The historical origins of mechanistic pharmacokinetic–tumour growth inhibition (PK–TGI) modelling are usually located in the later twentieth century. However, many of the essential ideas were already present in the 1930s, although not brought together in a single formal framework. In 1937, Torsten Teorell published a physiological theory of drug absorption, distribution, and elimination based on transport across biological boundaries and exchange between anatomical spaces. Five years earlier, W. V. Mayneord showed that the growth of Jensen’s rat sarcoma was more naturally described on a linear dimension than on tumour volume and explained this behaviour mechanistically by assuming proliferation within a thin outer rim surrounding a necrotic core. Read together, these papers contain the key ingredients of a physiological PK–TGI model: Teorell provides the concentration–time function, C(t), and Mayneord provides a growth law expressed on tumour radius, dR/dt = g. The missing link is an effect term coupling exposure to inhibition of radial growth. In its simplest form, this yields dR/dt = g - ψ(C). This article is not intended as an exhaustive review. Rather, it argues that the 1930s should be recognised as a formative period in mechanistic biomedicine in which the conceptual foundations of physiological PK–TGI modelling were already available in print. Selected later examples are used only to show that, even when tumour growth is recast in exponential, Gompertzian, reaction-diffusion, agent-based, or modern semi-mechanistic PK–TGI language, the field repeatedly returns to the same central point: for a solid tumour, net growth is governed by the behaviour of a viable outer region rather than by the bulk alone.
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