Recent decades have seen our understanding of biology and our technological capabilities develop at an astounding rate. From these advancements synthetic biology – a merging of complex biology and trusted engineering doctrine – has developed from a theoretical concept to an expansive discipline.
An interdisciplinary rationale
The rationale of synthetic biology fuses principles of biology, engineering, and computer science with the overarching aim of engineering biological systems with novel and practical functions. To this end, synthetic biology is rooted in the manipulation of biological systems in a standardised and systematic approach. This approach stipulates that maximum efficiency and reliability of a biological system can be attained in a manner akin to the output of an assembly line – by rationally engineering the system to perform a single function with as few auxiliary processes as possible (Garner, 2021).
The modular approach
From traditional engineering disciplines, synthetic biologists have adopted the concept of the modular component – a distinct and standardised part that can be independently designed, tested, and combined in various configurations. In a biological context, a functional component is encoded by a defined DNA sequence (referred to as the biopart) and can vary in complexity, but typically comprises a single protein or protein complex. Once defined, bioparts are catalogued in repositories for accessibility.
The modular approach is designed to facilitate rapid prototyping and iteration, accelerating the rate of scientific advancement and lowering development costs by minimising resource intensive trial-and-error. Vital to this is the incorporation of advanced computational models which enable the design and simulation of biological systems prior to their physical construction. When employed successfully, this approach enables the efficient construction of highly specialised biological systems whose potential applications are wide-ranging and far-reaching (Endler et al., 2009; Chandran et al., 2009).
Standardisation and simplification
Viewed through the lens of engineering, living organisms take the form of information-processing systems equipped with sensors, actuators, and code (Garner, 2021). As such, synthetic biology operates on the principle that a living system can be heavily modified or even designed de novo by utilising modular bioparts, preferably with as few “moving parts” as possible. It is from this perspective that the need for standardisation becomes evident. By standardising and cataloguing bioparts, they can be assembled first into functional systems in a predictable process with the aid of predictive software platforms (Khalil & Collins, 2010). The philosophy of standardisation extends even into the external environment, which supplies and modulates any biological system within and is therefore rendered a form of component in itself. Once defined and catalogued, an environment is referred to as a chassis and can be retrieved for use as a basis in the modelling and assembly of modular systems (Garner, 2021).
Furthermore, standardisation goes hand-in-hand with simplification. A common tenet of engineering is that minimising the number of components required for proper functionality of a specialised system helps to maximise its efficiency and reliability. This principle has given rise to proponents of the minimal cell and cell-free approaches, both of which aim to radically and maximally simplify the machinery present in a biological system designed for the biosynthesis of valuable substances, even to the point of removal of the cell membrane in the latter (Yue et al., 2019).
Bioengineering and synthetic genomics
Bioengineering and synthetic genomics constitute two approaches of synthetic biology through which the implementation of modular bioparts and simplified systems is achieved. Of the two, bioengineering is the more standardised and widely adopted, focusing on the design and implementation of novel components and pathways (Khalil & Collins, 2010). This is typically achieved by the modification of existing organisms, for example for the output of biosynthetic products on an industrial scale. The synthetic genomics approach differs in that it is centred around the use of genomes which are artificial in large sections or, in some projects, in their entirety (Gibson et al., 2010; Zhang et al., 2020). Although not yet utilised at scale, synthetic genomes show promise for powerful applications. For example, investigations are underway into their use as minimal “chassis genomes” (not to be confused with the environmental chassis) which can be rapidly built upon with bioparts for the introduction of new functions (Sung et al., 2016).
An evolving domain
A fusion of established principles and methodologies, synthetic biology continues to adapt and advance as a discipline in its own right. The continued incorporation of new technologies and approaches is of vital importance if the field is to achieve its extensive aims and be truly applicable in the face of real-world challenges. A critical question however that underpins the research approach predominantly being adopted, is whether the disciplines used successfully in engineering and software transfer to the reality of how biology functions. Is the delivery of targeted biological function feasible by deploying a modular approach of assembling the parts? Time will tell but the teachings of evolutionary genomics suggest otherwise.
