Synthetic Biology

The aim of this paper is to contribute to a prospective science and technology assessment (ProTA) of synthetic biology in order to enable an early societal shaping of this emerging wave of technoscience. To accomplish this goal, a philosophical approach towards the technoscientific core of synthetic biology—provided by philosophy of science and philosophy of technology—will be taken. The thesis is that if there is any differentia specifica giving substance to the umbrella term “synthetic biology”, it is the idea(l) of harnessing self-organization for engineering purposes. To underline that we are likely experiencing an epochal break in the ontology of technoscientific systems, this new type of technology is called “late-modern technology." I start by analyzing the three most common paradigms and visions of synthetic biology (Sect. 2). Then I argue that one particular paradigm deserves more attention because it underlies the others: the paradigm of self-organization (Sect. 3). However, synthetic biology does not stand alone in making use of self-organization; it is a governing vision in robotics, ubiquitous computing, nano- and neuro-technologies (Sect. 4). Further, I show that instabilities constitute the conditions and, hence, the technoscientific core of self-organization (Sect. 5). Given the relevance of instabilities, I consider the inherent limits of late-modern (self-organization) technology in construction/design and control/monitoring, and in particular I elaborate why it is so difficult to control biosynthetic systems (Sect. 6). I end by drawing conclusions for the early-stage approach of ProTA and sum up the characteristics of late-modern technology as a challenging subject area of philosophy of technology (Sects. 7 and 8).

What happens when some of the traditional questions and concerns of the philosophy of science are brought to the non-traditional field of synthetic biology? Given that synthetic biology is a very diverse field, this might serve to highlight the many ways in which it is business as usual. However, prominent concepts and research practices of synthetic biology can be seen to confound established ideas of how knowledge is produced and validated in the sciences. By highlighting and readying for discussion the tension between alternative images of knowledge production in synthetic biology, this paper seeks to open up debate among philosophers of science, and within the diverse community of synthetic biologists. With the advance of emerging technosciences like synthetic biology what is at stake is not primarily how they might or might not change the world. At stake, first of all, are epistemic values, the ethos and authority of science, and the relation of knowledge and power. Building on ongoing discussions, the paper begins by exhibiting contested notions of understanding, rational engineering, and design. In a second step, it turns to different conceptions of biological “systems” by presenting divergent accounts of the origin of synthetic biology and of how systems biology gave rise to synthetic biology. Finally, it seeks to focus the debate on a definition of synthetic biology, according to which it builds, for constructive purposes, on achievements of technical control of biological complexity, that is, that it uses these achievements to generate, rather than reduce, complexity.

Synthetic biology aims at the design or redesign of living systems for useful purposes. This aim requires a predictable and reliable behavior of synthetic cells in their environment. The inherent complexity of biological systems renders any strict calculations impossible and thus poses an enormous challenge to synthetic biology. Two alternative strategies have been adopted by synthetic biologists to deal with this problem: (1) Reduction of complexity by applying engineering principles to biology like standardization and modularization and (2) orthogonalization through chemical or biological modification of synthetic cells to prevent genetic interactions with other organisms. While the first strategy aims at a transformation of biology into an engineering science, the second reduces complexity at the ecological level but not at the individual level. I will discuss both strategies and show that they also follow different safety concepts. The engineering branch of synthetic biology builds on extensive control of synthetic cells via their predictive behavior. The safety of chemically modified organisms will be provided by a genetic firewall due to their chemical or genetical incompatibility with existing cells.

Basic research in synthetic biology is rapidly advancing. A Google search for the term “synthetic biology” revealed more than 3 million hits (accessed 15 January 2014). 793 scientific articles indexed with this term are found in the Web of Science database for the year 2013. It can be expected, that applications developed by synthetic biology will be commercialized in the not-so-distant future. However, significant commercial use of “biological principles” in industrial biotechnology already exists. The adaptation of results of synthetic biology by industry will not only depend on their scientific “beauty,” but also on existing economic and environmental constraints and the socio-economic context. In the following chapter, we will give an overview of the economic context of industrial biotechnology, and identify major opportunities for future applications of synthetic biology in industrial processes.

