Waddington redux: models and explanation in stem cell and systems biology

Abstract

Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology, the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to triangulate between stem cell and systems approaches. This simple abstract model represents development as an undulating surface of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial but circumscribed role in explanations of cell development.