Regulation and Policy
Risk assessments, regulation of gene drive, and thought leadership on gene drive policy
Report of the ad hoc technical expert group on risk assessment
16095Ad Hoc Technical Expert Group on Risk Assessment, Convention on Biological Diversity, 2020-04-15 15:54:41.
The Conference of the Parties serving as the meeting of the Parties to the Cartagena Protocol further decided to extend the Online Forum on Risk Assessment and Risk Management to assist the AHTEG and invited submissions of information relevant to the work of the online forum and the AHTEG from Parties, other Governments, and indigenous peoples and local communities. The AHTEG is to submit the outcomes of its work for consideration by the Subsidiary Body on Scientific, Technical and Technological Advice at its twenty-fourth meeting, prior to the tenth meeting of the Parties to the Protocol.
GENE DRIVE ORGANISMS: Implications for the environment and nature conservation
16092M. Dolezel, S. Simon, M. Otto, M. Engelhard and W. Zughart, Umweltbundesamt, 2020-04-09 15:46:47.
Recent advances in biotechnology aim at the genetic modification of wild living populations. Some potential applications consider self-propagating genetic elements to generate gene drive organisms (GDOs), also for nature conservation. Due to the potential of GDOs to spread spatially and temporally unlimited, impacts on the environment and ecosystems may be irreversible and are difficult to predict. This technical report summarizes the status of gene drive applications currently discussed in the scientific literature. It outlines their potential implications for the environment and nature conservation and highlights challenges with respect to the environmental risk assessment and post-release monitoring of GDOs, in particular in a context of high complexity and uncertainty.
The value of existing regulatory frameworks for the environmental risk assessment of agricultural pest control using gene drive
8194J. Romeis, J. Collatz, D. C. M. Glandorf and M. B. Bonsall, Environmental Science & Policy, 108:19-36. 2020-03-27 20:20:04.
The application of (synthetic) gene drives is a powerful tool to control populations of insects that are agricultural pests, vectors of diseases, or a threat to biodiversity potentially leading to the local or global eradication of a species. The potential use of gene drive organisms has triggered a heated discussion regarding their environmental impacts and regulatory oversight. However, experience exists in assessing the environmental impacts of a number of established agricultural pest control methods that require the release of living organisms, that provide high levels of area-wide control and that might be irreversible. This includes classical biological control, the sterile insect technique, the incompatible insect technique that is based on the cytoplasmic incompatibility caused by Wolbachia endosymbionts, and genetically modified insects containing self-limiting traits. The different technologies are described, the regulatory practice and experience is summarized and pathways through which these control technologies could harm valued ecosystem services are presented. With a focus on the application of gene drives in agriculture, using the invasive Drosophila suzukii (Diptera: Drosophilidae) as a case study we then discuss to what extent the existing frameworks could assist the risk assessment of insects carrying gene drives. We suggest that drawing on existing practices, experiences and legislative frameworks will provide a pragmatic and proportionate approach to evaluate the environmental risks of novel solutions based on gene drive technologies.
Stakeholder workshop “Problem formulation for the environmental risk assessment of gene drive modified insects” (15 May 2019, Brussels)
8192European Food Safety, A., Devos, Y., Gallani, B. & Firbank, L. G, A. European Food Safety, Y. Devos, B. Gallani and L. G. Firbank, 17:1819E. 2020-03-09 20:12:26.
Recent advances in molecular and synthetic biology are enabling the engineering of gene drives that spread genes of interest through interbreeding populations at a frequency greater than the rate expected by simple Mendelian inheritance. At present, insects represent the most likely cases of gene drive modified organisms for deliberate release into the environment. Through an open workshop, the European Food Safety Authority (EFSA) aimed to engage with stakeholders to discuss potential environmental risks associated with the deliberate release into the environment of gene drive modified insects. Workshop participants were invited to contribute to an example problem formulation to: (1) identify relevant broad protection goals and make them operational for use in environmental risk assessment; (2) formally devise examples of plausible pathways to harm that describe how the deployment of gene drive modified insects could be harmful; (3) formulate example risk hypotheses about the likelihood and severity of such events; (4) identify possible information that would be useful to test these risk hypotheses; and (5) identify how to acquire new data for hypothesis testing when existing information is deemed insufficient for regulatory decision-making. The problem formulation exercise was run for two hypothetical case studies (i.e. self-sustaining low threshold gene drives to control disease-spreading mosquitoes (Aedes albopictus, the Asian tiger mosquito) and agricultural pests (Drosophila suzukii, the spotted-wing Drosophila)). Points raised by the workshop participants reveal different often contrasting opinions/perspectives toward gene drive and their risk assessment. Overall, there was agreement that the problem formulation process is fit-for-purpose for the environmental risk assessment of gene drive modified insects, but it was acknowledged that practical challenges may be encountered. Points raised by the workshop participants, on defining protection goals, formulating specific pathways to harm and on structuring risks, have been considered by EFSA's Panel on genetically modified organisms during its deliberations.
Toward the definition of efficacy and safety criteria for advancing gene drive-modified mosquitoes to field testing
7971S. L. James, J. M. Marshall, G. K. Christophides, F. O. Okumu and T. Nolan, Vector Borne and Zoonotic Diseases, 20:237. 2020-03-09 14:54:00.
Mosquitoes containing gene drive systems are being developed as complementary tools to prevent transmission of malaria and other mosquito-borne diseases. As with any new tool, decision makers and other stakeholders will need to balance risks (safety) and benefits (efficacy) when considering the rationale for testing and deploying gene drive-modified mosquito products. Developers will benefit from standards for judging whether an investigational gene drive product meets acceptability criteria for advancing to field trials. Such standards may be formalized as preferred product characteristics and target product profiles, which describe the desired attributes of the product category and of a particular product, respectively. This report summarizes discussions from two scientific workshops aimed at identifying efficacy and safety characteristics that must be minimally met for an investigational gene drive-modified mosquito product to be deemed viable to move from contained testing to field release and the data that will be needed to support an application for first field release.
Risk assessment challenges of synthetic gene drive organisms
12529E. Sirinathsinghji, TWN Biosafety Briefing, 2020-03-01 15:12:11.
Regulation of GM Organisms for Invasive Species Control
6701H. J. Mitchell and D. Bartsch, Frontiers in Bioengineering and Biotechnology, 7:1-11. 2020-01-21 18:17:37.
Invasive species can cause significant harm to the environment, agriculture, and human health, but there are often very limited tools available to control their populations. Gene drives (GD) have been proposed as a new tool which could be used to control or eliminate such species. Here, GD describes a variety of molecular biology applications which all enable the introduction of genetic elements at a higher than expected frequency. These elements can change the genotypes in target populations rapidly with consequences either for (intrinsic) fitness or host-parasite interaction, or both. Beneficial applications are foreseen for human and animal health, agriculture, or nature conservation. This rapidly developing technology is likely to have major impacts in the fight against various diseases, pests, and invasive species. The majority of GD applications involve genetic engineering and novel traits. Therefore, applicants and GMO regulators need to interact to achieve the benefits in innovation while cautiously avoiding unacceptable risks. The release into the environment may include transboundary movement and replacement of target populations, with potential impact on human/animal health and the environment. This article summarizes knowledge-based discussions to identify information gaps and analyzes scenarios for responsible introduction of GD organisms into the environment. It aims to connect the latest scientific developments with regulatory approaches and decision-making.
Irreversible ecosystem engineering with Gene Drive Organisms
8178Save Our Seeds, Save Our Seeds, 2020-01-18 19:56:07.
Gene drive technology is a particular application of the new genetic engineering tool CRISPR/Cas9. It is designed to genetically modify, replace or eradicate wild populations or entire species. So far it works in mosquitos, mice, flies, yeast and nematodes. But in principle it could be used to genetically modify any sexually reproducing organism. Gene drive organisms (GDOs) are meant to mate with their wild relatives and spread their engineered genes to ALL of their offspring. This forced inheritance pattern circumvents natures normal rules of inheritance. It triggers a genetic chain reaction in which the genetic engineering tool CRISPR/Cas9 and sometimes an additional new gene are passed on from generation to generation. Genetic changes induced by a gene drive can lead to sterility or the change of sex ratio of their descendants, leading to a crash in their population. First field trials in nature are foreseen for the near future.
