Mathematician Robert Rosen tackled this question but reframed it in the process. In his 1991 book, "Life Itself", Rosen suggests that a better question is, "Why are organisms different than machines?" His answer addresses the unfractionability, or self-causing unity, of life; he states "a material system is an organism if, and only if, it is closed to efficient causation." The supporting work behind this definition of life embodies his "relational theory of systems". The scientific paradigm behind this theory represents a radical departure from the mainstream mechanical and reductionist paradigm dating back to Newton and Descartes.
Theoretical ecologist Robert Ulanowicz builds on work by Rosen and others to develop a comprehensive "ecological metaphysic". In his book, "Ecology, the Ascendent Perspective", Ulanowicz develops an ecological metaphysic and contrasts it with the older, mechanical Newtonian counterpart.