1 Introduction

Genetically modified organisms (GMOs) are plants, animals, bacteria, or viruses that have been genetically altered by gene transfer or gene removal. Genetic modification is achieved through a number of gene editing technologies such as recombinant DNA technology, transcription activator-like effector nucleases (TALENs), Zinc-finger nucleases (ZFNs), and CRISPR/Cas9. These techniques facilitate the precise addition, elimination, or replacement of genes in the organism's genome to create transgenic organisms with new or enhanced attributes (Asfaw and Assefa, 2019). Applications of GMOs vary across various fields such as medical and biological research, agriculture, pharming, and xenotransplantation (Gacovski et al., 2015). Gene alteration has found use in animals to improve disease resistance, enhance productivity, and make biomedical research simpler.

The advent of genetic modification in animals has also brought with it significant ethical and welfare concerns. These concerns relate to the potential unintended consequences of genetic modifications, the moral status of genetically modified animals, and the overall implications for animal welfare and integrity (Khalid et al., 2018). The ethical issues are the danger of suffering from unforeseen health problems, the ethical rationale of altering the animal genome, and the integrity and naturalness impact on animals. Environmental dangers are also associated with releasing genetically altered animals into the wild and their potential cross-breeding with local populations (Bovenkerk, 2020). Public opinion and acceptance of GM animals also have an important role to play, as ethical factors tend to drive regulatory decisions and public acceptance.

This study explores technological progress, ethical dilemmas and welfare impacts, analyzes the current situation and future development prospects of ethical review and welfare protection of transgenic animals, and provides new perspectives and insights for the responsible application of animal genetic modification technology (Eriksson et al., 2018). Research combines a multidisciplinary perspective of life science, ethics and socioeconomic background to provide policy recommendations and ethical guidelines to support the sustainable development and application of transgenic animals. On this basis, the research aims to minimizing potential risks and properly addressing relevant ethical issues while fully exploiting the benefits of genetic modification technology. Providing policy suggestions and ethical guidelines from a multidisciplinary perspective not only provides theoretical support for the development and application of transgenic animals, but also lays a foundation for balancing technical benefits with potential risks and properly coping with ethical challenges, which has important practical and theoretical significance.

2 Current Research and Applications of GMO Animals

2.1 GMO animals in basic research

Genetically modified (GM) animals have become invaluable research reagents, particularly in the analysis of gene function and regulation. Transgenic animals such as pigs are used to model human disease extensively, which allows researchers to study genetic determinants and disease mechanisms under controlled conditions (Bratlie et al., 2019). These models are critical to deepen our knowledge about complex biological processes and the design of new therapeutic strategies.

2.2 Applications in agriculture and food production

In agriculture, GM animals are being engineered to boost productivity, disease resistance, and nutritional value of animal food. For instance, gene editing technologies like CRISPR have been employed to produce pigs that grow faster, have leaner meat, and are more resistant to diseases (Tu et al., 2022). These innovations not only aim to meet growing food demands but also aim to reduce the environmental footprint of livestock farming by making it efficient and sustainable.

2.3 Progress in medical research and biopharmaceuticals

The healthcare industry has witnessed great progress with the use of GM animals. Transgenic pigs, for example, are being developed as sources of high-quality biopharmaceuticals, such as recombinant proteins, and as potential organ donors for xenotransplantation (Kumar and Sharma, 2020) (Figure 1). Additionally, GM animals like rabbits and cows have also been engineered to yield human polyclonal antibodies and recombinant human lactoferrin, respectively, which prove themselves to be fit for pharmaceutical usage (Spicer and Molnár, 2018). These developments do well to underscore the practicality and flexibility of GM animals for advancing medical study and the production of biopharmaceuticals.

2.4 Global regulatory and commercialization developments

Commercialization of GM animals is regulated by regulatory actions and socio-economic factors. Technology has developed much more quickly, but regulatory procedures are behind, tending to restrain the commercialization of GM animal products. There are some regional variations in regulations, while others, like the European Union, have more rigorous regulations that restrict innovation (Hryhorowicz et al., 2020). However, countries like China and Argentina are emerging as leaders in the industry, implementing more pro-GM policies that can realign the global GMO regulatory environment. The need for a coherent regulatory environment facilitating innovation without jeopardizing safety and public trust is being realized ever more (Xu, 2024).

