Five hard truths for synthetic biology

Can engineering approaches tame the complexity of living systems? Roberta Kwok explores five challenges for the field and how they might be resolved.

Roberta Kwok

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To read some accounts of synthetic biology, the ability to manipulate life seems restricted only by the imagination. Researchers might soon program cells to produce vast quantities of biofuel from renewable sources, or to sense the presence of toxins, or to release precise quantities of insulin as a body needs it — all visions inspired by the idea that biologists can extend genetic engineering to be more like the engineering of any hardware. The formula: characterize the genetic sequences that perform needed functions, the 'parts', combine the parts into devices to achieve more complex functions, then insert the devices into cells. As all life is based on roughly the same genetic code, synthetic biology could provide a toolbox of reusable genetic components — biological versions of transistors and switches — to be plugged into circuits at will.

Such analogies don't capture the daunting knowledge gap when it comes to how life works, however. "There are very few molecular operations that you understand in the way that you understand a wrench or a screwdriver or a transistor," says Rob Carlson, a principal at the engineering, consulting and design company Biodesic in Seattle, Washington. And the difficulties multiply as the networks get larger, limiting the ability to design more complex systems. A 2009 review¹ showed that although the number of published synthetic biological circuits has risen over the past few years, the complexity of those circuits — or the number of regulatory parts they use — has begun to flatten out.

Challenges loom at every step in the process, from the characterization of parts to the design and construction of systems. "There's a lot of biology that gets in the way of the engineering," says Christina Agapakis, a graduate student doing synthetic-biology research at Harvard Medical School in Boston, Massachusetts. But difficult biology is not enough to deter the field's practitioners, who are already addressing the five key challenges.

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