A Synthetic Biology Roadmap for the UK

8/11/2019 A Synthetic Biology Roadmap for the UK

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UK SYNTHETIC BIOLOGY ROADMAPCOORDINATION GROUP


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ContentsForeword ......................................................................................................03

Executive summary .....................................................................................04

Introduction ................................................................................................. 06

Global trends and the role of synthetic biology ..........................................07

UK strengths ............................................................................................... 09

Synthetic biology ........................................................................................ 12

A technology roadmap ................................................................................14

Themes ........................................................................................................16

Theme 1: Foundational science and engineering ......................................17

Theme 2: Continuing responsible research and innovation ......................19

Theme 3: Developing technology for commercial use ...............................22

Theme 4: Applications and markets ...........................................................25Theme 5: International cooperation ............................................................27

Realising the vision ......................................................................................30

Recommendations ......................................................................................31

Membership of the UK Synthetic BiologyRoadmap Coordination Group ....................................................................34

Published by Technology Strategy Board on behalf of UK Synthetic Biology Roadmap Coordination Group

Technology Strategy BoardDriving Innovation


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A synthetic biology roadmap for the UK

UK SYNTHETIC BIOLOGY ROADMAP COORDINATION GROUP | 03

ForewordThe excellence of the UK researchcommunity provides an opportunity forfuture economic growth. Derivingsignicant benets also relies on the abilityof business to develop products andservices and on the expectation of asizeable global market. The TechnologyStrategy Board highlighted synthetic

biology as an emerging technologymeeting all these key criteria and offeringparticularly strong growth potential in theUK. A coordination group was formedtowards the end of 2011 to chart a suitableway forward.

The capacity of synthetic biology todevelop useful applications has onlybecome a practical option in recent years.Progress over the past decade has beendriven by a combination of factors, notleast an ever deepening understanding of

biological systems and remarkableadvances in the efciency of DNAsequencing and synthesis. Specicapplications are already emerging, but itslong-term potential remains largelyuntapped. The sharing of understandingacross the constituent biological andengineering disciplines, pooling ofexpertise and resources, anticipation ofcritical challenges and the enthusiasticcommitment of all stakeholders willsignicantly enhance our capacity tobenet. Synthetic biology has the potentialto increase prosperity and address someof the major challenges facing our planet but much work needs to be done, and ithas to be done responsibly.

Engaging the synthetic biology communityin shaping this roadmap has alsocontributed a rst step towards itsrealisation, through making newconnections and building a shared vision.Further initiatives, such as the recentformation of a special interest group, willcontinue to stimulate interest and facilitate

cooperation. This roadmap is not a one-offlong-term plan towards a xed point. Itprovides a compass-bearing for thecommunity, helping to align intereststowards future growth opportunities whilstidentifying the resources and standardsneeded to accelerate progress in theshorter term.

As an independent panel we set out toreect a representative view drawn fromacross the UK community. We believe wehave achieved this, but we also recognise

the need for ongoing and broadeningengagement to complement what hasbeen possible within the practical and timeconstraints of this exercise. Cooperationon an international scale will also helpdetermine success. We have outlined arst step in the journey and see aleadership council helping to manage theongoing process.

I have been impressed and delighted atthe interest, energy and enthusiasm shownby those who have contributed to this

roadmap and I thank them all. In particular,members of the coordination group whohave worked tirelessly for six months topull together and structure all the material.

Lionel Clarke

ChairmanUK Synthetic Biology RoadmapCoordination GroupJuly 2012


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04 | UK SYNTHETIC BIOLOGY ROADMAP COORDINATION GROUP

Executive summaryThis publication sets out a shared syntheticbiology roadmap for the UK pulledtogether by an independent panel ofexperts at the request of the Departmentfor Business Innovation and Skills (BiS).

Synthetic biology is the design andengineering of biologically based parts,

novel devices and systems as well as the

redesign of existing, natural biological systems. It has the potential to deliver important new applications and improveexisting industrial processes resulting ineconomic growth and job creation.

It is a rapidly developing technologyapplicable to a wide range of biologicalsystems, and has developed over the lastdecade due to the conuence of a numberof factors. It could help to solve a numberof major global challenges including in theelds of healthcare, energy and theenvironment.

The UK was amongst the rst to recogniseand respond to the opportunities raised bysynthetic biology. Publicly-funded academic

studies coupled with meaningful publicdialogue have established the foundationsupon which the sector is now being built.Multidisciplinary expertise is alreadyenabling the UK to make signicantcontributions to international researchprogrammes, and also to assimilate andrespond to global developments as they

arise.Our goal is to build upon these foundations,identifying and stimulating initiatives thatwill help companies develop new products,processes and services of clear publicbenet, and generate economic growthand create jobs. Applications couldinclude biosensors to identify infectionsand diseases and trigger localised drugdelivery; more personalised medicines,tailored to an individuals specicrequirements; improved waste treatments

and bioremediation; and more cost-effective routes to renewable chemicals,materials and fuels, leading ultimatelytowards more efcient solar energyconversion and storage as envisaged viaarticial photosynthesis. A recentassessment by BCC research on behalf ofGlobal Information Inc concluded that thevalue of the global synthetic biologymarket will grow from $1.6bn in 2011 to$10.8bn by 2016.

Synthetic biology is still at an early stage of

development and relatively unproven, butits potential is widely considered to be veryhigh. It is a platform and translationaltechnology linking a broad range offoundational science with an extensiverange of possible applications, somealready progressing towards market.Research is moving fast, but developingspecic processes to commercial scalewill invariably take time and encounter newchallenges. This roadmap takes a holisticview of the innovation process, toanticipate issues and facilitate progressionof applications and services towards theultimate goal of realising a clear vision fora UK synthetic biology sector.

Five core themes for the roadmapemerged from this work. They were:

foundational science andengineering: the need for sufcientcapabilities for the UK to maintain aleading edge

continuing responsible researchand innovation: including the need for

awareness, training and adherence toregulatory frameworks

developing technology forcommercial use

applications and markets: identifyinggrowth markets and developingapplications

international cooperation.

An essential rst stage is the building of acohesive stakeholder community includingacademics, industrialists, public and

private organisations. Workshops held todate have already begun this process,helping to shape the vision. Energising thisgrowing community around the vision,supported as needed through effectiveresourcing and training, will stimulate thedevelopment of applications of signicantvalue.

To accelerate the contribution syntheticbiology could make towards a vibranteconomy, it will be necessary to buildupon the many factors that make the UK

an excellent location to progress syntheticbiology, whilst identifying and reducing thecommonly encountered stumbling-blocksanticipated along the pathway tocommercially viable products andservices, particularly on behalf of smallerand start-up companies that may otherwiselack sufcient capacity or nance.

A number of factors may enhance theprobability of success of a given venture,for example, being clearer on what ispossible, understanding earlier in theprocess what is needed, gaining access toa wider range of resources includingrelevant training and advice, having moreeffective mechanisms to share ideas and

Our vision is of a UK syntheticbiology sector that is:

economically vibrant, diverse andsustainable: where businesses havesuccessfully developed andintroduced new products, processes

and services leading to signicantrevenues and employment

cutting edge: leading scienti cadvances and with a resilientplatform of underpinningtechnologies delivering clearadvantages in applicationdevelopment

of clear public bene t: an exemplarof responsible innovation,incorporating the views of a range ofstakeholders and addressing global

societal and environmentalchallenges within an effective,appropriate and responsiveregulatory framework.


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best practice across the community andhaving access to a wider network ofpotential partners and sources of publicand private funding.

Initiatives have already been taken in theUK to establish a multidisciplinarycommunity, supported via dedicated

educational programmes and facilities,including the establishment of a Centre forSynthetic Biology and Innovation. Butmore must be done to nurture andadvance these foundations if the UK is toretain its relatively strong and innovativeposition on the global stage.

Our recommendations, summarised right,therefore seek to strengthen, stimulate andbetter integrate knowledge-generationwithin the UK academic research basewhilst simultaneously developing routes to

commercialisation. Demonstrating aconsistent, long-term commitment, basedaround a clearly stated and broadlysupported vision will be very important inensuring the stability needed to attract

ongoing investments and in assistingalignment of core research interests.

Synthetic biology in the UK operates withinthe existing regulatory framework androutinely takes account of social andethical issues. Nevertheless, we highlightthe need to continue practisingresponsible research and innovation at all

stages. To ensure that practitionerscontinue to be fully aware of potentialissues, and that regulatory frameworksremain current with leading-edgedevelopments, it will be important tomaintain effective open-doormechanisms for dialogue. These, in turn,will inform, and be informed by, ongoingformal national policy and internationalregulatory review mechanisms.

