Humans have 30,000 cochlear and vestibular hair cells. By contrast, the human retina has 120 million photoreceptors. The 30,000 hair cells, arranged in four rows and protected by the hard shell of the cochlea, determine how well you can hear. If you lose the outer cells, you suffer up to a 60-decibel hearing loss. That degree of hearing loss can usually be corrected with a hearing aid. If you lose the inner row of cells, you may have a total loss. The more inner cells damaged, the greater the degree of loss. Sharon Kujawa, speaking at the 2011 HLAA meeting, had described the damaged cells as lying flat, like a field of wheat after a storm. Stefan Heller drew an even more graphic picture of severe damage. The flattened cells, he said, may be “followed by a collapse of the tunnel of Corti, resulting in a structure that often features an unorganized mound of inconspicuous cells.”
Surrounding the inner and outer hair cells are the so-called supporting cells, which come in all varieties: Deiters’ cells, Claudius’ cells, Hensen’s cells, inner pillar, and outer pillar cells. Supporting cells are the magical cells that instigate regeneration in damaged inner ears of chicks and fish. And they are where someday regeneration may occur in humans.
That limited number of hair cells, as well as their fragility and inaccessibility has hampered research. In his 2010 Cell paper, Stefan Heller noted, “The inner ear shelters the last of our senses for which the molecular basis is unknown.” So little is known about the structure of the inner ear that, as Dr. Gates said, “we have a hard time clinically knowing how much [loss] is outer and how much is inner. That’s why we use the term sensorineural.”
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Ed Rubel’s photo on the University of Washington website shows a balding middle-aged man, elbows on the table, with two yellow chicks. That whimsical photo belies a seriously impressive academic c.v.: Virginia Merrill Bloedel Professor of Hearing Science; Professor of Otolaryngology—Head and Neck Surgery; Professor of Physiology and Biophysics; Adjunct Professor of Psychology. Dr. Gates referred to him as the godfather of hair cell regeneration.
Rubel and his colleagues at the Virginia Bloedel Hearing Research Center see four clinical scenarios that lend themselves to pharmaceutical fixes. The first would reverse sudden sensorineural hearing loss. The second would prevent ototoxic and/or noise-related hearing loss. The third would retard the progression of hearing loss, especially age-related hearing loss. The fourth would restore hearing after it had been lost.
Until 1985 it was thought that no animals could regenerate hair cells once they were destroyed. Rubel, then at the University of Virginia, discovered, quite inadvertently, that some do. The purpose of his research was to determine how long it took for ototoxic drugs to damage hair cells. He and his lab partners chose chicks as their animal model. Chicks have an easily accessible inner ear, and their ears in many ways resemble the human inner ear.
Rubel gave the chicks hair-cell-destroying aminoglycocides—a class of antibiotic known to be ototoxic—and then assigned the new guy at the lab, as Rubel put it in his talk at the conference, a resident named Raul Cruz, to sacrifice the chicks after a certain number of days and study the degree of deterioration in the hair cells. After eight days, Cruz found the chicks had, as expected, lost many cells. But when he studied the slides taken from chicks sacrificed at twenty-two days, instead of more dead cells they showed fewer. Where there had been dead cells, there were now healthy ones. “Raul, you must have mixed up your animals, go back and do it again,” Rubel recounted, adding, to laughs, “Because he was just a resident, he didn’t know what he was doing.”