Our discovery 35 years ago that cell-surface receptor activation leads to increased metabolic turnover of an inositol-containing phospholipid, phosphatidylinositol (PI), was serendipitous. Had there not been phospholipid-derived contaminants in an "RNA" fraction I was studying, Mabel Hokin and I probably would never have come across this important phenomenon. It turns out that the "PI effect" involves the release of components of inositol phospholipids that serve as second messengers.
The story begins in August 1949, when I arrived at H.A. Krebs' laboratory at the University of Sheffield, U.K., to work towards a biochemistry Ph.D. As was often his style, Krebs suggested that I formulate my own problem and work on it with little supervision. I was a rather independent fellow, far too independent given my limited experience in biochemistry, and I happily accepted his proposal. We therefore had little contact with each other, apart from brief exchanges in the hall before ...
