Edinburgh Research Explorer
Synthetic Biology
Citation for published version:
Calvert, J 2010, 'Synthetic Biology: Constructing Nature?' The Sociological Review, vol 58, no. s1, pp. 95-
112., 10.1111/j.1467-954X.2010.01913.x
Digital Object Identifier (DOI):
10.1111/j.1467-954X.2010.01913.x
Link:
Link to publication record in Edinburgh Research Explorer
Document Version:
Peer reviewed version
Published In:
The Sociological Review
General rights
Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)
and / or other copyright owners and it is a condition of accessing these publications that users recognise and
abide by the legal requirements associated with these rights.
Take down policy
The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer
content complies with UK legislation. If you believe that the public display of this file breaches copyright please
contact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately and
investigate your claim.
Download date: 10. Aug. 2016
1
Synthetic biology: constructing nature?
Jane Calvert
Published as: Calvert, J. (2010). Synthetic Biology: Constructing Nature? The Sociological Review,
58(s1), 95-112 doi: 10.1111/j.1467-954X.2010.01913.x
Introduction
Synthetic biology is a new scientific field which literally aspires to construct nature, by
building living things ‘from scratch’. Because of this approach, it challenges our ideas
about what we should think of as ‘natural’. An important aspect of how we understand
‘natural’ rests on what we oppose it to (see Keller 2008a). In synthetic biology the main
dichotomy is between the natural and the artificial. But other oppositions also become
relevant: particularly those between the natural and the social, and the natural and the
invented.
In what follows, I start with a brief description of synthetic biology and how it
distinguishes itself from previous biotechnologies. I analyse the principles of an
engineering approach to biology and show how these principles lead to aspirations
amongst synthetic biologists to eliminate or reduce biological complexity in their
synthetic creations. While some synthetic biologists want to ‘improve’ on nature (i.e. to
make it easier to engineer), others want to replace certain natural phenomena with
‘unnatural’ alternatives. However, sceptics and critics argue that these blatant attempts
to reduce complexity will not work, and that nature’s contingency will not be
successfully eliminated.
I then connect my discussion of synthetic biology to theoretical work by Paul
Rabinow and Hans-Jörg Rheinberger on earlier biotechnologies, and discuss their
analyses of the imposition of ‘society’ on ‘nature’ that we have seen in previous
attempts to re-write and engineer biological systems.
I go on to contextualise our understanding of synthetic biology and its
construction of nature by considering model organisms and intellectual property, both
of which attempt to impose uniform properties on natural entities, and which have the
potential to move their objects out of the realm of the natural and into the realm of the
artificial.
In the conclusions I show how pressures for engineerability, commodification
and standardization are all pulling in the same direction: towards a reconstruction of
nature which is instrumentalizable and utilizable for our purposes. These pressures
could have profound consequences for the kinds of living things that are brought into
the world by synthetic biology.
This chapter draws on two years of research on the emerging field of synthetic
biology. It is based on my experiences in being the social science member of a UK
working party on synthetic biology, a founder member of a UK cross-university
synthetic biology network, and my involvement in a synthetic biology ‘sandpit’(which
involved developing research proposals with synthetic biologists), as well as
participation in numerous workshops, conferences and meetings in synthetic biology,
from the largest conference in the field so far (Synthetic Biology 4.0 in Hong Kong in
2008), to meetings directed to young researchers and postgraduates (e.g. BioSysBio in
2
Cambridge 2009), to small discussion meetings internal to my own university and
elsewhere. Detailed records have been kept throughout of my observations,
conversations, interactions and reflections, so the empirical basis for this chapter is best
described as a multi-sited ethnography (Marcus 1995). Synthetic biologists are only
quoted here by name when I refer to a comment made in a public meeting; otherwise
they are quoted by anonymised code name. I also draw on the burgeoning scientific
literature in synthetic biology.
Synthetic biology
It is hard to provide a precise definition of any new and emerging scientific field, but
defining synthetic biology is particularly difficult because it incorporates a number of
disparate research activities under its banner. Broadly speaking, synthetic biology can
be described as a field which aims to construct living systems de novo. The new kinds
of biological entity it produces can be construed as being extremely unnatural and
‘synthetic’ – as the term ‘synthetic biology’ implies. Although ‘synthesis’ also has the
meaning of synthesizing or putting together (i.e. the opposite of ‘analysis’), it is the
meaning of synthetic as ‘artificial’ which is the one that many commentators draw upon
when discussing synthetic biology. In fact, attempts have been made to avoid the word
‘synthetic’ by naming the field ‘constructive biology’ or ‘intentional biology’ (Carlson
2006), but these names have not become widely adopted.
At the moment there is no consensus on the definition of the field. One of the
most common definitions is a two-pronged one, which includes the construction of
completely novel biological entities, and the re-design of already existing ones. For
example, a group of leading scientists in the field defines synthetic biology as ‘the
design and construction of new biological parts, devices, and systems and the re-design
of existing, natural biological systems for useful purposes’.1
Despite the lack of consensus, it is helpful to divide the disparate field of
synthetic biology into three broad approaches (see O’Malley et al. 2008). The first
approach, which is my main focus here, involves the building of interchangeable
biological parts and devices called ‘BioBricks’ (see Endy 2005). The second approach
covers work at the level of whole genomes, including both the synthesis of viral
genomes from scratch (e.g. Cello et al. 2002) and attempts to strip away excess DNA
from existing bacterial genomes, with the objective of producing the minimal genome
necessary for life (Glass et al. 2006). The third approach centres on the creation of
‘protocells’ from simple components such as lipid vesicles (see Deamer 2005; Luisi et
al. 2006).
An overriding principle which governs all three approaches is the attempt to
engineer life, to such an extent that synthetic biology is called ‘the engineer’s approach
to biology’ (Breithaupt 2006). For example, the ‘BioBricks’ school, which is the
dominant approach to synthetic biology, draws on the engineering principles of
standardization, decoupling and abstraction with the objective of developing biological
components which are interchangeable, functionally discrete and capable of being
combined in a modular fashion, along the lines of ‘plug and play’ (Isaacs and Collins
2005, Brent 2004). These synthetic biologists hope that they will succeed in making
biology into an engineering discipline where genetic ‘engineering’ failed (Breithaupt
2006; Endy 2005).