3 Ethical Debates and Review of GMO Animals

3.1 Ethical boundaries of genetic modification technology and animal rights issues

The ethical limits of genetic modification technology in animals are complex and subtle, involving issues of unforeseen effects, ownership, and the metaphysical status of genetically modified animals. The introduction of genetic modifications introduces basic norms and questions about the moral community and the boundaries of acceptable action (Bovenkerk, 2020). Ethical concerns extend beyond animal well-being to include consideration of animal integrity, naturalness, and potential harms of using these technologies on large scales. The debate usually hinges on whether or not genetic modification is in accordance with the inherent worth of animals or commodifies them. Furthermore, the ethical consequences of transgenically creating animals, as by inserting human genes in bovine genomes, highlight a subtle balance between potential beneficial consequences and sensitivity towards the rights of animals.

3.2 International frameworks for ethical review and comparative analysis

International frameworks for the ethical review of genetically modified animals vary significantly, reflecting diverse cultural, social, and regulatory landscapes. The European Union, for instance, has developed comprehensive policies that integrate social, environmental, and economic knowledge to address the ethical and policy concerns associated with GM animals (Coles et al., 2015). These frameworks often involve public engagement and the application of ethical matrices to ensure that diverse perspectives are considered in policy development. Comparative analyses reveal that public perceptions and regulatory approaches differ across regions, with European attitudes generally more cautious compared to North America and Asia. The interdisciplinary nature of these frameworks underscores the importance of integrating ethical considerations with scientific and economic assessments to formulate balanced and inclusive policies.

3.3 Role of social acceptance and public participation in ethical review

Social acceptance and public participation are equally significant in the ethical evaluation of genetically modified animals. Public opinions are shaped by a variety of factors, including risk and benefit perceptions, moral concerns, and the naturalness of genetic alteration (Wright et al., 2022). Studies have indicated that the social attitudes towards GM animals are influenced by cultural, socio-economic, and historical contexts, which can encourage or discourage the acceptance of these technologies. Public engagement in ethical reflection and decision-making is essential to resolve underlying conflicts and build trust among regulatory processes governing GM animals. Not only does public engagement assist in resolving and identifying issues of ethics but also it confirms that development and application of genetic modification technology concur with expectations and society's values.

4 Welfare Protection of GMO Animals

4.1 Impacts of genetic modification on animal health and behavior

Genetic modification (GM) can have varying impacts on the health and behavior of animals. While certain changes aim to promote welfare through the reduction of susceptibility to illness or elimination of undesirable characteristics, others can, without realizing, lead to ailments. A case in point is the insertion of human growth hormone genes into pigs, which caused acute health problems such as arthritis and lung ailments, which later led to the experiment being discontinued (Zintzsch et al., 2020). Similarly, genetic changes in mice are often to result in extreme distress, particularly when the animals are utilized as models of human disease (Whelan et al., 2023). Not all gene changes are harmful, however; some, e.g., production of hornless cattle, will improve welfare through reducing injury to animals and also enhancing worker health.

4.2 Welfare assessment in experimental and production environments

Assessing the welfare of transgenic animals requires holistic and multi-faceted approaches. Welfare can be measured in relation to indicators such as deviant behavior, physiological response, rate of diseases, and life span (Shriver, 2020). The rapid generation of new GM lines, particularly mice, requires the integration of welfare evaluation into phenotype databases to identify unforeseen welfare issues and address humane endpoints efficiently. Furthermore, applied standards of harm assessment, especially concerning genetically modified animals, mandate future benefit-harm analysis to enable ethically acceptable project assessments (Bovenkerk, 2020). In intensive animal production, animals are separated from their indigenous evolutionary and environmental contexts (Figure 2), and actors in animal production systems commodity them as "production units" or artefacts. They are actually reduced to function within the system, in which there is little room for capacity and behavior aside from "giving to offspring, milk production and death". This notion is actually based on the ethical argument of virtue.

4.3 Technical, managerial, and legal frameworks for welfare protection

Protection of welfare in genetically modified animals is underpinned by technical, managerial, and legal frameworks. Technically, advances in molecular biology and biotechnology equipment enable identification of genes associated with welfare traits, allowing selection or editing of the animal for improved welfare. Managerially, integrating management practice into genetic and genomic tools can synergize to enhance both production and welfare traits in a manner that satisfies public and consumer demands (Ritter et al., 2019). Legally, the conservation of welfare principle, whereby genetically modified animals should not suffer more than the parent stock, needs to be implemented globally and legally ingrained within regulations to maintain public trust and ensure ethical standards.

