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About synthetic biology research

Synthetic biology research and development has three defining characteristics. These are:

  • Knowledge-based design
  • Biological systems engineering (that will normally result in a modified biological outcome that does not occur without intervention in nature)
  • A defined translational application

Synthetic biology research is closely linked with, and often dependent upon, three principle types of underpinning research which:

  • Develop the knowledge base that informs SB design
  • Develop biological resources and toolkits for SB engineering
  • Develop data systems, bioinformatics, and modelling tools to support the Knowledge and Design components of SB

The safety of synthetic biology: Safer by Design

Fears are generally excessive and misplaced. But it is up to us to explain this and why, not simply to carry on and ignore the people who ‘don’t get it’. This is not the beginning of the opportunities to make new and terribly dangerous bacteria. This was possible (and has been done) long ago by microbiologists working for multiple governments behind closed doors – and never has so much work been done that could underpin people doing terrible things than in recent years in the name of ‘biodefense’. Whatever horrible thing you might like to imagine as a plot for a thriller has quite probably already been done somewhere, if it is possible to do it. The people who have done this, and who might do so – are not the ‘synthetic biologists’. And, the only reassuring thing about all of this is that nobody has used these things – except to horribly contaminate a small Scottish island with anthrax.

It is true that the field is lacking in useful guidelines in some areas. The existing definitions of what is and what is not an organism with pathogenic potential to people is somewhat more fuzzy than most people will imagine. It is also true that ethical and safe practices seem to differ substantially between institutions, countries, and companies –some of which probably far exceed the standard in academia, and some of which do not. These things and others need to be addressed, though the hazard and risks are lower than what I have just said might make some people think.

The most reassuring thing about synthetic biology is the fact that it is design-led and inherently predictive as to outcome. In the past, many studies have been performed in which one or more random changes have been made to remove genes, change genes, and variously change biological systems –without the slightest clue about what the consequences would be. The use of this type of screening experiment has been wide-spread and addressed many different biological processes and organisms, and perhaps surprisingly nothing has gone horribly wrong (if we ignore the cancer researchers who mutated themselves and got cancer, and other local casualties).

In bioprocessing and other areas that used bacteria people would simply look for a strain that did the closest thing to what was wanted that they could find. The background knowledge of its other properties, gene content, behaviours, and the risks that it might present were close to none. Now, we work with highly characterized strains, for which we have knowledge on all of the genes that are present, and can look for and when useful specifically remove genes that make them safer than anything similar that occurs naturally. This increasing background knowledge should not be a source of complacency, because ‘reduced risk’ is not necessarily ‘no risk’ – but it is a substantial improvement on what has been done for many decades previously.

In synthetic biology the changes are targeted, specific, and deliberate. They are based upon knowledge-based design in which the components used are applied to result in a clearly intended function, and this is subsequently confirmed – and intended outcomes or unintended consequences are identified. There are not mixtures of hundreds or thousands of unknown changes to be assessed by a range of relevant and not relevant tests for whatever might have happened (like before). Now there are a few deliberate changes, which are tested with highly relevant assays. This is inherently a much more rational and safer approach.

Also, the synthetic biology process, especially using the ‘synthetic systems biology’ approach has further increased safety consequences because multiple changes are being made that combine to take an organism further and further away from what nature and evolution has created as the most viable and survivable biological solution. What an industrial or other designed solution seeks to develop is a ‘biological component’ for a process with a number of process-determined properties. Changing just one aspect of the central behaviour and metabolism of an organism is likely to reduce its fitness in other contexts – although with single or closely clustered changed this cannot be assumed. But, when it involves multiple changes the cumulative effect will almost inevitably be a progressively less and less naturally fit, and less and less risky in all ways – including within the wider natural environment, in which it would be unlikely to prosper and survive. Life has already generated the optimum solutions – in the wider world the synthetic organisms would be uncompetitive and very unlikely succeed.

This is not to say that it would not be possible to specifically engineer something with increased fitness potential. But this is not the typical synthetic biology objective, and should be considered (and if necessary) regulated as a special case if it was appropriate (for example, a mosquito engineered to compete with the malaria transmitting species – which is not what we do). Typically, the synthetic biology objective is to create a strain of something which makes a lot of something useful and valuable, which past a certain level is usually poisonous to the cell making it, and the better it gets at doing this engineered thing – the more unfit for normal life it becomes.

The ethics of synthetic biology

Like any new technology, synthetic biology is feared by some, especially by those who do not have personal understanding of the underlying science and who have a general distrust of the corporations that are often involved, or the ‘big science industry’. The people with these concerns are not reassured by some of the language (and perhaps egos) involved in discussions of making new life, and also by concepts that are genuine aspects of the field about the lack of complete predictability of the behaviours of complex systems (of which cellular and environmental life is certainly an example) and ‘emergent properties’. To discount these fears as irrational or not worthy of consideration and engagement is not reasonable, because to the people that hold them they are not unreasonable in the context of their knowledge and experience. Equally, it is important to continuously consider any potential risks, to monitor and be aware of unexpected outcomes, and to protect both society (of which scientists are also part, we are not some other type of life) and our environment.

