Synthetic biology has been significantly shaped by modular design principles through analogies to electrical and computer engineering. Although convenient, these parallels often break down in practice, and we are still largely unable to engineer sophisticated systems that behave as predicted. As nature has achieved robust and intricate programs without requiring strict modularity, we may want to revisit genetic circuit design approaches. Rather than pursuing modularity, we could aim for a robust and scalable design framework that embraces the uncertainty that context dependence brings to engineering in a biological chassis. Systems and control theory offer a starting point, but a substantial conceptual leap will be needed to quantitatively predict system behavior and establish flexible context-aware design processes. Only by overcoming these hurdles shall we be able to capitalize on synthetic biology in particular—and on biotechnology in general—for medicine, environmental engineering, and energy production.
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