Considering these various needs, werecommend a package of measures thatshould support and develop the UK-wideresearch and industrial communities byenhancing the availability of essentialresources and information.

Specically, we recommend the creationof a network of multidisciplinary centres,including a dedicated innovation andknowledge centre (IKC), to both strengthenand expand our foundational and appliedresearch base and facilitate businessexploitation. These should all be basedwithin existing higher-educationinstitutions. Investment plans for early-stage and larger demonstrator projectsand for feasibility studies should also bemade in the near future to facilitateindustrial applications of the technology.

A variety of mechanisms should beintroduced via the Technology StrategyBoard, research councils and others asappropriate, to extend the UK-widesynthetic biology community. Suchmechanisms may include the formation ofan overarching network for syntheticbiology through the formation of aspecial interest group (SIG), holding anannual forum and funding competitions tosupport the development of novel

applications. Forming a coherent,energised synthetic biology communityshould stimulate an innovative can doculture and create an environmentconducive to attracting inward investment.It should also facilitate increased levels ofinteraction between the research communityand other stakeholders including the public.

Realising the vision for synthetic biologyshould allow the UK to make a positivecontribution to the global response tochallenges in areas such as health and theenvironment. In this way, the UK mayreasonably seek to build on its currentstrengths and assume a leading internationalrole in synthetic biology, helping to setstandards and shape future regulations.This may be achieved through a variety ofmechanisms, such as participating intrans-national grant funding, hostinginternational conferences and continuingto foster coordinated efforts in syntheticbiology through research partnerships.

Finally, a leadership council should be setup to own and oversee continualdevelopment and delivery of the vision.This will provide a focal structure forassessing progress and updatingrecommendations and priorities within theroadmap.

Recommendations1. Invest in a network of

multidisciplinary centres to establishan outstanding UK synthetic biologyresource

2. Build a skilled, energised andwell-funded UK-wide synthetic

biology community3. Invest to accelerate technology

responsibly to market

4. Assume a leading international role

5. Establish a leadership council

The UK is an excellent place toprogress synthetic biology becauseit has:

a healthy ecosystem for new andestablished businesses (UK ranked*in the top 5% of countries for easeof doing business)

a strong academic base in syntheticbiology, linked to a very stronginnovative culture and heritageacross the life sciences, engineeringand physical sciences

a strong and internationally networkedindustrial base in application areasfor synthetic biology

agile and responsive funding agencies

proportionate and robust regulatoryframeworks that are internationallyrecognised and well regarded

strong UK Government support.

*World Bank Survey 2011


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IntroductionIndustry, academia, governmentorganisations, funders and othershave joined forces to produce aroadmap for the formation of aworld-leading synthetic biology sectorin the UK. Synthetic biology couldhelp to tackle major global challengesin areas such as healthcare, energyand the environment and is alreadystarting to deliver high-quality jobs.Synthetic biologys contribution tothe knowledge-based bio-economy(and the wider economy) is predictedto grow increasingly in the short,medium and long term.

The UK was amongst the rst to recogniseand respond to the opportunities raised bysynthetic biology. Publicly-fundedacademic studies, coupled withmeaningful public dialogue, have

established the foundations upon whichthe sector is now being built.Multidisciplinary expertise is alreadyenabling the UK to make signicantcontributions to international researchprogrammes and to assimilate andrespond to global developments. Our goalis to build upon these foundations,stimulate a vibrant innovation culture withinthe UK and lead towards the delivery ofproducts and services of clear economicand public benet.

This publication sets out a sharedroadmap for the UK drawn together by anindependent panel of experts at therequest of the Department for BusinessInnovation and Skills (BIS). The vision andrecommendations for the UK grew out of aseries of workshops attended by morethan 70 people representing a broad

range of stakeholders from industry, publicbodies, academia and other organisations.It also draws upon the large and rapidlygrowing body of world literature and thenumerous conferences, symposia anddiscussion forums that have recentlyfocused on synthetic biology. Althoughspecically a roadmap for the UK, workingwith international stakeholders remains anessential part of implementing theroadmap (as reected in ourrecommendations). We reviewed anumber of thematic areas in reaching a setof recommendations, which, if advancedeffectively, will establish and grow asuccessful synthetic biology sector.

The denition of synthetic biology we usedis adapted from the 2009 Royal Academyof Engineering study.

Synthetic biology is the design andengineering of biologically basedparts, novel devices and systems aswell as the redesign of existing,natural biological systems. It has the

potential to deliver important newapplications and improve existingindustrial processes resulting ineconomic growth and job creation.

Our vision is of a UK synthetic biologysector that is:

economically vibrant, diverse andsustainable: businesses havesuccessfully developed and introducednew products, processes and services leading to signicant revenues andemployment

cutting edge: leading scienticadvances and with a resilient platformof underpinning technologies delivering clear advantages inapplication development

of clear economic and publicbenet: an exemplar of responsibleinnovation, incorporating the views of arange of stakeholders and addressingglobal societal and environmentalchallenges within an effective,appropriate and responsive regulatory

framework.


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Global trends and the role of synthetic biologyThe world is becoming increasinglyinterconnected and the ability togenerate, share and interpret data ona massive scale is accelerating ourability to understand highly complexsystems. The emergence of syntheticbiology as a distinct discipline throughthe rst decade of this century is aclear example of this trend.

Potential applications of synthetic biologyarise wherever biological systems play arole, or could play a role in future. Fields ofincreasing interest at individual andsocietal levels include well-being (such asprediction and prevention of diseases,personalised healthcare, improvedlifestyle, employment), security (includingfood, water and energy security) andsustainability (meeting the challenges ofmanaging natural resources, reducing

dependence on non-renewable resourcesand nding ways to mitigate climatechange). Objectives for envisagedsynthetic biology applications in theseelds include reduction in costs, extended

or novel functionality and greaterselectivity. However, as an emergingplatform technology, the potential forsynthetic biology to develop valuableapplications in areas as yet unconsideredremains a signicant future possibility.

Addressing these elds of interest andother global challenges will continue to

generate a wealth of potential applications.There are no unique solutions to theseglobal challenges the issues arecomplex and changing, and effectiveresponses will require a combination ofscientic, technological and politicaloptions. Nevertheless, as strategies formaintaining or improving quality of life andthe environment play out within anexpanding global population, we expectthe ongoing development of biologicalsystems to play an important role in the

global quest for solutions and to providean expanding channel for relevantapplications of synthetic biology.

Synthetic biology is still at an early stage ofdevelopment and relatively unproven, butits potential is widely considered to begreat (and from some perspectivesrevolutionary). It is a platform technologywith an extensive range of possibleapplications, a few of which are alreadyprogressing towards market, with many

others under consideration.It can take many years to developtechnologically robust, safe andcommercially viable solutions, yet theneed for effective solutions to social andenvironmental challenges is increasinglyurgent. This roadmap anticipates some ofthe mechanisms and resources we needto consider now in order to better respondto emerging opportunities and challenges.

It is too early to assess the full extent towhich synthetic biology will address thesechallenges over the longer term.Nevertheless, the relevant global marketsare substantial and growing. For example,biopharmaceuticals (pharmaceuticals

Well- being Security Sustainability

Predict/ p revent diseases

Employment

Food

Water

Energy

Manage natural resources

Reduced dependence onnon- renewable sources

Climate change mitigation

Personalised healthcare

Population

Quality of Life Environment

Figure 1: No unique solution can fully address the material needs of a growing global population, but technology developments inthe biological sciences can play a role in responding responsibly to the underlying needs for security, sustainability and well-being.This in turn provides a number of channels where synthetic biology may make potentially signicant long-term contributions.

Global needs with links to synthetic biology


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derived using biotechnology) are nowestimated to be around 20% of allmedicines, effectively double what theywere a decade ago. As synthetic biologystarts to play an increasing role inmedicines and healthcare, it is becomingpossible to assess the global scale of thefuture market, at least in the near future.

Other established markets provide furtherbenchmarks for potential application forexample, it is estimated that 2010 revenuesfrom industrial biotechnology in the USalone were approximately $100bn 1. It isalso estimated that P 5bn may be added tothe European bio-economy by 2025 fromongoing research activities 2.

