Synthetic

biology
2 and 3 June 2008

scientific
discussion meeting
SUMMARY

web royalsociety.org
Contents
1 Introduction 1

2 Key points 1

3 The discussion meeting 1

4 Introducing synthetic biology 2

5 Designing genetic switches, circuits and networks 3

6 Genome evolution and expanding the genetic code 4

7 Foundation technologies 5

8 Designing organisms and systems 5

9 Synthetic and systems biology 8

10 The future development of synthetic biology 9

11 Further information and resources 11

12 Appendix A: Discussion Meeting programme 12

1 Introduction Synthetic biology will be aided by
understanding the cell response to
Synthetic biology is broadly understood as the engineering. Organisms may react to oppose
deliberate design of novel biological systems and engineering and this is currently a significant
organisms that draws on principles elucidated challenge to synthetic biologists
by biologists, chemists, physicists and engineers.
Fully characterized, standardized, modular
It is an emerging field of increasing scientific
parts that have defined properties or perform
and public policy interest, and the UK synthetic
defined functions independent of context will
biology community is growing. To capture the
be useful, as will orthogonal parts that are
enthusiasm surrounding synthetic biology, the
invisible to the organism
Royal Society held a Discussion Meeting to
showcase some of the most exciting research There are likely to be intellectual property and
in the field. Participants discussed: technical ownership issues around key technologies and
advances; applications including novel ways to processes
produce bioenergy, materials and drugs; and the
social contexts of this research. Synthetic biology raises important ethical
and social issues which need to be widely
discussed in the short term and as the field
2 Key points matures

Synthetic biology is concerned with producing The dual-use potential of synthetic biology
biological based entities (e.g. parts, devices, (that is, the technology and knowledge could
systems, organisms) which perform a new be used for and against public health and
function. From these entities, applications in national security) may require the development
areas such as medicine, energy, environment of governance and oversight frameworks
and materials may be developed
Public dialogue will assist policy makers and
Synthetic biology also aims to increase our scientists develop synthetic biology, and the
understanding of biology field will be served by open and accurate
communication with the public.
Research reported at the Meeting illustrated
the viability, power and potential of synthetic
biology 3 The discussion meeting
The UK has a growing synthetic biology Around 120 leading academics, policy makers
community, and is already strong in related and other stakeholders from the UK, USA and
areas such as systems biology Europe participated in the Meeting. Presentations
and discussion explored: the general principles
Healthy numbers of undergraduate and
and scope of synthetic biology; specific research
postgraduate students are choosing to study
programmes including the design of genetic
synthetic biology
switches, circuits and networks; broader
The continued development of synthetic applications, from rewriting the genetic code
biology requires synergy amongst a range to producing materials and pharmaceuticals;
of disciplines including biology, engineering, enabling technologies; engineering challenges;
chemistry and information technology insights for synthetic biology from systems
biology; and current and planned UK research
Development also requires advances in funding opportunities. A plenary session widened
the automation and scaling of enabling discussion to issues such as the continued
technologies such as low cost DNA synthesis development of the synthetic biology community,
and genome assembly. In silico (computer- governance and oversight, and public dialogue.
based) technologies and modelling should be
increasingly useful

