Drew Endy

Massachusetts Institute of Technology, Cambridge, USA

A biological engineer searches for simplicity.

Several years ago, a good colleague suggested that I read about a discussion held in 1864 on nuts and bolts (J. Franklin Inst. 77, 344–351; 1864). The focus was a paper by one William Sellers that argued for the adoption of a uniform system of screw threads — 60° angles, squared off along the edges.

Machinists across the United States eventually started producing nuts and bolts according to Sellers' scheme. As a result, hardware stores now offer a wide selection of standardized parts that can be used in combination and behave as expected.

Inspired by this example and others, I have been studying how synthetic biological parts might be made as regular and easy to use as Sellers' nuts and bolts.

The starting complexity of nature has led some distinguished researchers to doubt such work is practical. But given that there has been little research on manufactured bio-simplicity, this seems premature.

And there are examples: a team at the California Institute of Technology in Pasadena recently developed a uniform system for engineering simple biological switches made from ribonucleic acids (M. N. Win and C. D. Smolke Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0703961104; 2007).

The 'nuts and bolts' of the switches are RNA sensor and actuator domains. The method for combining any sensor domain to an actuator domain through a third communication domain provides the 'uniform screw threads'. Because such switches are produced by a standard process, many switches could be quickly programmed to control diverse cellular functions in response to myriad molecular inputs, from small molecules, to peptides, to nucleic acids.

I suspect that further efforts to engineer biological simplicity will have similarly powerful results.

Discuss this paper at http://blogs.nature.com/nature/journalclub