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for Environment Policy FUTURE BRIEF: Synthetic and

September 2016 Issue 15

Environment Science for Environment Policy This Future Brief is written and edited by the Science and biodiversity Communication Unit, University of the West of England (UWE), Bristol Email: [email protected]

Contents To cite this publication: Science for Environment Policy (2016) Synthetic biology and bidiversity. Future Brief 15. Produced for the European 1. 1. Introduction: What is synthetic biology? 3 Commission DG Environment by the Science Communication Unit, UWE, Bristol. Available at: 2. 2. What are the applications of synthetic biology? 9 http://ec.europa.eu/science-environment-policy 2.1 Synthetic biology in Europe 12 3. What are the potential impacts of synthetic biology 13 Acknowledgements on biodiversity? We wish to thank the Dr Todd Kuiken (North Carolina State University & Society Center) for 4. Case study: new breeding 17 his input to this report, and Dr Matthew Gentry (Swedish 5. What are the ethical issues associated with synthetic 24 University of Agricultural , Uppsala) for his review. Final responsibility for the content and accuracy of the report, biology? however, lies solely with the author. 6. What are the safety issues associated with synthetic 25 biology, and how can we manage them? 7. Regulatory implications 28 7.1 Research needs and areas for future development 29 8. Summary and recommendations 30 References 31

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Introduction What is synthetic biology?

Synthetic biology is an emerging field and industry, with a growing number of applications in the pharmaceutical, chemical, agricultural and sectors. It may propose solutions to some of the greatest environmental challenges, such as climate change and scarcity of clean water, but the introduction of novel, synthetic may also pose a high risk for natural . This Future Brief outlines the benefits, risks and techniques of these new technologies, and examines some of the ethical and safety issues.

Glowing plant. Source: Ow et al. (1986) Science/AAAS Vol. 234, Issue 4778: 856-859. DOI: 10.1126/science.234.4778.856

All living organisms have a , which contains all 10 000 years ago (Clutton-Brock, 1981; West, B.R., the information necessary for that ’s . 2002; Wood and Orel, 2001). has The genome is the complete set of in a or traditionally focused on of , and sheep organism. Genes contain the information needed to make for agricultural purposes, as well as domestic . , which perform the cellular functions necessary are now the most genetically diverse species on for . For thousands of years, have deliberately Earth thanks to centuries of selective breeding by humans, altered the genes of and animals (Beadle, G.W., beginning with the of wolves (Adams, J. 1980; RSPCA, n.d.). 2008; Anthes, 2013).

Selective breeding, a term first coined by Darwin After the discovery of DNA in the 1950s, scientists began in 1859, is a way of selecting for desirable traits and has to learn rapidly about the genetic basis of characteristics been practiced since pre-history, beginning approximately and soon began to isolate and manipulate the genetic SYNTHETIC BIOLOGY AND BIODIVERSITY 4

material of organisms. techniques essentially allowing scientists to ‘cut and paste’ DNA. In enabled scientists to take genetic material associated with 1972, the first paper was published using this recombinant a useful trait in one organism and insert it to another, and DNA technique, reporting its application to produce thus to develop new of plants and animals more transgenic (Cohen et al., 1972). The ability to quickly than before (Synthetic Biology Project, 2015). insert foreign DNA into an organism’s genome, known under the umbrella term of genetic engineering, has Building on understanding of how DNA is regulated, since enabled the production of disease-resistant crops and copied and repaired, molecular advanced further bacteria that can produce the insulin. in the 1970s when restriction were discovered Techniques have continued to evolve at a rapid pace, (the scientists involved were later awarded the Nobel Prize including development of the Chain Reaction for their efforts1). These enzymes cut DNA at a particular (PCR) in the 1980s, which can produce millions of place which can then be combined with other stretches, copies of DNA in a matter of hours. Further advances

Genetic engineering. © iStock / nicolas_ in DNA synthesis and technology have made it As well as molecular biology, synthetic biology interfaces much quicker and easier to construct and copy DNA. with engineering, , physics, computer science and (ERASynBio, 2013) and is focused With advances in technology and rapidly falling costs of on developing more rapid and simple methods to produce DNA and synthesis, scientists begun to create genetically modified organisms (GMOs) by adding or entirely new sequences of DNA, allowing them to develop removing genes, or creating genetic elements from scratch organisms with novel functions, such as producing fuels (European Commission, 2015; SCENIHR, SCCS, or pharmaceuticals. This latest development is termed SCHER, 2014). ‘synthetic biology’, a field which shares features with modern and builds on traditional molecular Unlike traditional genetic engineering, which typically biology techniques to control the , characterisation involves the transfer of individual genes between cells, and construction of biological parts, devices and systems synthetic biology involves the assembly of new sequences (CBD, 2015). of DNA and even entire (Biotechnology Innovation Organization, 2016). The distinction between

1. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1978/press.html SYNTHETIC BIOLOGY AND BIODIVERSITY 5 A history of genetic modification synthetic biology and traditional genetic engineering is important. Although synthetic biology builds on the techniques of classical genetic engineering, many elements are entirely novel (and thus require fresh evaluation).

Synthetic biology aims to fulfill the goals of classical genetic engineering, but goes further, attempting to design life according to humanity’s needs (Engelhard, 2016). Indeed, synthetic biology involves designing and constructing new biological parts, devices and systems — going far beyond the modification of existing cells by inserting or deleting small numbers of genes. Cells can be equipped with new functions and entire biological systems can be designed. Compared to traditional GMOs therefore, synthetic organisms involve much larger-scale interventions, and it is important to bear this in mind when considering and debating the new field of synthetic biology (Engelhard, 2016).

Synthetic biology provides tools to better understand biological systems and can also produce valuable products, such as drugs, fuels, or raw materials for industrial processes or food. By reducing the time, cost and complexity of developing these products, the field represents opportunities for a range of industries and has been linked to future economic growth and job creation (ERASynBio, 2013). One report (McKinsey Global Institute, 2013) suggests that the field could be worth $100 billion by 2025.

Although the term came to prominence in the 1970s, there remains no universally accepted definition of synthetic biology. SYNTHETIC BIOLOGY AND BIODIVERSITY 6

BOX 1. Definitions of synthetic biology

“The deliberate design of biological systems and living organisms using engineering principles” (Balmer & Martin, 2008)

“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” (Synthetic Biology.org, 2016)

“The design and construction of novel artificial biological pathways, organisms and devices or the redesign of existing natural biological systems” (The Royal Society, 2016)

“The use of computer-assisted, to design and construct new synthetic biological parts, devices and systems that do not exist in and the redesign of existing biological organisms, particularly from modular parts” (International Civil Society Working Group on Synthetic Biology, 2011)

“A field that aims to create artificial cellular or non-cellular biological components with functions that cannot be found in the natural environment as well as systems made of well-defined parts that resemble living cells and known biological properties via a different architecture” (Lam et al., 2009)

“A new research field within which scientists and engineers seek to modify existing organisms by designing and synthesising artificial genes or proteins, metabolic or developmental pathways and complete biological systems in order to understand the basic molecular mechanisms of biological organisms and to perform new and useful functions” (The European Group on in Science and New Technologies, 2009)

In 2013, the three independent EU Scientific Committees the environment and biodiversity and research priorities, (Scientific Committee on Emerging & Newly Identified respectively. The first lays the foundation for the two Risks — SCENIHR, on Consumer Safety other opinions with an overview of the main scientific — SCCS, and on Health and Environmental Risks developments, concepts, tools and research areas in — SCHER) were requested to adopt a set of three synthetic biology. Additionally, a summary of relevant opinions addressing a mandate on synthetic biology regulatory aspects in the European Union, in other from the European Commission (Directorates Health countries such as Canada, China, South America and the & Consumers, Research and Innovation, Enterprise and USA, and at the United Nations level, is included. This Environment). is available from: http://ec.europa.eu/health/scientific_ committees/emerging/opinions/index_en.htm. The first opinion concentrated on the elements of an operational definition of synthetic biology, Although there is no universally accepted definition, that while the two opinions that followed focus on risk provided by the European Commission constitutes a assessment methodologies and safety aspects, and risks to robust framework for understanding synthetic biology.

