1 Introduction

Gene drive systems represent a groundbreaking advancement in genetic engineering, enabling the propagation of specific genetic traits through populations at an accelerated rate compared to traditional Mendelian inheritance. These systems have garnered significant attention due to their potential applications in various fields of environmental management. For instance, gene drives can be employed to control populations of insect vectors responsible for transmitting diseases, manage agricultural pests, and mitigate the impact of invasive species on native ecosystems (Rode et al., 2019; Kim et al., 2023). Additionally, gene drives hold promise for conservation efforts, such as rescuing endangered species by introducing beneficial genetic traits.

Despite the promising applications, the release of gene drive systems into the environment raises substantial ecological and ethical concerns. The potential for unintended consequences, such as the spread of gene drives to non-target species or ecosystems, necessitates a thorough ecological risk assessment (ERA) (Landis et al., 2019; Rode et al., 2019; Kim et al., 2023). The complexity of gene drive interactions with natural populations and ecosystems underscores the need for robust risk management frameworks to address uncertainties and mitigate potential adverse effects (Golnar et al., 2020; Then et al., 2020). Moreover, the irreversible nature of gene drive propagation amplifies the importance of precautionary measures and comprehensive monitoring strategies (Romeis et al., 2020; Naegeli et al., 2020).

This study aims to develop a comprehensive framework for the ecological risk assessment and monitoring of gene drive systems. The objectives are threefold. First, to synthesize current knowledge on the ecological risks associated with gene drive releases, including potential impacts on non-target species and ecosystems. Second, to evaluate existing risk assessment methodologies and identify gaps that need to be addressed to ensure the safe deployment of gene drive technologies. Third, to propose a dynamic and adaptive monitoring framework that integrates pre-release modeling with post-release surveillance to manage uncertainties and ensure ecological safety. By addressing these objectives, this study seeks to provide a scientifically grounded and socially responsible approach to the environmental release of gene drive systems, balancing potential benefits with ecological safety.

2 Mechanisms and Types of Gene Drive Systems

2.1 Explanation of different gene drive mechanisms

Gene drive systems are genetic engineering technologies designed to propagate specific genes throughout a population by biasing the inheritance process. Several mechanisms have been developed to achieve this, including CRISPR-based systems, homing endonucleases, and transposable elements. CRISPR-based gene drives utilize the CRISPR-Cas9 technology to cut DNA at specific sites, allowing for the insertion of desired genetic elements. These drives are highly efficient and can spread rapidly through populations by ensuring that the engineered gene is inherited more frequently than would occur through normal Mendelian inheritance (DiCarlo et al., 2015; Noble et al., 2016a; Noble et al., 2016b). Homing endonuclease gene drives use homing endonucleases, which are enzymes that recognize and cut specific DNA sequences. The cell's repair mechanisms then use the drive-containing chromosome as a template to repair the cut, thereby copying the drive to the homologous chromosome. This mechanism has been extensively studied, particularly in insects, and has faced challenges such as unintended repair outcomes and “leaky” expression (Verkuijl et al., 2022). Transposable elements are DNA sequences that can change their position within the genome. They can be engineered to carry gene drive elements, allowing them to insert the desired genes into new locations within the genome. This method is less commonly used compared to CRISPR and homing endonucleases but offers a different approach to gene drive implementation (Akbari et al., 2015).

2.2 Overview of gene drive types

Gene drives can be broadly categorized into two types based on their intended ecological impact: population suppression and population modification. Population suppression drives aim to reduce the population size of a target species. They achieve this by spreading genes that reduce fertility or viability. For example, toxin-antidote systems can be designed to disrupt essential genes, leading to population suppression (Champer et al., 2019). Population modification drives aim to alter the traits of a population without necessarily reducing its size. These drives can be used to spread genes that confer resistance to diseases or reduce the ability of pests to transmit pathogens. CRISPR-based systems and daisy-chain drives are examples of this type, where the goal is to achieve local fixation of beneficial traits without uncontrolled spread (Figure 1) (Noble et al., 2016a; Esvelt, 2016).

