1 Introduction

Genetically modified organism (GMO) animals are playing an increasingly significant role in agriculture, medicine, and biological research, offering new possibilities for improving productivity, disease resistance, and scientific understanding. However, the use of GMO animals also raises complex ethical concerns, including questions about species boundaries, animal rights, and the legitimacy of experimental purposes (Eriksson et al., 2018). These concerns are further complicated by issues of animal welfare, the potential for unintended consequences, and the broader societal impacts of genetic modification (Myhr and Myskja, 2018; Bovenkerk, 2020; Shriver, 2020; Cimadori et al., 2025).

The ethical review and welfare protection of GMO animals have become central topics in both regulatory and academic discussions. Current frameworks, such as those in the European Union, often reveal inconsistencies and gaps in the regulation of gene-edited and selectively bred animals, with animal welfare sometimes inadequately protected under existing laws (Cimadori et al., 2025; Shriver, 2020). Ethical considerations extend beyond animal suffering to include principles of animal integrity, naturalness, and the broader societal and environmental impacts of genetic modification (Bovenkerk, 2020). Public perception and trust, as well as the responsibilities of breeding organizations and regulatory authorities, play crucial roles in shaping the governance of GMO animal use (Eriksson et al., 2018; Myhr and Myskja, 2018).

This study will critically examine the current ethical review systems and welfare protection practices related to GMO animals, provide an overview of global ethical review and regulatory frameworks, analyze the practical implementation and challenges of animal welfare protection, and explore future trends and governance pathways. The aim is to offer essential support and guidance for establishing a responsible and humane framework for the development and use of genetically modified animals.

2 Major Applications and Ethical Background of GMO Animals

2.1 Typical application fields

GMO animals are widely used in medical research to create disease models that mimic human conditions, enabling the study of disease mechanisms and the development of new treatments. Transgenic pigs, for example, are engineered for xenotransplantation, offering potential solutions to organ shortages for human transplantation (Eriksson et al., 2018).

In agriculture, genetic modification is applied to enhance traits such as growth rate, disease resistance, and stress tolerance. Notable examples include AquaBounty’s transgenic salmon, which grows faster than conventional salmon, and genome-edited cattle designed to eliminate the need for dehorning or to improve udder health. These applications aim to increase productivity and animal welfare but also raise questions about the broader impacts on food systems and ecosystems (Eriksson et al., 2018; Winther, 2024).

Beyond food and medicine, GMO animals are developed for industrial and environmental purposes, such as serving as biosensors for environmental monitoring or as bioreactors for producing pharmaceuticals and other valuable substances. These novel applications expand the scope of genetic modification but introduce new ethical and regulatory challenges (Eriksson et al., 2018).

2.2 Core ethical controversies

A central ethical concern is the potential instrumentalization and commodification of animals, where their intrinsic value is overshadowed by their utility as tools for human benefit. This raises questions about animal rights and the moral legitimacy of using animals primarily as means to human ends (Eriksson et al., 2018; Winther, 2024).

The irreversibility of genetic modifications and the risk of unintended consequences-such as unforeseen health issues in animals or ecological disruptions-pose significant moral risks. The complexity of genetic backgrounds and the unpredictability of large-scale applications make it difficult to fully anticipate long-term outcomes (Eriksson et al., 2018; Winther, 2024).

Genetic modification often challenges traditional notions of species boundaries and naturalness, leading to public resistance and ethical debate. Concerns include the potential loss of biodiversity, threats to species integrity, and the perception that GMOs are “unnatural,” which can influence both consumer acceptance and regulatory decisions (Verhoog, 2003; Pakseresht et al., 2021; Winther, 2024).

3 Current Landscape of Global Ethical Review and Regulatory Frameworks

3.1 International regulations and ethical guidance

The World Organisation for Animal Health (OIE) provides international standards emphasizing animal welfare in the context of biotechnology, including the need for risk assessment, animal health protection, and ethical oversight in the use of transgenic animals. These principles guide member countries in developing national regulations that prioritize animal welfare and responsible use of biotechnology (Hallerman et al., 2024).

International organizations such as the OECD and WHO have issued policy recommendations focused on risk assessment, ethical governance, and harmonization of regulatory approaches for GMO animals. The Codex Alimentarius, for example, has influenced many national frameworks by providing guidelines for food safety and risk management in genetically modified organisms, including animals. These recommendations encourage science-based, transparent, and proportionate regulation to ensure both safety and ethical acceptability (Hallerman et al., 2024; Wray-Cahen et al., 2024).

