Damage to hair cells buried deep inside our ears is a leading cause of deafness and other hearing impairments. Topped with distinctive bundles of fine bristles that quiver in response to sound waves, these sensory cells generate electrical signals that are processed by the brain and interpreted as the babbling of a baby, the barking of a dog, the blaring of a car horn, or any of the kaleidoscope of sounds in the world around us. A. James Hudspeth has spent his career exploring the inner workings of hair cells, with the goal of understanding how they work, why they are so vulnerable to damage, and ultimately, how they may be protected, repaired, or even replaced.

Growing up in the rural outskirts of Houston proved to be an ideal backdrop for nurturing Hudspeth's early interest in science and nature. He and his younger brother were passionate collectors of rocks, fossils, and shells, and their collection eventually grew to include more than 200 live animals—a menagerie of dogs, cats, toads, frogs, birds, snakes, lizards, turtles, and a raccoon. This enthusiasm for learning about living things in nature helped Hudspeth land his first research job at 13, working part-time in the laboratory of the late Peter Kellaway, a neurophysiologist at the Baylor College of Medicine. His interest in hearing was sparked later, while pursuing M.D. and Ph.D degrees at Harvard, when he was assigned to deliver a lecture on the topic to medical students. "In preparing for that lecture, I was struck that so little was known—especially in modern, cell-biological terms—about the operation of a sense as important as hearing," Hudspeth recalled.

That lack of knowledge drove him into the laboratory, where he began to study the mechanics of hearing in the inner ear. One of his first challenges was to develop a way to study hair cells, which are naturally protected in living animals by the skull. He soon devised a method to remove living hair cells from bullfrogs, whose ears are structurally similar to those of mammals, and record the electrical changes that occur when their mechanoreceptive hair bundles are prodded by a vibrating probe. This work showed that each bundle operates like a light switch: When the bundle is nudged in one direction, the hair cell is turned on; when the bundle is moved in the opposite direction, the hair cell is turned off. Hudspeth and his colleagues determined that the cells are so sensitive that prodding the tip of a hair bundle by the width of an atom is enough to elicit a response.

His current research projects are aimed at further clarifying hair-cell function. One project involves searching for genes that code for proteins involved in the hair-cell's responsiveness. Using zebrafish as a model, Hudspeth has identified certain mutants that fail to execute a classic startle reflex triggered when a sudden burst of sound stimulates hair cells. In one case, zebrafish carrying a mutation in the choroideremia gene have abnormally formed hair cells and are completely unresponsive to acoustic stimulation, he has noted.

Hudspeth is also working to identify a poorly understood amplification mechanism of the inner ear that causes it not only to receive sounds but to emit them as well. "The ear is about 100 times more sensitive than we can explain," he notes. "If you put a microphone in it, you can detect noises that the ear itself generates." This phenomenon may occur when hair cells generate feedback, much like a public address system that is turned up too high, and it may account for some unusual cases of tinnitus, or ringing in the ear.

Jim Hudspeth studies the biophysical and molecular bases of hearing and equilibrium; in particular, he is interested in the development and operation of the inner ear's sensory receptors, the hair cells.