Just as we have a responsibility to be careful, responsible, professional, expert practitioners, we also have a responsibility to act for the common good when the opportunity to do so exists. New and sustainable economic activity and profit are not inherently bad things – especially when the proceeds of this activity provide jobs, pay for hospitals and social care, public services, schools, libraries, education, and all of the other vital elements of society. One of the important things about synthetic biology is not that it provides an alternative to industrial models, but that it provides much better new alternatives to the existing options. Ultimately, synthetic biology has the option to create many chemicals and materials, drugs, plastics, and many other things from raw materials that are derived from completely renewable resources (ultimately the sun and the rain); to be used to make products that are recyclable or biodegradable so that ultimately waste becomes fertilizer; to turn unsustainable industries based upon the exhaustion of limited non-renewable resources into new ones that do no harm; to avoid polluting chemical processes and petrochemical-based industrial processes; to create natural solutions to life’s problems – and even repair harm done previously, for example through bioremediation.

Life presents inherently sustainable solutions. It is not only the parts, processes, and systems that are useful to create new living systems and properties that matter. The example of biology itself is also important. Learning from life, and learning to work with and with sustainable living processes as a template for integrated cooperative processes, for closed loop recycling, and for the ways in which processes can be made to self-healing and zero waste are important not only to maximize the chances of new bioprocesses and products to be affordable and adopted, but also as examples of the ultimate ‘circular economy’. Life does not exploit any short supply non-renewable resources wastefully – and it illustrates that we do not need to either. The best and most viable synthetic biology solutions should mirror this.

It is the motives that matter. If a desire for profit is pursued without reference to other factors and peripheral risks and damage, that is wrong no matter what technology is used. That is not our objective. Our objective is to see the best ways to make the greatest positive difference using the new opportunities that the current state of the art in biology has to offer. Ultimately, there is a fundamental issue of trust. To deny this is foolish, and to attempt to justify what is done on the basis of power (by companies) or authority (by academic establishments or governments) is counter-productive – or at best ‘not useful’. Synthetic biologists must be prepared to discuss and explain, and when necessary justify not only what they are doing, but also why and how. This is not always possible for those working within the competitive commercial sector, where the release of critical information could lead to the loss not only of product and profit – but also possibly of good, desirable, new solutions to real-world problems. But, for those of us who can talk about at least some of our work – we must be prepared to openly do so. And, we must engage even when it involves saying things that are difficult and lead to further discussions with people who don’t understand or agree with us.

What is synthetic biology for?

The range of potential applications for synthetic biology is as wide ranging and diverse as life itself. Indeed, one of the challenges faced by synthetic biologists is prioritization and focus, when the options are so many, and the potential so great.

Our current areas of interest in Technologies for Gene Therapy are in the areas of:

  • Vector development for effective gene therapy
  • Assessing and avoiding the risks of gene therapy (genotoxicity)
  • Using the technologies of gene therapy to give new insights into cancer development

Our current areas of greatest effort in the area of Microbial BioEngineering are in the areas of:

  • The use of under-used and waste biomaterials from biomass and biodiesel manufacture
  • The generation of products currently derived from petrochemicals from natural non-polluting sources
  • The generation of bacteria to increase the performance (and hence longevity and reduce use) of cement
  • The generation of bacteria optimized for the production of clean proteins
  • The identification of new processes for the degradation of persistent environmental pollutants, including pollutants of water
  • Using resources developed for synthetic biology to investigate ways to address antibiotic resistance in medically important bacteria
We are exploring other areas, and are open to developing new lines of research that will make the best use of the strain and widely applicable tools for strain assessment and development, especially when they are directed at projects that have sustainability as part of what they seek to achieve.

What is new about synthetic biology?

Biotechnology, industrial bioprocessing, the development of strains of plants, animals, and microbes are not new. The ideas and a range of tools and approaches for molecular biology, genetic engineering, and a wide-range of experimental resources for synthetic biology are also not new. Thus, in this context and these terms, it is not immediately apparent why Synthetic Biology is described as a new, emergent, and disruptive technology – and a priority focus for national and international research strategies and investment.

What is new is the context in which these disciplines are being practiced. The experimental resources are progressing rapidly for genetic engineering, the scope for laboratory automation and accelerated research is developing quickly, but the most critical development is the information and knowledge context in which Synthetic Biology can be developed. It is not that any of the constituent concepts or components of Synthetic Biology are new, it is that the combination of technologies exist in a new context to which genome sequencing, bioinformatics, functional genomics, systems biology, evolutionary biology, population biology, metabolomics, and other essential foundations mean that the research community, expertise-base, and the tractability of a wide range of problems that were until recently simply intellectually, experimentally, and technologically inaccessible – are now possible. The primary reason that Synthetic Biology is new is because this context is new, and now there are opportunities to understand, work with, and develop living biological solutions to significantly improve upon and replace many aspects of currently unsustainable practices.