5 Challenges in Technology and Ethics

5.1 Precision and off-target effects of genetic modification technology

The precision of genetic modification technologies, such as CRISPR-Cas9, is of great concern because of potential off-target effects. Such indirect modifications will introduce unforeseen genetic changes that will affect animal welfare and health. The behavior of complex genetic backgrounds in animals makes it difficult to predict the total effect of these modifications, especially for large-scale breeding (Coles et al., 2015). Ethical considerations must balance the advancement of technology with the dangers that can be associated with off-target effects, in order not to compromise animal welfare (Lanzerath, 2018).

5.2 Potential environmental and ecological impacts

Genetically modified animals have the potential to cause major ecological and environmental impacts. The introduction of transgenic animals into the ecosystem can disrupt existing species relationships and ecological balance. For instance, transgenic fish released in the wild could overwhelm native species, leading to a loss of biodiversity (Thompson, 2021). Further, long-term ecological implications of releasing genetically modified organisms are not fully realized, which requires caution in deploying them. Ethical frameworks have to take into account the wider environmental context and ensure sustainable practice (Saeed et al., 2015).

5.3 Conflicts between technological applications and societal ethical perceptions

The application of genetic modification technology in animals often conflicts with the ethical views of society. The acceptability of genetically modified animals is influenced by individuals' concern regarding animal welfare, naturalness, and the ethical permissibility of altering animal genomes. Ethical controversy also revolves around the commercialization and patenting of genetically modified animals, potentially expanding global inequalities and questioning the moral justifiability of the practice (Eriksson et al., 2018). To solve these ethical dilemmas and reconcile technological progress with public values, it is essential to interact with various stakeholder views and to have open discussion.

6 Global Regulatory Policies and Case Studies

6.1 Comparison of management policies and standards for GMO animals across countries

The regulatory landscape for genetically modified organisms (GMOs), including genetically modified animals (GMAs), varies significantly across countries. In the European Union (EU), the regulatory landscape is stringent, and all gene-edited organisms have to undergo the same approval procedure as traditional GMOs under EU Directive 2001/18/EC. This has been blamed for stifling innovation and advancement in the field of GMAs (Fan et al., 2021). On the other hand, the United States follows a more flexible approach, where the focus is laid on the final product rather than the process used to make it. This allows for a faster approval process for GMAs, which can accelerate their commercialization.

China and Argentina are emerging as global leaders in the field of GMAs with pro-GM policies that contrast sharply with the more restrained policies of the EU and the USA. These countries are leveraging their regulatory frameworks to foster innovation and commercialization in the biotechnology sector. Regulatory diversity is further highlighted by the fact that emerging economies like Mexico, China, and South Africa are adopting elements of both US and EU models of regulation, creating unique hybrids that fit their specific socio-economic and political realities.

6.2 Challenges in international cooperation and legal framework coordination

One of the chief problems of international collaboration and coordination of legal systems for GMAs is that they lack regulatory convergence. Polarization around US and EU model regulation has created a splintered global regulatory landscape, making it challenging to devise one global approach towards GMO regulation. This regulatory divergence is further strengthened by the speed of innovation in gene-editing technology, which existing structures have challenges in covering (Eriksson et al., 2020).

There has to be a new system of governance that guarantees technological innovation with regulatory oversight is necessary. It must be flexible enough to be able to respond to emerging scientific advances but also public confidence and security. Harmonization internationally is not straightforward because the levels of regulation vary as well as the triggers (process-oriented vs. product-oriented) used by countries to regulate GMOs.

6.3 Case studies in research and commercialization of GMO animals

Several case studies illustrate the complexity and the issues at stake in the research and commercialization of GMAs. For instance, GM rabbits for the production of human polyclonal antibodies and GM cows for the production of recombinant human lactoferrin illustrate the socio-economic and regulatory issues that can hinder the commercial success of GMAs. These case studies suggest that the success of GMAs relies on a precise intersection of scientific, market, and public policy factors (Bratlie et al., 2019).

In the pharmaceutical market, GM animals have been promising but are normally suppressed by regulatory and ethical issues during their commercialization. The EC consortium with an interdisciplinary team (PEGASUS project) investigated these in the EU context, pointing to a necessity for balance considering public attitude, ethical considerations, and the competitiveness of the animal production sector (Van Eenennaam, 2017). In the food industry, social acceptability of GMAs remains an on-going barrier. China and the USA have both launched reforms of regulation for better commercialization of genetically modified food animals (GMFAs), but trust on the part of the population and ethical factors continue to serve as barriers. Having a social license system that categorizes GMFAs by their genetic modifications can help regulators and the general public make better-informed decisions (Eckerstorfer et al., 2019).

