Science for Environment Policy
FUTURE BRIEF:
Synthetic biology and
biodiversity
September 2016
Issue 15
Environment
Science for Environment Policy
This Future Brief is written and edited by the Science
Communication Unit, University of the West of England
(UWE), Bristol
Email: [email protected]
Synthetic biology and biodiversity
Contents
1. 1. Introduction: What is synthetic biology?
3
2. 2. What are the applications of synthetic biology?
2.1 Synthetic biology in Europe
9
12
3. What are the potential impacts of synthetic biology 13
on biodiversity?
4. Case study: new plant breeding technologies
17
5. What are the ethical issues associated with synthetic 24
biology?
6. What are the safety issues associated with synthetic
biology, and how can we manage them?
25
7. Regulatory implications
7.1 Research needs and areas for future development
28
29
8. Summary and recommendations
30
References
31
Images:
Reproduced with permission by the relevant author or
publisher, or otherwise publicly authorised for use.
With thanks to the following creators:
(iStock) Soybean, Diane Labombarbe; Cotton plant, kristina-s;
Gene editing technology, a_crotty; Sheep, Capreola; Tobacco
leaves, plalek; Fruits and vegetables, Fleren.
(Flaticon)
Freepik; Tomato,
Roundicons;
Cheese,
Madebyoliver; Mouse, Carla Gom Mejorada.
(Noun Project) Christopher Holm-Hansen; P J Souders;
Yorlmar Campos; Cassie McKown; Icon Fair; Elliott Snyder;
Tomas Knopp; parkjisun; Razlan Hanafiah; Chad Remsing;
Arthur Shlain; last spark; NAMI A; Creative Stall.
To cite this publication:
Science for Environment Policy (2016) Synthetic biology
and bidiversity. Future Brief 15. Produced for the European
Commission DG Environment by the Science Communication
Unit, UWE, Bristol. Available at:
http://ec.europa.eu/science-environment-policy
Acknowledgements
We wish to thank the Dr Todd Kuiken (North Carolina
State University Genetic Engineering & Society Center) for
his input to this report, and Dr Matthew Gentry (Swedish
University of Agricultural Sciences, Uppsala) for his review.
Final responsibility for the content and accuracy of the report,
however, lies solely with the author.
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3
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 energy 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 organisms may also pose a high risk for natural ecosystems. 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 genome, which contains all
the information necessary for that organism’s function.
The genome is the complete set of genes in a cell or
organism. Genes contain the information needed to make
proteins, which perform the cellular functions necessary
for life. For thousands of years, humans have deliberately
altered the genes of plants and animals (Beadle, G.W.,
1980; RSPCA, n.d.).
10 000 years ago (Clutton-Brock, 1981; West, B.R.,
2002; Wood and Orel, 2001). Selective breeding has
traditionally focused on species of wheat, rice and sheep
for agricultural purposes, as well as domestic animals.
Dogs are now the most genetically diverse species on
Earth thanks to centuries of selective breeding by humans,
beginning with the domestication of wolves (Adams, J.
2008; Anthes, 2013).
Selective breeding, a term first coined by Darwin
After the discovery of DNA in the 1950s, scientists began
to learn rapidly about the genetic basis of characteristics
and soon began to isolate and manipulate the genetic
in 1859, is a way of selecting for desirable traits and has
been practiced since pre-history, beginning approximately
4
material of organisms. Molecular biology techniques
enabled scientists to take genetic material associated with
a useful trait in one organism and insert it to another, and
thus to develop new breeds of plants and animals more
quickly than before (Synthetic Biology Project, 2015).
Building on understanding of how DNA is regulated,
copied and repaired, molecular genetics advanced further
in the 1970s when restriction enzymes were discovered
(the scientists involved were later awarded the Nobel Prize
for their efforts1). These enzymes cut DNA at a particular
place which can then be combined with other stretches,
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essentially allowing scientists to ‘cut and paste’ DNA. In
1972, the first paper was published using this recombinant
DNA technique, reporting its application to produce
transgenic bacteria (Cohen et al., 1972). The ability to
insert foreign DNA into an organism’s genome, known
under the umbrella term of genetic engineering, has
since enabled the production of disease-resistant crops and
bacteria that can produce the human hormone insulin.
Techniques have continued to evolve at a rapid pace,
including development of the Polymerase Chain Reaction
(PCR) in the 1980s, which can produce millions of
copies of DNA in a matter of hours. Further advances
Genetic engineering. © iStock / nicolas_
in DNA synthesis and cloning technology have made it
much quicker and easier to construct and copy DNA.
With advances in technology and rapidly falling costs of
DNA sequencing and synthesis, scientists begun to create
entirely new sequences of DNA, allowing them to develop
organisms with novel functions, such as producing fuels
or pharmaceuticals. This latest development is termed
‘synthetic biology’, a field which shares features with
modern biotechnology and builds on traditional molecular
biology techniques to control the design, characterisation
and construction of biological parts, devices and systems
(CBD, 2015).
As well as molecular biology, synthetic biology interfaces
with engineering, chemistry, physics, computer science
and systems biology (ERASynBio, 2013) and is focused
on developing more rapid and simple methods to produce
genetically modified organisms (GMOs) by adding or
removing genes, or creating genetic elements from scratch
(European Commission, 2015; SCENIHR, SCCS,
SCHER, 2014).
Unlike traditional genetic engineering, which typically
involves the transfer of individual genes between cells,
synthetic biology involves the assembly of new sequences
of DNA and even entire genomes (Biotechnology
Innovation Organization, 2016). The distinction between
1. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1978/press.html
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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.
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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, biological engineering to design and construct new synthetic
biological parts, devices and systems that do not exist in nature 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 Ethics in Science and New Technologies, 2009)
In 2013, the three independent EU Scientific Committees
(Scientific Committee on Emerging & Newly Identified
Health Risks — SCENIHR, on Consumer Safety
— SCCS, and on Health and Environmental Risks
— SCHER) were requested to adopt a set of three
opinions addressing a mandate on synthetic biology
from the European Commission (Directorates Health
& Consumers, Research and Innovation, Enterprise and
Environment).
