Pluripotent stem cells: private obsession and public expectation

In the 1960s it was shown that a rare type of tumour called a teratocarcinoma contains cells that are both pluripotent and self-renewing (Kleinsmith & Pierce, 1964). Pluripotent means the capacity of an individual cell to give rise to all other cell types of the body and the germline. This property is normally restricted to a brief window in early development. Selfrenewal is the production of identical daughter cells while retaining the ability for differentiation. It is the defining feature of a stem cell. The study of teratocarcinoma stem cells led to particular culture conditions that allowed them to be propagated ex vivo without differentiation. In 1981 Martin Evans, Matt Kaufman and Gail Martin found that cells from early mouse embryos exposed to the same culture environment can suspend developmental progression and continue to multiply while remaining pluripotent (Evans & Kaufman, 1981; Martin, 1981). These are embryonic stem (ES) cells. I was completing my undergraduate studies in Oxford at that time and was fortunate to learn about this rather esoteric research from a wonderful teacher, Chris Graham. Chris also talked about parallel discoveries of growth factors and the provocative idea that they might regulate cell fate. I was captivated by the idea of understanding and controlling the pluripotent state and that has beenmy obsession ever since.