Such assessments depend greatly on theassumptions used, not least the denitionof synthetic biology itself and what is, or isnot, appropriate to include in the denition

of the market sector. One of the mostcomprehensive assessments available isthat by BCC Research on behalf of GlobalInformation Inc. By surveying dataavailable from leading companies, lifescience research institutions, thoughtleaders and numerous secondarysources, they compile an assessment ofglobal applications and forecast salesrevenues over the coming ve-year period.They conclude that the value of the globalsynthetic biology market will grow at asubstantial rate, from $1.6bn in 2011 to$10.8bn by 2016. In the longer term,synthetic biology also has the potential todeliver into new, as yet undiscovered,markets in response to emerging futureneeds. Regardless of the accuracy ofthese estimates, there is strong evidencefrom this and the indicators above that theprospects for future growth are substantial.

1 Biodesic 2011 Bioeconomy Update : www.biodesic.com/ library/Biodesic_2011_Bioeconomy_update.pdf

2 Innovating for Sustainable Growth: A Bioeconomy forEurope . Communication from the commission to theEuropean Parliament, the Council, the EuropeanEconomic and Social Committee and the Committee ofthe Regions, Brussels 13.2.2012 COM(2012) 60 nal.


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The UK has a long tradition of world-leading intellectual activity. We have areputation for punching above ourweight, possessing world-leadinggroups that over many years haveconsistently delivered signicantbreakthroughs in a wide range ofdisciplines, including bioscience,engineering and ICT.

Our innovative culture is one of independentand progressive research, which has at itsheart ideas and products that challenge thestatus quo. The UK is a healthy ecosystemfor new and established businesses.We have moderate levels of corporationtax with patent box arrangementsfor exploiting intellectual property, andgenerous company tax breaks toencourage research and development.

We need to reduce the risks encounteredalong the pathway to commercially viablesynthetic biology products. This will beachieved through a variety of tailoredmechanisms, including a highly skilled,exible workforce trained by our excellentuniversities and colleges. Furthermore, UKresearch and development is protected

and enabled by ethical and regulatoryframeworks that are recognised aroundthe world as robust and proportionate.

Substantial government investmentunderpins UK knowledge-basedinnovation. Total public investment in theresearch base, through the researchcouncils and the Higher EducationFunding Council for England (HEFCE),is around 6bn a year. The TechnologyStrategy Board, the UKs innovation agency,

invests a further 350m a year helping4,000 companies across all technologydomains and business sectors developnew products, processes and services.

Recent UK government announcementscommitted 75m for the ELIXIR researchinfrastructure to handle the rapidly growingvolume of biological data from high-

throughput experiments such as DNAsequencing and 145m to improveBritains e-infrastructure to drive growthand innovation. An investment of 380mhas been made by EPSRC in cutting-edgemanufacturing research with over 340current research grants and 1100collaborating companies. This includes a45m recent investment in nine newCentres for Innovative Manufacturing,all working closely with businesses to

UK strengths

TSB, BBSRCand EPSRClaunchindustrialfeasibility call6.5m

BBSRC,EPSRC, MRCand Dstl fundJoint SyntheticBiologyInitiative 2m

Policy activities

BBSRCBioscience forSociety syntheticbiology sub-panelformed

BBSRC-commissionedSynthetic biology:

social and ethicalchallenges published

EPSRC and NSFfund SyntheticBiology Sandpit:collaboration6m

BBSRC fundsMRes insyntheticbiology 250k

BBSRC andEPSRCSyntheticBiology Dialogue

ERA-NET insynthetic biologylaunched withBBSRC as aleading partner

BBSRC and NSFfund enhancingphotosynthesisgrants 6.1m

EPSRC Scienceand Innovation

Award: ICSTMCentre for SyntheticBiology andInnovation 4.7m

BBSRC fundslarge strategicgrant on clickchemistry 4.2m

EPSRC fundsinfrastructureplatformtechnologygrant 5.0m

BBSRC and EPSRCco-fund the ESFSynthetic BiologyEUROCORES grants2m

Funding activities

2007 2008 2009 2010 2011 20122006

BBSRC, EPSRC,ESRC and

AHRC fundNetworks inSynthetic Biologyfunded 900k

BBSRC large strategicgrants call in 2011 &2012 includessynthetic biologypriority (assessment inprogress)

EPSRC fundsleadership fellows2.2m

EPSRC and ESRC-commissionedscoping study inresponsibleinnovation published

BBSRC and EPSRCprioritise syntheticbiology in responsivemode funding

Figure 2: Funding for synthetic biology has been consistently applied by UK research councils since 2007, totalling more than62m ($95m) to date.

Acronyms: NSF (United States, National Science Foundation) ICSTM (Imperial College of Science, Technology and Medicine),Dstl (Defence Science and Technology Laboratory), ESF (European Science Foundation), MRes (Masters in Research) andERA-NET (European Research Area Networks)


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stimulate growth in a number of areas. An investment of 250m has been madeby the BBSRC, including 26 strategicscience programmes and 14 key nationalresearch capabilities, to meet challengessuch as sustainably feeding the growingworld population and nding alternativesto dwindling fossil fuels. The Technology

Strategy Board is to invest 200m in sevenCatapults a network of technology andinnovation centres. Other recentlyannounced investments in supportinginfrastructure include 16m in robotics(12m from the Government to 19universities, with a further 4m fromindustry) providing access to specialistlaboratories, equipment and expertiseacross a number of sectors.

A recent study has identied that syntheticbiology research is now being funded in

40 countries via more than 500 fundingorganisations, and carried out by aresearch community comprising anestimated 3000 researchers. The UK issecond only to the US in publicationoutput 3. Publication output from Europe as awhole is comparable to the US. This placesthe UK in a pivotal position to inuenceand benet from this internationallyexpanding eld.

In terms of synthetic biology, there is avery signicant presence in those sectors

that are expected to commercialise thetechnology, especially in chemicals,biosciences and pharmaceuticals,advanced materials and energy. Forcompanies in these sectors, indeed in allsectors, the UK is recognised as anexcellent place to do business. It wasranked in the top 5% (7th out of 183countries globally) for ease of doingbusiness according to a World Bank 2011

survey4. According to the ChemicalIndustries Association, it remained, in2009, the number one inward investmentdestination in Europe, with almost one fthof the total accumulated stock of foreigndirect investment. In 2007/08, the UKattracted 1,573 foreign direct investmentprojects from 48 countries, a record-

breaking performance. The UK accountsfor 57% of the whole European privateequity and venture capital market 5.

The UK chemical industry comprises amajor sector in the UK, with over 3,000companies in 2009 (generating an annualturnover of around 55bn). Growth in thissector in recent years has been roughly5% a year, with the UK having in excess of8% of the world market.

The UK has one of the most dynamic andinnovative healthcare industries in theworld. It has developed over 20% of the

worlds top 100 selling medicines (secondonly to the US, and more than the rest ofEurope combined). Every one of the top 10pharmaceutical companies in the worldhas a presence here. GlaxoSmithKline 6 has recently committed to invest morethan 500m across its manufacturing sitesin the UK to increase production of key

active ingredients for its pharmaceuticalproducts and vaccines. Together with AstraZeneca, these two companies alonereport a combined turnover of 42bn(approximately 9% of the global market).In 2007, the value of UK pharmaceuticalexports was 14.6bn, bringing in a tradesurplus of 4.3bn. The pharmaceuticalsector in the UK consists of around 600companies and employs some 67,000people. According to the Department forBusiness Innovation and Skills (BIS) 2009R&D Scoreboard, pharmaceutical andbiotechnology R&D expenditure in the UK

UK biotechnology built on strong heritageThe UK has a strong heritage in biotechnology which underpins not only world-classacademic research, but also a vibrant biotechnology industry.

The discovery by James Watson and Francis Crick of the structure of DNA in 1953 andseminal follow-up work by Crick in 1961 that cracked the DNA-to-protein code, laid thefoundations on which all synthetic biology designs now rely. UK expertise led to thediscovery of reverse transcriptase (now an indispensible part of molecular biology) andthe development by Frederick Sanger in 1977 of a vastly improved sequencing method.

This led to huge scientic advances including the Human Genome Project.In the 1990s, Professor Shankar Balasubramanian and Professor David Klenerman ofthe University of Cambridge invented Solexa sequencing: an ultrafast method forsequencing DNA that improved cost and speed by 1,000 to 10,000 fold on previoustechnologies. Solexa was sold to Illumina for $600m in 2007 and is the global marketleader in next generation sequencing. This expertise has continued to the present day.Oxford Nanopore Technology (ONT) has developed a new sequencing technologybased on fundamental research from the University of Oxford which works by running astrand of DNA through a tiny hole called a nanopore. Developments like these areleading to a point where DNA can be sequenced in real time, opening up exciting newpossibilities for medicine and biotechnology.

