64 bit applications have existed ad least since the early 1990's e.g. DEC Alpha running OpenVMS or OSF/1.
In those days, very few organizations could afford multiple gigabytes of physical memory, so in those days, the only real application was handling big data bases. In a programming language, you simply declare a multiple terabyte array and doing an assignment statement like C = Arr[i] will cause a page fault and a page load into physical memory, using the normal page fault loading from one of the disks in a big disk farm, if the page had not already been loaded into physical memory.
Conceptually, the main memory is just a cache (some would call it L3. others L4) and the actual data is stored somewhere on the rotating disks.