Peering into the Black Box of the Mind: The Ingenuity of Eric R. Kandel

Kayla Huber
Department of Biology
Lake Forest College
Lake Forest, IL 60045
In 1939, a nine-year-old boy left Vienna, Austria in order to escape persecution from the Nazi regime, a political party that believed his Jewish heritage placed him into an inferior racial category. Sixty-one years later, he stood before King Carl XVI Gustaf and received one of the highest intellectual honors in the world—the Nobel Prize in Physiology or Medicine. In Search of Memory: The Emergence of a New Science of Mind is equal parts autobiography and a scientific almanac, detailing Eric R. Kandel’s quest for how the brain produces memories. This bold scientific endeavor demonstrated that research is not lifeless, but nurtured by collaboration and envy, by articulate hypotheses and shots in the dark, and by childhood memories and dreams of the future.
Eric Kandel’s desire to elucidate the cellular mechanisms of short and long term memory originated from two unlikely events: driving a toy car and dinner with his girlfriend’s parents. A nine-year-old Kandel was playing with his beloved remote-controlled model car when he heard loud banging upon the apartment door. Two Nazi policemen entered, demanding that his family relocate to a stranger’s home. The events that followed—awkwardly imposing themselves upon a wealthy Jewish family, returning to a desolate apartment, and reuniting with his father after he had been held in an army barrack—had been imprinted in Kandel’s memory. This eventually led him to wonder, “How did terror sear the banging 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?” (Kandel, 2006, pg. 6).
As a junior studying modern European history and literature at Harvard College, Kandel fell in love with Anna Kris. Her parents, Ernst and Marianna Kris, both esteemed psychoanalysts from Freud’s cycle, cultivated his interest in the growing field of psychoanalysis. The human brain suddenly became a battlefield of unconscious desires and motivations, rallying to dictate behavior. Kandel had a particular affinity for the three main psychic structures—the ego, the id, and the superego. However, he recalled Kris Ernst’s claim that, “neither trained introspection nor creative insights would lead to the systematic accretion of knowledge needed for the foundation of a science of mind. That sort of foundation requires more than insight, it requires experimentation” (Kandel, 2006, pg. 40). Kandel, initially seeking a biological explanation for Freud’s structural theory, gravitated toward experimentation and empirical evidence at a time when the infantile field of neuroscience was largely theoretical.
In the mid-twentieth century, rigorous study of the brain was severely limited by a lack of methodology and advanced equipment. Kandel became disheartened when his first laboratory advisor at Columbia University, Harry Grundfest, suggested that a biological understanding of Freud’s postulations “was far beyond the grasp of contemporary brain science. Rather…to understand mind we needed to look at the brain one cell at a time” (Kandel, 2006, pg. 55). While this suggestion shocked him initially, Kandel would later become one of the strongest proponents of this reductionist approach. Acknowledging that evolution is a “tinkerer, not an engineer” (Jacob, 1977), many biological processes are conserved across diverse species. In addition, it is much easier to study aspects such as learning and memory in organisms with smaller and simpler nervous systems. It is this logic that lead Kandel to utilize the giant marine snail Aplysia in his studies of memory storage.
While the use of appropriate model organisms is common practice in science today, it was a radical concept in early neuroscience. A majority of researchers believed that the nervous system of invertebrates had no relevance to the workings of the mammalian brain. Despite the dissenting remarks he received from colleagues, Kandel decided to uproot himself and his wife, Denise, in order to conduct research with Ladislav Tauc in Paris (one of two researchers in the world who was working on Aplysia in 1959). This was a potentially fatal decision for his career, yet he stood by his decision, as “there are many situations in which one cannot decide on the basis of cold facts alone—because facts are often insuffi- cient. One ultimately has to trust one’s unconscious, one’s instincts, one’s creative urge. I did this again in choosing Aplysia” (Kandel, 2006, pg. 149).
With time, Kandel gained many converts to the reductionist approach as he methodically uncovered the molecular underpinnings of short and long term memory in the giant sea slug. However, such success cannot be attributed to the young scientists’ choice of model organism alone. Kandel is quick to admit his ignorance, yet this never prevented him from seeking out the knowledge and technical expertise of his colleagues. His willingness to immerse himself in topic literature, draw upon the strengths of those who entered his lab, and master new techniques was what ensured that his experiments were fruitful.
During Kandel’s time at the National Institutes of Mental Health (NIMH), his lab chief, Wade Marshall, nurtured his creativity. The insatiable need to know the answer to novel questions and the ability to formulate unique ways of empirically testing those questions are not only hallmarks of Eric Kandel’s personhood, but the scientific method itself was. When reflecting upon his career, Kandel claims that, “the fun of doing science is to explore domains of knowledge that are relatively unknown. Like anyone who ventures into the unknown, I have at times felt alone, uncertain, without a well-trodden path to follow” (Kandel, 2006, pg. 419). Had he heeded to the warnings of others and pursued “safer” research, the area of memory may still be shrouded in mystery and speculation.
Kandel was fortunate to encounter many individuals who shared his innovative spirit in his lifetime. When the area of biotechnology began to flourish in the 1980s after the production of insulin by Genentech, Kandel was convinced to jump on the bandwagon by his close colleague, Fred Adler. He founded Neurogenetics in 1987, which focused on cloning dopamine and serotonin receptors and screening pharmaceutical drugs. Due to the fact that a number of mental disorders are implicated with these receptors, such work could have a profound impact upon the quality of life of those afflicted with mental illness. In 1996, Kandel co-founded Memory Pharmaceuticals, which was “based on the idea that the study of memory will expand into an applied science and that one day our growing understanding of the mechanisms of memory function will lead to treatments for disorders of cognition” (Kandel, 2006, pg. 327).
Eric Kandel was wise enough to know that the future of science does not reside in an isolated laboratory, but intimately woven into each of our lives. Due to the fact that one in nine people age 65 and older is currently afflicted with Alzheimer’s disease (Alzheimer’s Association, 2014, pg.16), researchers play a significant role in remedying societal issues. So as long as such researchers possess the ingenuity and audacity of Eric Kandel, science will continue to progress at a rapid pace (and perhaps stumble upon solutions along the way). After all, it is not where we are that matters, but where we have the capacity to be.