3 Synthetic Biology: Mapping the Scientic Landscape ;Oldham, P; Hall, S; Burton; G. (2012), PLoS ONE 7,4

4 World Bank. Ease of doing busin ess survey 2011. www.doingbusiness.org/rankings

5 UKTI.Chemicals the UK advantage . 2009.6 www.gsk.com/media/pressreleases/2012/2012-pressrelease-994808.htm


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in 2008 was 9.6bn. The medicaltechnology sector in the UK consists ofaround 2,800 companies, employing52,000 people and generating around10.6bn of turnover a year.

The UK clinical and health sciencesresearch base is second only to the US interms of global impact. It has provided a

creative crucible for the discovery of newmedicines over many decades. The UKhas several universities that regularlyappear in the top ten of university ranking,and a strong legacy of Nobel laureates inthe areas of medicine, physiology orchemistry. Over the last decade, UKuniversity bioscience departments havegenerated over 200 spin-out companies 7,8.

The UK also has major strengths in advancedengineering, manufacturing and design.The potential for synthetic biology toproduce high-tensile-strength and otheradvanced materials may well nd value inapplication elds such as aeronauticalengineering.

Bioenergy accounts for 3% of total primaryenergy consumption in the UK, with themajority (65%) being used in powergeneration and contributing towards thedelivery of the UK renewables target 9.Both Royal Dutch Shell and BP havesignicant global biofuel interests, and,together with their partnerships and jointventures, promote some of the worldslargest research, development andcommercial renewable fuel programmes.

In 2010, the energy supply industry in theUK contributed approximately 4% of GDP(60bn), 10% of total investment, 52% ofindustrial investment, and directlyemployed approximately 173,000 people 10.

The UK energy research community alsoproduces recognised high-quality research 11 across a variety of energy technologies.The Biotechnology and BiologicalSciences Research Councils (BBSRC)Sustainable Bioenergy Centre is a 27minvestment in bioenergy research. Thecentre brings together six world-class

research groups and 15 leading industrialassociates.

7 Royal Society (2010). The scientic century. Securingour future prosperity . http://royalsociety.org/policy/ publications/2010/scientic-century/

8 Ofce for Life Science and UK Trade and Investment(2010). Life science. The UK: collaboration for success .http://webarchive.nationalarchives.gov.uk/20110120011807/bis.ecgroup.net/publications/ uktradeinvestment/uklifescience/10579.aspx

9 UK Bioenergy Strategy, 201210 UK Energy In Brief 2011, DECC.

11 Report of the International Panel for the 2010 RCUKReview of Energy


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Synthetic biology is the design andengineering of biologically basedparts, novel devices and systems aswell as the re-design of existing,natural biological systems. The stepchange in the synthetic biologyapproach is to engineer biologicalsystems to perform new functions in amodular, reliable and predictable way,allowing modules to be reused indifferent contexts. It has the potentialto deliver important new applicationsand improve existing industrialprocesses across many sectorsincluding healthcare, energy,pharmaceuticals, materials, andremediation resulting in economicgrowth and job creation.

Synthetic biology has developed over thelast decade. The eld arose from the

conuence of a number of factors. First,the revolution in molecular biology that hasoccurred over the last 60 years and inwhich the UK has played a leading role.

A signicant development was DNAsequencing, which during the 1990s andearly 2000s yielded the genomesequences of a handful of importantspecies. From the standpoint of syntheticbiology, efciency gains from next-generation sequencing have led toindustrial-scale enterprises with potentialto open up natures vast reservoir ofbiological information and, with it,identication of novel biological parts.Coupled to this, the development ofreliable, chemically based, DNA synthesisis allowing the alteration and constructionof DNA sequences, their use in existingbiological chassis, and the possibility ofbuilding whole genomes from scratch.Second, the development of ourunderstanding of biological systems andhow to manipulate them is advancing atpace through systems biology,

bimolecular sciences and related elds.This all means that we can now attemptthe design and engineering of biologicalsystems with increased condence andsuccess.

Importantly, synthetic biology is atranslational eld that takes foundationalresearch from a range of elds (forexample, biochemistry, systemsengineering, molecular biology, plantsciences, chemical engineering,informatics, microbiology) and integrates

and builds upon these ndings throughthe application of engineering designprinciples. This is possible becausebiological systems are inherently modular

and biological function usually expressedthrough proteins and RNA is primarilyencoded in DNA. In addition, biologicalcontrol and regulatory elements can bedened (for example, logic gates, feedbacksystems, ampliers and oscillators). Anobjective of the eld is therefore to utilise

the diversity of biological parts (genomesand metagenomics, synthetic parts/ components) to build new biologicaldevices and systems with dened function.

1988 1993 1998 2003 2008 2011

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Cost: sequencingCost: short oligoCost: gene synthesis

Synthetic biology

Clicking DNA and RNA

Professors Tom Brown (University of Southampton) and Andrew Turbereld (Universityof Oxford) are leading a collaboration developing a technique for producing DNA andRNA structures more efciently and on a larger scale than is possible using currentenzyme-based technologies. They have clicked DNA and RNA segments togetherusing a chemical method which could allow long strands of DNA to be produced in

large amounts for industrial-scale applications. The ability to click DNA together opensup the possibility of producing new DNA structures decorated with a variety of usefulchemical modications for industrial uses in the UK bioeconomy, including in clinicalapplications, for example to switch-off disease genes.

Cost per base of DNA sequencing and synthesisRob Carlson, June 2011, www.synthesis.cc

Figure 3: The cost of DNA sequencing has plummeted over the past two decades whilst moremodest reductions have been achieved to date in synthesis


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The engineering concepts ofmodularisation, characterisation andstandardisation are central to the eld.Here, modularisation is dened as theprocess of breaking down a biologicalsystem into a series of well-dened,

standard parts or components (forexample, a gene, protein, a pathway, amicrobe in a culture). Characterisation isthe process of dening the behaviour andfunction of these parts in particularcontexts in order to understand how theycan be used in human-dened design.Standardisation means that the designprocess is based on well-dened standardmodules that can be interfaced to producea device or system. It is accepted thatinterfacing biological parts will bechallenging, and issues relating to contextdependency, predictability and robustnesswill need to be tackled. The standardisationof components and processes generatedsignicant advances in mature engineering

disciplines, and a major challenge forsynthetic biology is to put biologicalsystems engineering on the same footing.

Synthetic biology comprises a translationalprocess achieved through the deploymentof platform technologies, within aframework of robust engineering principlesand practices. These platforms harnessinformatics (for example, databases,Bio-CAD software), analytical technologies(DNA synthesis and assembly,sequencing, metabolic and proteomicproling) and biological technologies (forexample, host cell systems) in the processof systematic design. Another keycomponent of the translational process isinterplay between experiment and theory,and the application of a synthetic biology

design cycle. The cycle comprises thefollowing steps: specication, design,modelling, implementation, testing andvalidation. These approaches are centralto enabling the creation of industrial

products when integrated with newscale-up methodologies, andindustrialisation is one important end pointof synthetic biology. Another importantend point is the contribution that syntheticbiology will make to the fundamental

understanding of bioscience, which,combined with rapid and signicantdevelopments across the relatedunderpinning biosciences themselves, willstimulate further generations of industrialproducts made using this approach.

Synthetic biology is now poised to have animportant industrial future in a range ofelds. Figure 4 illustrates how theunderpinning academic disciplinescontribute to the methodology to createdevices, networks and systems as part of

the synthetic biology translation process.This leads to industrial processes which, inturn, leads to products.

Figure 4: Synthetic biology is both a platformtechnology (building a systematic basis fordesign combining biological, engineeringand computational capabilities) and atranslational technology (providing the linkbetween a wide range of underpinningdisciplines ranging from biochemistry tosystems theory and practical applicationsin a wide range of different market sectors)


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The primary purpose of thistechnology roadmap is to establish avision for synthetic biology in the UK,and to identify the processes thatmust be applied to realise it. Itprovides a framework within which toconsider future options andcoordinate actions. Because syntheticbiology is an emerging and fast-developing sector, the purpose of theroadmap is not to provide a detailedproject plan but, more importantly, todetermine those core elements thatneed to be put in place as a secureplatform upon which innovativedevelopments may build in future.The process of generating theroadmap is itself an integral part ofopening up stakeholder discussion,seeking consensus and starting theprocess of building an informed,energised and effectively supportedUK-wide community.

