To Circuitry and Beyond

Abstract

This issue of Cell Systems explores the variety and diversity of the synthetic biology community and how its different strains of thought connect to other fields. With an eye toward the future while acknowledging the past, we asked a host of synthetic biologists what they consider to be the future of circuit engineering. Their responses—all 21 of them—provide a fascinating glimpse into how biology and engineering disciplines are converging and just why whole-system thinking may prove to be a fruitful means of addressing long-standing problems.A convenient starting place in a discussion of synthetic biology is the electronic circuit. Many self-identified synthetic biologists come from an intellectual lineage of electrical and computer engineering. The allure of thinking about genetic and biochemical circuits in terms of input-output relationships, reusable components with rigorously defined spec sheets, and catalogs of bricks and parts to be combined at will was a powerful siren song that fueled justifiable early excitement in the field. But as every budding engineer—and molecular biologist!—soon finds out, solutions to real-world problems are constrained by technological limitation and incompleteness of knowledge, especially for complex systems.Many of our respondents confirm that circuits and their design will continue to feature prominently in synthetic biology. But at the same time, they caution that electrical and biological circuits are not directly parallel. Their diversity of responses paint a picture of the nature of this schism. First, our respondents contend that fields seeking to engineer biology must push past the electronic circuit paradigm in order to enable real-world applications, especially human therapeutics (Voices, pp. 370–372). Next, many people noted that building biologically realistic circuits will require embracing the constraints and principles of variation, environment, evolution, and ecology. Lastly, the field of synthetic biology is poised to move beyond gene circuits and gene expression as an actuator, to take advantage of other biological processes, such as metabolism or chemical modification. It would be wise indeed to heed the lessons emerging from synthetic biology’s early years and let these new substrates dictate design rules and enable new functionalities.To foster an on-going dialog and to give each of our respondents a sufficient share of the spotlight, we are publishing a set of nine Voices comments this month (pp. 370–372) and will be publishing the others over the next two issues of the journal. Would you like to add to the discussion? We are issuing an open call for Letters to the Editor, Commentaries, and contributions to our Cell Systems Call series, which highlights papers recently published in other journals (Cell Systems Call, pp. 366–369; See also Editorial in Cell Syst. 1, 307). Submit these directly online or contact the editorial team at systems@cell.com for more information.Also this month, we are beginning the first of several expansions of our editorial board. We enthusiastically welcome eight new board members: Matthew Chang, Domitilla Del Vecchio, Paul Freemont, Martin Fussenegger, Michael Jewett, John Rogers, and Christina Smolke. Their interests and expertise include biosensors, control theory, RNA circuits, bio-based production, cell-free systems, cell-based therapies, and bioelectronics, although many of their interests overlap. As with other editorial board members, they will provide high-level strategic advice and a sounding board for the editorial team. What will not change is that all manuscripts will still be handled by our in-house team of full-time editors, who remain, as always, providers of what we hope is valuable service to and for the scientific community.Contemporary synthetic biology as a field is poised for growth, proliferation, and differentiation. In fact, at Cell Systems, it is our belief that many investigators, departments, and institutions that may not self-identify with “synthetic biology” fall under the overarching umbrella of convergence now underway between biology and engineering disciplines. In this respect, we all—synthetic, systems, and other types of biologists—recognize that the paradigms that have structured our lines of research in the past must change as we learn more about the complexities of living systems. We at Cell Systems aim to foster such pushes into new frontiers and beyond.