Eric Kandel

Eric Richard Kandel (born November 7, 1929) is an Austrian-American neuropsychiatrist and recipient of the 2000 Nobel Prize in Physiology or Medicine, shared with Arvid Carlsson and Paul Greengard. His research entails the physiological basis of memory storage in neurons.

• As knowledge advances and scientific disciplines change, so do the disciplines impinging on them.
  • Psychiatry, Psychoanalysis, and the New Biology of Mind (2008)

• In the period from 1920 to 1960, psychiatry derived its main intellectual impetus from psychoanalysis. During this phase, its most powerful antidisciplines were philosophy and the social sciences. Since 1960, psychiatry has begun (again) to derive its main intellectual challenge from biology, with the result that neurobiology has been thrust into the position of the new antidiscipline for psychiatry.
  • Psychiatry, Psychoanalysis, and the New Biology of Mind (2008)

• In the near future, neurobiology will address a matter of more general and fundamental importance: the biology of human mental processes. ...Psychology and psychiatry can illuminate and define for biology the mental functions that need to be studied if we are to have a meaningful and sophisticated understanding of the biology of the human mind.
  • Psychiatry, Psychoanalysis, and the New Biology of Mind (2008)

• The Age of Insight is a product of my... fascination with the intellectual history of Vienna from 1890 to 1918, as well as my interest in Austrian modernist art, psychoanalysis, art history, and the brain science that is my life's work. ...I examine the ongoing dialogue between art and science that had its origins in fin-de-siècle Vienna and document its three major phases.
  • The Age of Insight (2012)

• Five separate pulses of serotonin, designed to simulate five shocks to the tail, strengthened the synaptic connection for days and led to the growth of new synaptic connections... that did involve the synthesis of new protein.

• Jacques Monod... published a paper entitled "Genetic Regulatory Mechanisms in the Synthesis of Protein." Using bacteria as a model system, they made the remarkable discovery that genes can be regulated—that is, they can be switched on and off like a water faucet.

• What is learning but a set of sensory signals from the environment, with different forms of learning resulting from different types or patterns of sensory signals?

• Jacob and Monod found that in bacteria, genes are switched on and off by other genes. This led them to distinguish between effector genes and regulatory genes. Effector genes encode effector proteins... which mediate specific cellular functions. Regulatory genes encode proteins called regulatory proteins, which switch the effector genes on or off.

• Jacob and Monod not only outlined a theory of gene regulation, they also discovered the first regulators of gene transcription. These regulators come in two forms—repressors, genes that encode the regulatory proteins that shut genes off, and as later work showed, activators, genes that encode the regulatory proteins that turn genes on.

• In the Jacob-Monod model, signals from a cell's environment activate regulatory proteins that switch on the genes encoding particular proteins. This led [Philip] Goelet and me to wonder whether the crucial step in switching on long-term memory in sensitization might involve similar signals and similar gene regulatory proteins.

• Even though I had long been taught that the genes of the brain are the governors of behavior, the absolute masters of our fate, our work showed that, in the brain as in bacteria, genes are also servants of the environment. ...An environmental stimulus... activates modulatory interneurons that release serotonin. The serotonin acts on the sensory neuron to increase cyclic AMP and to cause protein kinase A and MAP kinase to move to the nucleus and activate CREB. The activation of CREB, in turn, leads to the expression of genes that changes the function and the structure of the cell.

• CREB's opposing regulatory actions provide a threshold for memory storage, presumably to ensure that only important, life-serving experiences are learned. Repeated shocks to the tail are a significant learning experience for an Aplysia, just as, say, practicing the piano or conjugating French verbs are to us: practice makes perfect, repetition is necessary for long-term memory. In principle, however, a highly emotional state... could bypass the normal restraints on long-term memory. In such a situation, enough MAP kinase molecules would be sent into the nucleus rapidly enough to inactivate all of the CREB-2 molecules, thereby making it easy for protein kinase A to activate CREB-1 and put the experience directly into long-term memory.

