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Definitions and Applications A tool to help people understand what synthetic biology is and how it is being applied
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Definitions and Applications A tool to help people understand what synthetic

biology is and how it is being applied

Definitions and Applications

• This resource is designed for people who are exploring the area of synthetic biology in an effort to understand what it is and whether it is relevant to them.

• It provides a range of definitions of synthetic biology and examples of how the technology is currently being applied.

• It is also designed to enable insight into a range of perspectives that people may have on these applications. Because of the complexities involved, there is no right or wrong perspective, and there will never be consensus. To get a holistic view of any application therefore, it is important to understand the different perspectives. It is therefore essential that any exploration is done with empathy.

• One of the challenges many raise when trying to understand synthetic biology is the lack of a commonly agreed definition. And many contain jargon that is not easily understood by those outside of the field. Each one reflects in some way the perspective of the writer, often drawing attention to a particular area of concern or opportunity on the accompanying Comfort Infographic. We are unlikely to arrive at a globally agreed definition soon. It is therefore essential that anyone exploring this area is aware of the lenses that people use when applying the term synthetic biology.

• Another question that people raise when trying to understand synthetic biology is the difficulty in understanding whether an application is on balance a good idea or bad. This is more often than not a subjective value judgement. This tool tries to convey some of those different perspectives so that people can come to their own conclusions.

• By carefully considering the definitions, applications and understanding different perspectives, users of this slide deck will have a more holistic view of the area and be able to take part in constructive dialogue and exercise more considered judgment about whether and how to apply the technologies

How it works

• This tool can be used by individuals or in a group setting. The more conversation that it promotes the better. It will require time and thought. This is an area of science fraught with complexity. It deserves very careful consideration.

• We suggest that you meet the people and consider the definitions first, and then take time to understand the application examples.

• The examples are at- or near-market applications of synthetic biology. We have not included more speculative concepts or ideas.

• These examples are by no means exhaustive. Instead they are designed to be indicative, in order to help you understand whether this area is important for you to understand – as a risk or opportunity.

• We are not advocating any of these applications, or synthetic biology in general. • The examples have been sourced from publicly available data. • The examples are grouped into five sections: two that are significant areas of development currently and three

that are more general: – Yeast derived products, where the yeast has been produced using synthetic biology e.g. dairy free milk and synthetic vanilla – Algal oil derived products, where the algal oil has been produced using synthetic biology e.g. household cleaning products – Organisms as products or ‘deliverables’ in their own right e.g. the glowing plant – Other applications e.g. synthetic rubber – Possible bioterrorism applications e.g. dangerous pathogens

• The characters are purely fictitious. They represent people that have some sort of interest in relation to synthetic biology. We purposefully have not included an apathetic perspective. You can find out why, along with more detail on the lives and views of the people, in the accompanying Human Perspectives resource. They are not stereotypes, but individuals with a unique set of complexities – reflecting the reality of the human being. We provide short excerpts that help you understand their views, as well as showing a red flag to indicate the areas that they feel are the most important.

• When considering the example applications, the first section provides an overview of different groups of synthetic biology applications. The second section draws out a few specific examples from the groups

Meet the people For more in-depth pen portraits, please see the accompanying Human Perspectives resource

Zahra

Javier George

Audrey Ravish Jo

A mother of two with another on the way. Works at the local café as a waitress. Money is a real worry. Each month it is a struggle to cover the bills. Not familiar with ‘synthetic biology’. Nervous of biotechnologies because, deep down, she mistrusts the science. She likes to think she avoids foods containing GMO and would be outraged to know that that’s not true in reality. She may consider it if it could help solve her son’s health problems and doesn’t mean additional costs.

Recently married in an understated ceremony to Bella, who he met at a festival five years ago. Award winning freelance writer and photographer, specialising in indigenous communities in Latin America. He has some understanding of synthetic biology and thinks it introduces unnecessary and unknown risks which, on past experience, will not be well regulated because economic interests will triumph. Inequality is where our efforts should be focused.

A grandfather of six, George lives alone having been widowed two years ago. He draws great comfort from his fellow worshippers and is active in running his parish. He has some understanding of synthetic biology having lectured in biology for 40 years but feels we need to recognise our own limits. It is too much like playing God, even for a man passionate about science. If we can’t solve problems without doing so, so be it. This is stepping over the line of what we have the wisdom to do as a species.

Gained recognition in the field of biotechnology for her ground breaking PhD looking at its application to chemical clean up operations. Prefers to be hands on and believes some bureaucracy unnecessarily slows down new development. In her view our knowledge of genetics is rocketing, and the capabilities to develop and deploy synthetic biology safely (with minimal and broadly quantifiable risks) exist. She is very in favour of self-government and openness, care and transparency .

Despite being one of the youngest and most respected board members in retail, Ravish still comes second to his Doctor older brother as the apple of his mother’s eye . He is desperate to start a family but his wife refuses so long as he spends 80% of his life away from home. He knows a little about synthetic biology and feels we would embrace technological advancement generally. The 8 billion people in this world have the right to a standard of living that is taken for granted in West, and he feels synthetic biology could help make that possible more quickly.

Recently promoted into a strategic role at a government office on a fast-track graduate programme. Jo has just bought her first home and is now paying off her first mortgage with boyfriend Simon. She has a low understanding of synthetic biology and is fascinated with systems and their inherent unpredictability. Se would embrace synthetic biology if the public health risk was low and all the performance risks could be managed, but would be nervous of unintended consequences.

Author of definition Definition

David Drubin et. al A variety of experimental approaches that either seek to modify or mimic biological systems.

ETC & UK Royal Society

An emerging area of research that can broadly be described as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.

EU NEST (New and Emerging Science and Technology) Experts

The synthesis of complex, biologically based (or inspired) systems, which display functions that do not exist in nature. This engineering perspective may be applied at all levels of the hierarchy of biological structures—from individual molecules to whole cells, tissues and organisms.

European Commission The application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms.

Friends of the Earth US A variety of new, and many would say, “extreme” genetic engineering approaches, including computer generated DNA, directed evolution, and site specific mutagenesis.

Greenpeace UK At its core, synthetic biology is engineering applied to biology to deliberately (re)design and construct biological systems. Put another way, tailored biological systems are produced for specific purposes using a great degree of manipulation.

RCUK The engineering of biology: the deliberate (re)design and construction of novel biological and biologically based parts, devices and systems to perform new functions for useful purposes, that draws on principles elucidated from biology and engineering.

www.sytheticbiology.org

Two part - a) the design and construction of new biological parts, devices and systems and b) the re-design of existing natural biological systems for useful purposes.

A selection of the definitions

Main application groups Group Description Applications

Yeast Yeast can be made to produce a range of materials. This technology explores large numbers of gene combinations in yeast (billions of new yeast cells) and finds those gene combinations necessary to potentially biosynthesize a given ingredient through fermentation.

Food/Nutrition: Stevia; Vanilla; Agarwood; Resveratrol; Saffron Medicine: EV077 – Treats diabetic complications; EV035 – Anti-bacterial compound; Anti-malarial drug artemisinin

Algal Oil Algae capture solar energy and C02. By using genetic coding to optimize metabolic pathways, developers suggest algae can be made to produce oil very efficiently. This oil can then be used in various forms.

Industrial surfactants and lubricants; household cleaners and personal care products; biofuels; nutrition – algal flour and whole algal protein; Personal Care - Alguronic Acid® (labelled as a “protective regenerative compound”); Microalgae Oil, (labelled as a “rich source of oleic acid and other nutrients”); and the Algasome™ complex (labelled as “a concentrated source of vitamins and antioxidants”)

Organisms as deliverables

These applications involve engineering traits in organisms with the intention to deliver the organism itself, rather than use them to produce materials.

Self-fertilizing plants (engineering nitrogen-fixing devices within photosynthetic cells); Bioluminescence in plants and domestic fish; Release of Insects with Dominant Lethality – engineering male mosquitoes with a gene that causes offspring to die, thus aiming to prevent spread of malaria.

Other example applications (current and potential)

Application Description

Increasing Rates of Natural Fermentation for Polymers

Through a microbial fermentation process, the base polymer PHA is produced within microbial cells and then harvested. Substitute for petroleum-based polymers.

Manufacturing Isoprene in plants Can be used in synthetic tyres, replacing petrochemical sources.

Bioacrylic from microbes OPXBIO’s EDGE (Efficiency Directed Genome Engineering) uses synthetic biology to produce bioacrylic from microbes able to use renewable sources of carbon and energy (e.g. corn, sugar cane, or cellulose) in a commercial bioprocess.

Biofuels from sugars produced from non-food biomass

Enzymes are engineered into biomass. After harvest, these enzymes are activated in a way that the developer claims greatly reduces the energy, chemical and other pre-treatments traditionally required to convert the plant material to sugar.

Surfactants from soybean hulls Modular has developed an engineered microorganism that converts soybean hulls into a surfactant for use in personal care products and other formulations

Adipic acid (used in nylon production)

Verdezyne is developing what it calls a “cost-advantaged, environmentally friendly (uses less energy) fermentation process” for adipic acid (used in nylon production). The company’s proprietary metabolic pathway can utilize sugar, plant-based oils or alkanes.

Diesel alternatives LS9 has developed microbial cells that can perform a one-step conversion of carbohydrates (sugars) to two diesel alternatives, a fatty acid methyl ester (biodiesel ASTM 6751) and an alkane (ASTM D975).

Bioprocessing pharmaceuticals Synthetic biology could be used to speed up the bioprocessing of pharmaceuticals and the development of vaccines

Industrial enzymes Production of enzymes for direct use in food and surfactants

Arsenic detection A method that allows rapid communication between bacterial cells across long distances enables the cells to detect arsenic collectively, and to report it as an oscillatory output.

Detecting meat spoilage The Food Warden concept uses bacteria to detect and flag meat spoilage

Misapplication or misuse

Making information available on how to synthesise genetic material could mean that it is applied in a negative or harmful way. ‘Rogue’ applications are possible, though not necessarily likely. Commentators that suggest this is low risk say that synthetic biology processes are not suitable for DIY production at scale. There are enormous challenges even for highly trained professionals in industrial labs. Other commentators point out that we already have dangerous natural pathogens that are obtainable, and that the fact that they exist does not necessarily mean that they will be used. For others however this risk is too high. It is essential to manage this risk as, although the likelihood of a large or small scale attack using synthetic biology is low, it remains real. How might synthetic biology be misused? *Easy to acquire genetic sequences for pathogens The complete genetic sequences for all 82 pathogens identified by the US government as select agents that pose an extreme threat to public health are now available through the Internet. These might be built using synthetic biology techniques. *Possible to engineer a dangerous virus from scratch Many commercial companies now provide DNA synthesis services and it’s possible to outsource to them. Average cost is as low as 3 US cents per base pair. These might be used to build dangerous viruses (amongst other things) using synthetic biology techniques. *Possible to enhance the virulence or increase the transmissibility of known pathogens, creating novel threat agents Whilst this is said to be technically challenging, synthetic biology techniques might be employed to do this.

PERSPECTIVES ON SPECIFIC APPLICATIONS

Cases

Synthetic Artemisinin A medical application

• Artemisinin is an antimalarial drug precursor

• It is naturally produced by a plant, Artemisia annua but there are challenges with meeting demand as it is weather and harvest dependent. As a result, both the supply and price of the drug have fluctuated substantially over the past decade (1)

• According to an article in Nature (May 2014 12.5) (2) “the successful synthesis and recent entry of semi-synthetic artemisinin into commercial production is the first demonstration of the potential of synthetic biology for the development and production of pharmaceutical agents.”

• This application is in production and commercial use

Sources: 1) World Health Organisation. WHO informal consultation with manufacturers of artemisinin-based pharmaceutical products in use for the treatment of malaria (WHO, 2007). 2) Paddon, C.J. & Keasling, J. D. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development Published in Nature May 2014, Volume 12, Number 5.

Group: Yeast

How do the definitions apply to Synthetic Artemisinin?

BBSRC- Fits

David Drubin et al.- Probably fits

ETC & UK Royal Society - Fits

www.syntheticbiology.org- Fits

Greenpeace UK- Fits

EU NEST Experts- Fits

European Commission- Fits

Friends of the Earth US- Might fit

Perspectives on Synthetic Artemisinin

Zahra

Javier

George

Audrey

Ravish

Jo

As a mother, I know what it’s like when your child is ill. I still struggle to trust the promises being made, but if the claims are

accurate, alleviating malaria seems like an appropriate application of this technology.

The problem of malaria in the developing world is devastating. I have seen it first hand in my work as a photographer in Latin America. There are many actions that can be taken to reduce it however, like bed nets

and public health campaigns. Only when these are exhausted am I interested in considering synthetic biology as a solution.

I have a lot of sympathy for those in the world plagued by disease. But there are other ways we can help them. This is not the only solution

science has presented us with. God did not intend for us to debase his creation for these purposes.

This is precisely why this technology exists – to solve the big issues of our time. A lot of smart people have done the groundwork in laboratories to develop this application. Let’s not waste the

opportunity to use it.

There could potentially be an enormous market for pharma drugs based on this application in tropical countries. Let companies bring it

to market, make money, and help people. It’s a win-win.

It’s certainly a worthwhile goal to alleviate disease in the world. But mosquitos and malaria must have some use in the ecosystem. Have we

thought enough about the consequences of taking this course of action?

Synthetic Vanillin A food and fragrance application

• Natural vanilla is derived from the seed pods of vanilla orchids

• According to Evolva – the synthetic vanillin producer “Vanilla and vanillin are together among the most important fragrance and flavouring products in the world, with the total market worth approximately USD 600 million (and a total volume of approx. 18,000 tonnes). Only a small fraction of this volume consists of natural vanilla, with the vast majority being synthetic vanillin” (1)

• According to Friends of the Earth US, synthetic vanillin is “the first major use of a synbio ingredient in food” (2)

• Evolva uses “a yeast-based fermentation route” (1) to produce the synthetic vanillin which is where synthetic biology is applied

• This application is in production and commercial use

Sources: 1) Evolva website Jan 2015 http://www.evolva.com/products/vanilla (2) Friends of the Earth US website Jan 2015 http://www.foe.org/projects/food-and-technology/synthetic-biology/No-Synbio-Vanilla

Group: Yeast

How do the definitions apply to Synthetic Vanillin?

BBSRC- Fits

David Drubin et al.- Probably fits

ETC & UK Royal Society - Fits

www.syntheticbiology.org- Fits

Greenpeace UK- Fits

EU NEST Experts- Fits

European Commission- Fits

Friends of the Earth US- Fits

Perspectives on Synthetic Vanillin

Zahra

Javier

George

Audrey

Ravish

Jo

I’m very concerned about this food additive going into my body or my kids’ bodies. I’d much rather stick to the natural vanilla. But I’m

also conscious of how expensive vanilla is. Would it make a significant difference to the cost of my food?

We don’t need food additives and even if we did they certainly shouldn’t come from this technology. This is a trivial application that could have serious impacts on the livelihoods of vanilla farmers. I’m

against it.

If you want vanilla, get it from vanilla beans! That’s why God put them there!

It’s fine to use the technology for this purpose but why waste it? We can do so much more with it than create cheap food additives.

The market will work out whether we need this. If we can make a product cheaper at a profit and provide more food, then it’s a win.

I’m not sure about all the repercussions, but this doesn’t seem to pose any big risks in terms of security. Do we know enough about the safety

angle of ingesting this?

Household Cleaning Products A home and personal care application

• Currently palm oil is used in most household cleaners.

