A. James Hudspeth

Hudspeth was born on November 9, 1945, in Houston, Texas, to Chalmers Hudspeth, a lawyer, and DeMaris Hudspeth, , who ran the home. As a teenager, James Hudspeth spent his summers working as a technician in the lab of neurophysiologist Peter Kellaway at Baylor College of Medicine. He completed both programs and received his PhD in 1973 and MD in 1974, both from Harvard University. He began a postdoctoral fellowship with Åke Flock at the Karolinska Institute, but returned soon afterwards to Harvard Medical School. == Career ==

Following his postdoctoral training, Hudspeth was a professor at Caltech from 1975 to 1983. Hudspeth was an HHMI investigator from 1993. Research Hudspeth's research is focused on sensorineural hearing loss, and the deterioration of the hair cells, the sensory cells of the cochlea. Hudspeth's bold interpretation of the data obtained in his careful experimental research combined with biophysical modelling lead him to propose for the first time that the sense of hearing depends on a channel that is opened by mechanical force: The hair cells located in the inner ear perceive sound when their apical end -consisting of a bundle of filaments- bends in response to the movement caused by this sound. The activated hair cell rapidly fills with calcium entering from the outside of the cell, which in turn activates the release of neurotransmitters that start a signal to the brain. Hudspeth proposed the existence of a "gating spring" opened by direct mechanical force that would open a hypothetical channel responsible for the entry of calcium ions. The hypothesis was based on the following evidence: 1) Part of the energy needed to bend the filament bundle was mysteriously lost, but could be explained if it was used to opening this gating spring, 2) The entry of calcium ions was microseconds long, this is so fast that only direct opening -without a cascade of chemical reactions- could account for it and 3) Hudspeth tested a model analogue to the opening of a door with a string attached to the door knob and demonstrated that a similar process was taking place when the filaments of the hair cell moved. Furthermore, microscopic evidence showed the existence of such a string-like structure tethering the tip of one filament to the side of and adjacent filament that could be the elusive gating spring; and the mechanosensitive channel is still controversial 30 years later. Hudspeth's hypothesis was correct and fundamental for the understanding of the sense of hearing. == Death ==

Hudspeth died of brain cancer on August 16, 2025, in Manhattan, at the age of 79. == Noted publications ==

• Holton T & A.J. Hudspeth A Micromechanical contribution to cochlear tuning and tonotopic organization. Science (1983); 222 (4623): 508–510 • D.P. Corey, A.J. Hudspeth Kinetics of the receptor current in bullfrog saccular hair cells. J. Neurosci., 3 (1983): 962-976 (note: this research was continued several years later taking advantage of newly available technology) • A.J. Hudspeth How hearing happens. NEURON (1997): 19(5): 947-950 • Lopez-Schier H, Starr CJ, Kappler JA, Kollmar R, A.J. Hudspeth Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish. Dev CELL (2004): 7(3):401–412 • Chan DK, A.J. Hudspeth Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro. Nature Neuro (2005): 8(2):149–155 • Kozlov AS, Risler T, A.J. Hudspeth Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels. Nature Neuro (2007): 10(1):87–92 • Kozlov AS, Baumgart J, Risler T, Versteegh CP, A.J. Hudspeth Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale. Nature. (2011): 474 (7351):376–9 • Fisher JA, Nin F, Reichenbach T, Uthaiah RC, A.J. Hudspeth The spatial pattern of cochlear amplification Neuron (2012): 76(5):989–9 == Awards ==

• 1985 W. Alden Spencer Award • 1991 K.S. Cole Award, Biophysical Society • 1994 Charles A. Dana Award • 1996 Rosenstiel Award • 2002 Award of Merit, Association for Research in Otolaryngology • 2003 Ralph W. Gerard Prize, Society for Neuroscience • 2010 Guyot Prize, University of Groningen • 2018 Kavli Prize in Neuroscience (shared with Christine Petit and Robert Fettiplace) as well as fellowship in the Norwegian Academy of Science and Letters. • 2020 Louisa Gross Horwitz Prize (shared with Christine Petit and Robert Fettiplace). == References ==