For this reason, synthetic biologists commonly distinguish their work from
genetic engineering. There are two ways in which they do this. One is in terms of the
3
methods used. It is argued that since synthetic biology uses standardised parts and
follows a formalised design process, the tools and intellectual approach of engineering
are adopted in a way which makes synthetic biology more authentically like
engineering. Another distinction is in terms of the ‘sophistication’ of the work. In
genetic engineering one gene at a time is modified or added, whereas in synthetic
biology a whole specialised metabolic unit can be constructed. This means that in
synthetic biology we see engineering at the systems level, rather than at the level of the
individual components. It should also be noted that another reason why synthetic
biologists may be keen to distinguish their field from genetic engineering is because of
some of the perceived negative social implications of genetic engineering.
The reason why synthetic biologists want to make biology into an engineering
discipline is because they want to replicate the successes of engineering in a biological
context. Synthetic biologists draw inspiration from the technological achievements of
other branches of engineering, such as aircraft and computers, and conclude that it is
“economically and socially important that we improve the efficiency, reliability and
predictability of our biological designs” (Arkin 2008, p.774). Parallels are often drawn
between today’s synthetic biology and the early days of the nascent computer industry,
with the intended implication that the technological revolution that synthetic biology
brings will be as important as the revolution in ICTs brought about by electrical
engineering (Barrett et al. 2006, NEST 2005).
As with other types of engineering, the range of applications of synthetic
biology is potentially very broad, although the field is currently at an early stage of
development. Examples of potential applications include microbial biofuel production
(Keasling and Chou 2008), bioremediation, biosensors, new drug development
pathways and synthetic vaccines (Royal Academy of Engineering 2009). Most notably,
synthetic biology has successfully been used to produce a precursor for an antimalarial
drug (Martin et al. 2003).
The reduction of complexity
While other emerging areas of biology (such as systems biology), embrace the
complexity of biological systems, a key feature of the engineering approach to synthetic
biology is the attempt to reduce biological complexity. Programmatic statements along
these lines are common. For example, Heinemann and Panke (2006) say: ‘As the
complexity of existing biological systems is the major problem in implementing
synthetic biology’s engineering vision, it is desirable to reduce this complexity’
(p.2793). Leading synthetic biologist Tom Knight also sees this aspiration to get rid of
complexity as an integral part of the engineers’ approach in maintaining that ‘an
alternative to understanding complexity is to get rid of it’ (quoted in Ball 2004). One of
the founders of synthetic biology, George Church, adopts a similar line: ‘You focus on
parts of the science that you do understand and clean out the parts that you don’t
understand’ (quoted in Breithaupt 2006, p.22-3).
4
The approach we see here towards the complexity of nature is that it is better
dispensed with, and that we will be more successful if we attempt to construct living
systems from scratch without the unnecessary detritus that they have accumulated over
evolutionary time. An example of this approach towards complexity is seen in the key
paper ‘Refactoring Bacteriophage T7’ (Chan et al. 2005). The word ‘refactoring’ here is
borrowed directly from computer software, and it means improving computer software
by rationalising it and ‘cleaning it up’.2
For some this reduction of complexity is not merely an instrumental aim, but is
based on a faith that synthetic biology will ultimately lead to ‘the elucidation of the
underlying simplicity’ of nature (Palsson 2000:1149). The pervasive idea of the
simplicity of nature, and its connection to truth, is found throughout the history of
biology (often in tension with ideas about its complexity – see Keller 2008b), and
perhaps the most striking example of this is the iconic image of the double helix,
famously described by Crick and Watson in 1953. Synthetic biologists draw inspiration
from discoveries such as these and hope that the complexity of biological systems will
be shown to be an eliminable accident of historical accumulations over evolutionary
time (Balaram 2003).
Modularity in synthetic biology
A key requirement for the reduction of complexity is the assumption of modularity.
Modularity is not a straightforward concept, but in engineering terms a module is
defined as ‘a functional unit that is capable of maintaining its intrinsic properties
irrespective of what it is connected to’ (Sauro 2008, p.1). Modular entities are very
important in engineering because they can be extracted from one part of a system and
inserted in another with no change in their function (Sauro 2008).
Modularity is crucial to the BioBricks school of synthetic biology where there is
an on-line ‘Registry of Standard Biological Parts’3
which contains modular BioBricks
that, in theory, can be connected to one another in a manner similar to pieces of lego (an
analogy explicitly exploited by the Registry).
The issue of modularity is very interesting in the context of the discussion of
nature. The key question here is whether biological systems are actually comprised of
functional modules, or if they are simply best understood as such by the engineering
approaches that are adopted in synthetic biology. There is no consensus on this issue.
Arkin and Fletcher (2006) say that ‘The key observation that biological systems exhibit
some degree of modularity underlies the current belief that useful and ‘engineerable’
design principles exist’ (p.2). And there are examples of entities that, at first glance, do
appear to be modular and discrete, such as cells (Kitano 2002), ribosomes (Hartwell et
al. 1999) and antibiotics (Synthetic biologist 5, November 15, 2008).
But there are others who see the idea of modularity as one that is imposed by the
scientists and engineers involved. For example, even the proponents of abstraction
hierarchies (the division of synthetic biology into parts, devices and systems that
underlies the BioBricks approach) admit that these hierarchies are ‘a human invention
designed to assist people in engineering very complex systems by ignoring unnecessary
details’.4
We cannot necessarily deduce from this statement that these synthetic
biologists think that modules are impositions of the engineer upon the biological
substrate, but we can see a recognition that some aspects of synthetic biology are
imposed on nature, rather than found within it. Other synthetic biologists argue that
5
modularity and standardisation in nature are myths, because biological function is
always context dependent (Synthetic biologist 5, November 15, 2008).
Most synthetic biologists, however, do maintain that the modularity they aspire
to find and build is present in biology, but even when agreement is reached on this
issue, there is still a great deal of discussion over what constitutes a module, and
whether this varies depending on the disciplinary perspective one adopts. The problem
is that “modules mean different things to different specialists: the module of the
developmental biologist is not the same as the module of the molecular geneticist”
(Morange 2009, p.S50). Furthermore, biological entities have evolved to survive and
not to be conveniently structured so that scientists can understand them (Keller 2008b).
This means that what a cell regards as a functional module may be different from what a
synthetic biologist regards as one (Oliver 2008). It may be that we are carving out
modules in nature to fit our desires for biological understanding. Keller (2008b) warns
that even if an assumption of modularity is helpful in the sense of enabling us to gain an
understanding of biology (in an epistemological sense), we must be careful that we are
not confusing epistemology with ontology.
There is also the point that all scientific knowledge must involve simplification
and decontextualisation to an extent, in order to better focus on the subject of interest.
As Barnes and Dupré (2008) note, in all attempts to gain knowledge some kind of
reduction of complexity is perhaps inevitable: even perception involves reduction and
simplification in order to prioritise the perceptual inputs that are most important.
But synthetic biology is particularly interesting in respect to modularity, because
even if biology is not modular, perhaps synthetic biologists can make it so. The
engineers’ approach to eliminating annoying noise and crosstalk may result in an
organism that is actually more modular than ‘natural’ organisms are. (This raises
interesting questions about what such organisms might look like, and animals made of
lego – one of the favourite analogies of the BioBricks school – spring to mind as a
visual aid).
There is also the important point that attempts to break biological systems down
into modular components not only makes biological complexity easier to deal with, but
also makes these components more similar to software code which is modular,
standardised and re-useable. One advantage of modularity is that several different
researchers can work on different parts simultaneously, meaning that the field can
develop faster. In this way, modularity is well-suited to open source principles, and
many synthetic biologists are ideologically committed to open source, to such an extent
that the aspiration to make their work open source is a guiding principle of the field.
Improving on nature
The idea of making living things more modular than they are ‘naturally’ gives rise to the
potential of synthetic biology to improve upon nature. The idea underlying much
synthetic biology is that making biological systems from scratch will make them better
than they are in nature. Vitor Martins dos Santos (2008) describes synthetic biology
along these lines as following three steps: understand the wiring, ‘reprogram’ and
simplify. And the tag line which appears at the bottom of every page of the website of
the BioBricks school is ‘making life better, one part at a time’.5
It is pertinent here to ask what understanding of ‘better’ is being adopted in this
tag line. From the perspective of a synthetic biologist, making life ‘better’ is making it
easier to engineer. Here there is the potential for the imposition of engineering
6
principles on the form of living things, and arguably this is something that we are
already starting to see. One of the main research objectives in synthetic biology has
been to build analogues of engineering, such as oscillators and logic gates, in biological
systems.6
We see here the hope that synthetic biology will mimic the successes of
electrical engineering, and it is it is telling that Hartwell et al. (1999) proclaim that ‘The
next generation of [biology] students should learn how to look for amplifiers and logic
circuits’ (p.C52). But these types of synthetic biological creations have been constructed
on the basis of the assumptions that biological systems are modular and that feedback
loops are important in explaining their operation. However, it has not been proven that
these assumptions apply to ‘natural’ biological systems (Loettgers 2007).
Some of the more sceptical commentators see this approach as an imposition of
the engineering mentality on natural systems, arguing that oscillators are rare in actual
living systems (Synthetic biologist 6, 25th January 2008). Pottage and Sherman (2007)
also make the point that ‘the image of synthetic biology as an exercise in ‘engineering’
building blocks and programmable logic gates synthesised from inanimate materials,
extends the mechanical and instrumental vision of nature into the deep texture of life’
(p.545).
A good example of the way in which engineering principles are imposed by
synthetic biology is found in one of the most important papers in the field which
describes the building of a ‘repressilator’ (Elowitz and Leibler 2000), a genetic
regulatory network that exhibits stable oscillation (although from an engineering point
of view it is noisy and inflexible, Kitney 2008). What is interesting about the
construction of the repressilator is that the aim of the work was not to reproduce
experimental findings as accurately as possible. Instead, the researchers ‘designed a
network which would allow them to study not natural network designs but possible
network design’ (Loettgers 2007, p.141 emphasis added), so that they could learn more
about how to develop alternative biological structures.
Although these synthetic networks may be functioning primarily as heuristic
tools at the moment, in the process of doing synthetic biology these heuristic tools
become material constructions. Again, there is the potential for the blurring of ontology
and epistemology, because the reshaping of nature in synthetic biology is tied up with
scientists’ own epistemic practices.
Another rather audacious example of how epistemic practices can come to
influence biological materiality is given by synthetic biologists who say that if they
discover that their models of biological phenomena do not work, then they will simply
engineer the biological parts to fit the model better (Synthetic biologist 8, 16th January
2009), rather than changing the model to make it a more accurate representation of the
biological system, which is how biological research would have proceeded in the past.
A different kind of example of the imposition of engineering principles onto the
natural world is the attempt to create a minimal ‘chassis’ into which biological functions
can be slotted. The most cited example is the Venter Institute’s work were scientists are
attempting to strip away excess DNA from an existing microbial genome until they are
left with the minimal genome which is necessary for life (Glass et al. 2006). Although
the chassis school of synthetic biology is distinct from the BioBricks school, the
aspiration is that the two will coincide in the future because the chassis will provide the
substrate into which new BioBricks can be embedded.
It is worth reflecting on the metaphor of a ‘chassis’ here, and thinking about
what work is being done with this familiar mechanical analogy: can we really think of
7
cells in these terms and consider slotting in different functional modules of DNA? The
idea that it is possible to reduce ‘life’ down to its bare minimum, and then insert new
functional parts into this minimum is a clear demonstration of an instrumentalist
approach.
Changing nature
As well as attempts to make nature ‘better’ by stripping away unnecessary complexity,
there are also attempts to make a biology that is different from that which is found in
nature altogether. One of the objectives driving this work is to push the boundaries of
natural systems and in this way learn more about them. Examples of this approach are
Chin’s work which involves producing amino acids from 4 instead of the normal 3
codons (see Chin 2008). An interest in the limitations of natural systems also drives
research which attempts to develop new nucleic acids beyond the familiar As, Ts, Cs
and Gs (Pollack 2001).
One motivation for this creation of ‘unnatural’ biological systems is to make
modularity more successful. The idea here is that ‘orthogonal’ parts, could be designed,
which perform the same function as their natural counterparts, but, because they are not
naturally found in the cell, do not interfere with the existing cellular context and thus are
more likely to be easily separable and manipulable (Weiss 2008).
This idea of orthogonal, alternative versions of natural systems is interestingly,
and somewhat counter-intuitively, also used to argue for the safety of synthetic
biological constructs. For example, it has been suggested that synthetic organisms could
be made to be dependent on nutrients that are not found in nature (De Vriend 2006), or
that they could have built-in safety features such as ‘fail-fast’ mechanisms (Endy 2005).