• Exceptionally good memory exhibited by some people may stem from genetic differences in CREB-2 that limit the activity of this repressor protein in relation to CREB-1.

• The same CREB switch is important for many forms of implicit memory in a variety of other species, from bees to mice to people.

• CPEB is the first self-propogating form of a prion known to serve a physiological function... perpetuation of synaptic facilitation and memory storage.

• The fact that a gene must be switched on to form a long-term memory shows clearly that genes are not simply determinants of behavior but are also responsive to environmental stimulation, such as learning.

• The growth and maintenance of new synaptic terminals makes memory persist. ...The ability to grow new synaptic connections as a result of experience appears to have been conserved throughout evolution. As an example... the cortical maps of the body surface are subject to constant modification in response to changing input from sensory pathways.

• Implicit memory is responsible not only for simple perceptual and motor skills but also, in principle, for the pirouettes of Margot Fonteyn, the trumpeting techniques of Wynton Marsalis, the accurate ground strokes of Andre Agassi, and the leg movements of an adolescent. Implicit memory guides us through well-established routines that are not consciously controlled.

• For all of us, explicit memory makes it possible to leap across space and time and conjure up events and emotional states that have vanished into the past yet somehow continue to live in our minds.

• Recall of memory is a creative process. What the brain stores is... only a core memory. Upon recall, this memory is then elaborated upon and reconstructed, with subtractions, additions, elaborations, and distortions.

• What biological processes enable me to review my own history with such emotional vividness?

• Mountcastle discovered that tactile sensation is made up of several distinct modalities; for example, touch includes... hard pressure on the skin as well as a light brush... He found that each distinct submodality has its own private pathway within the brain and that this segregation is maintained at each relay...

• Cajal revealed the precision of the interconnections between populations of individual nerve cells. Mountcastle, Hubel, and Wiesel revealed the functional significance of those patterns of interconnections. They showed that the connections filter and transform sensory information on the way to and within the cortex, and that the cortex is organized into functional compartments, or modules.

• Each sensory system first analyzes and deconstructs, then restructures the raw, incoming information to its own built-in connections and rules—shades of Immanuel Kant.

• Aspects of visual perception—motion, depth, form, and color—are segregated from one another and conveyed in separate pathways in the brain, where they are brought together and coordinated into a unified perception.

• Segregation occurs in the primary visual area of the cortex, which gives rise to two parallel pathways. ...the "what" pathway, carries information about the form of an object... the "where" pathway, carries information about the movement of the object in space: where the object is located.

• The idea that different aspects of visual perception might be handled in separate areas of the brain was predicted by Freud at the end of the nineteenth century. ...a cortical defect that affected [the] ability to combine aspects of vision into a meaningful pattern. ...defects, which Freud called agnosias (loss of knowledge)...

• What strategy does the brain use to read itself out? That question, which is central to the unitary nature of conscious experience, remains one of the many unresolved mysteries of the new science of mind.

• The firing of individual nerve cells involved in perceptual and motor processing is modified by attention and decision making.

• Birds in which spatial memory is particularly important—those that store food at a large number of sites, for example—have larger hippocampuses than other birds. ...London taxi drivers have a larger hippocampus than others the same age. ...the size of their hippocampus continues to increase with time on the job.

• Long-term potentiation helps stabalize the internal representation of space, and... attention, a defining feature of explicit memory storage, modulates the representation of space.

• O'Keefe... argued that many forms of explicit memory (for example, memory for people and objects) use spatial coordinates... we typically remember people and events in a spatial context.

• Because we do not have a sensory organ dedicated to space, the representation of space is a quintessentially cognitive sensibility: it is the binding problem writ large.

• For some representations of space the brain typically uses egocentric coordinates (centered on the receiver)... For other behaviors... the brain uses allocentric coordinates (centered on the world).

