Regulation and Policy
Risk assessments, regulation of gene drive, and thought leadership on gene drive policy
Genetic Control in Historical Perspective: The Legacy of India’s Genetic Control of Mosquitoes Unit
19652R. Wilbanks, Hastings Center Report, 51:S11-S18. 2021-12-14 18:54:15.
Abstract In the early 1970s, a World Health Organization-initiated and United States-funded project released lab-reared mosquitoes outside New Delhi in the first large-scale field trials of the genetic control of mosquitoes. Despite partnering with the Indian Council of Medical Research and investing significantly in outreach to local communities at the release sites, the project was embroiled in controversy and became an object of vehement debate within the Indian parliament and diplomatic contretemps between the United States and India. This early episode of genetic control research demonstrates how a scientific collaboration was entangled in geopolitics and shaped by the legacy of colonialism. This historical case study has implications for public deliberation in the present, pointing to the challenges of shared decision-making in the context of structural inequality, the way that a backdrop of military interest in a technology can impede trust, and the long-term consequences of projects that foster mistrust.
Deficits of Public Deliberation in U.S. Oversight for Gene Edited Organisms
19650J. Kuzma, Hastings Center Report, 51 Suppl 2:S25-s33. 2021-12-14 18:49:23.
Environmental releases of gene edited (GEdOs) and gene drive organisms (GDOs) will likely occur under conditions of high uncertainty and in complex socioecological systems. Therefore, public deliberation is especially important to account for diverse interpretations of safety, risks, and benefits; to draw on experiential and public wisdom in areas of proposed release; to ameliorate dangers of technological optimism; and to increase the public legitimacy of decisions. Yet there is a "democratic deficit" in the United States' oversight system for GEdOs and GDOs, as unconflicted experts, publics, and skeptical stakeholders are most often excluded from decision-making and unavailable to critically examine potential risks and benefits or raise broader concerns about socioeconomic or cultural impacts. This article argues for the need to open up decision-making for GEdOs and GDOs, discusses the challenges for doing so within the current oversight framework, and finally, proposes institutional, policy, and attitudinal changes that are likely important for overcoming barriers to public deliberation.
Public Deliberation about Gene Editing in the Wild
19648M. K. Gusmano, G. E. Kaebnick, K. J. Maschke, C. P. Neuhaus and B. C. Wills, Hastings Center Report, 51 Suppl 2:S2-s10. 2021-12-14 18:42:52.
Genetic editing technologies have long been used to modify domesticated nonhuman animals and plants. Recently, attention and funding have also been directed toward projects for modifying nonhuman organisms in the shared environment-that is, in the "wild." Interest in gene editing nonhuman organisms for wild release is motivated by a variety of goals, and such releases hold the possibility of significant, potentially transformative benefit. The technologies also pose risks and are often surrounded by a high uncertainty. Given the stakes, scientists and advisory bodies have called for public engagement in the science, ethics, and governance of gene editing research in nonhuman organisms. Most calls for public engagement lack details about how to design a broad public deliberation, including questions about participation, how to structure the conversations, how to report on the content, and how to link the deliberations to policy. We summarize the key design elements that can improve broad public deliberations about gene editing in the wild.
Empowering Indigenous Knowledge in Deliberations on Gene Editing in the Wild
19646R. Taitingfong and A. Ullah, Hastings Center Report, 51 Suppl 2:S74-s84. 2021-12-14 18:38:07.
Proposals to release genetically engineered organisms in the wild raise complex ethical issues related to their safe and equitable implementation. While there is broad agreement that community and public engagement is vital to decision-making in this context, more discussion is needed about who should be engaged in such activities and in what ways. This article identifies Indigenous peoples as key stakeholders in decisions about gene-editing in the wild and argues that engagement activities need not only include Indigenous peoples but also be designed, conducted, and analyzed in ways that confront longstanding power imbalances that dismiss Indigenous expertise. We offer specific recommendations to guide deliberative activities to not only be inclusive of Indigenous peoples but also to empower their diverse, situated knowledges. We call on those committed to the inclusive design of broad public deliberation to pursue strategies that shift dominant power dynamics to include Indigenous communities in more meaningful ways.
The Decision Phases Framework for Public Engagement: Engaging Stakeholders about Gene Editing in the Wild
19643S. K. Barnhill-Dilling, A. Kokotovich and J. A. Delborne, Hastings Center Report, 51 Suppl 2:S48-s61. 2021-12-14 18:30:37.
