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.

Once an optimist, always an optimist? Studying cognitive judgment bias in mice.

Individuals differ in the way they judge ambiguous information: some individuals interpret ambiguous information in a more optimistic, and others in a more pessimistic way. Over the past two decades, such "optimistic" and "pessimistic" cognitive judgment biases (CJBs) have been utilized in animal welfare science as indicators of animals' emotional states. However, empirical studies on their ecological and evolutionary relevance are still lacking. We, therefore, aimed at transferring the concept of "optimism" and "pessimism" to behavioral ecology and investigated the role of genetic and environmental factors in modulating CJB in mice. In addition, we assessed the temporal stability of individual differences in CJB. We show that the chosen genotypes (C57BL/6J and B6D2F1N) and environments ("scarce" and "complex") did not have a statistically significant influence on the responses in the CJB test. By contrast, they influenced anxiety-like behavior with C57BL/6J mice and mice from the "complex" environment displaying less anxiety-like behavior than B6D2F1N mice and mice from the "scarce" environment. As the selected genotypes and environments did not explain the existing differences in CJB, future studies might investigate the impact of other genotypes and environmental conditions on CJB, and additionally, elucidate the role of other potential causes like endocrine profiles and epigenetic modifications. Furthermore, we show that individual differences in CJB were repeatable over a period of seven weeks, suggesting that CJB represents a temporally stable trait in laboratory mice. Therefore, we encourage the further study of CJB within an animal personality framework.