• We did not realize that the hippocampus is concerned with perception of the environment and therefore represents multisensory experience...

• Unlike vision, touch, or smell, which are prewired and based on Kantian a priori knowledge, the spatial map presents us with a new type of representation, one based on a combination of a priori knowledge and learning. The general capability for forming spatial maps is built into the mind, but the particular map is not. Unlike neurons in a sensory system, place cells are not switched on by sensory stimulation. Their collective activity represents the location where the animal thinks it is.

• By merely observing the electrical activity in the brain, Libet could predict what a person would do before the person was actually aware of having decided to do it. This finding caused philosophers of mind to ask: If the choice is determined in the brain before we decide to act, where is free will? ...choice in action, as in perception, may reflect the importance of unconscious inference. Libet proposes that... just before the action is initiated, consciousness is recruited to approve or veto the action.

• Pernkopf was only one of many Austrians who were "rehabilitated" in the postwar period. Their rehabilitation underscores the tendency of Austria to forget, suppress, and deny the events of the Nazi period. ...Anton Pelinka ...has called this phenomenon the "great Austrian taboo." It is precisely this moral vacuum that induced Simon Wiesenthal to establish his documentation center for Nazi war crimes in Austria, not Germany.

• The history of Austrian culture and scholarship in the modern era largely paralleled the history of Austrian Jewry.

• The Viennese Kultusgemeinde... was going bankrupt... European governments typically compensate Jewish agencies... but the Austrian government's compensation was not adequate. ...I owe my existence in the United States to the generosity of the Viennese Kultusgemeinde.

• My hope is that the difference in the three generations' attitudes may signal a lessening of anti-Semitism in Austria.

• I continue to explore the science in which I work almost like a child, with naïve joy, curiosity, and amazement.

• I was astonished to discover that working in the laboratory—doing science in collaboration with interesting and creative people—is dramatically different from taking courses and reading about science.

• The life of a biological scientist in the United States is a life of discussion and debate—it is the Talmudic tradition writ large. ...The egalitarian structure of American science encourages this camaraderie. ...this would not—could not—have taken place in the Austria, the Germany, the France, or perhaps even the England of 1955.

• I have at times felt alone, uncertain, without a well-trodden path to follow. Every time I embarked on a new course, there were well-meaning people... who advised against it. I had to learn early on to be comfortable with insecurity and to trust my own judgement on key issues.

• We now understand that every mental state and every mental disorder is a disorder of brain function. Treatments work by altering the structure and function of the brain.

• ...in various types of organisms, from snails to flies to mice to people. ...learning and memory, as well as synaptic and neuronal plasticity, represent a family of processes that share a common logic and some key components but vary in the details of their molecular mechanisms.

• I would like to develop a reductionist approach to the problem of attention by focusing on how place cells... create an enduring spatial map only when an organism is paying attention to its surroundings.

• The idea that we are unaware of much of out mental life, first developed by Hermann Helmholtz, is central to psychoanalysis. Freud has added the interesting idea that although we are not aware of most instances of mental processing, we can gain conscious access... by paying attention.

• Cori Bargmann... has studied two variants of C. elegans... The only difference between the two is one amino acid in an otherwise shared receptor protein. Transferring the receptor from a social worm to a solitary worm makes the solitary worm social.

• Giacomo Rizzolatti... calls these "mirror neurons" and suggests that they provide the first insight into imitation, identification, empathy, and possibly the ability to mime vocalization—the mental processes intrinsic to human interaction. Vilayanur Ramachandran has found evidence of comparable neurons in the premotor cortex of people. ...one can see a whole new area of biology opening up... that can give us a sense of what makes us social, communicating beings. An ambitious undertaking of this sort might... teach us something about the factors that give rise to tribalism, which is so often associated with fear, hatred, and intolerance of outsiders.

• The overarching ideas that have influenced my work and fueled my interest in conscious and unconscious memory derive from a perspective on mind that psychiatry and psychoanalysis opened up for me.

