Inter-species differences in the development, physiology, and pathology limit the utility of animal models in the study of human disease and development of new treatments. Human-focused researchers therefore have a strong need for realistic, human-derived tissues and mini-organs that can be studied in culture. The shortage of transplantable organs, and the desirability of having perfect immune compatibility between transplant and host, creates an additional demand for production of human tissues and organs from patient-specific stem cells especially for commonly transplanted organs such as the kidney. Typical approaches to making human tissues work by exposing pluripotent stem cells (e.g. hiPS cells) to a sequence of signalling environments that mimic what cells would experience in an embryo, if they happened to end up developing into the desired tissue. The result, when the procedure works, is the differentiation and self-organization of cells into tissue elements that are anatomically and physiologically realistic at a micro-level, but the system is symmetrical (the same everywhere), and lacks macroscopic (organ-scale) organization. Kidney tissue produced this way, for example, produces multiple nephron and collecting duct tubules with none of the natural organization of the kidney around a single collecting duct tree, and no exit ureter. We have been using murine and human renal systems to explore the reasons for this limitation. Careful analysis of embryonic development has identified localized cues that break the symmetry of the naturally developing system. We have designed renal differentiation systems to include artificial versions of these symmetry-breaking cues, and ave shown that their inclusion greatly improves the realism of the result. Instead of producing jumbled renal tissues, these systems can produce mini-organs with cortex and medulla, proper organization around a single collecting duct tree, and a urothelial exit tube. We have also used fluorescent tracers to verify that these mini-organs show realistic tubular transport physiology, and have used reporter genes to enable cultures to report automatically their exposure to nephrotoxic compounds in a blind-coded screen. This lecture will conclude by indicating how its concepts can be extended to other systems and also how the science of synthetic biology can be used to extend further the capabilities of tissue engineering.