Figure 1 Comparison of self-propagating and daisy-chain gene drive (Adopted from Noble et al., 2016a) Image caption: (A) Self-propagating CRISPR gene drives distort inheritance in a self-propagatingmanner by converting wild-type (W) alleles to drive alleles in heterozygous germline cells. (B) A daisy-drive system consists of a linear chain of seriallydependent, unlinked drive elements; in this example, A, B, and C are on separate chromosomes. Elements at the base of the chain cannot drive and aresuccessively lost over time via natural selection, limiting overall spread. (C) Family tree resulting from the release of a single daisy-drive organism in aresident wild-type population in the absence of selection. On the right is a graphical depiction of the total number of alleles per generation. Throughout,chromosome illustrations represent genotypes in germline cells (Adopted from Noble et al., 2016a)

2.3 Current status of gene drive research and development

Gene drive research is rapidly advancing, with significant progress in both theoretical and practical aspects. CRISPR-based gene drives have shown promise in laboratory settings, demonstrating the ability to spread engineered traits through populations of organisms such as yeast and insects (DiCarlo et al., 2015; Noble et al., 2016b). However, challenges such as resistance allele formation and ethical concerns about unintended ecological impacts remain significant hurdles. Recent developments include the creation of self-exhausting gene drives, such as the daisy-chain drive, which are designed to limit their spread to local populations, thereby addressing some of the ethical and ecological concerns (Noble et al., 2016a). Additionally, toxin-antidote systems are being explored for their potential to provide robust and regionally confined gene drive solutions (Champer et al., 2019). Overall, while the potential applications of gene drives in areas such as disease-vector control and conservation are vast, the field is still in the developmental stage, with ongoing research focused on improving efficiency, safety, and ethical deployment (Akbari et al., 2015; Tanaka et al., 2017; Devos et al., 2020).

3 Ecological Impacts of Gene Drive Systems

3.1 Potential ecological consequences of gene drive releases

The release of gene drive systems into the environment can have significant ecological consequences, including the potential for species extinction and disruption of ecosystems. Gene drives are designed to spread genetic modifications rapidly through populations, which can lead to the suppression or even eradication of target species. For instance, gene drives have been proposed to control invasive species and disease vectors, but their release could inadvertently lead to the extinction of non-target species that play crucial roles in their ecosystems (Romeis et al., 2020; Devos et al., 2022; Wolf et al., 2023). The rapid spread of gene drives can also cause eco-evolutionary feedbacks, where the interaction between ecological and evolutionary processes could lead to unpredictable outcomes (Kim et al., 2023).

3.2 Impact on non-target species and biodiversity

One of the primary concerns with gene drive technology is its potential impact on non-target species and overall biodiversity. Gene drives can spill over from target populations to non-target populations, potentially causing ecological catastrophes. For example, differential-targeting gene drives aim to limit spillover, but under high migration rates, the gene drive could still fixate in non-target populations, leading to severe ecosystem disruptions (Figure 2) (Greenbaum et al., 2019). Additionally, hybridization between gene drive-modified organisms and closely related non-target species could result in the unintended spread of gene drive elements, further threatening biodiversity (Wolf et al., 2023). The potential for gene drives to affect non-target species necessitates thorough risk assessments and the development of strategies to mitigate these risks (Devos et al., 2022).

Figure 2 Schematic depiction of gene-drive models (Adopted from Greenbaum et al., 2019) Image caption: (A) Model of CRISPR-based gene drive in an isolated population (Eq 1). Shown is the change of the allele frequency of the gene-drive allele A over one generation, from t to t + 1. Each genotype contributes to the frequency of A in generation t + 1 depending on its frequency in generation t and the genotype fitnesses: the AA genotype contributes an A allele (red arrows), and the heterozygous genotype Aa contributes 1 (purple arrow) or 1/2 allelic copies (green arrow), depending on whether gene drive conversion occurs (at rate c). (B) A two-deme configuration with migration. The gene drive is introduced to the target population, and it can spread to the non-target population through migration. Differential targeting, when possible, would produce convergence to a stable state in which gene-drive frequencies are high in deme 1 and low in deme 2. (C) A two-deme model of gene-drive dynamics in which migration occurs before selection. Black arrows denote migration (Eq 2). The colored arrows (red, green, and purple) represent the contributions of the different genotypes to the next generation’s pre-migration gene pool. q0 i is calculated by normalizing the relative contributions to the frequency of A by the mean fitness of the post-migration population (Adopted from Greenbaum et al., 2019)

