It was founded by the English Jesuit Robert Persons in 1592, when Roman Catholicism was illegal in England, to provide his native country with priests.
The dedication of the college to St Gregory recalls the Gregorian mission of AD 596, which resulted in the Anglo-Saxons being converted to Christianity.
Teaching staff included Richard Smith who developed different ideas from Persons about the project.
It was supported by the Jesuits until 1767 when Charles III, in a surprise move, expelled the order from Spain.
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