The stated purpose of the American Society of Anesthesiologists Excellence in Research Award is to recognize outstanding research that has had a major impact on the practice of anesthesia and advancement of the science of anesthesiology. This purpose is embodied in the career and accomplishments of this year's awardee, Mervyn Maze. Mervyn'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 thinking about central issues in our field such as sedation and analgesia, and have inspired his colleagues and trainees.
Mervyn Maze's journey of discovery began in South Africa, where he was born and educated at the height of the apartheid regime. He received his medical degree from the University of Capetown and served 2 years as a house officer in Respiratory Medicine and Gastroenterology at Groote Schuur Hospital. As a strong opponent of apartheid, he was eager 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, Mervyn moved to Stanford University 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, Mervyn's wife, his brother Aubrey, and his cousins Dick Mazze and Sheila Cohen were all in the Department of Anesthesiology at Stanford; their infectious enthusiasm and powers of persuasion led Mervyn to enroll as an anesthesia resident and to apply his interest in membrane proteins to the field of anesthesia. 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 although β-adrenergic receptors are the predominant subtype in heart, halothane sensitization involved an α-adrenoreceptor. 1
More important, this work focused the next two decades of his research on α-adrenergic receptors and their role in sedation and analgesia.
In the early 1980s, Dr. Maze set out to understand whether activation of α2
adrenergic receptors altered volatile anesthetic requirements. These studies quickly led to the seminal observation that α2
adrenergic receptor agonists were “anesthetic” agents in their own right. 2
He 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 α2A
receptor was rendered nonfunctional to demonstrate that the α2A
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 it was α2A
adrenergic neurons specifically located in the locus ceruleus, a small nucleus harboring noradrenergic neurons in the brainstem, that 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 Anesthetics 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 γ-aminobutyric acid receptor type A receptors located in specific brainstem nuclei that are involved in endogenous sleep production. The sedative actions of α2
agonists, in contrast, are mediated by α2A
receptors that are also located in the endogenous sleep pathway. 5
Through this work they have demonstrated that although 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, Maze et al.
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, Mervyn Maze has also contributed richly to each of the stops on his journey of discovery. He has trained over 60 undergraduate, graduate, and postgraduate students. He has served as Associate Chair for Research in the Department of Anesthesia at Stanford and is the Head of the Department of Anesthetics 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 and is currently an Editor of Anesthesiology. He has authored more than 150 original research articles and 22 book chapters, and has edited three textbooks.
Aside from his tangible accomplishments, Mervyn Maze is a whirlwind of energy and charm who epitomizes 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, Mervyn has friends in dozens of cities on every habitable continent. Most important, Mervyn is a loving husband of 30 years, a dedicated father, and a doting grandfather.
The specialty of anesthesiology owes a debt of gratitude to Mervyn Maze. When he began his career, the mechanisms of anesthesia were virtually a “black box.” Through his work, we largely understand the mechanism whereby α2 agonists produce sedation and analgesia. Thanks to Mervyn, we now have two α2 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. Mervyn has also provided us with an understanding of the circuitry involved in the mechanisms of analgesia and sedation for several other anesthetics, including nitrous oxide. Finally, he has provided inspirational research leadership to our specialty through his example, his enthusiasm, and his encouragement of others. The ASA Excellence in Research Award serves as a well-deserved tribute to Mervyn Maze.
Figure. Mervyn Maze,...Image Tools
1. Maze M, Smith CM: Identification of the receptor mechanism mediating epinephrine-induced arrhythmias during halothane anesthesia in the dog. A nesthesiology 1983; 59: 322–6
2. Doze VA, Chen, B-X, Maze M: Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors. A nesthesiology 1989; 71: 75–9
3. Lakhlani PP, MacMillan LB, Guo T-Z, McCool BA, Lovinger DM, Maze M, Limbird LE: Substitution of a mutant alpha-2A-adrenergic receptor via “hit and run” targeting reveals the role of the subtype in sedative, analgesic and anesthetic-sparing responses. Proc Natl Acad Sci USA 1997; 94: 9950–5
4. Correa-Sales C, Rabin BC, Maze M: A hypnotic response to dexmedetomidine, an alpha-2 agonist, is mediated in the locus ceruleus in rats. A nesthesiology 1992; 76: 948–52
5. Nelson LE, Guo T-Z, Lu J, Saper CB, Franks NP, Maze M: The sedative component of anesthesia is mediated by GABA(A) receptors in an endogenous sleep pathway. Nat Neurosci 2002; 5: 979–84
6. Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Kobilka BK, Hashimoto T, Maze M: Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of alpha-2B adrenoceptors. J Neurosci 2000; 20: 9242–51
7. Kingery WS, Agashe GS, Guo T, Sawamura S, Davies MF, Clark JD, Kobilka BK, Maze M: Isoflurane and nociception: Spinal α2A
adrenoceptors mediate antinociception while supraspinal α1
adrenoceptors mediate pronociception. A nesthesiology 2002; 96: 367–74
8. Wilhelm S, Ma D, Maze M, Franks NP: Effects of xenon on in vitro and in vivo models of neuronal injury. A nesthesiology 2002; 96: 1485–91
© 2003 American Society of Anesthesiologists, Inc.