Murray showed that cyclin synthesis drives the cell cycle and, later, that ubiquitin regulates levels of cyclin by marking the cell-cycle molecule for destruction. His lab discovered and purified many of the components involved in cell cycle progression, including anaphase promoting complex (APC), the complex that ubiquitinates cyclin B. A second noted finding was his discovery, with Tim Mitchison, of the dynamic instability of microtubules, In mitosis, for example, microtubules form the spindle that separates the chromosomes. The first step in spindle formation is the nucleation of microtubules by microtubule-organizing centers, which then grow in all directions. Microtubules that attach to a chromosome are stabilized and are therefore retained to form part of the spindle. Because of dynamic instability, some individual microtubules that are not stabilized are at risk of collapse (or “catastrophe” as Kirschner named it), allowing re-use of the tubulin monomers. This recognition of self-organization in biological systems has been highly influential, and helped shape the view of the cytoplasm as a collection of dynamic molecular machines. Kirschner is also interested in the evolutionary origins of the vertebrate body plan. Together with John Gerhart, he was instrumental in developing the acorn worm Saccoglossus kowalevskii into a model system that could be used to study the divergence between hemichordates and chordates, and the evolution of the chordate nervous system. Kirschner is a pioneer in using mathematical approaches to learn about central biological questions. For example, a model of the Wnt pathway he developed in collaboration with the late Reinhart Heinrich showed that new properties and constraints emerge when the individual biochemical steps are combined into a complete pathway. A talk he gave on mathematics and the future of medicine at a retreat for Department Chairs at Harvard Medical School in 2003 inspired the Dean, Joseph B. Martin, to found a new Department, the Department of Systems Biology, with Kirschner as founding chair. Since then, Kirschner's lab has attracted many students and post-docs from theoretical backgrounds who wish to make the transition into biology. His lab is now a leader in using mathematical tools to analyze signaling pathways, cell size control, and the selectivity of drugs. In two books co-authored with John Gerhart, Kirschner has described the cellular and developmental underpinnings of the evolution of organisms, and the concept of "evolvability". In the most recent book, Kirschner and Gerhart proposed a new theory of "facilitated variation" that aims to answer