A decade of intense debate, a science ready to move forward. Can regulation become the bridge, not the barrier?

This version (Version 1) was created on 30 October 2025

Almost fifteen years after the first proof of concept studies on gene drives, no field trial has yet taken place. In several African countries, research teams have built modern insectaries, trained local scientists and prepared community engagement plans. Still, permission to release even a few modified mosquitoes into contained field sites has not been granted.

Lanzaro and Kormos (2025) suggest that the problem is not scientific but regulatory. They explain that small, confined field trials are being treated as if they were large, cross-border releases. This confusion has created many overlapping guidelines and recommendations, which make it difficult to know who is responsible for what and what kind of evidence is needed.

The authors recognise that ethical and safety questions are important, but they warn that the discussions around them have become repetitive and unhelpful. Instead of supporting progress, those discussions have produced many “soft governance” documents that are difficult for regulators to use in practice. Without data from real field conditions, risk assessment cannot improve, and without a clear assessment, no authority is ready to give approval.

This situation has created frustration among researchers, donors and national partners. The authors argue that, unless small and ecologically contained field trials start soon, the whole gene drive effort could lose direction before it is properly tested.

To understand how regulation arrived here, the following visual summary traces six key dimensions of the debate covered in this review:

1. From the Cartagena Protocol to gene drives: Institutional foundations of regulation

Gene drive research did not start in a vacuum. It grew within the existing biosafety systems that already governed genetically modified organisms. Research institutions had their biosafety boards and containment rules; these worked well enough for bench science. But once the conversation shifted from labs to open air, the question became different: who decides when a lab experiment is ready to be tested under natural conditions?

At the global level, the Convention on Biological Diversity (CBD) and its Cartagena Protocol on Biosafety provide the legal backbone for living modified organisms. Their language is cautious by design. Parties are required to manage cross-border risks, and most of their machinery (the expert groups, the working documents, the conferences) is built around one principle: the precautionary approach. The logic is sound when the aim is to protect biodiversity, but probably less so when the goal is to save lives from malaria. The CBD’s guidance tends to favour small, tightly confined experiments, mirroring the world of crops rather than mosquitoes (Thizy et al. 2020).

The CBD system is evolving. Its Ad Hoc Technical Expert Group on Risk Assessment recently issued voluntary guidance for case-by-case evaluations of organisms containing engineered gene drives (CBD 2024). This document is a welcome step, especially for countries that are still building regulatory capacity or need practical examples to guide their assessments. It can help make the language of biosafety more consistent across regions. Yet, for agencies with more mature systems, the addition of another non-binding text may create uncertainty about which reference to follow. The challenge ahead is not only to produce more guidance, but to ensure that new tools clarify rather than complicate decision-making.

In contrast, the World Health Organization (WHO) speaks a different language. Its committees, especially the Vector Control Advisory Group, see gene drives through the lens of public health, not biodiversity. Their focus is on safety and efficacy: can this tool reduce disease?

The WHO’s Guidance Framework for Testing Genetically Modified Mosquitoes outlines ethical and practical standards, from laboratory containment to community consent (WHO 2021). Building on that guidance, Connolly et al. (2024) describe a phased approach that moves gradually from indoor cages to field releases, always informed by data. It is pragmatic and familiar to public health researchers, but appears conceptually separate from the CBD’s biodiversity framework.

Regional efforts have tried to bring order to this dance. The African Union Development Agency (AUDA-NEPAD) has issued its own Guidelines for Risk Analysis for the Testing and Deployment of Genetically Modified Mosquitoes (AUDA-NEPAD, 2022a) and Guidelines for Containment Facilities for Testing of Genetically Modified Mosquitoes (AUDA-NEPAD, 2022b). These documents aim to align biosafety and public health oversight. Most African countries must navigate both, as biosafety authorities cite the CBD, while health ministries follow WHO advice.

Beyond these main actors, others hover in the background. The International Union for Conservation of Nature shapes opinion on conservation uses of synthetic biology; the European Food Safety Authority advises the EU on environmental risks; and the OECD sets testing standards that end up in every application dossier. None of these institutions has direct authority over gene drives, yet each one leaves fingerprints on the rules (Kelsey et al, 2020; Raynolds, 2020).

Add older treaties such as CITES, the Biological Weapons Convention and the Environmental Modification Convention, and the web grows denser, according to Raynolds (2020, 2021). It is no wonder that a regulator in Uganda or Ecuador may feel overwhelmed by guidance that ranges from biodiversity to biosecurity, from ethics to entomology.

The deeper problem, as Raynolds (2020) reminds us, lies in international law itself. States have both the right to use their own resources and the duty to prevent transboundary harm. The CBD, sitting between these two poles, seems to prioritise the environment over human wellbeing. According to the author, that imbalance would make it not very well suited for a technology that aims to protect people by altering nature.

This tension between mandates is not the only obstacle. Kelsey et al. (2020) describe what they call a pacing problem: scientific advances moving faster than the systems designed to oversee them. Even when institutions agree on goals, the speed of innovation leaves policymakers struggling to keep up. Yet, Kelsey et al., argue that paralysis is not inevitable. The absence of a single global rulebook does not mean countries cannot act. Existing GMO frameworks can support confined trials, provided governance remains adaptive and coordination is clear. Their reminder feels timely: not every new idea needs a new treaty, but the existing ones must learn to move faster.

The gaps that Thizy et al., (2020) identified remain wide: overlapping guidance, uncertainty about community consent, and insufficient thought about how local communities benefit when research stretches over years. Reynolds (2021) puts it bluntly: these are not just technical gaps, they are political choices.

2.  Africa’s pioneering role: Building capacity for gene drive

Africa has become the natural testing ground for engineered gene drive mosquitoes. The malaria burden is highest here, and so is the motivation to explore new tools for control. The African Union’s High-Level Panel on Emerging Technologies (APET) has already identified gene drives as a regional research priority (Ogoyi et al. 2024), and several countries, including Benin, Eswatini, Kenya, Nigeria and Uganda, have established frameworks that could guide their evaluation (Rabuma et al. 2024).

These foundations remain uneven, but they are steadily growing stronger. Rabuma et al. (2024) report that African regulators are increasingly aware of the need to align their approaches and build capacity. They call for more training, stronger regional collaboration and harmonised definitions for risk assessment. Initiatives under the AUDA-NEPAD, such as the aforementioned guidelines  and the APET report on Gene Drives for Malaria Elimination in Africa (APET, 2025), aim to do precisely that. Together, they show how biosafety development can move faster when driven from within the region rather than externally imposed.

On the research side, activity has expanded well beyond a single project. Target Malaria, working in Ghana and Uganda, is developing Anopheles gambiae population-suppression drives to reduce malaria transmission. Transmission Zero, in Tanzania, brings together the Ifakara Health Institute and the National Institute for Medical Research to test a similar approach in local mosquito populations. Further west, the University of California Malaria Initiative is preparing a population-modifying drive in São Tomé and Príncipe, aiming to make Anopheles coluzzii mosquitoes resistant to Plasmodium infection. Together, these efforts form a regional network of innovation: they are not only building insectaries and data but also experience, dialogue and confidence among African scientists and communities.

This growing regional leadership is also reflected in how African experts approach governance. Ogoyi et al. (2024) describe multi-country consultations that identified common protection goals for post-release monitoring, ranging from potential shifts in malaria transmission to ecological and water-quality impacts. The result is not a checklist dictated from abroad but a context-sensitive framework emerging from African discussions. It signals that regional actors are now defining not only what should be monitored but why.

Of course, building such capacity does not erase the importance of public confidence. Here, the past offers valuable lessons. Quemada (2022) reminds us that genetically modified crops, despite technical success, faced deep mistrust in Africa, shaped by European market pressures, corporate concentration and limited local ownership. Those experiences explain why many African governments still approach new biotechnologies cautiously. Yet gene drives arrive in a different setting: their development is largely led by public or university-based groups pursuing a clear health goal, not by multinational corporations. This distinction, if paired with transparent communication and diversified funding, could help avoid the perception of outside control and thus strengthen trust in national decision-making.

3.  When ethics shape policy: Expert and principle-based governance

As African research programmes take the lead in preparing for possible field trials, another layer of governance continues to evolve in expert groups, advisory panels and consensus documents. These are not regulatory bodies, yet their influence is substantial. They operate in the wide space between science and law. In this sense, expert- and principle-based approaches serve as a form of “early governance”: they guide behaviour and build norms while institutions learn how to regulate.

Graeff et al. (2021) captured this dynamic through interviews with professionals involved in gene drive development and oversight. Their views converged on the importance of community engagement, ethics and shared responsibility, but diverged sharply on what those terms actually mean. For some, engagement was an issue of justice. For others, it was instrumental, a way to secure acceptance or avoid backlash. The study also exposed tensions between researchers from high-income countries, where most engineered gene drives are designed, and those from low- and middle-income countries, where releases are most likely. Several interviewees warned that without concrete mechanisms for co-ownership, the rhetoric of “co-development” risks sounding hollow.

This diversity of views matters because it shapes how norms become policy. Graeff et al.'s respondents debated whether gene drives require exceptional treatment or can be governed under existing environmental frameworks. That disagreement reveals a core regulatory dilemma: defining how new a “new technology” really is. When experts cannot agree on whether gene drives are ordinary or exceptional, it becomes harder for regulators to know which precedents apply. In this way, expert discussions do not simply reflect uncertainty but they help create it.

Hartley et al. (2022) examined a different but related sphere: the growing corpus of principle-based documents that now accompany almost every debate on gene drives, in this case applied for conservation purposes. From this literature emerged seven recurring principles: broad and empowered engagement, public acceptance, inclusive decision-making, international cooperation, ethical reflection, diverse expertise and self-regulation. These ideas are becoming the moral vocabulary of gene drive governance. They fill a vacuum left by the absence of binding rules, helping to articulate what “responsible innovation” should look like. Yet, as Hartley et al. note, their power is symbolic more than operational. Principles provide direction, but not procedures. Without translation into concrete standards, like who is involved in the engagement, how consent is defined, or what “ethical” oversight entails, they risk adding another layer of soft governance without real accountability.

The effort to make ethics more tangible has inspired initiatives such as the Code of Ethics for Gene Drive Research (Annas et al. 2022). It extends the discussion from general values to personal and institutional duties: to protect human dignity, ensure fair distribution of risks and benefits and practice ecological stewardship. It also addresses dual-use concerns and calls for transparency throughout the research cycle, from design to post-release monitoring. The inclusion of such commitments suggests that in emerging biotechnologies, ethical self-regulation is not optional, but a condition of legitimacy.

In the broader context of regulation, these expert frameworks act as scaffolding. They help align expectations while governments and international bodies work out the details of legal oversight. They also reflect a shift in governance: from command-and-control regulation towards anticipatory, participatory and reflexive models that rely on shared norms. But the challenge remains to avoid paralysis by principle. When guidelines multiply without clear authority, they risk fragmenting rather than harmonising decisions.

Some of these tensions have already been encountered in neighbouring fields, where experience with containment, reversibility and public trust can offer lessons for gene drive regulation.

4.  Lessons beyond the lab: Cross-sector insights for gene drive regulation

When looking for regulatory parallels, it helps to ask where else science has tried to control living populations under real-world uncertainty. Engineered gene drives are not the first technologies to raise these questions. Tools such as the sterile insect technique (SIT), Wolbachia-based methods and other biocontrol approaches have already forced regulators to balance innovation, precaution and practicality.

The SIT is a strong example of how biological interventions can be developed under a structured, risk-managed framework. Bouyer et al. (2024) describe the SIT as an environmentally friendly method that releases irradiated sterile males to suppress wild populations. Decades of use against agricultural and veterinary pests have demonstrated that area-wide, species-specific control can succeed without introducing genetically modified organisms. Importantly, SIT has progressed under clear operational phases; each with training, data collection, community engagement and external review before moving forward. These phases, endorsed by the WHO’s Vector Control Advisory Group, create a controlled progression that reduces both ecological and financial risks. They show how transparency and staged evaluation can coexist with innovation.

