AUTHOR=Budisa Nediljko , Levin David B. TITLE=Historical paradigm shifts in defining life: from spontaneous generation and vitalism to the Pasteurian Wall and the quest for artificial creation JOURNAL=Frontiers in Synthetic Biology VOLUME=Volume 3 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/synthetic-biology/articles/10.3389/fsybi.2025.1692648 DOI=10.3389/fsybi.2025.1692648 ISSN=2813-818X ABSTRACT=For much of recorded history, the question “Where does life come from?” was answered with certainty: Aristotle’s doctrine of spontaneous generation and staged “ensoulment” defined both natural philosophy and Christian scholasticism. Life, in this view, could spring from nonliving matter, and human personhood emerged only after a gradual developmental process. The Scientific Revolution began to unravel this consensus. Lavoisier’s chemistry embedded life within universal physical laws, while the invention of the microscope exposed previously invisible worlds. Science often advances through profound epistemic ruptures, not gradual accumulation. Individual discoveries acted as paradigm shifts that, together, constituted a non-Kuhnian revolution, redefining humanity’s understanding of nature. This study explores how successive revolutions in methods and technologies transformed both scientific and societal understandings of life’s origins. We distinguish four dimensions of their impact: technological (new instruments and techniques), ideological (emergent political and social philosophies), cultural (changes in art, literature, and everyday thought), and epistemological (shifts in what counts as knowable or real). Our analysis focuses primarily on the last, how each technological advance reconfigured the boundaries of knowledge itself. The chemical revolution, from Lavoisier’s demolition of phlogiston to Wöhler’s synthesis of urea, progressively undermined vitalism by showing that “organic” substances obey the same principles as inorganic matter. Pasteur’s swan-neck flask experiments overthrew the millennia-old assumption of spontaneous generation and enshrined omne vivum ex ovo (“all life comes from an egg”) as biological dogma. Yet these advances built new intellectual boundaries, culminating in what we term the Pasteurian Wall, a barrier that has constrained experimental abiogenesis and remains unbreached today. By tracing these historical transformations, we show how revolutions in methods and technologies both expand and restrict the scope of inquiry, reshaping not only what we can investigate, but how we imagine life, its origins, and its possible artificial creation.