This review will appear in a forthcoming issue of The FASEB Journal. Reprinted with permission of the publisher.
À la Recherche du Temps Kandel
by Gerald Weissmann, MD
Perhaps the European twentieth century was the only time when a man could be envied for having no memory. |
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Eric Kandel has written a gripping memoir of the European twentieth century that any author might envy. He has also written an American account of discoveries in the neurosciences that any scientist might envy. Both genres are skillfully entwined in his civilized, generous and stylish book In Search of Memory. Its Proustian title suggests that we will be treated to a memoir raised to the level of art by insight; its authorship by a Nobel laureate (in Physiology or Medicine, 2000) assures us that we'll learn why the study of memory is at the leading edge of our new biology. For that twin achievement, In Search of Memory belongs on that small shelf of scientific autobiographies that rank as literature, wedged between Walter B. Cannon's The Way of an Investigator and François Jacob's The Statue Within, works that relate the life of science to the Age of Anxiety.
The biographical theme in this book is more than the common family romance. We follow Kandel as a Jewish child whose family survived slights and persecution in pre- and post-Nazi Vienna, one who was exiled from language and culture in a parochial corner of New York. We follow an efflorescent career in science that took him from Brooklyn to Harvard College, the NYU School of Medicine, the NIH, back to Harvard (as a psychiatry resident), to discover Aplysia in Paris and finally on to Columbia, where he is now a University Professor. His own work in the lab is perhaps the most contextual in neuroscience, not only because of his experiences in psychiatry, but also his broad interests in history, art, and literature. Along the way Eric Kandel learned not only how science was done, but also when, and by whom and why. On his prize-laden path to Stockholm, he wed an accomplished wife, became a proud paterfamilias, and collected a covey of serious mentors and colleagues. Each gets a gracious bow in the narrative: Denise Kandel, Harry Grundfest, Dominick Purpura, Alden Spencer, Ladislav Tauc, James Schwartz, Stephen Kuffler, Richard Axel, etc., etc.
The city of Vienna plays the role of Proust's madeleine. Indeed, two Viennese critical for Kandel's career bob up and down in the story: Hitler and Freud. Freud is in residence on page 12, Hitler enters town on Page 18. Kandel says of Freud, who studied crayfish before disembarking the Cythera of science for the couch: "Perhaps if a scientific career could have ensured a living wage then, as it does today, Freud would be known as a neuroanatomist and a co-founder of the neuron doctrine, instead of as the father of psychoanalysis." Or, as Kandel implies, had he not been Jewish. The love-hate relationship twixt Kandel and his native city is a major theme in the book: Kandel notes that "the fierce attachment of so many Jews to a city that throughout the years demonstrated its deep-rooted hate for them remains the greatest grim irony of all." At various stages in his career, he reverts to Vienna and is in turn honored, ignored, feted, and enlisted. In 1980, he and Stephen Kuffler are invited to Vienna.
We were both invited to Vienna to be inducted as honorary members of the Austrian Physiological Society. We were introduced to the medical faculty of the University of Vienna by Wilhelm Auerwald, a pretentious academic who had accomplished little scientifically and who acted as if nothing out of the ordinary had caused these two sons of Vienna to flee the country. The professor blithely remarked that Kuffler had attended medical school in Vienna and that I had lived in Severingasse, literally around the corner from the university. His silence regarding our actual experiences in Vienna spoke volumes. Neither Steve nor I responded to his comments. |
With his analytic insight, Kandel will appreciate that this anecdote is an illustration of Harry Harlow's experiments (discussed on page 373) which showed that primates deprived of their warm, supportive mothers will cling for love to cloth-covered wooden dummies or even attempt to cuddle hard, metal surrogates, the "wire mommies."
