(A) The photon budget creates a tug-of-war between different desirable optimization strategies in photonic imaging. Whereas the ideal imaging experiment would push the limits of each property on the corners of the tetrahedron, the finite size of the photon budget sets a fundamental limit on the combined optimization of all four corners. Pushing one corner to its extreme limit implies giving up on the performance of the others. (B) The (epi)-genome contains all the information necessary to produce an entire organism. However, characterization of the functional output of the genome requires the ability to monitor multiple observables simultaneously. These include nuclear architecture, dynamics, occupancy by regulatory factors, and the biological output. Current technologies (showing here only a small number for simplicity) hardly accomplish a subset of these tasks in a single experiment.