“Synthetic Biology is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms” (SCENIHR, SCCS, SCHER, 2014) SYNTHETIC BIOLOGY AND BIODIVERSITY 7

BOX 2. Key terms

BioBricks: The technical standard for genetic parts, such as DNA, sequences, domains and protein-coding sequences, which can be assembled to engineer biological systems. Over 20 000 parts are currently available in the Registry of Standard Biological Parts. Biodiversity: The variability among organisms from all sources including terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part (including diversity within and between species and of ecosystems). Biotechnology: The application of techniques, including recombinant DNA techniques, that overcome natural physiological reproductive or recombination barriers and that are not used in traditional breeding and selection. DNA-based circuits: The rational design of DNA sequences to create biological circuits with predictable, discrete functions, which can be combined in various cell hosts. : Genetic systems that circumvent the traditional rules of sexual and increase the odds that a gene will be passed on to offspring, allowing them to spread to all members of a . Gene drive systems can be used to spread particular genetic alterations through targeted wild over many generations. By altering the traits of entire populations of organisms, gene drive systems have been posited as a powerful tool for the management of ecosystems. Genetic engineering: The techniques/methodologies used for genetic modification. Genetic material: Any physical carrier of information that is inherited by offspring, such as DNA. Genetic modification: The processes leading to the alteration of the genetic material of an organism in a way that does not occur naturally by mating and/or natural recombination. Genetically modified organism: An organism in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination. Living modified organism: Any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology. Living organism: Any biological entity capable of transferring or replicating genetic material, including sterile organisms, and viroids. : The simplest possible component able to sustain reproduction, self-maintenance, and . : The study and development of life forms based on not found in nature. This includes xeno-nucleic acids (synthetic alternatives to the natural nucleic acids DNA and RNA) and amino acids that are not found in the natural of organisms. Xenobiology could provide a tool by preventing interactions between synthetic organisms and the natural world (xeno-nucleic acids can prevent genetic exchange with wild organisms, as they cannot hybridise with natural genetic material).

Sources: Article 2 of the Convention on Biological Diversity; Cartagena Protocol on Biosafety; CBD 2015a; Pinheiro and Holliger, 2012; SCENIHR, SCCS, SCHER, 2014; Schmidt, 2010; Shetty et al., 2008; Wyss Institute, n.d. SYNTHETIC BIOLOGY AND BIODIVERSITY 8

Genetically Engineered Animals

1 New traits can be introduced Generation of the DNA Construct into animals. Here’s how it A. Milk Protein Promoter DNA: works for animals engineered to Allows for expression only produce a human pharmaceutical. in goat mammary glands.

B. Therapeutic Protein Gene: Encodes a protein known 2 to treat disease in people. The DNA construct is created by combining C. Sequence: A, B, C and D. Assures that only the gene of interest is controlled by A.

D. Other DNA Sequences: Helps with the introduction of the new combination DNA strand.

Native goat DNA

6 The drug to be used to Native goat DNA 3 treat human disease is purified from the goat’s milk.

This new DNA strand is then introduced by any of a number of methods into an cell, such as an egg, that is then used to produce a genetically engineered animal.

5

The offspring of the first 4 genetically engineered goats, referred to as production animals, The first genetically are milked. The milk is transferred engineered goat is to a purification facility. produced.

FDA Consumer Health Information / U.S. Food and Drug Administration www.fda.gov/ForConsumers/ConsumerUpdates/UCM143980.htm

How goats are genetically engineered to produce ATryn ©FDA, US Food and Drug Administration, 2009 http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm143980.htm SYNTHETIC BIOLOGY AND BIODIVERSITY 9

2. What are the applications of synthetic biology?

Synthetic biology is still an emerging field but there are Other medical applications of synthetic biology include growing numbers of applications in the pharmaceutical, engineering bacteria to attack cells (Anderson et al., chemical, agricultural and energy sectors. In 2012, the 2006) and designing new antibiotics (ERASynBio, 2013). World Economic Forum in Davos listed synthetic biology as an area which is likely to have a ‘major impact’ on the There are also reams of synthetic biology studies that world economy in the future. The UK government has have possible benefits for the environment. There are also named it as one of eight great technologies that will projects underway to produce for polluted support future growth in the economy (Midven, 2016). water for example (Aleksic et al., 2007). It is also possible to develop organisms that can process waste and purify Commercial applications tend to focus on creating water (and therefore restore damaged sites) by removing (such as E. coli, baker’s and contaminants such as heavy metals and pesticides. One microalgae) that can synthesise valuable products, such as fuels, food and pharmaceuticals. A notable example is the engineering of yeast cells that synthesise , a drug used to treat malaria. American scientists first reported the engineering of yeast to produce the precursor of artemisinin in 2006, which could be transported, purified and chemically converted to the full drug (Ro et al., 2006). Algal biofuel ©Flickr/Sandia Labs 2008. CC BY 2.0. This process has since been enhanced and commercial production of semi- group of scientists (Kane et al., 2016) recently developed synthetic artemisinin is now underway by pharmaceutical E. coli able to degrade methylmercury, a toxic metal that company Sanofi (Paddon and Keasling, 2014), which may can accumulate up the food chain. provide a model for the production of other pharmaceutical agents by synthetic biology. Biofuels produced by engineered organisms such as algae could be a more sustainable alternative to fossil fuels, as In 2006, the EU Agency issued a license for they can be farmed without using arable land (Georgianna a synthetically produced drug called ATryn, which is & Mayfield, 2012). As photosynthetic organisms, algae extracted from the milk of genetically engineered goats also remove CO2 from the air, reducing it into energy- (EMA, 2015). ATryn is an anticoagulant, used to prevent rich hydrocarbons (Schmidt, 2010). Synthetic biology blood clots in patients with a rare genetic disease. This has for some time been hailed as a potent contributor to therapeutic protein can be derived from the milk of goats food security, by developing new crop varieties that are whose genes have been altered to include a segment of resistant to pests or that have enhanced nutritional value. DNA that instructs their cells to produce antithrombin — a protein that occurs naturally in humans. In 2009, the US Although synthetic biology may have benefits for society, also approved ATryn — its first approval for a biological there are many scientific uncertainties surrounding product produced by genetically engineered animals the development of synthetic life, cells and genomes, (FDA, 2009; see facing page). especially in terms of their impact on the environment.. SYNTHETIC BIOLOGY AND BIODIVERSITY 10

BOX 3. The case of glowing plants

As well as applications which promise to solve grand societal challenges, there are concerns about purely commercial applications.

The ‘Glowing Plant project’ began as a Kickstarter project to engineer the thale cress () to emit light, using synthetic variants of genes from fireflies and jellyfish. This was the first crowdfunding campaign for a synthetic biology project. It was successfully funded and is now available to the American public to pre-order, in the form of the already grown plant or its seeds.

