Our research effort addresses a major extension of the usual studies of quantum entanglement, allowing us to investigate both the nature of reality and the quantum measurement problem. Specifically, we will attempt to test quantum effects, for the first time, directly via the human visual system, using precise photon sources, new theoretical modeling and experimental paradigms to overcome perceptual limitations. In Phase 1 of this thrust, we will use true single-photon and N-photon states to investigate the single-photon response and visual sensitivity function of the human eye. In Phase 2 we will use human observers to look for differences between superposition and mixed quantum states. Initial modeling shows that we will be sensitive to slight deviations from standard QM predictions, allowing us to address the validity of QM in biological systems. Finally, in Phase 3 we will attempt a test of quantum nonlocality where one of the photon detectors is replaced by a human observer. Positive results for any of these experiments would be extremely significant; even 'non-surprising' outcomes would represent a major step forward in our ability to ask -- and answer-- questions about the nature of reality, the reality of nature, and the applicability of quantum theory beyond the atomic realm.