In Search of Memory: The Emergence of a New Science of Mind
By Eric R. Kandel
Few can interlace their autobiography with the evolution of a scientific paradigm. Even fewer can weave such a story seamlessly. Eric Kandel is one of these. His career, from his training in Harry Grundfest's laboratory at Columbia University in New York more than fifty years ago to a remarkably productive present, also at Columbia, epitomizes his ardent reductionist approach to the neural sciences. Its formal pinnacle was the Nobel Prize in Physiology or Medicine, which Kandel shared in 2000 with Arvid Carlsson and Paul Greengard for their discoveries concerning signal transduction in the nervous system.
Kandel's intellectual journey in neuroscience can be traced back to his first encounter with Grundfest. The enthusiastic medical student, with a strong background in history and literature, proposes unveiling the brain substrates of Freud's three psychic structures, the ego, superego and id, in six months. Grundfest, the seasoned professor of neurology, suggests a different agenda, no less grandiose: to understand the mind, he replies, we need to look at the brain one cell at a time. The narrative of the brain sciences in the past century is made up of attempts to negotiate between these two extremes. In his admirable personal version of this narrative, Kandel is still a grundfestian, but appreciates that the bottom-up approach still has a long way to go.
Nowhere, perhaps, is this conflict between reductionism and global approaches to the brain more evident than in memory research. Memory is a term applied nowadays to a wide gamut of functions, ranging from experience-dependent modification of reflexes in brainless organisms to the recollection of personal events in their investigators. Even if such an inclusive definition is accepted, the distinction should still be made between memory as a process and as an item with mental content.
The process is assumed to be subserved by the plasticity of synapses, the functional contacts between nerve cells. One could further assume that the basic building blocks of the plasticity machinery were conserved in evolution. If this is the case, why not approach memory by studying its simplest forms in the simplest of organisms? This philosophy has guided Kandel and given the timid sea-slug Aplysia a prominent position in textbooks of neuroscience. The approach, anchored in the achievements of molecular biology, has proved highly productive in identifying plasticity mechanisms that subserve memory. What it doesn't address satisfactorily is the content and meaning of memory items. This requires an understanding of how brains encode specific pieces of mental information. Many would argue that this calls for the spatiotemporal codes of neuronal populations to be deciphered. Furthermore, given the immense difference in complexity and the likelihood of emergent properties, it is unlikely that probing the ganglia of Aplysia can tell us how our brain recalls our first love or our father's face.
Nevertheless, the reductionist approach to behavioural plasticity, of which Kandel's work is the prime example, is a success story that has given us models of molecular and cellular plasticity that propose how experience affects nerve cells. It is now for those who follow Kandel to link the molecular and cellular level with the systems level of analysis. This integration is the major challenge facing the science of memory, and might require, in addition to new methodologies, a change of zeitgeist or an amalgamation of approaches.
Kandel's book is enthusiastically recommended as a captivating account of the career of a prominent leader in contemporary neuroscience. The author is not only an authoritative scholar but also a marvellous popularizer and narrator, who brings to the story an attractive mix of facts, personal touches and wisdom, seasoned with reflective humour. But In Search of Memory is not just about science: it is also about history and identity. Kandel is a devoted scientist, humanist, family man and proud Jew. He follows, by his own definition, the “Talmudic tradition writ large. But rather than annotate a religious text, we annotate texts written by evolutionary processes working over hundreds of millions of years.”
Kandel was just a child when he emigrated from Austria to the United States, but the Holocaust and the trauma of European Jewry are deeply embedded in his memory. His contempt for racism is clear. In the background hovers the terrible awareness that many of his generation perished, unknown, in concentration camps before they had a chance to explore and contribute to the world. When the Austrian president contacts Kandel and expresses his desire to honour the new Nobel laureate of Viennese origin, Kandel's reaction is to organize a symposium in Vienna to acknowledge Austria's central role in the Nazi atrocities and evaluate the significance for scholarship of the disappearance of the Jewish community in Vienna. Kandel's accounts of incidents during this visit to Vienna should be read carefully by those who ignore lingering undercurrents of anti-Semitism.
The Greek poet Constantine Cavafy, in his poem Ithaka, which recounts the return of Odysseus to his homeland, advises his hero not to hasten:
As you set out for Ithaka, Hope the voyage is long, Full of adventure, full of discovery... Better if it lasts for years... Ithaka gave you the marvellous journey Without her you would not have sailed away.
The reward, according to Cavafy, is the journey, rather than the goal. Both the young Kandel who met Grundfest and the mature, imaginative investigator of the Aplysia epoch seem to have valued the goal at least as much as the journey. But reading these memoirs, one senses that, over the years, Kandel's appreciation of the journey itself has increased. Is Ithaka attainable for those who study memory? If the goal is to chart and analyse plasticity in neuronal terrain in fine detail, then the kandelian Aplysia paradigm is a tremendous leap forwards. If it is to understand how recollecting humans think, feel and plan, we might need more Kandels.