evolving engineering

TheScientist | After 10 years of tinkering with biological circuits, we need to explain—once again and clearly—the rationale for doing synthetic biology. Despite the musings of some, the field is not limited to toy projects. Metabolic engineers have clearly articulated their goals of manufacturing cheap alkane fuels and much-needed drugs, such as the antimalarial drug artemisinin.¹ (See “Tinkering with Life.”) But for building DNA nanostructures or whole bacterial genomes, the rationales have been less clear—initially confined to cartoonish shapes and watermark sequences, respectively. Recent advances, however—such as a DNA nanostructure that combines cell targeting, molecular logic, and cancer-fighting ability², and a new E. coli genome well on its way to possessing multivirus resistance³—have demonstrated the discipline’s incredible potential.

Much of the progress can be credited to engineers who have developed a deeper appreciation of life’s power. While synthetic biology has brought a welcome injection of rigorous engineering principles to biology, including hierarchical abstractions, computer-aided design (CAD), and interoperable parts, biological mechanisms also offer some distinctive qualities of their own—a handful of underexploited strategies previously rare in engineering fields, such as replication at low cost and natural selection.

In just 6 years, researchers have reduced the cost of genome reading by a millionfold, and we are now accomplishing a similar effort in writing DNA—thanks to a new technique for harvesting synthetic oligonucleotides from chips, which can generate 60 million linked bases for just $900.⁴ Moreover, we can now create expansive genetic libraries, generating billions of genome variants per day using targeted mutagenesis. Those combinations can then be pitted against each other in an evolutionary footrace, allowing researchers to quickly ferret out the good gene combinations—for example, those that yield high levels of a desired compound—from the bad.

Biologically inspired devices also offer other advantages that may increasingly allow them to compete with silicon-based electronics. DNA is over a billion times more compact per bit than the densest electronic storage or Blu-ray Disc, and polymerase steps are 10 million times more energy efficient than conventional computer unit operations. Indeed, these properties are allowing hybrid bio/optical/electronic systems to grow in diversity and complexity (See, for example, “The Birth of Optogenetics,” The Scientist, July 2011).