Determining the Safety of Transgenic Insects


Genetically modified insects (GMI) have generated intense interest among
a number of interested parties: the lay-public and environmental
communities because of potential adverse ecosystem and health impacts;
scientific circles that envision revolutionary construction and
application of novel organisms for pest and health management;
legislators facing challenging new ideologies regarding the assessment of
risk, philosophy of creation issues, and identification and protection of
intellectual property rights as this new technology develops and reaches
field application phases; and multi-national business concerns that may
realize huge financial gains from the development of novel organisms that
benefit agricultural industries or alleviate human health threats. The
controversy surrounding the potential pros and cons of genetic
engineering is so well entrenched in mainstream media that it is commonly
the subject of discussion in newspapers, magazines, popular books,
television, and radio.

Genetic engineering (GE) of plants, insects, animals, and microorganisms
differs from traditional genetic selection for desirable traits in a
number of ways:
(1) GE by necessity involves in vitro genomic manipulations of the target
(2) GE requires the molecular engineer to have certain information (DNA
sequences, or position or restriction enzyme sites) for the relevant
region of DNA that is to be manipulated;
(3) GE requires physical isolation of small useful pieces of DNA from the
donor region of interest for manipulation and insertion;
(4) GE typically involves the characterization of genotypes prior to the
analysis of phenotypes, whereas in traditional breeding programs
phenotypes are usually analyzed for desirable traits;
(5) viruses, plasmids, microinjection, or gene guns are used to introduce
foreign DNA into the target organism rather than recombination using
gametes or compounds that induce mutagenesis from which viable organisms
are then screened.
Often the genetic constructs inserted into the recipient genome contain
material that originated from organisms in different phyla or even
kingdoms and the resulting organisms express traits that could never have
been achieved with traditional genetic manipulations. Consequently, this
new technology may present sets of unique inherent risks that have not
been seen before with traditional genetic modification strategies.

There is intense intellectual and practical interest in creating insects
that are refractory to disease, in particular arthropod borne pathogens
that cause human maladies. Several research laboratories are attempting
to develop transgenic mosquitoes that contain novel genetic constructs
that interfere with the transmission of pathogens that cause malaria, and
dengue and yellow fevers in humans. Limited critical laboratory
examination of the fitness of these transgenic mosquitoes has begun, and
it is envisioned that field trials are still several years away. As
potential future field trials with GMIs (e.g., mosquitoes and pink boll
worms) become more likely, the movement of these organisms from secure
laboratory facilities for release and establishment in natural systems
raise critical issues regarding regulatory oversight, safety evaluation,
risk assessment, and potential non-target impacts. With respect to these
preceding issues, classical biological control, the deliberate
introduction and release of exotic organisms for the control of non-
native invasive pests, may provide guidance in developing protocols for
issues pertaining to GMI releases. Many issues that proposed GMI releases
will eventually face are fundamentally similar to releases of non-GMI
classical biological control agents from secure quarantine facilities and
(1) assessment of the potential benefits and hazards arising from release;
(2) procedural assessments to adequately determine safety and explore
risk to receiving ecosystems;
(3) identification of non-target species that would be at risk from GMIs
(i.e., either direct attack, food web perturbations, or gene transfer);
(4) development of mechanisms that can be adopted to mitigate potential
risk; and
(5) assessment of public opinion on the acceptability of GMIs as a
necessary management strategy in support of or replacement of traditional
control practices such as pesticide applications for mosquito control.

Regulatory Oversight of Proposed GMI Releases

Currently in the US, there is no agreed upon process for assessing safety
of GMIs and their risk to the receiving ecosystem prior to release, nor
has it been definitively determined which state and federal regulatory
agencies will be involved with deciding what constitutes acceptable data
concerning safety and risk assessment and how these data should be
assessed scientifically1. Given the diversity of GMIs that could
potentially be created for pest, vector, and disease management in a
variety of ecosystems including natural, agricultural, and urban
settings, the Food and Drug Administration (FDA), Environmental
Protection Agency (EPA), and the US Department of Agriculture (USDA), may
have input into regulatory oversight. As scientists begin the application
process for permission to conduct field trials, overlapping
jurisdictional boundaries across government agencies are likely to cause
confusion, duplication of effort, and anxiety as to whether the necessary
paperwork has been completed to satisfy all regulatory requirements.
Coordination of oversight and division of responsibility across several
government agencies is seen as an impediment in need of resolution before
field testing of GMIs can be made possible2.