One of the arguments made in favour of an alternative biological constructs is that we
would not see ‘interbreeding’ between artificial and natural organisms (Lancet 2008).
Here the assumption is that making synthetic organisms less natural will make them less
risky, because they will be more easily separable from the natural world.
However, others point out that pushing the boundaries of natural systems in this
way could lead to new and completely unexpected problems. Putting genes together that
were previously separate could lead to the creation of new organisms that have
unpredictable emergent properties (Tucker and Zilinskas 2006), making the risks of
accidental release very difficult to assess in advance (De Vriend 2006).
Limitations to the reduction of complexity
The attempt to reduce complexity which underlies much of this work may not be
achievable at all, however. The key question here is: ‘Can the basic biological,
evolutionary, non-linear aspects of living systems be engineered out?’ (Rabinow in
Lentzos 2008, p.315). Synthetic biologists are aware of these difficulties. For example,
one says that the non-linearity of living systems makes them different from
conventional engineering systems (Synthetic biologist 7, 5th Feb 2008), and Pam Silver
describes a living organism as ‘A long series of kludges…not necessarily a well-oiled
machine’ (Silver 2008). The philosopher William Wimsatt (2007) colourfully elaborates
by saying we should think of ‘Nature as a reconditioned parts dealer and crafty
backwoods mechanic, constantly fixing and redesigning old machines and fashioning
new ones out of whatever comes easily to hand’ (p.10).
8
Synthetic biologists such as those in Ron Weiss’ group in Princeton advise that
‘it may be prudent to treat some biological uncertainties as fundamental properties of
individual cell behavior’ (Andrianantoandro et al 2006:13). They argue for a ‘middle
way’; acknowledging the complexity of biological systems but simultaneously not
assuming that every single biological part is going to be a one-off. This leads Weiss to
the conclusion that in synthetic biology it becomes important to think hard about ‘what
makes the biological substrate not like the other substrates we usually deal with’ (Weiss
2008).
Others are more pessimistic and argue that we will see synthetic biology
continually eluded in its quest to isolate the properties of living systems. The concern
here is that by attempting to eliminate complexity and contingency, synthetic biologists
might end up losing sight of the emergent properties that define living systems, which
are themselves historical accumulations, being the result of billions of years of
evolution (Balaram 2003 and Dupré forthcoming 2010). If this is correct we should not
be optimistic about the attempts to construct life from modular and substitutable parts,
which, in some guises, is the guiding objective of synthetic biology.
However, some commentators argue that those who point to the limitations of
applying engineering principles to living systems are suffering from ‘urea syndrome’,
i.e. they are assuming that there is something special and irreducible about living things
and that it is by definition impossible to recreate them using scientific methods. This
was the argument made about organic compounds before the successful synthesis of
urea in 1828, which sent shockwaves through the scientific community of the time
(Lazebnik 2002).
Nature modeled on culture
The previous discussion has shown how synthetic biology, like other biotechnologies
that preceded it, works by ‘extending the reach of human manufactures into the texture
of life itself’ (Pottage 2007, p.324). In this way, the attempts to manipulate and control
nature that we see in synthetic biology are not new, and there are important continuities
between synthetic biology and previous biological research. As Franklin (2006) says:
‘The biologization of human values is in some ways as old as horticulture, when human
preferences began to be nudged into seedlings, and mutated corn began to be selected
for its ears’ (p.179), but (to paraphrase her) this does not mean that synthetic biology
does not have its own specificity. We could argue that what we see in synthetic biology
is an extension of the potential of biotechnology, with improved capabilities for actually
manipulating nature. It is not just that nature is being tamed, as it was with previous
biologies. In synthetic biology nature is being explicitly remade.
9
The remodelling of the natural on the basis of an analogy with engineering that
we see in synthetic biology is very similar to Rabinow’s (1999[1992]) idea of
‘biosociality’, where, he says, ‘nature will be modeled on culture’ (p.411). He calls this
‘biosociality’ because he reverses ‘socio-biology’, where culture is ‘constructed on the
basis of a metaphor of nature’ (p.411). This leads to an inversion of the temporal order
in which we normally think about nature and culture, as Franklin (2000) explains:
‘culture becomes the model for nature instead of being ‘after nature’, as if a kind of
successor project’ (p.194-5). A consequence of this is that ‘biodiversity becomes a
product of design choices, and industrial and political imperatives…rather than
evolutionary pressures’ (Allenby 2006).
Rabinow anticipates the developments in synthetic biology by saying that
‘Nature will be known and remade through technique and will finally become artificial’
(p.411). His work was written at the time of the sequencing of the human genome, and
he predicts that what will be most interesting about the human genome is that it ‘will be
known in such a way that it can be changed’ (p.408 emphasis added). The modification
of nature has perhaps always been the objective of the biotechnological enterprise. But
we could argue that this remaking, or re-writing, has only really become properly
possible with synthetic biology.
Rheinberger (2000) traces the potential for changing nature back to the
development of recombinant DNA techniques. He describes this development by saying
that in early molecular biology there was an ‘an extracellular representation of
intracellular configurations’ (p.19). In other words, the scientific objective was merely
to represent what was going on inside the cell. But with the advent of recombinant DNA
‘a radical change of perspective ensued. The momentum of gene technology is based on
the prospects of an intracellular representation of extracellular projects – the potential
‘rewriting’ of life’ (p.19). In this way ideas about what nature should be (i.e.
extracellular, ‘cultural’ projects), could come to influence the intracellular environment.
Rheinberger says that this potential for ‘rewriting’ makes molecular engineering
‘substantially different from traditional intervention in the life sciences and medicine’
because it involves ‘re-programming metabolic actions, not just interfering with them’
(p.25). Rheinberger sees a technological potential here for intervening in a real sense, a
potential which is being exploited by synthetic biology.
This leads Rheinberger to a very similar conclusion to Rabinow: ‘the very
essence of our being social is not to supersede, but to alter our natural, that is, in the
present context, our genetic condition. We come to realise that the natural condition of
our genetic makeup might turn into a social construct, with the result that the distinction
between the ‘natural’ and the ‘social’ no longer makes good sense’ (p.29).