3.3 Gene flow and horizontal gene transfer risks

Gene flow and horizontal gene transfer are significant risks associated with the release of gene drive systems. Gene flow occurs when gene drive alleles spread from the target population to non-target populations through hybridization or other means. This can lead to the unintended spread of gene drive elements, potentially causing ecological harm (Conner et al., 2003; Wolf et al., 2023). Horizontal gene transfer, where genetic material is transferred between different species, could also result in the spread of gene drive elements beyond the intended target, posing additional risks to ecosystems. The potential for gene drives to spread uncontrollably highlights the need for robust containment and monitoring strategies to prevent unintended ecological impacts (Tanaka et al., 2017; Landis et al., 2019).

4 Risk Assessment Methodologies

4.1 Current frameworks and methodologies for ecological risk assessment of gene drive systems

Current frameworks for the ecological risk assessment of gene drive systems are evolving to address the unique challenges posed by these technologies. Traditional risk assessment methodologies, such as those used for genetically modified organisms (GMOs), are being adapted and expanded to accommodate the specific characteristics of gene drives. For instance, the European Food Safety Authority (EFSA) has reviewed its guidelines for the risk assessment of genetically modified insects and concluded that while existing frameworks are a good starting point, they are insufficient for gene drive modified insects (GDMIs) and require further guidance (Naegeli et al., 2020). Additionally, the National Academy of Sciences has provided guidelines emphasizing phased testing and ecological risk assessments to ensure responsible conduct in gene drive research (Esvelt et al., 2016).

A modular, phased approach to authorizations has been recommended to manage risks and uncertainties incrementally, allowing for adaptive management as more data becomes available (Devos et al., 2022). This approach includes pre-release modeling and post-release monitoring to dynamically manage uncertainty. Furthermore, the relative risk model, which employs Bayesian networks, has been applied to various environmental contexts and is now being adapted for gene drive systems (Landis et al., 2019).

4.2 Key factors to consider in risk assessment

Several key factors must be considered in the risk assessment of gene drive systems. The release context is a crucial factor, involving the specific ecological and socio-economic context of the release site. This includes understanding the local ecosystem, potential non-target effects, and the socio-political landscape (Dolezel et al., 2020; Romeis et al., 2020). Gene drive stability must be assessed over time and across different environmental conditions. This involves evaluating the potential for mutations that could alter the behavior of the gene drive (Kim et al., 2023). Reversibility is a significant concern in gene drive risk assessment. The ability to reverse or mitigate the effects of a gene drive release is critical, and strategies for containment and reversal, such as the development of counter-drives, need to be considered (Frieß et al., 2019). Long-term and large-scale risks also need to be evaluated. This includes assessing the potential for gene drives to spread beyond the target population or region and understanding the possible unintended ecological consequences at the population and ecosystem levels. Comparative risk assessment is necessary to provide a comprehensive understanding of the potential risks and benefits of gene drives. This involves comparing them with alternative pest control methods or interventions to determine the most suitable approach (Devos et al., 2022).

4.3 Case examples of risk assessment studies for gene drive systems

Several case studies illustrate the application of risk assessment methodologies to gene drive systems. In agricultural pest control, gene drives have been considered for controlling pests such as the invasive Drosophila suzukii. The use of gene drives in this context has been evaluated using existing regulatory frameworks for pest control methods, which include assessing the environmental impacts and the regulatory oversight required for gene drive applications in agriculture (Romeis et al., 2020). For disease vector control, gene drives designed to reduce the population of vectors, such as mosquitoes, have been extensively studied. These studies often involve mathematical and computational models to predict the population-level behavior of gene drives and their potential ecological impacts (Kim et al., 2023). In the case of synthetic biology-derived organisms, the relative risk model has been applied to organisms with gene drives, focusing on altering the fitness of specific populations. This model has been used to estimate risks and impacts in various environmental contexts, demonstrating its applicability to gene drive systems (Landis et al., 2019).