Metaphor, Trust and Support for Non-native Species Control
13833P. A. Kohl, S. J. Collins and M. Eichholz, Environmental Communication, 14:672-685. 2020-01-07 15:29:47.
This experimental study used a representative sample of U.S. residents (N = 1,042) to test whether the use of the term "invasive" increases support for non-native species control efforts. The term invasive had a small influence on support for two out of three non-native species control methods. We also found stronger support for control methods using gene editing technologies than control methods using poison.
Technology Factsheet: Gene Drives
7265J. Lunshof, C. Shachar, R. Edison, A. Jayanti, Belfer Center for Science and International Affairs, 2020-01-01 17:03:29.
Gene drives can be defined as genetic elements that pass from parents to unusually high numbers of their offspring due to biased inheritance (sometimes referred to as the possession of “selfish” genetic elements).1,2 There are different ways of achieving this biased inheritance needed for a drive, but the shared outcome is one where the offspring of a parent carrying a certain genetic variant has over a 50% likelihood of inheriting it. With regular inheritance, in the absence of a gene drive, each of the two alleles carried by a parent are equally likely to be inherited by offspring. By implementing modern gene editing technology, such as CRISPR, gene drives can be manufactured by humans to intentionally suppress a target population or spread a trait through a population. For example, gene drives could be used to target weeds, spreading a trait that would reverse their evolved resistance to non-toxic herbicides. Gene drives could also be used for human health purposes, in particular for the control of vector-borne diseases, such as malaria through populations of mosquitos. There are many outstanding governance questions with regards to the specific research, development, testing, and deployment of gene drives—including who should be taking ownership of drafting regulations and policy. At this stage, few countries currently have regulations that are defined specifically for gene drive, and in most countries the closest relevant regulations are those written for a broader swath of gene editing technologies. As there becomes more momentum around the potentially unique opportunities of gene drives though, it is important for U.S. legislators and policymakers to remain engaged in the technology’s technical, ethical, and practical progress and consider technology-specific governance.
A typology of community and stakeholder engagement based on documented examples in the field of novel vector control
6032C. E. Schairer, R. Taitingfong, O. S. Akbari and C. S. Bloss, PLoS Neglected Tropical Diseases, 13:e0007863. 2019-12-30 20:46:44.
Background Despite broad consensus on the importance of community and stakeholder engagement (CSE) for guiding the development, regulation, field testing, and deployment of emerging vector control technologies (such as genetically engineered insects), the types of activities pursued have varied widely, as have the outcomes. We looked to previous CSE efforts for clarity about appropriate methods and goals. Our analysis yielded a typology of CSE, and related vocabulary, that describes distinctions that funders, organizers, and scholars should make when proposing or evaluating CSE. Methods We compiled available formal documentation of CSE projects, starting with projects mentioned in interviews with 17 key informants. Major features of these examples, including the initiators, target groups, timing, goals, and methods were identified using qualitative coding. Based on these examples, subcategories were developed for a subset of features and applied to the identified cases of CSE in the documents. Co-occurrence of subcategorized features was examined for patterns. Results We identified 14 documented examples CSE projects, which were comprised of 28 distinct CSE activities. We found no clear patterns with respect to timing. However, we found that grouping examples according to whether initiators or targets could enact the immediate desired outcome could help to clarify relationships between goals, methods, and targets.
Articulating ‘free, prior and informed consent’ (FPIC) for engineered gene drives
5800George, D. R., T. Kuiken and J. A. Delborne, Proceedings of the Royal Society B: Biological Sciences, 286:20191484.. 2019-12-19 14:30:32.
Recent statements by United Nations bodies point to free, prior and informed consent (FPIC) as a potential requirement in the development of engineered gene drive applications. As a concept developed in the context of protecting Indigenous rights to self-determination in land development scenarios, FPIC would need to be extended to apply to the context of ecological editing. Without an explicit framework of application, FPIC could be interpreted as a narrowly framed process of community consultation focused on the social implications of technology, and award little formal or advisory power in decision-making to Indigenous peoples and local communities. In this paper, we argue for an articulation of FPIC that attends to issues of transparency, iterative community-scale consent, and shared power through co-development among Indigenous peoples, local communities, researchers and technology developers. In realizing a comprehensive FPIC process, researchers and developers have an opportunity to incorporate enhanced participation and social guidance mechanisms into the design, development and implementation of engineered gene drive applications.
