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The hospital opened on 1st December 1858 at 32 Soho Square as the Dental Hospital of London. The origins of all regulated and scientific dental practices can be found in the inception of the Dental Hospital and School. Before 1858 the dental profession had no regulation and anyone could set themselves up as a dental practitioner. This led to poor standards and a realisation of the need for proper training and an official qualification for dental practitioners. The Dental Hospital was established to achieve this and gained the backing of the Royal College of Surgeons to approve diplomas. The Dental School opened on 1st October 1859 to provide regulated, structured training for students in dental medicine. The hospital emphasised the need to regard dental medicine as connected to all other branches of medicine and to look at the wider picture when treating patients.
In 1874 the Dental Hospital moved to Nos. 40 and 41 Leicester Square the premises at 32 Soho Square having become too small and limited in resources for the number of patients being seen. The number of patients being treated had risen from 2,116 in 1859 to 22,627 in 1872. By 1882 they had reached 35,893 and there were once again complaints about a lack of space, these were appeased with the addition of the Tower House, adjoining the Hospital property and given to them by Sir Edwin Saunders. The addition of this extra space almost doubled the hospital's operating space. The problem of space did not end there. The Dental Hospital was now in a position where their efforts to increase resources to meet rising demand resulted in even greater demand. By 1886 patient attendances had reached 43,745, a 12% increase on the previous year and nearly double that of 1874. This resulted in further overcrowding and a need for further expansion. An attempt was made to incorporate No. 42 Leicester Square into the Hospital, but these plans were held up by difficulties over fire regulations. It was not until 1888 that the extension was opened. This was only a temporary solution to a long-term problem, and the Dental hospital looked at obtaining a new site for the construction of a purpuse built hospital building. By the end of 1893 the Board of Management had purchase Nos. 35, 35a and 36 Leicester Square, Nos. 22 and 23 Green Street, Nos. 1-5 Longs Court and had a deposit down for The Duke's Head, No. 37 Saint Martin's Street, all of which were contained within the same block. This had entailed an expenditure of £20,398, three-quarters of which had to be borrowed from the bank. Plans were in place for the purchase of the other buildings in the block and this was achieved by 1896, when plans were set in place to rebuild. The site was cleared in 1896 and the building work commenced in 1897. The Hospital moved into the new building in March 1901, and the old site was sold for £18,000. At this time the Hospital also received the patronage of King Edward VII and changed its name to the Royal Dental hospital. The Hospital at this time had developed the shape and organisation that were to stay in place for the next 75 years, but it had also gained a burden of debt that was not to be paid off until 1930.
In 1911 the Royal Dental Hospital of London School of Dental Surgery became a school of the University of London and as well as their own Licence in Dental Surgery a University Degree in Dental Surgery was offered. This development allowed the Dental School to become involved in many of the developments in dental surgery that occurred in the early twentieth century. However the burden of debt did also mean that the School and Hospital did not develop as rapidly during this period as some of their competitors. The technological development of the Hospital was slowed down by the financial pressures and by the internal politics of the teaching and practice of Dental Surgery at this time.
The Royal Dental Hospital and School stayed open throughout the Second World War. Most of the other specialist dental schools and departments had either closed down or moved out of London with their parent organisations, leaving the Royal Dental hospital as the only place for the public to get specialist dental care. The building was damaged by a land mine in October 1940 but was quickly repaired and back in service. Other difficulties due to reduce income and staff shortages meant that the referral of patients for consultant opinion was discouraged, but other wise a full service was offered. The establishment of the NHS in 1948 saw the Royal Dental Hospital grouped with the Saint George's Hospital and Medical School, located on Hyde Park Corner and the Atkinson Morley in Wimbledon as the Saint George's Hospital Teaching Group. The School of Dental Surgery became a self-governing body, affiliated with Saint George's Hospital Medical School. The problems over space were still an issue. In 1957 plans to renovate the interior of the hospital to provide more space and better equipment were approved and the Hospital and School accomodation was reorganised, the School moved most of its non-clinical facilities into the newly acquired Ciro Club on Orange Street.
During the 1960's and 1970's the big issue was the transfer of the Dental School to Tooting with Saint George's Hospital and Medical School, which were to be rebuilt there. The Royal Dental Hospital was not at first happy with this and tried to delay the move, which was also held up by the Ministry of Health due to the finacial situation of the time. However Saint George's finally moved in 1975 and in 1976 the School of Dental Surgery's pre-clinical departments moved to Tooting. It was decided that the dental service required in Tooting was not that offered by the Royal Dental Hospital and the 1980's were spent preparing of the closure of the Hospital. The Dental School was amalgamated with the United Medical School of Guy's and Saint Thomas' Hospitals and the remaining dental services transferred to Tooting. The Royal Dental Hospital closed in 1985 and the site in Leicester Square was developed as the Hampshire Hotel.