Eric Kandel - A Nobel Laureate Looks Back and Looks Forward

In the first piece to this series, I reported how a young refugee from Nazi-occupied Austria began studying Freud as a way to comprehend the brutality of man, but instead became a rising star in neurobiology. In the second piece, I reported how Dr Kandel's ground-breaking research (with his unlikely lab partner, the California sea snail) helped map out the biology of memory and how neurons communicate with each other. In this final installment, Dr Kandel reflects on his extraordinary life.

"Matisse had it right when he pointed out that life is a circle," 2000 Nobel Laureate Eric Kandel told a packed auditorium at the American Psychiatric Association’s annual meeting in Atlanta in May 2005. In other words, if you follow your unconscious, you often find you come back to the themes that interested you in the beginning.

In 1990, while still working on snails, Dr Kandel returned to studying mammalian hippocampal neurons, mapping out the higher memory functions in mice. In the lab, he was able to reverse age-related memory loss in his animals.

"If you’re a mouse," he joked, "we can do a lot for you. For people, we’re not sure as yet."

Then Dr Kandel extended his focus to the amygdala, which governs fear. Fear, he explained, is the one behavior so far we can observe in animals. A mouse that receives a shock accompanied by the sound of a bell will soon crouch in fear to just that sound. Dr Kandel’s lab discovered that this kind of fear resulted in the release of the peptide GRP in the amygdala of the animals. Mice bred without the capacity to produce GRP lost their inhibition.

"Maybe in some disease states," Dr Kandel commented, "inhibitory restraint is compromised."

But that is not the end of the story. What would happen, he wondered, if you set out to investigate the mirror image of fear? This time, Dr Kandel’s team trained mice to associate a particular sound with safety. As expected, the animals’ sense of security dampened activity in the amygdala. But the investigators also discovered a circuit connecting the amygdala to the dorsal striatum (caudoputamen), an area of the brain associated with happiness and reward.

"We don’t like being miserable," Dr Kandel explained. "What we really want to do is to be happy, to be secure, to be confident." He quoted the first line of Anna Karenina: "Happy families are all alike …"

"That really is inspiring to a neurobiologist," Dr Kandel joked, "because if you find the gene it is going to be unbelievably universal." So as well as identifying new targets for anxiety drugs, he explained, we may also find targets for enhancing positive affect.

Dr Kandel has written extensively on integrating his first love – psychoanalysis – with his vocation, neurobiology. Despite some signs that psychoanalysis is joining the real world, however, he does continue to scold this branch of the profession for its insularity, disregard for patient outcomes, and lack of scientific rigor – traits not shared, he says, by practitioners in many other fields of talking therapy.

"A major need of psychiatry in the future," he stated, "is to put the psychotherapeutic arm of psychiatry on the same solid biological footing as the pharmacological aspect of psychiatry." He was very much moved by Kay Jamison who said if it wasn’t for lithium she would be dead, but that it was really psychotherapy that gave her a coherent view of her life, that allowed her to tie the various strings of her life together.

"We’re in a fantastic phase of psychiatric thought," he concluded. The biology of the mind is the central scientific challenge of the twenty-first century. Molecular genetics and molecular biology, he said, have given us insights that would have been inconceivable 20 or 30 years ago. These advances will revolutionize psychiatry, but hardly eliminate it. Instead, psychiatry will synthesize with molecular biology into what he describes as "the new science of the mind."

Dr Kandel - an avid lover of fine art, classical music, and opera - resides in the Riverdale section of the Bronx with his wife of 50 years, Denise. As a girl in Nazi-occupied France, Denise hid in a convent without knowing the whereabouts of her parents. Denise is a professor in the Department of Psychiatry and School of Public Health at Columbia and a pioneer in the epidemiology of drug use in adolescents. They have two children and a number of grandchildren.

Writes Dr Kandel in his Nobel autobiography:

"In retrospect it seems a very long way for me from Vienna to Stockholm. My timely departure from Vienna made for a remarkably fortunate life in the United States. The freedom that I have experienced in America and in its academic institutions made Stockholm possible for me, as it has for many others."