Rheinberger makes heavy use of the metaphors of writing and programming,
claiming that ‘Within a timespan of less than twenty years, molecular geneticists have
learned not only to understand the language of genes in principle, but to spell it’ (p.24).
Both these metaphors are ubiquitous in synthetic biology. For example, leaders of the
field regularly talk about being able to ‘write DNA’ (Endy 2004). For this metaphor to
have clout, DNA is assumed to take the form of information, which can be read (with
the techniques of gene sequencing), and now written (using the techniques of synthesis)
(Villalobos et al. 2006).7
Many synthetic biology papers also talk about ‘reprogramming’
totally uncritically (Heinemann and Panke 2006, Dueber et al 2003,
Gallivan 2007). To give an example, Gallivan (2007) says that ‘One of the main goals
of synthetic biology is to reprogram organisms to autonomously perform complex tasks’
10
(p.612). Slightly more reflection is found in a Science article which at least recognises
that there is a gap between the organism and the computer programme in saying that
‘Synthetic biologists eventually aim to make bacteria into tiny programmable
computers.’ (Ferber 2004, p.160).
Work by Rabinow and Rheinberger shows how culture and nature can be
inverted, with ‘cultural’ frameworks (such as engineering and computation) having
profound effects on the ways in which we construct living things. I hope to have
demonstrated that these theoretical discussions help elucidate and enrich our
understanding of synthetic biology.
Model organisms and intellectual property
Work in other areas can also contribute to an analysis of synthetic biology, and in this
section I briefly discuss the attempts to standardise and control nature that we see in
model organisms and intellectual property.
The modular biological parts that synthetic biologists are attempting to create
have many similarities to the model organisms that have been standardized and
homogenized so that they can be used reliably and predictably in laboratory work
(Kohler 1999). For example, a key objective behind the development of the model
worm C. elegans was ‘reducing complex data to a conceptually and experimentally
tractable system’ (Ankeny 2000, p.S270). This is very reminiscent of the attempts to
reduce complexity that we find in synthetic biology. In the case of the experimental
mouse, the aim was to create mice which were so similar to each other that they were
exchangeable, which is what we currently see in the development of modular
BioBricks. We even see the use of the ‘plug’ metaphor in the mouse case:
‘standardization is about what happens when one ‘plugs in’ a purified,
specialized mouse into a research process (experiment, breeding program). If
one such mouse is substitutable for another, then the mouse meets a standard of
purity’ (Griesemer and Gerson 2006, p.S366, italics in original).
The stabilization that we find in model organisms, which allows them to be useful
laboratory tools, is also found in intellectual property, this time so that the living things
can be easily exchanged in the market place (see Calvert 2008). For example, an
argument made in favour of patenting microorganisms is that they ‘are formed in such
large numbers that any measurable quantity will possess uniform properties and
characteristics.’ (Judge Bastarache, Canada Supreme Court, 2002 in Dutfield 2008, p.3,
emphasis added). If living organisms are uniform then they can be more easily treated
as commodities.
A similar argument was made in the 1930 plant patent act. It was maintained
that since asexually reproduced plants did not vary, they should be considered
patentable (Pottage and Sherman 2007). Furthermore, the reproduction of a new plant of
this kind could not be accomplished by nature, but had to involve human intervention.
In this way the role of the breeder ‘was to normalise the abnormal, to stabilise and
standardise nature’s deviants, mutations and aberrations’ (Pottage and Sherman 2007,
p.559). With this stabilization and standardization work, the buyer would know that
they were getting a reliable product. This emphasis on standardisation and
homogenisation, and the attempt to eliminate aberrations is again very reminiscent of
synthetic biology. The catalogues that plant breeders produced so that their wares could
11
be bought as replicable copies (Pottage 2009) bear strong similarities to the ‘catalog of
parts and devices’ that can be found on the BioBricks website.8
We see attempts to standardize in both model organisms and in intellectual
property, but the two areas are linked in another way because model organism
communities often share views about ownership. For example, the Drosophila
community adopted strong norms of ‘sharing and free exchange’ (Kohler 1999:345),
and Drosophila researchers are known for being particularly cooperative, even today.
Similarly, the scientist who first produced the standardized experimental mouse did not
aspire to profit from it, instead ‘He favored traditional, cooperative exchange of
materials as a service to the community of researchers’ (Griesemer and Gerson 2006,
p.366). The C. elegans community is also ‘often celebrated as a model of scientific
cooperation’ (Ankeny 2000, p.S262). It seems as if model organism communities have
accompanying norms which favour the sharing of their standardized organisms. Perhaps
this sharing is necessary in a context where scientists are attempting to encourage buyin
to a particular standard.
We saw above how an open source approach was favoured by many synthetic
biologists, and that modularity could be seen as facilitating such an approach. This is
another demonstration of the similarities between synthetic biology and model organism
communities, and in this light, it is interesting how at the closing session of the
Synthetic Biology 4.0 conference in Hong Kong in 2008, explicit parallels were drawn
between the synthetic biology community and the C. elegans community.
Another particularly important point about the model organism communities
was how in the historical cases described above, the model organism, the social
arrangements and the intellectual property norms were all produced together (Kohler
1999). In synthetic biology we also see explicit attempts among certain leaders of the
field to build a community that shares a certain set of norms about open source (and
also about biosafety), at the same time as we see the building of the BioBricks and the
chassis that are the material building blocks of synthetic biology. This is a clear
example of how natural and social orders are co-constructed (Jasanoff 2006). And in
this example, as in many others in this volume, ‘it is abundantly clear that technoscience
and its artefacts are central to remaking society and nature simultaneously’ (Braun and
Castree 1998, p.29).
The open-source strand of synthetic biology is not the only one, however. There
are also synthetic biologists who are keen to gain proprietary ownership over their
synthetic creations.
As mentioned above, the ‘unnaturalness’ of synthetic organisms is used to argue
for their safety, and their unnaturalness can also be useful in a patenting context,
because it can be used to argue for their inventiveness. This is because the ‘product of
nature doctrine’ holds that if something already exists in nature then it is not patentable,
because it is not a novel invention. This doctrine can be traced back to the landmark
Diamond versus Chakrabarty decision on a patent on a modified microorganism, where
the court concluded that something could only be patented if it was ‘a nonnaturally
occurring manufacture or composition of matter – a product of human ingenuity’ (447
US § 303 [1980], p. 309 in Conley and Makowski 2004). Since synthetic biology aims
to de-complexify and improve on natural biological systems, its creations are clearly
different from what is found in nature, so an argument can be made that they are human
inventions, and that they deserve the reward of a patent.