• It is much more meaningful and enjoyable to read the scientific literature about experiments you are involved in yourself than to read about science in the abstract.

• Once I have gotten into a problem, I find it extremely helpful to get a complete perspective, to learn what earlier scientists thought about it. I want to see not only what lines of thought proved to be productive, but also where and why certain other directions proved to be unproductive.

• I was very much influenced by the psychology of Freud and by early workers in the field of learning and memory—James, Thorndike, Pavlov, Skinner, and Ulric Neisser. Their thinking, and even their errors, provided a wonderfully rich cultural background for my later work.

• Nothing is more stimulating for self-education than working in a new area.

• Having been trained in history and the humanities, where one learns early on how depressing life can be, I am delighted to have ultimately switched to biology, where a delusional optimism still abounds.

• I entered Harvard to become a historian and left to become a psychoanalyst, only to abandon both... to follow my intuition that the road to a real understanding of mind must pass through the cellular pathways of the brain.

The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present

• The intellectual life of turn-of-the-century Vienna is in my blood: my heart beats in three-quarter time.

• The Age of Insight is a product of my subsequent fascination with the intellectual history of Vienna from 1890 to 1918, as well as my interest in Austrian modernist art, psychoanalysis, art history, and the brain science that is my life's work. In this book I examine the ongoing dialogue between art and science that had its origins in fin-de-siècle Vienna...

• This dialogue between the ongoing research in brain science and art continue to this day. ...Such dialogues could help us explore the mechanisms in the brain that make perception and creativity possible, whether in art, the sciences, the humanities, or everyday life. In a larger sense, this dialogue could help make science part of our everyday experience.

• The portraits of the Viennese modernists, with their conscious and dramatic attempts to depict their subject's inner feelings, represent an ideal example of how psychological and biological insights can enrich our relationship with art.

• One of the characteristic features of Viennese life at this time was the continual, easy interaction of artists, writers, and thinkers with scientists.

• The function of the modern artist was not to convey beauty, but to convey new truths.

• The Vienna School of Art History, influenced in part by Sigmund Freud's psychological work, began to develop a science-based psychology of art that was initially focused on the beholder. Today, the new science of mind has... again focused on the beholder.

• I outline in simple terms... our current understanding of the cognitive psychological and neurobiological basis of perception, memory, emotion, empathy, and creativity. ...the principles of the viewer's response to art are applicable to all periods of painting.

• A brain scan may reveal the neural signs of depression, but a Beethoven symphony reveals what that depression feels like. Both perspectives are necessary if we are to fully grasp the nature of mind, yet they are rarely brought together.

• Much as Leonardo da Vinci and other Renaissance artists used the revelations of human anatomy to help them depict the body more accurately and compellingly, so, too, many contemporary artists may create new forms of representation in response to revelations about how the brain works.

• Reductionism can expand our vision and give us new insights into the nature and creation of art.

• Science may explain aspects of art but it will not replace the inspiration that art evokes...

• Like other modern artists faced with the advent of the photography, Klimt sought newer truths that could not be captured by the camera. He... turned the artists view inward—away from the three-dimensional outside world and toward the multidimensional inner self and the unconscious mind.

• As the art historian Emily Braun has documented, Klimt read Darwin and became fascinated with the structure of the cell... Thus, the small iconographic images on Adelle's dress are not simply decorative... they are symbols of male and female cells: rectangular sperm and ovoid eggs. ...designed to match the sitter's seductive face and her full-blown reproductive capacities.

• The remarkable insight that characterized Klimt's later work was contemporaneous with Freud's psychological studies and presaged the inward turn that would pervade all fields of inquiry in Vienna in 1900. This period... was characterized by the attempt to make a sharp break with the past and to explore new forms of expression in art, architecture, psychology, literature, and music. It spawned an ongoing pursuit to link these disciplines.

