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The University has its origins in the School of Medicine and Surgery which was established in Newcastle upon Tyne in October 1834, providing basic lectures and practical demonstrations to around 26 students. In June 1851, following a dispute amongst the teaching staff, the School was split into two rival institutions: the majority forming the Newcastle College of Medicine, with the others establishing themselves as the Newcastle upon Tyne College of Medicine and Practical Science. By 1852 the majority college was formally linked to the University of Durham and its teaching certificates were recognised by the University of London for graduation in medicine. The two colleges amalgamated in 1857 and renamed the University of Durham College of Medicine in 1870.

Attempts to realise a place for the teaching of sciences in the city were finally met with the foundation of the College of Physical Science in 1871. The college offered instruction in mathematics, physics, chemistry and geology to meet the growing needs of the mining industry, becoming the Durham College of Physical Science in 1883 and then renamed after William George Armstrong as Armstrong College in 1904. Both these separate and independent institutions later became part of the University of Durham, whose 1908 Act formally recognised that the University consisted of two Divisions, Durham and Newcastle, on two different sites. By 1908, the Newcastle Division was teaching a full range of subjects in the Faculties of Medicine, Arts, and Science, which also included agriculture and engineering.[7]

Throughout the early 20th century, the medical and science colleges vastly outpaced the growth of their Durham counterparts and a Royal Commission in 1934 recommended the merger of the two colleges to form King's College, Durham. Growth of the Newcastle Division of the federal Durham University led to tensions within the structure and on 1 August 1963 an Act of Parliament separated the two, creating the University of Newcastle upon Tyne.