Genetic Biocontrol for Invasive Species

Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries

Intended Consequences Statement in Conservation Science and Practice

As the biodiversity crisis accelerates, the stakes are higher for threatened plants and animals. Rebuilding the health of our planet will require addressing underlying threats at many scales, including habitat loss and climate change. Conservation interventions such as habitat protection, management, restoration, predator control, trans location, genetic rescue, and biological control have the potential to help threatened or endangered species avert extinction. These existing, well-tested methods can be complemented and augmented by more frequent and faster adoption of new technologies, such as powerful new genetic tools. In addition, synthetic biology might offer solutions to currently intractable conservation problems. We believe that conservation needs to be bold and clear-eyed in this moment of great urgency

Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive

Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous population genomic surveys to evaluate population connectivity, taxonomic identification, and to inform design of gene drive localization mechanisms. One proposed approach leverages the predicted shifts in genetic variation that accompany island colonization, wherein founder effects, genetic drift, and island-specific selection are expected to result in locally fixed alleles (LFA) that are variable in neighboring nontarget populations. Engineering of guide RNAs that target LFA may thus yield gene drives that spread within invasive island populations, but would have limited impacts on nontarget populations in the event of an escape. Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications

Locally Fixed Alleles: A method to localize gene drive to island populations

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population

Genetic Biocontrol for Invasive Species

Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries

Population genomics of invasive rodents on islands: Genetic consequences of colonization and prospects for localized synthetic gene drive

Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous population genomic surveys to evaluate population connectivity, taxonomic identification, and to inform design of gene drive localization mechanisms. One proposed approach leverages the predicted shifts in genetic variation that accompany island colonization, wherein founder effects, genetic drift, and island-specific selection are expected to result in locally fixed alleles (LFA) that are variable in neighboring nontarget populations. Engineering of guide RNAs that target LFA may thus yield gene drives that spread within invasive island populations, but would have limited impacts on nontarget populations in the event of an escape. Here we used pooled whole-genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications

Locally Fixed Alleles: A method to localize gene drive to island populations

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population

Core commitments for field trials of gene drive organisms

We must ensure that trials are scientifically, politically, and socially robust, publicly accountable, and widely transparent. Gene drive organisms (GDOs), whose genomes have been genetically engineered to spread a desired allele through a population, have the potential to transform the way societies address a wide range of daunting public health and environmental challenges. The development, testing, and release of GDOs, however, are complex and often controversial. A key challenge is to clarify the appropriate roles of developers and others actively engaged in work with GDOs in decision-making processes, and, in particular, how to establish partnerships with relevant authorities and other stakeholders. Several members of the gene drive community previously proposed safeguards for laboratory experiments with GDOs (1) that, in the absence of national or international guidelines, were considered essential for responsible laboratory work to proceed. Now, with GDO development advancing in laboratories (2–5), we envision similar safeguards for the potential next step: ecologically and/or genetically confined field trials to further assess the performance of GDOs. A GDO’s propensity to spread necessitates well-developed criteria for field trials to assess its potential impacts (6). We, as a multidisciplinary group of GDO developers, ecologists, conservation biologists, and experts in social science, ethics, and policy, outline commitments below that we deem critical for responsible conduct of a field trial and to ensure that these technologies, if they are introduced, serve the public interest. Includes Supplementary materials

Core commitments for field trials of gene drive organisms

Gene drive organisms (GDOs), whose genomes have been genetically engineered to spread a desired allele through a population, have the potential to transform the way societies address a wide range of daunting public health and environmental challenges. The development, testing, and release of GDOs, however, are complex and often controversial. A key challenge is to clarify the appropriate roles of developers and others actively engaged in work with GDOs in decision-making processes, and, in particular, how to establish partnerships with relevant authorities and other stakeholders. Several members of the gene drive community previously proposed safeguards for laboratory experiments with GDOs (1) that, in the absence of national or international guidelines, were considered essential for responsible laboratory work to proceed. Now, with GDO development advancing in laboratories (2–5), we envision similar safeguards for the potential next step: ecologically and/or genetically confined field trials to further assess the performance of GDOs. A GDO\u27s propensity to spread necessitates well-developed criteria for field trials to assess its potential impacts (6). We, as a multidisciplinary group of GDO developers, ecologists, conservation biologists, and experts in social science, ethics, and policy, outline commitments below that we deem critical for responsible conduct of a field trial and to ensure that these technologies, if they are introduced, serve the public interest