This roadmap has been produced during2012 by an independent panel of expertsat the request of the UK Department forBusiness Innovation and Skills. Itincorporates material generated duringtwo UK roadmap workshops attended by70 participants representing a broad rangeof stakeholders from industry, publicbodies, academia and other organisations.The workshops followed a processestablished through extensive experienceby the Institute for Manufacturing (IfM) inCambridge, ensuring substantialengagement of all participants andgenerating a wealth of valuable materialand insights. The roadmap has also beenheavily informed by the large and rapidlygrowing body of world literature and theoutputs of the numerous conferences,symposia and discussion forums that havefocused on synthetic biology in recent years.

Fundamental to the roadmap study, asapplied in the workshops, has been theneed to consider the activity as a whole,taking an integrated overview of all keyinuences upon and stages within theprocess, whilst informing the discussionwith essential details and knowledge fromexperts representing a broad cross-

section of stakeholders. Our intentionthroughout has been to identify early thesteps that must be taken along thejourney, to avoid delay in anticipating andresponding to the opportunities andchallenges that lie ahead, and torecognise that there are many otherstakeholders whom we would encourageto engage in further shaping the wayforward as the community develops.

The workshops considered the roadmaplandscape as a whole, across a range of

timeframes, stretching out towards a post2030 vision. This was populated in detailfrom both a top-down perspective,considering trends and drivers, and abottom-up perspective, consideringenablers, capabilities and technology,leading to consideration of value-creationopportunities and value-chainperspectives. Key outcomes aresummarised in the A3 fold-out UKSynthetic Biology in the UK: RoadmapLandscape graphic at the back of thispublication. The individual elementscaptured in this diagram are not intendedto represent a comprehensive set ofactivities with precise timings, but rather torepresent, through their entirety, anillustration of the broad landscape, theoptions available and the timescale thatmust be considered. It is clear thatsynthetic biology should not beapproached in a sequential, piecemealfashion, but as an integrated whole,addressing issues across the entirelandscape in the short term, whilst

maintaining a long-term perspective.

By focusing on value-chain perspectives,and considering the various processesthat apply when nurturing ideas to market,for example, from academia through SME/ start-up companies to large industry, wewere better able to identify key needs thatshould be addressed in nurturing theemergence of a vibrant future industry.

Important considerations identied in theworkshops included the need to be clearwhat should be the main areas of focus,recognising the need for genuine marketpull for products and for selecting keycategories in which the UK can excel, andhow to accelerate progress reducingdevelopment time to market acknowledging the essential role of publicfunding.

A wide spectrum of applications can beenvisaged, each specic application

having its own particular trajectory inscope and time, from concept through tocommercialisation. Although eachindividual application will face its own veryspecic development programme issues,a number of generic success factors couldbe identied from the many workedexamples we considered. By addressingthose generic factors, we can create amore broadly supportive operatingenvironment and facilitate progress acrossthe entire range of potential applications.

A fundamental challenge is to reduce thedevelopment time and cost to market.Effective links between academia andindustry are important throughout,although the balance of engagement willshift towards industry as the concept stepstowards market deployment. Taking anintegrated approach to the whole is criticalto rapid development, but, in practice,development and scaling-up of a concepttends to be stepwise as new challengesemerge. This approach is capturedschematically in gure 5, opposite. Thereare many different ways of clustering anddening the various stages, but this is notcritical to the scheme. For illustration, weconsider progression through four stages,

A technology roadmap


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A number of recurring ideas,observations and issues emerged thatwe consider directly relevant to thegeneration of a UK roadmap forsynthetic biology. We have gatheredthese into ve core themes.

The rst theme foundational science andengineering relates to the underpinning

technological potential of synthetic biologyand the need to establish sufcient andaccessible capabilities within the UK tomaintain a leading edge.

The second theme continuing responsibleresearch and innovation is the recognitionthat the ground-breaking opportunitiesand benets arising from synthetic biologyalso come with the potential forunintended consequences, which can beavoided through awareness, training andadherence to prevailing regulatoryframeworks.

The third theme developing technology forcommercial use recognises that it can bevery difcult to take an idea from thelaboratory environment through to afully-scaled industrial product or service.Steps need to be taken to help overcomethe more challenging hurdles so thatimportant opportunities do not fail forreadily avoidable reasons.

The fourth theme applications andmarkets is the identication of futuregrowth markets and the development ofsuitable applications that would gain frommore effective interactions between theacademic and industrial communities.

The fth theme we consider here isinternational cooperation. Realising the

vision for synthetic biology should allowthe UK to play a positive role in theinternational response to global challenges,including helping to set standards andsuitable operating frameworks.

It will be clear that these core themes aremutually linked and must be addressedcollectively to achieve a successful outcome.

Themes


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Synthetic biology is an emerging areaarising out of the conuence ofseveral core disciplines. It integratesknowledge, principally from biology,engineering and chemistry, to createnew products and processes. Aby-product of this process isincreased understanding of biologicalsystems. The UK already possessesworld-class expertise within thesecore disciplines this provides thestrong foundation upon whichsynthetic biology is being built. Astrong message that emerged from theroad mapping workshops was thatinnovation in academia andmultidisciplinary conuence are keydrivers of the eld.

To date, UK research funding for syntheticbiology has come principally from the

Biotechnology and Biological SciencesResearch Council (BBSRC) and theEngineering and Physical SciencesResearch Council (EPSRC). The fundinghas supported community networks toinitiate research partnerships, a specialistcentre, strategic funding for technologiesand applications, and high-risk/high-rewardstudies to explore potential in new areas.International collaboration has resulted infunding to UK universities from a range ofsources including the EU, the GatesFoundation and joint programmes with theUS National Science Foundation. Thesegrants are important because they establishcollaboration with other leading internationalgroups and show the quality of the UKacademic base in synthetic biology.

Multidisciplinary centresand funding

There is a need to capitalise on theseinvestments and the research undertaken.The UK has one funded centre in synthetic

biology at Imperial College and severalother large-scale investments alsodeveloping platform technologies(Southampton and Oxford; Warwick) andapplications including second generation

biofuels (Nottingham). A recentdevelopment is the formation of aconsortium for synthetic biologycomprising Imperial College, Cambridge,Edinburgh and Newcastle universities andKings College London. This aims tofurther establish a signicant infrastructureand resource for synthetic biology withinthe UK and in support of internationalcollaborations 13. In addition to thesespecic examples, there are many othersignicant groups actively engaged indirectly related research, funded byvarious research councils, industry andother funding bodies (the BBSRC andEPSRC alone support more than 30different higher education institutions inrelated elds). For the UK to fully leverageits capabilities as a basis for industrialgrowth, it will be important to coordinatesupport for synthetic biology researchcentres and corresponding researchagendas that can facilitate the integrationof the UKs research and training capabilityin the eld, ensure good access toleading-edge equipment and generatemore opportunities to interface with industry.

It has already been proposed that aninnovation and knowledge centre (IKC) forsynthetic biology should be established asan important mechanism towards drivingtechnology towards commercialisation.This is described in more detail in theme 3.It is, however, essential to establish how

the hub will integrate with the researchcentres the concepts of multidisciplinaryresearch centres and a commercialisationcentre must be developed as an integratedwhole. Concentration of research fundinginto academic centres of excellence is afeature of synthetic biology investment inthe US, China and EU. The UK centres arenecessary to build on our strongfoundations and to create bioengineeredsolutions to underpin the UK bioeconomy.Recognition of the social sciences andhumanities research effort in syntheticbiology, together with potentialapplications in the biomedical arena, maylead to an increase in strategicallycoordinated research councils funding.

In 2007, the UK research councilsestablished seven research networks insynthetic biology to bring together different

disciplines, to develop a common languageand to develop potential research projects.The networks integrated a strong socialand ethical dimension into their activitiesand involved ten universities withconsiderable researcher outreach.The grants for the existing sevennetworks have recently come to an end.The roadmap workshops have identiedthe need for continued multidisciplinarynetworking activities. These includeacademic-to-academic networking;academic-to-industry networking; and anumber of supporting activities. A pan-UKnetwork could bring together the work ofthe seven previous networks under acommon umbrella. This would provide a

Theme 1:

Foundational science and engineering

Bacterial logic gatesProfessors Richard Kitney and Martin Buck (Imperial College London) havedemonstrated that we can build logic gates, like those used for processing informationin computers and microprocessors, out of harmless gut bacteria and DNA. Logic gatesare fundamental building blocks in silicon circuitry. The researchers have replicatedthese logic gates using biological parts and showed that they behaved like theirelectronic counterparts. The new biological gates are also modular, which means that

they can be tted together to make different types of logic gates, paving the way formore complex biological processors to be built in the future.

