“There's a divinity that shapes our ends; rough hew them how we will,” wrote Shakespeare in Hamlet. But is anatomy indeed destiny? As an assistant professor at Stanford University in the 1980s, and after years of growing cells in culture and staring at them under the microscope, I could not believe that once cells differentiated, their fate was sealed forever. Why was differentiation 'one way'? I still remember my excitement when our heterokaryon experiments, in which human differentiated cells were fused with mouse muscle myotubes, demonstrated that the 'terminally' differentiated state of human cells could be altered. The revelation of cell fate plasticity was thrilling. If understood mechanistically, this plasticity might be enlisted for new medical applications. That was the turning point in my career.
Perhaps this insight was facilitated by my own evolution as a person in response to changes in my environment. Aged nine, I lived with an Austrian family, where I learned German, milked cows, experienced the rich taste of freshly laid eggs, and rode Lipizzaner horses. At fourteen, I lived in France, climbing trees to pick fresh figs, cutting grapes in a vineyard, descending the farmer's well in a bucket, eating live sea urchins with a swipe of a baguette, and learning French. As an undergraduate student in England, I became a devotee of tea and crumpets, rubbing brasses in remote Yorkshire churches, and singing Irish ballads in pubs. My London relatives were delighted to note that I had developed an accent indistinguishable from theirs. Clearly, these diverse locales changed me: my tastes, behaviour and language. So why shouldn't the environment of a cell do the same?
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