Genetically engineered insects: From agricultural pests to entomological warfare

In January 2023, Union Minister Dr Jitendra Singh inaugurated the National Genome Editing & Training Centre (NGETC) at National Agri-food Biotechnology Institute (NABI) in Mohali, Punjab. Alongside the launch of the organisation, the Union Minister also inaugurated the International Conference on Food and Nutritional Security (IFANS), which was organised to discuss the country’s venture into food enhancement and security, and genomic editing, which is a collaborative effort between NABI, the Centre for innovative and Applied Bioprocessing (CIAB), and the International Institute of Plant Biotechnology. With the implementation of organisations like NABI and the focus on genetics and epigenetics in the current National Biotechnology Development Strategy, India has seen a resurgence in its focus on bioengineering and genomic editing. Genomic editing under these programmes overlooks plant modification for food enhancement, reduced climate impact, and food resilience. One significant implication of genomic editing is the editing of live organisms, like insects, which can be used for many different purposes, including healthcare.

Genetic engineering of insects

Genetic engineering is a field of research that covers the genome construction of all living creatures, from plants to animals. These engineering forms rely on genetic manipulation that may include Zinc Finger Nucleases (ZFN), Transcriptional Activator-like Effector Nucleases (TALEN), and the more popularly known Clusters of Regularly Spaced Short Palindrome Repeats (CRISPR). These have emerged as programmable nucleases, making genome manipulation a frequently relied upon process for its many uses.

The United States Defence Advanced Research Project Agency (DARPA) was experimenting with “cyborg” insects, which would be remote controlled and additionally could be used as surveillance drones.

CRISPR has its origins in studies on bacterial adaptive immune systems. However, with its applicability and success rate, this subsect of bioengineering has sometimes been applied to larger organisms like insects. This application is not limited to research on gene functionality but has also been used in applied sciences. That is, genetically modified insects can be used in pest control, disease control, ecological impact, and even human impact.

Using insects in warfare

The scope of using these insects in war is another possible outcome of human intervention. Conventionally, this is called entomological warfare and comes under the current understanding of biological warfare. Over a decade ago, the United States Defence Advanced Research Project Agency (DARPA) was experimenting with “cyborg” insects, which would be remote controlled and additionally could be used as surveillance drones. Though this project was scrapped, the potential for entomological warfare does not stop with technologically enhanced insects. With gene manipulation now possible, the scope of using insects as tools of warfare to spread disease, rather than treat it, has now returned. The Biological Weapons Convention (BWC) bans the use of biological weapons by prohibiting the use or trade of listed toxins and spread through listed vectors. The broad spectrum of toxins listed under the BWC also extends to insects that may be used to spread disease; so the ban is extended to insects' intentional and trackable impact. However, due to the possible nature of such weapons, the effect can be misdiagnosed as a naturally occurring outbreak that still needs to be considered and governed.

The Biological Weapons Convention (BWC) bans the use of biological weapons by prohibiting the use or trade of listed toxins and spread through listed vectors.

To curb the concerns around this, research has moved its interest from biowarfare to inspiration from insect biology in civil applications as well as warfare applications. Using insects as inspiration for military applications has allowed for inventions that have civil applications too. These applications have moved from genetic enhancement or toxin development to biological inspiration. Some examples include using cuticle shapes from beetles to inspire alloy use in military vehicles that can resist bullet penetration; creating microdrones that mimic dragonflies and bees are also newer innovations under development for surveillance applications. Due to their innovative and non-harmful nature, these innovations are more easily trackable, fair, and ethical.