• Viennese life at the turn of the century provided opportunities in salons and coffeehouses for scientists, writers, and artists to come together in an atmosphere that was at once inspiring, optimistic, and politically engaged. ...science was no longer the narrow and restrictive province of scientists but had become an integral part of Viennese culture. ...a paradigm for how an open dialogue can be achieved.

• Modernism began in the mid-nineteenth century as a response not only to the restrictions and hypocrisies of everyday life, but also as a reaction to the Enlightenment's emphasis on the rationality of human behavior. ...The founders of the Royal Society thought of God as a mathematician who had designed the universe according to logical and mathematical principles. The role of the scientist—the natural philosopher was to... decipher the codebook that God had used in creating the cosmos.

• The Modernist reaction to the Enlightenment came in the aftermath of the Industrial Revolution, whose brutalizing effects revealed that modern life had not become... mathematically perfect...

• As astronomy and physics inspired the Enlightenment, so biology inspired Modernism. ...This new view led to a reexamination in art of the biological nature of human existence, as evident in Édouard Manet's Déjeuner sur l’Herbe... Manet's painting... reveals a theme... the complex relationship between the sexes and between fantasy and reality. ...also startlingly modern because of its style. Several decades before Cézanne began to collapse three dimension into two, Manet here had already flattened the viewer's sense of perspective...

• In Vienna, Modernism had three main characteristics. The first was the new view of the human mind as being largely irrational by nature. ...they questioned what constitutes reality, what lies below the surface appearances of people, objects, and events. ...They discovered that ...people harbor not only unconscious erotic feelings, but also unconscious aggressive impulses that are directed against themselves as well as against others. Freud later called these dark impulses the death instinct.

• The Copernican revolution... revealed that the earth is not the center of the universe... The second, the Darwinian revolution... revealed that we are not created divinely or uniquely but instead evolved from simpler animals by a process of natural selection. The third great revolution, the Freudian revolution of Vienna 1900, revealed that we do not consciously control our own actions but are instead driven by unconscious motives. This... later led to the idea that human creativity... stems from conscious access to underlying, unconscious forces.

• The realization that our mental functioning is largely irrational was arrived at by several thinkers at the same time, including Friedrich Nietzsche... Freud, who was much influenced by both Darwin and Nietzsche... was its most profound and articulate exponent. ...Schnitzler, Klimt, Kokoschka, and Schiele also discovered and explored new aspects of our unconscious mental life. They understood women better than Freud... and they saw more clearly than Freud the importance of an infant's bonding to its mother. They even realized the significance of the aggressive instinct earlier than Freud did. ...Plato discussed unconscious knowledge ...pointing out that much of our knowledge is inherent in the psyche in latent form. ...Hermann von Helmholtz... advanced the idea that the unconscious plays a critical role in human visual perception.

• The fundamental mechanisms that Eric Kandel has revealed [in Aplysia] are also applicable to humans... Even if the road towards an understanding of complex memory functions still is long, the results... have provided a fundamental building stone. It is now possible to continue and, for instance, study how complex memory images are stored in the nervous system, and how it is possible to recreate the memory of earlier events...
  • 2000 Nobel Prize Committee

• In the early 1960s, Kandel made the bold decision to conduct research on an unlikely animal, the large sea snail Aplysia californica. Kandel found this invertebrate attractive for neuroscience research because it has fewer and larger neurons than more traditional laboratory animals. This simple neural system would subsequently serve as an invaluable model for understanding the cellular basis of learning.
  • Kelly Lambert, Craig H. Kinsley, Clinical Neuroscience (2004)

• Throughout his career, Kandel has also been a student of the history of neuroscience. ...Kandel's fascination with the "giants" of neuroscience, as he calls them, became ironic when Kandel himself became a part of the history of neuroscience...
  • Kelly Lambert, Craig H. Kinsley, Clinical Neuroscience (2004)

• Eric R. Kandel, M.D. @Columbia University Medical Center, Department of Neuroscience