INRAE policy on the use of genome-editing technologies in farm animals

Animal farming is key to ensuring food security and fostering the development of healthy and sustainable agrifood systems. It helps maintain circular systems and diverse ecosystem services; generates value from regions and resources that cannot be used in other ways; and bolsters economic security and nutrition security in many populations, down to the family level. Moderate consumption of animal products is part of a balanced diet. However, current animal farming systems must be completely transformed to achieve sustainable development goals. INRAE is working to design farming systems that incorporate agro-ecological principles; combine economic and environmental sustainability; and meet societal expectations, especially with regards to animal welfare.

To this end, INRAE's world-renowned experts are carrying out research in animal biology (e.g., reproduction, nutrition, physiology, microbiology, immunology, neurosciences, ethology, genetics, and genomics), the economic sciences, the social sciences, and animal husbandry. In particular, the institute's scientists are developing tools and methodologies to create effective strategies for sustainably managing and enhancing genetic diversity in farm animals.

Scientific background: Technologies that allow targeted genome modifications form an essential part of fundamental biological research. They can also complement conventional methods for genetically improving domesticated animals for practical purposes (e.g., adapting to climate change, boosting animal health).

Regulatory framework: The European Court of Justice (July 25, 2018 decision) and the French Council of State (February 7, 2020 decision) have declared that organisms whose genomes have been modified using the mutagenesis techniques described in Directive 2001/18/EC are to be treated as genetically modified organisms (GMOs). The directive’s definition of GMOs and regulatory standards are to be applied in such cases.

Opinion issued by the Joint INRAE-CIRAD-IFREMER Ethics Advisory Committee: Following up on its opinion on new plant-breeding techniques (NPBTs) [1], the Joint INRAE-CIRAD-IFREMER Ethics Advisory Committee has issued an opinion [2] on the use of genome-editing technologies employing targeted mutagenesis (notably CRISPR-Cas9) in farm animals and animals classified as pests.

The committee underscored that these technologies play a key role in advancing knowledge. It recommended the prudent application of such technologies when employed for agricultural purposes and emphasised that benefits to animals, consumers, and society should remain at the forefront. The committee also formulated a list of recommendations, which placed social responsibility at the heart of fundamental and targeted research efforts.

As with NPBTs [3], INRAE wishes to clarify its position on the use of new genome-editing technologies in farm animals. The utilisation of gene drives, particularly in insects, will be discussed in greater detail in a separate opinion.

1 - Certain technologies are essential for acquiring knowledge

Technologies that allow researchers to modify genomes via targeted mutagenesis are indispensable tools in the quest to understand living organisms. They provide a unique means of studying the function, regulation, and evolution of genes and make it possible to explore how genetic variability affects trait expression. As a result, new scientific frontiers are opening up that INRAE must explore to better understand living organisms and their modes of functioning.

2 - INRAE must cultivate the requisite expertise to fulfil its public research responsibilities

Since new genome-editing technologies are likely to be applied in animal farming systems, INRAE feels it is crucial to research the risks and benefits of such applications. More specifically, there must be analyses of the technologies' precision, reliability, and safety. It is also important to carry out multicriteria evaluations of the technologies' strengths and limitations for managing genetic diversity or generating genetic improvements; comparisons with conventional methods (e.g., pedigree- or genome-based selection, crossbreeding) should be employed. Finally, it is crucial to assess the ethics and safety of products created using these technologies.

The institute feels that the above work should not simply be handed over to foreign public and private stakeholders, leaving France without the expertise needed to guide political, regulatory, economic, and/or environmental actions.

3 - INRAE has established clear internal standards for animal research

Animals are legally recognised as sentient beings capable of feeling emotions and pain (Article 515-14 of the French Civil Code). The INRAE internal memo published on January 6, 2021, [4] Principes d'INRAE en matière d’utilisation d'animaux à des fins scientifiques [INRAE's guiding principles for animal research], sets out the rules governing all animal research carried out within the institute. These rules apply to any research employing genome-editing technologies. The institute forbids projects whose outcomes would adversely affect the physiological integrity, health, or welfare of animals; all work must contribute to INRAE's primary objective of developing sustainable agro-ecological farming systems.

4 - INRAE strictly adheres to external standards for animal research

Research using animals with edited genomes and/or their descendants is carried out in full accordance with strict French and European regulatory and ethical standards. Researchers espouse the principles of parsimony and the 3Rs.

Any projects on farm animals that intend to breed and rear individuals with edited genomes are to be examined by a committee of experts affiliated with INRAE's General Directorate for Science and Innovation; this assessment will take place before the project is submitted for approval by regulatory authorities. The committee will evaluate whether the project's objectives require the use of live animals and, if necessary, whether the project aligns with INRAE's values and principles.

5 - INRAE views genome-editing technologies as complementary to conventional methodologies

INRAE considers that conventional genetic improvement methods remain the best means of managing and enhancing genetic diversity in farm animals. The ways in which genome-editing technologies could be used to complement conventional tools must be evaluated on a case-by-case basis, using a systemic analysis of the potential benefits and risks, the ability of the same goals to be achieved more conventionally, and the technologies' compatibility with the common good.

6 - INRAE supports open innovation

INRAE reaffirms its support for open innovation: genetic resources and information that can help produce knowledge and genetic advances should be made freely accessible. INRAE will publish and provide open access to findings obtained using genome-editing technologies. The institute will not patent the products arising from these technologies.