According to the developers, the plants could one day be used to light streets at night, thus saving energy use and reducing CO2 emissions. However, others say the project is ‘frivolous’ and has limited value to society (Callaway, 2013).

Beyond this, there are concerns about the risk this project may represent, as it provides an example of the unregulated release of a synthetic organism. The glowing plants are not regulated by the US Animal and Plant Health Inspection Service (APHIS) as they are not deemed to pose a risk (Callaway, 2013). This is because the APHIS jurisdiction to regulate GM plants depends on the use of a ‘plant pest’, and the technique does not use any elements that meet the definition of a plant pest within the US Plant Protection Act2.

2. US Department of , Animal and Plant Health Inspection Service (2000) Plant Protection Act. Text available from: http://www.aphis.usda.gov/brs/pdf/PlantProtAct2000.pdf

GLOWING2. What PLANTS: are the Aapplications TIMELINE of synthetic biology? SYNTHETIC BIOLOGY AND BIODIVERSITY 11

Although a regulated plant pest (, able to transfer DNA to plants and therefore used frequently in genetic engineering) was involved in the process, it was used to modify the foreign genes before producing plants for distribution. Once the team showed the worked using the bacteria, they inserted the same DNA sequence into the plant using a (Shin, 2013), which is generally considered safe and does not rely on plant pests. The Glowing Plant therefore does not use genetic material from a plant pest, does not use a plant pest as a recipient organism, and no plant pest is used to modify the genes of the plant (Synthetic Biology Project, 2015). The transgenic plant consequently does not satisfy any of the regulatory criteria that would be subject to the oversight of APHIS (Evans, 2014).

Although the USDA does not appear to have any regulatory concerns about the project, scientists and policymakers have questioned its societal value and risks — including the impact on public opinion of synthetic biology and the need to apply the precautionary principle.

It is unclear whether these plants pose any risks to human health or the environment, but allowing their entry to the market based on the absence of plant pests rather than an assessment of potential risk is of concern to many. A lack of regulation in future commercial projects could be more risky, and poses important ethical and legal questions.

For now however the risk remains hypothetical, as the team at glowingplant.com are yet to produce a completely functional glowing plant, highlighting the difficulties of producing working genetic elements in complex living systems (Regalado, 2016).

http://www.glowingplant.com/ SYNTHETIC BIOLOGY AND BIODIVERSITY 12

2.1 Synthetic biology in Europe which provides the world’s most comprehensive range of freely available molecular databases. Furthermore, in Europe is well placed to take advantage of the ‘synthetic 2013, there were an estimated 150 companies engaged biology revolution’ due to its leading academic institutions in synthetic biology research in Europe, including those and strength in biotechnology research. Researchers in working on agricultural, environmental, medical and Bristol, UK are developing a toolkit of novel proteins food applications (ERASynBio, 2013). which could be used as building blocks for biomaterials, including hollow spheres able to carry drugs (Bromley Although synthetic biology may have benefits for society, et al., 2008). Elsewhere, a collaborative team involving there are many scientific uncertainties surrounding researchers from Belgium, France and Germany has the development of synthetic life, cells and genomes, developed a of E. coli with the T bases in its especially in terms of their impact on the environment. DNA replaced by an artificial base. This provides proof of concept for the use of xeno-nucleic acids and may An inventory of synthetic biology-based products and have potential as a safety mechanism, whereby synthetic applications, covering the US and Europe, is available organisms are dependent on lab-supplied nutrients for via the Synthetic Biology Project’s website (http:// survival (ERASynBio, 2013). www.synbioproject.org/cpi/). This tool allows citizens, researchers and policymakers to explore products on Europe is also home to the European Molecular Biology or close to market. Although not comprehensive, this Laboratory (EMBL), which has the highest citation inventory provides a good overview of currently available impact in molecular biology and genetics outside of synthetic biology based products and the companies that the US, and the European Bioinfomatics Institute, produce them.

Synthetic Biology projects funded by the Sixth Framework programme for NEST (New and Emerging Science and Technology): BioModularH2 This project aims to use synthetic biology to produce hydrogen, by designing devices that use the natural ability of cyanobacteria to produce hydrogen as a by-product of atmospheric . https://www.shef.ac.uk/synbio/biomodularh2 BioNano-Switch Aims to develop a using biological molecular motors. The project hopes to facilitate ‘lab-on-a-chip’ technologies — which enables operations that normally require a laboratory, on a miniature scale, such as infectious disease diagnosis. http://synbiosafe.eu/project/bionano-switch/ Eurobiosyn Working on the synthesis of oligosaccharides from E. coli, chemicals which are used to create many pharmaceuticals. http://www.eurobiosyn.org FuSyMem Cell membranes are important in sensory perception, drug action and signal recognition. This project aims to understand and ultimately control cell membranes to develop applications such as biosensors. http://archiveweb.epfl.ch/fusymem.epfl.ch/ NANOMOT This project aims to engineer building blocks that can be assembled into controllable ‘nano- engines’, with lab-on-a-chip technologies and chemical nanoreactors as potential applica- tions. http://synbiosafe.eu/project/nanomot/ PROBACTYS Aims to construct a bacterial cell containing coordinated genetic circuits that can transform chloro-aromatic chemicals into high-added-value products. http://www.2020-horizon.com/PROBACTYS-Programmable-bacterial- catalysts(PROBACTYS)-s20599.html SYNTHCELLS SYNTHCELLS aims to bio-engineer minimal cellular constructs with applications including and drug delivery systems. http://cordis.europa.eu/project/rcn/85168_en.html Table 1. Source: Pei et al., 2012 SYNTHETIC BIOLOGY AND BIODIVERSITY 13

3. What are the potential impacts of synthetic biology on biodiversity? In many ways synthetic biology presents a dilemma; it non-renewable energy sources and thus mitigate climate may propose solutions to some of the greatest challenges change (CBD, 2015; Redford et al., 2014), which has facing the environment, such as climate change and negative effects on biodiversity. scarcity of clean water, but also poses a high risk for natural ecosystems. The introduction of novel, synthetic Applications in bioremediation could benefit organisms may therefore have both constructive and biodiversity. Bacteria such as Rhodococcus and Pseudomonas destructive effects on the conservation and sustainable naturally consume and breakdown into less use of biodiversity. toxic byproducts. Synthetically engineered microbes could be used to degrade more persistent chemicals such Benefits as dioxins, pharmaceuticals, pesticides or radioactive substances (which might otherwise be sent to hazardous Several synthetic biology applications aim to respond waste landfills). A team at theSpanish National Center to environmental challenges, including those associated for Biotechnology are engineering microbes that survive with energy, wildlife and agriculture. These may have in harsh conditions by replacing non-essential genes indirect or direct positive impacts on biodiversity. For with metabolic circuits that direct microbes away from example, some GM crops have provided both livelihood simple sources of carbon (such as glucose) towards and conservation benefits (Redford et al., 2014). Bacillus thuringiensis (Bt) cotton — genetically modified to produce an insecticide — has been shown to reduce pest damage in developing countries such as India, contributing to agricultural growth in small-scale farms. Several other GM, -resistant and herbicide-tolerant crops have benefitted farmers in developing countries by increasing yield (Carpenter, 2010; Waim and Zilberman, 2003).

