I speak with a friend and colleague of mine with whom I worked in Yorkhill.  He is now a Professor of Clinical Genetics at the MRC Genetics Unit in Edinburgh and has devoted his life and career to understanding the genetic and metabolic basis of severe developmental disorders.  In particular he is fascinated by the concept of genetic disease that is not inherited.  We talk through his career and some of the important discoveries that he and colleagues have made which radically advance our understanding of severe developmental disorders.  I illustrate the concept of de novo genetic disease by re-visiting Sophie, the girl with Dravet syndrome, and taking you through the recognition of the genetic basis of this severe epileptic encephalopathy and some of the exciting advances that are just around the corner in terms of potential genetic treatments for this condition.