Some experts and advocates propose environmental biotechnologies such as genetic engineering, gene drive systems, and synthetic biology as potential solutions to accelerating rates of species loss. While these tools may offer hope for a seemingly intractable problem, they also present potential governance challenges for which innovative decision-making systems are required. Two of the perennial governance challenges include, when are broader stakeholder groups involved in these decisions and who exactly should be involved? We propose the decision phases framework-which includes research and development, regulatory review, and deployment, management, and monitoring-as a framework for identifying which stakeholders might be best suited for different phases throughout the innovation and deployment of emerging environmental biotechnologies for species protection.
The economic value of genetically engineered mosquitoes as a Malaria control strategy depends on local transmission rates
19788K. Lacy, K. A. Schaefer, D. P. Scheitrum and E. Y. Klein, Biotechnology Journal, 10. 2021-12-06 14:26:13.
This paper assesses the economic value of genetically engineered (GE) Anopheles gambiae mosquitoes as a malaria control strategy. We use an epidemiological-economic model of malaria transmission to evaluate this technology for a range of village-level transmission settings. In each setting, we evaluate public health outcomes following introduction of GE mosquitoes relative to a "status quo" baseline scenario. We also assess results both in contrast to-and in combination with-a Mass Drug Administration (MDA) strategy. We find that-in low transmission settings-the present value (PV) public health benefits of GE mosquito release are substantial, both relative to status quo dynamics and MDA. In contrast, in high transmission settings, the release of GE mosquitoes may increase steady-state infection rates. Our results indicate that there are substantial policy complementarities when GE mosquito release is combined with local MDA-the combined control strategy can lead to local eradication.
Public Perceptions Regarding Genomic Technologies Applied to Breeding Farm Animals: A Qualitative Study
19920F. Z. Naab, D. Coles, E. Goddard and L. J. Frewer, BioTech, 10. 2021-12-03 09:13:38.
The societal acceptability of different applications of genomic technologies to animal production systems will determine whether their innovation trajectories will reach the commercialisation stage. Importantly, technological implementation and commercialisation trajectories, regulation, and policy development need to take account of public priorities and attitudes. More effective co-production practices will ensure the application of genomic technologies to animals aligns with public priorities and are acceptable to society. Consumer rejection of, and limited demand for, animal products developed using novel genomic technologies will determine whether they are integration into the food system. However, little is known about whether genomic technologies that accelerate breeding but do not introduce cross-species genetic changes are more acceptable to consumers than those that do. Five focus groups, held in the north east of England, were used to explore the perceptions of, and attitudes towards, the use of genomic technologies in breeding farm animals for the human food supply chain. Overall, study participants were more positive towards genomic technologies applied to promote animal welfare (e.g., improved disease resistance), environmental sustainability, and human health. Animal “disenhancement” was viewed negatively and increased food production alone was not perceived as a potential benefit. In comparison to gene editing, research participants were most negative about genetic modification and the application of gene drives, independent of the benefits delivered.
New Arthropod Containment Recommendations Provide Essential Guidance for Safety of Gene Drive Research
19467S. James and D. O’Brochta, The American Journal of Tropical Medicine and Hygiene, tpmd211148. 2021-11-30 14:49:53.
Gene drive technologies have not yet been field tested, however, there are no data on the possible environmental or health effects of releasing gene drive–modified organisms. For this reason, there have been widespread calls for additional guidance on risk assessment and management, and some have even proposed a moratorium on gene drive research until such guidance is in place. One immediate need has been for guidance on appropriate containment measures that researchers should follow when investigating gene drive–modified organisms, given that these are meant to spread their transgenes by inter breeding with compatible local species. For example, a 2020 survey of biosafety professionals revealed that the majority felt existing guidance was inadequate for making risk assessments and containment decisions regarding gene drive–modified arthropods. Lack of standard guidance can lead to uneven application of containment measures among institutions and decreased public confidence in the research. The American Committee of Medical Entomology (ACME)of the American Society of Tropical Medicine and Hygiene has responded to this need with the recent publication of an addendum to its widely influential Arthropod ContainmentGuidelines. The new addendum6provides specific recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive.
New molecular genetic techniques: regulatory and societal considerations
19403Nielsen, K. M., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 18:07:46.