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 1
 This report summarises key issues raised during Like most emerging technologies, the boundaries
the course of the Meeting. It is, in the main, a between synthetic biology and other technologies
summary of the technical work presented. Wider and disciplines are blurred. A synthetic biology
issues that arose in discussions and the plenary are approach can be usefully distinguished from
also described. systems biology and genetic engineering. Systems
biology can be understood as a top-down
The report describes views expressed at the approach to the description and analysis of the
Meeting. It does not necessarily represent the dynamic interactions between components of
views of the Royal Society or a consensus opinion a biological system in order to understand the
of participants. We are extremely grateful to: behaviour of that system. Synthetic biology takes
Professor Brian Spratt FRS (Imperial College a bottom-up approach and seeks to understand
London); Professor Richard Kitney FREng (Imperial and engineer genetic networks and systems by
College London); Professor Paul Freemont (Imperial constructing and altering basic components (such
College London); and Dr Jason Chin (MRC LMB, as genetic switches and circuits). It is this bottom-
University of Cambridge) who organised the up approach that facilitates the major aim of
Meeting and reviewed this report. The Meeting synthetic biology: the design of novel organisms
programme is at Appendix A. or cells, including totally synthetic organisms,
that provide new devices and materials with
applications in areas that include health, materials,
4 Introducing synthetic the environment, defence and energy production.
biology As described below, mutual understanding and
collaborative research between systems and
Synthetic biology covers an increasingly wide area synthetic biology communities benefits both
of modern biology and although difficult to define, individually.
in essence it is about redesigning life. Synthetic
biology draws in the main on two established Genetic engineering similarly seeks to change
disciplines: engineering and bioscience. Engineering some aspect of biological function, yet does so
provides much of the conceptual framework and with relatively poorly defined and characterised
the material to which this is applied is biological. components, and with relatively weak control
Knowledge of key properties of cells and sub- over inputs and outputs. Synthetic biology, in
cellular processes is then essential, and additional contrast, builds switches, networks and systems
disciplines such as chemistry and information and from components and modules that are well
communication technology (ICT) facilitate the characterised and easily connected, and which
endeavour. The broad aim of this convergence encode for properties with known functions.
of tools and knowledge is the (re)design and (re) Controlling design, characterisation and
assembly of biological systems which may lead to construction aims to increase the predictability of
applications in areas such as healthcare, energy and the properties of the designed systems.
environment (see Box 1).
In short then, the synthetic biologist seeks to
Marrying an engineering approach to biology build a bespoke system (such as an organism) by
follows from parallel developments in both re-designing an existing system or constructing
parent disciples. Fifty or more years of a sub- one from scratch using parts taken from nature
cellular molecular and genetic understanding of or specially designed. This approach can lead to
life, including the elucidation of the structure of organisms, networks and systems with properties
DNA, gene regulation, genetic engineering, rapid not found in nature (such as bacteria that produce
DNA sequencing and advances in synthesis of spider silk or cells that change colour when they
DNA, have converged with parallel developments divide).
in engineering and information technology, in
particular miniaturisation and computer chip design.

2 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
Box 1: Applying synthetic biology
Applications discussed at the Meeting, some near to market, some in the very earliest stages of
development, included:

Molecular computers (see 5.2) Salmonella engineered to secrete spider silk

(see 8.1)
DNA-like polymers for novel materials
(see 6.3) Gene therapies (see 8.2)

New protein therapeutics, e.g. human Microbial factories for generating energy
growth hormone (see 6.4 ) and fuel (see 8.1 and 8.2)

Production of the antimalarial artimisinin Development of drugs for tuberculosis

from yeast (see 8.1) (see 8.2) and trypanosomiasis
(sleeping sickness; see 9.2)

5 Designing genetic positive feedback loops, a double toggle

switch was created which resulted in biological
switches, circuits and memory. It was also shown that the hysteresis
exhibited by the positive feedback loop could
networks be eliminated by the addition of a negative
Work was described that sought to construct feedback loop.
integrated rationally designed molecular circuits
that emulate electronic circuits. This requires 5.2 Biological computing
well characterised and predictable molecular Designing and characterising simple systems,
components and a method of programming such as the above, assists the development of
biological behaviours. Simple synthetic model a library of interchangeable and transferable
systems are a useful tool for learning about parts with predictable properties. These can then
component parts and how they interact. be used to construct more complex systems.
Reported research demonstrated molecular Research was reported that constructed simple
switches, biological memory and the linking circuits with around ten components, including
of component parts to perform computing DNA-based gates and logic circuits. These
operations. share features of electronic circuits such as
Boolean logic functions and signal restoration by
5.1 Molecular switches and threshold and amplifier gates. Gate design and
biological memory circuit construction are modular and use single
Work was described in which two positive stranded nucleic acids as inputs and outputs.
feedback loops, each exhibiting weak hysteresis, Although circuit activation is substantially slower
were added together to produce strong than seen in electronic circuits, it is unlikely that
hysteresis. (Hysteresis is a property of a system this will be a limiting factor in all foreseeable
where the present state of that system depends uses of the technology. Potential applications are
on its immediate history.) The first of these envisaged in bioengineering and biotechnology
two positive feedback loops was for a LacY for example in the construction of smart drugs
transporter that transports the inducer that and biomedical diagnostics. Next steps include
increases its expression. The second of these the construction of a molecular compiler for
was a synthetic genetic clock which produced logic circuits and chemical reactions.
sustained damped oscillations in Escherichia
coli (E. coli) populations. By linking these two