Kapranas et al. (2022) and Romeis et al. (2020) add a regulatory dimension to this picture. Both note that sterile insects are now explicitly recognised within international phytosanitary standards and regional frameworks, such as those of the European Plant Protection Organisation and the North American Plant Protection Organisation. The consensus is that the SIT can be safely managed under existing biosafety and plant protection rules, provided authorities have clear responsibilities and technical expertise. Where obstacles arise, they often come not from risk itself, but from institutional uncertainty: who decides, under what law and with which evidence. This experience is highly relevant for engineered gene drive mosquitoes, where similar jurisdictional questions are emerging.

The Wolbachia approach provides another instructive precedent. These maternal host-inherited bacteria manipulate host reproduction in ways that can suppress or replace mosquito populations (Wang et al. 2025). As Romeis et al. (2020) outline, Wolbachia-infected host population releases have been regulated differently across countries: the USA’s Environmental Protection Agency treats them as biopesticides, Australia’s Veterinary Medicines Authority as “substances” and European agencies as biocidal products. Despite this diversity, authorisations were achieved through a pragmatic interpretation of existing law. The common ingredient was regulatory clarity; identifying what the product is and which agency has competence. This experience suggests that even when legal definitions vary, consistent pathways can emerge when authorities focus on function and risk rather than novelty alone.

A parallel debate has also taken shape in the conservation arena. Hartley et al. (2022) explored how gene drive proposals to manage invasive alien species, such as rodents on islands or invasive mosquitoes in sensitive ecosystems, are testing the limits of existing conservation law. Many of these potential applications blur the line between pest control and species eradication, raising questions about reversibility, ecological cascading and the moral boundaries of intervention. In this space, governance cannot rely solely on biosafety law. It must also account for conservation principles, Indigenous people’s rights and differing national definitions of what constitutes an “invasive species”. The authors argue that this complexity has slowed policy alignment, but it has also pushed the conservation community towards broader engagement and ethical reflection.

Grieger et al. (2024) extend the comparative horizon even further, pairing gene drive organisms with a radically different emerging technology: solar radiation modification. Authors argue that both deal with high uncertainty, systemic interdependencies and potentially irreversible outcomes. Their analysis points to two shared governance strategies. The first is planned adaptive regulation: a system that allows policies to evolve as evidence accumulates, incorporating monitoring, iterative review and feedback loops. The second is responsible research and innovation, which aligns science with societal priorities early in development. Grieger et al. also note that gene drive governance could borrow from climate governance by investing more in decision-modelling and cost–benefit analysis, areas where biotechnology remains weak. This kind of economic reasoning could help regulators and funders decide when and where gene drive trials provide the greatest return relative to other control tools.

Classical biological control also provides a long record of adaptive oversight and post-release learning, though it falls beyond the scope of this article.

Together, these experiences offer more than analogies. They show that regulation can evolve pragmatically, without waiting for perfect certainty. Each field found ways to balance caution with progress, often through stepwise testing, adaptive monitoring and transparent stakeholder involvement. For gene drive organisms, this means that workable pathways already exist: identify the product clearly, assign the competent authority, build technical and social capacity, and learn from evidence as trials advance.

5.  Unanswered questions and the search for regulatory clarity

Even with the scientific and procedural lessons available from other biological control technologies, engineered gene drive organisms face a set of unique regulatory questions that remain unresolved. The problem is not the absence of frameworks, but the absence of clarity about which ones apply, to what, and under whose authority.

James and Santos (2023) describe how the most immediate challenge lies in bridging laboratory success with field evaluation. While SIT, Wolbachia and other genetic biocontrol approaches have demonstrated efficacy in Aedes mosquitoes, engineered gene drives for Anopheles are still confined to cage studies. Moving beyond that point requires not only a solid scientific case but also regulatory certainty.

At present, most malaria-endemic countries are Parties to the Cartagena Protocol on Biosafety, which means that engineered gene drive mosquitoes are likely to be treated as living modified organisms. Yet this classification alone does not specify how to evaluate their health or environmental benefits, nor how to manage their gradual, self-propagating spread.

A key ambiguity lies in product definition. As James et al. (2023) explain, conventional genetically modified crops or self-limiting mosquitoes are regulated as discrete, manufactured entities. In contrast, engineered gene drive mosquitoes are live, self-replicating organisms intended to modify wild populations. This raises the question: is the “product” the released mosquito itself, or the modified wild population that follows? Different interpretations lead to different legal routes. If seen as a biological control agent, gene drive organisms may fall under environmental or agricultural oversight. If classified as a health intervention, the Ministry of Health may be responsible for approval, similar to vaccines or vector control tools. The distinction matters because it affects everything from risk assessment to liability and post-release monitoring.