A rapidly expanding toolbox of techniques available for genome editing provides the basis for a new continuum in types of modifications that can be introduced into a genome and blur the bimodal GMO vs. non-GMO (genetically modified organism) divide. Site-directed nucleases (SDN) are now used to modify existing nucleotides within genomes instead of adding recombined DNA as transgenes. Moreover, new gene drive approaches are in development based on SDNs. A number of potential drive applications have been reported, but uncertainties in trait stability and limitations in knowledge of the affected system at various temporal and spatial levels slow down their current uses. Adoption of new genome targeted technology takes place in a social context. The context will vary between countries and cultures, expressed in values, ethics, politics and priorities - that are translated into different regulatory approaches. Some developed products using new genome editing techniques clearly fall under internationally negotiated regulations of GMOs. However, other product outcomes of editing techniques challenge our current understanding and definition of GMOs. There is an urgent need for further research, for building international consensus and harmonizing regulatory approaches to facilitate categorization, predictability, transparency, trust and trade.
Genome editing and its applications for insect pest control: Curse or blessing?
19401Hacker, I. , and Schetelig, M. F, AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 18:00:39.
Gene and genome editing are described as cutting-edge research tools with the potential to tackle urgent global challenges in the management of agricultural pests and human disease vectors such as mosquitoes. The field is defined by the chances and challenges to interlink the disciplines of insect genomics, molecular biology, and pest control together with the need for clear risk assessment, policy development and public approval of the application of such novel technologies. The goal is to generate innovative and sustainable pest control solutions applied in the best interest for the environment and human society. Here, starting from available genome editing technologies, the current strategies and applications for insect pest control are discussed, including approaches to overcome the evolution of resistance alleles and other potential pitfalls to be expected from selective pressures resulting from gene drive applications. They are supplemented by views on regulatory, policy and ethical considerations that in our opinion will be necessary to define how the different tools can be used in the future in a safe and responsible way.
Procedurally Robust Risk Assessment Framework for Novel Genetically Engineered Organisms and Gene Drives
19376Kuzma, J., Regulation and Governance, 15:1144-1165. 2021-11-29 17:13:52.
In this article, a new framework for improving risk assessments of novel genetically engineered organisms (GEOs) is developed and applied. The Procedurally Robust Risk Assessment Framework (PRRAF) provides a set of principles and criteria for assessing and enhancing risk assessment protocols for GEOs under conditions of high uncertainty. The application of PRRAF is demonstrated using the case of a genetically engineered mosquito designed to kill its wild population and therefore decrease disease transmission. Assessments for regulatory approval of this genetically engineered insect fall short of several PPRAF criteria under the principles of humility, procedural validity, inclusion, anticipation, and reflexivity. With the emergence of GEOs designed to spread in ecosystems, such as those with gene drives, it will become increasingly important for regulatory agencies and technology developers to bolster their risk analysis methods and processes prior to field testing. PRRAF can be used as a flexible guide for doing so within a variety of institutional, regulatory, and governance contexts.
CRISPR-based gene drives for combatting malaria: Need for an early stage technology assessment.
19374Liebert, W., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 17:09:24.
The potential power of CRISPR-based gene drives makes it necessary to engage in science and technology assessment already in early stages of research and development. In order to argue for efforts to address this urgent need, gene drives to combat malaria-transmitting mosquitoes are discussed using the concept of prospective technology assessment. First, development risks are described, followed by considerations about anticipatable risks and irreversible consequences, as well as unforeseeable effects and uncertainties. Afterwards, fundamental problems in connection with the development of gene drives against malaria mosquitoes are raised. Opportunities for shaping technology are briefly discussed, before alternatives, in particular the World Health Organization's elimination strategy, are considered. Finally, several normative questions are put forward.
AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application
19371Hendrichs, J. Pereira, R., Vreysen, M. J. B., AREA-WIDE INTEGRATED PEST MANAGEMENT: Development and Field Application, 2021-11-29 17:04:54.
