2012 Prize Recipient
Kandel explored how nerve cells (neurons) change during learning. His research, involving the sea slug Aplysia and mice, uncovered the basis of short- and long-term memory. Kandel shared the 2000 Nobel Prize for Physiology or Medicine with fellow neuroscientists Arvid Carlsson and Paul Greengard. Kandel's research could lead to the development of treatments for Alzheimer's disease and other conditions related to memory loss.
After graduating from Harvard in 1952, Kandel entered New York University's medical school. By his senior year there, Kandel felt he needed to learn more about the biology of the mind. NYU did not have a faculty member working in basic neural science, so Kandel studied the subject at Columbia University in New York City. In 1955, he began working in the Columbia lab with Harry Grundfest. Kandel was encouraged in his work by a friend whose family fled the Holocaust. Denise Bystryn, a native of France, met Kandel while she studied at Columbia for a doctorate in medical sociology. Kandel graduated from medical school in 1956 and married Bystryn. He then divided his time between a medical residency at Montefiore Hospital and work in the lab. In 1957, Kandel began doing research at the National Institutes of Health Laboratory of Neurophysiology.
Kandel's early research focused on the biology of cells in the hippocampus, the part of the brain related to memory and learning. After working with mammals, Kandel wanted to take a biological approach using a less complex animal model. That work would initially involve invertebrates, creatures with no backbones. Some neurobiologists and psychologists thought Kandel was making a mistake, one that would hurt his career. They believed that a mammal's brain was so complex that research results could not be compared with studies involving invertebrates. Kandel knew that some comparative behavior researchers like Konrad Lorenz had discovered that humans and simple animals sometimes behaved the same way when they learned. Kandel reasoned that since nothing was known about the cell biology of learning, any insight would be highly informative. After researching subjects including crayfish, lobsters, and snails, Kandel decided to concentrate on Aplysia. While the human brain contains billions of nerve cells, the sea slug only has 20,000.
Kandel arranged to study in Paris, with Ladislav Tauc, one of two researchers working with Aplysia. Before going to France, Kandel needed to complete a two-year residency in psychiatry. In 1960, he began residency training at the Massachusetts Mental Health Center of Harvard Medical School. The following year, Denise gave birth to Paul, the Kandels' first child. In September 1962, Kandel moved with his family to Paris. In France, Kandel and Tauc started research on the gill-withdrawal reflex of the sea slug. If the slug is touched on or near its gill, it instinctively protects itself by withdrawing and covering the gill area with a skin flap. Stimuli used to cause the reflex included touching the tail or pricking the sea slug with a needle. Repeatedly touching the Aplysia eventually caused the slug to withdraw less, thus exhibiting a learned behavior.
After 16 months in Paris, Kandel returned to Harvard Medical School. He served on the faculty of the Department of Psychiatry until 1965. That year, he joined the faculty of New York University as an associate professor—and became a father to daughter, Minouche. Three years later, Kandel was named a professor at NYU.
In 1974, Kandel became founding director of the Columbia University's Center for Neurobiology and Behavior. In addition to work as a professor, Kandel would research memory. Kandel wanted to know how, in his Paris-based experiments, Aplysia had learned to avoid exhibiting a reflex response to the touch stimuli. At Columbia, his gill-withdrawal research showed that memory and learning were the result of changes in the synapse, the place where communication between adjacent neurons occurs. The lab showed that cells communicate by signal transduction, meaning a message is sent from one cell to another through chemical transmitters. A weaker stimulus in slugs resulted in short-term memory that lasted several hours or days. The formation of short-term memory involved a process called adenosine monophosphate (AMP). A stronger stimulus produced long-term memory that lasted weeks. Kandel's lab discovered that memory was triggered by variations of a molecule called CREB (cyclic-AMP-response element-binding protein). CREB changes the short-term memory into long-term memory that in humans can last months or years. In that process, the shape of the synapse changes.
Kandel left the lab in 1984 to become a senior investigator at Howard Hughes Medical Institute at Columbia. He continued to research and teach. During the 1990s, Kandel broadened his research to include mice and found that they experienced many of the changes that Aplysia did, indicating that his findings about memory in invertebrates also applied to mammals. Mouse research also showed that a process called long-term potentiation (LTP) increased the efficiency of neural signals and is an essential process in the area of the brain that stores memories. Kandel's research could lead to the development of treatments for memory-related conditions like Alzheimer's disease. In 1998, Kandel co-founded Memory Pharmaceuticals with Walter Gilbert, PhD, a Nobel Laureate and a Harvard professor specializing in molecular genetics. The company, licensed in agreement with Columbia University, explores drug treatments for memory disorders.
Kandel's other honors include the National Medal of Science and the Lasker Prize.