12
Some synthetic biologists even purposely increase the unnaturalness of their
creations, and make them more proprietary by marking them. Most notably, Craig
Venter has ‘watermarked’ his name and the names of his collaborators into the code of
his minimised bacterial genome, by inserting codons that produce proteins which
correspond to the appropriate letters of the alphabet (Highfield 2008). This is a good
example of a way in which synthetic biology plays with the boundary between the
natural and the artificial, in the context of intellectual property.
There is a broader point here. Some commentators see the whole of intellectual
property law as drawing on an entrenched distinction between the natural and the
artificial. When something becomes intellectual property it is moved out of the realm of
the natural into the realm of the artificial; it becomes an artefact (Biagioli 2007). But
there are problems with presupposing that there is such a divide between the natural and
the artificial, because it assumes that there is a stable concept of nature ‘as such’ – some
kind of ‘a pre-given substrate’ (Pottage 1998). As we saw above, the arguments made
by Rabinow and Rheinberger showed that culture can become a model for nature,
making it very difficult to decide where culture ends and nature begins. Franklin points
to exactly this problem when she says that
‘The twentieth-century transformation of life itself has had the consequences
that the grounding or foundational function of nature as a limit or force in itself
has become problematic and lost its axiomatic, a priori, value as a referent or
authority, becoming instead a receding horizon’ (Franklin 2000, p.190).
Conclusions
This chapter has examined the ways in which synthetic biology is constructing nature. It
is literally constructing nature by building new types of biological entity, but it is also
constructing a new understanding of nature by challenging our notions of what is
‘natural’. For example, we have seen how some synthetic biologists see themselves as
improving on nature, while others emphasize the unnaturalness of their creations, to fit
with patent demands or to produce orthogonal systems that do not interfere with
existing biological contexts. However, although ‘synthetic’ is sometimes used as a
synonym for ‘artificial’, it is unlikely that we will happily allocate all synthetic
biological creations to the realm of the artificial. The standardized, modular,
decomplexified creations of synthetic biology will inevitably start to infect our
understandings of what is ‘natural’, which, as we have seen, is itself a ‘receding
horizon’ defined primarily in terms of what it is opposed to.
I have argued that the objective behind the (re)construction of nature in synthetic
biology is instrumental: the aim is to ‘improve’ on nature in order to make it easier to
engineer. A key aspect of this improvement is the reduction of complexity, because ‘the
more dramatically researchers can reduce the complexity of biological organisms, the
better they can turn these organisms into instrumentalizable media’ (Pottage 2007,
p.330). These tendencies may be a symptom of the ‘instrumentalist epistemology of
modern scientific culture overall’ (Wynne 2005, p.77), which Wynne sees as driving
research towards prediction and control and the potential for exploitation.
I have shown how synthetic biology is not exceptional in its attempts to
instrumentalise nature, but that there are a confluence of different factors which all push
in the same direction, and which include engineering, modularity, scientific practices,
13
model organisms, standardization, exchangeability, intellectual property, and even open
source.
But we have also seen how the desire for prediction and control may be
thwarted, and how there is a tension between the standardization which synthetic
biologists attempt to impose on the biological substrate, and nature’s apparent
unruliness. Even in an ‘age of biological control’ (Wilmut et al. 2000), we see the noncooperation
of nature. A key objective of synthetic biology is to overcome this
recalcitrance, which is why it is common to hear leading synthetic biologists talk of
‘mastering nature’ (Silver 2009), and of wanting to ‘manipulate biology to give us the
kind of things we want and not accept what nature gave us’ (Keasling 2009). It will be
fascinating to see how this tension will resolve itself in the context of synthetic biology,
and what limitations the exuberance of nature will impose on the scientists and
engineers’ desires for control.
I will end by suggesting that that the example of synthetic biology can give us
some very interesting insights into how ‘the world ‘outside’ the laboratory comes to
mirror the world inside’ (Braun and Castree 1998, p.27). For example, we have seen
how the epistemic ideal of modularity is imposed on the materiality of living things, and
how synthetic biologists prefer to change nature than change their models, if they
discover their models do not work as predicted. This goes further than Hacking’s (1992)
observation that technoscience enacts worlds that are fit for its methods, because the
powers of intervention in synthetic biology are potentially much greater than those of
previous biotechnologies. In synthetic biology we are seeing a reconstruction of nature
that is utilizable and instrumentalizable, and is a product of epistemic ideals and design
choices. This reconstruction may have profound consequences for the types of living
things that are brought into the world in the future.
14
References
Allenby, B (2006) ‘Biology as cultural artifact’ http://www.greenbiz.com/blog/2006/10/01/biologycultural-artifact
(accessed 30th May 2009)
Andrianantoandro E, Basu S, Karig DK, and Weiss, R (2006) ‘Synthetic biology: new engineering
rules for an emerging discipline’ Molecular Systems Biology, doi: 10.1038/ msb4100073
Ankeny, RA (2000) ‘Fashioning Descriptive Models in Biology: Of Worms and Wiring Diagrams’
Philosophy of Science, Vol. 67, Supplement. Proceedings of the 1998 Biennial Meetings of
the Philosophy of Science Association. Part II: Symposia Papers, (Sep., 2000), pp. S260-
S272
Arkin, A (2008) ‘Setting the standard in synthetic biology’ Nature Biotechnology, 26, 7: 771-774
Arkin AP, Fletcher DA. (2006) ‘Fast, cheap and somewhat in control’ Genome Biol 7:114
Balaram, P (2003) ‘Synthesising life’ Current Science, vol. 85, no. 11, 1509-1510
Ball, P (2004) 'Starting from scratch' Nature (7th October 2004), 431: 624-6.
