Interview: Speaking of Memory

Considered a renegade by his peers, Nobel Prize-winner Eric Kandel used a simple model to probe the neural circuitry of memory.

Oct 1, 2011
Edyta Zielinska

DIETMAR TEMPS

Sixty-four years ago, inspired by cell and molecular biologists who studied complex questions in the simplest available model systems, neuroscientist Eric Kandel bucked then-current trends in brain research by choosing to explore memory using an evolutionarily ancient organism, rather than human subjects.

Kandel began his career in neuroscience studying cells in the human hippocampus, which had been identified as the seat of memory formation by Brenda Milner from McGill University, but he soon realized that it would take a long time to tease apart memory in such a complex system. He shifted his focus to the sea slug Aplysia, a model in which the neural pathway of a simple reflex could be delineated. Aplysia only has 20,000 neurons, and many of them are so large and distinctive that they had been named and their functions identified. Kandel worked out the neural circuitry that was established during learning and memory, and examined what molecular changes occurred in the cells of that circuit. By taking this reductionist approach, considered radical at the time, Kandel set an example for scientists who would use Aplysia and other model organisms to trace the circuits responsible for many different behaviors. His approach netted him a share of a 2000 Nobel Prize for insights into signal transduction in the nervous system. Here Kandel reminisces about his early days in the field, discusses the evolution of cognitive neuroscience, and shares his thoughts on love.

What was neuroscience like when you started working in the field?

When I started in the field, it was a minority science that very few biologists were interested in because it was technically quite arcane. The two major tools for brain science were anatomy, which most people found boring, and electricity, which most people found incomprehensible. So that combination was enough to put off most biologists. But now everybody and his uncle want to work on the brain. The number of people applying to graduate schools, MD/PhD programs, is really extraordinary. It’s a big change.

How has the field changed from then until now?

When I entered the field in 1957, it was a very small and very primitive discipline. One of the characteristic features was that its three main subdisciplines—the anatomy of the brain, the biochemistry of the brain, and the physiology of the brain—were all separate fields. One of the early strides forward occurred when Harvard’s Stephen Kuffler launched the field of neurobiology, a discipline that combined all three of them into a coherent whole.

Some professors held the view that there are two kinds of people: people who like people, and people who like science. I thought this was the most absurd position in the world.

The second step forward was the bringing together of neurobiology and psychology—the science of the brain and the science of the mind—into cognitive neuroscience. We did the first experiments on a simple level doing this in terms of Aplysia, where we combined behavioral and cellular analyses. But people were beginning to do this in flies, in rats, and in monkeys—more complicated organisms.

And a final step in the evolution of field was the merger of molecular biology and cognitive neuroscience, to develop a new science of the mind—a new approach to thinking about the brain and its mental functioning.

I think the major change that has occurred during my career is the fact that people no longer study the nervous system simply as a set of abstract subsystems, without recourse to behavior. They now almost invariably study the nervous system in relationship to one or another behavior. And the realization on the part of psychologists, most of whom, of course, were there and knew this, that all mental processes come from the brain and that neuroscience and psychology are really different sides of the same coin.

What were the biggest obstacles you faced?

For the longest time psychiatry was heavily influenced by psychoanalysis. And psychoanalysis has a lot of strengths, but doing basic research is not one of them. So in psychiatry, when I was a resident, we were discouraged from doing science. I was an exception in being allowed to do it because I had done science before. But the official policy was, “You learn best from your patients. You don’t learn that much from science.” There were some professors who held the view that there are two kinds of people: people who like people, and people who like science. I thought this was the most absurd position in the world.

Did others in the field think that you wouldn’t find anything when you turned to Aplysia?

Yes, and that I was wasting my time. There was a hierarchical system in neurobiology, and working in invertebrate animals was not looked upon favorably, except in a very special case: the squid giant axon. People thought that the mammalian brain was what you had to understand and that behavioral and learning principles would not apply across species. And that was wrong. Giving up my work in the mammalian brain to go work on invertebrates, they thought, was a major step backwards. It proved for me to be a step in the right direction.

Are there unanswerable questions in neuroscience; ones that should be left to philosophers and poets?

I see no reason to believe that science can’t solve, in a meaningful way, all the problems of the brain. At least there is no impediment that has occurred so far. Who’s to know what will emerge 50 to 100 years from now. But for the foreseeable future I think it’s our lack of ingenuity that is limiting, not the intrinsic difficulties; the problems are difficult—but not insurmountable.

Even love?

The biology of love? Well, it depends on what level you want to call love. Love will always have features that, moment to moment, would not be understood. But the principles underlying love, I think we will understand. Why specific people fall in love with one another—one can probably even now define certain ground rules. But I think there’ll always be magic to life, even though science explains a great deal.

Eric Kandel is a professor at Columbia University in New York, and a Howard Hughes Medical Institute Senior Investigator.