These case studies highlight the importance of adapting existing risk assessment frameworks and developing new methodologies to address the unique challenges posed by gene drive technologies. By considering the specific factors relevant to gene drives and employing a phased, adaptive approach, researchers and regulators can better manage the potential risks and benefits of these innovative technologies.

5 Case Study: Ecological Risk Assessment of a Gene Drive for Malaria Control

5.1 Background on the gene drive system designed for malaria vector control

Gene drive systems, particularly those based on CRISPR-Cas9 technology, have been proposed as a promising strategy for malaria vector control. One such system targets the doublesex locus (dsxF CRISPRh) in the malaria mosquito vector Anopheles gambiae. This gene drive has demonstrated the ability to increase rapidly in frequency and suppress laboratory populations of these mosquitoes (Connolly et al., 2021). The primary goal of these gene drives is to either suppress mosquito populations or replace them with genetically modified populations that are less capable of transmitting malaria (Leung et al., 2021). The African Union has identified gene drive mosquitoes as a priority technology for malaria elimination, with field trials expected in countries like Uganda, Mali, or Burkina Faso within the next 5-10 years (Hartley et al., 2021).

5.2 Specific ecological risks identified in the risk assessment process

The ecological risk assessment process for gene drive mosquitoes involves identifying potential hazards and pathways to harm. Key risks include several critical considerations. One significant risk is increased disease transmission. There is a potential for enhanced transmission of diseases to humans and animals if gene drive mosquitoes interact with other pathogens, or if the suppression of Anopheles gambiae leads to ecological niches being filled by other, potentially more harmful species (Figure 3) (Connolly et al., 2021; Kormos et al., 2023). Another concern is invasiveness and persistence. Gene drive mosquitoes could potentially spread beyond the target area, resulting in unintended ecological consequences. This includes the risk of horizontal gene transfer to non-target species. Impact on biodiversity is also a key consideration. The suppression or modification of mosquito populations could have cascading effects on the ecosystem, potentially affecting species that prey on or compete with mosquitoes (Teem et al., 2019). Finally, evolutionary stability poses a risk. The gene drive could mutate or become ineffective over time, leading to unpredictable ecological outcomes. These risks highlight the importance of comprehensive risk assessment frameworks for managing the deployment of gene drive technologies in mosquito populations.

Figure 3 Conceptual pathway to harm for the potential hazard: increase in malaria due to emergence of target pathogens with transmission advantage (Adopted from Kormos et al., 2023) Image caption: The release of the genetically engineered mosquitoes (GEM) imposes selection pressures that lead to the emergence of parasites resistant to the effector molecules (top left and center). Two outcomes are possible, the first of which produces mosquitoes with no changes in transmission dynamics and malaria prevalence reverts to pre-release levels (top right). The second outcome results in parasites with an advantage that leads to an increase in prevalence above pre-release levels (bottom right) (Adopted from Kormos et al., 2023)

5.3 Mitigation strategies and their effectiveness

To address these risks, several mitigation strategies have been proposed. Phased testing and monitoring involve a modular, phased approach to testing gene drive mosquitoes. This begins with confined laboratory studies, followed by small-scale field trials, and gradually increasing the scale of release based on safety and efficacy data (James et al., 2018; Devos et al., 2022). Stakeholder engagement is crucial for the success and acceptance of gene drive technologies. Engaging local communities and stakeholders includes transparent communication about the risks and benefits, as well as involving stakeholders in the decision-making process (Hartley et al., 2021; Toe et al., 2021). Pre-release modeling and post-release monitoring emphasize the dynamic interplay between these two processes to help manage uncertainties. This strategy involves using models to predict ecological impacts and monitoring actual outcomes to adjust strategies as needed. Regulatory and ethical approvals are essential to ensure all releases are subject to rigorous scrutiny. This includes obtaining approvals from relevant authorities and adhering to international guidelines for the safe and ethical testing of gene drive mosquitoes. These strategies aim to balance the potential benefits of gene drive technologies in controlling malaria with the need to minimize ecological risks and ensure the safety and acceptance of these interventions.

