From Mice to Monkeys? Beyond Orthodox Approaches to the Ethics of Animal Model Choice

Abstract

Recent developments in genome editing tools, along with limits in the translational potential of rodent models of human disease, have spurred renewed biomedical research interest in large mammals like nonhuman primates, pigs, and dogs. Such scientific developments raise ethical issues about the use of these animals in comparison with smaller mammals, such as mice and rats. To examine these ethical questions, we first consider standard (or “orthodox”) approaches, including ethics oversight within biomedical research communities, and critical theoretical reflections on animal research, including rights-based and utilitarian approaches. We argue that oversight of biomedical research offers guidance on the profession’s permitted uses of animals within a research setting and orthodox approaches to animal ethics questions when and whether animals should be used in biomedicine; however, neither approach sufficiently investigates the nuances of ethical practices within the research setting. To fill this lacuna, we consider a virtue ethical approach to the use of specific animal models in biomedicine. From this perspective, we argued that limitations on flourishing for large mammals in a research setting, as well as potential human-animal bonds, are two sources of likely ethical tensions in animal care and use in the context of larger mammals.

Animal and Cell Culture Models for Cystic Fibrosis

“…In addition, development of an NHP CF model could lead to the use of fewer animals overall because of improved relevance of scientific investigations. 108 Renewed interest in the use of NHPs for modeling human diseases has resulted from significant advances in genetic engineering technologies that now allow for the genomes of large mammals to be precisely modified. Although technically feasible, gene editing NHPs has additional challenges when compared with that in rodents.…”

“…107 The increased lifespan of NHPs also means they may take longer to exhibit the desired disease state. 108 A CF NHP is likely to exhibit meconium ileus, and like CF pig and ferret models, they are expected to require expensive and ongoing medical care to manage life-threatening disease aspects. However, certain disease traits can be well managed or altogether mitigated (eg, fatal gut obstruction could be transgenically corrected by expressing CFTR in the intestines, as has been done with other CF models).…”

Transplantation of a 3D Bioprinted Patch in a Murine Model of Myocardial Infarction

“…While large animals still represent a more clinically relevant model to test cardiac regenerative properties 5 , 14 , the versatility and feasibility of the mouse model lends itself to this fast-moving area of study. This may avoid some of the pitfalls typical of large animal studies, including (but not limited to): 1) high animal mortality (unless diagonal coronary arteries are ligated leading to unpredictable segmental infarcts 14 , or the distal end of the LAD is occluded followed by reperfusion instead of permanent ligation 5 ); 2) ethical issues with the relatively increased harm caused by large animal protocols compared to mice 18 ; 3) increased cost and/or feasibility issues, for instance the relative unavailability of large animal equipment such as MRI scanners 14 . It is also important to consider that given the extensive duration and commitment typical of large animal studies, they have the potential to become outdated before they are finished, especially with the rapid developments typical of this field.…”

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

“…Efforts have been made to bridge the gap between humans and animals using humanized mouse models, which are implanted with functional human cells and tissues; however, this approach still entails important limitations due to species-specific differences (e.g., residual innate immune system, cytokines, and humoral responses) (Walsh et al, 2017). Moreover, ethical concerns exist regarding the use of animal models (Walker and Eggel, 2020). Therefore, the pressing need for alternative platforms to investigate human pathophysiology in vitro has led to the development of 3D in vitro tissue models.…”