A transportation vehicle with an autonomous driving control has a set-up mode, an active drive mode, a safe shutdown mode, and an emergency response mode. The active drive mode autonomously navigates along a driving route specified in the set-up mode. A driver sensing system senses a driver presence in the driver seat and a driver's physiological state. Active drive mode is not entered from set-up mode unless the driver is present in the driver seat and the physiological state matches a normal condition. While in active driving mode, an elapsed time period is measured whenever the driver presence is not detected. If the time period increases above a first threshold then a notice is given to the driver that the active drive mode may be interrupted. If the time period increases above a second threshold then the active drive mode is terminated and the safe shutdown mode is initiated. A sensed physiological state is compared to a predetermined emergency condition and if a match is found then the autonomous driving control terminates the active drive mode and the emergency response mode is initiated.