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 3
 6 Genome evolution and 6.3 Expanding polymerases
Research was reported that sought to engineer
expanding the genetic polymerases by directed evolution. Directed
code evolution develops molecules with desired traits
through successive rounds of isolated replication
Synthetic biology can be used to understand and mutation. Compartmentalised self-
genome evolution and to harness selection to replication (CSR) has been used to evolve new
rapidly evolve organisms and systems. forms of polymerase (an enzyme that catalyzes
the formation of new DNA or RNA from an
6.1 Genome evolution
existing strand of DNA or RNA). Based on a
Synthetic model systems can be used to simple feedback loop consisting of a polymerase
understand genome evolution. Deletion, that replicates only its own encoding gene, CSR
rearrangement and duplication play important can be used to modify polymerase function
roles in the evolution of gene networks. Large- in order to read or write genetic material in
scale insertions usually involve the duplication new ways. For example, polymerase can be
of part of the genome. Research was reported engineered to amplify templates that could
that experimentally duplicated genes to better not otherwise be read, such as the recovery of
understand the effect of adding new regulatory ancient DNA sequences from archaeological and
links to gene networks and consequent effect on paleontological specimens. The technique has
network evolvability. been used to obtain informative DNA sequences
from cave bear bones around 45,000 years old.
Around 600 new regulatory links were added to
a wild-type E. coli. The bacteria tolerated 95% Designer polymerases may also allow the
of new networks, including rewired transcription writing of novel, DNA-like polymers. The
hubs, and most were expressed. Very few programmability of DNA makes it an ideal
altered growth. This result might be surprising material for nanotechnology and the production
from a bioinformatics perspective, which may of interesting and exciting materials.
suggest that rewiring hubs would be lethal.
Selection pressure was applied to the rewired 6.4 Expanding Ribosomes
gene networks and certain networks consistently Ribosomes, organelles found in the cytoplasm
survived over wild type. This demonstrates of living cells, are made of protein and RNA
the potential for evolution from acquired subunits and catalyze the synthesis of proteins
network connections. Similar experiments in guided by a messenger RNA (mRNA) template.
other organisms, including mammals, have not Reported research aimed to create ribosomes
been undertaken, but would indicate whether with expanded chemical scope to act as novel
tolerance towards rewiring is a general feature cellular translation systems able to synthesise
of evolved biological networks. unnatural proteins.If successful, the end goal
of encoding amino acids which do not occur in
6.2 Expanding the genetic code
nature will be to assist scientists in re-writing the
As well as work with material taken from nature, genetic code.
a distinguishing ambition of synthetic biology
is to expand natural genetic chemistry for To date, experiments have demonstrated sets
novel applications. Participants at the meeting of ribosome-mRNA pairs which are able to
discussed work that sought to expand chemistry translate new proteins, and that it is possible to
linked to polymerases and ribosomes. create ribosomes which can be switched on and
off.This is the first demonstration of creating a

4 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
parallel translational machinery which evolves DNA synthesis techniques with engineered
new functions and modifies how it reads genetic recombination strategies to manipulate native
information. genomes and introduce synthetic DNA elements.
E. coli has proved a useful test bed for this
The next stage of this work is to create new work. An engineered strain of E. coli, in which
and expanded ribosome functions which will the entire genome has been recoded, opens
allow scientists to evolve components within this microbe to a broad set of applications,
cells to aid the study of molecular biology. This such as the incorporation of non-natural
methodology could also be used to look at amino acids with novel biochemical properties.
protein interactions.In addition, this technology Techniques are being developed to automate the
would enable the expansion of genetic codes simultaneous introduction of libraries of DNA
and allow the creation of more efficacious constructs into cells, making the process hands-
protein therapeutics, for example, human off and efficient.
growth hormone.
As well as improving techniques for making
large-scale, site-specific direct manipulations of
7 Foundation genomes, researchers are working toward tight