In this way, synthetic Clover in a field margin CC0 @Pixabay /glarcombe biology could reduce the impact of human land use on biodiversity, by, for example, reducing the need industrial chemicals (Schmidt, 2010). The application of for pesticide use (which can have negative impacts on these bacteria could remove pollutants that are currently non-target wildlife). Furthermore, currently persistent, and more rapidly, thus helping to restore unavailable to wildlife due to energy installations for damaged sites and facilitate conservation. example could be made available by the introduction of new methods of energy production, such as algae Synthetic biology can be used to synthesise that use carbon to produce fuel (Redford et al., 2014). products currently extracted from plants Biofuels have also been posited to reduce reliance on and animals. Engineering biosynthetic pathways provides an alternative and cost-effective method of SYNTHETIC BIOLOGY AND BIODIVERSITY 14

producing drugs of natural origin, such as morphine and aspirin (Khalil and Collins, 2011). This may reduce the pressure on species that are currently threatened by hunting or harvesting (CBD, 2015).

The ability of synthetic biology to restore and even extinct species has been widely reported. Using synthetic biology to re-create extinct species has captured the imagination of the public, through projects such as ‘Revive and Restore’ (The Long Now Foundation, 2015). No longer solely the realm of , the restoration of extinct species has become a subject of valid scientific research and planning. Although DNA can Wooly Mammoths: a target for de- © iStock/Aunt_Spray only survive for limited periods, it has been found and sequenced for wild that have been extinct for 700 000 years, and work has already Risks begun to bring back the passenger pigeon and woolly mammoth (Charo and Greely, 2015; The Long Now While there are certain opportunities for protecting Foundation, 2015). While this aspect of synthetic biology biodiversity, there are also risks to consider. The escape has understandably garnered lots of attention, there are or release of novel organisms into the environment concerns that such projects may distract attention (and could radically and detrimentally change ecosystems. funds) from more deserving and essential conservation Genetically engineered microbes could have adverse effects projects. There are unclear benefits, and unknown long- in the environment due to their potential to persist and term risks, due to the restoration of previously extinct transfer their genetic material to other microorganisms. species. The organisms may become invasive, and, by exchanging genetic material, form hybrids that out-compete wild More immediate benefits could be derived from species. Indeed, the transfer of genetic material protecting at-risk species by genetically to wild populations is a major risk. Genes could be modifying bees to be resistant to pesticides or mites transferred through horizontal or vertical gene transfer, for example (Redford et al., 2014). Synthetic biology which could lead to a loss of genetic diversity and the could be used to engineer solutions to other threats to spread of harmful characteristics. Even without genetic biodiversity, including infectious diseases like nose transfer, these organisms could have toxic effectson , a fungal disease that affects hibernating . other organisms such as soil microbes, , plants and animals. They may also become invasive and have an It is also possible to use synthetic biology for control adverse effect on native species by destroying or of disease vectors. Using gene drive systems, it disrupting the food web for example (CBD, 2015). is possible to change the genomes of populations of mosquitoes to make them less dangerous (e.g. resistant to Many of the supposedly beneficial applications of the parasite that causes malaria) (Ledford and Callaway, synthetic biology could also have negative side-effects. 2015). Gene drive systems can also be used to lessen For example, gene drive systems designed to suppress the threat from other insect vectors of diseases, reverse populations of disease vectors could have unintended pesticide resistance or eradicate invasive species, which consequences for biodiversity, such as introducing are significant threats to biodiversity (Redfordet al., new diseases by replacing the population of the 2014). original disease vector with another (CBD, 2015). Using SYNTHETIC BIOLOGY AND BIODIVERSITY 15

gene drives to change entire populations very rapidly in Iran, but can now be synthetically produced by yeast. could have other unforeseeable implications, including Each hectare of natural saffron growing in Iran provides potentially devastating effects on entire ecosystems. jobs for around 270 people a day – replacing that with synthetic versions therefore threatens livelihoods (ETC Similarly, while replacing natural products with synthetic Group, 2016). A growing range of products (such as palm ones could reduce pressure on natural habitats, it could oil, rubber and artemisinin) are beginning to be provided also disrupt conservation projects and by synthetic biology, which may deprive farmers of their displace small-scale farmers (CBD, 2015). only source of income and raises serious and Saffron for example is usually picked from crocus flowers complex issues of global justice.

BOX 4. Synthetic biology and the Aichi Biodiversity Targets

Synthetic biology may both contribute to the Aichi Biodiversity Targets (shown in green) and impede progress towards them (shown in red).

Address the underlying causes of biodiversity loss (Targets 1-4) • May promote a to more sustainable consumption and production • The ability to change the genetics of an organism may change people’s perceptions of nature and biodiversity • Distract policymakers from addressing the underlying causes of biodiversity loss

Reduce direct pressures on biodiversity and promote sustainable use (Targets 5-10) • New potential for ecological restoration • Synthetic organisms in agriculture may reduce land conversion and protect wild habitats • Organisms may become invasive

Improve the status of biodiversity by safeguarding ecosystems, species and genetic diversity (Targets 11-13) • Synthetic organisms may threaten protected areas • Restoring extinct species may help to meet targets for conservation while still allowing new to occur, due to a counter-balancing effect • Society may become less willing to support efforts to protect endangered species • May make off-site conservation more attractive than on-site, reducing support for existing protected areas

Enhance the benefits from biodiversity and services (Targets 14-16) • Could remove justification for conservation by providing ecosystem services such as clean water and air • Private ownership of genetic material may restrict access for public benefit

Adapted from Redford et al., 2013 SYNTHETIC BIOLOGY AND BIODIVERSITY 16

Another major concern relates to the large-scale According to the civil society organisation the ETC increase in the use of biomass. A large group (2010), biomass-based economies will develop, number of synthetic biology applications involve which are market driven and — unlike biodiversity- organisms that convert biomass into valuable products. based economies — view nature in terms of its Cellulosic biomass, such as wood and grass, represents commercial value and profit potential. They a renewable source of sugars that can be used as suggest that major changes to land-use will occur, such as feedstock for . Several microorganisms can increases in the number of plantations in former forests naturally degrade cellulosic biomass, but with synthetic (a major source of biomass), which have little value for biology, organisms can be engineered to convert the biodiversity and significant negative impacts on water sugars in biomass into useful products, such as fuels or and soil. pharmaceuticals (French, 2010; French et al., 2013). Although use of feedstock could benefit the environment These land-use changes may also have adverse impacts by representing a shift away from non-renewable on food and livelihood security (Redford et al., resources, increased demand for biomass could also lead 2014). The increased production of biomass could reduce to increased extraction of biomass from agricultural land access to local natural resources and cause small, self- (CBD, 2015). Fuel production may require particularly sufficient farms to be replaced by large-scale commercial large amounts of biomass, which could reduce farming (CBD, 2015). soil fertility and and contribute to biodiversity loss due to the conversion of natural land Finally, there are deeper concerns that synthetic biology (CBD, 2015). Indeed, a number of studies suggest that may act as a ‘sticking plaster’ rather than providing a extracting biomass from existing agricultural practices profound solution to biodiversity loss. In other words, is already causing a decline in soil fertility and structure synthetic biology may distract policymakers, (CBD, 2015). scientists and industry from the deeper underlying causes of biodiversity loss.

Biofuel feedstocks @Flickr/Idaho National Laboratory 2013. CC BY 2.0. SYNTHETIC BIOLOGY AND BIODIVERSITY 17

4. Case study: new technologies

A separate although interconnected issue is that of new plant breeding techniques, which aim to create new traits in plants using genetic engineering. Unlike synthetic biology — which generally involves major genetic changes (such as altering entire metabolic pathways) — plant breeding typically involves smaller changes, such as changing individual genes or even bases in DNA.