The first opinion concentrated on the elements of an
operational definition of synthetic biology,
while the two opinions that followed focus on risk
assessment methodologies and safety aspects, and risks to
the environment and biodiversity and research priorities,
respectively. The first lays the foundation for the two
other opinions with an overview of the main scientific
developments, concepts, tools and research areas in
synthetic biology. Additionally, a summary of relevant
regulatory aspects in the European Union, in other
countries such as Canada, China, South America and the
USA, and at the United Nations level, is included. This
is available from: http://ec.europa.eu/health/scientific_
committees/emerging/opinions/index_en.htm.
Although there is no universally accepted definition, that
provided by the European Commission constitutes a
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)
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BOX 2.
Key terms
BioBricks: The technical standard for genetic parts, such as DNA, promoter sequences, protein 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 in vitro nucleic acid 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.
Gene drive: Genetic systems that circumvent the traditional rules of sexual reproduction and increase the
odds that a gene will be passed on to offspring, allowing them to spread to all members of a population.
Gene drive systems can be used to spread particular genetic alterations through targeted wild populations
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, viruses and viroids.
Protocell: The simplest possible component able to sustain reproduction, self-maintenance, metabolism
and evolution.
Xenobiology: The study and development of life forms based on biochemistry 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 genetic code of organisms. Xenobiology could provide a biosafety
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.
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Genetically Engineered Animals
1
New traits can be introduced
into animals. Here’s how it
works for animals engineered to
produce a human pharmaceutical.
Generation of the DNA Construct
A. Milk Protein Promoter DNA:
Allows for expression only
in goat mammary glands.
B. Therapeutic Protein Gene:
Encodes a protein known
to treat disease in people.
2 The DNA construct is
created by combining
A, B, C and D.
C. Terminator Sequence:
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
treat human disease
is purified from the
goat’s milk.
Native goat DNA
3
This new DNA strand is then
introduced by any of a number of
methods into an animal cell, such as
an egg, that is then used to produce
a genetically engineered animal.
5
The offspring of the first
genetically engineered goats,
referred to as production animals,
are milked. The milk is transferred
to a purification facility.
FDA Consumer Health Information / U.S. Food and Drug Administration
4
The first genetically
engineered goat is
produced.
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
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2. What are the applications of synthetic biology?
Synthetic biology is still an emerging field but there are
growing numbers of applications in the pharmaceutical,
chemical, agricultural and energy sectors. In 2012, the
World Economic Forum in Davos listed synthetic biology
as an area which is likely to have a ‘major impact’ on the
world economy in the future. The UK government has
also named it as one of eight great technologies that will
support future growth in the economy (Midven, 2016).
Commercial applications tend to focus on creating
microorganisms (such as E. coli, baker’s yeast and
microalgae) that can
synthesise
valuable
products, such as
fuels,
food
and
pharmaceuticals.
A
notable example is the
engineering of yeast
cells that synthesise
artemisinin, 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).
This process has since
been enhanced and commercial production of semisynthetic artemisinin is now underway by pharmaceutical
company Sanofi (Paddon and Keasling, 2014), which may
provide a model for the production of other pharmaceutical
agents by synthetic biology.
In 2006, the EU Medicines Agency issued a license for
a synthetically produced drug called ATryn, which is
extracted from the milk of genetically engineered goats
(EMA, 2015). ATryn is an anticoagulant, used to prevent
blood clots in patients with a rare genetic disease. This
therapeutic protein can be derived from the milk of goats
whose genes have been altered to include a segment of
DNA that instructs their cells to produce antithrombin —
a protein that occurs naturally in humans. In 2009, the US
also approved ATryn — its first approval for a biological
product produced by genetically engineered animals
(FDA, 2009; see facing page).
Other medical applications of synthetic biology include
engineering bacteria to attack cancer cells (Anderson et al.,
2006) and designing new antibiotics (ERASynBio, 2013).
There are also reams of synthetic biology studies that
have possible benefits for the environment. There are
projects underway to produce biosensors for polluted
water for example (Aleksic et al., 2007). It is also possible
to develop organisms that can process waste and purify
water (and therefore restore damaged sites) by removing
contaminants such as heavy metals and pesticides. One
Algal biofuel ©Flickr/Sandia Labs 2008. CC BY 2.0.
group of scientists (Kane et al., 2016) recently developed
E. coli able to degrade methylmercury, a toxic metal that
can accumulate up the food chain.
Biofuels produced by engineered organisms such as algae
could be a more sustainable alternative to fossil fuels, as
they can be farmed without using arable land (Georgianna
& Mayfield, 2012). As photosynthetic organisms, algae
also remove CO2 from the air, reducing it into energyrich hydrocarbons (Schmidt, 2010). Synthetic biology
has for some time been hailed as a potent contributor to
food security, by developing new crop varieties that are
resistant to pests or that have enhanced nutritional value.
Although synthetic biology may have benefits for society,
there are many scientific uncertainties surrounding
the development of synthetic life, cells and genomes,
especially in terms of their impact on the environment..
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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 (Arabidopsis thaliana)
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 Agriculture, Animal and Plant Health Inspection Service (2000) Plant Protection Act. Text available from:
http://www.aphis.usda.gov/brs/pdf/PlantProtAct2000.pdf
GLOWING
TIMELINE of synthetic biology?
