Jim Smith is renowned for his work on cell-to-cell signalling in the early development of the amphibian embryo. His discovery of a mesoderm-inducing factor secreted by a cell line and establishing its identity as activin transformed the study of induction in the early embryo. He also showed that activin specifies different cell types at different thresholds and that characteristic genes like Brachyury are turned on at specific concentrations. His earlier work demonstrated threshold responses in chick limb development and also showed that the mitogenic response to growth factors can be active when attached to the extracellular matrix.