Lionel Penrose (1898–1972) was an important leader during the mid-20th century decline of eugenics and the development of modern medical genetics. However, historians have paid little attention to his radical theoretical challenges to mainline eugenic concepts of mental disease. Working from a classification system developed with his colleague, E. O. Lewis, Penrose developed a statistically sophisticated and clinically grounded refutation of the popular position that low intelligence is inherently a disease state. In the early 1930s, Penrose advocated dividing “mental defect” (...) (low intelligence) into two categories: “pathological mental defect,” which is a disease state that can be traced to a distinct genetic or environmental cause, and “subcultural mental defect,” which is not an inherent disease state, but rather a statistically necessary manifestation of human variation in intelligence. I explore the historical context and theoretical import of this contribution, discussing its rejection of typological thinking and noting that it preceded Theodosius Dobzhansky’s better-known defense of human diversity. I illustrate the importance of Penrose’s contribution with a discussion of an analogous situation in contemporary medicine, the controversial practice of using human growth hormone injections to treat “idiopathic short stature” (mere diminutive height, with no distinct cause). I show how Penrose’s contributions to understanding human variation make such treatments appear quite misguided. (shrink)