Prof Richard Kitney, Co-Director SynbiCITE

It is almost a decade and a half since Tom Knight introduced the concept of BioBricks, or standard biological parts, which can be combined to form a gene circuit. Coupled to this has been the development of the hierarchical concept derived from engineering that biological systems can be created from standard biological devices and standard biological parts (e.g. BioBricks or BioParts).

What can engineering teach us?

The other concept widely used in synthetic biology is ‘design, build, test and learn’, the synthetic biology design cycle^[1]. Many of these ideas are derived directly from engineering science and its application to electronics and other fields. Such models have sometimes led to significant criticism by members of the biological community, who point out that biological systems are much more complex than electronic systems.

This criticism is not completely valid though. Professional design engineers would never argue that a complicated electronic circuit can be built simply by combining standard components. The whole approach of combining standard components is far more complex than such a simplistic interpretation. In synthetic biology it is interpreted in the context of the tenets of modularity, characterisation and standardisation. The use of standard components is only part of the story. Much of the work in circuit design revolves around the effective interfacing of the sections of the electronic circuit, often described as “stages”, which comprise standard components. This is not to mention such issues as fabrication and optimisation.

Biodesign in the bioeconomy

Recognition is growing of the importance of bio-design in the context of the bioeconomy and there are a of number of international reports stressing the importance of the bioeconomy in relation to economic growth^[2][3]. Synthetic biology, the engineering of biology, is seen as a key driver in the future growth of the bioeconomy through industrial translation.

Following a well-established path

Electronic circuit and component design went through various stages in its evolution from the single transistor to the Intel Core i7 with 1.4 billion transistors in 2012, a period of 65 years. The development path involved increasing levels of modularisation, characterisation and standardisation - coupled to more and more automation and the application of business process management techniques involving sophisticated quality control and quality assurance procedures in the manufacturing process. What underlies such an approach is the need for a high level of reproducibility. I would argue that in the process of industrial translation from the lab to the factory, synthetic biology will go through a conceptually similar process.

Automation will improve results

Whilst liquid handling robots have been available and used for some time, it is really only with the introduction of DNA foundries and the associated workflow that automation is being much more comprehensively applied in synthetic biology using integrated workflows. Such an approach will force the use of standard operating procedures and the more rigorous experimental design. These steps are essential for the levels of reproducibility necessary for industrial translation. Another advantage of the foundry approach is being able to undertake many parallel experiments to optimise a particular gene circuit design. Unlike electronic circuits, where the components are joined with wires, in biological constructs there are no wires, only a biological medium. The physical configuration of the components can therefore make a very significant difference to the operation of the circuit. In the future, such optimisation may well be possible using computer design software; however, at present, the ability to undertake parallel runs of multiple configurations and components is a fairly effective method of optimisation.

Accelerating progress

Although it took 65 years from the development of the transistor to the Intel Core i7 chip, progress in the engineering of biology is likely to be more rapid. The field is sometimes referred to as digital biology. If this is the case then many of the techniques and processes developed in the information and communication technology (ICT) revolution over the last fifty years can be modified and applied in synthetic biology. This has another advantage for entrepreneurial scientists - investors understand the digital world.

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[1] Synthetic biology – A Primer (Revised Edition) Freemont and Kitney – Imperial College Press

[2] Biodesign for the Bioeconomy https://connect.innovateuk.org/documents/2826135/31405930/BioDesign+for+the+Bioeconomy+2016+DIGITAL+updated+21_03_2016.pdf/d0409f15-bad3-4f55-be03-430bc7ab4e7e

[3] Industrialization of Biology: A Roadmap to Accelerate the Advanced Manufacturing of Chemicals – http://www.nap.edu/catalog/19001/industrialization-of-biology-a-roadmap-to-accelerate-the-advanced-manufacturing