2. WhatPLANTS:
are the Aapplications
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Although a regulated plant pest (agrobacterium, 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 designs worked using the bacteria,
they inserted the same DNA sequence into the plant using a gene gun (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 host 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/
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2.1 Synthetic biology in Europe
Europe is well placed to take advantage of the ‘synthetic
biology revolution’ due to its leading academic institutions
and strength in biotechnology research. Researchers in
Bristol, UK are developing a toolkit of novel proteins
which could be used as building blocks for biomaterials,
including hollow spheres able to carry drugs (Bromley
et al., 2008). Elsewhere, a collaborative team involving
researchers from Belgium, France and Germany has
developed a strain of E. coli with the T bases in its
DNA replaced by an artificial base. This provides proof
of concept for the use of xeno-nucleic acids and may
have potential as a safety mechanism, whereby synthetic
organisms are dependent on lab-supplied nutrients for
survival (ERASynBio, 2013).
Europe is also home to the European Molecular Biology
Laboratory (EMBL), which has the highest citation
impact in molecular biology and genetics outside of
the US, and the European Bioinfomatics Institute,
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which provides the world’s most comprehensive range
of freely available molecular databases. Furthermore, in
2013, there were an estimated 150 companies engaged
in synthetic biology research in Europe, including those
working on agricultural, environmental, medical and
food applications (ERASynBio, 2013).
Although synthetic biology may have benefits for society,
there are many scientific uncertainties surrounding
the development of synthetic life, cells and genomes,
especially in terms of their impact on the environment.
An inventory of synthetic biology-based products and
applications, covering the US and Europe, is available
via the Synthetic Biology Project’s website (http://
www.synbioproject.org/cpi/). This tool allows citizens,
researchers and policymakers to explore products on
or close to market. Although not comprehensive, this
inventory provides a good overview of currently available
synthetic biology based products and the companies that
produce them.
Synthetic Biology projects funded by the Sixth Framework programme for
NEST (New and Emerging Science and Technology):
BioModularH2
BioNano-Switch
Eurobiosyn
FuSyMem
NANOMOT
PROBACTYS
SYNTHCELLS
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
nitrogen fixation.
https://www.shef.ac.uk/synbio/biomodularh2
Aims to develop a biosensor 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/
Working on the synthesis of oligosaccharides from E. coli, chemicals which are used to create
many pharmaceuticals.
http://www.eurobiosyn.org
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/
This project aims to engineer building blocks that can be assembled into controllable ‘nanoengines’, with lab-on-a-chip technologies and chemical nanoreactors as potential applications.
http://synbiosafe.eu/project/nanomot/
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-bacterialcatalysts(PROBACTYS)-s20599.html
SYNTHCELLS aims to bio-engineer minimal cellular constructs with applications including
bioreactors and drug delivery systems.
http://cordis.europa.eu/project/rcn/85168_en.html
Table 1. Source: Pei et al., 2012
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3. What are the potential impacts of synthetic biology
on biodiversity?
In many ways synthetic biology presents a dilemma; it
may propose solutions to some of the greatest challenges
facing the environment, such as climate change and
scarcity of clean water, but also poses a high risk for
natural ecosystems. The introduction of novel, synthetic
organisms may therefore have both constructive and
destructive effects on the conservation and sustainable
use of biodiversity.
Benefits
Several synthetic biology applications aim to respond
to environmental challenges, including those associated
with energy, wildlife and agriculture. These may have
indirect or direct positive impacts on biodiversity. For
example, some GM crops have provided both livelihood
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, insect-resistant
and
herbicide-tolerant
crops have benefitted
farmers in developing
countries by increasing
yield (Carpenter, 2010;
Waim and Zilberman, 2003).
In this way, synthetic
biology could reduce
the impact of human land use on
biodiversity, by, for example, reducing the need
for pesticide use (which can have negative impacts on
non-target wildlife). Furthermore, habitats currently
unavailable to wildlife due to energy installations for
example could be made available by the introduction
of new methods of energy production, such as algae
that use carbon to produce fuel (Redford et al., 2014).
Biofuels have also been posited to reduce reliance on
non-renewable energy sources and thus mitigate climate
change (CBD, 2015; Redford et al., 2014), which has
negative effects on biodiversity.
Applications in bioremediation could benefit
biodiversity. Bacteria such as Rhodococcus and Pseudomonas
naturally consume and breakdown petroleum into less
toxic byproducts. Synthetically engineered microbes
could be used to degrade more persistent chemicals such
as dioxins, pharmaceuticals, pesticides or radioactive
substances (which might otherwise be sent to hazardous
waste landfills). A team at the Spanish National Center
for Biotechnology are engineering microbes that survive
in harsh conditions by replacing non-essential genes
with metabolic circuits that direct microbes away from
simple sources of carbon (such as glucose) towards
Clover in a field margin CC0 @Pixabay /glarcombe
industrial chemicals (Schmidt, 2010). The application of
these bacteria could remove pollutants that are currently
persistent, and more rapidly, thus helping to restore
damaged sites and facilitate conservation.
synthesise
products currently extracted from plants
and animals. Engineering biosynthetic pathways
Synthetic biology can be used to
provides an alternative and cost-effective method of
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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 genetic diversity
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 science
fiction, the restoration of extinct
species has become a subject
of valid scientific research and
Wooly Mammoths: a target for de-extinction © iStock/Aunt_Spray
planning. Although DNA can
only survive for limited periods, it
has been found and sequenced for wild horses that have
Risks
been extinct for 700 000 years, and work has already
begun to bring back the passenger pigeon and woolly
While there are certain opportunities for protecting
mammoth (Charo and Greely, 2015; The Long Now
biodiversity, there are also risks to consider. The escape
Foundation, 2015). While this aspect of synthetic biology
or release of novel organisms into the environment
has understandably garnered lots of attention, there are
could radically and detrimentally change ecosystems.
concerns that such projects may distract attention (and
Genetically engineered microbes could have adverse effects
funds) from more deserving and essential conservation
in the environment due to their potential to persist and
projects. There are unclear benefits, and unknown longtransfer their genetic material to other microorganisms.
term risks, due to the restoration of previously extinct
The organisms may become invasive, and, by exchanging
species.