13 www.epsrc.ac.uk/newsevents/news/2012/Pages/ syntheticbiology.aspx


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forum for the research centres, as well assmaller research groups in other institutions,to discuss a range of topics, exchangebest practice and act as a showcase forthe presentation of work with applicationsin a range of industry sectors. It isenvisaged that the network should usetraditional formats and virtual

communication, such as socialnetworking, to build an integrated syntheticbiology community. The plant sciencesGARNET model14 provides an example ofa pan-UK network that undertakes tasksthat mirror those required in syntheticbiology. As discussed under theme 3,these networking concepts could be takenforward by the recently formed specialinterest group (SIG).

Training

The UK has been very proactive in thearea of education and training relating tosynthetic biology over a number of years.For example, in the session on educationand training at the Fourth InternationalMeeting on Synthetic Biology (SB4.0), UKuniversities were singled out (along withsome US universities) as leaders in thisarea. This activity has taken a number offorms. There are now a number ofprogrammes in operation. These includeundergraduate nal-year options, MScs

and MRes/PhD programmes. In addition,UK teams have been highly successful atiGEM15 (an international undergraduatecompetition) over a number of years.There may now be a need to streamlinethe existing education and trainingprogrammes and, where appropriate, tointroduce new courses to address theindustrial translation process and, moregenerally, to meet the needs of industry.

It is important to recognise that specialisttraining is required to produceprofessional, responsible synthetic biologyresearchers. The road mappingworkshops identied the need to build,maintain and develop the skills base andto enhance interdisciplinary graduatetraining. It is also important to recognise

that synthetic biology training andeducation needs to take place at all levels from school outreach (potentiallyincluding more practical engagement andlearning, as for example being promotedelsewhere via iGEM High School 16) toundergraduate and postgraduate trainingand beyond and that mechanisms needto be tailored to meet the needs of specicstudent groups. Hands-on experience ofsynthetic biology should start at theundergraduate level with taught modulesgiven by teams of research-active staffwith direct experience of wet-lab biology,engineering design and modelling, andexpertise in the ethical and societalaspects of synthetic biology. Such coursesshould attract students drawn from anumber of disciplines, for example biology,engineering and chemistry.

Postgraduate training must be intrinsicallymultidisciplinary. In addition to theexperience derived from existingprogrammes in synthetic biology aroundthe world, it is important to learn fromprogrammes in associated areas, forexample, systems biology. Suitablestudents should be identied to study at,

or in association with, the researchcentres. In this regard, it should be notedthat many of the most successful researchcentres in synthetic biology around theworld have, from their inception, includeda multidisciplinary training environment.Students should follow the one-year MResplus three-year research project modelthat has been very successful in a numberof areas. The approach also includescross-disciplinary co-supervision, togetherwith professional internships within UKcompanies and summer schools. Inaddition, students should be educated insocietal and ethical issues, andopportunities for technical andmanagement training should be explored.Short courses for existing industrialpersonnel should be envisaged.

Any course in synthetic biology will have ahigh content of engineering and physicalscience. Hence, synthetic biologistsaiming to practise in industry may benetfrom professional as well as academicqualications (compare chartered status inengineering). Accreditation of courses, inthis context, would be carried out by theappropriate professional institutions (forexample, the Institute of Engineering andTechnology).

14 See www.garnetcommunity.org.uk/ 15 See http://igem.org/Main_Page

16 iGEM High School is now in its second year andexpanding internationally: http://igem.org/High_School_Division


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Theme 2:Continuing responsible research and innovationIt is crucial that this technologycontinues to be developed in asocially responsible fashion, and thatrelevant stakeholders, regulators andthe public are engaged in researchand innovation processes from theoutset. Responsible research andinnovation encompasses, but is notconned to, operating within an

effective risk regulatory framework.The UK needs to be, and to be seen tobe, leading the way in frameworks andmethodologies for responsibleinnovation. The UK has alreadyinitiated public dialogue in syntheticbiology and encouraged interactionbetween regulators and funders.

Since synthetic biology is a new eld, thereis much uncertainty surrounding both therisks and benets of its research andapplications. While stringent riskmanagement is crucial for responsibleresearch and innovation, inescapableuncertainty must be acknowledged andaccounted for. The aim of responsibleresearch and innovation is not simply topredict and proactively manage negativeoutcomes, but also to shape decision-making procedures that recognise suchuncertainty across the whole life cycle ofinnovation. To foster successful innovation,governance must be exible, transparent,open to wider participation, andresponsive to emerging evidence andchanging social priorities.

Public acceptability

Public acceptability is widely recognisedas a crucial issue for synthetic biology, butit cannot be adequately dealt with throughcommunication aimed at reassuring thepublic. Prior public controversies onemerging technologies demonstrate that itis essential for debates to go beyond thecommunity of experts to open updiscussions about the purpose of innovationand about uncertainties and complexitiessurrounding both the benets and risksassociated with particular applications.Research has shown that the public is nota singular pre-existing mass that accepts orrejects particular technologies according to

xed preconceptions. The direction takenby innovation pathways, and their perceivedsocial consequences, themselves shapepublic responses. The responses anddecisions of many and varied socialgroups alongside those of academicresearchers and rms help to determinetechnological pathways and the realisationof benets. These include institutions

involved in health, safety and environmentalregulation, intellectual property, researchfunding, and capital investment, as well asintended users and beneciaries, and civilsociety groups. New social groups alsoemerge alongside innovation (newpressure groups may come into beingwhen, for example, a new drug isdeveloped to extend the life of patientswith a specic terminal cancer). All ofthese groups need to be actively engaged,throughout the process, in the governanceof synthetic biology research and innovation.

In the UK, public acceptability wasrecognised as crucial from an early stageand led to a large-scale synthetic biologydialogue in 2010. Findings from the dialogueshowed there was support for syntheticbiology but that this was conditional. Whilethere was great enthusiasm for thepossibilities of the science and its application,there were also fears of control and misuseand concerns about how to govern thisnovel area when there is uncertainty overits outcomes. One of the key ndings ofthe dialogue which is consistent with a

large body of social science research was the emergence of these ve keyquestions that synthetic biologists shouldbe willing and able to answer 17:

what is the purpose? why do you want to do it? what are you going to gain from it? what else is it going to do? how do you know you are right?

To build on this successful dialogue, it iscrucial that these questions are at theforefront of ongoing decisions about thecommercialisation, translation andregulation of synthetic biology. Indeed,BBSRC, on behalf of the UK researchcouncils, posed those questions in theclosing session of the Six-Academy

Synthetic Biology Symposium II inShanghai in October 2011 18. Althoughaddressing health, environmental andsecurity risks is important, this will not initself lead to broad public acceptabilityunless innovation in synthetic biology isdemonstrably directed towards:

new products, processes and servicesthat can bring clear public benetsincluding, but not limited to,employment, improved quality of lifeand economic growth

solutions to compelling problems thatare more effective, safer and/or cheaperthan existing (or alternative) solutions.

Integrating social sciences, humanitiesand arts researchers can help withunderstanding of, and engagement with,such issues and thus foster responsibleinnovation. The UK is at the forefront ofexperimenting with such cross-domaincollaborations: the seven synthetic biologynetworks included social scientists, artists,philosophers, and legal scholars; and the

Imperial College Centre for SyntheticBiology and Innovation (CSynBI) was setup as a joint centre between scientists andengineers at Imperial College and socialscientists at the BIOS research group 19.

18 Six Academies Synthetic Biology Symposium II Shanghai 12 14 October 2011, www.sibs.ac.cn/ synbio/programme.asp

19 BIOS a centre for Biological Sciences originally basedat the London School of Economics (LSE) and nowbased in Kings College London

17 BBSRC/EPSRC (2010) Synthetic Biology Dialogue.Swindon, Biotechnology and Biological SciencesResearch Council (BBSRC) and the Engineering andPhysical Sciences Research Council (EPSRC), p.7.