Innovation in plant breeding is deemed by many to be essential to meet the challenges of population growth and of interest (Espinoza et al., 2013) and are more similar to climate change. Plant breeding techniques have been crops that may occur by conventional breeding. around for decades, but a number of very new techniques (developed after the 2001 review of the EU Directive on While is the transfer of genes from the same the deliberate release of GMOs) are creating concern, or closely related species, intragenesis is the and are surrounded by legislative uncertainty. of a reorganised region of a gene from the same species (EASAC, 2015), and is therefore further removed from These new techniques differ from the methods traditional breeding. Although it also describes the traditionally used to create GMOs (such as transgenesis) introduction of a gene that originates from the same because they involve specific and targeted changes to or a crossable species, intragenes are hybrids, which the genome, and do not involve any foreign DNA. means they may contain elements from different genes. Traditional plants contain genes from transgenic Intragenesis enables the development of new genetic another species, such as containing proteins from combinations, and thus GMOs with more innovative Bacillus thuringiensis to make it resistant to insects. properties (Espinoza et al., 2013). Both methods provide Mixing genetic materials between species that could not viable alternatives to transgenic crops. hybridise naturally has previously generated concern among the public and regulatory agencies (Holme et al., In 2012, the European Food Safety Authority (EFSA) 2013). reviewed the risk of cisgenic and intragenic plants by comparing them to conventional plant breeding Two newer (and potentially safer) techniques are techniques. The Panel established that similar hazards are and . Unlike transgenesis, cisgenesis intragenesis associated with cisgenic plants and conventionally bred cisgenesis involves transferring genes between members plants. However, plants created through intragenesis may of the same species, or closely related species that could present novel hazards. Overall, they concluded that the naturally. The term cisgenic plant, introduced frequency of unintended effects may differ based on the less than 10 years ago, can be defined as ‘a crop plant that breeding technique used and risks must be assessed on a has been genetically modified with one or more genes case-by-case basis (EFSA, 2012a). isolated from a crossable donor plant’ (Schouten et al., 2006). As such, cisgenic crops contain only the gene(s) SYNTHETIC BIOLOGY AND BIODIVERSITY 18

The genetics of plant breeding SYNTHETIC BIOLOGY AND BIODIVERSITY 19

Classical selective breeding Conventional cross-breeding between species that could naturally SYNTHETIC BIOLOGY AND BIODIVERSITY 20

Genome editing techniques (A-B)

A

New plant breeding techniques (B)

B1

A further technique is engineering with the ‘ Zinc finger nucleases were the first targeted gene-editing nuclease’, a class of enzymes that cut DNA in targeted technique, although more sophisticated techniques places and use the natural machinery of the cell to repair have been developed since — such as the break. This can be used to edit existing genes and activator-like effector nucleases (TALEN), restriction insert new ones (Carroll, 2011). The EFSA Panel also enzymes that can be engineered to cut almost any DNA assessed the risk of plants developed using the zinc finger sequence (Boch, 2011) and the CRISPR/Cas9 system nuclease 3 technique, which allows the integration of (which enables precise genomic modifications in a wide gene(s) into a predefined insertion site in the genome of organisms; see box 5). of the recipient species. The Panel concluded that its existing guidance documents can be used for plants Applications using these new techniques are already in developed using this technique. Furthermore, as the use. In the US, agricultural trait development company zinc finger nuclease inserts DNA to a predefined region, Cibus has used new plant breeding techniques to create they deemed it to have less risk of disrupting genes and/ herbicide-resistant oilseed rape. The variant (which does or regulatory elements than transgenesis. Although not contain any foreign material) was planted in the US there is some risk of off-target, unintended genetic in 2015. The US has also approved a variant with changes, these are expected to be fewer in number and reduced bruising and browning, developed using RNA similar in with respect to mutagenesis techniques (a nucleic acid like DNA) that reduces the expression of used in conventional breeding (EFSA, 2012b). the enzymes responsible for these processes (a method SYNTHETIC BIOLOGY AND BIODIVERSITY 21

B2

B3

called RNA interference, which also does not involve extremes, crops with enhanced nutritional quality, foreign DNA) (EASAC, 2015). In the EU, field trials increasing genetic diversity and reducing crop losses in Belgium and the Netherlands have bred potatoes (ADAS, 2015; EPRS, 2016; STOA, 2013). resistance to the responsible for ‘late blight’ using cisgenesis (EPRS, 2016). However, there are certainly downsides to consider. As well as the potential unforeseen risks that may occur There are many possible benefits to these new techniques: due to unintended genetic changes or gene transfer, increasing yield, improving crop quality, developing some argue that these new plant breeding techniques resistance to pests and diseases, creating plants that use are incompatible with organic farming, which by resources more efficiently or can adapt to environmental definition excludes GMOs, and may therefore threaten SYNTHETIC BIOLOGY AND BIODIVERSITY 22

BOX 5. CRISPR/Cas9: A genetic modification power tool

As well as applications which promise to solve grand societal challenges, there are concerns about purely commercial applications.

Clustered regularly-interspaced short palindromic repeats (CRISPR) is an emerging genetic modification technique that has the potential to rapidly and precisely modify the genes of crops, animals, and even the human .

CRISPR are DNA sequences found in bacteria that can be used to edit genes. In concert with the Cas9 , CRISPR can cut the genome at any location of choice. A modification of the system has recently allowed researchers to change not just genes, but individual bases within genes (Komor et al., 2016). This is an important tool for synthetic , but also a challenge to the international regulatory landscape.

CRISPR has been used for medical purposes, fuelling a new generation of . In April 2015, scientists reported use of the technique to edit human , sparking an ethical debate. In agriculture, CRISPR is being used to engineer wheat and rice resistant to disease and create vitamin-enriched fruit crops, and CRISPR-based gene drive systems could be used to eradicate populations of disease-carrying mosquitoes. Such environmental applications raise many concerns, including how to recognise a modified organism (as the changes made by CRISPR are difficult to differentiate from changes obtained by conventional breeding) and how changing or removing entire populations — and stores of genetic material — may affect the rest of the ecosystem. The major changes to genetic information enabled by CRISPR- Cas9 could have major impacts on biodiversity, especially if used on organisms with rapid reproduction cycles such as insects, microbes or annual plants. Furthermore, because it is difficult to identify these synthetic organisms, it will be challenging to monitor or control them. In the context of plant breeding, there is fear that these techniques will have significant economic consequences for the organic sector.

Regulatory authorities around the world are considering the social, ethical and environmental. implications of this system. Indeed, this is an international issue, as organisms and effects could easily spread across borders. A recent report from the US National Academies concluded that laboratory studies conducted to date are not sufficient to support a decision to release gene-drive modified organisms into the environment, recommending field research to refine CRISPR/Cas-9 based gene drives and to understand how they might work under different environmental conditions (National Academies, 2016b). Similarly, a policy report from the Netherlands’ National Institute for Public Health and the Environment (Westra et al., 2016) concluded that the use of gene drives is a cause for concern, and that current methods for assessing the risks to human health and the environment are insufficient.

Source: Ledford, 2015. SYNTHETIC BIOLOGY AND BIODIVERSITY 23

its development. Other arguments include increased be exempt from regulations for GMOs. Overall, the production costs for farmers and reduced freedom of plant breeding industry argues that these new breeding choice for , farmers and consumers (IFOAM, techniques should not be subject to GMO legislation 2015). (EPRS, 2016).

