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I am very happy that @MKrzywinski and Naomi Altman gave us the opportunity to contribute an article on the #standardizationfallacy to their legendary #pointsofsignificance column in @naturemethods https://www.nature.com/articles/s41592-020-01036-9
It all started 20 (actually 21) years ago with this 
correspondence on behaviour and the standardization fallacy in @NatureGenet https://www.nature.com/articles/ng1100_263
correspondence on behaviour and the standardization fallacy in @NatureGenet https://www.nature.com/articles/ng1100_263
It was my response to this famous paper in @ScienceMagazine by John Crabbe and colleagues showing that behavioural phenotypes of mouse mutants may turn out to be lab specific https://science.sciencemag.org/content/284/5420/1670.full
famous paper in @ScienceMagazine by John Crabbe and colleagues showing that behavioural phenotypes of mouse mutants may turn out to be lab specific https://science.sciencemag.org/content/284/5420/1670.full
At that time, rigorous standardization - in the sense of minimizing both genetic and environmental variation - was dogma in laboratory animal science and was even promoted as a means to reduce animal use from a #3Rs perspective
Heterogenization - the deliberate introduction of genetic and/or environmental variation into study design - was received with little enthusiasm (to say the least...) and so it took a while for me to get back to it
The next step was a perspectives article with Helene Richter and Joe Garner in @naturemethods presenting a proof-of-principle that standardization is a cause of, rather than a cure for, poor #reproducibility https://www.nature.com/articles/nmeth.1312
This was followed by our first empirical evidence showing that #heterogenization of environmental factors can improve reproducibility (same team with help from Corinna Auer and Joachim Kuhnert) https://www.nature.com/articles/nmeth0310-167?proof=t
However, not everybody was convinced and Jonker and colleagues questioned our analysis in a correspondence to the editor of @naturemethods https://www.nature.com/articles/nmeth.2439
Wolfinger, a statistician invited to settle the case, remained diplomatic... https://www.nature.com/articles/nmeth.2438
...while we maintained our position but agreed that further research was needed https://www.nature.com/articles/nmeth.2446
In the meantime, we had put our hypothesis that heterogenization improves reproducibility to an empirical multi-laboratory test - the results were encouraging but far from convincing https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0016461
Then it took a while until Bernhard Voelkl joind my team and took this research to the next level by more formally integrating it with the concept of #reactionnorm and phenotypic plasticity https://doi.org/10.1016/j.tips.2016.05.003
Next, him and Lucile Vogt ran simulations using large existing datasets of preclinical research provided by @CAMARADES_ and together with @drEmilySena we found that #reproducibility improves with heterogeneity of study samples https://doi.org/10.1371/journal.pbio.2003693
Encouraged by these findings, Bernhard organised a workshop to develop our framework further, which led to a great collaboration with fantastic colleagues and this comprehensive perspective paper https://www.nature.com/articles/s41583-020-0313-3
comprehensive perspective paper https://www.nature.com/articles/s41583-020-0313-3
Furthermore, using prize money from an @NC3Rs award to Bernhard and some University funds, we were able to develop a whiteboard animation with @cleverclip to illustrate the principle of heterogenization
And so even after 21 years, I am far from being bored by the standardization fallacy - and if neither you are: stay tuned, there is more to come....
