Eric Kandel | |
|---|---|
 Kandel in 2013 | |
| Born | Erich Richard Kandel (1929-11-07)November 7, 1929 (age 96) Vienna, Austria |
| Education | Harvard University (BA) New York University (MD) |
| Known for | Physiology oflearning andmemory |
| Spouse | |
| Children | 2 |
| Awards | Karl Spencer Lashley Award(1981) Dickson Prize(1983) Lasker Award(1983) National Medal of GSS(1988)[1] Harvey Prize(1993) Wolf Prize in Medicine(1999) Nobel Prize in Physiology or Medicine(2000) |
| Scientific career | |
| Fields | Psychiatry,Psychoanalysis andNeuroscience |
| Institutions | Columbia University College of Physicians and Surgeons |
| Notable students | James H Schwartz Tom Carew Kelsey C. Martin Priya Rajasethupathy Scott A. Small Christopher Pittenger |
Eric Richard Kandel (German:[ˈkandəl]; born Erich Richard Kandel,[2] November 7, 1929[3]) is an Austrian-born American[3]medical doctor who specialized inpsychiatry. He was also aneuroscientist and aprofessor ofbiochemistry andbiophysics at theCollege of Physicians and Surgeons atColumbia University. He was a recipient of the 2000Nobel Prize in Physiology or Medicine for his research on thephysiological basis ofmemory storage inneurons. He shared the prize withArvid Carlsson andPaul Greengard.
Kandel was from 1984 to 2022 a Senior Investigator in theHoward Hughes Medical Institute.[4] He was in 1975 the founding director of the Center for Neurobiology and Behavior,[5] which is now the Department of Neuroscience at Columbia University.[6] He currently serves on the Scientific Council of theBrain & Behavior Research Foundation. Kandel's popularized account chronicling his life and research,In Search of Memory: The Emergence of a New Science of Mind,[7] was awarded the 2006Los Angeles Times Book Prize for Science and Technology.
Eric's mother, Charlotte Zimels, was born in 1897 inKolomyia,Pokuttya (modernUkraine). She came from anAshkenazi Jewish family. At that time Kolomyya was part ofAustria-Hungary. His father, Hermann Kandel, was born in 1898 inOlesko,Galicia (then part of Austria-Hungary). At the beginning ofWorld War I, his parents moved toVienna,Austria, where they met and married in 1923.[citation needed]
Eric Kandel was born on November 7, 1929, in Vienna. Shortly after, Eric's father established a toy store. Although thoroughly assimilated and acculturated, the family sensed the Nazi danger and, unlike others, left Austria after the country had beenannexed by Germany in March 1938 at great expense. As a result ofAryanization (Arisierung), attacks on Jews had escalated and Jewish property was being confiscated. When Eric was 9, he and his brother Ludwig, 14, boarded theGerolstein atAntwerp, Belgium, and joined their uncle inBrooklyn on May 11, 1939, to be followed later by his parents.[8]
After arriving in the United States and settling in Brooklyn, Kandel was tutored by his grandfather in Judaic studies and was accepted at theYeshiva of Flatbush, from which he graduated in 1944. He attended Brooklyn'sErasmus Hall High School in theNew York City school system.[9]
Kandel's undergraduate major atHarvard was History and Literature. He wrote an undergraduate honors thesis on "The Attitude Toward National Socialism of Three German Writers:Carl Zuckmayer,Hans Carossa, andErnst Jünger". While at Harvard, a place where psychology was dominated by the work ofB. F. Skinner, Kandel became interested inlearning andmemory. However, while Skinner championed a strict separation of psychology, as its own level of discourse, from biological considerations such as neurology, Kandel's work is essentially centered on an explanation of the relationships between psychology and neurology.
The world of neuroscience was opened up to Kandel as a consequence of his favorite literature teacher at the time,Karl Viëtor's, sudden passing in 1951 and leaving Kandel's next term schedule at Harvard, besides feeling "deep personal loss" over Viëtor's death, unexpectedly empty.[10] Around that time Kandel had met Anna Kris, whose parentsErnst Kris andMarianne Rie were psychoanalysts fromSigmund Freud's Vienna-based circle. Freud was a pioneer in revealing the importance of unconscious neural processes, and his lines of thought are at the root of Kandel's interest in the biology of motivation andunconscious andconscious memory.[11] Kandel changed his course to pursue and began his M.D. program atNew York University in 1952.