Associated with these potential downsides, there is an However, as they are still techniques of genetic intense debate regarding whether these newly bred modification, others suggest that they should be plants should come under EU legislation on GMOs. subject to the traceability and labelling requirements The testing and release of genetically modified plants is (Regulations EC 1829/2003 and 1830/2003) that tightly regulated in the EU in order to prevent negative apply to GMOs. The German Federal Agency for effects on human or environmental health, which some Nature Conservation (BfN) for example argues that the argue constrains innovation and agricultural potential. fact that the modifications are carried out purposefully and lead to incorporation of new genetic material into a As these new techniques involve precise changes to host organism is more important than the fact that the the genome and do not involve foreign DNA, some could also occur naturally, and therefore that suggest that they should not be regulated by existing the techniques should fall under the GMO legislation GMO legislation. The European Academies Science (EPRS, 2016). Advisory Council (formed by the national science academies of EU Member States) for instance argues The International Federation of Organic Agriculture that plants produced through these methods are Movements (IFOAM) EU Regional Group recently different from GMOs produced previously, as they developed a position paper on New Plant Breeding enable precise and targeted changes in the genome. For Techniques, recommending that the European several of the techniques, the resultant plant does not Commission considers these techniques as GMOs. The contain any foreign genes and could also be developed paper cites concerns such as unknown consequences by conventional breeding (EASAC, 2015). As such, for biodiversity and economic damage to the organic EASAC recommended that farming sector (IFOAM, 2015). Should they not fall (when they do not contain foreign DNA) should not under GMO legislation, it could mean that it would fall within the scope of GMO legislation and that the be for the Member States to decide. This could be EU should regulate the agricultural trait or product problematic, as national authorities do not yet have the rather than the technology itself. capacity to properly evaluate potential impacts. The European Parliamentary Research Service (EPRS, 2016) Several other bodies have supported the view that the recently published a brief on the applicability of EU safety of new crop varieties should be assessed based on legislation on GMOs to new plant breeding techniques, their characteristics, not how they are produced (EPRS, which discusses these arguments in more detail. 2016). The US National Academies also recommends that the product, not the process, should be regulated The debate is ongoing and the European Commission and emphasises a tiered approach to has been requested to clarify whether GM regulations based on likely risk to human health or the environment apply to these new techniques (see also section — regardless of how the plant was bred (National 7. Regulatory implications, p. 28) Academies, 2016a). Likewise, Schouten (2006) argues that, as cisgenic plants are similar to traditionally bred plants, they present similar safety concerns and should SYNTHETIC BIOLOGY AND BIODIVERSITY 24

5. What are the ethical issues associated with synthetic biology?

Beyond the impacts on biodiversity discussed above, synthetic biology raises complex ethical issues. Wider use of synthetic biology could generate shockwaves in the global economy, causing a shift towards biotechnology-based economies, or those based on the use of biological resources. This may have particularly significant impacts on the rural economy and low-income tropical countries (Redford et al., 2014), which could be sources of biomass (needed as feedstock for synthetic biology processes). Synthetic biology could provide benefits to these areas, or further reinforce inequities in trade, depending on the policies in place. Furthermore, natural products that are currently grown or harvested in low-income countries could be Hedgehog and cowslip @Pixabay/TomaszProszek displaced by industrial production with the and therefore challenges ideas about what is natural help of genetically engineered organisms. Government (Calvert, 2010). It may reduce how much people value policies in both high- and low-income countries will what are now precious natural resources, and reduce have a large influence on these new bio-economies and support for conservation efforts in the expectation that the social impacts they have (CBD, 2015a). extinct species can be brought back to life. There are many questions about the use of synthetic Linked to this are philosophical debates about the biology techniques, how they are controlled and who creation of life, prompting fears about scientists will profit from their use. Many ethical and economic ‘’; concerns that have been voiced since issues are related to the role and place of synthetic biology the beginning of modern biotechnology (Dabrock, in the fair and equitable sharing of benefits arising from 2009). In 2010, a team of scientists led by the use of genetic resources, which is the third objective (Gibson et al.) produced an entirely synthetic genome of the CBD. While the Nagoya Protocol3 provides a and introduced it to bacteria without any genetic framework for the fair sharing of benefits arising from material, allowing the cells to grow and replicate. In the use of genetic resources, it is not clear whether it 2014 (Malyshev et al.) the first entire living organism would be applicable to all synthetic biology (Bagley & with artificial DNA was produced, when a team Rai, 2013). For example, the Nagoya Protocol would engineered E. coli to replicate a genetic code containing not seem to cover digitally stored genetic information unnatural base pairs – representing the first organism to which may be used as a basis for synthetic biology, and propagate an expanded genetic alphabet. More recently as such would not capture an increasingly important (Hutchison et al., 2016), Venter’s lab built a bacterium dimension of the potential value of genetic material. with the smallest genome of any free-living organism, This issue may have to be addressed by the Parties to a cell that is able to survive and self-replicate with just the Protocol. 473 genes. (For comparison, humans have around 21 000 genes and even the fruit has around 17 000 Yet another and broader ethical concern is how the (Kimball, 2016)). The construction of ‘life’ in this ability to engineer biology may affect people’s perception manner raises questions about what ‘life’ really means of nature, and the value they attribute to it. Synthetic and our relationship with the natural world. biology aims to create living organisms from scratch

3. https://www.cbd.int/abs/ SYNTHETIC BIOLOGY AND BIODIVERSITY 25

The line between changing the genetics of an existing society. To assist with this, the newly established organism and creating an entirely new being is blurred, Scientific Advice Mechanism (SAM) has been given prompting some scientists to find a definition of ‘life’ the mandate to provide independent and high quality — what it is, where it begins, and how complex it scientific advice to the European Commission. SAM is must be. To assist this, some have proposed a modified now hosting the secretariat of the European Group on version of a Turing test (which is used to test whether Ethics in Science and New Technologies (EGE)4, which a machine’s intelligence is equivalent to a human) for was requested by the President of the Commission to life imitation. While this may have some use, such a provide independent advice on the scientific, ethical, definition is unlikely to allay deeper concerns about the legal, governance and policy implications of synthetic blurring of the boundary between the synthetic and the biology in 2008. An opinion on the ethics of synthetic natural (Balmer & Martin, 2008), especially as machine biology adopted by the EGE in 20095 concluded that learning is starting to rival world-class human game the responsible development of synthetic biology must players. be based on ethical principles, enshrined in conventions and declarations. The general framework As this section highlights, beyond the immediate safety developed in this opinion remains valid, although an issues, there is a need for robust ethical governance update to take account of the most recent developments of synthetic biology to protect the environment and in the field could be valuable.

6. What are the safety issues associated with synthetic biology, and how can we manage them?

As the field continues to develop at breakneck pace, through populations (gene drives) to cause the spread of there are huge uncertainties regarding not only what disease. Other potential malicious applications include the potential of synthetic biology may be, but also production of biological weapons (e.g. modified the risks it may pose. The accidental release of GMOs pathogenic viruses) or microorganisms engineered to into the environment is a clear concern, as organisms produce toxins. could evolve, proliferate and interact in unexpected ways, potentially adversely affecting ecosystems. There are many scientific uncertainties and potential unforeseen consequences to do with the manipulation and transfer of genetic material, such as the integration of modified cells with living organisms or transfer of genetic material to wild organisms.

