their creative use of genetics and molecular biology to define how sex is determined in Drosophila. Their experiments have shown how the ratio of sex chromosomes to autosomes can initiate a novel regulatory pathway involving RNA processing. 1993 Peter S. Kim for his pathfinding research in structural biology, which has elucidated both the pathway of protein folding and mechanisms of macromolecular recognition. 1994 Gerald F. Joyce and Jack W. Szostak for independently developing in vitro evolution of RNA catalysts. Their work produced RNA enzymes with novel specificities, while illuminating our view of natural selection. 1995 for his elucidation, by experiments elegant in their simplicity, of the relationship between the ends of yeast chromosomes and transcriptional silencing. 1996 Michael S. Levine for his insightful contributions to our understanding of gene regulation networks and molecular mechanisms governing the development of organisms with a segmented body plan. 1997 Richard H. Scheller and Thomas C. Südhof for their performance of elegant experiments to resolve the molecular components responsible for controlling neurotransmitter vesicle release and chemical communication within the nervous system. 1998 Philip Beachy for his studies of a developmental morphogen, its processing and structure, and its covalent attachment to cholesterol. 1999 Clifford Tabin for his contributions in analyzing genes that establish asymmetric body patterns and control limb development in vertebrates. 2000 Patrick O. Brown for his intellectual leadership in functional genomics, most notably the development of a reliable and accessible DNA microarray system to measure genome-wide gene expression. 2001 Erin K. O'Shea for contributions to our understanding of signal transduction, regulation of protein movement into and out of the nucleus, and how phosphorylation controls protein activity. 2002 Stephen J. Elledge for his innovative contributions at the forefront of the field of cell cycle checkpoints and his elucidation of pathways and mechanisms involved in DNA damage responses. 2003 Andrew Z. Fire and Craig C. Mello for inventing methods to inactivate genes by RNA interference and helping to elucidate their underlying mechanism and biological function. 2004 Xiaodong Wang for his biochemical studies of apoptosis which have resolved a molecular pathway leading in and out of the mitochondrion. 2005 David Bartel for his discoveries on the repertoire of catalytic RNA and the analysis of micro RNA genes and their targets. 2006 Ronald Breaker and for establishing a new mode of regulation of gene expression in which metabolites regulate the activity of their cognate pathways by directly binding