genetic material, form hybrids that out-compete wild
species. Indeed, the transfer of genetic material
More immediate benefits could be derived from
to wild populations is a major risk. Genes could be
protecting at-risk species by genetically
transferred through horizontal or vertical gene transfer,
modifying bees to be resistant to pesticides or mites
which could lead to a loss of genetic diversity and the
for example (Redford et al., 2014). Synthetic biology
spread of harmful characteristics. Even without genetic
could be used to engineer solutions to other threats to
transfer, these organisms could have toxic effects on
biodiversity, including infectious diseases like white nose
other organisms such as soil microbes, insects, plants and
syndrome, a fungal disease that affects hibernating bats.
animals. They may also become invasive and have an
adverse effect on native species by destroying habitat or
It is also possible to use synthetic biology for control
disrupting the food web for example (CBD, 2015).
of disease vectors. Using gene drive systems, it
is possible to change the genomes of populations of
Many of the supposedly beneficial applications of
mosquitoes to make them less dangerous (e.g. resistant to
synthetic biology could also have negative side-effects.
the parasite that causes malaria) (Ledford and Callaway,
For example, gene drive systems designed to suppress
2015). Gene drive systems can also be used to lessen
populations of disease vectors could have unintended
the threat from other insect vectors of diseases, reverse
consequences for biodiversity, such as introducing
pesticide resistance or eradicate invasive species, which
new diseases by replacing the population of the
are significant threats to biodiversity (Redford et al.,
original disease vector with another (CBD, 2015). Using
2014).
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gene drives to change entire populations very rapidly
could have other unforeseeable implications, including
potentially devastating effects on entire ecosystems.
Similarly, while replacing natural products with synthetic
ones could reduce pressure on natural habitats, it could
also disrupt conservation projects and
displace small-scale farmers (CBD, 2015).
Saffron for example is usually picked from crocus flowers
15
in Iran, but can now be synthetically produced by yeast.
Each hectare of natural saffron growing in Iran provides
jobs for around 270 people a day – replacing that with
synthetic versions therefore threatens livelihoods (ETC
Group, 2016). A growing range of products (such as palm
oil, rubber and artemisinin) are beginning to be provided
by synthetic biology, which may deprive farmers of their
only source of income and raises serious and
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 transition 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
extinctions 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 ecosystem 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
16
large-scale
increase in the use of biomass. A large
Another major concern relates to the
number of synthetic biology applications involve
organisms that convert biomass into valuable products.
Cellulosic biomass, such as wood and grass, represents
a renewable source of sugars that can be used as
feedstock for fermentation. Several microorganisms can
naturally degrade cellulosic biomass, but with synthetic
biology, organisms can be engineered to convert the
sugars in biomass into useful products, such as fuels or
pharmaceuticals (French, 2010; French et al., 2013).
Although use of feedstock could benefit the environment
by representing a shift away from non-renewable
resources, increased demand for biomass could also lead
to increased extraction of biomass from agricultural land
(CBD, 2015). Fuel production may require particularly
large amounts of biomass, which could reduce
soil fertility and structure and contribute to
biodiversity loss due to the conversion of natural land
(CBD, 2015). Indeed, a number of studies suggest that
extracting biomass from existing agricultural practices
is already causing a decline in soil fertility and structure
(CBD, 2015).
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According to the civil society organisation the ETC
group (2010), biomass-based economies will develop,
which are market driven and — unlike biodiversitybased economies — view nature in terms of its
commercial value and profit potential. They
suggest that major changes to land-use will occur, such as
increases in the number of plantations in former forests
(a major source of biomass), which have little value for
biodiversity and significant negative impacts on water
and soil.
These land-use changes may also have adverse impacts
on food and livelihood security (Redford et al.,
2014). The increased production of biomass could reduce
access to local natural resources and cause small, selfsufficient farms to be replaced by large-scale commercial
farming (CBD, 2015).
Finally, there are deeper concerns that synthetic biology
may act as a ‘sticking plaster’ rather than providing a
profound solution to biodiversity loss. In other words,
synthetic biology may distract policymakers,
scientists and industry from the deeper
underlying causes of biodiversity loss.
Biofuel feedstocks @Flickr/Idaho National Laboratory 2013. CC BY 2.0.
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17 4. Case study: new plant breeding 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
climate change. Plant breeding techniques have been
around for decades, but a number of very new techniques
(developed after the 2001 review of the EU Directive on
the deliberate release of GMOs) are creating concern,
and are surrounded by legislative uncertainty.
These new techniques differ from the methods
traditionally used to create GMOs (such as transgenesis)
because they involve specific and targeted changes to
the genome, and do not involve any foreign DNA.
Traditional transgenic plants contain genes from
another species, such as maize containing proteins from
Bacillus thuringiensis to make it resistant to insects.
Mixing genetic materials between species that could not
hybridise naturally has previously generated concern
among the public and regulatory agencies (Holme et al.,
2013).
Two newer (and potentially safer) techniques are
cisgenesis and intragenesis. Unlike transgenesis,
cisgenesis involves transferring genes between members
of the same species, or closely related species that could
crossbreed naturally. The term cisgenic plant, introduced
less than 10 years ago, can be defined as ‘a crop plant that
has been genetically modified with one or more genes
isolated from a crossable donor plant’ (Schouten et al.,
2006). As such, cisgenic crops contain only the gene(s)
of interest (Espinoza et al., 2013) and are more similar to
crops that may occur by conventional breeding.
While cisgenesis is the transfer of genes from the same
or closely related species, intragenesis is the insertion
of a reorganised region of a gene from the same species
(EASAC, 2015), and is therefore further removed from
traditional breeding. Although it also describes the
introduction of a gene that originates from the same
or a crossable species, intragenes are hybrids, which
means they may contain elements from different genes.
Intragenesis enables the development of new genetic
combinations, and thus GMOs with more innovative
properties (Espinoza et al., 2013). Both methods provide
viable alternatives to transgenic crops.
In 2012, the European Food Safety Authority (EFSA)
reviewed the risk of cisgenic and intragenic plants
by comparing them to conventional plant breeding
techniques. The Panel established that similar hazards are
associated with cisgenic plants and conventionally bred
plants. However, plants created through intragenesis may
present novel hazards. Overall, they concluded that the
frequency of unintended effects may differ based on the
breeding technique used and risks must be assessed on a
case-by-case basis (EFSA, 2012a).
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The genetics of
plant breeding
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Classical selective
breeding
Conventional cross-breeding between
species that could breed naturally
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Genome editing techniques (A-B)
A
New plant breeding techniques (B)
B1
A further technique is engineering with the ‘zinc finger
nuclease’, a class of enzymes that cut DNA in targeted
places and use the natural machinery of the cell to repair
the break. This can be used to edit existing genes and
insert new ones (Carroll, 2011). The EFSA Panel also
assessed the risk of plants developed using the zinc finger
nuclease 3 technique, which allows the integration of
gene(s) into a predefined insertion site in the genome
of the recipient species. The Panel concluded that its
existing guidance documents can be used for plants
developed using this technique. Furthermore, as the
zinc finger nuclease inserts DNA to a predefined region,
they deemed it to have less risk of disrupting genes and/
or regulatory elements than transgenesis. Although
there is some risk of off-target, unintended genetic
changes, these are expected to be fewer in number and
similar in type with respect to mutagenesis techniques
used in conventional breeding (EFSA, 2012b).
Zinc finger nucleases were the first targeted gene-editing
technique, although more sophisticated techniques
have been developed since — such as transcription
activator-like effector nucleases (TALEN), restriction
enzymes that can be engineered to cut almost any DNA
sequence (Boch, 2011) and the CRISPR/Cas9 system
(which enables precise genomic modifications in a wide
variety of organisms; see box 5).
Applications using these new techniques are already in
use. In the US, agricultural trait development company
Cibus has used new plant breeding techniques to create
herbicide-resistant oilseed rape. The variant (which does
not contain any foreign material) was planted in the US
in 2015. The US has also approved a potato variant with
reduced bruising and browning, developed using RNA
(a nucleic acid like DNA) that reduces the expression of
the enzymes responsible for these processes (a method
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B2
B3
called RNA interference, which also does not involve
foreign DNA) (EASAC, 2015). In the EU, field trials
in Belgium and the Netherlands have bred potatoes
resistance to the fungus responsible for ‘late blight’
using cisgenesis (EPRS, 2016).
There are many possible benefits to these new techniques:
increasing yield, improving crop quality, developing
resistance to pests and diseases, creating plants that use
resources more efficiently or can adapt to environmental
extremes, crops with enhanced nutritional quality,
increasing genetic diversity and reducing crop losses
(ADAS, 2015; EPRS, 2016; STOA, 2013).
However, there are certainly downsides to consider. As
well as the potential unforeseen risks that may occur
due to unintended genetic changes or gene transfer,
some argue that these new plant breeding techniques
are incompatible with organic farming, which by
definition excludes GMOs, and may therefore threaten
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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 germline.
CRISPR are DNA sequences found in bacteria that can be used to edit genes. In concert with the Cas9
enzyme, 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 biologists, but also a challenge to the international regulatory landscape.
CRISPR has been used for medical purposes, fuelling a new generation of gene therapy. In April 2015,
scientists reported use of the technique to edit human embryos, 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 CRISPRCas9 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.
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its development. Other arguments include increased
production costs for farmers and reduced freedom of
choice for breeders, farmers and consumers (IFOAM,
2015).
be exempt from regulations for GMOs. Overall, the
plant breeding industry argues that these new breeding
techniques should not be subject to GMO legislation
(EPRS, 2016).
Associated with these potential downsides, there is an
intense debate regarding whether these newly bred
plants should come under EU legislation on GMOs.
The testing and release of genetically modified plants is
tightly regulated in the EU in order to prevent negative
effects on human or environmental health, which some
argue constrains innovation and agricultural potential.
However, as they are still techniques of genetic
modification, others suggest that they should be
subject to the traceability and labelling requirements
(Regulations EC 1829/2003 and 1830/2003) that
apply to GMOs. The German Federal Agency for
Nature Conservation (BfN) for example argues that the
fact that the modifications are carried out purposefully
and lead to incorporation of new genetic material into a
host organism is more important than the fact that the
mutations could also occur naturally, and therefore that
the techniques should fall under the GMO legislation
(EPRS, 2016).
As these new techniques involve precise changes to
the genome and do not involve foreign DNA, some
suggest that they should not be regulated by existing
GMO legislation. The European Academies Science
Advisory Council (formed by the national science
academies of EU Member States) for instance argues
that plants produced through these methods are
different from GMOs produced previously, as they
enable precise and targeted changes in the genome. For
several of the techniques, the resultant plant does not
contain any foreign genes and could also be developed
by conventional breeding (EASAC, 2015). As such,
EASAC recommended that new breeding techniques
(when they do not contain foreign DNA) should not
fall within the scope of GMO legislation and that the
EU should regulate the agricultural trait or product
rather than the technology itself.
Several other bodies have supported the view that the
safety of new crop varieties should be assessed based on
their characteristics, not how they are produced (EPRS,
2016). The US National Academies also recommends
that the product, not the process, should be regulated
and emphasises a tiered approach to risk assessment
based on likely risk to human health or the environment
— regardless of how the plant was bred (National
Academies, 2016a). Likewise, Schouten (2006) argues
that, as cisgenic plants are similar to traditionally bred
plants, they present similar safety concerns and should
The International Federation of Organic Agriculture
Movements (IFOAM) EU Regional Group recently
developed a position paper on New Plant Breeding
Techniques, recommending that the European
Commission considers these techniques as GMOs. The
paper cites concerns such as unknown consequences
for biodiversity and economic damage to the organic
farming sector (IFOAM, 2015). Should they not fall
under GMO legislation, it could mean that it would
be for the Member States to decide. This could be
problematic, as national authorities do not yet have the
capacity to properly evaluate potential impacts. The
European Parliamentary Research Service (EPRS, 2016)
recently published a brief on the applicability of EU
legislation on GMOs to new plant breeding techniques,
which discusses these arguments in more detail.
