I once found myself in the simulator building with 2 hours to spare before my 747-400 detail. Decided to look at some of the other machines. The sim engineers said the 747-200 wasn't needed for a while and that I could have a play if I wanted. Had a good look at the F/Es panel and figured out what was what. To cut a long story short, I managed to start it up, taxi out and fly a couple of circuits, finishing off with a half decent landing.
So to answer your question: Yes it would be possible to 'fly' one of these jets without an F/E (but I'm sure that the AFM requires three crew) so to 'operate' one properly one needs a trained and qualified guy or gal in each of the three seats.
On the other hand, Charlton Heston managed it in Airport 1977 so it must be OK!