The concept of area-wide integrated pest management (AW-IPM), in which the total population of a pest in an area is targeted, is central to the effective control of such populations through the integration of genetic, biological and other pest suppression technologies. Insect movement, occurring sometimes over long distances, is generally underestimated. As a consequence, most conventional pest management is implemented as a localized or field-by-field, un-coordinated action against segments of a pest population, not taking in consideration insect movement, resulting very often in an unsustainable spiral of insecticide application and eventual resistance of the pest against the used insecticides. On the other hand, an AW-IPM approach adopts a preventive rather than a reactive strategy, whereby all individuals of the pest population are targeted in time and space and selecting a time when the pest populations are more vulnerable (e.g. during certain times of the year when the population densities are naturally low), requiring in the longer term fewer inputs and resulting in more cost-effective and sustainable pest management. It involves a coordinated effort over often larger areas, including not only agricultural, but also natural and other areas with pest presence. By addressing these sources of reinfestation in the surroundings of the agricultural areas, satisfactory pest control is achieved in the whole area and fewer control actions are required. This new textbook on AW-IPM assembles a series of selected papers that attempts to address various fundamental components of AW-IPM, e.g. the importance of relevant problem-solving research, the need for essential baseline data, the significance of integrating adequate tools for appropriate control strategies, and the value of pilot trials, etc. Of special interest are the numerous papers on pilot and operational programmes that pay special attention to practical problems encountered during the implementation of insect pest control programmes. A significant number of contributions to this book resulted from oral and poster presentations at the Third FAO/IAEA International Conference on “Area-wide Management of Insect Pests: Integrating the Sterile Insect and Related Nuclear and Other Techniques”, which was successfully held from 22-26 May 2017 at the Vienna International Centre, Vienna, Austria. The conference was attended by 360 delegates from 81 countries and six international organization. However, the book contributions were selected beyond the work presented at the conference and a number of experts dealing mainly with action programmes were invited to present their work in this publication
A Household-Based Survey to Understand Factors Influencing Awareness, Attitudes and Knowledge towards Wolbachia-Aedes Technology
19435L. T. Soh, Z. Ong, K. Vasquez, I. Chen, X. Li, W. Niah, C. Panchapakesan, A. Sheldenkar, S. Sim, L. C. Ng and M. O. Lwin, International Journal of Environmental Research and Public Health, 18. 2021-11-15 20:37:00.
In 2016, Singapore introduced the release of male Wolbachia-Aedes mosquitoes to complement vector control efforts and suppress Aedes aegypti mosquitoes in selected study sites. With ongoing expansion of Project Wolbachia-Singapore to cover larger areas, a household-based survey was conducted between July 2019 to February 2020 in two Project Wolbachia study sites using a structured questionnaire, to evaluate current sentiments and assess the need for enhanced public messaging and engagement. The association of factors that influence awareness, attitudes, and knowledge towards the use of Wolbachia-Aedes technology was analysed using Pearson's Chi-square test and binary logistic regression. Of 500 respondents, 74.8% were aware of Project Wolbachia-Singapore. Comparatively, the level of knowledge on Wolbachia-Aedes technology was lower, suggesting knowledge gaps that require enhanced communication and messaging to address misinformation. Longer exposure to the project predicted greater awareness, whereas higher education levels predicted higher knowledge levels. Younger age groups and higher education levels were associated with high acceptance towards the project. High levels of trust and acceptance towards the project were also observed across the population. The public's positive perception of the project is a testament to the effective public communication undertaken to date and will facilitate programme expansion.
Containment Practices for Arthropods Modified with Engineered Transgenes Capable of Gene Drive Addendum 1 to the Arthropod Containment Guidelines, Version 3.2
19069American Committee of Medical Entomology, Vector-Borne and Zoonotic Diseases, 2021-10-28 20:19:33.
Responsible conduct of research is a cornerstone of rigorous scientific discovery. Institutional committees, independent advisory panels, and expert steering groups are among the frameworks in academia meant to provide guidance and assurances that research activities do not result in harm to the environment, research staff, or public safety. For research involving arthropods of public health importance, several documents currently exist to guide investigators in methodologies to consider for reducing risks from arthropod escape. However, to date, there has been no standardized set of recommendations on containment practices for arthropods modified with engineered transgenes capable of gene drive. This document is meant to serve as a practical reference to fill that gap. Recommendations outlined here address containment considerations when a risk assessment indicates a possibility of establishment of a new arthropod vector species or genetically modified arthropods in the local environment.
Ecological vulnerability analysis for suppression of Drosophila suzukii by gene drives
19082C. R. Lalyer, L. Sigsgaard and B. Giese, Global Ecology and Conservation, 32:e01883. 2021-10-17 20:44:52.
