Dr. A. James Hudspeth, a neuroscientist at the Rockefeller University in Manhattan who was pivotal in discovering how sound waves are converted in the inner ear to electrical signals that the brain can perceive as a whisper, a symphony or a thunderclap, died on Aug. 16 at his home in Manhattan. He was 79.
His wife, Dr. Ann Maurine Packard, said the cause was glioblastoma, a brain cancer.
Scientists have long understood how sound waves enter the ear canal and cause the eardrum to vibrate. They have also understood how the vibrations travel through the three small bones of the middle ear, then to the cochlea in the inner ear, a tiny organ about the size of a chickpea that is filled with fluid and is shaped like a snail’s shell.
And they have long known that microscopic receptor cells in the cochlea play a role in the process of hearing. But by the time Dr. Hudspeth began his research in the 1970s, it was still unclear how these cells — known as hair cells (the name derives from tufts of cylindrical, hairlike rods known as stereocilia) — transformed the mechanical vibrations of sound waves into nerve impulses that the brain could interpret as, say, a child crying or a dog barking.
Dr. Hudspeth “provided the major framework” for this understanding, the committee that awarded him and two other scientists (Robert Fettiplace and Christine Petit) the Kavli Prize in Neuroscience for their pioneering work on the processes of hearing wrote in its citation in 2018.
Each cochlea contains about 16,000 hair cells. Atop each cell, 20 to 300 of these rods are gathered in a bundle — the shortest to the tallest — in rows that resemble a staircase or a pipe organ. Hair cells line the cochlea, with each tuned to a narrow frequency range that collectively decodes the broad spectrum of tones in every sound.
As sound waves enter the cochlea, the stereocilia rods begin to slide next to one another. Dr. Hudspeth theorized that this motion toward the tallest rods created tension on elastic tethers that pulled open tiny pores — essentially trap doors — on the tips of the stereocilia.
His hunch was supported by another scientist, James Pickles, who discovered that each rod is attached to neighboring rods by an elastic protein filament, a kind of microscopic rubber band or spring.
Dr. Hudspeth revealed that when the trap doors open, positively charged ions of potassium and calcium flood into the cells, creating an electrical signal that is carried by the auditory nerve to the brain.
The opening and closing of the trap doors, Dr. Hudspeth found, happens in microseconds, a speed 1,000 times as fast as that of our other senses. The stereocilia, he said, can create a signal that the brain detects by moving only the width of a water molecule.
He showed that hearing depends not only on speed but also on a built-in amplifier system, which can boost a sound signal by about 1,000-fold and sharpens frequency tuning, making it easier to tell voices apart and understand nuances in speech.
Dr. Hudspeth “was the one who really figured out how hair cells worked,” David Corey, a neuroscientist at Harvard and one of his former graduate students, said in an interview.
Albert James Hudspeth was born on Nov. 9, 1945, in Houston. His father, Chalmers Hudspeth, was a lawyer. His mother, Demaris (De Lange) Hudspeth ran the household.
From an early age, Jim, as he was known to his colleagues, was drawn to the orderliness of nature. He and his brother, Tom, amassed a menagerie at home of 200 animals, including box turtles, toads, raccoons, opossums and armadillos.
He attended Harvard, where he received a bachelor’s degree in biomechanical sciences in 1967, a master’s degree in neuroscience in 1969, a Ph.D. in neuroscience in 1973 and a Doctor of Medicine degree in 1974. He joined the Rockefeller University’s faculty in 1995 and was a member of the National Academy of Sciences.
His 50-year career deciphering the process of hearing began by accident, he said. He was more interested in brain research. But, while he was in graduate school, one of his professors asked him to deliver a paper on hearing and balance.
“I was so amazed that so little was known about hearing, yet it’s so manifestly important,” he said in a 2020 Kavli Prize lecture.
Torsten Wiesel, a Nobel laureate who was Dr. Hudspeth’s graduate faculty adviser at Harvard, described him as impatient with small talk but brilliant and brimming with ideas. He said an interview that he had nominated Dr. Hudspeth for a Nobel Prize three times, including this year, adding, “I hoped he would get the prize before he died.”
In the mid-1970s, while Dr. Hudspeth was at the California Institute of Technology, he and his lab began to explore whether the movement of the bundles atop hair cells created electric signals. A challenge for studying the human cochlea is that it is tiny, fragile and inaccessible, so Dr. Hudspeth studied the dissected inner ear of bullfrogs. Under a microscope, he used a small glass rod to push gently against the tips of hair bundles.
He continued his work at the University of California, San Francisco, in the 1980s. For one experiment, he needed a quiet space so one of his postdoctoral students could conduct extraordinarily sensitive measurements of how far trap doors move when opening to allow ions to flow into the cells and create an electrical signal. (The answer: one ten-thousandth of the width of a human hair.)
So Dr. Hudspeth set up a lab in an abandoned swimming pool in the basement of his office building. Dr. Corey of Harvard said that Dr. Hudspeth had truckloads of cement brought in to fill and stabilize the pool.
“It worked absolutely brilliantly,” Jonathon Howard, his postdoctoral student and now a professor of physics at Yale University, told The Transmitter, an online publication devoted to neuroscience. “We were just absolutely single-mindedly going after it.”
In the latter stages of his career, Dr. Hudspeth and colleagues found a way to keep a sliver of the cochlea of a gerbil functioning outside the body, which was related to his study of potential ways to reverse hearing loss.
Once human hair cells die — from such means as repeated exposure to loud noises, aging, and certain diseases and medications — they do not regenerate. An estimated 1.5 billion people experience some degree of hearing loss, according to the World Health Organization.
Dr. Hudspeth explored — along with many other scientists — possible ways to restore hair cells, which many nonmammalian animals like fish and birds can do. One method involved druglike compounds that release the genetic brake that stops cells from multiplying during development.
Along with his wife, Dr. Hudspeth is survived by a daughter, Ann Hudspeth; a son, James Hudspeth; a grandson; and his brother, Tom.
Just before Dr. Hudspeth died, the Rockefeller University optioned technology regarding promising research into restoring hair cells in mice and rabbits. The technology, developed in Dr. Hudspeth’s lab, has been enhanced by one of his former postdoctoral researchers, Ksenia Gnedeva, now a professor at the University of Southern California.
“If all goes well,” Dr. Gnedeva said in an email, “these compounds will soon be tested in human clinical trials. It pains me deeply that Jim will not be here to see where our work leads.”
Jeré Longman is a Times reporter on the Obituaries desk who writes the occasional sports-related story.
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