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 enrolled in a graduate program in neurobiology to avoid being drafted into the military, but a year later the policy was changed, requiring him to enter medical school for exemption.

[1][2] He began a postdoctoral fellowship with Åke Flock at the Karolinska Institute, but returned soon afterwards to Harvard Medical School.

[5] 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:[6] 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 hypothesis was based on the following evidence:[7] 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.