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"Pablo and the iGEM-Team Freiburg delve deep into biological theory and philosophy without losing sight of ethical implications of these issues.
A truly impressive accomplishment!"

Dr. Joachim Boldt
Institute of Ethics and the History of Medicine, Albert-Ludwigs-University of Freiburg

1.1 Philosophical essay

Synthetic biology aspires to be an engineering discipline, with the aim of constructing artificial living systems as means to human ends. The products of synthetic biology ought to be living machines. The ‘international Genetically Engineered Machine competition’ is prospectively raising a whole generation of future scientists trained in the methods of this novel field of synthetic biology. We believe that in this context the ‘Know How’ (procedure) needs to be accompanied with the ‘Know Why’ (causal knowledge), but most important by the often forgotten ‘Know What’ (meaning), because the emerging of every new engineering discipline brings not only chances but also risks, uncertainties, and worries. There is no doubt that the field of synthetic biology promises a large number of meaningful applications and solutions for many present problems. However, at the same time, many social, ethical and legal problems are being revealed by the claim of the creation of ‘artificial living systems’ or ‘living machines’. We need to ask ourselves: ‘what are we actually doing?’, ‘what are living machines good for?’ and also ‘what are they in themselves?’. Any ad-hoc answer to these questions would lead to a misjudgement of the arising problems.

Our iGEM-team tried to leave aside any preconceived opinion and to make a profound critical analysis of the actual source of the nascent public concerns (dual-use-dilemma, ‘playing god’, biosafety, biosecurity, etc). We did not only meet for lab meetings, but for philosophical evenings as well: Together with scholars from diverse fields of science, we discuss core philosophical aspects of synthetic biology, focussing on the ontology of the products of synthetic biology (see 'Chronicle of philosophical evenings'). What do we actually mean by expressions like ‘living machines’ and ‘artificial life’? To answer these questions, we studied modern approaches of philosophy of language (e.g. theory of conceptual metaphors), philosophy of technology (e.g. ICE-theory for the ascription of technical functions), philosophy of biology (e.g. organisational account of biological functions) and diverse bioethical theories (e.g. Taylor’s biocentric position). Through our deliberations, we came to the conclusion that many apparent ontological and ethical problems concerning synthetic biology and its aimed products are actually epistemological and semantical ones, which arise due to its ‘intentional epistemology’ and the unreflective use of innovative metaphors such as ‘living machine’. Our analysis pointed out important epistemological deficits of synthetic biology such as the unjustified methodological principle of ‘knowing by doing’, a tailor-made notion of life and the metaphoric character of its main terms. Pablo Rodrigo Grassi, one of our team members, took the challenge and collected the different thoughts of our discussions building a coherent text:

'‘LIVING MACHINES’, METAPHORS AND FUNCTIONAL EXPLANATIONS – Towards an epistemological foundation of synthetic biology

The analysis of the innovative term ‘living machine’ in this essay describes a novel argumentation, which combines advanced theories of philosophy of technology and philosophy of biology and allows us to make clear distinctions between organisms and machines. Out of the exposed accounts in the essay, is it justified to assert that living beings emerge and develop ‘naturally’ and are, in their development, under no circumstances dependent on human agency. This makes any ontological distinction between ‘living machines’ and ‘living organisms’ and between ‘artificial life’ and ‘natural life’ pointless. Therefore, it is not warranted to use hybrid expressions (e.g. ‘synthetic life’, ‘living machines’, ‘genetically engineered machines’) as proper terms; however, their usage as metaphors may be warranted. This essay argues for the reflexive and not constitutive use of metaphors in the language of the synthetic biology in order to avoid faulty inferences. On the one hand, this essay enables to allay the global unease concerning the idea of creation of life and the notion of ‘living machine’, because, according to our argumentation, no creation of life and no ‘living machine’ is possible at all. On the other hand, this essay shows some important aspects which are required for consolidating a clear and coherent epistemology of synthetic biology. Moreover, based on the conduced analysis of biological functions in our essay, the outline of a consistent biocentric ethic which also includes the products of synthetic biology, is possible.