The 3Rs principle—Replacement, Reduction, and Refinement—remains a cornerstone of ethical review in GMO animal research. Regulatory frameworks globally require that animal experiments involving GMOs minimize animal use, reduce suffering, and seek alternatives wherever possible, aligning with broader animal welfare objectives (Hallerman et al., 2024; Cimadori et al., 2025).

3.2 Comparative review of major national and regional systems

The European Union adopts a highly precautionary stance, with mandatory ethical assessments, comprehensive risk evaluations, and strong emphasis on transparency and public participation. All gene-edited and transgenic animals are regulated under strict GMO legislation, requiring pre-market authorization, traceability, and labeling. The EU’s approach is characterized by a high level of protection for animal welfare and public involvement in decision-making, but has been criticized for regulatory complexity and potential barriers to innovation (Spicer and Molnár, 2018; Bratlie et al., 2019; Bruetschy, 2019; Choriyeva, 2024; Cimadori et al., 2025).

In the United States, GMO animals are primarily regulated by the FDA and USDA, with a focus on the characteristics of the final product rather than the process used to create it. Ethical considerations are less emphasized, and the regulatory process is generally more streamlined, aiming to facilitate innovation while ensuring safety. This product-based approach has enabled some biotech animals to reach commercialization, though the high cost and complexity of approval remain challenges (Hallerman et al., 2024; Wray-Cahen et al., 2024; Lim and Choi, 2023).

China and Japan are progressively establishing ethical review systems for GMO animals, with a strong orientation toward supporting scientific research and technological innovation. Both countries have prioritized the development of biotechnology for economic and research competitiveness, leading to rapid advances in genetic modification and genome editing. However, their regulatory and ethical oversight frameworks are still maturing, often lagging behind scientific progress. This research-driven approach can result in regulatory gaps, particularly regarding comprehensive ethical review and public engagement, as the focus remains on enabling innovation and commercialization rather than on robust ethical governance (Choriyeva, 2024; Wray-Cahen et al., 2024).

3.3 Implementation challenges and disputes

A major challenge globally is the absence of harmonized ethical review standards for GMO animals. Regulatory requirements and ethical expectations vary widely between countries and regions, leading to inconsistencies in animal welfare protection and public trust. This lack of uniformity complicates international collaboration and the commercialization of GMO animal products (Frewer et al., 2013; Choriyeva, 2024; Wray-Cahen et al., 2024).

Rapid developments in genetic modification and genome editing technologies frequently outpace the evolution of ethical and regulatory frameworks. This creates uncertainty for researchers, regulators, and industry stakeholders, as existing guidelines may not adequately address the risks, welfare concerns, or societal implications of new biotechnologies. The unpredictability of genetic interventions, especially in large-scale or long-term applications, further complicates ethical oversight (Schuppli et al., 2004; Eriksson et al., 2018; Choriyeva, 2024; Wray-Cahen et al., 2024).

There are ongoing tensions between the drive for commercial innovation and the need to uphold ethical standards. High regulatory costs and complex approval processes can discourage investment and slow the adoption of beneficial technologies, while insufficient ethical scrutiny may undermine animal welfare and public confidence. Balancing economic incentives with ethical responsibilities remains a persistent dispute in the governance of GMO animals (Frewer et al., 2013; Eriksson et al., 2018; Choriyeva, 2024; Wray-Cahen et al., 2024).

4 Welfare Protection Practices and Challenges in GMO Animals

4.1 Dimensions of welfare impact assessment

Welfare assessments of genetically modified (GMO) animals must consider their physical health, including factors such as pain, deformities, and changes in lifespan. For decades, selective breeding and genetic editing aimed at improving productivity have often come at the cost of animal welfare, resulting in increased suffering or health issues. As a result, there is a growing call for regulatory frameworks to prioritize animal welfare and ensure that genetic modifications do not cause more severe health problems than those found in non-GMO animals (Cimadori et al., 2025). For example, traditional dehorning procedures are commonly used to prevent injuries among cattle and to ensure handler safety, but these procedures cause stress and pain. In recent years, gene editing technologies such as CRISPR have been successfully applied in cattle breeding to precisely knock out the POLLED gene, which controls horn growth, thereby producing naturally hornless cattle. This approach not only improves animal welfare by eliminating the need for painful procedures but also reduces human intervention risks and lowers labor and operational costs (Figure 1) (Shriver, 2020).

