In Search of Memory: The Emergence of a New Science of Mind
http://www.100md.com
《新英格兰医药杂志》
In his largely autobiographical book, In Search of Memory, Nobel laureate Eric Kandel takes us, in a tour de force, on the two complementary voyages — one private, one professional — that have encompassed his life. Kandel elucidates the transformation of psychiatry from the dominant Freudian-based psychoanalysis to a molecular science capable of resolving behavioral abnormalities in terms of molecular biology and gene expression. In considering his life, Kandel is quick to point out that for him, science is not a solitary activity but needs to be integrated into a full life that incorporates family and friends. Throughout the book, he lavishly praises and gives credit to colleagues, students, friends, and family members for enriching his scholarship and his life.
Kandel describes his youth in Vienna, the trauma of anti-Semitism, and the rise of the Nazis in Austria that forced his family to flee and emigrate to Brooklyn, New York. Like many of his Viennese immigrant peers, Kandel has a love for the romance, culture, and intellectuality of Vienna that has endured throughout his evolving intellectual life and culminated with an invitation from the Austrian government to return triumphantly as a Nobel laureate and scientific hero of Austrian birth. It appears that from an Austrian point of view — troubling times notwithstanding — once a Viennese, always a Viennese. Kandel, however, demanded that the price of his return include a symposium on Austria and the Holocaust.
In his undergraduate years at Harvard College as a history and literature major, Kandel strove to understand his heritage, and in a senior honors thesis he analyzed the work of three Austrian writers who spanned the political spectrum from liberal to National Socialist (Nazi). It was also during this time that Kandel, through the agency of Radcliffe student Anna Kris and her parents, became entranced with the intellectuality of the psychoanalytic movement and its quest to understand human behavior in rational terms. Consequently, he resolved to become a medical psychoanalyst and pursue a medical degree. In an act of extreme flexibility (perhaps a lesson to all committees on admission), the New York University School of Medicine accepted Kandel on the basis of an academic record that did not include the requisite premedical courses, with the understanding that he would complete the courses before he matriculated.
Kandel found the basic science years of medical school unexciting, but loved the clinical experiences of the later years. In his final year of medical school, he chose a 6-month elective to learn about the brain in Harry Grundfest's laboratory at Columbia University. As Kandel recounts, when Grundfest, a noted neurophysiologist, asked Kandel how he wanted to spend his time in the laboratory, Kandel replied that he wanted to locate the sites in the brain containing the id, ego, and superego. Grundfest, amused, responded that such a project was unfeasible and too complex and suggested that Kandel would do better to study the electrophysiology of related neuronal responses in the crayfish; Kandel did so and in the process learned a fundamental lesson about planning for productive work in science.
Kandel's fascination with Freud and psychoanalysis continues to this day and is evident in his book. Just as Freud borrowed from thermodynamics, a dominant science of his day, to explain sexual drive in terms of libido, or packets of sexual energy, Kandel used molecular biology to investigate the basis of memory — something beyond the ken of psychiatry of the 1950s, which largely ignored brain neurophysiology. One can only speculate as to whether Freud, if he had lived during the same era as Kandel, would have explained the id, ego, and superego in terms of genes and the regulation of genetic expression.
The key element in Kandel's quest for understanding memory was his realization that to probe the basis of memory, he would need a model organism that was less complex than the human brain and its billions of neurons. With wisdom and brilliance, he recognized that the solution of such a complex problem required a reductionist approach. He chose for his model the aplysia, a marine snail with only 20,000 neurons that was nonetheless capable of simulating many of the conditions of memory in higher forms. Kandel's major breakthrough arose when he found that memory could be associated with the relation of the strength of neuronal connections to a universal signaling molecule, cyclic adenosine monophosphate (cAMP). He and his colleagues were able to show that short-term memory was related to cAMP-mediated protein kinase A activity, which catalyzed cytosolic protein phosphorylation and thereby led to changes in potassium channels. Long-term memory also involved cAMP and protein kinase A, but in this case a transcription factor, cAMP responsive element–binding (CREB) protein, was phosphorylated and bound to nuclear DNA to activate genes, resulting in the synthesis of proteins that potentiated long-term memory. Over the years, Kandel has extended these observations to mice. CREB protein has now been shown to play a major role in brain physiology and continues to be an exciting area of investigation. This work, for which Kandel, along with Arvid Carlsson and Paul Greengard, was awarded the Nobel Prize in Physiology or Medicine in 2000, laid down some universal principles that govern memory and other dynamics of neurobiology.
Kandel intersperses autobiography with the development of molecular neuroscience in a seamless and lucid fashion. In addition, In Search of Memory serves as a handbook of advice for both beginning and mature scientists. Its message is that for a successful life in science, the selection of scientific problems must parallel one's interests and become one's passion. It also conveys that in the practice of science, hypotheses guide scientific accomplishment; the choice of experimental system and design is critical to progress; and a learning community of exciting, creative, and interactive colleagues is optimal for success. Kandel demonstrates an extraordinary ability to communicate scientific theory, experimental design, and progression of understanding, together with a passion for life and a gift for understanding people and events. These qualities make this multidimensional book an inspiring and valuable resource for both students and practitioners of science, for historians, and for the scientifically minded general reader. I have given copies to all of the trainees in my own laboratory. It is likely that In Search of Memory will become a classic scientific memoir.
