30 September 2016
Synthetic biology has been described as both an “extreme” form of genetic engineering that threatens to wipe out humanity and as a panacea that will cure diseases and solve global problems from climate change to world hunger. It encompasses other innovative techniques such as CRISPR-Cas9 gene editing and enables controversial projects such as the creation of artificial life and the Human Genome Project-write. Furthermore, synthetic biology was identified in 2013 as one of the eight great technologies that would propel the UK to future growth. There is certainly a lot of hype - both positive and negative - but what is the reality?
Synthetic biology - hot or not? View the full infographic here
Synthetic biology is essentially the application of engineering design principles to biology. It can be defined as the design and construction of novel biological functions or systems where they do not exist as well as the redesign of existing biological systems for useful purposes. The emergence of synthetic biology has been driven by the development of commercially available and inexpensive, rapid and reliable methods for DNA sequencing, editing and synthesis.
Synthetic biology works by putting together biological parts in new ways to create novel functions.Parts are sequences of DNA that code for basic biological functions (e.g. promoters, protein coding regions) and are either derived from existing organisms through genetic engineering or synthesised from scratch. Complex functions are created through assembling multiple parts to create devices, and then combining these in host organisms to produce synthetic biological systems. This is similar to the components, logical circuits and devices used to build a computer, with the DNA sequence rather than software telling synthetic biological systems what to do.
Synthetic biology is coming up with innovative solutions for the treatment of some of the most challenging diseases. It promises to advance personalised medicine by offering earlier detection of disease and more effective targeting as well as customisation of therapies. For example, a key obstacle for cancer treatment is effectively killing cancer cells whilst keeping surrounding healthy cells intact. T-cells have been engineered to express specific receptors allowing them to precisely do just this. Theranostic devices are another emerging application - these are biological circuits that couple detection of biomarkers to the production of a therapeutic response –thus combining diagnostics with therapy. They are designed to be hosted in cells and implanted into patients, where they can switch on at the first sign of abnormality and act on endogenous metabolic networks to restore and maintain normal function, eliminating the need to visit a clinician. The acceptability of this type of continuous autonomous therapy remains to be seen. Similar technology is being used to combat antimicrobial resistance and synthetic circuits have even been freeze-dried onto paper discs to create cell-free portable diagnostic bioassays for Ebola. Ultimately, the potential uses are only limited by the creativity and ingenuity of scientists to come up with ways of using synthetic biology to perform the useful functions that we want and need.
Synthetic biology is still an emerging technology and there are some important issues to overcome before these applications (most of which are in the preclinical testing stages) reach the clinic – primarily stemming from the intrinsic complexity of biological systems. Although a fundamental engineering principle brought to synthetic biology is that of rational design, biology is unpredictable and cells are constantly adapting and evolving often resulting in a laborious, and costly, trial and error design approach. Researchers, are working to address this challenge by improving standardisation of biological parts, in order to build libraries of well-characterised parts that can be selected and assembled in a plug and play manner. Biological unpredictability also raises important safety issues when considering the use of synthetic devices in humans, where they can interact with host metabolism. However, the beauty of synthetic biology is that it allows for “safety by design”, that is safety mechanisms such as “kill switches” can be built into devices. Until synthetic biology technologies are proven to be predictable, reliable, safe (and economical) - no trivial feat - we are unlikely to experience the practical benefits.
Synthetic biology is currently covered under existing EU directives and UK regulations on genetically modified organisms (GMO). However, while GMOs usually only involve engineering of a single function, synthetic biology can introduce multiple complex functions within a single system. As the field progresses and new applications arise, new regulations will certainly be needed. Legal issues relating to patentability of biological parts and innovations also need to be addressed.
The ethical concerns around synthetic biology broadly echo those of genetically modified organisms, with the additional fears that seem to surround all discussion of artificial life – fears that hinge on exaggerated claims about risks to biosafety, bioterror and uncontrollable new life forms that might be on the horizon despite current technological limitations making these unrealistic. It is encouraging that the UK synthetic biology community is developing a framework for responsible research and innovation in the field which involves public engagement and anticipation of the implications of current research but sensible perspective is required.
Synthetic biology certainly has disruptive potential in healthcare and the pace of progress is rapid. We are now approaching the stage when applications are on the verge of moving out of the lab and entering the clinic but there are huge technical hurdles relating to safety and scaling up that need to be overcome before this potential is realised. Perhaps a greater challenge will be to ensure that a transparent regulatory framework, based on robust scientific evidence regarding the potential harms and risks, develops at a pace to match this burgeoning field.