I recently found out the British Avro Lancaster only had a single pilot at the controls with a flight engineer sitting next to him who had no flight controls. The Lancaster would perform long range, strategic bombing from England against Germany especially at night with missions that ran long for over 8 hours. How did a single pilot with no modern autopilot (meaning hand flying the entire time) manage such long missions? What happened when the pilot needed to relieve themselves, or eat, or got tired? And finally, do we have any sense for how many losses of Lancasters were caused purely due to pilot fatigue?
I am not sure what you mean by "no modern autopilot," but the Lancasters and other RAF heavy bombers were equipped with an autopilot that could maintain a heading and altitude. Such equipment was pretty much standard in multiengine aircraft of the time. If you read accounts of Bomber Command missions, the autopilot is normally referred to as "George."
Those same accounts will also often point out that another crewman, usually the flight engineer, had received rudimentary training in flying the aircraft, if only from a safety-minded pilot. Note that the flight engineer on a Lancaster did not just mind gauges but had duties with respect to the throttle and flaps. On the other hand, unlike many of his USAAF counterparts, the Lancaster flight engineer was not a gunner and so did not have to hop into a turret when enemy aircraft were expected.
Indeed, an autopilot and another crewman trained as a backup pilot who could at least get the aircraft back to friendly territory (if not land) were part of the "New Deal" whereby Bomber Command convinced itself in 1941-42 that its heavy bombers could be safely operated by only one pilot.
So between "George" and the flight engineer or other ersatz co-pilot, the pilot could take short breaks, and the crew had some hope of survival if the pilot became a incapacitated during a mission. Moreover, the pilot did not have to keep his hands on the controls the entire time.
One thing to keep in mind when thinking about the pilot's workload is that the RAF's heavy bombers typically flew at night but did not have to maintain formation like the USAAF's heavy bombers did.
Denis Richards, RAF Bomber Command in the Second World War: The Hardest Victory (1995) covers the decision to assign only one pilot to each heavy bomber and the requirement for an autopilot and backup pilot.