Tell me where dwell the thoughts, forgotten till thou call them forth?
Tell me where dwell the joys of old, and where the ancient loves,
And when will they renew again, and the night of oblivion past,
That I might traverse times and spaces far remote, and bring
Comforts into a present sorrow and a night of pain?
Where goest thou, O thought? To what remote land is thy flight?
If thou returnest to the present moment of affliction,
Wilt thou bring comforts on thy wings, and dews and honey and balm,
Or poison from the desert wilds, from the eyes of the envier?
Thus did William Blake ponder how distant memories can make us laugh or cry. Memory is the underlying theme of Eric Kandel’s new book. A pioneer of investigations into the biological nature of memory, Kandel was awarded the Nobel Prize for Physiology or Medicine in 2000 for his contributions to neurobiology. Interwoven with descriptions of Kandel’s professional work are many of his personal memories.
“In Search of Memory” is therefore part memoir and part textbook; it begins with some of Kandel’s earliest childhood memories. The opening passages reminded me of my favourite poem, and brought it flooding back to my mind. Like Blake, Kandel describes memory as “a form of mental time travel [which] frees us from the constraints of time and space.” It is the brain’s amazing ability to store a seemingly infinite number of facts, figures and experiences which enables Kandel to travel back in time and across space to retrieve the autobiographical material with which he furnishes this volume.
Kandel fondly recalls his early years in Vienna: family gatherings on Jewish holidays, his first sexual experiences with a seductive housekeeper, and his ninth birthday. These memories are full of both the comforts and the poison of which Blake speaks. The pleasure with which Kandel recollects these aspects of his childhood stand in stark contrast to the recollection of the anti-Semitism prevalent in Austria at that time and the fear he felt when Hitler marched into Vienna.
The idyllic memory Kandel has of playing with his shiny blue remote-controlled car, a present given to him by his parents for his ninth birthday, is suddenly interrupted by another, terrifying memory – a loud banging on the door of the apartment, which signals the appearance of Nazi policemen, who order Kandel and his family to pack their things and leave. The situation is exaserbated by the disappearance of Kandel’s father, who, it later transpires, was taken by the Nazis to an army barracks with hundreds of other Jewish men.
“How did terror sear the banging on the door of our apartment into the molecular and cellular fabric of my brain with such permanence that I can relive the experience in vivid visual and emotional detail more than half a century later?” he asks. The personal and the professional are for Kandel intimately connected: “My interest in the nature of memory,” he writes, “was rooted in my childhood experiences in Vienna”; the last year he spent in Vienna would, in fact, be a defining one for Kandel.
Kandel recreates the climate in Austria in the months leading up to Kristallnacht, the nationwide pogrom which took place in Austria and Germany on November 9th, 1938, and which coincided with his ninth birthday and his family’s encounter with the Nazi regime; his personal memories of that time are reinforced by the academic study of European history he would undertake later in his life.
Soon after his ninth birthday, Kandel and his older brother Ludwig are shipped off to stay with an aunt in Brooklyn, New York, to be followed by their parents six months later.Kandel would soon be enrolled in a yeshivah in Flatbush, and then a local high school. He would then read modern European History and Literature at Harvard, and an interest in psychiatry would lead him to study medicine and enter into neurobiological research.
Something that emerges from the book is the link between history and memory. History can be regarded as a form of collective memory. Historical events that are not recorded accurately may quickly be forgotten. Genocide involves not just the extermination of a race, but also erasing the memory of that race from history; and, of course, “never forget” is a mantra for survivors of the Nazi Holocaust.
Kandel’s career spans a very exciting time in modern science. Within a year of his entry into medical school, James Watson and Francis Crick discovered the molecular structure of DNA, revolutionizing every aspect of biology in the process. This discovery paved the way for investigating the molecular machinery of the mind, something which Kandel would go on to pioneer. He is therefore a perfect guide for a whistle-stop tour through the history of modern neuroscience, from the work of Santiago Ramon y Cajal, via classical experiments in the 1950s which provided leaps in our understanding of brain function, to the molecular mechanisms such as long-term potentiation (LTP) which underly memory formation.
Much of the work Kandel describes was crucial for his own discoveries. For example, Schwann and Schleiden had by the mid-19th Century established that the cell was the basic functional unit of which plant and animal tissues were composed. By the end of the century it was accepted that every tissue in the human body was also composed of cells – every tissue except the nervous system, which was believed to be composed of a large continuous tissue, or ‘reticulum’.
The subsequent development of increasingly powerful microscopes and the staining technique of Camillo Golgi eventually enabled neoroanatomists to resolve the 40 nanometre-wide synapse at the junction of neurons. Cajal, an outstanding Spanish neuroanatomist, would then suggest that Schwann and Schleiden’s cell theory also applied to nervous tissue; thus the neuron doctrine was born. <
Around half a century later, the work of John Eccles, Bernard Katz and Stephen Kuffler on peripheral synapses would determine that synaptic transmission is chemical and not electrical in nature. Alan Hodgkin and Andrew Huxley used microelectrodes to perform intracellular recordings in the giant squid axon, and determined the movements of ions that generate the action potential.
Memory is a complex cognitive process that is still very much a mystery to neuroscientists. In the early twentieth century, Karl Lashley tried to determine the locus of memory in the brains of rats. He placed rats in a maze; when they had memorized the route to escape from it, he lesioned their brains in an effort to erase the trace, or ‘engram’ of the memory. Lashley found that no matter where he made a lesion, the memory trace could not be erased, and concluded that there is no single location in the brain where memories are formed and stored. We know that there are different kinds of memories, and several areas in the brain, such as the hippocampus, are involved in the process.
Donald Hebb first suggested in 1949 that synaptic plasticity was crucial for memory formation; he further posultated that neurons were organized into ‘cell assemblies’, with the trace of a memory being distributed over the entire neuronal circuit rather than being localized at a single synapse.
According to the theory of LTP, the current theory of how memories are formed, experience affects the strength of synaptic connections. A lot of Kandel’s professional career has been spent looking at how sensitization, habituation and classical and operant conditioning modify synapses in ganglia isolated from the sea slug Aplysia californica. Kandel’s research during the 1970s led to the discovery that the second messenger molecule cyclic adensine monophosphate (cAMP) and the enzyme cAMP-dependent protein kinase (PKA) are both required for experience-dependent synapse modidification in Aplysia.
In 1983 Kandel helped form the Howard Hughes Medical Institute at Columbia University, where he has since continued to elucidate the molecular mechanisms of memory. Work in his lab is focused on the unconscious (implicit) recall of motor skills in Aplysia; genetically engineered mice are also being used to investigate conscious (explicit) memory storage.
“In Search of Memory” is an elegantly written book by an individual who has collosal status in neuroscience. Kandel’s memories evoke strong emotions in the reader, and his enthusiasm for history and passion for science jump out from every page. Students of neuroscience will find the book very beneficial, and academics already familiar with the science will still enjoy reading it.
In this film, Kandel is interviewed by John Spitzer of the University of California, San Diego: