Nature editorial on synthetic biology
Ten years of synergy
It was an eclectic crowd of engineers, chemists, computer scientists — and, yes, a few biologists too — that gathered in Irvine, California, in November for the US National Academies Keck Futures Initiative discussion on the future needs of 'synthetic biology'. Their very definitions of the field were correspondingly divergent. But when pressed to focus on concrete examples, most discussion groups, at one point or another, pointed to a defining pair of experiments in tailored gene regulation that were published on 20 January 2000: the first synthetic biological oscillator — the 'repressilator' (M. B. Elowitz and S. Leibler Nature 403, 335–338; 2000) — and a bistable gene-regulatory network, or 'toggle switch' (T. S. Gardner et al. Nature 403, 339–342; 2000). So those in the field may not agree on what it is, but they seem to know when it started.
Since then there have been ten years of vibrant interdisciplinary science, and much public discussion both in policy circles and in the media. No such fame could have been predicted at the outset. 'Synthetic biology' was not a common phrase, and many considered the gadgets merely practical extensions of genetic engineering at best, or irrelevant tricks at worst.
Both of those pioneering experiments transposed two great traditions of physics to biology: first, to understand something one must build it, and second, start from the simplest imaginable principles. These directives have set the basic-science agenda for synthetic biology: to design, and thus define, the minimal systems sufficient to produce a given function. As this multidisciplinary field grew, practitioners envisaged bolder applications, such as building collections of interchangeable parts and devices, and transforming microorganisms into factories for biofuels or drugs.
Bringing these applications to reality has proved much harder than was originally hoped (see page 288). But the difficulties have proved instructive. Indeed, the decade-old papers raised several new and fundamental issues in biology, for example by pointing to the crucial role of noise in gene expression, both as a nuisance and as a great computational opportunity. It is now an active area of research.
More importantly, the difficulties encountered when building such basic circuits announced the demise of intuition as a reliable guide to biological understanding. It took endeavours in synthetic biology to illustrate what systems biology perhaps should mean: to enlist mathematical formalism in producing biological insights that are beyond the reach of mere intuition. In that aspect, synthetic and systems biology now seem indissociable, a theme illustrated by the selection of 'synthetic systems biology' papers published in Nature over the past ten years, and gathered in this week's web focus (http://go.nature.com/Dq38zq).
Undoubtedly some strands of synthetic biology are media friendly and run the risk of hype. But it is not an overstatement to say that the potential of synthetic biology remains enormous: clean and sustainable biofuels, cheap drug production and synthetic organs are just a few of the applications that have been advanced, albeit through small, painfully incremental steps, in the past decade. Full realization of such elating prospects demands patience as well as the efforts and ingenuity of a rich diversity of biologists, physicists, chemists, mathematicians and engineers.
New gadgets will not be the only outcome. One goal of synthetic biology is to synthesize larger and more complex biological systems, as exemplified by the quorum of genetic clocks displayed by Tal Danino et al. in this issue (see page 326). As it develops along this and other paths, synthetic biology itself will demand more by way of new fundamental biological knowledge — quantitative, systematic, computational and biophysical. And conversely, one of the deepest lessons from these first ten years is that biological knowledge will require synthetic approaches if it is to become a mature and reasonably predictive science.