From crisis to opportunity: Linking research on animal personality and reproducibility

生命科学正面临着可重复性危机。最初，这场危机是由于在不同时间和地点重现调查结果的单一惊人失败而产生的。如今，系统的研究表明，不可重复研究的盛行率实际上超过了50%。从一个相当愤世嫉俗的角度来看，费特的实验室定律“永远不要重复成功的实验”因此被赋予了一种全新的意义。在这方面，动物研究受到了特别的审查，因为在研究伦理和社会影响方面都有很高的风险。为了解决这个问题，有必要确定再现性差的来源，并消除这些故障。从跨学科的角度来看，我们在这里开发了一种全新的方法来解决可重复性差的问题，并增加了生物变异实验结果的力量。更具体地说，通过行为表型研究的例子，我们建议整合进化生物学的知识，并将稳定的个体间行为差异，即所谓的“动物个性”，作为迄今为止在动物实验中完全被忽视的变异来源加以关注。我们的项目计划包括四个工作包（WP），其中WP I- iii为WP IV的可重复性原理验证研究建立了必要的实验基础。简而言之，WP I旨在阐明如何可靠地评估实验室小鼠行为的时间一致性，而WP II则研究人格差异是否解释了动物实验中广泛宣称的“残余变异”的相当大比例。它进一步打算验证老鼠性格的“预测标记”，可以用最小的努力来识别不同的性格类型。WP III研究了动物性格与示范治疗之间的潜在相互作用，从而阐明了性格是否是一个可以严重影响动物研究结果的因素。最后，WP IV旨在将动物人格的概念与可重复性研究联系起来，并提出一种在实验设计中考虑人格差异的新策略，以提高统计能力，从而提高可重复性。研究结果预计将对动物个性研究和动物实验的规划和实施产生影响，包括基础和临床前动物研究。

Life sciences are 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. Taking an interdisciplinary perspective, we here develop an entirely new approach to tackle poor reproducibility and increase the power of experimental findings in light of biological variation. More specifically, by the example of behavioural phenotyping studies, we propose to integrate knowledge from evolutionary biology and put stable behavioural inter-individual differences, so called “animal personalities”, into focus as a so far completely neglected source of variation in animal experiments. Our project plan comprises four work packages (WPs), from which WPs I-III build the essential experimental basis for a proof-of-principle study on reproducibility in WP IV. Briefly, WP I intends to clarify how temporal consistencies in the behaviour of laboratory mice can be assessed reliably, while WP II investigates whether personality differences explain a considerable proportion of the widely declared “residual variation” in animal experiments. It furthermore intends to validate “predictive markers” of mouse personality that can be used to identify different personality types with minimal efforts. WP III examines potential interactions between the animals’ personality and exemplary treatments, thereby elucidating whether personality is a factor that can critically affect the outcome of an animal study. Lastly, WP IV aims at linking the concept of animal personality to reproducibility research and propose a novel strategy for considering personality differences in the experimental design to improve the statistical power, and hence the reproducibility. Findings are expected to have implications for both the study of animal personality and the planning and conduct of animal experiments in basic and preclinical animal research.