328 CORNELIUS A. TOBIAS 



of control of instinctive behavior by production of lesions that decerebrate 

 the animals. In 1959, Leksell, who has pioneered in the applications of radia- 

 tions to brain surgery, and the Uppsala team initiated proton neurosurgical 

 applications by producing bilateral cutting lesions in the frontothalamic 

 bundles in a patient with schizophrenia (Leksell, 1961). Sourander and 

 associates (Andersson ct al., 1961) have supplied very interesting neuro- 

 histopathological studies. 



While studies with deep lesions were in progress with high energy nucleons, 

 another group of approaches took place with particles of a few million volts 

 per nucleon. Pollard (1953) and associates have used protons for basic 

 studies of enzyme molecules and phage particles. Zirkle and Bloom (1953) 

 applied a microbeam of protons to partial cell irradiation. Soon after the 

 nature of cosmic ray primaries were known (Freier et al., 1948) speculations 

 arose that heavy primary cosmic rays could exert great radiobiological effects, 

 particularly in the brain, where it was believed no recovery from radiation 

 effects would take place (Schafer, 1950; Tobias, 1952). The first exposure 

 of living cells to carbon particles was done in 1952 at the cyclotron (Sayeg 

 et al., 1959), and an increased biological effectiveness of heavy ions on yeast 

 cells was demonstrated. In 1957, both at Berkeley and at Yale University new 

 accelerators became available which can deliver particles up to argon nuclei 

 with about 10 Mev energy per nucleon, and detailed information is becom- 

 ing available on the manner of action of these radiations (Brustad, 1960; 

 Hutchinson, 1960). The chairman of this session and his associates (Malis 

 et al., 1957) showed that a monoenergetic beam of protons can produce 

 in animals "laminar" lesions in the brain only about 80 microns thick, run- 

 ning quite closely parallel to the exposed brain surface. Malis et al. (1961) 

 are presenting new data here. Haymaker and associates have traced the 

 nature of pathological development of such radiolesions with alpha particles 

 (Janssen et al., 1961). Van Dyke et al. (1961) have pointed to the great 

 variation of radiosensitivity of the brain among different species and demon- 

 strated the vulnerability of the blood-brain barrier by showing that fluores- 

 cent dyes can penetrate the irradiated region early in the course of lesion 

 development. It was also shown that very high doses in rat cerebellum with 

 low energy beams can lead to sharp surface lesions with scarring virtually 

 absent. 



Today, accelerated particles can be used for the production of a variety 

 of well-defined radiation lesions. Work is in progress not only on the involved 

 steps that lead to the development of radiation-induced necrosis, but also the 

 accurately placed lesions are being utilized to obtain answers for many 

 pressing problems. The role of histologically defined neuronal zones in the 

 gray matter, anatomical studies of retrograde degeneration, the problem of 

 regeneration, and that of the origin and nature of the electrical function of 