New Zealand and Australia have some of the most stringent legislative
requirements for regulating genetically modified organisms (GMOs which
include plants, animals, and microbes). New Zealand’s Hazardous
Substances and New Organisms Act 1996 (HSNO) places incumbent obligations
on proponents of GMOs requiring them to provide adequate data on which
assessments for release can be based, and this includes consideration of
international concerns that incipient programs may raise. This
legislation (i.e., HSNO) provides a solid framework within which risks
and benefits of proposed GMO use can be weighed, and decisions made in
accordance with presented data. The Environmental Risk Management
Authority (ERMA) administers the review process for the release of GMOs
which includes extensive public consultation and consideration of
concerns raised by Maoris, New Zealand’s indigenous peoples. ERMA and
HSNO also provide guiding frameworks for proposed importation and
releases of exotic biological control agents in New Zealand.

In Australia, the Gene Technology Bill (2000) is the cornerstone
legislative act that provides a national regulatory structure governing
GMOs. Within this framework, the Gene Technology Regulator prepares a
risk assessment and management plan for every proposed GMO release into
the environment. Risk assessment includes the potential of the GMO of
concern to cause adverse environmental impacts, to persist for inordinate
periods of time, and to spread geographically or via exchange of genetic
material. As with ERMA, extensive consultation with stakeholders is
mandatory3. The regulatory frameworks adopted by New Zealand and
Australia may provide legislative inspiration to federal regulators in
the US who are facing similar hurdles as releases of GMIs draw near.

Safety Evaluations and Risk Assessment

Major concerns surrounding permanent establishment of GMIs in nature
include the potential for creating new pests and for disrupting
ecosystems, because they may transmit novel genetic material to wild
relatives or exhibit an increased ability to inhabit areas that exclude
non-transformed conspecifics. Realization of these negative impacts will
depend on the fitness and competitiveness of GMIs, the dispersal ability
of the GMI and its environmental tolerances, and the permissiveness of
the receiving environment. Additionally, adverse effects may manifest
themselves via non-target organisms that use the GMI as a resource or are
displaced by competition. These issues are similar to those posed by the
importation and release of exotic biological control agents. Evaluation
of traits likely to enable GMIs to become pestiferous need to be
identified and evaluated prior to release. Rigorous protocols similar to
those used for weed biological control agents may provide important
starting points for deliberation in the development of novel testing
regimens for GMIs. A major new area of investigation will be concerning
scenarios facilitating unwanted gene flow into unintended recipient
populations and the outcomes should this occur. Consideration of factors
promoting gene flow is a major departure from testing protocols for
biological control agents. Interpretation of what constitutes acceptable
levels of safety and risk will undoubtedly be interpreted differently
depending on varying tolerance perspectives of the analyzing parties in
the country of release and adjacent neighbors.

Mitigating Non-Target Impacts

Despite rigorous applied laboratory tests, small-scale field trials, and
modeling of results, there is the potential for unintended consequences
to manifest themselves, as answers to questions pertaining to safety and
risk are influenced by temporal, spatial, and myriad biotic and abiotic
factors that cannot be easily replicated experimentally. A logical step
for mitigating non-target effects from GMIs would be built in mechanisms
to prevent continued persistence and spread. One safeguard would be the
inclusion of marker genes to readily identify GMIs from non-transformed
conspecifics. This technology is already in place and would allow
population monitoring and measurement of spread. An additional safeguard
would be incorporation of safety devices that could be activated to
disable GMIs thereby countering their adverse effects should they arise.
Greater research into the development of safety options will most likely
occur as GE technology advances and field trials become more likely.


Legislative guidelines and protocols for scientifically addressing issues
of safety and risk of GMIs is in need of increasing attention, as
organisms developed in the laboratory steadily approach the field testing
phase. Similar issues concerning the outdoor release of GMIs have faced
the biological control community. Growing disquiet generated by prominent
ecologists and conservationists have increased awareness of non-target
impacts and the difficulty of predicting unforeseen ecosystem
perturbations caused by exotic natural enemies used for the biological
control of exotic pests. Recognition of these issues has increased
research effort by biological control practitioners to experimentally
address factors pertaining to safety and unforeseen risk within
prescribed experimental and regulatory arenas. Where consideration of
analogous issues pertaining to the release and use of GMIs in the
environment is necessary, lessons learned by the biological control
community could form a sound starting basis for molecular biologists and
vector ecologists developing good practice guidelines.


1. Minkel, J.R. 2004. Bugging for guidance. Scientific American 291 (1): 34.
2. Pew Charitable Trusts 2004. Bugs in the system? Issues in the science
and regulation of genetically modified insects.
3. Henzell, R., and Murphy, E. 2002. Rabbits and possums in the GMO
potboiler. Biocontrol News and Information 23: 89N-96N.

Mark S. Hoddle
Biological Control Specialist
Department of Entomology
University of California

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