Synthetic gene drives are transgenic constructs that aim to bias heredity and thereby influence the characteristics and fate of populations regarding abundance and evolution. Aside from irreversible effects in ecosystems that could be triggered by the release of a gene drive, research on confinable drives or even the reversibility of gene drives is underway and shows first success under laboratory conditions. However, their effectiveness under realistic conditions is not entirely clear unless first test releases have taken place. Since a potentially irreversible intervention into ecosystems is created, a prospective assessment is needed. We present an approach of prospective ecological vulnerability analysis for the proposed control of the invasive pest Drosophila suzukii by using gene drives. The analysis considers the accidental spread of the gene drive to the native habitat of Drosophila suzukii, with a focus on Japan. It contains a mapping of potential impacts as a consequence of the suppression of the insect. Multiple cascading effects were identified including the potential spread of the gene drive in geographic range or potential hybridization with non-target species. Determining the vulnerability of an ecosystem requires information regarding specific characteristics at different organizational levels. The vulnerability analysis of an affected ecosystem will initially serve to identify gaps in knowledge. Reducing complexity and breaking down the potential events that might arise from a gene drive population suppression enables to better understand endpoints i.e. concrete effects. Three potential effects have been selected for a specific analysis of the vulnerability of populations and species. A high vulnerability was obtained for the suppression of non-target (native) populations of Drosophila suzukii as well as for a decrease in specialized parasitoid abundance. The paper proposes the outline of a comprehensive prospective approach to understand the susceptibility of an ecosystem to unintended and irreversible harm.
Gene drive and RNAi technologies: a bio-cultural review of next-generation tools for pest wasp management in New Zealand
19000S. Palmer, P. K. Dearden, O. R. Mercier, A. King-Hunt and P. J. Lester, Journal of the Royal Society of New Zealand, 1-18. 2021-10-14 15:09:43.
There is a global need for novel, next-generation technologies and techniques to manage pest species. We review work on potential step-changing technologies for large landscape (>1000 hectares) pest management of social Vespula wasps. We also review M?ori perspectives on these controls to gauge social and cultural acceptability to research, test and use of novel controls. Approaches discussed are the use of gene silencing (RNAi) and gene drives (CRISPR-Cas 9) involving genetic modification, which has potential for pest control but vary in feasibility, cost, benefits and off-target risks. RNAi may be better suited for wasp control in high-value cropping systems due to scaling inefficiencies. Gene drives offer potential for large-scale control but would require legislative and wide social deliberation due to their status as genetic modification. Both RNAi and gene drives will require consultation with tangata whenua. M?ori interest groups agreed that exotic wasps must be controlled and expressed aversion to non-targeted traditional control methods. We present a diversity of opinions in parallel with scientific research underscoring the need for continued dialogue with M?ori. Novel biotechnological controls must satisfy a broad range of social and cultural criteria, receive regulatory approval, along with being demonstrated as safe, selective, and cost-effective.
Small-scale release of non-gene drive mosquitoes in Burkina Faso: from engagement implementation to assessment, a learning journey
18910L. Pare Toe, N. Barry, A. D. Ky, S. Kekele, W. Meda, K. Bayala, M. Drabo, D. Thizy and A. Diabate, Malaria Journal, 20:395. 2021-10-11 14:50:37.
This study provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework-using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community. RESULTS: This paper shows the importance of this first phase of work to innovate and learn about engagement processes for responsible research in the field of genetic approaches for malaria vector control. The function of these assessments is crucial for the learning agenda. The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research.
Gene Drive Organisms: A new dimension of genetic engineering
18790V. Henn and M. Imken, Save Our Seeds, 2021-09-21 13:42:53.
Enabled by new genetic engineering techniques such as CRISPR/Cas9, so-called gene drives have been developed in recent years that enable humans to spread new genes throughout the genome of wild animal populations. Gene drives force the inheritance of newly introduced genes to be inherited by all offspring, even if this lowers the survival chances of the affected species. In the most extreme case, gene drive technology could drive an entire species to extinction or replace wild populations with genetically modified organisms.
The international governance of gene drive organisms
18320F. Rabitz, Environmental Politics, 2021-08-29 13:07:16.
Gene Drive Organisms (GDOs) are a proposed biotechnological intervention that might generate significant benefits for the conservation and sustainable use of biological diversity while also raising critical biosafety issues. Despite their inevitable transboundary effects, their implications for international institutions remain undertheorized. This text develops a theoretical analysis of international GDO governance. First, it elaborates the problem-structural characteristics of GDOs that turn them into a novel and distinct governance challenge, focusing on leverage, cost-benefit distributions, irreversibility, as well as uncertainty and unpredictability. Second, it derives the implications of problem structure for institutional design by focusing on pre-release risk assessment and authorization, as well as post-release monitoring and liability. Third, it uses these institutional implications for benchmarking the Cartagena Protocol on Biosafety, the focal point in international biotechnology regulation, for effective GDO governance. The text concludes that institutional reforms are required for folding GDOs into international biodiversity policy.
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