Figure 1 Gene editing can improve animal welfare by eliminating the need for dehorning (Adopted from Shriver, 2020)

GMO animals may experience restrictions on natural behaviors, such as limited social interaction or inadequate space for movement, especially in intensive production systems. Addressing behavioral needs is essential for comprehensive welfare protection, and there is a growing call for management practices that allow animals to express species-specific behaviors and minimize stress (Alonso et al., 2020; Daigle et al., 2021).

Psychological welfare, including anxiety and reduced adaptability, is a critical but often under-assessed dimension. Welfare assessments should account for the mental well-being of GMO animals, recognizing that genetic modifications and husbandry conditions can impact psychological states (Daigle et al., 2021).

4.2 Welfare management in experimental and husbandry settings

Ethical oversight of GMO animal use in research is typically conducted by Institutional Animal Care and Use Committees (IACUCs) or equivalent bodies. These committees are responsible for ensuring that animal experiments adhere to ethical standards, including the application of the 3Rs principle (Replacement, Reduction, Refinement) to minimize harm and maximize welfare. However, the effectiveness of IACUCs can be challenged by rapid scientific advances and inconsistencies in regulatory frameworks (Bert et al., 2016).

Professional housing facilities, effective anesthesia and analgesia management, and the establishment of humane endpoints are critical for minimizing suffering in GMO animals. The invasiveness of genetic engineering procedures, the large numbers of animals required, and the unpredictability of welfare outcomes necessitate vigilant monitoring and the use of humane endpoints to prevent unnecessary pain or distress. Veterinarians and animal care professionals play a key role in implementing these practices, especially during the development of new genetically engineered strains (Ormandy et al., 2011).

Long-term monitoring and contingency mechanisms are essential to address unforeseen consequences in GMO animals. The complexity of genetic interventions can result in unexpected health and welfare issues, such as insertional mutations, abnormal offspring, or increased susceptibility to disease. Systematic risk assessment protocols and comprehensive welfare monitoring throughout the animal’s life are recommended to identify and mitigate adverse effects, ensuring that technological progress does not come at the expense of animal well-being (Van Reenen et al., 2001; Ormandy et al., 2011).

4.3 Tensions between welfare and technological efficacy

Breeding programs focused on productivity traits—such as rapid growth or increased yield—have historically compromised animal welfare, leading to increased stress, health problems, and suffering. While genetic modification can be used to address some welfare issues (e.g., polled cattle to avoid dehorning), it can also exacerbate the conflict between maximizing output and minimizing animal burden (Van Reenen et al., 2001; Eriksson et al., 2018; Cimadori et al., 2025). The lack of complete understanding of complex traits further complicates the prediction and management of welfare impacts (Eriksson et al., 2018).

There is often a disparity in welfare prioritization between animals used in research and those in commercial production. Regulatory frameworks tend to be stricter for experimental animals, with more robust ethical oversight and welfare protocols, while commercial animals may be subject to less rigorous standards, especially when economic interests are at stake. This asymmetry raises ethical concerns and highlights the need for consistent welfare protection across all contexts of GMO animal use (Ormandy et al., 2011; Cimadori et al., 2025).

5 Public Attitudes and Ethical Awareness

5.1 Differences in social acceptance and moral sensitivity

Public acceptance of GMO animals is generally lower than that of GMO plants, especially in the context of food production. Studies show a significant acceptance gap, with people expressing more concern about the use of genetic modification in animals than in plants, often due to ethical considerations such as animal welfare, naturalness, and perceived risks (Marques et al., 2015). Acceptance is also context-dependent: the public tends to be more tolerant of GMO animals used for medical research or welfare improvements (e.g., hornless cattle to avoid dehorning) than for food production, where skepticism remains high (Eriksson et al., 2018; McConnachie et al., 2019; Van Eenennaam, 2024). Cultural and regional differences further shape these attitudes, with European consumers typically less accepting than those in the US or Asia, though Asian consumers may express stronger ethical concerns (Frewer et al., 2014).