Exterminator genes: The right to say no to ethics dumping
5654Bassey-Orovwuje, M., J. Thomas and T. Wakeford, Development, 62:121-127. 2019-12-17 18:09:38.
The scientific-industrial complex is promoting a new wave of genetically modified organisms, in particular gene drive organisms, using the same hype with which they tried to persuade society that GMOs would be a magic bullet to solve world hunger. The Gates Foundation claims that GDOs could help wipe out diseases such as malaria. Powerful conservation lobby groups claim GDOs will protect engendered species. Not only are the benefits from GDOs based, like their predecessors, on flawed ecological thinking, but they are backed by the same agri-business interests that have devastated agroecological farming systems. The rights of communities to say ‘no’ to new genetic technologies is being eroded, despite United Nations agreements, such as the Convention on Biological Diversity, which call for the free, prior and informed consent of affected communities to be respected. By exporting their field trials to countries with weak regulatory regimes and lowering of the standards of consent the Gates Foundation’s Target Malaria project has already been guilty of ethics dumping. These developments demonstrate the urgent need to democratize the development of new technologies.
A cross-sectional survey of biosafety professionals regarding genetically modified insects
5650O’Brochta, D. A., W. K. Tonui, B. Dass and S. James, Applied Biosafety, 2019:1-9. 2019-12-17 17:57:33.
Background:Genetic technologies such as gene editing and gene drive create challenges for existing frameworks used to assess risk and make regulatory determinations by governments and institutions. Insect genetic technologies including transgenics, gene editing, and gene drive may be particularly challenging because of the large and increasing number of insect species being genetically modified and the degree of familiarity with these organisms and technologies by biosafety officials charged with making containment decisions.Methods:An anonymous online survey of biosafety professionals was distributed to the membership of ABSA International, a global society of biosafety professionals, to investigate their perspectives on their preparedness to meet these new challenges.Results:Existing guidance used to make containment decisions for nongenetically modified insects was widely seen as adequate, and most respondents thought the available guidance for making containment decisions for genetically modified insects with and without gene drives was inadequate. Most respondents reported having less confidence in their decisions concerning containment of genetically modified insects compared to decisions involving genetically modified microbes, (noninsect) animals, and plants.Conclusions:These results reveal a need for additional support for biosafety professionals to improve the quality of and confidence in containment decisions regarding genetically modified insects with and without gene drive. These needs might be addressed by increasing training, updating existing guidance, creating new guidance, and creating a third-party accreditation entity to support institutions. Sixty percent of the respondents said they either would or might use a voluntary third-party accreditation service to support insect containment decisions.
Plasmodium falciparum (Haemosporodia: Plasmodiidae) and O’nyong-nyong virus development in a transgenic Anopheles gambiae (Diptera: Culicidae) strain
5634Mumford, J. D., C. A. Long, S. C. Weaver, K. Miura, E. Wang, R. Rotenberry, E. M. Dotson and M. Q. Benedict, " Journal of Medical Entomology, 56:936-941. 2019-12-17 16:55:10.
ransgenic Anopheles gambiae Giles (Diptera: Culicidae) mosquitoes have been developed that confer sexual sterility on males that carry a transgene encoding a protein which cuts ribosomal DNA. A relevant risk concern with transgenic mosquitoes is that their capacity to transmit known pathogens could be greater than the unmodified form. In this study, the ability to develop two human pathogens in these transgenic mosquitoes carrying a homing endonuclease which is expressed in the testes was compared with its nontransgenic siblings. Infections were performed with Plasmodium falciparum (Welch) and o’nyong-nyong virus (ONNV) and the results between the transgenic and nontransgenic sibling females were compared. There was no difference observed with ONNV isolate SG650 in intrathoracic infections or the 50% oral infectious dose measured at 14 d postinfection or in mean body titers. Some significant differences were observed for leg titers at the medium and highest doses for those individuals in which virus titer could be detected. No consistent difference was observed between the transgenic and nontransgenic comparator females in their ability to develop P. falciparum NF54 strain parasites. This particular transgene caused no significant effect in the ability of mosquitoes to become infected by these two pathogens in this genetic background. These results are discussed in the context of risk to human health if these transgenic individuals were present in the environment.