Barnes, SB and Dupré, JA (2008) Genomes and What to Make of Them, University of Chicago Press
Barrett C.L., Kim T.Y., Kim H.U., Palsson B.Ø. and Lee, S.Y. (2006). Systems biology as a
foundation for genome-scale synthetic biology. Current Opinion in Biotechnology, 17(5), 1-
5
Biagioli, M (2007) ‘Denaturalizing the public domain: How to use science studies to rethink IP’,
Talk at the University of Edinburgh, 10th December 2007
Braun, B and Castree, N (1998) Remaking reality: nature at the millennium. Routledge: London and
New York
Breithaupt, H (2006) ‘The Engineer’s Approach to Biology’ EMBO Reports 7 (1), 21-24
Brent, R (2004) ‘A partnership between biology and engineering’ Nature Biotechnology, 22(10),
1211-1214
Calvert, J (2008) ‘The commodification of emergence: systems biology, synthetic biology and
intellectual property’ BioSocieties 3(4): 385-400
Carlson, R (2006) Synthetic biology 2.0, Part IV: What’s in a name?
http://synthesis.typepad.com/synthesis/2006/05/synthetic_biolo_1.html (accessed 1st
December 2008)
Cello J, Paul AV, Wimmer E. (2002) ‘Chemical Synthesis of Poliovirus cDNA: Generation of
Infectious Virus in the Absence of Natural Template’ Science 297: 1016-1018
Chan LY, Kosuri S, Endy D (2005) ‘Refactoring bacteriophage T7’ Mol Sys Biol DOI:
10.1038/msb4100025.
Chin, J (2008) ‘Life and perpetuation of life of a synthetic bacterium’ EMBL/EMBO Science and
Society Conference, Heidelberg, Germany, 7th-8th November 2008
Conley, JM and Makowski, R (2004) 'Rethinking the product of nature doctrine as a barrier to
biotechnology patents in the United States – and perhaps Europe as well ', Information &
Communications Technology Law, 13:1, 3-40
Deamer D. (2005) ‘A giant step towards artificial life?’ Trends in Biotechnology 23:336–338
Dupré, J (forthcoming 2010) ‘Is it not possible to reduce biological explanations to explanations in
chemistry and/or physics’ in Francisco Ayala and Robert Arp (eds) Contemporary Debates
in Philosophy of Biology Wiley
Dueber, JE, Yeh, BJ, Chak, K, Lim, WA (2003) ‘Reprogramming control of an allosteric signaling
switch through modular recombination’ Science 301, 1904–1908
Dutfield, G (2008) ‘Who invents life - intelligent designers, blind watchmakers, or genetic
engineers?’ SIBLE Seminar Series, University of Sheffield, 5 March 2008
Elowitz, MB and Leibler, S (2000) ‘A Synthetic Oscillatory Network of Transcriptional Regulators’
Nature. Jan 20; 403(6767):335-8
Endy, D (2004) ‘Parts, devices & systems: engineering biology at MIT’ Synthetic Biology 1.0, MIT,
10th-12th June 2004
Endy, D (2005) ‘Foundations for Engineering Biology’ Nature 438 (24 November 2005), 449-453
Ferber, D (2004) ‘Microbes made to order’ Science, 303 (9 January 2004), 158-161
15
Franklin, S (2000) ‘Life Itself: Global Nature and the Genetic Imaginary’, pp. 188-227 in Franklin, S
Lury, C and Stacey, J Global Nature, Global Culture. London: Sage
Franklin, S (2003) ‘Kinship, genes, and cloning: Life after Dolly’ in A Goodman, D Heath, & S
Lindee (eds), Genetic Nature/Culture: Anthropology and Science Beyond the Two-Culture
Divide, 95–110. Berkeley: University of California Press.
Franklin, S (2006) ‘The Cyborg Embryo: Our Path to Transbiology’ Theory, Culture and Society 23;
167-187
Gallivan, JP (2007) ‘Toward reprogramming bacteria with small molecules and RNA’ Curr Opin
Chem Biol. 2007 December; 11(6): 612–619.
Glass, JI., Assad-Garcia, N, Alperovich, N, Yooseph, S, Lewis, MR, Ma-ruf, M, Hutchison III, CA.,
Smith, HO., and Venter, JC (2006) ‘Essential Genes of a Minimal Bacterium’ Proc Nat Acad
Sci 103 (2), 425-430.
Griesemer, JR and Gerson, EM ‘Essay review. Of mice and men and low unit cost’ (review of
Making mice: Standardizing animals for American biomedical research, 1900–1955. Karen
A. Rader; Princeton University Press, Princeton, NJ, 2004)’ Stud. Hist. Phil. Biol. & Biomed.
Sci. 37 (2006) 363–372
Hacking, I, (1992) ‘The Self-Vindication of the Laboratory Sciences’, pages 29–64 in Pickering, A.,
(ed.), Science as Practice and Culture, Chicago and London: Chicago University Press
Hartwell LH, Hopfield JJ, Leibler S, Murray AW. (1999) ‘From molecular to modular cell biology’
Nature 402, C47–C52
Heinemann M and Panke, S (2006) ‘Synthetic biology – putting engineering into biology’
Bioinformatics, 22(22), 2790-2799
Highfield, R (2008) ‘‘Watermarks’ written in first artificial genome’ Telegraph, 01 Feb 2008
Isaacs, FJ and Collins, JJ (2005) ‘Plug and play with RNA’ Nature Biotechnology, 23(3), 306-307
Jasanoff, S (2006) States of Knowledge: The Co-Production of Science and the Social Order. New
York: Routledge
Keasling, J (2009) ‘Keynote lecture’ Launch Event for the Centre of Synthetic Biology at Imperial
College, 12th May 2009
Keasling, JD and Chou, H (2008) ‘Metabolic engineering delivers next-generation biofuels’ Nature
Biotechnology 26, 298 - 299
Keller, EF (2008a) ‘Lecture: nature and the natural’ BioSocieties, 3, 117–124
Keller, EF (2008b) ‘Systems biology: new paradigm or just fashion’ EMBL/EMBO Science and
Society Conference, Heidelberg, Germany, 7th-8th November 2008
Kevles, DJ (2002) A History of Patenting Life in the United States with Comparative Attention to
Europe and Canada A report to the European Group on Ethics in Science and New
Technologies, 12th Jan 2002 Luxembourg: Office for Official Publications of the European
Communities
Kitano, H (2002) ‘Computational systems biology’ Nature, 420, 14th November 2002, 206-210
Kitney, R (2008) ‘Overview of Design Principles’ Synthetic Biology 4.0, Hong Kong, 10th-12th
October 2008
Kohler, RE (1999) ‘Moral economy, material culture, and community in Drosophila genetics’ in
