Beyond Discovery

Ask many retiring scientists what they will miss and few will reply “my students.” Indeed, the single-minded quest for the discovery that will make your name in the field is often believed to be at odds with the other requirements of an academic career—teaching and mentoring students. Not so for Robert Y. Moore, MD, PhD, and it is part of what makes him both an extraordinary scientist and a remarkable educator.

Moore’s discoveries in sleep medicine are legendary. Among other achievements, he located the master circadian clock in the suprachiasmatic nucleus of the hypothalamus and teased out the intricate system linking that clock with the brain’s other regions. What we today know about how the body’s internal clock works and the disorders that disrupt that clock begins in large part with Moore’s research.

So how did he fit in time to mentor students and treat patients between publishing and running labs and departments? The two sides of an academic’s career—teaching and research—were never at odds, he explains. Rather teaching informed his research as much as anything he did in the lab.

“I have learned more from teaching than any other endeavor,” he says. “Anyone who says it is a burden is missing a tremendous opportunity. Teaching first of all pushes you to really know your subject. Second, it is the students asking questions that helps shape your thinking. It is the student question that you can only answer with ‘I don’t know. I’ll have to get back to you on that,’ that has led me to many new research questions.”

MORE THAN JUST A LEADING SCIENTIST

It is his role as a mentor as much as his own impressive research that has led to both the National Sleep Foundation and the Harvard Medical School Sleep Medicine Division to honor Moore with lifetime achievement awards last year.

One former student was Vincent M. Cassone, PhD, professor and chair of the Department of Biology at the University of Kentucky in Lexington.

“As a mentor, [Moore] was a steady comb on my sometimes wild, creative hair,” says Cassone. “I can remember that he would say to me during lab meetings, ‘Vinnie, that is an inherently bad idea,’ but, at the same time, encourage me to do that crazy experiment anyway—and pay for it, too.”

Moore’s ability to see beyond his own academic interests to the broader implications of his research is part of what made him such an effective teacher, physician, and scientist. However, if it had not been for some happy accidents of time and location, his life might have taken a different turn.

A ROAD NOT TAKEN

Everyone’s life and career is shaped by moments and meetings that send them in new directions. For Moore, one such pivotal moment was discovering what he was not good at.

Moore was born in 1939 in Chicago and began his undergraduate education in 1948 at Kenyon College, a small liberal arts college in Gambier, Ohio.

“I entered the literary critic program and soon discovered that I wasn’t very good at it and I didn’t like it,” he says.

Transferring to Lawrence University in Appleton, Wis, Moore had a class with a young psychology professor named John Bucklew.

Bucklew was interested in the idea that various brain functions are localized in different areas of the brain. He had Moore read a great deal about the concept of localization of function. Before long, Moore was doing basic research on brain development in frog larvae and thinking seriously about pursuing a joint medical doctorate and PhD in order to become a researcher. He graduated with honors from Lawrence in 1953 with a bachelor’s degree in zoology and entered the University of Chicago in the fall to start his graduate work.

THINKING IN 3D

From today’s perspective, the technology available to researchers on brain function was very primitive in the 1950s. There was no computed tomography (CT) or positron emission tomography (PET) scanning to view inside a living brain. Most research depended on animals, and crunching numbers was often easier to do with pen and pencil than with the enormous early computers that filled whole rooms and relied on punch cards to enter the data. Still, compared to what was available just a few years before, the technology had developed at an astounding pace.

Molecular biology, upon which so much of modern biological research and medicine is based, also was still in its infancy. When Moore entered college, the double helix structure of DNA was as yet unknown.

Moore compensated for this with his ability to think about the brain’s structure and function in a three-dimensional way.

“He had an excellent eye for the three-dimensional nature of neuroanatomical relationships in an era when computer-assisted three-dimensional reconstruction was in its infancy,” Cassone says. “He used his brain, and he taught those of us who chose to listen how to see the brain in this way.”

LIGHT LEADS THE WAY

Moore received his medical degree from the University of Chicago in 1957 and completed an internship in neurology at University Hospital in Ann Arbor, Mich, in 1959. This was followed by his PhD in biophysiology, which he completed in 1962 at the University of Chicago, and his residency in neurology, which he completed in 1964, also at the University of Chicago.

While at the University of Chicago, Moore became interested in visual pathways to the brain and how light mediated the circadian clock. When animals were kept in complete darkness, they would still follow a regular sleep and wake cycle, but the timing would slowly begin to drift to be slightly longer than the normal 24-hour day. Something in the body was taking light input and using it to keep the body’s circadian clock on time, but what and how?

Moore collaborated with the National Institutes of Health (NIH) and began working with Julius Axelrod, PhD, a biochemist, who won the Nobel Prize in 1970 for his work on the release, reuptake, and storage of the neurotransmitters epinephrine and norepinephrine. They published their first paper together in 1966.

Axelrod had studied the pineal gland and found that it played an important role in controlling circadian rhythms. It was not the master circadian clock, however. That breakthrough came when Moore studied what happened to rats whose suprachiasmatic nucleus had been damaged. The rats seemed to lose their ability to correct their circadian clock.

