Synthetic Biology: EXPAND the potential of nature to improve the quality of life

VAP Martins dos Santos, PJ Schaap, G Eggink, J Kortekaas, J Wells, M Verweij,

M Pikkemaat, EJ Kok, E van den Ende, D de Ridder, D Bosch

1. Global Challenges and Synthetic Biology Our world is changing fast. Populations are growing, and the rapidly increasing prosperity, particularly in emergent economies, generates an enormous demand for more and diversified food, products, energy and services. Already now, this results in an unprecedented draw on natural and

fossil resources, challenging severely the quality of our environment and climate (soil, water and air).

This warrants the development of new sustainable strategies to secure the availability of sufficient food, energy and ever more and new industrial and medical products. At the same time, life expectancy is generally increasing worldwide.

Ageing populations demand for new lifestyles and the availability of accompanying products and services (healthy food, healthcare, services) to safeguard a prolonged and stable wellbeing.

These developments call for drastic changes in the way we use our natural resources. We have to

move from exploiting the food, fuel and pharmaceuticals we find in nature to designing and engineering reliable biological systems and new products that solve a targeted problem, leave

a minimal environmental footprint and are sustainable in the long term. Synthetic biology, a field of research that arose over the last decade,

offers the concepts and methods to significantly contribute to this aim.

2. Perspectives offered by Synthetic Biology. Following a widely accepted definition, “Synthetic Biology aims to design and engineer biologically-based parts, novel devices and systems as well as redesigning existing, natural biological systems to perform new functions for useful purposes”.1,2 It builds upon principles, concepts and methodologies from biology, physics and engineering. Analogous to a car assembly line, Synthetic Biology aims to design and build biological systems in a modular,

flexible, reliable and predictable way, allowing biological units to be assembled, shared and reused in different contexts. It differs from traditional genetic engineering and biotechnology

in that it applies true engineering principles - systems perspective, separation of design and fabrication, standardization, modularization, model-driven design – to biological questions3. This multi-disciplinary, integrated approach promises to reduce the time, cost and complexity of developing (novel) biological systems,

products and services in response to societal needs. As such, it easily integrates with complementary strategies to improve the quality of life as well as our environment. As exemplified below, Synthetic Biology opens up new opportunities in a range of sectors including industrial biotechnology and medicine, energy, environment and agriculture, promoting wellbeing, economic growth, resource

security and job creation.

3. Strategic implementation of Synthetic Biology at the WUR, Synthetic Biology is one of the five Strategic Choices in the Strategic Plan of the WUR for 2015-2018. Its successful and seamless implementation entails considering the following questions:

1 ERA-Net SynBio Vision document [link] 2 OECD, UK SynBio RoadMap 2012, EU-NEST 2009 [links] 3 NAS report 2010, UK SynBio report 2010, Acatech 2010, NWO 2011 [links]

“Scientists study

the world as it

is; engineers

create the world

that has never

been”. Theodore

von Kármán

Figure 1 – The “House of Synthetic Biology” in SynthCity.

No single solution can provide sufficient resources for a

growing global population and increasing demand of

goods and services, but conceptual and technology

developments in the biological sciences can play a major

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 is

bound to make significant long-term contributions.

a) How will it synergise with the WUR mission and vision?

Owing to its very nature and goals, Synthetic Biology builds strongly on the mission of the WUR, by not only exploring but EXPANDing the potential of nature to improve the quality of life. In this way, it contributes to our ambition of being at the forefront in research addressing the global challenges outlined above. It is a logical step to realise the applied potential of Systems Biology (which provides knowledge and (mathematical) model frameworks, concepts and tools for a systems understanding of the biological questions at stake). Notably, Synthetic Biology synergises and complements seamlessly

with several other WUR Strategic Choices to meet societal challenges, in particular with One Health, Resource Efficiency and Resilience, as becomes clear from the example areas below. b) What is the Unique Selling Point of the WUR? A hallmark of the research ethos at the WUR is its integrated approach for addressing technical and societal questions, and by considering the complete chains: i) product and value chains, from raw

materials to process and product, and accounting for issues such as consumer perception, environmental and societal footprints, as well as governance and regulation at all stages; ii) knowledge chains, intertwining fundamental knowledge and research, with training and education at different

levels to address life science applications. It is largely owing to this way of conducting research and education that the WUR has achieved its strong national and international positioning. Synthetic Biology can strongly contribute to consolidate and expand this approach.

c) Where can Synthetic Biology have an impact for the WUR? Figure 1 summarizes societal drivers and needs, and indicates WUR-relevant areas to which Synthetic Biology is bound to have a major impact. These include: o Health & nutrition: new antibiotics and pharmaceuticals; (animal) vaccines; biosensors;

diagnostics; personalised (4Ps) and systems medicine, nutraceuticals and ingredients; modulation of (intestinal) microbiota and immunity through nutrition; precision nutrition

o Biobased economy: replacement of petrochemical based-chemistry by biobased production of platform (bulk and fine) chemicals; light-driven bio-production and control of bioprocesses;

o Biofuels and energy: new generation biofuels from waste; artificial photosynthesis; o Environment: bioremediation; bionsensors for quality control and monitoring: low energy input

production processes, green chemistry; o Food & feed security: sustainable production of food & feed (precision breeding, ingredients,

resources, bioprocessing, biosensors for production control); o Biomaterials and (nano-)devices: bio-plastics; regenerative biomedical materials; artificial nose;

detection systems; Besides these application areas, Synthetic Biology is expected to heavily impact fundamental research in all the life sciences. Its concepts, (mathematical) models, methods, workflows and tools will allow researchers to (re)design

molecules, cells and ecosystems. The insights thus obtained will support the generation of new ideas and knowledge underpinning future developments to tackle societal challenges. d) What is the embedding at the WUR and its position in the world? In addition to the specific expertise available at the WUR in the many fields underpinning the research

in the areas above, all Science Groups have (had) research activities related to Synthetic Biology. A

non-exhaustive list of ongoing research projects on Synthetic Biology (in various cases, with industrial partnerships) is presented in Annex 1. Many of those activities stem from and are embedded in initiatives such as the Wageningen Centre for Systems Biology (WCSB), CBSG, BE-BASIC, CVI and others. Accordingly, various Wageningen UR researchers have been involved, nationally (CoGEM, NWO, KNAW, STW) and internationally (EU, OECD, NAS, NSF, EPRSC, BBSRC, BMBF, ESF, ERA-NETs etc.) in strategic and policy advising activities in Synthetic Biology, including those on ethical, social, and legal

implications (IRGC, CoGEM, EU). Furthermore, as a result of strategic choices in the area, a Chair in Systems and Synthetic Biology was established 5 years ago and structured research and training programmes (as detailed below) have been set up. WUR researchers lecture and publish widely in the area, and have made (and make) substantial contributions to many Synthetic Biology topics. Moreover, a number of WUR scientists have initiated and/or are in the board of a number of national and international Synthetic Biology research programs, act as invited speakers and chairs on international meetings, have co-organised a good number of congresses and specialised meetings in

field – including the initiation of the Gordon Conference series on Synthetic Biology4 and the EU-US

task force on Standards in Synthetic Biology5) – and are engaged actively in pubic dialogue. Clearly,

4 www.grc.org/programs.aspx?year=2013&program=synthbio 5 ST-FLOW, TARPOL

“What I cannot

create, I do not

understand”.

Richard Feynman

individual researchers already have a name in

Synthetic Biology; investing in Synthetic Biology as a Strategic Choice further improves the positioning of WUR as a whole in the field, and underscores the ambition of WUR to contribute to our global societal challenges.

e) How to implement Synthetic Biology research at the WUR? By seamlessly integrating Synthetic Biology workflows into its research pipelines and by stimulating projects that mobilize knowledge and expertise over de whole chain (including ethical,

social and legal implications), the WUR will be able to substantially enhance its ability to carry out research and education in accordance to its

mission. It will thereby strengthen its positioning in the research landscape nationally and internationally, and become ever more attractive for a range of stakeholders, including industrial,

environmental and healthcare partners, students at various levels, and professionals in the various areas above. Figure 2 exemplifies this integration. The workflow draws on the “Engineering Cycle” design-build-test6 that is at the heart of “traditional” engineering disciplines and industries.

f) How is education and training in Synthetic Biology accounted for? The job market for synthetic biologists has dramatically grown over the last decade in areas ranging from industry, energy to medicine and health, and agriculture and environment. Students are most enthusiastic about the prospect of using biological principles to actually create “things” that impact

society. This is demonstrated by the tremendous success of the International Genetically Engineered Machines competition (www.iGEM.org), in which undergraduate student teams develop and implement

synthetic biology projects over a semester. Outstandingly, Wageningen came second (out of 245 teams) in the 2014 worldwide competition, having performed on top in all previous participations. WUR is a world-leading institution in the life sciences. To maintain and consolidate this position and to provide WUR graduates with the skills and knowledge needed to succeed in the future job market requires education in the “New Biology”7. This relies heavily on systems and synthetic biology, both requiring a solid understanding of quantitative methods and engineering principles. Education in these

subjects should include molecular, micro-, and cell biology, bioinformatics, mathematical modeling and scientific programming, engineering principles, physics and biochemistry and experimental and bioengineering methods (omics techniques, optogenetics tools, design of synthetic genetic elements and standardized building blocks etc.). Synthetic biology is also strongly embedded into a socio-economical, environmental and ethical/regulatory context. This makes it a perfect vehicle for the integrated beta-gamma educational programs typical of WUR. In addition to specific courses on

Introduction to Systems & Synthetic Biology and Tools in Synthetic Biology, many of these elements

are already part of the BSc programmes ‘Molecular Life Science’ and ‘Biotechnology’, making these most suited as foundations for more specialized, tailored education in synthetic biology (a track) at the Master level. g) How to engage stakeholders and address public dialogue? The development of Synthetic Biology worldwide has been, since the very beginning, integrally

embedded in a societal context with intense public engagement on the ethical, social, and legal implications in its many facets, as well as governance and policy8. Along these lines, the implementation of Synthetic Biology will entail early public dialogue with stakeholders ranging from regulators to industry and citizens organisations, in connection to social scientific and philosophical research. Synthetic biology touches upon basic and sensitive questions about the nature of life, and philosophical reflection at early stage may help to avoid that these questions are too easily hijacked in polarised discussions between proponents and opponents of specific technologies. Moreover, to

facilitate the application of Synthetic Biology knowledge in solving current societal challenges in a

6 UK Synbio Applications report, 2009 7 KNAW, 2011 8 NAS, 2011, IRGC, 2009, Acatech, Rathenau Report, SynBiosafe, Synthetic Genomics, UK ELSI report.

Figure 2 – The WUR value and knowledge chains (as

per 3b above) and how a Synthetic Biology workflow

(insert) can underpin their developments to

strengthen WUR’s positioning in the research and

societal landscape. As an illustration, examples are

given for bio-based production of new generation

biofuels and designer vaccines.

responsible and sustainable way, Synthetic Biology will address risk perception and risk/safety

governance, and appropiate intellectual property regimes as an integral aspect in the developmental process. The WUR has under its umbrella all disciplines that allow the development of innovative products and processes in a way that, from the inception phase, biosafety, ethical, legal and socio-economic aspects are an integral part of any research programme. 4. Vision

Where will we be in 5 to 10 years? In as far as forecasts can be made about any topic, Synthetic Biology will be underpinning and increasingly pervasive throughout the full spectrum of research & development. Worldwide, new processes, products, concepts and technologies based on Synthetic Biology workflows will be developed and implemented. Some long-sought goals for sustainable bio-based production of chemical building blocks will be attained, contributing to the much-wanted global shift from a petrochemical-

based to a biobased society. New antimicrobials, smart/adaptative design (animal) vaccines and antibodies will be available for potential use, as well as a range of nutraceuticals, ingredients and processes in the feed and food industries. Also foreseeable are the development of sophisticated

biological based nano-devices and biomaterials tailored for a range of applications (biomedical and regenerative devices, bioplastics, etc.). Engineering of microbial communities through modulation of surrounding and operating conditions may lead to directed, optimized functional behavior in health and environmental applications. Light-driven processes (in particular conversions of light and CO2 to

valuable compounds), optogenetics, multiplexed light control of bioprocesses and, possibly, advancements in light-powered production of fuel molecules and artificial photosynthesis may start to become realistic. Any technical research will follow the principles of responsible innovation and will be embedded strongly in a societal context. What will be certainly much more advanced and established, are the enabling concepts, methodologies and tools that will underlie and drive the research in the field, thus providing a solid basis for responsible development and innovation. Also, we will have seen the implementation of Synthetic Biology products and approaches in other, complementary strategies

to meet our global challenges. What is needed to reach the goals of Synthetic Biology? As shown above, the scope and research workflows to tackle societal questions in an integrated

manner are already part of the WUR soul. There is already some solid groundwork done and expertise is available in various areas related to Synthetic Biology, including in its societal context. Reaching the

goals set above requires foremost supporting the establishment of common Synthetic Biology workflow (insert of Figure 2), which can be subsequently applied to a variety of societal challenges across the WUR to leverage its impact. This entails investing and re-focusing resources and energy in joint, targeted, collaborative research projects, (access to) infrastructure, training and education. 6. Recommendations Fostering world-leading and innovative Synthetic Biology research and education at the WUR will drive

and yield significant economic impact and enable to address the grand societal challenges the WUR has set as priority. It will thereby strongly contribute to strengthen the positioning of the WUR in the research, innovation and educational landscape nationally and internationally. To achieve this, we recommend to: 1 - Invest in integrated, innovative cross science-group explorative projects on the core conceptual

and enabling aspects of SyntCity research. Support logistically and financially the establishment of a

framework fostering intra WUR networking (project meetings, retreats, seminars, conferences etc), thereby synergising with the Wageningen Centre for Systems Biology for increased logistic and research leverage. 2 – Support proactively and from our own strength, a networked, multidisciplinary and national research and policy advising community. Involve thereby other Dutch universities, companies and stakeholders, also in relation to the top-sectors. Similar efforts n the UK have resulted in at least 150

Mi GBP over 5 years on dedicated budget to Synthetic Biology research. 3 - Coordinate training and education in Synthetic Biology. Set up introductory courses in bioengineering and synthetic biology in relevant BSc curricula, and specialized and tailored education in synthetic biology (track) at MSc level. Support the development of complementary teaching methods, foremost the “iGEM model” (by extending the concept to problem-driven team work). Explore the potentially ample opportunities for distance learning 4 – Communicate and engage in public dialogue with stakeholders at the various stages of

development. Foster the development of responsible innovation by embedding ethical, legal en social

implications seamlessly.

Annex I – Current projects and programs at the WUR on SynBio.