Synthetic biology allows the generation of complex recombinant systems using libraries of modular components. Two major near-market applications are whole-cell biosensors and biocatalysts for conversion of lignocellulosic biomass to biofuels and chemical feedstocks. Whole cell biosensors consist of cells genetically modified so that binding of a specific analyte to a receptor in the cell triggers generation of a specific output which can be detected and quantified. Since these systems are intrinsically modular in nature, with separate systems for signal detection, signal processing, and generation of the output, they are well suited to a synthetic biology approach. Likewise, effective degradation of cellulosic biomass requires a battery of different enzymes working together to degrade the matrix, expose the polysaccharide fibres, hydrolyse these to release sugars, and convert the sugars to useful products. Synthetic biology provides a useful set of tools to generate such systems. In this chapter we consider how synthetic biology has been applied to these applications, and look at possible future developments in these areas.

The expansion of cellular functions via novel modular building blocks, namely unnatural amino acids, their site-selective genetically encoded cotranslational incorporation into proteins, requires the redesign and expansion of the translational network with additional components, the orthogonal tRNA and tRNA synthetase. At the next level protein tectons (tecton = architectural building block) constitute complex genetically encoded “material libraries” inside the cell. These protein tectons are architectural building blocks allowing for complex supramolecular self-assembly inside the cell, forming cellular compartments or constituting 3D matrix mimicry of the extracellular matrix outside the cell. In addition they form the basis for biohybrid materials in protein/enzyme engineering, nanotechnology and regenerative medicine. The defined modification of protein tectons utilizing chemical biology allows for the selective bioconjugation e.g. of unnatural amino acids, via bioorthogonal chemical reactions introducing novel chemical entities expanding the repertoire of “posttranslational” protein modifications in vitro and in vivo for various applications.

By default synthetic biology refers to construction of synthetic genetic programs. Yet, programs must be expressed within a machine, and the elusive but multipurpose “chassis” is usually taken for granted. The program replicates while the chassis reproduces, showing that maturation, ageing and senescence are core processes which must be taken into account in order to explore realistic outcomes. Functional analysis reveals the essential functions that we need to consider. Some are listed in the present chapter, with emphasis on the role of information recruitment. This is a built-in process of living organisms whose outcome is the production of an ever young progeny as a way to cope with ageing and senescence. Life innovates using Maxwell’s demons-like nanomachines. This is at odds with standard engineering practices, opening up new perspectives for synthetic biology.

In early stages of research and innovation a precise investigation of technological risks, as well as the analysis of particular beneficial features, is confronted with a lack of knowledge about exact process or product qualities, application contexts and intentions of users. Therefore, an appropriate identification of anticipated risks, accompanied by the achievements of synthetic biology, should rather focus on basic properties and functionalities of the objects of synthetic biology which will be exploited in future products and processes. Accordingly, the aim of this chapter is to determine major risk factors of synthetic biology creations with a focus on the technology itself. In consideration of the demand to cover these risks by appropriate counter measures, the question is raised, whether there are suitable strategies to achieve a high level of safety. In this regard, the discussion will be extended to feasible alternatives, e.g. by introducing trophic and semantic isolation strategies for synthetic organisms as an approach to overcome major drawbacks of classical biosafety mechanisms. Finally, functional reduction, a concept which is already aspiring to achieve efficient biosynthesis, is suggested as a measure for the reduction of risk-related functionalities. This strategy is worth further investigation if the full potential of synthetic biology is to be obtained in a safe and sustainable way.