technologies expression control of introduced DNA. RNA

based molecular switches are an attractive route
Like synthetic biology, the research field of to control. Work was reported on engineered
genetic engineering seeks to alter genetic RNA switches which allow tuneable control of
codes. Genetic engineering typically involves the expressions of target genes. Researchers are
serial changes in the genome by inserting or now working toward a modular library of RNA
removing one or a few short sequences of DNA. switches.
In contrast, synthetic biology typically considers
engineering at the whole cell (or organism)
level and seeks greater efficiency. Engineering 8 Designing organisms
at the level of the genome for example aims to
change as much as all nucleotide sequences in
and systems
the genome of an organism in order to produce A large part of discussion at the Meeting
cells with new functions. To do this predictably revolved around the design and redesign of
and with control requires comprehensive organisms and systems for better understanding
understanding of cell behaviour and the of biology and for constructing organisms with
development of technologies to efficiently and useful functions.
predictably alter the properties of genetic and
biochemical molecules in interaction. 8.1 Designing organisms
Work was reported on developing technologies
Research reported at the Meeting described
to design and synthesise bacterial cells.The
technologies that assist the pursuit of controlled,
initial goal of this research is to construct
efficient molecular changes. Two particular
a synthetic cell, the minimal version of
enabling technologies relate to new methods to
Mycoplasma genitalium. M. genitalium was
change the DNA of cells efficiently and at scale,
taken as the model of choice since it has a small
and new ways of changing and controlling gene
genome and minimal metabolic complexity
expression.
and may become the platform of choice for
Toward the former, researchers are working understanding how the simplest possible cell
on new methods that combine large-scale works. Two key technologies for the design of

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 5
 synthetic cells are genome assembly (assembly no negative effects on the growth and viability
of overlapping cassettes of genome segments) of the cell; indeed toxicity impedes growth and
and genome transplantation (the installation viability only when secretion is prevented. Spider
of the synthesized genome into a receptive silk is as strong as Kevlar and ten times more
cytoplasm, such that the donor genome elastic and has significant industrial potential.
becomes the new operating system of the cell). The challenge now is to scale up production to
Work was described that used these techniques an industrially useful level.
to demonstrate synthesis and transplantation
into host bacteria of the largest chemically Isoprenoids are another class of naturally
derived molecule to date. Next steps for this occurring organic chemicals of interest to
work include construction of a true minimal cell synthetic biologists and industry. Isoprenoids
by taking away all of the non-essential genes of include chemicals used as flavours, fragrances,
M. genitalium. This would enable scientists to fuels and therapeutics including artemisinin, the
learn more about the essential basics of cellular most effective known anti-malarial drug.
life. End goals for this work include creating
Derived from the plant Artemisia annua, the
useful bacteria, for example, with applications
varied therapeutic benefits of artemisinin have
in areas such as energy and the environment.
been known to the Chinese since at least
The work with M. genitalium presently uses the
150BC. Artemisinin is currently considered
known genome sequence. The extent to which
prohibitively expensive for treating the majority
the genome can be redesigned to produce
of the malaria sufferers in the world. It is
a radically novel synthetic organism by this
estimated that 700 tons of artimisinin would
method is of considerable interest.
be sufficient to treat all malaria sufferers, and
Rather than stripping away dispensable genes synthetic biologists are investigating ways to
to produce a minimal chassis, other striking engineer microbes to produce this quantity of
work in synthetic biology seeks to add to natural the drug cheaply.
organisms and engineer them to produce useful
The development of both E. coli and yeast
materials and substances that they do not in
engineered to produce artemisinic acid was
their wild type form. For example, the pathogen
described. A precursor to artimisinin, artemisinic
Salmonella typhimurium transports some
acid falls under a different regulatory burden
proteins completely out of the cell via a needle-
to the drug itself: the acid is regulated as a
like biomachine know as the type three secretion
chemical, not a pharmaceutical. This means
system (T3SS). Experiments were described that
that the process of production can be changed
harnessed this system to produce proteins of
without again triggering the regulatory
industrial interest, in this case spider silk.
process. Increased efficiencies in the process
Attempts have been made to engineer bacteria can therefore be applied as they arise. This will
to produce spider silk before, but it is toxic assist researchers achieve their target of enough
to the cell. The advantage of the T3SS is that affordable artimisinin for all malaria sufferers.
it reduces the period of time the protein is Artimisinin derived from yeast is likely to be
resident in the cell. It also avoids difficulties on the market in 2-3 years, initially at a price
in extracting and preserving the protein of directly comparable but soon undercutting the
interest. By creating synthetic spider silk gene traditionally derived version.
sequences, inserting these into S. typhimurium
It was reported that no one is making a profit
and controlling the T3SS, researchers have
from this production of artimisinin from yeast
experimentally produced spider silk that can be
and it is anticipated that artimisinin sold to
drawn into threads. The system appears to have

