From Robust Synthetic Biological Parts to Whole Systems: Theoretical Practical and Ethical Challenges

Synthetic Biology is a new research field which aims in designing new or modifying existing biological pathways in order to produce systems with superior or different properties, usually for a novel application. In the related field of systems biology, it is recognized that it is impossible to infer the biological network behaviour by just listing its components but rather the whole feedback mechanism linking them needs to be considered; the same is true in every Synthetic Biology design. However, these designs need to be implemented inside a cellular environment and a major challenge that synthetic biology has to face is that the effect of the interactions of the new pathways with the cellular environment need to be taken into account during the design or redesign process. This is unlike any other engineering design procedure, such as electrical circuit or computer engineering design, where the behaviour of simple parts (e.g., resistors), of more complicated components (e.g., transistors) or even of whole systems (e.g., complete circuits) can be predicted (and eventually measured and verified) efficiently after implementation. Therefore this poses a challenge to engineering and mathematics. At the same time, many engineering disciplines, such as control and computer engineering, have for years been dealing with the analysis and design of complex systems that have to operate in uncertain environments in a robust way and therefore have a lot to contribute towards this major challenge in Synthetic Biology: how to construct biological modules, whether these are parts, pathways, artificial cells or cultures/tissues with performance guarantees within an uncertain environment. The proposed network in Synthetic Biology will bring together people working in Synthetic and Systems Biology as well as systems/control, electrical, chemical and computer engineers, physicists and mathematicians to address the theoretical and practical challenges of creating robust biological networks that can function inside uncertain biological environments, all the way from parts to whole systems. The network will also focus on ethical, societal and economical concerns that are raised by advances in Synthetic Biology, creating a fruitful discussion on how such concerns can be balanced by the potential usefulness of the many applications, such as environmental cleanup and fuel generation. Legal and other measures that need to be taken in order to ensure that Synthetic Biology research outcomes are not used against society and risk safety of the social structure will be proposed.

Synthetic biology is a rapidly developing research field that aims to design new or modify existing biological circuits for achieving diverse functionality for a particular application. Its objectives resemble those of other engineering disciplines, e.g., electrical and systems engineering, but Synthetic Biology currently faces a number of challenges that make it unique. One of the main differences from traditional engineering design disciplines is that every proposed modification or new pathway needs to be implemented inside the uncertain environment of the cell and therefore has to perform irrespective of the uncertainties, disturbances or unmodelled dynamics of the biological environment. Also, the lack of measurement devices to monitor its performance means that it is difficult to understand how a designed system operates or, more importantly, why it fails. Moreover, there are a number of ethical, economical, legal and other concerns that Synthetic Biology research raises, however beneficial some of the early findings may be. This Network in Synthetic Biology will bring together control/electrical/computer engineers, biologists and researchers from the social sciences and humanities to exchange ideas and expertise and to discuss how to robustly design, implement and evaluate the performance of biological devices, all the way from simple oscillator circuits to whole systems. In three 3-day annual workshops we will discuss this challenge at various organizational levels, as well as the ethical, philosophical, social, economical and legal consequences of research in this area. Co-funding provided by EPSRC, AHRC and ESRC under the Networks in Synthetic Biology initiative.