Monday, December 05, 2005

Don't Worry, Be Happy

Nobel Laureate Eric Kandel explains how genetic research could lead to a new generation of anti-anxiety drugs.

By Emily Singer

Five Nobel Laureates recently got together to talk about the future of the brain at a symposium to inaugurate MIT's new Picower Institute for Learning and Memory. One of them was Eric Kandel, a neuroscientist at Columbia University in New York, who won the 2000 Nobel Prize in Physiology or Medicine for seminal experiments on sea snails that illuminated the neurobiology of learning and memory. In a conversation on December 1 with TechnologyReview.com's biotechnology editor, Emily Singer, Kandel explained how researchers are on the verge of understanding serious psychiatric diseases -- and that they may even unlock the biological key to happiness.

Technology Review: Are we on the brink of understanding the major psychiatric diseases? What kinds of developments can we expect to see over the next few decades?

Eric Kandel: We have had an explosion of progress in neurology because of molecular biology, but we have not seen comparable developments in psychiatry. I fully expect in the next 20 to 30 years we'll see this. We know little about anatomical substrates underlying most mental illnesses. We know that the genes involved are complex, but we haven't been able to identify them. So we haven't been able to do what people have done in Huntington's disease and other neurological diseases, which is take these gene defects and put them into animals and try to delineate the mechanisms of pathogenesis. But that's beginning to be possible. We're beginning to identify these genes.

TR: Which of the psychiatric diseases are going to yield their genetic secrets the soonest?

EK: The best examples are the anxiety disorders. We know a lot about the amygdala, a structure that lies deep in brain in all mammals, including humans, and is involved in mediation of emotion. We can make animal models that have panic attacks. We can use those models to understand the neurobiology of fear.

TR: You published a paper in November showing that you could create a fearless mouse by knocking out a single gene that's involved in encoding fearful memories. Normal mice freeze when they hear a tone that has been associated with an electric shock, but when the mutant mice heard the tone, they wandered happily around their cages. Will mice like this help us discover new treatments for anxiety disorders?

EK: Yes. Once we have genes that enhance or reduce fear, we can manipulate the neural circuitry involved in fear. This experiment might present a new way of treating anxiety. You could develop drugs that modify the action of that gene in the amygdala.