6 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
western tourists will subsidise that delivered to Mycobacterium tuberculosis (the cause of
the developing world. The chassis constructed tuberculosis) which was then used to screen
for the production of anti-malarial drugs may for efficient tuberculosis treatments. For
now be adapted to produce profitable biofuels. example, ethionamide is an antibiotic used
This is in line with the engineering ethos of in the treatment of malaria, but has side-
synthetic biology, where tools and techniques effects for humans. The synthetic circuit was
developed for one application can be transferred successfully used to explore ways to knock
to another. down the ethionamide-resistance pathway of
M. tuberculosis. This increased its sensitivity to
Work elsewhere is already underway to engineer ethionamide which could then be delivered in
microorganisms for energy production. Work lower dosage. Next steps involve testing this
was reported with the long term goal of creating intervention in animal and then human models.
microbial solar cells that produce hydrogen.
Choosing cyanobacteria as the model organism, Synthetic constructs, such as gene control
research to date has concentrated on gene circuits, need to be well interconnected with the
level analysis of responses to light. Ultimately it host cell's existing networks. Moreover, these
is hoped that this and other properties of the interconnections need to be well characterised
organism can be harnessed to produce hydrogen and predictable. It is possible to test this
from sunlight. understanding by building an artificial system
and comparing its behaviour with its natural
8.2 Designing systems counterpart. Synthetic gene circuits have been
Because most biological functions result from used in such a manner over the last eight
interplay of components and modules, synthetic years. In most cases, the scientist has tried to
biology requires knowledge beyond individual simplify the system in order to insulate it from
molecular function. As described above, the underlying cell physiology. In taking this
assembling networks from individual modules approach, the host cell is considered to be an
increases understanding of natural processes invariable chassis, with a well-defined interface
and facilitates hypothesis testing. Synthetic between the circuit and the host. The dominant
gene networks are designed to emulate natural observed function is usually attributed to circuit
gene expression behaviour, and may open up design. However, simplified circuits do not
new pathways to engineer therapeutics and always reflect what is observed in the natural
foster progress in gene therapy and tissue state where there may be hidden interactions
engineering initiatives. Research was described between the circuit and the cell. For instance,
that used a synthetic gene network to assemble there may be cross-talk between the circuit and
and test human-compatible transgene control endogenous compounds, or the circuit may
technologies. Success has been obtained modulate cell physiology to produce unexpected
with upstream gas inducible transcription behaviour. This may be thought of as faulty
control in mice, and with epigenetic toggle circuit design. However, using two simple
switches that lock transgene expression in circuits, it was shown that the unexpected
response to administration of inducer molecule behaviour can be explained by cell interactions
concentration. impacting on circuit dynamics.

The latest synthetic mammalian gene networks The first example given was a circuit which
imitate ecosystems and reveal cross-talk generates bistable gene expression in E. coli,
dynamics between species sharing the same for a protein which determines cell cycle entry.
habitat. Work was reported that constructed A very simple circuit consisted of a positive
a network containing mammalian cells and feedback loop alone. It was expected that this

