Stephen F. Heinemann (1939–2014)

Stephen F. Heinemann Steve Heinemann, one of the fathers of modern molecular neuroscience and a pioneer in neurotransmitter receptor biology, passed away on August 6, 2014, in La Jolla, California. Steve was well known in the neuroscience community as a genuinely nice guy with an unorthodox approach to research. For almost four decades in an extraordinarily productive career he helped to drive a quantum leap forward in elucidating the molecular components and cellular basis of excitatory neurotransmission in the mammalian CNS. These efforts paved the way for new insights into fundamental aspects of nervous system function, which led to advances in our understanding of neurological and psychiatric disorders. Born in Boston in 1939, Stephen Fox Heinemann obtained a bachelor in science degree from the California Institute of Technology in 1962. He pursued his PhD in biochemistry at Harvard University in 1967 under the mentorship of Matthew Meselson, where he studied the structure of DNA. His postdoctoral training was carried out at the Massachusetts Institute of Technology and Stanford University School of Medicine, during which time he made contributions to the understanding of the genetics of the bacteriophage lambda life cycle. Soon after, his interest shifted to the nervous system, and he joined the Salk Institute for Biological Studies in 1970, where he became one of the founders of the Molecular Neurobiology Laboratory at the newly minted research institute that would become his second home. The Salk Institute, a masterpiece of Louis Kahn, one of the most influential architects of the 20 century, was designated a historical landmark in 1991, following his father’s ‘‘even a brick wants to be something’’ prophecy. A similar destiny was to be followed by the Molecular Neurobiology Laboratory, a program to be ranked number one in world neuroscience in the late 1980s, in part due to discoveries arising from the Heinemann laboratory. In his early days at the Salk Institute, Steve focused on the neurotransmitter receptors present at the neuromuscular junction. This was the model system widely used to understand synaptic transmission before brain synapses became tractable. His landmark early work, in collaboration with Jon Lindstrom and others, established that myasthenia gravis, a disease that leads to muscle weakness, fatigue, and paralysis, is the consequence of the presence of autoantibodies to nicotinic acetylcholine receptors (nAChRs) present at the neuromuscular junction. Steve’s primary interest, however, was to understand the structure and properties of these acetylcholine receptors. In 1970, JeanPierre Changeux and coworkers used biochemical methods to characterize the nAChR as a ligand-gated ion channel formed by five homologous subunit proteins. In order to isolate DNA complementary to the mRNA encoding specific receptor subunit proteins, Steve decided to use a strategy based on recently developed molecular cloning methods. Biochemical methods had previously yielded short stretches of amino acid sequences from one of the muscle nAChR proteins; using this information, one could clone the full-length sequence