Genetically Modified Insects Contents

Chapter 2: The science behind GM insects

8.GM insect technology is an emerging field across many disciplines in biology, including molecular genetics, ecology, environmental management and synthetic biology. GM insects are created by inserting genes into an insect’s DNA (deoxyribonucleic acid) in order to alter its function or reduce its fitness. In this way, insects which transmit diseases or damage crops can be modified.

9.Many potential genes have been identified that influence the biology of insects. Short sequences of carrier genetic material, usually DNA or RNA (ribonucleic acid), are used to integrate a novel gene into an insect’s genome. By injecting this genetic package into insect eggs or embryos, genetically modified strains can be created.

10.Currently, recombinant4 DNA technology has been used to create transgenic5 insects with:

11.GM insect technologies build on methods developed in the mid-twentieth century (for instance, sterile insect technique—explained below). These technologies represent a form of biological control in contrast to the use of chemical controls, such as insecticides, which have dominated the management of insect disease vectors and pests historically. GM insect technologies can be grouped into population suppression or population replacement strategies. We will explain these strategies in turn.

Population suppression

12.A population suppression strategy seeks to reduce the size of an insect population by introducing a lethal gene whereby offspring cannot survive. A population of so-called sterile7 insect males is reared in the laboratory and released into the environment to mate with wild females. The resulting offspring are non-viable and as such the insect population is reduced.

13.GM insect population suppression strategies are based on the traditional Sterile Insect Technique (SIT) used in pest management. This approach involves a large-scale (inundative8) release of mass-reared sterile male insects into wild, native insect populations so that there is a highly skewed sex ratio of sterile males to wild females.

14.Traditional SIT approaches usually achieve sterilisation using radiation or chemicals. SIT has been applied most widely against agricultural pests, particularly screwworm, Mediterranean fruit fly and Mexican fruit fly. There have been some attempts to use this sterile insect technique for the control of insect vectors9 such as mosquitoes.

15.GM analogues of the traditional SIT technique arguably present a more precise approach to population suppression strategies. Genes can be specifically targeted to be active in particular insect life stages, hence making it more likely that the viability and fitness of the modified insect are not compromised.

Population replacement

16.Population replacement strategies aim to modify an insect with heritable traits in order to affect insect physiology or, in the case of disease vectors, render a pathogen harmless in the insect. This involves introducing a genetic modification into an insect that is designed to be inherited and so, over time, an entire insect population can be altered to include this modification.

17.Population replacement strategies require less mass-rearing than population suppression strategies and it is expected that the heritable constructs will spread through populations by means of gene drive mechanisms. It is anticipated that these modifications will be persistent in an environment.

Gene drive and gene editing

18.The aim of gene drive is to cause a gene to spread through a population at a greater rate than would be the case with natural inheritance. Recent advances in molecular biology provide an array of techniques for editing genes and engineering gene drive mechanisms.10 These molecular methods cut genes at specific sites and can be used to insert novel genes or disrupt specific gene function. For instance, CRISPR-Cas9 endonucleases11 cut specific gene sequences, and together with specific RNAs (ribonucleic acid), can be guided to specific sites in a genome. After the cut, gene repair mechanisms replace the original sequence with an altered version of the sequence. Recent developments, based on the CRISPR-Cas9 gene-editing method, have shown that this gene drive can be used to modify insect populations rapidly.

19.One recent piece of research, published in the Proceedings of the National Academy of Sciences in November 2015, reported that US based scientists had successfully used the CRISPR gene editing method so that a modified mosquito resistant to a pathogen passed these new resistance genes onto almost all of its offspring, not just half, as would normally be expected.12 This offers the possibility of a gene resistant to the parasite that causes malaria being able to spread quickly through a wild population of mosquitoes. The principal investigator behind this research, Professor Anthony James, submitted evidence to our inquiry.13 Just before we went to press in early December 2015, scientists, including Professor Austin Burt who gave oral evidence to our inquiry, announced findings that could speed up the development of techniques to suppress mosquito populations to levels that would not support malaria transmission.14

Figure 1: A simplified depiction of natural inheritance versus inheritance with a gene drive construct

Image comparing natural inheritance from normal reproduction and inheritance with a gene drive construct

A red fly will leave only a few offspring under normal reproduction. A gene drive that favours ‘red’ colour can ensure that nearly all offspring inherit the ‘red’ colour gene causing it to spread rapidly through the population.