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 7
 circuit would exhibit monostability, and that an
additional protein titration component would
9 Synthetic and systems
be needed for the circuit to show bistability. biology
However, even the minimal circuit generated
Discussion at the Meeting confirmed close
bistable gene expression. It was found that this
affinity between the disciplines of synthetic
could be explained by circuit activation inhibiting
and systems biology; indeed the design and
cell growth, with the combination of growth
construction of systems that exhibit complex
modulation and the positive feedback loop
dynamic behaviour remain major goals of
resulting in bistability. The interaction between
synthetic biology. Work was reported at the
the circuit and the cell physiology can therefore
Meeting on new methods for modelling gene
explain the dynamics of the circuit.
interactions, and on techniques to engineer
The second example described the insertion recalcitrant systems.
into cells of a simple cell suicide circuit
containing a quorum sensing module. Bacteria
9.1 Modelling gene interactions
employ quorum sensing (a form of cell-cell Work was described in which metabolic models
communication) to sense changes in population were used to identify functional models within
density and control bacterial population size networks and predict interactions between
by regulating gene expression. At high levels, genes. A list of all metabolic reactions for
the protein produced (ePop) blocks cell wall Saccharomyces cerevisiae (a species of yeast)
synthesis and induces cell death (popping). has been defined and analysis of deletion
In small populations of bacteria, synchronised mutants used to describe functional modules
popping is seen which leads to sustained for the organism. Specific lethal interactions
oscillations in population size in macroscopic between genes were sought to isolate functional
batch cultures. However, oscillations were also modules. These are cases where knocking out
observed without the quorum sensing module two different genes results in a sick organism.
in the circuit. The oscillations must be produced Such lethality can be the result of either
via hidden interactions with the cell. This can redundant gene duplicates or the existence
be explained by diffusible factors produced by of alternate cellular pathways. Computer
the cell which accumulate at high density and simulation of all possible double and triple gene
induce expression of the ePop protein. deletions of non-essential genes can be used to
predict cases of synthetic gene lethality with a
These two examples illustrate the challenge success rate of approximately 56%.
of constructing fully predictable biological
parts and systems, and show that unintended Further experiments have been carried out
interactions between the synthetic circuit and on the metabolism of Buchnera aphidicola,
underlying cell physiology can impact circuit a relative of E. coli. Using in silico modelling,
function. These problems are likely to get worse genes were deleted at random and if this had
as network complexity increases and will be a no impact, another was deleted and so on.
challenge to the design of biological circuits that This predicted with around 80% accuracy the
have anything like the precision and durability of metabolic network of the actual organism.
electronic circuits.
A robot scientist, which can generate a
hypothesis, design a test and analyse results,

8 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
has also been used to design modules. Novel species Trypanosoma brucei and transmitted by
modules or pathways can be introduced and the tsetse fly. One possible novel intervention
their performance observed. In a model of interferes with the glucose transport system of
aromatic amino acid biosynthesis in yeast, T. brucei whilst resident in its mammalian host.
a robot was given deletion mutants and It is fooled into reacting as if in the tsetse fly
background knowledge of the metabolic (where ambient glucose levels are lower) and
pathway. The robot was set the task of this apparently robust response is instead turned
discovering which genes encode enzymes for into fragility. This intervention waits testing
metabolic reactions which it did not yet know. within host tissue, but demonstrates that auto-
Sometimes this approach cast new light on the robustness mechanisms can be used to re-make
known gene, sometimes the robot was wrong, networks successfully for biotechnological and
and sometimes it confirmed what was already therapeutic benefit.
known.

9.2 Engineering recalcitrant 10 The future

systems
development of
Perhaps one of the more significant challenges
for synthetic biology is that living systems synthetic biology
actively oppose engineering. They are robust and The meeting included a plenary session that
have evolved to be self-sustaining, responding widened discussion on synthetic biology beyond
to perturbations through adaptation, mutation, technical foundations and achievements. The
reproduction and self-repair. This presents a following section summarises key aspects of this
strong challenge to efforts to redesign existing discussion.
life. One approach to meet the challenge is to
turn to systems thinking and try to motivate 10.1 Engineering biology
a system to produce the required behaviour or
The many successful research projects and
product by asking what is preferable from the
experiments reported at the meeting were taken
perspective of the recalcitrant system. In one
to show that biology is open to engineering.
experiment, researchers disabled lactic acid
One goal of synthetic biology is to make biology
pathways and engineered diacetyl production in
easier to engineer, and it does this through
bacteria Lactococcus lactis. Initial steps included
better characterisation and predictability of
quantifying the importance of each step in the
easily connected parts and modules, and
lactic acid pathway to determine which may
better understanding of these in interaction.
be inactivated with least overall effect on the
Synthetic biology may then be considered the
organism.
full conceptual realisation of an engineering
In silico modelling can help determine the approach to biology.
degree to which one can interfere with
There was a suggestion that the newness of
molecular processes without reducing overall
synthetic biology is sometimes presented in
system function. Experiments have shown
ambivalent ways. For example, sometimes it is
that impairing robustness at some point in a
presented as something very new, sometimes as
network reduces overall robustness: robustness
a continuation of some 25+ years of engineering
is not conserved. However, network fragility
biology (for example, insulin production by
turns out to be a conserved property and
E. coli was achieved in the late 1970s using
this has been exploited to develop drugs to
recombinant DNA technology). Discussion
combat trypanosomiasis (sleeping sickness).
tended toward suggesting that synthetic
This parasitic disease is caused by protozoa of
biology is both old and new: old in the sense

