Mervyn Maze, M.D., Ch.B.

The purpose of the ASA Award for Excellence in Research is to recognize an outstanding researcher who has had a major impact on the practice of anesthesiology and advancement of the science of anesthesiology. This purpose is embodied in the career and accomplishments of 2003 awardee Mervyn Maze, M.D., Ch.B. Dr. Maze’s career has been a remarkable journey of discovery spanning 25 years and three continents. His discoveries have led to the introduction of new drugs and approaches to the practice of anesthesiology, have fundamentally changed our thinking about central issues in our field such as sedation and analgesia and have inspired his colleagues and trainees.

Dr. Maze’s journey of discovery began in South Africa where he was born and educated at the height of apartheid. He received his medical degree from the University of Capetown and served two years as a house officer in respiratory medicine and gastroenterology at Groote Schuur Hospital. As a strong opponent of apartheid, he was anxious to leave South Africa and did so the day his wife, Janet Wyner, graduated from medical school. Immigrating to the United Kingdom, he trained in internal medicine at the Royal Free Hospital with plans to pursue a career in academic gastroenterology. At the advice of his mentor, Dame Sheila Sherlock, M.D., Dr. Maze moved to Stanford University in California in 1977 to pursue training in basic science.

At Stanford, he worked as a postdoctoral fellow in the section of gastroenterology, studying the pathobiology of functional membrane proteins in the brush border of the small intestine. Fortuitously, Dr. Maze’s wife, his brother Aubrey Maze, M.D., and his cousins Richard I. Mazze, M.D., and Sheila E. Cohen, M.B., were all in the department of anesthesiology at Stanford; their infectious enthusiasm and powers of persuasion led Dr. Maze to enroll as an anesthesiology resident and to apply his interest in membrane proteins to the field of anesthesiology. His initial investigations focused on the mechanism whereby halothane sensitizes cardiac adrenergic receptors to the effects of epinephrine. These studies led to the unexpected finding that while ß-adrenergic receptors are the predominant subtype in the heart, halothane sensitization involved an a-adrenoreceptor.¹ More importantly, this work focused the next two decades of Dr. Maze’s research on a-adrenergic receptors and their role in sedation and analgesia.

In the early 1980s, Dr. Maze set out to understand whether activation of a₂ adrenergic receptors altered volatile anesthetic requirements. These studies quickly led to the seminal observation that a₂ adrenergic receptor agonists were “anesthetic” agents in their own right.² Dr. Maze and his group promptly applied these findings in humans, leading to the introduction of dexmedetomidine as a sedative in clinical practice and the application of clonidine as a neuraxial analgesic agent. Rather than serving as an endpoint, this process of drug discovery and clinical application served as a jumping-off point for some key observations concerning the molecular, cellular and anatomic mechanisms of anesthesia.

First, Dr. Maze used transgenic mice in which the a_2A receptor was rendered nonfunctional to demonstrate that the a_2A receptor subtype was uniquely responsible for the hypnotic effects of dexmedetomidine.³ This was the first demonstration that elimination of a single membrane protein could prevent anesthesia; because other nonadrenergic drugs were still capable of producing anesthesia, these experiments also refuted the long-held theory (unitary theory of anesthesia) that all anesthetics worked via a common molecular mechanism. Second, he was able to show that a_2A adrenergic neurons specifically located in the locus coeruleus, a small nucleus harboring noradrenergic neurons in the brainstem, were responsible for the sedative actions of dexmedetomidine.⁴ This was the first demonstration that anesthetics acted at distinct anatomic loci within the central nervous system to produce specific behavioral effects.

In 1999, Dr. Maze was recruited to the United Kingdom to become the Sir Ivan Magill Professor of Anaesthetics at the Medical School of Imperial College, London. There he has teamed up with Professor Nick Franks to continue their mutual pursuit of the mechanisms of anesthetic action. Together they have shown that the sedative actions of several anesthetics are mediated by GABA_A receptors located in specific brainstem nuclei that are involved in endogenous sleep production. The sedative actions of a₂ agonists, in contrast, are mediated by a_2A receptors that also are located in the endogenous sleep pathway.⁵ Through this work, they have demonstrated that while different anesthetics affect different receptors, their actions converge on the same neuronal pathways, thus producing a common behavioral endpoint-sedation. In keeping with this concept, Dr. Maze and colleagues have subsequently elucidated the specific molecular targets and neural substrates for the analgesic actions of several anesthetics, including nitrous oxide and isoflurane.^6,7 Most recently, Dr. Maze has focused his attention on a new field, neuroprotection. Together with Professor Franks, he has recently shown that xenon is a potent neuroprotectant in several models.⁸ Consistent with his history as a translational researcher, Dr. Maze is now initiating clinical trials probing the safety and efficacy of xenon as a clinical neuroprotective agent.

Throughout his career, Dr. Maze has contributed richly to each of the stops on his journey of discovery. A fellow of the Royal College of Physicians, he has trained more than 60 undergraduate, graduate and postgraduate students. He has served as Associate Chair for Research in the department of anesthesiology at Stanford University and is the head of the Department of Anaesthetics and Intensive Care at Imperial College, London. He is also the Director of Research and Development and the campus dean at the Chelsea and Westminster Hospital in London. He is currently an editor for Anesthesiology, has authored more than 150 original research articles and 22 book chapters and has edited three textbooks.

Aside from his tangible accomplishments, Dr. Maze is a whirlwind of energy, charm and charisma. His energy is manifest in his passion for sports (especially rugby), theater, bicycling, politics and, of course, science. His charisma and intellect are palpable and have inspired students, colleagues and acquaintances. He always sees the best in people and encourages them to be even better. Not surprisingly, Dr. Maze has friends in dozens of cities on every habitable continent. Most importantly, he is a loving husband of 30 years, a dedicated father and a doting grandfather.

The specialty of anesthesiology owes a debt of gratitude to Dr. Mervyn Maze. When he began his career, the mechanisms of anesthesia were virtually a “black box.” Through Dr. Maze’s work, we largely understand the mechanism whereby a₂ agonists produce sedation and analgesia. Thanks to Dr. Maze, we now have two a₂ agonists with specific clinical indications in the field of anesthesiology, clonidine for treatment of neuropathic pain and dexmedetomidine for sedation in the intensive care unit. He also has provided us with an understanding of the circuitry involved in the mechanisms of analgesia and sedation for several other anesthetics, including nitrous oxide. Finally, Dr. Maze has provided inspirational research leadership to our specialty through his example, his enthusiasm and his encouragement of others. The ASA Award for Excellence in Research serves as a well-deserved tribute to Mervyn Maze, M.D.

Alex S. Evers, M.D., is the Henry E. Mallinckrodt Professor and Chair, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri.