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.
Highlights
The ability to manipulate the genome of research animals and the explosion in the use of genetically engineered mouse and zebrafish models has enabled huge strides in understanding of biology and human disease (Vandamme, 2014; Leung & Jia, 2016)
In late 2018, the NAS held a workshop to explore the scientific opportunities afforded by new transgenic and chimeric non-human primate (NHP) models in neuroscience (Bain et al, 2019), along with a related workshop on the care, use and welfare of marmosets used in gene editing-based biomedical research (Anestidou & Johnson, 2019)
Serious animal welfare concerns arise from the generation and use of genetically altered (GA) NHPs, which can be grouped into five broad categories—the welfare impacts of the procedures to generate the GA monkeys, the mother-infant separation, the genetic modification itself, the procedures used to study the GA monkeys, and the housing in the laboratory
Summary
The ability to manipulate the genome of research animals and the explosion in the use of genetically engineered mouse and zebrafish models has enabled huge strides in understanding of biology and human disease (Vandamme, 2014; Leung & Jia, 2016). Transgenic macaques were first reported over 15 years ago, and the first transgenic macaque disease model over 10 years ago (Table 1) Despite these advances, the widespread adoption of GA NHP models appeared impractical until recently, given the paucity of methods for making precise genetic changes in NHP embryos (Vermeire et al, 2017). The widespread adoption of GA NHP models appeared impractical until recently, given the paucity of methods for making precise genetic changes in NHP embryos (Vermeire et al, 2017) Tools such as ZFNs (zinc finger nucleases), TALENs (transcription activatorlike effector nucleases), and CRISPR (clustered regularly interspaced short palindromic repeats, with RNA-guided nucleases such as Cas9) have made possible this once out-of-reach goal (Park & Silva, 2019).
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