What risk assessments of genetically modified organisms can learn from institutional analyses of public health risks
5628Rajan, S. R. and D. K. Letourneau, Journal of Biomedicine and Biotechnology, 2012:8. 2019-12-17 16:46:43.
The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem ofuncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects ofGMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large
Genetic frontiers for conservation: An assessment of synthetic biology and biodiversity conservation
16089K. H. Redford, T. Brooks, M., B. W. Nicholas and J. S. A. Macfarlane, International Union for Conservation of Nature, 2019-12-01 15:41:26.
This assessment is the beginning of a process that will lead to the development of an IUCN policy to guide the Union’s Director General, Commissions, and Members. The draft policy will be discussed in many fora before it is brought to vote at the World Conservation Congress in 2020. Far greater public attention to the topic of synthetic biology and biodiversity conservation is essential, given the potential impact of scientific discoveries and policy decisions that may be just over the horizon, and also given the need for broad partnerships to address the challenges that the conservation and synthetic biology communities will inevitably face
Efforts to enhance safety measures for CRISPR/Cas-based gene drive technology in Japan
6035T. Tanaka, N. Tanaka, Y. Nagano, H. Kanuka, D. S. Yamamoto, N. Yamamoto, E. Nanba and T. Nishiuch, Journal of Environment and Safety, 2019-10-07 20:47:13.
Gene drive is a powerful system that can spread a desirable genetic trait into an entire species and/or population of a certain region, bypassing Mendelian rules of inheritance. Recently, one of the genome editing technologies, CRISPR/Cas, has been developed, making it easier to use gene drive in many different organisms. However, gene drive has potential risks that impact genetic diversity when organisms produced by CRISPR/Cas-based Gene Drive Technology (CCGDT) are accidentally released; therefore, a high degree of prudence is required when CCGDT is used. In Japan, a Working Group on Gene Drive has been established in the Academic Association for Promotion of Genetic Studies (AAPGS), and a Statement on the Handling of Gene Drive was issued to the public including research institute across Japan, after comprehensive and extensive discussions by the working group in order to reduce risks posed by CCGDT. A national-wide survey on CCGDT was implemented. The survey revealed that those in managerial positions including members and secretariats of institutional review boards on recombinant DNA, and biosafety officers are conscious of CCGDT, and efforts to grasp experimental plans involving CCGDT are made by utilizing an application form for recombinant DNA experiment. In contrast, potential risks of CCGDT are not understood by many researchers. All stakeholders need to disseminate potential risks and preventive measures regarding CCGDT to all researchers who may wish to use this technology. Researchers should use CCGDT upon understanding its potential risks and taking necessary measures. This report refers to how safety measures for CRISPR/Cas-based gene drive technology which has potential risks to ecological system has been discussed and results of national-wide questionnaire survey on gene drive in Japan based on the poster presentation at the Asian Conference on Safety & Education in Laboratory 2018.
Gene Drives: Dynamics and Regulatory Matters-A Report from the Workshop “Evaluation of Spatial and Temporal Control of Gene Drives,” April 4-5, 2019, Vienna
12396B. Giese, J. L. Friess, N. H. Barton, P. W. Messer, F. Debarre, M. F. Schetelig, N. Windbichler, H. Meimberg and C. Boete, Bioessays, 41:3. 2019-10-07 18:26:19.
Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems. The recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.
Malaria eradication within a generation: ambitious, achievable, and necessary
12533R. G. A. Feachem, I. Chen, O. Akbari, A. Bertozzi-Villa, S. Bhatt, F. Binka, M. F. Boni, C. Buckee, J. Dieleman, A. Dondorp, A. Eapen, N. Sekhri Feachem, S. Filler, P. Gething, R. Gosling, A. Haakenstad, K. Harvard, A. Hatefi, D. Jamison, K. E. Jones, C., Lancet, 394:1056-1112. 2019-09-13 15:21:30.
50 years after a noble but flawed attempt to eradicate malaria in the mid-20th century, the global malaria community is once again seriously considering eradication. Momentum towards eradication has been building for decades, and more than half of the world’s countries are now malaria free.
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