This uncertainty extends across borders. Gene drives are designed to spread through interbreeding populations, so their movement cannot be managed by the traditional exporter–importer logic of biosafety protocols. As James et al. (2023) note, this makes regional coordination essential: data harmonisation, shared assessment standards and agreed procedures for joint decision-making could prevent regulatory paralysis and avoid conflicting decisions between neighbouring states. Similar mechanisms already exist for vaccines and vector control commodities; gene drives will need the same level of institutional alignment.

Clarity, however, is not only legal, but linguistic too. Alphey et al. (2020) remind us that even among scientists, terminology around gene drives remains inconsistent. Words like “spread”, “persistence” and “fixation” are used loosely or interchangeably, leading to misunderstanding in policy debates. This lack of common language spills into regulation: if regulators and developers do not share precise definitions, risk categories become blurred and communication with the public suffers. Alphey’s proposal for a consensus glossary (defining 78 key terms) was not just a semantic exercise, but a governance tool. Without shared vocabulary, it is difficult to build shared rules.

6.  Regulation at a crossroads: From roadblock to enabler of innovation

After almost twenty years of research, gene drives remain in the space between promise and practice. Laboratory studies have shown what is possible; modelling has refined our expectations; community work has laid the foundations for trust. Yet the first field trials are still pending.

Lanzaro and Kormos (2025) captured a sentiment that many in the field share: that regulation, though essential, has become the main bottleneck to progress. The intention was to ensure responsibility and preparedness, but the result seems to be confusion about who decides, under what framework, and at what level of risk.

Still, I think this is not a story of failure. The history of biotechnology shows that sound regulation takes time and trust to build. What we are seeing is a system learning to accommodate a new category of organism, one that does not fit easily into existing definitions of product, pesticide or medicine. This learning process is demanding, but it is also healthy. It forces us to think more carefully about boundaries, consent and responsibility before action.

The next step does not require dismantling the system that we have but clarifying and connecting it. International instruments, regional frameworks and national biosafety laws already exist; their coherence is what will make them credible. Field trials, when they happen, should not be seen as an endpoint but as part of this process; small, transparent and reversible steps that allow evidence to guide policy rather than speculation.

Like many colleagues, I see in gene drive research not only a technological innovation but also a test of our ability to govern innovation wisely. We owe it to the science, to the communities affected, and to the institutions that we serve to make that test a fair one. Progress will depend less on speed than on shared confidence that the steps taken are sound. When that confidence is in place, the first field release will not mark the end of debate, but the beginning of genuine understanding.

7.  References

Alphey, L. S., Crisanti, A., Randazzo, F., & Akbari, O. S. (2020). Standardizing the definition of gene drive. https://doi.org/10.1073/pnas.2020417117

Annas, G. J., Beisel, C. L., Clement, K., Crisanti, A., Francis, S., Galardini, M., Galizi, R., Grunewald, J., Immobile, G., Khalil, A. S., Muller, R., Pattanayak, V., Petri, K., Paul, L., Pinello, L., Simoni, A., Taxiarchi, C., & Joung, J. K. (2022). A code of ethics for gene drive research. https://doi.org/10.1089/crispr.2020.0096

APET. (2025). Gene drives for malaria control and elimination in Africa. https://apet.fra1.cdn.digitaloceanspaces.com/GENE%20Drive%202nd%20Edition%20Report.pdf

AUDA-NEPAD. (2022a). Guidelines for risk analysis for the testing and deployment of genetically modified mosquitoes. https://www.nepad.org/file-download/download/public/139458

AUDA-NEPAD. (2022b). Guidelines for containment facilities for testing of genetically modified mosquitoes. https://www.nepad.org/file-download/download/public/139455

Bouyer, J. (2024). Current status of the sterile insect technique for the suppression of mosquito populations on a global scale. https://doi.org/10.1186/s40249-024-01242-z