Resistance and resistance management

20.The development of resistance to control methods is an inevitable phenomenon; there will always be an evolutionary response to genetic changes resulting in altered characteristics in organisms. This will arise irrespective of the method by which the alterations occurred.

21.Many agricultural insect pests have evolved resistance to widely-used insecticides. Resistance evolution to gene modifications, although currently unreported, is entirely possible. The development of resistance would have economic and environmental effects due to loss of efficacy of the control intervention. Environmental costs would include the potential effects on ecosystems and human health of increased use of alternative control measures (insecticides) and/or the use of additional gene technologies.

22.We were told of the need to monitor resistance and include consideration of it in GM insect strategies. The Advisory Committee on Releases to the Environment (ACRE) said of resistance management:

“In general, we will need to harness our understanding of the mechanisms involved and apply this knowledge on a case by case basis. Where GM insects are used for biological control, integrating different approaches for controlling pest populations will be essential for a durable and resistant outcome.”15

The Wellcome Trust stated:

“Resistance would be expected to evolve both to the drive mechanism (e.g., mutations in the genomic region you were targeting making the drive mechanism ineffective) and towards any genetic trait you were modifying (e.g., the ability to resist a particular pathogen). In developing such technologies, it will be important to learn from the development of resistance in other pathogens.”16

23.Austin Burt, Professor of Evolutionary Genetics, Imperial College London, compared the evolution of resistance to GM insect strategies to the resistance developed to chemicals:

“Overall, I would say it is too early to say whether resistance is more or less likely to evolve compared to a chemical. What I would say is that when you get resistance to a chemical, often it is a whole class of chemicals that they become resistant to, so that takes them off the table. There is a possibility that the genetic approaches will lead to resistance to a specific construct, and by tweaking the construct it would be able to get around the resistance. However, that is a hunch, not something we have proved.”17

24.There may be a number of ways to combat resistance to GM insect strategies. The use of so-called multi-hit approaches may be one such means. Paul Eggleston, Professor of Molecular Entomology, Keele University, likened this approach to that used in combination drug therapy.18 In designing such an approach, a number of modifications can be built in so that the desired affect is achieved via a variety of modifications rather than a single means. Professor Eggleston described such an approach:

“A single intervention such as that may be something which parasites could work their way around. If you engineered your insect with two or three independent approaches that tackled the parasite or the pathogen from a number of different angles, it would be more difficult for those parasites or pathogens to evolve resistance. It is similar to combination drug therapy.”19

25.Scientific understanding of the evolution of resistance in GM insect strategies is a developing area. As such, on-going research and monitoring will be required in order to increase understanding and to allow for the design of strategies that can maximise the potential to delay the onset of resistance.

26.Using the techniques described above, GM insects could provide alternative and/or additional tools for the control of insect-borne infectious diseases as well as the control of agricultural pests. The next chapter elaborates on the potential applications of GM insect technologies.

4 Bringing together genetic material from multiple sources, thereby creating sequences that would not otherwise be found in the genome.

5 Modified via insertion of genetic material from another organism.

6 An organism that causes disease. For example, in dengue infection, the pathogen is a virus whereas in malaria infection, the pathogen is a unicellular parasite.

7 The term ‘sterile’ is commonly used although the male insects are able to reproduce; albeit to yield non-viable offspring. This is by way of analogy with the traditional SIT insect approaches that yield insects that are in fact reproductively sterile as a result of irradiation.

8 Inundative biological control involves the release of massive numbers of the control agent in order to control the pest rapidly.

9 A vector is any agent (person, animal or microorganism) that carries and transmits an infectious pathogen into another living organism.

10 These approaches include: zinc finger nucleases, TALENS (transcription activator-like effector nucleases) and new CRISPR (clustered regular interspaced short palindromic repeats) based techniques.

11 An enzyme (biological catalyst) which cuts strands of DNA at specific points.

12 ‘Gene drive mosquitoes engineered to fight malaria’, Nature (23 November 2015): [accessed 9 December 2015]

13 Written evidence from Prof Anthony James (GMI0004)

14 Andrew Hammond et al, ‘A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae’, Nature Biotechnology, (2015): [accessed 9 December 2015]

15 Written evidence from the Advisory Committee on Releases to the Environment (ACRE) (GMI0014)

16 Written evidence from the Wellcome Trust (GMI0025)

17 Q 50 (Prof Austin Burt)

18 Q 50 (Prof Paul Eggleston)

19 Ibid.

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