Ethical and Welfare Implications of Genetically Altered Non-Human Primates for Biomedical Research

Abstract

Breakthroughs in gene editing technologies have made it feasible to create genetically altered (GA) non-human primate (NHP) models of disease. This area of research is accelerating, particularly in China, Japan and the USA, and could lead to an increase in NHP use globally. The hope is that genetic models in animal species closely related to humans will significantly improve understanding of neurological diseases and validation of potential therapeutic interventions, for which there is a dire need. However, the creation and use of GA NHPs raises serious animal welfare and ethical issues, which are highlighted here. It represents a step change in how these highly sentient animals are used in biomedical research, because of the large numbers required, inherent wastage and the sum of the harms caused to the animals involved. There is little evidence of these important issues being addressed alongside the rapidly advancing science. We are still learning about how gene editing tools work in NHPs, and significant added scientific and medical benefit from GA NHP models has yet to be demonstrated. Together, this suggests that current regulatory and review frameworks, in some jurisdictions at least, are not adequately equipped to deal with this emerging, complex area of NHP use.

Developing Non-Human Primate Models of Inherited Retinal Diseases

“…Ethical concerns such as iatrogenic injury from procedures used to create the models and off-target effects leading to unintended phenotypic characteristics can have a negative impact on the welfare of these animals. Given the ease of utilizing gene editing tools, international discussion on relevant ethical policies are currently underway [ 64 ].…”

Review of Environmental and Health Factors Impacting Captive Common Marmoset Welfare in the Biomedical Research Setting

“…Transgenic marmoset models, including those of neurodegenerative disease among others, have been created by research teams around the globe [ 67 ]. This new age raises ethical concerns related to the use of NHPs to create transgenic models outlined in Prescott, 2020 [ 68 , 69 ]. While these technologies have been successful, they remain inefficient, which inherently results in the usage of a relatively higher number of NHPs compared to other areas of research.…”

Inducible nonhuman primate models of retinal degeneration for testing end-stage therapies

“…For inherited genetic disorders, an ideal model would be one that carries the mutation and shows similar symptoms as in humans, such as the one generated for Parkinson’s disease ( 7 ). However, generating NHP models by germline transmission is a cumbersome task and is not permitted in most countries because of national ethical laws ( 8 ). Some NHP facility screens have identified naturally occurring mutations for macular degeneration ( 9 ), retinitis pigmentosa ( 10 ), achromatopsia ( 11 ), and Bardet-Biedl syndrome ( 12 ).…”