Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Systematic variation improves reproducibility of animal experiments

Nature Methods volume 7, pages 167–168 (2010)Cite this article

Subjects

To the Editor:

Reproducibility is the cornerstone of any scientific method. We have recently shown in the pages of this journal that standardization in mouse experiments—that is, standardization in the characteristics of the animals used (such as age, sex, body weight and others), husbandry and test procedures—may generate spurious results, accounting for poor reproducibility1. This is contrary to the traditional assumption that such standardization guarantees reproducibility2. The problem is that standardization reduces within-experiment variation, which may limit inference to the specific experimental conditions3,4. We had shown that systematic variation of experimental conditions (heterogenization) may attenuate spurious results and improve reproducibility, thereby avoiding scientific uncertainty and unnecessary duplication of experiments1. However, our conclusions were challenged because they were based on retrospective analysis, and heterogenization may be logistically unfeasible5. Here we confirm our hypothesis empirically, showing that even simple heterogenization within experiments may improve reproducibility between experiments.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Effect of standardization and heterogenization on between-experiment variation.
Figure 2: Heterogenization improves reproducibility by increasing within-experiment variation as shown in the path length in a free exploration test.

References

  1. Richter, S.H., Garner, J.P. & Würbel, H. Nat. Methods 6, 257–261 (2009).

    Article  CAS  Google Scholar 

  2. Beynen, A.C., Gärtner, K. & van Zutphen, L.F.M. in Principles of Laboratory Animal Science 2nd edn. (eds., van Zutphen, L.F.M., Baumans, V. & Beynen, A.C.) 103–110 (Elsevier, Amsterdam, 2003).

    Google Scholar 

  3. Würbel, H. Nat. Genet. 26, 263 (2000).

    Article  Google Scholar 

  4. Crabbe, J.C., Wahlsten, D. & Dudek, B.C. Science 284, 1670–1672 (1999).

    Article  CAS  Google Scholar 

  5. Paylor, R. Nat. Methods 6, 253–254 (2009).

    Article  CAS  Google Scholar 

  6. Larkin, J.E., Frank, B.C., Gavras, H. & Quackenbush, J. Nat. Methods 2, 337–343 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft).

Author information

Authors and Affiliations

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

    S Helene Richter

  2. Animal Welfare and Ethology, University of Giessen, Giessen, Germany

    S Helene Richter & Hanno Würbel

  3. Animal Sciences, Purdue University, West Lafayette, Indiana, USA

    Joseph P Garner

  4. Mathematical Statistics and Applications in Nature Sciences, Technische Universität Dortmund, Dortmund, Germany

    Corinna Auer & Joachim Kunert

Authors
  1. S Helene Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph P Garner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Corinna Auer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joachim Kunert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanno Würbel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanno Würbel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4, Supplementary Methods (PDF 447 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richter, S., Garner, J., Auer, C. et al. Systematic variation improves reproducibility of animal experiments. Nat Methods 7, 167–168 (2010). https://doi.org/10.1038/nmeth0310-167

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth0310-167

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing