Ambiguous cells: the emergence of the stem cell concept in the nineteenth and twentieth centuries.

This paper elucidates the origins of scientific work on stem cells. From the late nineteenth century onwards, the notion of stem cells became customary in scientific communities of Imperial Germany. Adopting the term Stammzelle from Ernst Haeckel, Theodor Boveri was influential in introducing the concept in embryological studies and early genetics around 1900, describing a capacity of stem cells for self-renewal as well as differentiation. At the same time, blood stem cells were conceptualized by histologists such as Ernst Neumann and Artur Pappenheim in studies of physiological haematopoiesis and various forms of leukaemia. Furthermore, building on Julius Cohnheim's theory that tumours arise from 'embryonic remnants' in the adult body, pathologists aimed at identifying the cells of origin, particularly in the embryo-like teratomas. Embryonic stem cells thus assumed an ambiguous status, partly representing common heritage and normal development, and partly being seen as potential causes of cancer if they had been left behind or displaced during ontogeny. In the 1950s and 1960s experimental research on teratocarcinomas by Leroy Stevens and Barry Pierce in the USA brought together the strands of embryological and pathological work. Alongside the work of Ernest McCulloch and James Till at the Ontario Cancer Institute from the early 1960s on stem cells in haematopoiesis, this led into the beginnings of modern stem cell research.