As well as the accidental transfer of genes to wild populations, there is also the possibility of intentional destructive activity, such as engineering genes that quickly spread could have destructive effects on the environment © iStock /Bernd Wittelsbach

4. https://ec.europa.eu/research/ege/index.cfm 5. Opinion n°25 17/11/2009: http://ec.europa.eu/archives/bepa/european-group-ethics/docs/opinion25_en.pdf SYNTHETIC BIOLOGY AND BIODIVERSITY 26

Although the design and production of entirely novel with the external environment. They can also be placed pathogens for malevolent purposes is unlikely, there under contained use outside of labs, using physical are reasons to take the threat seriously, as anyone can measures to limit their exposure to the environment. potentially access public DNA sequences, design DNA using free software and order it for delivery (although Applications where organisms are intended for this requires rare expertise, and checks are in place to release into the environment will have different and ensure that sequences of pathogens cannot be ordered). potentially greater safety concerns than those intended Out of this has arisen a debate about publishing studies for restricted use. Thus, as well as physical restrictions, which could have security implications, such as the more sophisticated techniques to contain organisms description of -resistant mousepox (Jackson et are being explored, such as ‘integrated al., 2001) and the artificial synthesis of the polio traits’, which act as built-in safety controls. Examples (Cello et al., 2002). include ‘kill switches’, which cause the death of the engineered organism on a particular signal, such as the There is an understandable danger here, but publishing introduction of a chemical. A kill switch activated in such studies could also have benefits for science the presence of the chemical IPTG (commonly used as and banning them raises complex censorship issues. a trigger in molecular biology) has been demonstrated Another protective mechanism is for companies that in engineered microbes in soil, seawater and an animal synthesise DNA to screen all sequences for model (Knudsen et al., 1995). Other inducers include before processing an order (EGE, 2009). In fact, the heat and sugar (Moe-Behrens et al., 2013). International Gene Synthesis Consortium (http://www. genesynthesisconsortium.org/) — a consortium of the Other control measures include engineering bacteria to world’s leading gene synthesis companies — already be dependent on nutrients and self-destruct mechanisms screen the sequences of synthetic gene orders and the that are triggered once the population density exceeds a customers who place them to help prevent the misuse certain threshold (Balmer & Martin, 2008). A further of this technology. An alternative solution may be for possibility is the inclusion of nucleic acids containing the scientific to ‘self police’ research for elements not found in nature (xeno-nucleic acids), malevolent intent or for situations when legitimate which cannot mix with naturally occurring organisms research could be misused (Atlas, 2009). (CBD, 2015a).

To mitigate the possible negative impacts, there are While there are clearly a range of control strategies in also several methods of control that can be used on place, no biocontainment strategy can eliminate risk, the synthetic organisms themselves. Firstly, organisms which highlights the importance of robust risk and used for research purposes can be kept in confined safety assessment methods. conditions, with measures in place to prevent contact SYNTHETIC BIOLOGY AND BIODIVERSITY 27

BOX 1. Do-it-yourself (DIY) synthetic biology

As technology advances, synthetic biology has become simpler to use than traditional molecular biology techniques — and more affordable. In concert with this, its user base has expanded from scientists to interested amateurs, creating the ever-expanding field of ‘DIY Biology’.

There are thousands so-called DIY biologists worldwide, increasingly organised in formal groups. DIYBio.org for example (founded in 2008) has over 2000 registered members in over 30 countries. In the EU alone, there are over 15 countries registered, each with their own website. Most activities involve teaching and workshops, but some involve lab-based experiments.

Recent advances include ‘Cello’, a piece of software that allows people who are not trained biologists to design biological systems (Nielsen et al., 2016) and ‘Bento Lab’, a DNA analysis kit suitable for beginners the size of a laptop (Bioworks, 2014).

There are some concerns that citizen scientists may not follow the risk assessment and biosafety procedures required by the professional community. However, it requires not only materials but also knowledge to create biological systems that may cause harm, and there is no reason to expect the DIY Biology community to cause more harm than anyone else (Kuiken, 2016). Furthermore, the community has developed its own code of conduct (diybio.org/codes), which, alongside the ‘Ask a biosafety professional your question’ portal, demonstrates its sense of responsibility (ask.diybio.org).

In 2015, in its second opinion on risk assessment methodologies and safety aspects, the three European Commission Scientific Committees concluded that, in principle, DIY Biology does not pose a hazard to humans or the environment. Realistically, the greater threat is likely from state-level biological warfare programmes (Balmer & Martin, 2008).

However, because it is becoming more popular, established safety practices must be maintained. An independent biosafety body could be used for verification, and it is important that newcomers undergo the same biosafety training as professionals (European Commission, 2015). It is also important to proceed towards robust codes of conduct and regulations for safe and responsible research, developed through public dialogue.

In the EU, genetic engineering experiments can only be performed in GM-authorised labs, which places limits on DIY biology. Several groups in Europe already begun the process to create a certified lab for genetic engineering projects. For example, a Netherlands group began the process in 2013 and groups in Denmark and France are planning to follow suit (Seyfried et al., 2014).

The benefits of a responsible DIY Biology community in Europe could be far-reaching, raising public awareness of science and creating a participatory innovation process, perhaps developing products that would not have been conceived of by science or industry (Seyfried et al., 2014).

Sources: Kuiken, 2016; SCENIHR, 2015. SYNTHETIC BIOLOGY AND BIODIVERSITY 28

7. Regulatory implications

As discussed earlier in this brief, synthetic biology may synthetic biology and possible new breeding techniques). have unintended negative effects in the environment. Although the former would be simpler in political terms, Unanticipated interactions with natural organisms could perhaps the latter would be more appropriate to match the create risks which must be addressed by legislation if new risks presented by synthetic biology. synthetic biology is to be used responsibly. Clearly, future developments in synthetic biology will Due to the novelty of the field and how rapidly it is require changes to existing regulation, or entirely new changing, there are questions as to whether existing legislation, and there is a pressing need to explore other regulations can adequately address the risks and biosafety frameworks and identify the gaps in current implications of synthetic biology. Synthetic biology falls risk assessment methodologies. There is also a need to under a number of regulatory mechanisms, but most were think creatively about the potential unforeseeable events established before the field fully developed and therefore that could occur. Some argue that no-one can yet fully were not intended to cope with its impacts. understand the risks that synthetic biology poses to the environment, or even what information is needed to At the most recent meeting of the CBD’s Subsidiary Body perform risk assessment (CBD, 2015; Dana et al., 2012). on Scientific, Technical and Technological Advice, the advisory group agreed on a common understanding of Overall, existing biosafety frameworks and the general the terms components (parts used in a synthetic biology principles of the Cartagena Protocol on Biosafety provide process, such as a DNA ) and products (the a sound basis for risk assessment of the living organisms, output of a synthetic biology process, such as a chemical components and products developed by synthetic biology substance). Both of these elements are not living, unlike now and likely to be developed in the near future. the final element of the triad: organisms. The group agreed However, they should be updated and adapted for future that the organisms, components and products of synthetic developments and applications. It is important to assess biology fall within the scope of the Convention and its other regulatory frameworks that cover components and three objectives. This agreed terminology — organisms, products, such as EU chemicals legislation, and address components and products — will be valuable in future any remaining gaps under the CBD. political deliberations.

