Thinking about human systems integration is thinking human, system and human-system for designing and organizing system of systems from human-machine level to socio-technological level. For critical human in-theloop systems there is a strong need of reliability and consistency from modeling, development and life cycle systems. A main epistemic issue rises: does it exist a conceptual framework, both theoretical and experimental, that ensures reliability and consistency of human system integration design and organization? According to the Italian Renaissance painting perspective principles invention, our paper puts in perspective human systems integrations from theoretical biology to systems sciences, and it presents an isomorphic framework for modeling human systems integration especially adapted at the human machine level, for medicine, defense and aerospace.