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A NOBEL LAUREATE OFFERS BOTH PERSONAL HISTORY AND A ‘SCIENTIFIC TOUR DE FORCE’ ON MEMORY

Rowland, Lewis P. MD

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Dr. Rowland, Editor-in-chief of Neurology Today, is Professor of Neurology at Columbia University in New York.

A NOBEL LAUREATE OFFERS BOTH PERSONAL HISTORY AND A ‘SCIENTIFIC TOUR DE FORCE’ ON MEMORY

IN SEARCH OF MEMORY: THE EMERGENCE OF A NEW SCIENCE OF MIND

By Eric R. Kandel. 352 Pages. W.W. Norton & Co 2006

This is a wonderful self-help book for those who seek a Nobel Prize. All you need is the mind of a genius and a life-long obsession focused on finding the answer to a specific question; the answer must be “important” but not impossible to uncover, and the field should not be crowded with other seekers.

Figure. Dr. Lewis P....
Figure. Dr. Lewis P....
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You must be undaunted when science advances and demands learning new techniques. Flexibility must suffice for you to leave a satisfying occupation and, if you are into biomedical research, you will need manual skills (to insert electrodes into a single cell).

You need enough insight to know when to find a clever collaborator. But all that effort will get you nowhere unless you express yourself clearly in lectures and in writing; you should also find great cartoons to explain the most complicated biology. That is, you must be a great teacher. At least one physical characteristic may make you stand out in a crowd, perhaps a uniquely high-pitched laugh that is recognized by all, even in the most remote reaches of a vast auditorium.

How does that apply to Eric Kandel? We owe this remarkable book to the Nobel Institute, which requires winners of that distinguished prize to write an autobiography. Kandel has amplified his essay to a full-fledged book that is at once a personal history and a scientific tour de force.

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FROM CHILDHOOD TO MEDICAL SCHOOL

The story begins in Eric's childhood as he and his family are forced out of their native Vienna by the Hitlerian invasion in 1939; at age 9, Eric and his 14-year-old brother made their way alone from Austria to Brooklyn, NY, where they were taken in by grandparents. Eric quickly learned Hebrew first and then English.

At Erasmus Hall High School, he was captain of the track team. He was one of two from a class of 1,000 to be accepted at Harvard, where his first interests were in German history. He met brilliant psychoanalysts, and thought that would be a wonderful contemplative and inquiring career. To prepare, however, he would have to go to medical school. He crammed the requisite courses and was accepted by the New York University College of Medicine. There he met and married Denise Bystryn, a graduate student at Columbia; she had her own career in sociology, which she meshed with their long-lasting family life. Like Eric she had had her own encounters with Nazism; a Jewish child in occupied France, she had been hidden in a convent.

In his third year of medical school, Kandel spoke to Harry Grundfest, a renowned neurophysiologist at Columbia. Kandel told Grundfest he wanted to find the biological basis for psychoanalysis – to learn where in the brain are the ego, superego, and id. Grundfest replied that the brain “was beyond the grasp of contemporary brain science” and, instead “to understand the mind, we need to look at the brain one cell at a time.”

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WORK ON CELLULAR COMMUNICATION

That realization prompted Kandel to write here a 50-page crystal-clear history of the evolution of modern thought about the CNS and cellular communication. Then, he returns to autobiography.

In Grundfest's laboratory Kandel worked with a neurosurgeon-physiologist, Dominic Purpura, who himself achieved prominence as neuroscientist and Dean of the Albert Einstein College of Medicine from 1984 to 2006. Together the youthful neophytes tried to analyze the hallucinatory actions of a street drug, lysergic acid diethylamide (LSD). In doing so, Kandel learned how to deal with cats, electronic equipment, data, and ideas. However, cells in the visual cortex were too small to accept an electrode and Grundfest showed them a paper by Stephen Kuffler, who found cells large enough in crayfish.

After medical school, Kandel trained in medicine at Montefiore and returned to the Grundfest lab to work with Stanley Crain on cultured cells. Because Kandel needed some public service, Grundfest directed him to Wade Marshall's laboratory at the National Institute of Mental Health. There he met and teamed with his close friend, Alden Spencer; they aimed to find the seat of memory in the hippocampus. They managed to make some single cell records, including proof that action potentials could arise in dendrites; these and other achievements brought plaudits but did not explain memory.

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STUDIES OF APLYSIA

Kandel had benefited immensely at NIH but, after three years, he moved to find a simpler system. He needed an animal with brain cells that were fewer, identifiable, and large enough to be probed with an electrode. He found Ladislav Tauc in Paris, one of two biologists in the world working on the slug, Aplysia. They made arrangements to work together two years hence.

In the meantime, Kandel returned to Boston, setting up a laboratory while training in psychiatry. That experience strengthened his interest in laboratory research but dampened his interest in psychoanalysis. He returned to Paris for 14 months with Tauc and their work with Aplysia changed his life once again. He found that stimulating and recording electrodes in identified cells could set up paradigms for habituation and sensitization as forms of learning; he had found models of memory in simple systems.

He returned to Harvard as an instructor in psychiatry. He was promptly offered a position as Chief of Psychiatry at the Beth Israel Hospital – at age 36. But he was committed to lab work, not practice or administration. In the same vein, he realized he could not be a practicing analyst. Instead, he terminated his own psychoanalysis and left clinical Harvard for an appointment in Physiology at New York University. There, he was reunited with Alden Spencer and they were joined by James Schwartz, a biochemist.

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APPLYING METHODS OF MOLECULAR GENETICS

In 1974, the team moved to Columbia and with the help of Richard Axel, himself destined to be a Nobel laureate, Kandel used the methods of molecular genetics to understand the differences between short- and long-term memory. For instance, in short-term memory, synapses use cyclic AMP and protein kinase A to answer calls for more transmitter molecules. Kandel postulated that the enzyme moved from synapse to nucleus and there regulated gene action. In collaboration with Roger Tsien of San Diego, they found that long-term memory involves genes for CREB, a protein that modifies the action of cyclic AMP, one form facilitating gene expression in the nucleus, the other inhibiting it. Long-term memory results from gene changes in the nucleus and formation of new structures at the synapse. A major portion of the book explains the research that led to the Nobel Prize.

Many names appear as co-authors of Kandel's papers; most were probably postdoctoral fellows. The leader expresses his gratitude to them, for hard work, for the ideas they contributed, and for techniques they taught the teacher. Other co-authors of his papers include Nobelists Paul Greengard and Richard Axel. Kandel is skilled in leading teams of investigators, and sharing credit. He was 70 years old when he won the Prize in 2000. He has published 75 papers since then, continuing the flow of new and important contributions.

The world has surely changed but Kandel is still seeking a biologic basis for psychoanalysis and, sadly, for evidence of remorse by Viennese contemporaries for their role accepting Hitler. He describes valuable insights to guide thinking about consciousness and mental illness.

This compelling book would make a great motion picture. Aplysia may not be Hollywood handsome, but what a character!

©2006 American Academy of Neurology

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