Thread by @HannoWurbel

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
nature.com/articles/s4159…

It all started 20 (actually 21) years ago with this 👇correspondence on behaviour and the standardization fallacy in @NatureGenet nature.com/articles/ng110…

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 science.sciencemag.org/content/284/54…

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 nature.com/articles/nmeth…

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) nature.com/articles/nmeth…

However, not everybody was convinced and Jonker and colleagues questioned our analysis in a correspondence to the editor of @naturemethods
nature.com/articles/nmeth…

Wolfinger, a statistician invited to settle the case, remained diplomatic...
nature.com/articles/nmeth…

...while we maintained our position but agreed that further research was needed
nature.com/articles/nmeth…

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
journals.plos.org/plosone/articl…

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
doi.org/10.1016/j.tips…

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
doi.org/10.1371/journa…

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
nature.com/articles/s4158…

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....🤓