Inevitably when I post a blog on “human biology” I get a series of comments about the importance of non-human model organisms in drug discovery and development. My position is clear: pick targets based on causal human biology, and then use whatever means necessary to advance a drug discovery program to the clinic.
Very often, non-human model organisms are the “whatever means necessary” to understand mechanism of action. For example, while human genetic studies identified PCSK9 as an important regulator of LDL cholesterol, mouse studies were critical to understand that PCSK9 acts via binding to LDL receptor (LDLR) on the surface of cells (see here). As a consequence, therapeutic antibodies were designed to block circulating PCSK9 from the blood and increase LDLR-mediated removal of circulating LDL (and hopefully to protect from cardiovascular disease).
Moreover, non-human animal models are necessary to understand in vivo pharmacology and safety of therapeutic molecules before advancing into human clinical trials.
Beyond drug discovery, of course, studies from non-human animal models provide fundamental biological insights. Without studies of prokaryotic organisms, for example, we would not have powerful genome-editing tools such as CRISPR-Cas9. Without decades of work on mouse embryonic stem cells, we would not have human induced pluripotent stem cells (iPSCs).…