Dr Siobhan Yeats comments on the SynBio section of D5.1

Dr Siobhan Yeats, Director of Biotechnology at the European Patent Office (EPO) in Munich, read our report “Case Studies – Overview of Ethical Acceptability and Sustainability” with interest and sent us the following comment on the synthetic biology section. Siobhan also serves on the ProGReSS Advisory Board.

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SynBio represents a continuation of genetic engineering

A Commentary by Dr Siobhán Yeats, Director of Biotechnology, European Patent Office, Munich

There is no clear and generally accepted definition of SynBio that sharply delimits it from “ordinary” GM technology. SynBio is defined in the report as the engineering of biology in order to synthesise complex, biologically-based systems with functions that do not exist in nature. Engineering perspectives may be applied at all structural levels, from individual molecules to whole cells, tissues and organisms. The idea is to design biological systems in a rational and systematic way. Current research is directed, inter alia, to the development of minimal cells or genomes containing only basic essential functions, and to the creation of bioengineered microorganisms that can produce new medicines, biofuels and other products. The use of standardised parts that can be inserted into all kinds of cells to engineer them as desired is envisaged. 

The main issue is to what extent SynBio in practice really goes far beyond genetic engineering, as claimed in the report.  For the most part the report sets out what SynBio seeks to do, with less emphasis on what it has actually done up until now. Indeed, its far-reaching aims appear to be what really distinguishes SynBio from genetic engineering as it has been practiced for decades.  The actual achievements to date seem to represent rather a continuation of general genetic engineering, using the technical advances that have taken place in, for example, DNA sequencing and synthesis, rather than something going far beyond it.

The real issues to be considered seem likely to be determined by what has been done and what is likely to be achieved in our lifetimes. The concept of using standardised parts to engineer things in many types of cells is exciting, and it is not surprising that it has caught the world’s imagination. However, a bacterium is not like a car or a mobile phone, and a promoter that works in E. coli is usually inactive in a yeast or mammalian cell. The standardised parts approach may in the end be constrained by the natural limitations of biological systems. Likewise, minimal genomes have so far been created by stripping down natural ones, not by assembling artificial new ones.

No doubt the SynBio approach will lead to exciting new possibilities to produce substances in cells, such as biofuels. However, the question remains what is really new about this. Although SynBio seeks to produce new biological systems from scratch, results so far have involved adapting existing systems, not creating entirely new ones. The production of artemisinin in a yeast engineered to contain the artemisinin metabolic pathway, some dozen genes, was a tremendous scientific achievement by Keasling et al. and an important one for patients suffering from malaria. However, it seems debatable whether this represents a real paradigm shift. For several decades scientists have been engineering microorganisms and higher organisms to produce chemicals, or for use in bioremediation, by introducing genes encoding enzymes or even whole enzymatic pathways. One prominent case was the famous “golden rice”, which was engineered in the late 1990s to contain enzymes enabling the rice cell to produce beta-carotene.

In view of the interest SynBio has raised, a public debate on the issues mentioned in the report is necessary, and people must be heard and involved. However, virtually all these issues – risks of release, deliberate misuse, playing God, social justice – apply equally well (or not) to classical GM inventions, and they were discussed back in the 1970s and repeatedly since.

As far as the objection to playing God is concerned, human beings have been trying to improve on nature for thousands of years – none of today’s cultivated crops existed in their current form in nature, but they are rather the product of centuries of selective breeding. Genetic engineering speeds up the improvement process and enhances possibilities, but even it has not to date proved capable of creating “new life forms”.

Risks must always be considered, but they will depend on the kind of research to be performed. It hence seems most appropriate that risks should be assessed on a case by case basis, as mentioned in the report. Microorganisms with a minimal genome are likely to be non-viable in the wild, and if not they can easily be engineered to be so (by knocking out a gene encoding something essential that needs to be supplied in the culture medium, a time-honoured standard genetic method). Bacteria carrying numerous extra genes, such as those synthesising artemisinin, usually lose these genes rapidly in the wild, since the genes and their expressed protein products burden the cell machinery and are a disadvantage to it. So the problems associated with accidental release can easily be minimised and effective containment assured.

As for bio-terrorism, this cannot of course be ruled out, but there are plenty of natural pathological bugs available to terrorists, such as anthrax, that are much more likely to survive in the wild than artificial organisms created by SynBio for the reasons above. Indeed there is some concern about growing biosecurity risks linked to the increasing availability and decreasing price of DNA synthesis. This makes containment of hazardous biological material much more difficult because published (sequence) information is enough to make a deadly organism such as a modified H5N1 virus. The problems associated with SynBio are thus by no means unique to that area. 

The concerns about social justice are again not peculiar to SynBio, but could apply to all sorts of technical fields, not even just to biological ones. Such considerations have not stopped us from replacing humans with machines to do all sorts of things, from working in agriculture to selling train tickets. Few people would advocate going back to isolating all kinds of pharmaceutical substances from trees, as we used to. Indeed it could even be argued that it is more environmentally sustainable to make products in bacteria than to cut down trees for this. Social issues are always important, but it is difficult to argue that we could stop the development of science for such reasons. Technological development often brings new opportunities as well as losses, and we may hope that SynBio will do the same.

In conclusion, SynBio is a diffuse term that does not clearly delimit the area from mainstream GM science. Scientific results so far appear to support the notion that SynBio represents a continuation of genetic engineering rather than a quantum leap into the unknown. Its current risks and opportunities appear similar to those of GM in general. Ethical and safety concerns and social issues need to be debated in full, but they do not appear really different for SynBio than for other areas. 

This research should contribute to putting these issues into perspective and help to stimulate public debate and disseminate valuable information on SynBio. The more practically feasible applications proposed for SynBio undoubtedly hold promise to deliver useful products and new methods for society. Overemphasising other aspects, such as the creation of truly artificial life forms, may detract from the real nature and promise of the SynBio field.