The debate is ongoing and the European Commission
has been requested to clarify whether GM regulations
apply to these new techniques (see also section
7. Regulatory implications, p. 28)
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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
displaced by industrial production with the
help of genetically engineered organisms. Government
policies in both high- and low-income countries will
have a large influence on these new bio-economies and
the social impacts they have (CBD, 2015a).
There are many questions about the use of synthetic
biology techniques, how they are controlled and who
will profit from their use. Many ethical and economic
issues are related to the role and place of synthetic biology
in the fair and equitable sharing of benefits arising from
the use of genetic resources, which is the third objective
of the CBD. While the Nagoya Protocol3 provides a
framework for the fair sharing of benefits arising from
the use of genetic resources, it is not clear whether it
would be applicable to all synthetic biology (Bagley &
Rai, 2013). For example, the Nagoya Protocol would
not seem to cover digitally stored genetic information
which may be used as a basis for synthetic biology, and
as such would not capture an increasingly important
dimension of the potential value of genetic material.
This issue may have to be addressed by the Parties to
the Protocol.
Yet another and broader ethical concern is how the
ability to engineer biology may affect people’s perception
of nature, and the value they attribute to it. Synthetic
biology aims to create living organisms from scratch
3. https://www.cbd.int/abs/
Hedgehog and cowslip @Pixabay/TomaszProszek
and therefore challenges ideas about what is natural
(Calvert, 2010). It may reduce how much people value
what are now precious natural resources, and reduce
support for conservation efforts in the expectation that
extinct species can be brought back to life.
Linked to this are philosophical debates about the
creation of life, prompting fears about scientists
‘playing God’; concerns that have been voiced since
the beginning of modern biotechnology (Dabrock,
2009). In 2010, a team of scientists led by Craig Venter
(Gibson et al.) produced an entirely synthetic genome
and introduced it to bacteria without any genetic
material, allowing the cells to grow and replicate. In
2014 (Malyshev et al.) the first entire living organism
with artificial DNA was produced, when a team
engineered E. coli to replicate a genetic code containing
unnatural base pairs – representing the first organism to
propagate an expanded genetic alphabet. More recently
(Hutchison et al., 2016), Venter’s lab built a bacterium
with the smallest genome of any free-living organism,
a cell that is able to survive and self-replicate with just
473 genes. (For comparison, humans have around
21 000 genes and even the fruit fly has around 17 000
(Kimball, 2016)). The construction of ‘life’ in this
manner raises questions about what ‘life’ really means
and our relationship with the natural world.
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25
The line between changing the genetics of an existing
organism and creating an entirely new being is blurred,
prompting some scientists to find a definition of ‘life’
— what it is, where it begins, and how complex it
must be. To assist this, some have proposed a modified
version of a Turing test (which is used to test whether
a machine’s intelligence is equivalent to a human) for
life imitation. While this may have some use, such a
definition is unlikely to allay deeper concerns about the
blurring of the boundary between the synthetic and the
natural (Balmer & Martin, 2008), especially as machine
learning is starting to rival world-class human game
players.
As this section highlights, beyond the immediate safety
issues, there is a need for robust ethical governance
of synthetic biology to protect the environment and
society. To assist with this, the newly established
Scientific Advice Mechanism (SAM) has been given
the mandate to provide independent and high quality
scientific advice to the European Commission. SAM is
now hosting the secretariat of the European Group on
Ethics in Science and New Technologies (EGE)4, which
was requested by the President of the Commission to
provide independent advice on the scientific, ethical,
legal, governance and policy implications of synthetic
biology in 2008. An opinion on the ethics of synthetic
biology adopted by the EGE in 20095 concluded that
the responsible development of synthetic biology must
be based on ethical principles, enshrined in
conventions and declarations. The general framework
developed in this opinion remains valid, although an
update to take account of the most recent developments
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,
there are huge uncertainties regarding not only what
the potential of synthetic biology may be, but also
the risks it may pose. The accidental release of GMOs
into the environment is a clear concern, as organisms
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
through populations (gene drives) to cause the spread of
disease. Other potential malicious applications include
production of biological weapons (e.g. modified
pathogenic viruses) or microorganisms engineered to
produce toxins.
Bioterrorism 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
26
Although the design and production of entirely novel
pathogens for malevolent purposes is unlikely, there
are reasons to take the threat seriously, as anyone can
potentially access public DNA sequences, design DNA
using free software and order it for delivery (although
this requires rare expertise, and checks are in place to
ensure that sequences of pathogens cannot be ordered).
Out of this has arisen a debate about publishing studies
which could have security implications, such as the
description of vaccine-resistant mousepox (Jackson et
al., 2001) and the artificial synthesis of the polio virus
(Cello et al., 2002).
There is an understandable danger here, but publishing
such studies could also have benefits for science
and banning them raises complex censorship issues.
Another protective mechanism is for companies that
synthesise DNA to screen all sequences for toxicity
before processing an order (EGE, 2009). In fact, the
International Gene Synthesis Consortium (http://www.
genesynthesisconsortium.org/) — a consortium of the
world’s leading gene synthesis companies — already
screen the sequences of synthetic gene orders and the
customers who place them to help prevent the misuse
of this technology. An alternative solution may be for
the scientific community to ‘self police’ research for
malevolent intent or for situations when legitimate
research could be misused (Atlas, 2009).
