Systematic heterogenization revisited: Increasing variation in animal experiments to improve reproducibility?

Life sciences are currently facing a reproducibility crisis. Originally, the crisis was born out of single alarming failures to reproduce findings at different times and locations. Nowadays, systematic studies indicate that the prevalence of irreproducible research does in fact exceed 50%. Viewed from a rather cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. In this respect, animal research has come under particular scrutiny, as the stakes are high in terms of both research ethics and societal impact. To counteract this, it is essential to identify sources of poor reproducibility as well as to iron out these failures. We here review the current debate, briefly discuss potential reasons, and summarize steps that have already been undertaken to improve reproducibility in animal research. By the example of classical behavioural phenotyping studies, we particularly highlight the role strict standardization plays in exacerbating the crisis, and review the concept of systematic heterogenization as an alternative strategy to deal with variation in animal studies. Briefly, we argue that systematic variation rather than strict homogenization of experimental conditions benefits the robustness of research findings, and hence their reproducibility. To this end, we will present concrete examples for systematically heterogenized experiments and provide a practical guide on how to apply systematic heterogenization in experimental practice.