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It is time for an empirically informed paradigm shift in animal research

Nature Reviews Neuroscience volume 21, page 660 (2020)Cite this article

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In their recent Perspective article (Voelkl et al. Reproducibility of animal research in light of biological variation. Nat. Rev. Neurosci. 21, 384–393 (2020))1, Voelkl et al. recommend the use of systematic heterogenization in animal studies. The rationale for this recommendation lies in the current best practice of rigorously standardizing (that is, homogenizing) conditions within experiments. This practice has been repeatedly criticized to limit experiments’ inference to the specific experimental conditions used and hence to cause, rather than cure, poor reproducibility in animal experiments2,3. Instead, it has been suggested to embrace biological variation and to use it actively as a tool for making study populations more representative and the results more meaningful and reproducible (for example, see refs4,5). We greatly appreciate the recommendations of Voelkl et al. and agree on the importance of a paradigm shift in animal research. However, we would like to draw attention to some points that, from our perspective, deserve more attention.

It is right that “direct evidence for the standardization fallacy is currently limited to simulations across replicate studies and only a few dedicated experimental studies”1. However, we think it is even more critical to highlight the lack of studies going beyond the standardization fallacy, proving the benefits of systematic heterogenization. Hypothesis-driven comparisons of standardized and heterogenized designs are needed, demonstrating, for example, that the latter leads to the better reproducibility of treatment effects. Until now, only three empirical studies have adopted such an approach. A single-laboratory study showed that heterogenizing mouse study populations across two environmental factors improved the reproducibility of behavioural data3. However, in a multi-laboratory situation, the same approach did not yield similarly promising results6. A third, ecological study investigated different strategies in microcosm experiments, showing that genetic heterogenization lowered between-laboratory variation7.

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References

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  1. Department of Behavioural Biology, University of Münster, Münster, Germany

    S. Helene Richter & Vanessa von Kortzfleisch

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  1. S. Helene Richter
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  2. Vanessa von Kortzfleisch
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Correspondence to S. Helene Richter.

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Richter, S.H., von Kortzfleisch, V. It is time for an empirically informed paradigm shift in animal research. Nat Rev Neurosci 21, 660 (2020). https://doi.org/10.1038/s41583-020-0369-0

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