However, there are many grey areas. Living organisms Convention on Biological Diversity SBSTTA: developed through current applications are similar agreed terminology, April 2016 to living modified organisms (LMOs) defined by the Terminology Living or Does Cartagena Protocol on Biosafety. However, the non-living non-living? Cartagena components are not regulated by this protocol, and there Protocol may be cases in which there is no consensus on whether apply? the application is living or dead (e.g. ). And, as Components Non-living No the field evolves beyond techniques to manipulate nucleic (parts used in a acids in vitro to cause heritable changes, the methods used synthetic biology pro- to assess the risk of LMOs may become inadequate (CBD, cess, such as a DNA 2015). molecule) Products Non-living No There is also discussion of how existing legislation on (the output of a GMOs fits into this. Although synthetic biology results synthetic biology in genetic modification (altering the genetic material process, such as a of existing cells in a way that does not occur naturally) chemical substance) and therefore should be subject to existing EU GMO Organisms Living Yes legislation, several elements of synthetic biology escape the (developed via existing GMO regime. As a result, is has been suggested applications of synthetic (Engelhard, 2016) that new regulation is needed — which biology, similar to living either extends the scope and risk assessment or existing modified organisms) regulations, or takes the form of entirely new regulation that addresses biotechnology more broadly (including GMOs, Source: 20th meeting of the SBSTTA documents SYNTHETIC BIOLOGY AND BIODIVERSITY 29

7.1 Research needs and areas for The European Commission also supports the need to conduct research on the impacts of the organisms, future development components and products of synthetic biology, including In order to understand the potential ecological effects of socioeconomic, cultural and ethical considerations. It synthetic organisms, and thus regulate them effectively, aims to identify and reconcile knowledge gaps, and four areas of research have been proposed (Dana et al., identify how these impacts relate to the objectives of the 2012), to: 1) understand the physiological differences CBD. In its third opinion, the Scientific Committees between natural and synthetic organisms; 2) consider to the European Commission discussed the risks to how engineered microorganisms might alter habitats, the environment and biodiversity related to synthetic food webs or biodiversity; 3) determine the rate at biology processes and products, and identified gaps in which synthetic organisms evolve and whether they knowledge that may prevent reliable risk assessments could persist, spread or alter their behaviour in natural (SCENIHR, SCCS, SCHER, 2015b). environments; 4) understand gene transfer by synthetic organisms (for example, whether synthetic organisms The gaps they identified included a lack of information could transfer antibiotic resistance). and tools to predict the properties of complex unnatural biological systems, and to measure the differences In its opinion on the ethics of synthetic biology, the between natural and engineered organisms. They also EGE makes a number of recommendations for the discussed new methods that allow assessment and regulation of synthetic biology. The scientists to produce lots of variants at the same time. group recommended that the use of synthetic biology Although these methods allow more accurate and be conditional on safety issues and that risk assessment precise changes than traditional techniques, they are be conditional for financing of research. It also also producing organisms at an unprecedented scale recommends the development of a Code of Conduct for and speed, which may create new challenges for risk research on synthetic organisms which should ensure, for assessment. example, that organisms cannot survive autonomously if accidentally released into the environment. For Based on the major scientific gaps they identified, the organisms that are developed for environmental Committees made a number of recommendations for applications, ecological impact assessment studies future research. Vitally, they concluded that more work should be performed and authorisation procedures for is needed to develop standardised techniques to monitor synthetic biology derived materials should take into the survival of organisms in the environment. Indeed, the account risks for the environment and people. need to develop monitoring systems for the organisms, components and products of synthetic biology is key, The EGE discusses the existing regulatory framework as as emphasised in the recent recommendations from the ‘fragmented’ and says it may be not sufficient to regulate CBD’s Subsidiary Body on Scientific, Technical and current and emerging aspects of synthetic biology. It Technological Advice (CBD, 2016). re-iterates the importance of acting now to develop a robust governance framework for synthetic biology in As a party to the CBD, the EU has to clarify its position the EU, which should address all relevant stakeholders on synthetic biology. Key elements include adopting and make clear their responsibilities (EGE, 2009). an operational definition of synthetic biology and evaluating the tools available More recently (2014), ERASynBio (a European to detect and monitor the Research Area Network, originally funded by the organisms, components and European Commission) proposed a vision for European products of synthetic biology — Synthetic Biology, which also discussed the principles and their impacts on biodiversity. of good governance, highlighting the importance of Finally, in terms of regulation, the transparency, participation and accountability in policy. Nagoya and Cartagena Protocols The vision also suggests that regulation should consider may need to be re-assessed, in issues of safety and controls on synthetic organisms, order to determine if changes and that scientists should be required to demonstrate are needed to protect access and consideration of environmental risks, ethical and social benefit sharing, and effectively issues before proceeding with their work. assess the risks posed by synthetic biology. SYNTHETIC BIOLOGY AND BIODIVERSITY 30

8. Summary and recommendations

Synthetic biology is a new and exciting field with to be fit to protect biodiversity in the future. There is a vast range of potential applications, which might a need for further discussions to explore other existing have benefits for biodiversity. However, there are biosafety frameworks and identify possible gaps in also many scientific uncertainties surrounding regulations that need to be addressed and how. It is the manipulation and transfer of genetic material, also important to develop risk assessment protocols which may have matching adverse consequences for for the unlikely but highest impact consequences on biodiversity. There are also complex ethical issues biodiversity. Negotiations are ongoing within the to investigate, including how synthetic biology may CBD to achieve these goals. fundamentally change our perception of the natural world. Several things will be key to surmounting the Whatever is decided, regulations should be challenges presented by synthetic biology. continually updated and coordination between Member States will be vital. Underlying For example, an exploration of synthetic biology this, the precautionary principle must be central to commissioned by the UK Biotechnology and addressing the threats to biodiversity. In the EU, the Biological Sciences Research Council highlighted precautionary principle plays a key role in policy the importance of public engagement for achieving design: applied as a tool to follow developments in a (responsible) progress in the field. This requires sector and continuously verify that the conditions for involving the public in research and demonstrating, the acceptability of a given innovation are fulfilled but not overstating, the societal benefits of (EGE, 2009). In the case of synthetic biology, the applications. Public acceptance of synthetic precautionary principle is an important biology will inform policy, funding and element of ethical debates and legal decision making regulation and therefore how the issues are framed and will help to protect the environment from harm. is very important. Mainstream media coverage to date has focused on extraordinary stories of de- “The growing innovative powers of science seem to be extinction, neglecting the more nuanced benefits (or outstripping its ability to predict the consequences of risks) for biodiversity and complex ethical and social its applications,” warned the European Environment implications (Redford et al., 2014). As well as accurate Agency in 2001. Synthetic biology provides a reporting, the scientific community should openly prime example of technology outpacing debate the implications of their work and engage regulation, and highlights the need to identify with society about the issues it may raise (Balmer & the risks posed by new and Martin, 2008). via early warning systems. As with many such technologies, it is too early to foresee all the possible It is also imperative that a robust governance developments of synthetic biology. Developments framework is in place before synthetic biology’s newest could generate unexpected (and undesirable) side- applications come to fruition. This will involve an effects. Synthetic organisms that are initially useful in-depth review of the existing regulations as well as could later turn out to have harmful and wide- the development of new measures for environmental reaching effects (Engelhard, 2016). release, biosafety and (Balmer & Martin, 2008). Likened to Pandora’s box, it is important that action is taken now to ensure synthetic biology is safely While it seems that the existing regulatory instruments implemented. This sector could revolutionise the — such as the Cartagena Protocol — are broad way our industries and economies function, placing enough to address current issues in synthetic biology, policymakers in a unique position to protect the there are questions about whether they will continue environment throughout the transition. SYNTHETIC BIOLOGY AND BIODIVERSITY 31

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