CBD. (2024). Voluntary guidance to support risk assessments of LMOs containing engineered gene drives. https://www.cbd.int/doc/c/175e/90b0/89c0c71660cccc1539adf34f/cp-mop-11-09-en.pdf

Connolly, J. B., Burt, A., Christophides, G., Diabaté, A., Habtewold, T., Hancock, P. A., James, A. A., Kayondo, J. K., Lwetoijera, D. W., Manjurano, A., McKemey, A. R., Santos, M. R., Windbichler, N., & Randazzo, F. (2024). Considerations for first field trials of low-threshold gene drive for malaria vector control. https://doi.org/10.1186/s12936-024-04952-9

de Graeff, N., Jongsma, K. R., Lunshof, J. E., & Bredenoord, A. L. (2021). Governing gene drive technologies: A qualitative interview study. https://doi.org/10.1080/23294515.2021.1941417

Grieger, K., Wiener, J. B., & Kuzma, J. (2024). Improving risk governance strategies via learning: A comparative analysis of solar radiation modification and gene drives. https://doi.org/10.1007/s10669-024-09979-6

Hartley, S., Taitingfong, R., & Fidelman, P. (2022). The principles driving gene drives for conservation. https://doi.org/10.1016/j.envsci.2022.04.021

James, S., & Santos, M. (2023). The promise and challenge of genetic biocontrol approaches. https://doi.org/10.3390/tropicalmed8040201

James, S. L., Dass, B., & Quemada, H. (2023). Regulatory and policy considerations for the implementation of gene drive modified mosquitoes to prevent malaria transmission. https://doi.org/10.1007/s11248-023-00335-z

Kapranas, A., Collatz, J., Michaelakis, A., & Milonas, P. (2022). Review of the role of sterile insect technique within biologically based pest control – An appraisal of existing regulatory frameworks. https://doi.org/10.1111/eea.13155

Kelsey, A., Stillinger, D., Pham, T. B., Murphy, J., Firth, S., & Carballar-Lejarazu, R. (2020). Global governing bodies: A pathway for gene drive governance for vector mosquito control. https://doi.org/10.4269/ajtmh.19-0941

Lanzaro, G. C., & Kormos, A. M. (2025). Is gene drive research losing traction? https://doi.org/10.4269/ajtmh.25-0242

Ogoyi, D. O., Njagi, J., Tonui, W., Dass, B., Quemada, H., & James, S. (2024). Post-release monitoring pathway for the deployment of gene drive modified mosquitoes for malaria control in Africa. https://doi.org/10.1186/s12936-024-05179-4

Quemada, H. (2022). Lessons learned from the introduction of genetically engineered crops: Relevance to gene drive deployment in Africa. https://doi.org/10.1007/s11248-022-00300-2

Rabuma, T., Moronta-Barrios, F., & Craig, W. (2024). Navigating biosafety regulatory frameworks for genetic engineering in Africa: A focus on genome editing and gene drive technologies. https://doi.org/10.3389/fbioe.2024.1483279

Reynolds, J. L. (2020). Governing new biotechnologies for biodiversity conservation: Gene drives, international law, and emerging politics. https://doi.org/10.1162/glep_a_00567

Reynolds, J. L. (2021). Engineering biological diversity: The international governance of synthetic biology, gene drives, and de-extinction for conservation. https://doi.org/10.1016/j.cosust.2020.10.001

Romeis, J., Collatz, J., Glandorf, D. C. M., & Bonsall, M. B. (2020). The value of existing regulatory frameworks for the environmental risk assessment of agricultural pest control using gene drives. https://doi.org/10.1016/j.envsci.2020.02.016

Thizy, D., Coche, I., & de Vries, J. (2020). Providing a policy framework for responsible gene drive research: An analysis of the existing governance landscape and priority areas for further research. https://doi.org/10.12688/wellcomeopenres.16023.1

Wang, G.-H., Hoffmann, A., & Champer, J. (2025). Gene drive and symbiont technologies for control of mosquito-borne diseases. https://doi.org/10.1146/annurev-ento-012424-011039

WHO. (2021). Guidance framework for testing genetically modified mosquitoes. https://iris.who.int/server/api/core/bitstreams/f2a2a50e-9c8b-4885-8946-b0c0b0411bc3/content