6 Monitoring and Surveillance Strategies Post-Release

6.1 Importance of monitoring gene drive systems post-release

Monitoring gene drive systems post-release is crucial to ensure that the intended outcomes are achieved and to mitigate any unintended consequences. The release of gene drive modified organisms (GDMIs) into the environment carries potential risks, including ecological disruptions and irreversible changes to ecosystems (Naegeli et al., 2020; Devos et al., 2022). Effective monitoring allows for the early detection of adverse effects, enabling timely interventions to prevent or minimize harm. Additionally, continuous surveillance helps in assessing the long-term stability and behavior of gene drives in natural populations, ensuring that they do not spread beyond targeted areas or evolve in unexpected ways (Tanaka et al., 2017; Kim et al., 2023).

6.2 Design and implementation of monitoring frameworks

The design and implementation of monitoring frameworks for gene drive systems should be comprehensive and adaptive. Key components of such frameworks include genetic markers, population surveys, environmental monitoring, and dynamic modeling. Genetic markers are essential for tracking the presence and spread of gene drive alleles in target populations. This involves regular sampling and genetic analysis to monitor allele frequencies and detect any deviations from expected patterns (Frieß et al., 2019; Naegeli et al., 2020). Population surveys are conducted to assess changes in population dynamics, such as population size, structure, and distribution. These surveys help in understanding the ecological impact of gene drives and in identifying any unintended effects on non-target species (Tanaka et al., 2017; Kim et al., 2023). Environmental monitoring is implemented to detect changes in ecosystem parameters, such as biodiversity, species interactions, and habitat conditions. This holistic approach ensures that the broader ecological impacts of gene drives are captured (Golnar et al., 2020; Devos et al., 2022). Dynamic modeling is employed to predict the behavior of gene drives under various ecological scenarios. These models can guide the design of monitoring programs by identifying critical parameters and potential risk factors.

6.3 Case examples of monitoring programs for gene drive organisms

Several case examples illustrate the implementation of monitoring programs for gene drive organisms. Laboratory and confined field trials have been a focus of initial monitoring efforts, where gene drive-modified insects are released in controlled environments. These trials provide valuable data on gene drive behavior and help refine monitoring techniques before large-scale environmental releases (Naegeli et al., 2020). Mathematical and computational models have been developed by researchers to simulate the spread and impact of gene drives. These models incorporate ecological variables and provide insights into potential outcomes, guiding the design of monitoring frameworks (Tanaka et al., 2017; Kim et al., 2023). Stakeholder engagement is also a key component of effective monitoring programs. It involves ensuring that local communities, regulatory bodies, and other stakeholders are informed and involved in the monitoring process. This collaborative approach enhances the robustness and social acceptability of gene drive projects (Frieß et al., 2019; Devos et al., 2022). By integrating these strategies, monitoring frameworks can effectively track the performance and impact of gene drive systems, ensuring their safe and responsible use in addressing ecological challenges.

7 Challenges in Monitoring Gene Drive Systems

7.1 Technical challenges

Monitoring gene drive systems presents several technical challenges, primarily related to detection sensitivity and data interpretation. The ability to accurately detect and monitor gene drive-modified organisms (GDMOs) in the environment is crucial. Detection sensitivity must be high enough to identify low-frequency occurrences of GDMOs, which can be technically demanding due to the need for precise and reliable molecular tools (Naegeli et al., 2020; Devos et al., 2022). Additionally, interpreting the data collected from monitoring efforts can be complex. The rapid evolutionary processes and eco-evolutionary feedbacks associated with gene drives can complicate the prediction and understanding of their behavior in natural populations. This necessitates advanced computational models and robust data analysis frameworks to accurately interpret monitoring data (Landis et al., 2019; Kim et al., 2023).