Kandel recalls, "I entered Harvard to become a historian and left to become a psychoanalyst, only to abandon both of those careers to follow my intuition that the road to a real understanding of mind must pass through the cellular pathways of the brain." On the occasion of his Nobel prize in Stockholm it was remarked that when Kandel was young he wanted to be Sigmund Freud, but when Sigmund Freud was young and impaling crayfish, he would have wanted to be Eric Kandel. (Freud was himself nominated repeatedly between 1915 and 1938)
At the end of Kandel's book, on p 407, there appears a picture of Eduard Pernkopf, Nazi dean of the medical school of Vienna in the spring of 1938. Greeting the brown-shirted host in his own brown-shirted uniform, the dean informed his faculty that
What was the dream of our youth, what we dared not hope for, has become reality: we are one people, one Reich, one leader [Ein Volk, Ein Reich, Ein Führer], Adolph Hitler; he strides before us and we follow him gladly." The dean warns the faculty that "freedom, my comrades, in the liberal sense ... cannot and will not be permitted for science. Here we must have direction, planning, and goals ... for many it's been science for the sake of doing science; indeed for many it was the only sense of their work. Such a conception of our intellectual life strikes me actually not as a selfless endeavor, but rather the expression of a self-seeking narcissism of intellectual underachievers who wish to hide their vanity in the cloak of altruism. |
The other theme in Kandel's book is the perfect retort to Pernkopf: science done for the sake of doing science. Kandel gives a gripping account of the rise of cognitive neuroscience and of his own contributions to the field. He provides a pocket history that ranges from foundations laid by Helmholtz, Cajal, Gall, and Sherrington; to equations introduced by Huxley and Hodgkin, to circuits explored by Kuffler, to spatial organization laid out by Mountcastle, Hubel and Wiesel and, finally, to the analysis of memory and desire by means of biochemical genetics: Carlson, Greengard, and Kandel. The story of how Kandel decided that the giant sea snail Aplysia would become a prime model for the study of the varieties of memory (long-term vs short- term; explicit vs implicit, etc.) is a story of how scientific taste is molded by the larger culture.
The anatomy of the neural circuit is a simple example of Kantian a priori knowledge, while changes in the strength of particular connections in the neural circuit reflect the influence of experience. Moreover, consistent with Locke's notion that practice makes perfect, the persistence of such changes underlies memory. |
Kandel understood at the beginning of his quest that the nerve cell was not "simply a marvelous piece of biology." It was also the key to understanding how the brain works. By January of 1962, when he applied for a fellowship to learn about Aplysia from Ladislav Tauc at the Institut Marey in Paris, he had already defined his goal: "to trap a conditioned response in the smallest possible neural population." Easily impaled and studied, the Aplysia nervous system became the substrate for Kandel's onslaught on learning and memory. Alas, the Institut itself—named for the famous scientist/photographer—exists nowadays only in memory, razed to make room for an enlarged Roland Garros stadium. Kandel's lab has also extended its scope from snails to mammalian models: differentiating signals of short-term from long term memory, defining memory activator and suppressor genes (CREB-1, CREB2), and most recently, working out that a protein named CPEB is "the first self-propagating form of a prion known to serve a physiological function ... perpetuation of synaptic facilitation and memory storage."
Kandel's prose is limpid, his story-line clear and compelling; indeed, most of the book is as accessible to the layman as to the scientist. It's hard to put down this Bildungsroman, which reaches from an account of his childhood sexual awakenings with a Mitzi in Vienna "She sat down at the edge of my bed and touched my face ..." to his latest attempt at squaring psychoanalysis with molecular genetics "We now understand that every mental state is a brain state and every mental disorder is a disorder of brain function. Treatments work by altering the structure and function of the brain." Nowhere is his exposition more forthright than when this heir of Freud sums up the goals to which his career has pointed: "I like long-term commitments, not brief romances ... I would like to understand how the unconscious processing of sensory information occurs and how conscious attention guides mechanisms in the brain that stabilize memory." Eric Kandel's masterful book suggests that he's shown his successors the way to understand "unconscious processing," how the sensors of our brain scan the chips of memory and desire. It's also an answer to the Pernkopfs of today, who will never understand that the best science is done for the sake of doing science.