To mitigate the possible negative impacts, there are
also several methods of control that can be used on
the synthetic organisms themselves. Firstly, organisms
used for research purposes can be kept in confined
conditions, with measures in place to prevent contact
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with the external environment. They can also be placed
under contained use outside of labs, using physical
measures to limit their exposure to the environment.
Applications where organisms are intended for
release into the environment will have different and
potentially greater safety concerns than those intended
for restricted use. Thus, as well as physical restrictions,
more sophisticated techniques to contain organisms
are being explored, such as ‘integrated biocontainment
traits’, which act as built-in safety controls. Examples
include ‘kill switches’, which cause the death of the
engineered organism on a particular signal, such as the
introduction of a chemical. A kill switch activated in
the presence of the chemical IPTG (commonly used as
a trigger in molecular biology) has been demonstrated
in engineered microbes in soil, seawater and an animal
model (Knudsen et al., 1995). Other inducers include
heat and sugar molecules (Moe-Behrens et al., 2013).
Other control measures include engineering bacteria to
be dependent on nutrients and self-destruct mechanisms
that are triggered once the population density exceeds a
certain threshold (Balmer & Martin, 2008). A further
possibility is the inclusion of nucleic acids containing
elements not found in nature (xeno-nucleic acids),
which cannot mix with naturally occurring organisms
(CBD, 2015a).
While there are clearly a range of control strategies in
place, no biocontainment strategy can eliminate risk,
which highlights the importance of robust risk and
safety assessment methods.
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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.
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7. Regulatory implications
As discussed earlier in this brief, synthetic biology may
have unintended negative effects in the environment.
Unanticipated interactions with natural organisms could
create risks which must be addressed by legislation if
synthetic biology is to be used responsibly.
Due to the novelty of the field and how rapidly it is
changing, there are questions as to whether existing
regulations can adequately address the risks and
implications of synthetic biology. Synthetic biology falls
under a number of regulatory mechanisms, but most were
established before the field fully developed and therefore
were not intended to cope with its impacts.
At the most recent meeting of the CBD’s Subsidiary Body
on Scientific, Technical and Technological Advice, the
advisory group agreed on a common understanding of
the terms components (parts used in a synthetic biology
process, such as a DNA molecule) and products (the
output of a synthetic biology process, such as a chemical
substance). Both of these elements are not living, unlike
the final element of the triad: organisms. The group agreed
that the organisms, components and products of synthetic
biology fall within the scope of the Convention and its
three objectives. This agreed terminology — organisms,
components and products — will be valuable in future
political deliberations.
However, there are many grey areas. Living organisms
developed through current applications are similar
to living modified organisms (LMOs) defined by the
Cartagena Protocol on Biosafety. However, the non-living
components are not regulated by this protocol, and there
may be cases in which there is no consensus on whether
the application is living or dead (e.g. protocells). And, as
the field evolves beyond techniques to manipulate nucleic
acids in vitro to cause heritable changes, the methods used
to assess the risk of LMOs may become inadequate (CBD,
2015).
There is also discussion of how existing legislation on
GMOs fits into this. Although synthetic biology results
in genetic modification (altering the genetic material
of existing cells in a way that does not occur naturally)
and therefore should be subject to existing EU GMO
legislation, several elements of synthetic biology escape the
existing GMO regime. As a result, is has been suggested
(Engelhard, 2016) that new regulation is needed — which
either extends the scope and risk assessment or existing
regulations, or takes the form of entirely new regulation that
addresses biotechnology more broadly (including GMOs,
synthetic biology and possible new breeding techniques).
Although the former would be simpler in political terms,
perhaps the latter would be more appropriate to match the
new risks presented by synthetic biology.
Clearly, future developments in synthetic biology will
require changes to existing regulation, or entirely new
legislation, and there is a pressing need to explore other
biosafety frameworks and identify the gaps in current
risk assessment methodologies. There is also a need to
think creatively about the potential unforeseeable events
that could occur. Some argue that no-one can yet fully
understand the risks that synthetic biology poses to the
environment, or even what information is needed to
perform risk assessment (CBD, 2015; Dana et al., 2012).
Overall, existing biosafety frameworks and the general
principles of the Cartagena Protocol on Biosafety provide
a sound basis for risk assessment of the living organisms,
components and products developed by synthetic biology
now and likely to be developed in the near future.
However, they should be updated and adapted for future
developments and applications. It is important to assess
other regulatory frameworks that cover components and
products, such as EU chemicals legislation, and address
any remaining gaps under the CBD.
Convention on Biological Diversity SBSTTA:
agreed terminology, April 2016
Terminology
Living or
non-living?
Does
Cartagena
Protocol
apply?
Components
Non-living
No
Non-living
No
Living
Yes
(parts used in a
synthetic biology process, such as a DNA
molecule)
Products
(the output of a
synthetic biology
process, such as a
chemical substance)
Organisms
(developed via
applications of synthetic
biology, similar to living
modified organisms)
Source: 20th meeting of the SBSTTA documents
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7.1 Research needs and areas for
future development
In order to understand the potential ecological effects of
synthetic organisms, and thus regulate them effectively,
four areas of research have been proposed (Dana et al.,
2012), to: 1) understand the physiological differences
between natural and synthetic organisms; 2) consider
how engineered microorganisms might alter habitats,
food webs or biodiversity; 3) determine the rate at
which synthetic organisms evolve and whether they
could persist, spread or alter their behaviour in natural
environments; 4) understand gene transfer by synthetic
organisms (for example, whether synthetic organisms
could transfer antibiotic resistance).
In its opinion on the ethics of synthetic biology, the
EGE makes a number of recommendations for the
assessment and regulation of synthetic biology. The
group recommended that the use of synthetic biology
be conditional on safety issues and that risk assessment
be conditional for financing of research. It also
recommends the development of a Code of Conduct for
research on synthetic organisms which should ensure, for
example, that organisms cannot survive autonomously
if accidentally released into the environment. For
organisms that are developed for environmental
applications, ecological impact assessment studies
should be performed and authorisation procedures for
synthetic biology derived materials should take into
account risks for the environment and people.