Biagioli, M ed, The Science Studies Reader New York: Routledge
Lancet, D (2008) ‘Diversity: a driving force for life's inception and synthesis’ EMBL/EMBO Science
and Society Conference, Heidelberg, Germany, 7th-8th November 2008
Lazebnik, Y (2002) ‘Can a biologist fix a radio?—Or, what I learned while studying apoptosis’
Cancer Cell vol. 2, pp.179-182
Lentzos, F, Bennet, G, Boeke, J, Endy, D and Rabinow, P (2008) ‘Roundtable on synthetic biology:
visions and challenges in redesigning life’ BioSocieties 3, 311-323
Luisi PL, Ferri F, Pasquale, S (2006) ‘Approaches to Semi-synthetic Minimal Cells: A Review’
Naturwissenschaften 93 (1), 1–13
Loettgers, A (2007) ‘Model Organisms and Mathematical and Synthetic Models to Explore Gene
Regulation Mechanisms’ Biological Theory Spring 2007, Vol. 2, No. 2, 134-142
16
Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD. (2003) ‘Engineering a mevalonate
pathway in Escherichia coli for production of terpenoids’ Nature Biotechnology 21:796–802
Martins dos Santos, V (2008) ‘Powering Cell Factories’ Synthetic Biology 4.0, Hong Kong, 10th-
12th October 2008
Marcus, GE (1995) ‘Ethnography in/of the World System: The Emergence of Multi-Sited
Ethnography’ Annual Review of Anthropology Vol. 24: 95-117
Morange, M (2009) ‘A new revolution? The place of systems biology and synthetic biology in the
history of biology’ EMBO reports, vol. 10, pp.S50-S53
NEST (2005) Synthetic Biology: Applying Engineering to Biology Report of a NEST High-Level
Expert Group Luxembourg: Office for Official Publications of the European Communities
online at
ftp://ftp.cordis.europa.eu/pub/nest/docs/syntheticbiology_b5_eur21796_en.pdf (accessed 14th
September 2008)
Oliver, S (2008) ‘Synthetic and Systems Biology: Simplicity and Simplification’ Discussion Meeting
on Synthetic Biology, Royal Society, London, 2nd-3rd June 2008
O'Malley, MA, Powell, A Davies, JF, and Calvert, J (2008) ‘Knowledge-making distinctions in
synthetic biology’ BioEssays, 30 (1), 57-65
Palsson, B (2000) ‘The challenges of in silico biology’ Nature Biotechnology Vol 18 November
2000, pp.1147-1150
Pollack, A (2001) ‘Scientists Are Starting to Add Letters to Life’s Alphabet’ New York Times, 24
July 2001
Pottage, A (1998) ‘The inscription of life in law: genes, patents, and bio-politics’ Modern Law
Review 61: 740-65
Pottage, A (2007) ‘The socio-legal implication of the new biotechnologies’ Annual Review of Law
and Social Science 3:321-44
Pottage, A (2009) ‘La mécanisation propriétaire du vivant’ La co-définition du vivant et des droits de
propriété, Paris, 9 April 2009
Pottage A and Sherman, B (2007) ‘Organisms and manufactures: on the history of plant inventions’
Melbourne University Law Review, 31(2), 539-568
Rabinow, P (1999 [1992]) ‘Artificiality and Enlightenment: From Sociobiology to Biosociality’ in
Biagioli, ed., The Science Studies Reader (Routledge), pp 407-416.
Rheinberger, H-J (2000) ‘Beyond Nature and Culture: Modes of Reasoning in the Age of Molecular
Biology and Medicine’, in M. Lock, A. Young and A. Cambrosio (eds) Living and Working
with the New Medical Technologies: Intersection of Inquiry, pp. 19–30. Cambridge:
Cambridge University Press
Royal Academy of Engineering (2009) Synthetic Biology: Scope, Applications and Implications
Royal Academy of Engineering: London, May 2009 online at
http://www.raeng.org.uk/news/publications/list/reports/Synthetic_biology.pdf (accessed 5th
July 2009)
Sauro, HM (2008) ‘Modularity Defined’ Molecular Systems Biology 4:166
Silver, P (2008) ‘Designing Biological Systems’ Discussion Meeting on Synthetic Biology, Royal
Society, London, 2nd-3rd June 2008
Silver, P (2009) ‘Design Principles in Biological Systems’ Launch Event for the Centre of Synthetic
Biology at Imperial College, 12th May 2009
Tucker JB, Zilinskas RA. (2006) ‘The promise and perils of synthetic biology’ New Atlantis 12: 25-
45
Villalobos , A, Ness, JE, Gustafsson, C, Minshull, J and Govindarajan, S (2006) ‘Gene Designer: a
synthetic biology tool for constructing artificial DNA segments’ BMC Bioinformatics 7:285
doi:10.1186/1471-2105-7-285
De Vriend, H (2006) Constructing Life. Early social reflections on the emerging field of synthetic
biology. The Hague: Rathenau Institute; Working Document 97 online at
http://www.rathenauinstituut.com//showpage.asp?steID=2&item=2644 (accessed 25th
February 2008)
17
Weiss, R (2008) ‘The iGEM Undergraduate Competition’ Synthetic Biology 40, Hong Kong, 10th-
12th October 2008
Wimsatt, W (2007) Re-engineering philosophy for limited beings: piecewise approximations to
reality Cambridge, Massachusetts: Harvard University Press
Wilmut, I, Campbell, K and Tudge, C (2000) The Second Creation: The Age of Biological Control
by the Scientists Who Cloned Dolly London: Headline
Wynne, B (2005) ‘Reflexing complexity: post-genomic knowledge and reductionist returns in public
science’ Theory, Culture and Society, 22(5), 67-94
1
www.syntheticbiology.org (Accessed 30th April 2010)
2
http://www.refactoring.com/
3
http://partsregistry.org/Main_Page/ (Accessed 30th April 2010)
4
http://www.openwetware.org/wiki/Synthetic_Biology:Abstraction_hierarchy (Accessed 30th April
2010)
5
www.syntheticbiology.org (emphasis added) (Accessed 30th April 2010)
6
Oscillators and logic gates are common components of electronic circuits. An oscillator produces a
repetitive electronic signal and a logic gate switches the flow of electricity ‘on’ or ‘off’ depending on the
input.
7
For criticism of this understanding of DNA as informational see Barnes and Dupré (2008).
8
http://partsregistry.org/Main_Page (Accessed 30th April 2010)