“Robert Moore had a profound effect on sleep medicine, with his discovery that the master oscillator that controls our 24-hour activities is located in the suprachiasmatic nucleus,” says David C. Klein, PhD, chief of the Section on Neuroendocrinology at the National Institute of Child Health and Human Development within the NIH in Bethesda, Md. “This was a pivotal event in the history of circadian biology because it centralized thinking about our circadian system. With this advance, it was possible to configure thinking about daily rhythms in a logical A to B to C way of thinking. At the center of the system was the suprachiasmatic nucleus and all rhythms either were coordinated by the clock in this tissue or were driven by it.”

The discovery impacted sleep research by demonstrating very early in the history of the field that the suprachiasmatic nucleus controls the sleep/wake cycle in animals. “Now, all theories of sleep in man include at least two components: One is the suprachiasmatic nucleus and a second is sleep debt,” Klein explains. “Our sleep patterns are determined by the interaction of these two components. Moore’s discovery has been amplified in many ways, including education—all students learning about the brain and what it does will learn about the suprachiasmatic nucleus as the central oscillator, The Mind’s Clock as Moore describes it. His discovery is also amplified by the public press, where articles on circadian rhythms often include schematics with this structure clearly identified.”

BALANCING IT ALL

What makes Moore’s discoveries all the more remarkable is that as he was researching and publishing his work on the location of the body’s master circadian clock, he also was teaching anatomy and neurology to both graduate and undergraduate students at the University of Chicago, as well as seeing patients as a practicing neurologist. For some, these other duties might have proved a distraction, but for Moore they may have been as important to his work as the time actually doing hands-on research.

“I took a year off from my clinical work once to give myself more time for my research and I got no more done than I did when I was seeing patients,” Moore says.

Although many researchers are both physicians and scientists, few are as committed to both sides as Moore was.

“Moore is a true physician/scientist,” Cassone says. “His career as a clinical neurologist truly complemented his scientific interests in understanding structure/function relationships within the nervous system, whether it pertained to the understanding of auditory circuits, visual projections, or structures associated with biological rhythms and sleep. … As a physician, he was compassionate, and I remember on several occasions witnessing his personal distress if a patient of his was not doing well.”

CALIFORNIA BECKONS

Moore worked at the University of Chicago until 1974 when he left to become a professor of neuroscience at the University of California, San Diego (UCSD). The lab he set up there became a draw for many leading young researchers, including J. Patrick Card, PhD, who was accepted for postdoctoral study in Moore’s laboratory in 1979.

“I applied for postdoctoral study with Moore because of his many contributions to the literature related to systems neurobiology and functional organization of the hypothalamus,” says Card, who is now professor of neuroscience and co-director of the Center for Neuroanatomy with Neurotropic Viruses at the University of Pittsburgh. “I was particularly attracted by the many contributions that his laboratory had made to defining the organization of catecholamine systems in the brain and his discovery of the biological clock in the hypothalamus. The important role that these systems play in the regulation of behavioral state is now well known and widely accepted. Moore’s laboratory was on the ‘ground floor’ of experimental analyses of these systems and made many of the seminal contributions that the fields of circadian biology and sleep research are built upon.”

At the bucolic UCSD campus, Moore’s lab had that buzz that happens when young researchers are given resources and just enough guidance to focus their thinking without stifling their scientific curiosity and ambition.

“I remember my period of postdoctoral research in Moore’s laboratory to be extremely exciting,” Card says. “He attracted a diverse and motivated group of scientists to his laboratory, and the resulting intellectual environment was very stimulating. He had many important attributes as a mentor, but the one that I valued the most was the freedom that he provided in pursing scientific questions. He clearly understood that the best science would emerge from interested and engaged investigators, and he provided the opportunity and guidance that allowed his young colleagues to achieve their full potential. It was a real privilege and honor to have the opportunity to launch my professional career under his guidance, and I will be forever grateful for that experience.”

BACK TO THE EAST

In 1979, Moore and his family moved to New York where he was the chairman of the Department of Neurology, State University of New York at Stony Brook. After 12 years in this position, the University of Pittsburgh asked him to become the director of their Center for Neuroscience. He would remain in Pittsburgh for the rest of his career, taking on increasingly important roles for both the university and outside organizations. These included becoming the director of the Alzheimer Disease Research Center and the director of the National Institute of Mental Health Center for Functional Brain Imaging, both at the University of Pittsburgh; co-director of the University of Pittsburgh-Carnegie Mellon University Center for the Neural Basis of Cognition, and the National Parkinson Foundation Center of Excellence; and finally chairman of the Department of Neurology. His last positions held at the university were director of the Huntington Disease Clinic and chief of the Movement Disorders Section in the Department of Neurology.

While the sleep medicine community primarily knows Moore because of his work with the biological clock, he has also published many important findings about neurological disorders like Alzheimer’s and Parkinson’s disease. All total, Moore has authored more than 200 scientific publications in his long career.

He is now enjoying retirement near the Sonoma Valley wine region of California, close to children and grandchildren who live in the Bay Area. The sun and vineyards are well earned after many a cold Pittsburgh winter, and aside from teaching, he has few regrets about leaving research to the many younger researchers he mentored through the year.

The academic life was, after all, never just about accumulating findings and publications. For Moore, understanding the brain and how it functions was part of his own curiosity about what makes us human.

“I became fascinated with the nervous system because it is so complicated and there are so many interesting things to answer,” he explains. “Understanding it is to understand humanity.”

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Lena Kauffman is a freelance writer based in Ann Arbor, Mich. She is a former editor of Sleep Review. The author can be reached at [email protected].