The EGE discusses the existing regulatory framework as
‘fragmented’ and says it may be not sufficient to regulate
current and emerging aspects of synthetic biology. It
re-iterates the importance of acting now to develop a
robust governance framework for synthetic biology in
the EU, which should address all relevant stakeholders
and make clear their responsibilities (EGE, 2009).
More recently (2014), ERASynBio (a European
Research Area Network, originally funded by the
European Commission) proposed a vision for European
Synthetic Biology, which also discussed the principles
of good governance, highlighting the importance of
transparency, participation and accountability in policy.
The vision also suggests that regulation should consider
issues of safety and controls on synthetic organisms,
and that scientists should be required to demonstrate
consideration of environmental risks, ethical and social
issues before proceeding with their work.
29
The European Commission also supports the need
to conduct research on the impacts of the organisms,
components and products of synthetic biology, including
socioeconomic, cultural and ethical considerations. It
aims to identify and reconcile knowledge gaps, and
identify how these impacts relate to the objectives of the
CBD. In its third opinion, the Scientific Committees
to the European Commission discussed the risks to
the environment and biodiversity related to synthetic
biology processes and products, and identified gaps in
knowledge that may prevent reliable risk assessments
(SCENIHR, SCCS, SCHER, 2015b).
The gaps they identified included a lack of information
and tools to predict the properties of complex unnatural
biological systems, and to measure the differences
between natural and engineered organisms. They also
discussed new genome editing methods that allow
scientists to produce lots of variants at the same time.
Although these methods allow more accurate and
precise changes than traditional techniques, they are
also producing organisms at an unprecedented scale
and speed, which may create new challenges for risk
assessment.
Based on the major scientific gaps they identified, the
Committees made a number of recommendations for
future research. Vitally, they concluded that more work
is needed to develop standardised techniques to monitor
the survival of organisms in the environment. Indeed, the
need to develop monitoring systems for the organisms,
components and products of synthetic biology is key,
as emphasised in the recent recommendations from the
CBD’s Subsidiary Body on Scientific, Technical and
Technological Advice (CBD, 2016).
As a party to the CBD, the EU has to clarify its position
on synthetic biology. Key elements include adopting
an operational definition of synthetic biology and
evaluating the tools available
to detect and monitor the
organisms, components and
products of synthetic biology —
and their impacts on biodiversity.
Finally, in terms of regulation, the
Nagoya and Cartagena Protocols
may need to be re-assessed, in
order to determine if changes
are needed to protect access and
benefit sharing, and effectively
assess the risks posed by synthetic
biology.
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8. Summary and recommendations
Synthetic biology is a new and exciting field with
a vast range of potential applications, which might
have benefits for biodiversity. However, there are
also many scientific uncertainties surrounding
the manipulation and transfer of genetic material,
which may have matching adverse consequences for
biodiversity. There are also complex ethical issues
to investigate, including how synthetic biology may
fundamentally change our perception of the natural
world. Several things will be key to surmounting the
challenges presented by synthetic biology.
For example, an exploration of synthetic biology
commissioned by the UK Biotechnology and
Biological Sciences Research Council highlighted
the importance of public engagement for achieving
(responsible) progress in the field. This requires
involving the public in research and demonstrating,
but not overstating, the societal benefits of
applications. Public acceptance of synthetic
biology will inform policy, funding and
regulation and therefore how the issues are framed
is very important. Mainstream media coverage
to date has focused on extraordinary stories of deextinction, neglecting the more nuanced benefits (or
risks) for biodiversity and complex ethical and social
implications (Redford et al., 2014). As well as accurate
reporting, the scientific community should openly
debate the implications of their work and engage
with society about the issues it may raise (Balmer &
Martin, 2008).
It is also imperative that a robust governance
framework is in place before synthetic biology’s newest
applications come to fruition. This will involve an
in-depth review of the existing regulations as well as
the development of new measures for environmental
release, biosafety and biosecurity (Balmer & Martin,
2008).
While it seems that the existing regulatory instruments
— such as the Cartagena Protocol — are broad
enough to address current issues in synthetic biology,
there are questions about whether they will continue
to be fit to protect biodiversity in the future. There is
a need for further discussions to explore other existing
biosafety frameworks and identify possible gaps in
regulations that need to be addressed and how. It is
also important to develop risk assessment protocols
for the unlikely but highest impact consequences on
biodiversity. Negotiations are ongoing within the
CBD to achieve these goals.
Whatever is decided, regulations should be
continually updated and coordination between
Member States will be vital. Underlying
this, the precautionary principle must be central to
addressing the threats to biodiversity. In the EU, the
precautionary principle plays a key role in policy
design: applied as a tool to follow developments in a
sector and continuously verify that the conditions for
the acceptability of a given innovation are fulfilled
(EGE, 2009). In the case of synthetic biology, the
precautionary principle is an important
element of ethical debates and legal decision making
and will help to protect the environment from harm.
“The growing innovative powers of science seem to be
outstripping its ability to predict the consequences of
its applications,” warned the European Environment
Agency in 2001. Synthetic biology provides a
prime example of technology outpacing
regulation, and highlights the need to identify
the risks posed by new and emerging technologies
via early warning systems . As with many such
technologies, it is too early to foresee all the possible
developments of synthetic biology. Developments
could generate unexpected (and undesirable) sideeffects. Synthetic organisms that are initially useful
could later turn out to have harmful and widereaching effects (Engelhard, 2016).
Likened to Pandora’s box, it is important that action
is taken now to ensure synthetic biology is safely
implemented. This sector could revolutionise the
way our industries and economies function, placing
policymakers in a unique position to protect the
environment throughout the transition.
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