• Palm oil has environmental implications because it is often sourced from palm plantations that displace native tropical forests

• Developers claim algal oil is a potential substitute for palm oil in household cleaners

• The algal oil is derived by optimizing the metabolic pathways of natural algae.

• Several types of feedstock are being investigated, including sugarcane and agricultural and forest waste, to identify which is the most sustainable feedstock of those locally available

• This application is in production and commercial use

Group: Algae

Source: Ecover adopting algae-based laundry liquid to cut palm oil use, http://www.theguardian.com/environment/2014/apr/02/ecover-algae-laundry-liquid-palm-oil

How do the definitions apply to Household Soaps?

BBSRC- Fits

David Drubin et al.- Probably fits

ETC & UK Royal Society - Fits

www.syntheticbiology.org- Fits

Greenpeace UK- Fits

EU NEST Experts- Fits

European Commission- Fits

Friends of the Earth US- Might fit

Perspectives on Household Cleaning Products

Zahra

Javier

George

Audrey

Ravish

Jo

I’m very concerned about this going on my body or my kids’ bodies. I prefer to keep things natural for my family. I’m also worried that this could aggravate my son’s eczema. Do we know it won’t? I’m

not going to risk it.

It’s important to conserve rainforest and I appreciate the intent. But surely there are other alternative ingredients to palm oil. I’ve read that this relies on sugar as a feedstock, and I know there are real challenges

in that supply chain in terms of sustainability. I think I’ll avoid it.

This seems to be overcomplicating soap somewhat. In my day soap was made from tallow and worked just fine for us.

The rainforests are the lungs of the planet. Helping conserve them is a good use of this technology. I’m pleased that people are applying this

to the bigger challenges, rather than more frivolous applications.

I don’t understand why people got so up in arms about this. The soap company made a very reasonable business decision that aims to

benefit the environment. It’s interesting though from a brand and reputation point of view. Would we want to be associated with it?

This is one of those beautiful complex systems issues: how solving one problem can produce others. I think they have had to make a call with the level of uncertainty that they deem acceptable. I think that is all

you can do. I would be happy to use it.

Cow-free Milk An alternative to dairy

• The world population is soaring and less land is available for agriculture.

• Milk derived from yeast means scaling down the size of a milk-production vessel from a dairy animal to a microbe.

• It also removes the need for unethical dairy factory farms.

• This ‘synthetic’ milk is derived from yeast. The technology replicates the cellular machinery involved in biological synthesis of each individual component of milk in yeast. The chemical composition of milk is composed of six key proteins and eight key fatty acids.

• The developers claim this ‘synthetic’ milk is lactose and cholesterol free and does not require pasteurization.

• This application in is production and commercial use.

Group: Yeast

Source: Moo-ve over, Factory Farms: Muufri is Taking Dairy Milk Animal-free, http://synbiobeta.com/muufri-animal-free-milk/

How do the definitions apply to …

BBSRC

David Drubin et al.-

ETC & UK Royal Society -

www.syntheticbiology.org-

Greenpeace UK-

EU NEST Experts-

European Commission-

Friends of the Earth US-

Perspectives on…

Zahra

Javier

George

Audrey

Ravish

Jo

.

Third generation bioethanol An energy application

• First generation bioethanols are produced from cereal crops grown on land that is required to grow food or were forested. Second-generation bioethanols are derived from weeds and woods. Third-generation or "advanced bioethanol" is derived from algae rather than traditional land-grown crops. (1)

• Synthetic biology is used to enhance the rate of production of oils from the algae.

• Synthetic biology is also being applied to produce biodiesel. Renewable Energy Group for example are looking at using E.Coli bacteria (which has been altered using synthetic biology) to convert carbohydrates into biodiesel. (2)

Group: Algae

Sources: 1)Biofuel website Jan 2015 http://biofuel.org.uk/third-generation-biofuels.html 2) REG Life Sciences website Jan 2015 http://www.reglifesciences.com/technology/technology-overview

How do the definitions apply to …

BBSRC

David Drubin et al.-

ETC & UK Royal Society -

www.syntheticbiology.org-

Greenpeace UK-

EU NEST Experts-

European Commission-

Friends of the Earth US-

Perspectives on…

Zahra

Javier

George

Audrey

Ravish

Jo

.

Bioluminescent plant A lighting application

• In 2013, a Kickstarter campaign funded Glowing Plant - a plant that produces light

• They say that they “are using Synthetic Biology techniques and Genome Compiler’s software to insert bioluminescence genes into Arabidopsis, a small flowering plant and member of the mustard family, to make a plant that visibly glows in the dark (it is inedible)” (1)

• The developers also say that they publicised this application in an effort to raise the profile of synthetic biology

• This application is in development

Group: Organisms

Image from glowingplant.com

Sources: 1) Glowing Plant Kickstarter website Jan 2015 https://www.kickstarter.com/projects/antonyevans/glowing-plants-natural-lighting-with-no-electricit

How do the definitions apply to …

BBSRC

David Drubin et al.-

ETC & UK Royal Society -

www.syntheticbiology.org-

Greenpeace UK-

EU NEST Experts-

European Commission-

Friends of the Earth US-

Perspectives on…

Zahra

Javier

George

Audrey

Ravish

Jo

.

Mosquitos that control their own population A health and comfort application

• Oxitec and the Florida Keys Mosquito Control District (FKMCD) are collaborating on a field trial for the OX513A Aedes aegypti mosquito.

• With the objective of controlling the population of mosquitos that are a threat to the health and comfort of residents (1) on the Florida Keys, Oxitec has developed a synthetic Aedes aegypti mosquito.

• According to FKMCD the males containing synthesised genetic material, which cannot bite or transmit disease, are released to mate with wild females. Few of their offspring survive, which reduces the infestation in the next generation. After multiple releases, the local mosquito population is reduced. This solution has already been tested in the Cayman Islands and in Brazil with successful reductions of the Aedes aegypti populations by over 90% in the study areas.(1)

• This application is being trialled.

Sources: 1) FKMCD fact sheet: http://www.oxitec.com/wpcms/wp-content/uploads/Oxitec-FKMCD-mosquito-control-project-flyer-Oct2014.pdf

Group: Organisms

How do the definitions apply to …

BBSRC

David Drubin et al.-

ETC & UK Royal Society -

www.syntheticbiology.org-

Greenpeace UK-

EU NEST Experts-

European Commission-

Friends of the Earth US-

Perspectives on…

Zahra

Javier

George

Audrey

Ravish

Jo

.

Synthetic rubber for tyres A mobility application

• Due to the huge demand for rubber globally, synthetic rubber has been used in tyres for many years. Until 2012 it was invariably produced using petrochemical sources.

• DuPont, together with Goodyear, announced in March 2013 that they were “working together to develop BioIsoprene™, a revolutionary bio-based alternative for petroleum-derived isoprene. BioIsoprene™ can be used for the production of synthetic rubber—which in turn is an alternative for natural rubber—and other elastomers. The development of BioIsoprene™ will help reduce the tire and rubber industry’s dependence on oil-derived products.” (1)

• The prototype tyre was on display at the 2012 Geneva International Motor Show. (2)

• Synthetic biology is playing a part in developing what Dupont and Goodyear describe as a “reliable, high-efficiency fermentation-based process” for BioIsoprene™. (1)

• This application is in development. Sources: 1) Goodyear Press Release 6th March 2012 http://www.goodyear.com/cfmx/web/corporate/media/news/story.cfm?a_id=646; 2) Biotechnology Industry Organisation website Jan 2015 https://www.bio.org/articles/current-uses-synthetic-biology

Group: Other

How do the definitions apply to …

BBSRC

David Drubin et al.-

ETC & UK Royal Society -

www.syntheticbiology.org-

Greenpeace UK-

EU NEST Experts-

European Commission-

Friends of the Earth US-

Perspectives on…

Zahra

Javier

George

Audrey

Ravish

Jo

.


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