Imagine 2004, prior to the advent of induced pluripotent stem cells (iPS cells) and the realization that cellular identity is a tabula rasa that can be rewritten at will. It was widely accepted that once terminally differentiated cells were born, their identity — be it a brain, bone or blood cell — was fixed and immutable. This view was influenced by Waddington’s landscape model from his 1940 monograph, Organisers and Genes, which depicted cellular differentiation as an irreversible, one-way journey down a slope. However, in 1940, Haldane presciently presaged the decades to come; “Like other symbols in biology, I expect that this one will prove valuable for a time but may later be rather misleading.”

In the 1980s, Weintraub, Graf and others challenged this dogma by demonstrating that the forced expression of a single transcription factor could reprogramme the identity of cultured cells. Yet, these early studies encountered resistance, with some even dismissing reprogramming as an experimental artefact. This raised a critical question: are the identities of freshly isolated, differentiated cells similarly malleable?