Pluripotent human stem cells: Standing on the shoulders of giants

The advent of human pluripotent stem cells, with the first derivation of human embryonic stem cells in 1998, and of human induced pluripotent stem cells in 2007, has ushered in an era of considerable excitement about the prospects of using these cells to develop new opportunities for healthcare, from their potential for regenerative medicine to their use as tools for studying the cellular basis of many diseases and the discovery of new drugs. But as with the flowering of many new areas in science, the biology of human pluripotent stem cells has its roots in a long history of, sometimes, less fêted research. In a period when research funding is frequently driven by a desire to meet specific clinical or economic goals, it is salutary to remember that the opportunities offered by human pluripotent stem cells have their origins in curiosity driven research without any of those goals in mind. In this case, that research focused on the relatively rare gonadal cancers known as teratomas, tumors that have fascinated people since antiquity because their sometime grotesque manifestations with haphazard collections of tissues and sometimes recognizable body parts. Although well known to clinical pathologists it was the pioneering work of Leroy Stevens, who first discovered that teratomas occur at a significant rate in the 129 strain of the laboratory mouse and could be produced experimentally, that laid the foundations for our understanding of the biology of these tumors and the central role of the embryonal carcinoma cell, one of the archetypal tumor stem cells.