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Recognizing that physics is now at an important turning point, the authors put forward ideas relating to the nature of space and its role in the emergence of gravity, inertia, mass and, ultimately, the ‘reality’ thatderives from (scientific) observation and measurement. The essay cites relatively recent experiments and observations relating to phenomena such as the Casimir Effect, Unruh Effect, Zitterbewegung and the results from the ‘moving mirror’ experiment. Itargues that, when combined with older problems such as quantum entanglement,thesephenomena provide new evidence that might informa better understanding of the role of space in its interactionwith particle/field entities. Furthermore, it suggests that space may have a significant role in the creation of these entities. The authors suggestthat fresh creativeinsightwill beneeded for physics to address the scale of the challenge implicitin this new, and exciting, territory. However, this is unlikely to emerge withoutrevising the philosophical frameworkthat underpins physics. This wouldneed to reconcile quantum ontologies with non-quantum ontologies that may be scale dependent.In order to meet the many emerging challenges a more open, participatory and permissivephysics is envisioned.