7.2 Logistical challenges

Logistical challenges in monitoring gene drive systems include the scale of monitoring and resource allocation. The potential for gene drives to spread rapidly and widely means that monitoring efforts must cover large geographic areas, which can be resource-intensive and logistically challenging (Romeis et al., 2020; Dolezel et al., 2020). Effective monitoring requires substantial financial and human resources, as well as coordination among various stakeholders, including regulatory bodies, researchers, and local communities (Thizy et al., 2020). The need for long-term monitoring to assess the persistence and ecological impacts of gene drives further exacerbates these logistical challenges (Naegeli et al., 2020).

7.3 Addressing uncertainties in monitoring outcomes

Addressing uncertainties in monitoring outcomes is a significant challenge in the context of gene drive systems. The inherent uncertainties in predicting the ecological and evolutionary impacts of gene drives necessitate a dynamic and adaptive monitoring framework (Devos et al., 2022). This includes the development of pre-release modeling to anticipate potential outcomes and the implementation of post-release monitoring to validate these models and adjust strategies as needed (Landis et al., 2019). Additionally, uncertainties can arise from the variability in environmental conditions and the complex interactions between gene drives and ecological processes, which require continuous refinement of monitoring methodologies and risk assessment frameworks (Naegeli et al., 2020; Kim et al., 2023). Engaging stakeholders in the monitoring process can also help to manage uncertainties by incorporating diverse perspectives and local knowledge (Kuzma et al., 2017; Thizy et al., 2020).

8 Ethical and Social Considerations

8.1 Ethical implications of releasing gene drive systems into the environment

The release of gene drive systems into the environment raises significant ethical concerns. One primary issue is the potential for irreversible ecological impacts, as gene drives can spread rapidly and alter entire populations (Tanaka et al., 2017; Kim et al., 2023). The ethical debate extends beyond risk assessment and management to include broader considerations such as the alteration of conservation practices and value commitments. The instrumentalist perspective, which views gene drives as tools to achieve specific ends, must be complemented by a form-of-life perspective that considers how these technologies restructure the activities and relationships within ecosystems (Sandler, 2019). Additionally, the potential for unintended consequences, such as the accidental release of gene drives, necessitates a cautious approach to their deployment.

8.2 Public perception and acceptance of gene drive technologies

Public perception and acceptance of gene drive technologies are critical factors in their development and deployment. There is a need for transparent and inclusive public engagement to address concerns and build trust (Long et al., 2020; Devos et al., 2022). The ethical landscape of gene drive research includes questions about community engagement, consent, and the distribution of power and perspectives (Kormos et al., 2022). Effective communication and education about the potential benefits and risks of gene drives are essential to gain public support and acceptance (Callies et al., 2019). Moreover, the involvement of local communities in the co-development of gene drive technologies can help ensure that their perspectives and needs are considered.

8.3 Involvement of stakeholders in the decision-making process

The involvement of stakeholders in the decision-making process is crucial for the responsible development and deployment of gene drive systems. Stakeholders, including local communities, policymakers, scientists, and ethicists, should be actively engaged in discussions about the potential risks and benefits of gene drives (Long t al., 2020; Devos et al., 2022). The development of global frameworks, standards, and guidelines can help ensure that stakeholder engagement is meaningful and effective (Kormos et al., 2022). Additionally, the Institutional Analysis and Development (IAD) framework can be used to categorize variables associated with gene drive governance and inform the design of research programs and public engagement strategies (Kuzma et al., 2017). Ensuring that the decision-making process is inclusive and transparent can help address ethical concerns and build public trust in gene drive technologies.

9 Policy and Regulatory Frameworks

9.1 Current regulatory approaches to gene drive system releases

Current regulatory approaches to the release of gene drive systems are varied and evolving. Regulatory bodies are grappling with the unique challenges posed by gene drive-modified organisms (GDMOs), which include potential irreversible environmental impacts and ethical considerations. For instance, the European Food Safety Authority (EFSA) has reviewed its guidelines and found them to be adequate but insufficient for the comprehensive risk assessment of GDMOs, indicating a need for further guidance specific to gene drives (Naegeli et al., 2020). Additionally, the US National Academy of Sciences has released guidelines emphasizing phased testing and ecological-risk assessments to ensure responsible conduct of gene-drive research (Esvelt, 2016). These guidelines aim to address the potential risks and benefits of gene drive technology while ensuring public trust and safety.