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 9
 that it builds on accumulated knowledge and It was suggested that synthetic biology too often
understanding, new in the sense that it is the seems to focus on the cellular or sub-cellular
first full application to biology of engineering level and that this constrains the development
principles. of the field. This bias may derive from the early
domination of the field by researchers used
This new approach is leading to developments to working with bacteria. Nonetheless, work
that are genuinely novel; for example, the presented at the meeting showed that biology
very notion of a box of parts from which can can be engineered at a more complex level.
be assembled synthetic bespoke organisms. It was suggested that communication with
Biologists and engineers have not had that even wider communities, such as population
expansive capacity before. biologists and policy makers, may stimulate
complex integrated projects such as the design
A step change in synthetic biology productivity,
of ecosystems for pest management.
particularly parts and organisms, may be pushed
by quicker, cheaper and easier synthesis of One measure of engagement success is
accurate nucleotide sequences. The amount student uptake. Participants at the meeting
of DNA that can be synthesised per day has reported healthy student numbers entering
increased rapidly and looks likely to continue to undergraduate and postgraduate training and
do so for the next decade. that it is a popular option for women.

10.2 Community matters 10.3 Communication and dialogue

The continued development of synthetic biology Participants discussed public perception of
requires synergy between researchers in all synthetic biology. It was suggested that this
disciplines involved, including but not limited may be the moment to offer the public a new
to the core disciplines biology and engineering. promise, for example that synthetic biology will
Engagement with and between communities will allow an understanding of disease at a level
be served by demonstrating mutual benefits, for not previously possible. Others noted that,
example that synthetic biology offers biologists, again, there may be no discrete appreciation of
engineers and others technologies and concepts synthetic biology: people are more likely to be
that they may not have encountered before. It interested in the ways of tackling disease rather
will also be facilitated by the development of than means by which any intervention was
libraries of techniques, tools and standard parts developed.
for rapid take-up and deployment by diverse
researchers. Participants considered the need to continue to
open up synthetic biology to public discussion,
Demonstration of success is likely to engage and debated the nature and timing of public
specialist and lay audiences. There was some engagement activities. It was suggested that
debate on what might constitute the best form basic science is less controversial than application
of success. Completed work on new ways and that debate on synthetic biology may
to make therapeutic drugs is a considerable intensify along with any increased number of
achievement, but target audiences may not see products. Perceived benefits of continued public
this as a discrete success of synthetic biology, dialogue included: demonstrating positive and
especially if success is defined in terms of genuinely beneficial scientific developments;
previous approaches or paradigms. For example, assisting governments and others develop
to publicise the construction of a synthetic measures against misuse of this powerful
gene network may gain little notice over the technology; and understanding societal issues.
production of a new drug, even if that new drug
was a consequence of such a network.

10 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
Another suggested area for public discussion ethical, legal and social aspects including
was whether synthetic biology may become too regulatory frameworks and public concerns and
successful, for example by endowing humans aspirations.
with new functional capacities with profound
societal implications. Such considerations have To facilitate the development of synthetic
been the subject of recent reports by the military. biology, BBSRC and EPSRC, with ESRC and
AHRC, are funding networks in synthetic
10.4 Control and oversight biology. These will stimulate cross disciplinary
networking and communication between
Participants further discussed that synthetic
researchers in the biosciences, engineering and
biology could be used to develop harmful and
the physical sciences, with input from the social
nefarious applications. This possibility means
sciences and humanities.
that oversight and control cannot be overlooked.
The control of radioactive material shows that
potentially harmful knowledge and technology
can be successfully regulated. The burden of
11 Further information
ensuring the aversion of potential danger falls and resources
in part on the synthetic biology community and
Further information on synthetic biology can
the successful approach of risk assessment of
be accessed through the following Society web
experiments in genetic engineering provides a
page:
useful model.
royalsociety.org/syntheticbiology
10.5 Ownership and intellectual
property This includes an online resource on synthetic
There are unresolved ownership and intellectual biology. Updated regularly, the resource has
property issues. It was suggested that these information on policy activities in the UK, Europe
must be addressed in the near term to avoid and elsewhere as well as information on events
future difficulties. Participants relayed that there and conferences, discussion forums, courses,
are already some tensions between scientists journals and research centres. Suggest additional
and universities around innovative academic items for the resource to: synthetic.biology@
research on for example biofuels. Many synthetic royalsociety.org.
biologists prefer to reserve patents for products
The synthetic biology web pages also contain
(e.g. the organism that produces a biofuel)
information on the Synthetic Biology Policy
rather than underlying technologies (e.g. genes,
Coordination Group. This multi-stakeholder
devices, parts, tools). The BioBricks Foundation,
group, convened by the Society, has been set up
based at MIT, has a registry of standard DNA
to: share information of synthetic biology related
parts (BioBricks) that encode biological
activities; identify gaps in current policy work;
functions. These are open access and free to use.
and stimulate activities in identified gap areas.
10.6 Funding Contact
It was reported that the UK Research Councils
Please send any comments on this report to:
have sharpened their focus on synthetic
Matthew Harvey
biology, recognising opportunities for improved
The Royal Society
understanding of biological systems, a wide
6-9 Carlton House Terrace
range of potential applications and complex
London, SW1Y 5AG, UK
societal issues. As well as responsive mode
Tel: +44 (0)20 7451 2578
funding for technical research, work is being
e-mail: [email protected]
undertaken across the Research Councils on

