Synthetic biology and its alternatives

Leseprobe

1. Introduction

Just ten years ago, the sequencing of the human genome was celebrated as decoding “the language in which God created life”. The “revelation of […] the human book of life”, as it was also called, was associated with an expectation that, thanks to control of the genome, it would now easily be possible to make targeted interventions in the organism, defeat diseases and generate new capabilities.[1] However, attention soon turned to the question of precisely what biotechnological innovations could now be anticipated, and at this stage very different voices came to the fore: voices stressing that decoding the genome was “only a first step”; that the impact of the interaction between different genes and gene products in the metabolism must first be understood; and that many more years of hard work would be needed to isolate and control functional systems within the enormous complexity of a living cell.[2] It was also at this juncture that the simple translational logic of the genetic code suddenly ceased to seem quite so simple. Although the rule of the RNA-mediated translation of DNA base triplets into polypeptide chains retained its validity, it quickly became clear that the answers to many other questions cannot be read off the genome alone – such as the dynamics of when and how often the cell “reads” which DNA sequences, how it processes the RNA transcripts, which transcripts are then translated into proteins, or which proteins are finally deployed and how. This complexity of genetic regulations had long since sedimented into standard textbook knowledge,[3] yet conclusions were rarely drawn from it while the focus was on the sequencing of the genome. Several other unanswered questions initially remained largely unaddressed, such as how many functions a gene product can carry out in a particular biological context,[4] what tasks are fulfilled by those DNA sequences to which no genetic function can be attributed (what is known as “junk DNA”),[5] and how the discrepancy between the relatively small number of genes and the great diversity of chemical products in some organisms may be explained.[6]

Synthetic biology and systems biology – the two research paradigms so much discussed in recent years – can certainly be regarded as reactions to the rediscovered complexity of the cell: they are both strategies which expressly address that complexity, but they do so in very different ways. Systems biology, on the one hand, is concerned to integrate the deluge of data from biochemistry and molecular biology into a comprehensive model, something that is only possible at the price – sometimes a high one[7] – of translating organic substances and processes into computer simulations. Synthetic biology, in contrast, takes the avenue of reducing organic complexity itself, transforming substances into standardised building blocks and cell events into a limited number of controlled processes in order to create new functional systems.

As in the case of the decoding of the human genome ten years earlier, contemporary synthetic biology was initially dominated by the strident refrain that it was now becoming possible to design life on the drawing board, to construct it from simple components and to wire it up and program it at will. Although today the end of the “hype” phase is widely invoked,[8] the idea lingers that biological functional systems can be constructed by “engineering”. A typical definition of synthetic biology, thus, runs: “Synthetic biology is the engineering of biological components and systems”.[9] These components and systems are consequently described, in line with the engineering approach, as biological and living “machines”, in formulations such as “a combination of synthetic biology platforms with current metabolic and cellular engineering tools is expected to give rise to a new generation of microbes that function as highly robust and programmable biological machines”.[10] By referring to biomolecular systems as machines, the discourse of synthetic biology is articulating a generally apparatus-based understanding[11] of functional biological systems and their substructures (such as enzymes).[12]

What we will show in this paper is the following: the notion that synthetic biology will permit the “engineering” of biological machines rests on presuppositions which, once they are made explicit, render that conclusion somewhat ill-founded. In our view, it is highly implausible that systems with properties characteristic of life can really be constructed using only the specific methods of engineering.

Our argument proceeds firstly by clarifying the relationship between the concept of engineering and the concept of design (Section 2). Drawing on Descartes and Kant, we then show that the mode of “construction by design” presupposes the paradigm of a Cartesian machine, and identify the difficulties that arise from trying to make this paradigm compatible with the project of constructing the properties of living beings (Section 3). In response to this problem, we do not reject in general the usefulness of a machine concept for biological systems, but present alternative machine concepts that go beyond the Cartesian paradigm, in particular Gilbert Simondon’s concept of the “concrete machine”, which refers to a kind of adaptive machine (Section 4). Finally, we outline current perspectives in chemical, biochemical and molecular biological research that lend themselves far better to the paradigm of producing “concrete machines” than to the paradigm of “engineering by design” (without implying that a concept of machine is necessarily sufficient for the systems in question)(Section 5). As a perspective, a paradigm of biotechnological action emerges that differs significantly from the current engineering paradigm of synthetic biology.

[1] Quotations from the speeches by Bill Clinton and Francis Collins on the presentation of the results of the Human Genome Project, 26 June 2000, http://clinton5.nara.gov/WH/New/html/genome-20000626.html (last accessed 17 August 2011).

[2] We may think here of dynamic systems such as metabolic networks, signal transduction cascades or regulatory networks.

[3] See Alberts et al. (1998), p. 270.

[4] See Jeffery (1999).

[5] See Biémont and Vieira (2006).

[6] See Cerdá-Olmedo (1994).

[7] See Neuman (2008), p. 45.

[8] See Kwok (2010).

[9] The complete definition in the European Commission’s research programme “Synbiology” runs: “Synthetic biology is the engineering of biological components and systems that do not exist in nature and the re-engineering of existing biological elements; it is determined on the intentional design of artificial biological systems, rather than on the understanding of natural biology.” Synbiology (2006), p. i; see also NEST (2005), p. 5; Channon (2008).

[10] Leonard et al. (2008), p. 680.

[11] On mechanicism and synthetic biology, see Nicholson (2011): “Mechanicism has been one of the most influential schools of biological thought since the late seventeenth century. It has its origins in the physiological writings of Descartes, though the doctrine has had numerous incarnations through the centuries. […] Most recently, the emerging field of synthetic biology, with its aim to apply engineering principles in order to design and manufacture living cells from scratch, constitutes the newest expression of the mechanistic research program in biology.”

[12] The notion of using the term “biological machine” as a metaphor for the entirety of biological functional systems differs from the approach that Kay et al. developed for synthetic machines. In their paper on synthetic molecular motors and mechanical machines, they “choose to differentiate machines from other devices on the basis that the etymology and meaning of ‘machine’ generally implies mechanical movement – that is, a net nuclear displacement in the molecular world – which causes something useful to happen. Thus … ‘molecular machines’ are a defined subset of ‘molecular devices’ (functional molecular systems) in which some stimulus triggers the controlled, large amplitude or directional mechanical motion of one component relative to another (or of a substrate relative to the machine) which results in a net task being performed.” The authors emphasise the distinctions between biological molecular machines and man-made mechanical machines (for example, the fact that biological machines are pliant rather than inflexible, and that the dynamic structure and workings of biological machines are determined by intra- and intermolecular non-covalent interaction in which the liquid medium is often involved). They conclude that few details of the functions of biological machines have so far been understood, and that therefore biology is offering at present little information to explain the processes of synthetic machines. This reflects our own view. See Kay et al. (2006), pp. 73-74.