Genetic engineering in healthcare

CRISPR technology has implications beyond possible warfare in multiple fields of research, ranging from agriculture, food production, biotechnology, food enhancement, and medicine. Recently, CRISPR technology has been used increasingly in insects, including moths and butterflies, for their economic benefits in silk production. It has also been used to enhance insect genomes for pest control in agriculture without negatively affecting non-pest insects. Mosquitoes, specifically, are genetically enhanced for their ability to target insect-borne diseases. A research institute, Oxitec, has had successful trials using mosquitoes to reduce mosquito populations in areas that are vulnerable to mosquito-borne diseases. This is accomplished by gene editing mosquitoes so that male mosquitoes are unable to produce viable sperm, thus slowly reducing diseased mosquito populations in vulnerable areas. This genomic editing, after being tested in countries in South America, has also been backed by the World Health Organisation (WHO). After this success, sending the insects to treat dengue, malaria, and chikungunya rates in India was also under discussion. The World Mosquito Program has also expanded its outreach to Australia, Brazil, Colombia, Fiji, Indonesia, Kiribati, Laos, Mexico, New Caledonia, Sri Lanka, Vanuatu, and Vietnam, adding yellow fever to the list of diseases tackled. However, despite the success rate of genetically engineered insects in economic pursuits and medicine, the use of genetically engineered organisms is still controversial. Genetically modified insects have certain advantages that let scientists exercise more control over the outcomes than other forms of intervention like outbreak control medication or insecticides, as they allow single types of insects to be targeted, leaving the insects that complement the ecology unharmed. Second, since insects have high reproduction rates, genetic engineering can help control an otherwise uncontrolled rate of reproduction. Third, genetically engineered insects reduce dependence on insecticides that may be toxic to water supplies, plants, and other valuable insects and animals. Finally, the socio-economic barrier^<1> of medicine is removed when genetically engineered insects are used for disease control. While these advantages allow for great hope in using biotechnology, the same adds to the dual-use dilemma of any innovation and has its disadvantages. These disadvantages include ecological impact through horizontal transfer^<2> or an unexpected impact on other species as a negative externality. This transfer may create an unintentional ecological impact that can mutate in diverse ways, depending on the organism it has transferred to. An example of this is the horizontal jump of pesticide immunity that can transfer from the genetically altered insect, like silk-producing moths, to the intentional targets of pesticides, like plant-eating caterpillars.

Genetically modified insects have certain advantages that let scientists exercise more control over the outcomes than other forms of intervention like outbreak control medication or insecticides, as they allow single types of insects to be targeted, leaving the insects that complement the ecology unharmed.

This disadvantage also extends into the second, i.e., the reversibility of this method. Once released, the scope of impact and recall of intervention is not possible, especially with live organisms that are small like insects, that can reproduce at high rates, and that are not containable to certain locations and can travel far. This reduces the containment of a sample size and location. Further, live organisms cannot be recalled, unlike traditional healthcare, where records are kept of everyone who has been administered a dosage; the recall of the insects as vectors is impossible, extended by the inability to track their impact in exact numbers. While the earlier disadvantages mentioned can be categorised as negative externalities and will need to be controlled through further research and observation, the latter on entomological warfare and any other outcomes that are ungoverned come under existing biotechnology regulations that call for expansion.

India’s approach to genomic editing

With concerns of entomological warfare, India is undersigned to the Cartagena Protocol on Biosafety and the Biological Warfare Convention. Further, for national accountability of genetically modified organisms, including insects, the Ministry of Environment, Forest and Climate Change have, under the Environment (Protection) Act, formed rules that overlook the creation, use, trade, and research of genetically-modified organisms. These rules also include six committees for advisory, monitoring, and regulating. The rDNA Advisory Committee (RDAC) acts as an advisory firm. Regulation and management are governed by the Institutional Biosafety Committee (IBSC), Review Committee on Genetic Manipulation (RCGM) and Genetic Engineering Appraisal Committee (GEAC). Additionally, the State Biotechnology Coordination Committee (SBCC) and District Level Committee (DLC) aid in monitoring.

The regulations around these, thus, must curb its current disadvantages around lack of recall and uncontrolled scope of outcomes by increasing awareness of the design, assessment, and delivery mechanisms right up to the screening for and detection of insects carrying the mutation of interest.

India’s regulations regarding genetically modified organisms include heritable and non-heritable changes under its purview, surpassing the regulations of countries in the European Union. India’s National Biotechnology Development Strategy 2012-2025 also mentions improving and aligning gene editing regulations to global standards to implement new and emerging gene editing technologies. However, the rules released thus far mainly focus on plant gene editing and fall short on other organisms. As CRISPR technology continues to grow and find more avenues of impact, the need to optimise the technology and push its current limits will also expand. The successful editing of insect genomes using this technology will require careful attention. The regulations around these, thus, must curb its current disadvantages around lack of recall and uncontrolled scope of outcomes by increasing awareness of the design, assessment, and delivery mechanisms right up to the screening for and detection of insects carrying the mutation of interest. This risk assessment will subsequently require expanding definitions of genetic mutation and bioengineering, including medical intervention, ecological impact, and security. Finally, the reassessment of how genetically altered organisms are regulated, based on the latest science, will play an essential role in the possibility of the future release of CRISPR-edited insects into the environment. Under upgraded and current regulations, entomological enhancement through innovations like CRISPR and other biotechnologies have created a vast new economy in many impact areas, the future of which inspires greater hope for an ecological solution to economic and health problems.

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^<1> As insects are released in an area interact with humans indiscriminately and do not depend on who can afford medical treatment. ^<2> new genes engineered into the insects may “jump” into other species.

• Climate, Food and Environment
• Agriculture
• India
• agri-food
• biotechnology
• climate impact
• ecological impact
• Food
• food resilience
• surveillance drones

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