9.2 Comparison of international guidelines and frameworks

Internationally, there are several mechanisms and frameworks in place to evaluate and regulate gene drive research. The Convention on Biological Diversity and the Cartagena Protocol provide platforms for international dialogue on the governance of gene drives (Thizy et al., 2020). Regional entities, such as the African Union, are also developing specific frameworks to prepare for the oversight of gene drive organisms. In contrast, the European Union faces challenges in adapting its regulatory provisions to cover the potential risks associated with GDMOs, highlighting the need for fundamental adaptations and the development of adequate risk assessment methodologies (Dolezel et al., 2020). The existing regulatory frameworks for agricultural pest control, such as classical biological control and the sterile insect technique, offer valuable insights and practices that could be adapted for gene drive technologies (Romeis et al., 2020).

9.3 Recommendations for strengthening policy and regulatory oversight

To strengthen policy and regulatory oversight of gene drive systems, several recommendations have been proposed. These include developing more practical and specific risk assessment guidance to ensure appropriate levels of safety and making policy goals and regulatory decision-making criteria operational for use in risk assessment (Devos et al., 2022). Additionally, there is a need for a dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modeling and post-release monitoring. Incorporating ecological features into gene drive models is also crucial for realistically evaluating gene drive dynamics and potential outcomes (Kim et al., 2023). Furthermore, fostering open and responsive science, where researchers share their plans and invite feedback, can help build public trust and ensure that gene drive research serves the public interest (Esvelt et al., 2016). Implementing a modular, phased approach to authorizations can allow for incremental acceptance and management of risks and uncertainties associated with gene drive applications. By adopting these recommendations, regulatory bodies can enhance their preparedness and responsiveness to the unique challenges posed by gene drive systems, ensuring that the technology is developed and deployed responsibly and ethically.

10 Concluding Remarks

The study of the literature on the environmental release of gene drive systems highlights several critical points. Firstly, the potential of gene drives to address issues such as vector-borne diseases, agricultural pests, and invasive species is significant, but it comes with substantial ecological risks and uncertainties. Current regulatory frameworks and risk assessment guidelines are often deemed inadequate or insufficient for the unique challenges posed by gene drive-modified organisms (GDMIs). Recommendations for improving risk assessment include developing more practical guidance, ensuring dynamic interplay between risk assessment and management, and considering both potential risks and benefits. Additionally, incorporating ecological features into gene drive models is crucial for realistic evaluations of gene drive dynamics and outcomes. The need for open and transparent scientific practices is also emphasized to build public trust and ensure responsible research.

Future research should focus on several key areas to enhance ecological risk assessment and monitoring of gene drive systems. There is a need for more comprehensive and practical risk assessment frameworks that can address the unique challenges of GDMIs. This includes developing methodologies that incorporate ecological processes and feedback mechanisms. Further research is also needed to evaluate the long-term and large-scale risks at population and ecosystem levels, as well as to develop robust post-release monitoring strategies. Additionally, exploring the socio-ecological implications of gene drive releases through systems thinking and mapping can provide valuable insights for governance and public engagement.

To ensure the responsible development and deployment of gene drive systems, several recommendations for policy, practice, and public engagement are proposed. Policymakers should establish clear and operational criteria for risk assessment and regulatory decision-making, ensuring that what constitutes harm is well-defined. A modular, phased approach to authorizations can help manage risks and uncertainties incrementally. In practice, researchers should adopt open and transparent scientific practices, sharing their plans and results with the public and other stakeholders to build trust and facilitate collaborative problem-solving. Public engagement should be prioritized, with mechanisms for community involvement in the risk analysis process to ensure that societal values and concerns are adequately addressed. By implementing these recommendations, the potential benefits of gene drive technologies can be realized while minimizing ecological risks and fostering public trust.

Acknowledgments

EcoEvo Publisher thanks the anonymous reviewers for their insightful comments and suggestions that improved the manuscript.

Conflict of Interest Disclosure

The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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