7 Future Directions

7.1 Balancing technological innovation and ethical standards

The rapid advances in genetic modification and genome editing technologies present both opportunities and challenges in animal breeding and welfare. While these technologies also hold great potential for improving animal welfare, e.g., by eliminating deleterious traits or enhancing disease resistance, they also raise serious ethical issues (Li and Lin, 2024). It is necessary to balance technological progress with moral requirements in order not to compromise the well-being of genetically modified animals. Moral notions of animal integrity, naturalness, and risk perception should be considered when making decisions (Bert et al., 2016). Furthermore, the welfare conservation principle that posits genetically modified animals should not suffer more than their non-genetically modified equivalents should be accepted internationally and enshrined in legislation to maintain public trust and ensure ethical compliance (Kramer and Meijboom, 2021).

7.2 Strengthening legal protection and policy optimization for welfare

The increasing use of genetically engineered animals in sectors necessitates rigid legal regimes for protecting animal well-being (Bruetschy, 2019). National and EU legislations need to be adapted to address the unique difficulties genetic modification imposes. Strengthening legal protections involves not only amending existing law but ensuring new law is comprehensive and efficacious. Policy optimization should also entail risk-benefit assessment that considers human and animal health, environmental impact, and sustainable production (Shriver, 2020). Ethical as well as policy concerns should also be addressed through transdisciplinary approaches, including public engagement and the application of ethical matrix methods to ensure various perspectives are considered in policy formulation (Ritter et al., 2019).

7.3 The importance of public education and science communication in GMO animal applications

One key element in genetically modified animals' success and uptake is public opinion. Public education and science communication are required for debunking misconceptions and moral concerns about GMO animals (Devolder and Eggel, 2019). Studies have reported that the perceptions of consumers of genetically modified animals are influenced by perceived advantages such as improved animal welfare and ethical considerations (Eriksson et al., 2018). Therefore, open discussion about the objectives and benefits of genetic modifications, as well as the ethical safeguards in place, is necessary to create public trust. Systematic review and thematic analysis of consumers' and other stakeholders' opinions can inform future applications and assist in alleviating public anxieties (Ortega, 2023).

8 Concluding Remarks

Welfare protection and moral assessment of genetically modified organism (GMO) animals entail several significant concerns. One such concern is the integrity and naturalness principle that calls into question the morality of altering an animal's genetic make-up for human benefits. In addition, the welfare of the animals following modification is a significant issue as modification can lead to unforeseen health complications, as seen in the Beltsville pigs experiment, where there were extreme welfare issues like arthritis and lung problems. The welfare principle for conservation, which asserts that genetically modified animals should not experience more suffering than their non-modified counterparts, is also a very significant moral factor. Furthermore, public opinion and regulatory decisions are influenced by these ethical concerns, and therefore they need to be addressed comprehensively.

Despite progress made in the technologies of genetic modification, there are important gaps in research and management aspects. One of them is the lack of a complete understanding of the genetic foundation of complex traits, with this complicating the ability to predict the overall consequences of genetic improvement in large-scale breeding programs. In addition, a lack of information about the consumer perception of GM animals in the developing world and emerging economies is also important to commercially succeed in the products of GM animals. The second missing link is that ethics is not adequately brought into the development and deployment of such technologies because the practical development is always in front of the theoretical. Moreover, current regulatory frameworks may not be adequate to address the particular challenges posed by GM animals, and stronger and more reactive policies are required.

It's important to facilitate the sustainable development of technology and ethics through the creation of a general structure that can integrate scientific progress and ethics effectively. During technology development and application, there should be determined in practice ethical norms, such as "welfare protection principles", to ensure that genetic modification does not increase the suffering of animals compared to non-modified animals, preserving intact basic ethical values such as animal integrity and naturality. This should involve legal means by policy optimization and regulation improvement. In order to achieve this objective, one has to undertake science communication and public education. By openness in communication, the public would be able to identify the aim, benefits, and ethical guarantee of GM technology, so that social acceptance and credibility could be built up.

Acknowledgments

Members also thank the laboratory team for their support and cooperation.

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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