Three renowned neuroscientists—one psychiatrist and two neuropharmacologists—were awarded the 2000 Nobel Prize in Medicine last month. They were honored for their contributions to the understanding of brain physiology and the mechanisms that underlie learning and memory as well as Parkinson’s disease, schizophrenia, and depression. The three researchers’ work led to an explosion in pharmaceutical research producing new medications for the treatment of several mental illnesses.

Two Americans, Eric R. Kandel, M.D., professor of physiology and psychiatry and senior investigator at the Howard Hughes Medical Institute at Columbia University, and Paul Greengard, Ph.D., a professor of pharmacology and psychiatry and head of the Laboratory of Molecular and Cellular Neuroscience at Rockefeller University, were recognized along with Arvid Carlsson, M.D., professor emeritus of pharmacology at the University of Goteborg in Sweden. The three will share the $914,700 award.

The Nobel Assembly at Sweden’s Karolinska Institute said the three neuroscientists "have made pioneering discoveries concerning one type of signal transduction between nerve cells, referred to as slow synaptic transmission. These discoveries have been crucial for an understanding of the normal function of the brain and how disturbances in this signal transduction can give rise to neurological and psychiatric diseases. These findings have directly resulted in the development of new drugs."

Carlsson was recognized for his discovery that dopamine was an active neurotransmitter in the brain and his pioneering research into what happens when dopamine is not available to certain parts of the brain. His work led directly to the development of L-dopa as a pharmacological treatment for Parkinson’s disease.

Carlsson went on to discover a great deal more about the role of dopamine in the brain, in particular demonstrating the mode of action of drugs that were being used to treat schizophrenia.

Dopamine was also the focus of Greengard’s research. The Nobel committee recognized him for his discovery of how dopamine and other neurotransmitters act within the nervous system. It was Greengard who developed the cell-membrane receptor model that describes how a neurotransmitter binds to a receptor on the surface of the neuron, causing a series of events inside the cell that modify what he termed "key proteins." These proteins then regulate a variety of the neuron’s functions.

Greengard was responsible for detailing the modification of the key proteins, involving the addition of phosphate chemical groups (phosphorylation), or removal of the phosphate groups (dephosphorylation). With the addition or subtraction of phosphate groups, the structure and therefore the shape of the key protein changes and, consequently, so does its function.

Psychiatrist Kandel was recognized also for work involving phosphate groups. The Nobel Committee said it was rewarding him for his discoveries of how the efficiency of synapses can be modified and which molecular mechanisms take part in that modification. Kandel discovered that protein phosphorylation within a synapse plays a vital role in the development of a particular form of short-term memory. Kandel also detailed the importance of a change in protein synthesis within the neuron needed for long-term memory to develop. The change in protein synthesis lead to alterations in both shape and function of the synapse involved.

Kandel is also principal editor of the widely respected Principles of Neural Science. Often referred to as the "bible of neuroscience," the 1,400-page text was recently released in its fourth edition. "Medical students have been known on occasion to use it for weight lifting," one of Kandel’s students at Columbia told Psychiatric News.

"Dr. Kandel," said David I. Hirsh, M.D., interim dean of research at Columbia University College of Physicians and Surgeons, "is a superb human being whose lifelong journey to understand the molecular mechanisms of the mind is one of the finest examples of what can result when true scholarship and dedication are combined with scientific brilliance."

Throughout Kandel’s career, he has maintained an active interest in clinical psychiatry, as well as in advocating a strong interchange of ideas among diverse disciplines examining the relationship between mind and brain. In 1986, Kandel was awarded a Special Presidential Commendation by APA President Carol Nadelson, M.D., for his pioneering research in the neurosciences and his contributions to a unified theoretical model for psychiatry, and in 1989 he received APA's Distinguished Service Award. He has also been the recipient of the National Medal of Science, Lasker Award, and Wolf Prize and is a member of the National Academy of Sciences.

Kandel wrote a provocative article in the April 1998 American Journal of Psychiatry, titled "A New Intellectual Framework for Psychiatry." In the article Kandel outlined his view that it was time for psychiatry, "long an art more than a science, to reinvigorate itself by embracing biology." Kandel argued in the article that psychiatry should take advantage of the tremendous increase in knowledge in the biological basis of behavior.

In recognition of nearly 50 years of groundbreaking research, Kandel will receive the 2001 Marmor Award at APA’s annual meeting in New Orleans next May. PA President Daniel Borenstein, M.D., said he chose the theme for the meeting, "Mind Meets Brain: Integrating Psychiatry, Psychoanalysis, and Neuroscience," with Kandel in mind.

The Marmor Award, endowed last year by former APA President Judd Marmor, M.D., honors an individual who has significantly advanced the biopsychosocial model of psychiatry. Each year’s awardee presents a lecture at the annual meeting. Kandel’s lecture is tentatively scheduled for Monday, May 9.

The first annual Marmor Award was presented to Solomon Snyder, M.D., a professor of neuroscience, pharmacology, and psychiatry at Johns Hopkins University School of Medicine.

"Eric knows more neuroscience," Snyder said, "than any other person I know in the world."

APA Medical Director Steven Mirin, M.D., applauded the selection of the Nobel Prize winners. "The selection of Kandel, a psychiatrist, as well as Carlsson and Greengard, underscores the importance of the advances in neuroscience and psychiatric research that have enhanced our understanding of brain function and facilitated the development of more effective treatments for our patients. We are particularly proud of Dr. Kandel, an APA member who will give the Marmor Award lecture at next year's annual meeting."

The common thread among the three researchers is the many important contributions that each has made to the collective understanding of the brain and its functions, especially at the molecular level.

"The work of these three people," said Steven Hyman, M.D., director of the National Institute of Mental Health (NIMH), "is the platform on which we now stand to investigate the long-term changes in the nervous system that are at the heart not only of normal memory, but also of many mental illnesses and the treatment of these illnesses.

"These are the nitty-gritty molecular processes," Hyman continued, "that are going to allow us to design better therapies for lots of illnesses involving the brain."

"By discovering how nerve cells communicate with each other in areas of the brain that malfunction when these disorders occur," said Darrel Regier, M.D., M.P.H., director of APA’s Office of Research and the American Psychiatric Institute for Research and Education (APIRE), "it has been possible to develop a wide range of medications to improve the lives of people affected by these disorders."

Noting that Kandel is a distinguished member of APA, Regier told Psychiatric News, "Recognition by the Nobel Committee of the scientific importance of understanding the physiology of mental processes and the pathophysiology associated with mental disorders should stimulate even more efforts to develop better treatments and cures for our patients affected by these conditions."

Laurie Flynn, executive director of the National Alliance on Mental Illness, observed, "There is perhaps no better way to mark the closing days of the Decade of the Brain than the award of the Nobel Prize to these three individuals. Each scientist has contributed to a revolution in our understanding of the brain and its chemical mechanisms, which has opened the door to more effective treatments for schizophrenia and depression."

The Nobel Assembly’s announcement of the Prize in Physiology or Medicine is posted on the Web at <www.nobel.se/announcement/2000/medicine.html>. Kandel’s articles in AJP may be accessed at <www.psychiatryonline.org> by choosing AJP and searching by author.