When introducing new technologies, or dealing with uncertain situations in general, risk assessment is an established methodology to systematically and reliably consider whether intended benefits are gained or whether unwanted adverse effects are likely to occur. The German Advisory Council on Global Change (WBGU) distinguishes different risk categories according to the probability and extent of any possible damage. Building on that, the Gene-Risk Research Consortium elaborated a hierarchical risk assessment approach to analyze possible impact of the cultivation of genetically modified organisms (GMO). This approach is also adaptable to risks involved in the development of synthetic life forms. Since the use of GMO affects different levels of organization addressed by different scientific disciplines and stakeholders, the potential risks of GMO cultivation have to be denoted as being systemic and require interdisciplinary as well as transdisciplinary co-operation. Synthetic biology can build on risk management solutions which have been established for the use of GMO—at least to the extent that comparable risk dimensions have to be covered. For both technologies, risk assessment has to consider a wide spectrum of cause-and-effect chains and the potential impact over long time spans and large areas of space. It must also consider potential self-dispersal and subsequent evolutionary processes in the ecosphere after intended or accidental release into open ecosystems. A holistic risk assessment approach to GMO was settled upon by applying the concept of emergent properties structuring possible effects for different levels of organisation considering that interactions on lower levels (molecules, cells, organisms) in composition are supposed to bring up new interaction types on higher levels (populations, ecosystems, landscapes, biomes). In comparison with this structured approach, the current legal regulations, as established in the EU, can be improved in coherence and systematization by the proposed approach, in particular with regard to different ecological and economic implications of GMO (and in parallel potential releases of synthetic organisms). This is especially relevant on the landscape level; for instance, as a comprehensive systematization of region-specific adverse effects on non-target organisms, complex coexistence issues related to different production systems or some social ecological topics. In conclusion, human intervention involving self-reproducing entities by means of genetic engineering, as well as development of new synthetic life forms, should always evaluate the complete set of causal interactions on all levels of physical, biotic and social organisation in order to minimise the probability of unintended, undesirable and even harmful effects as far as feasible through anticipative assessment.

Assuming that synthetic biology (SynBio) will generate not only new benefits but also new risks to human health and the environment this article explores to what extent SynBio is already adequately supervised by the existing EU regulation of genetically modified organisms (GMOs). While the GMO regime is applicable to many kinds of SynBio activities, others are not covered, such as the complete replacement of the genetic material of a cell, the insertion of transgenes into an organism by other methods than those listed as qualifying as genetic engineering—or not—the construction of a protocell and minimal cell, the placing on the market of bioparts, and xenobiochemistry. The article then asks if the risk assessment methodology applicable to GMOs is suited for products from SynBio. This question is denied insofar as the familiarity principle which governs traditional GMO risk assessment is concerned. New and genuine methodology must be developed to identify hazards and evaluate risks. While the thrust of the article is on ex ante regulation, or administrative oversight, it also discusses ex post regulation, or civil liability for damage, concluding that liability schemes must also be adapted to the new characteristics of SynBio. In sum, it is time for regulators to take a closer look at SynBio.

Synthetic biology can give rise to euphoric utopian scenarios, as well as to frightening dystopian narratives. These scenarios and narratives are not based on a consequentialist analysis of synthetic biology as a value neutral means to given ends. In contrast, the hopes and fears of these future scenarios are based on an apprehension of different modes of action that are meant to be prevalent in synthetic biology. Utopian visions highlight synthetic biology’s potential to contribute to a society that lives and acts in “cooperation” with nature, whereas dystopian scenarios interpret synthetic biology as “disrupting” our connection to nature. It is argued that these differences can be philosophically spelled out in terms of a distinction between “communicative” versus “instrumental” modes of action. On this basis, a proposal is made to address what it might mean for a biotechnology to adhere to the communicative mode of action. In general, a communicative technology prefers to induce change by exploring and making use of the inner tendencies and interests of an organism. In contrast, an instrumental technology favors redesign to efficiently achieve given ends. As it turns out, the current main characteristics of synthetic biology, by and large, render it an example of the instrumental mode of action. As a consequence, from an ethical point of view extra effort is needed to make ideas of careful step-by-step approaches to innovation plausible in synthetic biology settings.

Two fields of reflection on synthetic biology are related to each other: the debate on the understanding of the specific scientific character of synthetic biology on the one hand with reference to the notion of technosciences, and the debate on Responsible Research and Innovation on the other. The target is asking for the consequences and implications of classifying synthetic biology as a technoscience which implies blurring the traditional distinction between basic and applied sciences—for attributing and distributing responsibility. To this end, the EEE model of responsibility will be introduced (empirical, ethical, epistemological). Building on this concept the specific responsibility constellation in the field of synthetic biology will be analysed. Concluding, the necessities of conceptualising ethics as an accompanying reflection on the scientific and technological advances including the consideration of their relationship to the governance of science within the democratic system are taken under consideration.