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A brief history of synthetic biology

Abstract

The ability to rationally engineer microorganisms has been a long-envisioned goal dating back more than a half-century. With the genomics revolution and rise of systems biology in the 1990s came the development of a rigorous engineering discipline to create, control and programme cellular behaviour. The resulting field, known as synthetic biology, has undergone dramatic growth throughout the past decade and is poised to transform biotechnology and medicine. This Timeline article charts the technological and cultural lifetime of synthetic biology, with an emphasis on key breakthroughs and future challenges.

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Figure 1
Figure 2: Examples of gene circuits reported during the foundational years of synthetic biology (2000–2003).
Figure 3: Examples of gene circuits reported during the intermediate years of synthetic biology (2004–2007).
Figure 4: Examples of gene circuits reported during the most recent era of synthetic biology (2008–2013).

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Acknowledgements

The authors thank T. Lu and J. Dueber for helpful discussions during the preparation of this Perspective article. This work is supported by the Howard Hughes Medical Institute.

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Glossary

Abstraction hierarchies

Organizational schemes that simplify the engineering process by describing building blocks according to modular properties, thus enabling the construction of increasingly complex systems. In synthetic biology, molecular elements that are categorized as 'parts' (which is the lowest level of the hierarchy) can be used to construct devices (which are parts assembled together to yield a desired function), which can, in turn, be further combined into systems.

Flux-balance analysis

A mathematical approach to simulate steady-state metabolism in a living system.

Forward-engineer

To move from an abstract description of a desired function to the physical implementation that produces that function. In the context of synthetic biology, it is the construction of genetic systems that produce a desired behaviour.

Logic gate

A device or system that carries out a Boolean logic operation by computing a set of digital inputs to generate a digital output; for example, a genetic circuit that activates gene expression only in the presence of a specified set of environmental signals would constitute an 'AND' gate.

Parts standardization

For an engineering discipline, the adoption of a widely used set of building blocks that have well-defined properties and modes of connectivity.

Reverse-engineer

To examine the constituent components of a system in order to understand their integrated function. In systems biology, this may involve making perturbations to a cellular network and then constructing a model that describes the relationship between the behaviour of the molecular components and that of the entire system.

Systems biology

An interdisciplinary approach that attempts to develop and test holistic models of living systems. A 'top-down' systems approach uses quantitative modelling to identify and describe the underlying biosynthetic and regulatory networks of a system, whereas a complementary 'bottom-up' approach attempts to model the systems-wide phenotypes that emerge from component interactions.

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Cameron, D., Bashor, C. & Collins, J. A brief history of synthetic biology. Nat Rev Microbiol 12, 381–390 (2014). https://doi.org/10.1038/nrmicro3239

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