Online at: www.bbsrc.ac.uk/web/FILES/Reviews/1006-synthetic-biology-dialogue.pdfFor a summary of how these same i ssues recurthroughout all the ScienceWise Dialogues, see Chilvers,J and Macnaghten, P. (2011) The Future of ScienceGovernance: A review of public concerns, governance

and institutional response . London: Sciencewise-ERC.Online at www.sciencewise-erc.org.uk


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Regulating synthetic biology

Building a culture of responsibility,evaluating health and environmental risksat all stages from the planning stageonwards, and increasing awareness ofthose risks are integral to good practice insynthetic biology research and innovationand in the subsequent development ofsynthetic biology products, processes andservices. Regulatory authorities recognisethat synthetic organisms may haveunintended harmful consequences; incertain circumstances they could transferDNA to other organisms, and unanticipatedinteractions between synthetic organismsand the environment or other organismscould cause unintended harm to theenvironment and public health. Such risksare currently covered by relevantconventions and legislation, and active

review processes exist to ensure theseremain informed by, and responsive to,emerging developments in syntheticbiology. Biosecurity issues also arise fromthe risk of deliberate actions intended tocause harm by people who pay no heed tolegislative regulations. Additional measuresmay be required for such scenarios andthese have been seriously considered innumerous studies in recent years 20,21.

At present, synthetic biology is regulatedby conventions and legislation that was

established to regulate the use ofgenetically modied organisms (GMOs).Regulations for the contained use anddeliberate release to the environment ofGMOs are determined at the EU levelthrough directives which are thentranscribed into UK law. In the future,certain applications of synthetic biologycould conceivably entail the deliberaterelease of modied organisms to the

environment. If this were to be the case,the legislation relating to the deliberaterelease of GMOs would apply. Under thissystem, decisions on research trials aremade at the national level, whereasdecisions on marketing applications aremade at the EU level. Currently there aresome problems with the operation of theEU clearance processes, and this couldact as a barrier to commercialisation ofcertain synthetic biology products. The UKgovernment is currently engaged in EUnegotiations with the aim of enabling moreeffective operation of the current regulatory

system. The Cartagena Protocol onBiosafety to the Convention on BiologicalDiversity is an international agreementwhich aims to ensure the safe handling,transport and use of living modiedorganisms (LMOs) resulting from modernbiotechnology that may have adverseeffects on biological diversity, taking alsointo account risks to human health 22. There

are 163 countries party to the CartagenaProtocol , including the UK.

Work in research laboratories involving thegenetic manipulation of organisms isrequired to comply with Contained UseRegulations 23. All persons carrying outsuch work must notify the Health andSafety Executive (HSE), and for higher riskwork must have consent before theyproceed. The controls required are basedon an assessment of the risks of potentialfor harm to human health and for damageto the environment. Any work with asubstance produced by synthetic biologyprocesses, which is not itself a geneticallymodied organism, but is potentiallyhazardous to human health (for exampletoxic or allergenic), would require riskassessment and appropriate controls toprotect the workers and any other personswho might be affected 24.

Regulations are kept under constantreview by the regulators, be they the HSE

Public dialogue on synthetic biologySynthetic biology has enormous potential but also raises questions around ethics,social justice and biosecurity. In 2010, the Biotechnology and Biological SciencesResearch Council (BBSRC) and the Engineering and Physical Sciences ResearchCouncil (EPSRC) published the results of a joint public dialogue on synthetic biology(with support from Sciencewise-ERC, the UKs national centre for public dialogue inpolicy-making involving science and technology issues).

The dialogue explored peoples hopes and fears for synthetic biology, aiming toensure that the research funded by the two councils sits comfortably with society.Four workshops in England, Scotland and Wales were attended by 160 members ofthe public. An additional 41 interviews were carried out with consumer groups, industryand scientists, focusing on the issues and the development of the science. Thedialogue revealed that most people are supportive of the research but with conditionson how and why it is conducted. The results of the dialogue have inuenced howBBSRC and EPSRC think about funding research in synthetic biology.

20 NIH Guidelines for Research Involving RecombinantDNA Molecules

21 Addressing biosecurity concerns related to SyntheticBiology : Report of the National Science Advisory Boardfor Biosecurity (NSABB), April 2010

23 Directive 2009/41/EC on the contained use ofgenetically modied micro-organisms; GMO(Contained Use) Regulations 2000

24 The Control of Substances Hazardous to HealthRegulations 2002.22 http://bch.cbd.int/protocol/


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or the Home Ofce, recognising thatscience continues to develop andregulation needs to reect those changes.The principles underlying currentregulations are that they:

place the protection of human healthand prevention of harm to theenvironment as the rst priority

take a risk-based approach, requiringproportionately more stringent controlsfor higher hazard work

allow novel work to be carried out,without unduly hindering innovation, butfor GM work require that riskassessments are reviewed and forhigher-risk work that the regulator givesconsent before the work begins.

Questions have been raised about theextent to which the risk assessmentframework for genetically modiedorganisms will be appropriate for syntheticbiology (due, for example, to the largernumber of genes transferred and thepossible use of synthetic genes with nowild-type comparator) 25. The currentgeneral consensus among regulators andscientic institutions is that existing GMregulations are broadly adequate andcould be adapted for synthetic biology, butthat regulators need to keep a watchingbrief as synthetic biology research develops.

The regulatory framework for the release ofgenetically engineered organisms remainscontested, most visibly in Europe, but alsoin the United States and around the world,albeit relating to technologies that precedeand are different from synthetic biology. Whatis contested is not so much Is it risky or not?but rather: What counts as risk? and Whodecides? It will be crucial, as syntheticbiology progresses, to continue developing

a robust regulatory and enforcement regimeinvolving scrutiny, evaluation and modicationof existing regulations to address issuessuch as indirect, delayed, and cumulativelong-term effects, including accumulatedeffects of approvals for different organisms;and appraisal of risks which consider howthe technology will be used in practice, inreal-world conditions. The latter includes thepotential for dual use at a time of increasingglobal uncertainty. (Science is primarily usedto benet humanity, but particular scientictechnologies can be misused, presentingscientists and others with an ethical quandaryknown as the dual-use dilemma 26.) It isalso essential to ensure that a broad rangeof scientic experts and other stakeholderscontinue to be involved in scrutinising andcontributing to the questions asked in risk

assessments. This must include internationalcollaboration, which will be essential toallow the UK to realise the full benets ofits synthetic biology sector.

In addition, in order to ensure that the spiritand not just the letter of the legislation isfollowed, it is important that researchersand regulators work together to ensurethat all novel entities and methods

produced through synthetic biology areencompassed by these GMO regulations,or are replaced with alternative legislationproviding appropriate risk safeguards.

In summary, responsible research andinnovation for synthetic biology requires:

that inescapable uncertainty isacknowledged and measures are put inplace to ensure safe, rapid and effectiveresponses to any unforeseen problems

that the UK maintains and develops itsregulatory and enforcement regimefor environmental, health and securityrisks relating to synthetic biology andthat it does so from an internationalperspective

that engagement means genuinelygiving power to a wide range of diversesocial groups, including those whowill be the end users or presumedbeneciaries of the technologies,taking their concerns seriously, andenabling them to participate throughoutthe whole pathway of technologicaldevelopment.

Checks and balancesThe Biotechnology and Biological Sciences Research Council (BBSRC) has a numberof checks and balances in place to ensure that the researchers it funds are aware ofany ethical and social issues that their research raises, and that they respond to theseappropriately. Applicants are required to consider the ethical issues raised by theirgrants, for instance, the need to use animals in an experiment or the potential formisuse. If any issues are identied by the peer reviewers or grant committees then

BBSRC can draw on a broad range of expertise via its Bioscience and Society Strategypanel and from third parties like the National Centre for the Replacement, Renementand Reduction of Animals in Research (NC3Rs). BBSRC will not start paying grantsuntil all issues have been resolved.

26 Rodemeyer, M (2009) New Life, Old Bottles: RegulatingFirst-Generation Products of Synthetic Biology WoodrowWilson International Center for Scholars; Dana GV,Kuiken T, Rejeski D, et al. Synthetic biology: Four stepsto avoid a synthetic-biology disaster . Nature 2012483(7387): 29.

26 Parliamentary Ofce of Science and Technology,Postnote, July 2009, Number 340


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In this third thematic area we considerhow to advance synthetic biologytechnologies so that they are t for usein a broad range of potentialapplications and markets. Implicit inthis activity is the desire to increasegrowth in the UK economy, generatingwealth and creating jobs, consistentwith the ongoing practice of responsibleresearch and innovation outlined intheme 2. Below, we set out some ofthe opportunities available in the UKto accelerate the development anduptake of this powerful technology.The work draws on the overarchingframework of the Technology StrategyBoards Emerging Technologies andIndustries Strategy, other roadmapsand literature, sector expertise andthe outputs of the two roadmappingworkshops. A key element is theiterative process of matching thecommercial requirements of a numberof potential markets to theperformance that is, or could be,achieved by the technology.

