Navigating Uncertainties: How to Assess Welfare and Harm in Genetically Altered Animals Responsibly—A Practical Guideline

SIMPLE SUMMARY: When using animals in research, ethical aspects must be included in the project evaluation process. As one important part, a harm–benefit analysis (HBA) should be carried out in order to approve projects in line with the EU Directive 2010/63/EU, which sets out the rules for animal experiments in Europe. These regulations state that the harms and benefits of a project should be assessed and weighed before the project starts. Assessment of harms caused by scientific procedure is a precondition for ethical evaluation. In this context, projects that involve genetically altered (GA) lines raise new issues. A significant lack of knowledge surrounds new GA lines, making it difficult and sometimes impossible to estimate harm prospectively with sufficient certainty since it is not predictable what sort of harm—if at all—the animals are going to experience. Therefore, this contribution aims to deal with the challenges of harm assessment in GA animals and their implications for welfare assessment and the HBA. A practical guideline is presented herein to serve as guidance for relevant harm factors and address the main challenges, particularly when dealing with uncertainties in project evaluation. ABSTRACT: The use of animals in research requires careful ethical consideration of whether the burden on the animals is justified. As one important part of the project evaluation, a harm–benefit analysis (HBA) must be carried out in order to approve projects in line with the EU Directive 2010/63/EU. This implies that harms and benefits must be assessed prospectively beforehand in order to weigh them. Although there are different methods of weighing, it is clear that an assessment of prospective harms and benefits is a precondition for any weighing procedure. In this context, projects that use genetically altered (GA) lines raise new issues. A unique challenge when using GA lines is the significant lack of knowledge in this context, making it difficult and sometimes impossible to estimate harm prospectively with sufficient certainty, since it is not predictable what sort of harm—if at all—the animals are going to experience. Therefore, this contribution aims to deal with the challenges of harm assessment in GA animals and their implications for welfare assessment and the HBA. A practical guideline is presented herein to serve as guidance for relevant harm factors and address the main challenges, particularly when dealing with uncertainties in the process of HBA.