In Search of Memory
Author: Eric R. Kandel

Background

This semi-autobiographical work by the Nobel Prize winning preeminent neuroscientist goes beyond the narrow confines of memory to explore the broader concept of what the author calls ‘the new science of mind‘. In a most exhaustive approach which provides ‘a new perspective of ourselves in the context of biological evolution‘, the author addresses diverse topics ranging from consciousness to spirituality. The book is also a detailed exploration of the cutting edge developments in molecular biology and cognitive neuroscience, and the author complements this with a thrilling narration of the history of the most important breakthroughs in neuroscience. At the heart of the book however is the author’s inspiring story of his groundbreaking inquiry into ‘how learning and memory are achieved in the cells of the brain’, and how these feed into ‘our very identity‘ and ‘make us who we are’. In doing this, he reviews such curious phenomena as exceptional memories, flashbulb memories, and benign senescent forgetfulness, and he draws out the implications of his research on such clinical disorders as anxiety, depression, and schizophrenia (pages xiii, xv and 115-116).

Synopsis

A most riveting feature of the book is its portrayal of the author’s remarkable life which highlighted the experiences that forced his family to migrate to the United States, and outlines how he rose to the top echelon of American neuroscience. He narrated the sad and degrading experience his family suffered under Nazi occupation in Austria, events which he said ‘are the most powerful memories of my early life’. He particularly attributed his family’s migration to the enthusiastic reception Hitler received from ‘a substantial majority of the population’ in Austria, a country that he nevertheless credited for furnishing him with ‘a solid education‘. The author described the sense of liberation he and other migrants experienced on arriving in America, pointing out how this ‘released boundless energy and inspired us to think in new ways‘. The author recounted the contributions of the mentors who grounded him in neuroscience, and prominent in this regard is Harry Grundfest, the neurologist who taught him that ‘to understand mind, we needed to look at the brain one cell at a time‘; this was a lesson which the author asserted was fundamental to his research. He also cited Dominic Purpura and Stanley Crain for teaching him the rudiments of scientific inquiry, and Felix Strumwasser for sharpening his thinking about how to carry out experiments (pages 5, 27-33, 55, 59, 106 and 141).

The book narrates a gripping and comprehensive history of neuroscience which highlighted countless remarkable pivotal breakthroughs, prominent among which was how Santiago Ramón y Cajal revolutionised the understanding of neurones. Portraying the Spaniard as ‘arguably the most important brain scientist who ever lived’, the author detailed how Cajal ‘laid the foundation of the modern study of the nervous system’, and  how he formulated the four principles of the neurone doctrine for which he was jointly conferred the Nobel Prize with his scientific adversary, the Italian Camillo Golgi. The book also described the similarly notable breakthroughs of Charles Sherrington who established the principles of reflexes and linked these to behaviour, and of Edgar Adrian who ‘developed methods of recording and amplifying the action potentials propagated along the axons’. The list of distinguished neuroscience innovators in the book is however almost inexhaustible, from Paul Broca, Carl Wernicke, Gustav Fritsch, Eduard Hitzig and Alan Hodgkin, to Andrew Huxley, Henry Dale, Otto Loewi, John Eccles, Bernard Katz and Stephen Kuffler (pages 61-78 and 83-102 and 120-123).

In chronicling the equally enlightening and inspiring account of the scientific understanding of the nature of memory, the book first reviewed the antiquated paradigms of memory formation; prominent amongst these was the idea advocated by psychologist Karl Lashley that there were no specialised brain areas for memory. The author then reviewed the enlightening studies which helped to define the biological substrates of memory, key amongst which was the research carried out by psychologist Brenda Milner on Patient HM; this was a seminal milestone which demonstrated that short and long term memories are stored in different brain areas. Another pioneer of memory research who helped to shape the author’s understanding of the subject was Louis Flexner, the biochemist who demonstrated that ‘drugs that inhibit the synthesis of proteins in the brain disrupt long-term memory if given during and shortly after learning, but they do not disrupt short-term memory‘. This insight was fundamental to the author’s work because it showed that ‘long-term memory storage requires the synthesis of new proteins’. Other influential memory researchers the book acknowledged were Georg Muller and Alfons Pulzecker who demonstrated that ‘memory storage is dynamic and sensitive to disruption’, and Hermann Ebbinghaus who established a link between repetition and strength of memory, and who delineated the phases of forgetting (pages 116-133 and 209-212).

The most fascinating account of the book is its illuminating reconstruction of the thinking and research that went into the author’s research into memory formation. Attributing his success to an uncanny ability to formulate simple and specific questions, the author demonstrated how this skill enabled him and Alden Spencer, his equally creative colleague, to obtain ‘the first intracellular signals ever recorded from the the pyramidal cells of the hippocampus, ‘the region of the brain that stores our fondest memories’. The author also attributed his scientific accomplishments to the ability to deploy the reductionist strategy of studying ‘the simplest instance of memory storage…in an animal with the simplest possible nervous system‘. Indeed he applied this method to good effect when he made the inspired decision to study the giant marine snail Aplysia; it was by studying habituation, sensitisation, and classical conditioning in this ‘large, proud, attractive, and obviously highly intelligent beast’ that the author discovered that learning occurs at plastic synaptic connections, and that these connections could be strengthened or weakened (pages 136-140, 143-147 and 158-171). 

The book’s elucidation of the physiology and genetics underlying learning and memory formation remarkably simplified what is clearly an intricately complex process. One of the elaborate pathways the author described is the one in which serotonin releases the second messenger molecule cyclic AMP; in reviewing this, he explains how cAMP then activates the phosphorylation enzyme protein kinase A, and how this then enhances the release of glutamate – ‘the major excitatory transmitter‘ responsible for learning. Even more fascinating is the author’s review of the genetic underpinnings of learning and memory which showed how critical regulatory genes and proteins such as CREB and CPEB act through a prion-like process to transform short-term into long-term memory. As a tribute to the important role of genetics in memory consolidation, the book also covered the major landmarks in the history of genetics with reference to pioneers of the field such as Gregor Mendel, Thomas Hunt Morgan, Oswald Avery, James Watson, Francis Crick, Sydney Brenner, Marshal Nirenberg, Har Gobind Khorana, Walter Gilbert, Frederick Sanger, Paul Berg, Herbert Boyer, Stanley Cohen, Francois Jacob and Jacques Monod (pages 222-234, 241-275 and 241-258).

Opinion

This is an exhilarating and revealing scientific adventures of a remarkable man. Conveying an overall inspiring ambience, the book relates the author’s development as a person and a neuroscientist. The book is enhanced by the author’s unique talent of disentangling even the most complex concepts he discussed, and by his approach of blending the historical and the academic dimensions of the science of memory. The phenomenal scope of this book is reflected in the way its academic themes transcend the spectrum of neuroscience, and its autobiographical narrative highlights the critical steps that enable scientific achievements.

Overall assessment

This important book links research to clinical practice, and it emphasises the values of collaboration and curiosity. By dispensing key lessons such as keeping research questions focused and using the simplest biological specimens, the book serves as an invaluable aid for researchers. The book is also enlightening in its exploration of the whole scientific enterprise, emphasising the importance of defining and refining scientific questions, and of choosing the appropriate biological agents to answer research questions. With sprinklings of gems of clinical and research wisdom acquired through a productive life, the book imparts invaluable lessons for healthcare, and I recommend it to all doctors.

Book details

Publisher, Place, Year: Norton Paperback, New York, 2007
Number of chapters: 30
Number of pages: 510
ISBN: 978-0-393-32937-7
Star rating: 5
Price: £12.89