The Institute was founded as a research group in October 1950 by Leon Orbeli, a physiologist and a longtime collaborator with Ivan Pavlov.
It subsequently expanded and transformed into the Laboratory of Evolutionary Physiology of the USSR Academy of Sciences, with the main object of studying functions of the nervous system in animals and man during ontogenesis, and also the effects of ionizing radiation on animals.
In 1956, the Laboratory became an Institute with Orbeli serving as the first Director of Evolutionary Physiology of the Academy of Sciences.
After Orbeli's death in 1958, the Institute was headed by his collaborator Professor Alexander Ginetsinsky.
From June 1960 to March 1975, the Institute was guided by Eugenie Kreps: a former pupil of Ivan Pavlov and collaborator of Orbeli's, Kreps is known for his fundamental studies in the field of comparative physiology and biochemistry of the nervous system.