Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields – evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation.

Many everyday dilemmas reflect a conflict between two moral motivations: the desire to adhere to universal principles (integrity) and the desire to improve the welfare of specific individuals in need (benevolence). In this article, we bridge research on moral judgment and trust to introduce a framework that establishes three central distinctions between benevolence and integrity: (1) the degree to which they rely on impartiality, (2) the degree to which they are tied to emotion versus reason, and (3) the degree to which they can be evaluated in isolation. We use this framework to explain existing findings and generate novel predictions about the resolution and judgment of benevolenceintegrity dilemmas. Though ethical dilemmas have long been a focus of moral psychology research, recent research has relied on dramatic dilemmas that involve conflicts of utilitarianism and deontology and has failed to represent the ordinary, yet psychologically taxing dilemmas that we frequently face in everyday life. The present article fills this gap, thereby deepening our understanding of moral judgment and decision making and providing practical insights on how decision makers resolve moral conflict.

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