Evaluating the Validity of Model Organisms: A Review and a New Framework for Biologists

Model organisms are central to biological research. Living organisms are models in the sense that the knowledge gained from their study is meant to be generalized. For example, experiments conducted on Drosophila or nematodes bring general knowledge on phenomena such as cell migration, studies in zebrafish or mice allow researchers to find therapeutical approaches applicable to human diseases, and results obtained from the study of Arabidopsis are generalized to the plant kingdom. Furthermore, new organisms gain the status of models, and non-traditional model organisms provide new perspectives on biological processes. However, the extent to which results can be generalized, or external validity, mostly relies on assumptions. Herein, a conceptual analysis is developed to justify the generalization of knowledge from one model organism to other species or human clinical contexts. After summarizing the concept of model as stated in philosophy of science, the specific features of model organisms are presented. The existing arguments put forward to justify the external validity of model organisms are then reviewed. In the second part of this article, a new framework is proposed that sets a system of criteria to assess model organisms' external validity. While grounded in concepts of philosophy of science that define the conditions under which empirical knowledge is valid, this framework is designed for use by biologists.