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Are some children and adults not only most vulnerable to adverse influences but also most susceptible to supportive environments?  Differential Susceptibility Theory, with specific and bold hypotheses about the interplay between nature and nurture, paved the way for a radically new approach to Gene X Environment research. In the Anne Treisman lecture 2016 I will present a series of primary and meta-analytical studies on markers of differential susceptibility, going beyond correlational studies to experimental  tests of GxE with much improved statistical power. Many outstanding questions on mechanisms and ethical implications wait to be addressed, but clearly Donald Hebb was entirely right when he argued that G and E determine development not unlike length and width determine the surface of a rectangle.