5.2 Influence of media and information environment

Media coverage and trust in information sources significantly influence public attitudes toward GMO animals. High media attention often correlates with increased skepticism, while trust in scientists and regulators is associated with more positive attitudes. Transparency and labeling systems are important tools for building public trust, as seen in Japan, where clear regulatory communication and voluntary information sharing have helped mitigate public opposition to gene-edited foods. However, current ethical communication and science outreach efforts are often limited, and misinformation or lack of accessible information can exacerbate public concerns and alienation (Wynne, 2001; Marques et al., 2015; Van Eenennaam, 2024).

5.3 Barriers to ethical consensus

Achieving ethical consensus on GMO animals is challenging due to diverse religious, cultural, and personal values that shape moral sensitivity and acceptance (Frewer et al., 2014; Ormandy and Schuppli, 2014; Eriksson et al., 2018). The boundaries between legal oversight and moral judgment remain ambiguous, with regulatory frameworks sometimes failing to address deeper ethical concerns or societal expectations (Wynne, 2001). This diversity complicates the development of universally accepted ethical standards and highlights the need for inclusive, transparent, and culturally sensitive engagement strategies.

6 Future Directions and Evolving Ethical Governance Pathways

6.1 Establishing global ethical coordination and information-sharing platforms

Harmonizing international ethical standards is crucial for responsible GMO animal governance. The literature highlights the need for differentiated, flexible regulatory frameworks that facilitate both innovation and robust oversight, while promoting inclusive public dialogue and trust. Creating global databases and mechanisms for public information disclosure would enhance transparency, comparability, and traceability of GMO animal research and applications, supporting informed policy and societal engagement (Bratlie et al., 2019). Such platforms can also help address the diverse interests and values of stakeholders across regions (Vàzquez-Salat et al., 2012; Frewer et al., 2013).

6.2 Evolving from “minimum harm” to “positive welfare” concepts

Ethical governance is shifting from a focus on minimizing harm to actively promoting positive welfare for GMO animals. This transition involves not only preventing suffering but also enhancing quality of life, considering animal agency, and exploring the concept of delegated artificial rights. Ethical frameworks are increasingly incorporating principles of animal integrity, naturalness, and welfare improvement, urging breeding organizations and companies to take a proactive role in welfare enhancement and ethical deliberation (Eriksson et al., 2018; Caballero-Hernández et al., 2020). These new paradigms challenge traditional risk–benefit analyses and call for broader, more inclusive ethical considerations.

6.3 Institutional innovation for ethics-science co-design

Integrated ethical–technical governance is emerging as a best practice, involving multi-stage reviews (ex ante, mid-term, ex post) to ensure ongoing ethical oversight throughout the lifecycle of GMO animal projects. The use of AI-assisted ethical risk assessment and simulation technologies is proposed to predict and manage potential ethical outcomes, supporting more dynamic and responsive governance (Bratlie et al., 2019). Such institutional innovations foster collaboration between ethicists, scientists, and stakeholders, ensuring that ethical considerations are embedded in scientific and technological development from the outset (Frewer et al., 2013; Eriksson et al., 2018).

7 Concluding Remarks

GMO animal technologies present significant opportunities for advancing agriculture, medicine, and food production, but their ethical challenges remain complex and unresolved. While these technologies can improve animal welfare in some cases—such as eliminating the need for painful procedures or enhancing disease resistance—they also raise concerns about animal integrity, naturalness, and unforeseen welfare impacts. The lack of comprehensive understanding of genetic backgrounds and long-term effects further complicates ethical evaluations and risk assessments.

Current ethical review systems and welfare protections are marked by inconsistencies in standards and implementation gaps across regions and regulatory frameworks. For example, the European Union’s approach to gene-edited and selectively bred animals reveals significant regulatory discrepancies, with gene-edited animals subject to stricter oversight than those produced by traditional selective breeding, despite similar welfare risks. This fragmented landscape can undermine animal protection objectives and erode public trust. Additionally, public misunderstanding and limited engagement in ethical discourse contribute to societal unease and resistance, highlighting the need for more transparent, inclusive, and reflective ethical communication.

To build a future-oriented ethical governance framework, interdisciplinary collaboration among scientists, ethicists, regulators, and industry stakeholders is essential. Achieving global consensus on ethical standards and regulatory practices will require harmonization of welfare protections, robust information-sharing platforms, and mechanisms for public participation in decision-making. Meaningful engagement with diverse cultural, religious, and societal values is also critical for fostering ethical awareness and social acceptance.

Acknowledgments

Thank you Ms. S.Y. Chen provided assistance during the process of literature review and analysis.

Conflict of Interest Disclosure

The author affirms 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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