In 1952 he started at theNew York University Medical School. By graduation he was firmly interested in the biological basis of the mind. During this time he met his future wife,Denise Bystryn. Kandel was first exposed to research inHarry Grundfest's laboratory, for six months in 1955-56, at Columbia University.[12] Grundfest was known for using theoscilloscope to demonstrate thatconduction velocity during anaction potential depends onaxon diameter. The researchers Kandel interacted with were contemplating the technical challenges ofintracellular recordings of the electrical activity of the relatively smallneurons of the vertebrate brain.
After starting his neurobiological work in the difficult thicket of theelectrophysiology of thecerebral cortex, Kandel was impressed by the progress that had been made byStephen Kuffler using a much more experimentally accessible system: neurons isolated frommarine invertebrates. After becoming aware of Kuffler's work in 1955, Kandel graduated from medical school and learned from Stanley Crain how to make microelectrodes that could be used for intracellular recordings ofcrayfish giantaxons.
Karl Lashley, a well-known American neuropsychologist, had tried but failed to identify an anatomical locus for memory storage in the cortex of the brain. When Kandel joined the Laboratory of Neurophysiology at the USNational Institutes of Health in 1957,William Beecher Scoville andBrenda Milner had recently described the patientHM, who had lost the ability to form new memories after removal of hishippocampus. Kandel took on the task of performing electrophysiological recordings from hippocampalpyramidal neurons. Working withAlden Spencer, he found electrophysiological evidence for action potentials in thedendritic trees of hippocampal neurons.[13] The team also noticed the spontaneous pacemaker-like activity of these neurons, as well as a robust recurrent inhibition in the hippocampus. They provided the first intracellular records of the electrical activity that underlies theepileptic spike (the intracellularparoxysmal depolarizing shift) and the epileptic runs of spikes (the intracellular sustained depolarization). But, with respect to memory, there was nothing in the general electrophysiological properties of hippocampal neurons that suggested why the hippocampus was special for explicit memory storage.
Kandel began to realize that memory storage must rely on modifications in thesynaptic connections between neurons and that the complex connectivity of the hippocampus did not provide the best system for study of the detailed function of synapses. Kandel was aware that comparative studies of behavior, such as those byKonrad Lorenz,Niko Tinbergen, andKarl von Frisch had revealed that simple forms of learning were found even in very simple animals. Kandel felt it would be productive to select a simpleanimal model that would facilitate electrophysiological analysis of the synaptic changes involved in learning and memory storage. He believed that, ultimately, the results would be found to be applicable to humans. This decision was not without risk: many senior biologists and psychologists believed that nothing useful could be learned about human memory by studying invertebrate physiology.[14]
In 1962, after completing his residency in psychiatry, Kandel went to Paris to learn about the marine molluskAplysia californica fromLadislav Tauc. Kandel had realized that simple forms of learning such as habituation, sensitization, classical conditioning, and operant conditioning could readily be studied withganglia isolated fromAplysia. "While recording the behavior of a single cell in a ganglion, one nerve axon pathway to the ganglion could be stimulated weakly electrically as a conditioned [tactile] stimulus, while another pathway was stimulated as an unconditioned [pain] stimulus, following the exact protocol used for classical conditioning with natural stimuli in intact animals."[citation needed] Electrophysiological changes resulting from the combined stimuli could then be traced to specific synapses. In 1965 Kandel published his initial results, including a form of presynapticpotentiation that seemed to correspond to a simple form of learning.
Kandel took a position in the Departments of Physiology and Psychiatry at theNew York University Medical School, eventually forming the Division of Neurobiology and Behavior. Working withIrving Kupferman andHarold Pinsker, he developed protocols for demonstrating simple forms of learning by intactAplysia. In particular, the researchers showed that the now famousgill-withdrawal reflex, by which the slug protects its tender gill tissue from danger, was sensitive to both habituation and sensitization. By 1971Tom Carew had joined the research group and helped extend the work from studies restricted toshort-term memory to experiments that included physiological processes required forlong-term memory.
By 1981, laboratory members including Terry Walters, Tom Abrams, and Robert Hawkins had been able to extend theAplysia system into the study ofclassical conditioning, a finding that helped close the apparent gap between the simple forms of learning often associated with invertebrates and more complex types of learning more often recognized in vertebrates.[15] Along with the fundamental behavioral studies, other work in the lab traced the neuronal circuits ofsensory neurons,interneurons, andmotor neurons involved in the learned behaviors. This allowed analysis of the specific synaptic connections that are modified by learning in the intact animals. The results from Kandel's laboratory provided solid evidence for the mechanistic basis of learning as "a change in the functional effectiveness of previously existingexcitatory connections."[citation needed] Kandel's winning of the 2000 Nobel Prize in Physiology or Medicine was a result of his work withAplysia on the biological mechanisms of memory storage.[15]
Starting in 1966James Schwartz collaborated with Kandel on a biochemical analysis of changes in neurons associated with learning and memory storage. By this time it was known that long-term memory, unlike short-term memory, involved the synthesis of new proteins. By 1972 they had evidence that thesecond messenger moleculecyclic AMP (cAMP) was produced inAplysia ganglia under conditions that cause short-term memory formation (sensitization). In 1974 Kandel moved his lab to Columbia University and became founding director of the Center for Neurobiology and Behavior. It was soon found that the neurotransmitterserotonin, acting to produce the second messenger cAMP, is involved in the molecular basis of sensitization of the gill-withdrawal reflex. By 1980, collaboration with Paul Greengard resulted in demonstration thatcAMP-dependent protein kinase, also known as protein kinase A (PKA), acted in this biochemical pathway in response to elevated levels of cAMP. Steven Siegelbaum identified a potassium channel that could be regulated by PKA, coupling serotonin's effects to altered synaptic electrophysiology.
In 1983 Kandel helped form theHoward Hughes Medical Research Institute at Columbia devoted to molecular neural science. The Kandel lab then sought to identify proteins that had to be synthesized to convert short-term memories into long-lasting memories. One of the nuclear targets for PKA is the transcriptional control proteinCREB (cAMP response element binding protein).[16] In collaboration withDavid Glanzman and Craig Bailey, Kandel identified CREB as being a protein involved in long-term memory storage. One result of CREB activation is an increase in the number of synaptic connections. Thus, short-term memory had been linked to functional changes in existing synapses, while long-term memory was associated with a change in the number of synaptic connections.
Some of the synaptic changes observed by Kandel's laboratory provide examples ofHebbian theory. One article describes the role of Hebbian learning in theAplysia siphon-withdrawal reflex.[17]
The Kandel lab has also performed important experiments using transgenic mice as a system for investigating the molecular basis of memory storage in the vertebrate hippocampus.[18][19][20] Kandel's original idea that learning mechanisms would be conserved between all animals has been confirmed.Neurotransmitters, second messenger systems, proteinkinases,ion channels, andtranscription factors like CREB have been confirmed to function in both vertebrate and invertebrate learning and memory storage.[21][22]
Since 1974, Kandel actively contributes to science as a member of the Division of Neurobiology and Behavior at the Department of Psychiatry at Columbia University. In 2008, he and Daniela Pollak discovered that conditioning mice to associate a specific noise with protection from harm, a behavior called "learned safety", produces a behavioral antidepressant effect comparable to that of medications. This finding, reported inNeuron,[23] may inform further studies of the cellular interactions between antidepressants and behavioral treatments.
Kandel is also well known for the textbooks he has helped write, such asPrinciples of Neural Science.[24] First published in 1981 and now in its sixth edition, the book is often used as a teaching and reference text in medical schools and undergraduate and graduate programs. Kandel has been a member of theNational Academy of Sciences since 1974.[25]
He has also been at Columbia University since 1974 and lives inNew York City.
When Kandel won the Nobel Prize in 2000, initially the media reported of an "Austrian" Nobel Prize winner, phrasing that Kandel found "typically Viennese: very opportunistic, very disingenuous, somewhat hypocritical". He also said it was "certainly not an Austrian Nobel, it was a Jewish-American Nobel". After that, he got a call from then Austrian presidentThomas Klestil asking him, "How can we make things right?" Kandel said that first, Doktor-Karl-Lueger-Ring should be renamed;Karl Lueger was an anti-Semitic mayor of Vienna, cited by Hitler inMein Kampf. The street was ultimately renamed in 2012 into Universitätsring.[31] Second, he wanted the Jewish intellectual community to be brought back to Vienna, with scholarships for Jewish students and researchers.[32] He also proposed a symposium on the response of Austria to Nazism,[33] which at that time had been wanting greatly.[34] Kandel has since accepted an honorary citizenship of Vienna and participates in the academic and cultural life of his native city,[35] similar toCarl Djerassi. Kandel's 2012 book,The Age of Insight—as expressed in its subtitle,The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present[36]—represents a wide-ranging historical attempt to place Vienna at the root of cultural modernism by focussing on the personal interconnections between doctors such asCarl von Rokitansky,Emil Zuckerkandl,Sigmund Freud, with artists such asGustav Klimt,Egon Schiele andOskar Kokoschka and the writerArthur Schnitzler, all of whom engaged with the "unconscious" in one way or another and influenced, Kandel claims, one another in the tight-knit salon ofBerta Zuckerkandl and related occasions.[37]
Kandel's discoveries showed that a simple animal model could provide unparalleled insight into the mysteries of the human condition.