Synthetic biology is still at a relatively earlystage of emerging from the science base,but it has truly disruptive potential. Alreadyit allows some things to be done that werenot previously possible. Many more thingswill follow. Even now it is beginning to offertotally new opportunities for existingbusinesses and new entrants. Below aresome of the ways in which thoseopportunities can best be realised.

Seeing the opportunity

The UK possesses outstanding expertisein its science and engineering base as wellas imaginative businesses that are bothwell established and newly formed. Thescience is rapidly advancing and marketsare changing almost as quickly. This istrue, not just in the core synthetic biologytechnologies, but also in the supportingtechnologies such as rapid sequencing,microuidics and bioCAD. It can bedifcult for individuals in businesses to

stay abreast of scientic developmentsacross the entire eld and to determinehow these can be best applied to theopportunities they see in their ownorganisations and markets. No individualor group of individuals is likely to be fullyaware of all of the most promisingbusiness opportunities. An opportunity

exists, therefore, to bring those at thecutting edge of science together withinnovators in business to nd the best tbetween commercial opportunity andscientic potential, and to help them towork together to develop their ideas: toenergise the new product supply chain,and to inform the science base.

Creating the industrialtranslation process

Synthetic biology is, by denition, an

applied approach. It draws on a range offundamental elds in the life sciences, asdescribed in the synthetic biology sectionand outlined in gure 4. The industrialtranslation process takes the idea througha development process from laboratory tomarket, as schematically captured in gure5. Output from the initial science andengineering phase may take any of a widerange of forms, such as newly characterisedbioparts within the registry, new industrialhosts or chassis, or new assembly methods.

The next step in the translation process isthe development of the industrialengineering methods appropriate for theapplications being developed, andultimately the development of biofactories.

All of the stages in the translation processlead through to products and, ultimately,to market. It is essential to developprocesses whereby industrialists andacademic researchers can moreeffectively collaborate to dene applicationprojects and requirements in terms of

industrial techniques and the market,including societal benets. Thesecollaborations are likely to be different inrelation to projects with large companiesand projects with SMEs.

Accelerating the journeyto market

Most modern technological products andservices exist in complex, and global,supply chains, and it takes time tointroduce and have adopted radicallydifferent propositions. Each organisationalong the chain has to evaluate the impacta new technology may have on itsoperations, and has to satisfy itself that itcan assure the quality and delivery of thecommercial offering. It has been shownthat one of the best ways to speed up thisprocess is to create demonstrators thatshow what is on offer in a compellingway27. Helping innovating organisations toproduce demonstrators of various kindswill advance the technology more quicklyto market. In some cases the type ofdemonstration needed will be

demonstration of scale, and access toproduction capability to assist scale-upwill be important. Some of the facilitiesneeded already exist in the UK. In othercases, demonstration will require accessto cutting-edge laboratory equipment, andit is important that critical equipment islocated within the UK it should be madeeasier for businesses to access theexpertise and facilities within the universitysector. This could be particularly valuablein highly specialised areas or where acombination of biology and electronics ormaterial sciences is used.

Reducing the commercialand technical risk

It is a regrettable fact that new productintroductions often fail, even where theproducts themselves can deliver benetsfor consumers and have economicpotential 28,29. A proven method of bringingmore products to market sooner is to help

Theme 3:

Developing technology for commercial use

27 Technology Strategy Board, Emerging Technologies and Industries Strategy 2010-13 (Feb 2010)www.innovateuk.org see under publications/strategy

28 Source: Stevens, G.A. and Burley, J., 3,000 Raw Ideas= 1 Commercial Success! ,(May/June 1997) ResearchTechnology Management, Vol. 40, #3, pp. 16-27.

29 Robert G Cooper, Winning at New Products , 3rd Edition,p10-12 (Basic Books, 2001)


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reduce the risk of technical failure, and toshare the nancial risk. This can be doneby bringing people from differentorganisations and with different capabilitiestogether to work jointly on collaborativeprojects. These organisations can ndbetter solutions to problems, and share theresearch and development costs, reducing

the burden on any individual one of them.In the next stages of the development ofsynthetic biology, whilst companies mayperceive that there is little or no technicalrisk in specic project areas, they certainlyperceive that there is commercial risk.

A three-component approach, comprisinginput in both cash and kind, has beenfound to be effective. The threecomponents of this hybrid model areindustrial resources, public resources anduniversity resources. The public funding

contribution would normally be in terms ofcash or the de-risking of the investment tomake it more attractive to other potentialfunders (such as venture capitalists). Themain university contribution is in terms ofresearch facilities and highly skilledresearch personnel. Industry maycontribute cash or know-how. The publicand university components of the modelact as a catalyst to counteract commoncauses of failure of application projects asseen from industry, for example throughprovision of training, mentoring andexpansion of partnering opportunities.Larger industries may also separately fundtheir own in-house research to addresstheir internal investment criteria.

In his keynote speech at the University ofEast Anglia Whats the Good ofGovernment? 30 the Minister of State forUniversities and Science David Willettssaid: The Government can bear the bigrisks of scientic innovation, which are toogreat for any individual company. This isnot to be interpreted as being an argumentfor a blank cheque from government forinnovative companies, but it does highlight

the potential for government to be an earlyadopter and to stimulate demand forpotentially valuable innovations that initiallyentail a high degree of risk. One suchmechanism potentially available togovernment might be use of the SmallBusiness Research Initiative (SBRI) scheme.SBRI could be used to procure syntheticbiology developments that potentially

meet the strategic and operational needsof government departments and theinterests of society that they serve whilstsimultaneously serving to de-riskcommercial developments for emergingprivate sector customers therebycreating new commercial markets as well.BIS has increased the funding for SBRIthrough the package of support for SMEsannounced in the Innovation andResearch Strategy 31 to be deliveredthrough the Technology Strategy Board.

Since the launch of the programme in2009, SBRI has awarded 914 contractsworth 78m to technology based SMEs.Some 55 per cent of these contracts havebeen awarded to either micro (fewer than10 employees) or small (fewer than 50employees) companies, typically the sort ofcompanies that the public sector has thegreatest difculty in contracting with. Theadditional funding is expected to enablethe Government to build on this success,and promote awareness and take-up ofSBRI across departments. Syntheticbiology could be considered a candidate

technology for the future use of the SBRIapproach 32.

Building a communityof practitioners

The UK has numerous well establishednetworks in the academic and businessdomains, and these have much tocontribute to a community of practice inthis space. Complex problems are oftenbest addressed by bringing a combinationof experienced and fresh minds to bear onthe topic. Applying a variety of mechanismsto build a networked community will beparticularly important in synthetic biologybecause of the wide range of disciplinesinvolved science, engineering, social,regulatory and others and the need todevelop common standards and protocols.

Creating momentum critical massWhen businesses cluster together they cancollectively be more effective. Examplesfrom the digital industry are well knownand include Silicon Valley, Silicon Fen, andTech City. With todays communications itis no longer essential for clusteringbusinesses to be located together, butproviding a nucleus for the activities ofvarious protagonists can add value. TheUK is fortunate in that three of the worldstop 10 life sciences universities (Cambridge,Oxford, Imperial) are relatively closegeographically and, indeed, the span of

Biotica/Amyris: from therapeutics to renewable fuelsPolyketides are compounds from bacteria and fungi that hold great promise in areasranging from clinical medicine to biofuels. Biotica, a company co-founded by ProfessorPeter Leadley, of the University of Cambridge, has signed a non-exclusive deal with

Amyris, an integrated renewable products company, that will see Amyris use Bioticaspolyketide engineering technology to make a range of compounds that are eitherdifcult or impossible to make by conventional methods. The agreement between

Biotica and Amyris could bring new routes to renewable fuels a step closer.

30 See www.bis.gov.uk/news/speeches/david-willetts-whats-the-good-of-government-2012

31 See www.bis.gov.uk/assets/biscore/innovation/docs/i/11-1387-innovation-and-research-strategy-for-growth.pdf

32 See w ww.innovateuk.org under publications/about ourprogrammes


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academic establishments working insynthetic biology and related disciplinesacross the UK as a whole is relativelycompact.

A characteristic of synthetic biology is theneed for multidisciplinary centres.Establishing

Documents

A Synthetic Biology Roadmap for the UK