Four billion years of evolution has yielded a biosphere packed with exquisitely optimised molecular components that enable life to evolve and thrive. Yet all of these components and systems are representatives of the last universal common ancestor (LUCA), a breakthrough organism that came to replace all alternative biologies. In the absence of the discovery of other biologies (on earth or beyond), it is impossible to establish universal principles and laws of biology. To paraphrase Carl Sagan, our biology, although amazingly diverse, is ‘provincial’, in contrast for example to the laws of physics, whose generality can be observed throughout the cosmos. I strongly support this Flagship Proposal for its ambition to go beyond the simple analysis and deconstruction of extant life and building ‘new biologies’ through modification, reconstruction and de novo construction and its promise of a fresh perspective and ultimately a better understanding of the unifying principles of living systems. The bottom-up construction of a synthetic cell with life-like properties like growth, heredity, division and evolution is in many ways the "moon shot" of synthetic biology. Comparable in ambition to the first genome sequencing projects, it will require input from chemistry, biology and physics and interdisciplinary collaboration across a wide range of disciplines. It will both stretch existing technology to the limit as well as create new ones including synthetic cells and tissues for uses in biotechnolgy and medicine. Finally, this new quasi-biological technology will provide fundamental insights into the inner workings of cells (and their origins) as well as present a foundational blueprint for the creation of evolvable nanostructures.
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