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

Abstract

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.

Figure 1

Theodor Boveri’s representations of the early embryonic development of the intestinal worm Ascaris megalocephala, showing self-renewal as well as differentiation of stem cells. The blackened circles along the horizontal line in Fig. 1 represent the ‘stem cells’ (‘Stammzellen’) with full chromatin content, starting with the fertilized egg cell and leading after five divisions to the ‘primordial germ cell’ (‘Urgeschlechtszelle’). The empty circles with surrounding black dots symbolize the ‘primordial somatic cells’ (‘Ursomazellen’), in which ‘chromatin diminution’ occurs as the initial step towards cell differentiation. The empty circles represent early somatic cells with reduced chromatin. Fig. 2 and 3 illustrate a ventral view respectively an optical section of the Ascaris embryo at a stage of about 120 cells, with two, just divided primordial germ cells shown in the centre of Fig. 2. From: T. Boveri, ‘Ueber die Entstehung des Gegensatzes zwischen den Geschlechtszellen und den somatischen Zellen bei Ascaris megalocephala, nebst Bemerkungen zur Entwicklungsgeschichte der Nematoden’, Sitzungsberichte der Gesellschaft für Morphologie und Physiologie in München 8, 114-125 (1892), p. 118. Bayerische Staatsbibliothek München, Signatur: Bavar. 2469 dz-7/8.

Figure 2

A haematopoietic stem tree by Artur Pappenheim. The multipotent stem cell (no. 1) in the middle of the scheme is emphasized by the bold circle. It is the origin of the ‘myeloleukoplastic branch’ (to the left), the ‘erythroplastic branch’ (to the right), ‘the lymphoplastic branch’ (in the middle, upwards), and the ‘splenoplastic branch’ (in the middle, downwards). From: A. Pappenheim, Atlas der menschlichen Blutzellen (Jena: Gustav Fischer 1905-12), vol. 1, p. 347. Staatsbibliothek zu Berlin, Signatur: 4” Kv 1955.