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 11
 12 Appendix A: Discussion Meeting programme

Day 1: Monday 2 June

Welcome and opening remarks

Mr Stephen Cox, Executive Secretary, the Royal Society
Professor Brian Spratt, Imperial College London

Session 1
Chair: Professor Richard Kitney, Imperial College London

Designing biological systems

Professor Pamela Silver, Harvard Medical School

Nucleic acid logic circuits for programming biology

Dr Georg Seelig, California Institute of Technology

A tale of two circuits: what I create, I may not understand

Dr Linchong You, Duke University

Building biological memory by the coherent linkage of positive feedback loops

Professor Alex Ninfa, University of Michigan

Session 2
Chair: Dr Jason Chin, University of Cambridge

Evolvability and hierarchy in rewired bacterial gene networks

Dr Mark Isalan, Centre for Genomic Regulation Barcelona

Synthetic mammalian gene networks

Professor Martin Fussenegger, Swiss Federal University of Switzerland

Engineering the secretion of spider silks from salmonella

Dr Danielle Tullman-Ercek, University of California San Francisco

Synthetic biology for synthetic chemistry

Professor Jay Keasling, University of California Berkeley

12 Synthetic biology The Royal Society - Scientific discussion meeting I August 2008
Day 2: Tuesday 3 June

Session 3
Chair: Professor Paul Freemont, Imperial College London

Ribosome engineering and new genetic codes

Dr Jason Chin, University of Cambridge

Design, synthesis and control of genetic and genomic systems

Dr Farren Isaacs, Harvard Medical School

Synthesis and replication of nucleic acids with expanded chemistry

Dr Phil Holliger, University of Cambridge

Synthetic genomics: progress on construction of a synthetic bacterial

Dr John Glass, J. Craig Venter Institute

Session 4
Chair: Professor Pam Silver, Harvard Medical School

Synthetic systems biology: engineering self-sustaining systems

Professor Hans Westerhoff, Manchester Interdisciplinary Biocentre

Synthetic and systems biology: simplicity and simplification

Professor Steve Oliver, University of Cambridge

Plenary Discussion
Synthetic biology: the Research Councils perspective
Dr Amanda Collis, Biotechnology and Biological Sciences Research Council

Synthetic biology The Royal Society - Scientific discussion meeting I August 2008 13
The Royal Society
69 Carlton House Terrace
London SW1Y 5AG
tel +44 (0)20 7451 2525
fax +44 (0)20 7930 2692
email [email protected]
web royalsociety.org/policy

Founded in 1660, the Royal Society is the independent scientific academy of

the UK, dedicated to promoting excellence in science.

As we prepare for our 350th anniversary in 2010, we are working to achieve

five strategic priorities:

Invest in future scientific leaders and in innovation

Influence policymaking with the best scientific advice

Invigorate science and mathematics education

Increase access to the best science internationally

Inspire an interest in the joy, wonder and excitement of scientific discovery

ISBN: 978-0-85403-716-2
Issued: August 2008 RS1268
Founded in 1660, the Royal Society
is the independent scientific academy
of the UK, dedicated to promoting
excellence in science
Policy document 16/08
Registered Charity No 207043 The Royal Society, 2008