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Realising European potential in synthetic biology | December 2010 |    9

The fi rst product class to emerge is likely to have a 

major infl uence on public expectations. From a policy 

perspective, what is perhaps more important than the 

short-term predictions of specifi c product outputs is 

the need to build the R&D infrastructure and culture 

for the longer-term to underpin the emergence of 

multiple applications, including those that are presently 


A recent survey of public perceptions commissioned by 

the Royal Academy of Engineering in the UK



that awareness of synthetic biology is low but that, when 

information is provided, members of the general public 

expressed great interest in the prospect of designing 

microorganisms to help manufacture biofuels and 

medicines. Concern was expressed, however, about 

deliberately releasing artifi cial organisms into the 

environment to tackle pollution. Public respondents 

wanted government to regulate synthetic biology 

but were concerned that regulation should not stifl e 

development of the area. Public views on patenting were 

mixed but there was understanding that investors are 

entitled to a return on their time and money, within the 

broader context of balancing returns on investment and 

social responsibility.

It is important for this work on public attitudes to be 

extended across the EU; there has already been some 

examination of societal attitudes in work funded by 

the European Commission (Appendix 2) and there is an 

Austrian study in progress




‘Synthetic Biology: public dialogue on synthetic biology’, The Royal Academy of Engineering, June 2009, at www.raeng.org.

uk/news/publications/list/reports/Syn_bio_dialogue_report.pdf . This public dialogue was held to complement the Academy’s 

inquiry, published in May 2009, ‘Synthetic biology: scope applications and implications’, at www.raeng.org.uk/synbio.


“COSY – Communicating Synthetic Biology”, at www.idialog.eu/index.php?page=cosy. Further information on this study and 

other societal aspects of synthetic biology was published in a special issue of the journal Systems and Synthetic Biology (Schmidt 



Public expectations of synthetic biology research and 



Realising European potential in synthetic biology | December 2010 |    11

The synthesis of increasingly complex unnatural net-

works embedded in living matter is an emerging theme in 

synthetic biology (Chin 2006). Such achievements have 

become possible because of the major improvements in 

the precision, speed and cost reduction in gene sequenc-

ing and DNA synthesis, coupled with the techniques of 

gene transplantation, genome assembly, model building 

and computational design.

Synthetic networks have enabled the generation 

of systems endowed with genetic components and 

expanded genetic code (see section 5.2). Broadly, there 

are two approaches to doing this: involving either the 

assembly of well-characterised, freely combinable, 

naturally occurring modules


 into novel networks or the 

creation of unnatural, standardised modules. Although 

the experimental approaches may vary widely, the 

common challenge is to exert the necessary molecular 

control in time and space to achieve the desired outcome. 

As Chin (2006) observes, endowing living organisms 

with new functions can be diffi cult for several reasons—

they are complex, open systems that operate far from 

thermodynamic equilibrium, there is lack of information 

on the cell-wide specifi city of molecular interactions, and 

components in vivo are much harder to defi ne and control 

than in vitro. Despite these challenges, signifi cant success 

has been achieved in demonstrating the novel techniques. 

Advances are also being made towards the objective of 

creating artifi cial cells de novo. Where possible, examples 

of research taking place in Europe are described in the 

following sections, but areas where Europe is lagging 

behind the USA are also highlighted. The examples 

have been chosen to illustrate key points rather than to 

be a comprehensive account of the fi eld and to cover 

approaches in vivo (sections 5.1–5.4) and in vitro 

(sections 5.5–5.6). The in vitro systems are, as yet, limited 

in relying on self-assembly but offer additional possibilities 

to sample the ‘chemical space’.

5.1 Minimal 


This is a major research area, initiated in the USA, to 

defi ne the minimal number of parts (genes) needed for 

life, based on a full description of those parts and their 

interaction, to serve as a basis for engineering minimal 

cell factories for new functions. Such work builds on 

advances in several areas of genomics and related 

disciplines—the use of comparative genomics approaches 

to identify shared core genome sequences across species; 

systematic gene disruption studies to explore function; 

the characterisation of naturally evolved minimal gene 

sets (for example in parasites or endosymbionts for 

survival in specialised environments); and the systems 

biology-based computational approach. Combining the 

insight gained from these research methodologies helps 

to identify an obligatory set of bacterial genes for survival 

in defi ned laboratory settings, with more genes required 

to survive in natural environments


. However, the size of 

this minimum gene set is still controversial. An estimate of 

500–800 genes was made based on detailed analysis (Pal 

et al. 2006; Feher et al. 2007) but subsequent work based 

on gene essentiality studies (which may underestimate 

the number of genes needed for independent life) 

indicates a range of 300–400 genes.

Based on the accumulating understanding of these 

minimal gene sets, the experimental approaches that 

can then be taken to construct the minimal genome 

can be described either as bottom-up, that is de novo 

synthesis, or top-down. The latter process involves 

stepwise reduction of different bacterial and eukaryotic 

genomes (e.g. E. coliBacillus subtilisSaccharomyces 

cerevisiaeCornebacterium glutamicumAspergillus 

oryzae) to a reduced gene set that allows them to 

function. It is noteworthy that the systematic deletion 

of mobile genetic elements (e.g. insertion elements, 

transposons and prophages) can increase genome 

stability (Posfai et al. 2006); this may be important for 

technical applications and for the construction of safe 


In a scientifi c breakthrough, bottom-up work was 

pioneered by researchers at the Craig Venter Institute 

(Gibson et al. 2008) synthesising the Mycoplasma 

genitalium genome


. This organism, with a small 

genome and minimal metabolic complexity, may become 

a platform for understanding how the simplest cell 

works. Assessing the resilience of such minimal cells, in 

particular how they behave under stressful conditions 

or in an industrial setting, represents an important 

topic for future research. The bottom-up approach has 

potential advantages in fl exibility of design and rapidity of 

construction, but relies on improvements in speed of DNA 

synthesis and genome transplantation. The top-down 

alternative is perhaps more controllable but the genetic 

tools are not yet available for many species. The greatest 

opportunity may reside in merging the approaches

where a modular core genome serves as a chassis for 

replacement by synthesised elements. For example, the 


A module is defi ned as a collection of molecules whose function can be perceived as discrete.


Other research funded by the Sixth and Seventh Framework Programmes (3D-REPERTOIRE and PROSPECTS respectively) 

provides detailed information on the cellular machinery required for Mycoplasma pneumoniae to survive independently 

(Kuhner et al. 2009).


In the period since the Working Group fi nalised their drafting of the EASAC report, this scientifi c team has made further very 

signifi cant accomplishments in synthetic biology (see footnote 1 in the Foreword to this report).

5  Methodological approaches in synthetic biology

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