He served as a professor of neurology at the Wistar Institute of Anatomy and Biology at the University of Pennsylvania and was a major influence on a generation of American neurologists and was a key promoter of the use of the rat as a laboratory research model.
Donaldson was born in Yonkers, New York, to banker John Joseph and Louisa Goddard (McGowan) both of Irish origins.
He studied the effect of digitalin on the heart and for his PhD, he examined the neurology of the temperature sense under G. Stanley Hall.
He then spent some time in Europe under Auguste Forel at Zurich, Theodor Meynert at Vienna and Camillo Golgi at Pavia.
Here he began to conduct experiments on rats, following his colleague Shinkishi Hatai, rather than the older model organisms, frogs.