Donald A. Chambers, Ph.D.
University of Illinois Medical Center
Chicago, IL 60612
donc@uic.edu(By Eric R. Kandel. 510 pp)
Kandel describes his youth in Vienna, the trauma of anti-Semitism, and the rise of the Nazis in Austria that forced his family to flee and emigrate to Brooklyn, New York. Like many of his Viennese immigrant peers, Kandel has a love for the romance, culture, and intellectuality of Vienna that has endured throughout his evolving intellectual life and culminated with an invitation from the Austrian government to return triumphantly as a Nobel laureate and scientific hero of Austrian birth. It appears that from an Austrian point of view — troubling times notwithstanding — once a Viennese, always a Viennese. Kandel, however, demanded that the price of his return include a symposium on Austria and the Holocaust.
In his undergraduate years at Harvard College as a history and literature major, Kandel strove to understand his heritage, and in a senior honors thesis he analyzed the work of three Austrian writers who spanned the political spectrum from liberal to National Socialist (Nazi). It was also during this time that Kandel, through the agency of Radcliffe student Anna Kris and her parents, became entranced with the intellectuality of the psychoanalytic movement and its quest to understand human behavior in rational terms. Consequently, he resolved to become a medical psychoanalyst and pursue a medical degree. In an act of extreme flexibility (perhaps a lesson to all committees on admission), the New York University School of Medicine accepted Kandel on the basis of an academic record that did not include the requisite premedical courses, with the understanding that he would complete the courses before he matriculated.
Kandel found the basic science years of medical school unexciting, but loved the clinical experiences of the later years. In his final year of medical school, he chose a 6-month elective to learn about the brain in Harry Grundfest's laboratory at Columbia University. As Kandel recounts, when Grundfest, a noted neurophysiologist, asked Kandel how he wanted to spend his time in the laboratory, Kandel replied that he wanted to locate the sites in the brain containing the id, ego, and superego. Grundfest, amused, responded that such a project was unfeasible and too complex and suggested that Kandel would do better to study the electrophysiology of related neuronal responses in the crayfish; Kandel did so and in the process learned a fundamental lesson about planning for productive work in science.
Kandel's fascination with Freud and psychoanalysis continues to this day and is evident in his book. Just as Freud borrowed from thermodynamics, a dominant science of his day, to explain sexual drive in terms of libido, or packets of sexual energy, Kandel used molecular biology to investigate the basis of memory — something beyond the ken of psychiatry of the 1950s, which largely ignored brain neurophysiology. One can only speculate as to whether Freud, if he had lived during the same era as Kandel, would have explained the id, ego, and superego in terms of genes and the regulation of genetic expression.
The key element in Kandel's quest for understanding memory was his realization that to probe the basis of memory, he would need a model organism that was less complex than the human brain and its billions of neurons. With wisdom and brilliance, he recognized that the solution of such a complex problem required a reductionist approach. He chose for his model the aplysia, a marine snail with only 20,000 neurons that was nonetheless capable of simulating many of the conditions of memory in higher forms. Kandel's major breakthrough arose when he found that memory could be associated with the relation of the strength of neuronal connections to a universal signaling molecule, cyclic adenosine monophosphate (cAMP). He and his colleagues were able to show that short-term memory was related to cAMP-mediated protein kinase A activity, which catalyzed cytosolic protein phosphorylation and thereby led to changes in potassium channels. Long-term memory also involved cAMP and protein kinase A, but in this case a transcription factor, cAMP responsive element–binding (CREB) protein, was phosphorylated and bound to nuclear DNA to activate genes, resulting in the synthesis of proteins that potentiated long-term memory. Over the years, Kandel has extended these observations to mice. CREB protein has now been shown to play a major role in brain physiology and continues to be an exciting area of investigation. This work, for which Kandel, along with Arvid Carlsson and Paul Greengard, was awarded the Nobel Prize in Physiology or Medicine in 2000, laid down some universal principles that govern memory and other dynamics of neurobiology.
Kandel intersperses autobiography with the development of molecular neuroscience in a seamless and lucid fashion. In addition, In Search of Memory serves as a handbook of advice for both beginning and mature scientists. Its message is that for a successful life in science, the selection of scientific problems must parallel one's interests and become one's passion. It also conveys that in the practice of science, hypotheses guide scientific accomplishment; the choice of experimental system and design is critical to progress; and a learning community of exciting, creative, and interactive colleagues is optimal for success. Kandel demonstrates an extraordinary ability to communicate scientific theory, experimental design, and progression of understanding, together with a passion for life and a gift for understanding people and events. These qualities make this multidimensional book an inspiring and valuable resource for both students and practitioners of science, for historians, and for the scientifically minded general reader. I have given copies to all of the trainees in my own laboratory. It is likely that In Search of Memory will become a classic scientific memoir.
Donald A. Chambers, Ph.D.
University of Illinois Medical Center
Chicago, IL 60612
donc@uic.edu(By Eric R. Kandel. 510 pp)