The principal figures associated with the Sorby Research Institute were Dr Kenneth Mellanby, Sorby Research Fellow of the Royal Society in the Zoology Department at the University of Sheffield (the Fellowship was itself named after Dr H.C. Sorby, FRS, an eminent scientist who played a prominent role in both Firth College and University College, forerunners of the University of Sheffield); Dr Hans Krebs, Lecturer in Biochemistry; and Walter Bartley, technician and assistant to Mellanby. Mellanby later became a distinguished figure in the fields of biology and ecology; Krebs became Professor of Biochemistry at Sheffield in 1945 before moving in 1954 to Oxford as Whitley Professor of Biochemistry, and while at Sheffield was in 1953 awarded a Nobel Prize for his discovery of the tricarboxylic acid cycle ("the citric acid cycle"); Bartley, who personally subjected himself to the experiments carried out in the Institute, and who had arrived in Sheffield on the first day of its Blitz, 12th December 1940, later became Professor of Biochemistry at Sheffield in 1963.

At the outbreak of war in September 1939, following consultations with the Ministry of Health, the Institute embarked on a series of experiments intended to benefit humanity, making use of volunteer conscientious objectors. Following Mellanby's initial interest in the problem of head lice it was suggested that the endemic parasitic skin disease scabies would be an important area of research, with the aims of discovering how it was transmitted and how it could be treated most effectively. Initially a team of 12 volunteers was formed, and the Institute acquired a large suburban house, "Fairholme", 18 Oakholme Road, Broomhill, which was adapted for the purpose. The scabies work, apart from its benefits to the population generally, also led to extensive observation and treatment of military personnel in a special hospital which Mellanby set up, and to the instruction of army medical officers at the Institute.

In the spring of 1942 an experiment to establish the level of water intake necessary to maintain health, which had obvious applications to shipwreck survival, was carried out. Following this came the first nutritional experiment. In consultation with the Government's official Food Policy Committee work was done on the dietary effects of high extraction (85%) wheatmeal as compared with 75% extraction flour on digestibility and calcium absorption. This was of crucial concern because wheat was a staple of the British diet, but, as much had to be imported, the food supply was under serious threat by U-boat action. It was shown that the higher extraction flour made a valuable contribution to the food supply, and the "national wheatmeal loaf" replaced white bread in the national diet.

The Medical Research Council's Accessory Food Factors Committee then asked for information on human vitamin requirements. An investigation was set up by the MRC's Vitamin A Sub-Committee. 23 men and women volunteered to live on a diet deficient in only vitamin A so that the effects could be observed and a treatment level for deficiency established. Because signs of deficiency took a long time to develop this experiment lasted considerably longer than expected, from July 1942 to October 1944, but eventually the aims of the experiment were achieved.

In late 1943 Mellanby left to join the army as a specialist in biological research, and Dr Hans Krebs took over responsibility for managing the volunteers. A similar experiment on vitamin C followed, set up by the MRC's Vitamin C Sub-Committee, and lasting from October 1944 to February 1946. Signs of vitamin C deprivation appeared, in the form of the serious disease scurvy, much more quickly than in the vitamin A work, and a safe daily intake was then established. The nutritional work of the Institute resulted in the publication of two MRC Special Reports.

The work of the Sorby Research Institute continued until early in 1946. Meanwhile, in 1944, an MRC Research Unit was established in Krebs' Department under his direction and called the "Unit for Research in Cell Metabolism", in which Walter Bartley also participated. This continued in being until 1967, but relocated to Oxford in 1954 with Krebs, together with most of his team, when he was appointed Whitley Professor of Biochemistry there.