go a long way towards reducing the pressure upon such threatened
ecosystems. A number of research efforts to develop systems for sterile fish production are being
made. The techniques include triploidisation, antisense transgenics, ribozymes and gene
targeting (Maclean, 2002; Uzbekova et al., 2001; Maclean, pers. com.).

Provided that the best containment measures (physical and biological) are adopted, in our
opinion, in general risks to biodiversity by GMOs per se are probably extremely small, but in
specific cases, the risks and consequences may be large. As a general rule and adopting a
precautionary approvah (OECD, 1995), it is, however, clear that each individual case needs
careful study and appraisal and the best possible containment measures before approval for
uptake into commercial production is given.

1.3 Animal welfare

The direct or indirect effects of transgenesis upon the welfare of fish GMOs in
aquaculture are very poorly understood. In part, no doubt, this is because notions of cruel or
unnatural treatment in mammalian species translate, for a variety of reasons, imperfectly to fish.
Nevertheless, as life forms with highly developed nervous systems and with a range of
behavioural phenotypes which flow from this, fish qualify for welfare consideration.

There are a few studies which bear on this. Thus, for example, Devlin et al. (1995b)
reported changes in colouration, cranial deformities and opercular overgrowth and lower jaw
deformation in coho salmon transgenic for AFP and GH. After one year of development
anatomical changes due to growth of cartilage in the cranial and opercular regions were more
severe and reduced viability was evident.

The larger body of data on species farmed terrestrially shows dysfunctional development
leading to acromegaly, lameness and infertility in some GH transgenics in pigs and sheep.
However, in pigs dietary modification influencing nutritional levels of zinc proved successful in
avoiding such abnormalities (Pursel and Solomon, 1993; Pursel, 1998).

We have been unable to find systematic data on the incidence, in fish GMOs, of effects
such as those described by Devlin et al. (1995b) and this is probably because animal welfare is
not sufficiently widely recognised as an issue in relation to the use of GMOs. This is well
illustrated in the otherwise comprehensive and balanced review by Sin (1997) in which the
section on ethical issues contains no reference to animal welfare. Nevertheless, if GMOs are to
be used in aquaculture (and there are weighty arguments for so doing), concerns on this issue
will need to be properly satisfied. The Royal Society report (2001) devotes a significant amount
of space to this issue.

1.4 Poor communities

This term rather than poor countries is used because all poor countries contain rich people and
rich communities. The possible economic disadvantages of use of transgenics centre on two
issues:

1.4.1 Dependence on external agencies for seed fish

If transgenic fish become widely grown because they are much more efficient, and if special
broodstock are required to produce fry for on-growing to adults, which, cannot be used as
broodstock, a dependency is created. This dependency may be benign or oppressive, depending
on the arrangements made for seed supply.

1.4.2 Intellectual property rights

This is a very difficult issue indeed. Since genes may now be patented and therefore, enjoy
commercial value, the opportunities for dispute about equitable treatment of stakeholders in
cases where ownership of genes and strains is contested, are legion.

A recently published report (Commission on Intellectual Property Rights, 2002) states that
developing countries are frequently disadvantaged in the use of, and access to, IPR because of
increasingly protective attitudes taken by owners of IPR. However, the report also indicates that
developing countries are very heterogeneous in respect of their ability to use and develop IPR.