Authors: Dustin Marshall, Craig R White, Van Savage, and Naomi Levine

Published in: Trends in Ecology & Evolution

Highlights

First-principles approaches underpin many biological theories, many of which claim to be firmly grounded in physics, such that their principles are inviolable.

Many predictions about how global change will affect biological systems are based on biological theories that purport to be based on first principles.

Many first-principles approaches are based on incomplete physics, while others have surprising biological assumptions at their core that are often overlooked.

We argue that first-principles approaches in biology can be powerful and hold tremendous promise, but biologists should increase their scrutiny of these approaches.

Abstract

First-principles approaches, based on physics or chemistry, are key pillars of biological theory. Despite their value, there are recurrent problems with many first-principles approaches in biology: they often include incomplete physics or are driven by unscrutinised biological assumptions. Meanwhile, debates about biological theories based on first principles usually focus on the fit of predictions to data—we argue such a focus confuses prediction with explanation.

A good fit of predictions to data is a necessary, but insufficient condition for a theory to be sound. First-principles approaches in biology will only be effective when the physics and biology are both sufficiently complete. Determining what elements are essential to include is an enduring but exciting challenge of science.

Marshall D, White CR, Savage V, Levine N (2026) Second thoughts about first principles in biology. Trends in Ecology & Evolution PDF DOI