1.2 Chronicle of the philosophical evenings
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In this section we would like to describe the development of our arguments and thoughts concerning the epistemological roots of synthetic biology and the different arising problems. Through these 'philosophical evenings' we examined in detail if the expression 'living machine' can really be considered to be a proper term or if it is necessarily a metaphor. We inquired together if this novel categorisation and kind-setting ('living machine') is actually warranted or not. Although our chronicles might wake the feeling of straightforwardness, this was not really the case. In fact, we needed hours of discussions, sanguine brainstorming and intensive reading to archieve our final arguments. Clearly, not all of the team members were the same opinion through our deliberations and it took time to find our common premises and starting points. But once we cleared up our diverse positions, we were able to do a fine work together! Although we also wanted to describe these different aspects and opinions through our discussions, we decided to simply present the thread and fruits of our philosophical evenings.

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'''First meeting - Introduction'''
After a short introduction to the ''definition, aims'' and ''different approaches'' of the synthetic biology ([1],[2],[3],[4]), we clarified some special philosophical terms in order to have a common basis for further discussion. During the first meeting, we soon realised that the synthetic biology grounds on a different epistemology than the fields of ‘pure sciences’ do. Publications we worked with: :[1] Arkin A et al (2009): Synthetic biology: what’s in a name? ''Nat Biotechn'' 27 (12): 1071–1073
:[2] Benner SA, Sismour AM (2005): Synthetic biology. ''Nat Rev Gen'' 6: 533-543
:[3] Boldt J, Müller O, Maio G (2009): ''Synthetische Biologie. Eine ethisch-philosophische Analyse''. EKAH, Bern
:[4] O'Malley M, Powell A, Davies JF, Calvert J (2008): Knowledge-making distinctions in synthetic biology.'' Bioessays'' 30: 57-65
'''Second meeting - Epistemology'''
In our second meeting we tried to work out what the special epistemological characteristics of an applied science are [5]. We expounded the general epistemological problems and possibilities of an engineering discipline. We noticed that ''causal knowledge'' and natural laws are not the main aim of an engineering discipline. Rather, the main aim is for ''efficient maxims'' and sufficient rules: In order to judge a technological system we only refer to it's efficiency - we just see if something works or not. In the epistemology of technological sciences the concept of efficiency plays a similar role to that which the concept of truth plays in the epistemology pure sciences, since scientific theories are judged by their truth value. Therefore, if the synthetic biology aspires to define itself as an engineering discipline, then the aim of knowledge-making is necessarily non-substantial [6]. Publications we worked with: :[5] Bunge M (1974): Technology as applied science. In: Rapp F (ed.) ''Contributions to a Philosophy of Technology: Readings in the Philosophical Problems of Technology.'' Free Press, New York. 19-39
:[6] Schummer J (2011): ''Das Gotteshandwerk. Die künstliche Herstellung von Leben im Labor.'' Suhrkamp, Berlin
'''Third meeting - Procedure'''
After asserting that synthetic biology follows an ‘intentional epistemology’, we analysed the conceptual procedure of synthetic biology. In view of the fact that the synthetic biology aims to create life, a consistent definition of the phenomena of life is needed, in order to have a reasonable goal ([7],[8]). Interestingly, the conception of life in synthetic biology matches with the settled purposes [9]. The understanding of life is adjusted to the notion of things that humans can make, modify and comprehend. Thus, the field of synthetic biology approaches ''biological systems as technological systems'' ([10],[11]). In this context, the ''analogical transfer'' from technological properties into the realm of the living can be understood as the epistemological program of synthetic biology. This transfer then promotes the aim of creating life, as it provides an understanding of life which makes such a feat possible in the first place. In short: within the field of synthetic biology, we encounter living beings ''as if'' they were machines. Publications we worked with: :[7] Brenner A (2007): ''Leben. Eine philosophische Untersuchung.'' EKAH, Bern
:[8] Brenner A (2011): Living life and making life. ''Analecta Husserliana'' 110: 91-102
:[9] Deplazes-Zemp A (2011): The Conception of Life in Synthetic Biology. Sci Eng Ethics doi:10.1007/s11948-011-9269-z
:[10] Deplazes A, Huppenbauer M (2009): Synthetic organisms and living machines: Positioning the products of synthetic biology at the borderline between living and non-living matter. ''Syst Synth Bio'' 3(1-4): 55-63
:[11] Schyfter P (2012): Technological biology? Things and kinds in synthetic biology. ''Biol Philos'' 27: 29-48
'''Forth meeting - Metaphors'''
Because synthetic biology approaches biological systems as technological systems by means of analogy, we examined the general concept of metaphors ([12],[13],[14]) and the epistemic value of inference from analogies. Through this examination, two problems became clear: First, because conceptual metaphors constitute of a way to see, think and act towards things [14], it is necessary to inquiry how our position towards life might change in the light of it as a machine [3]. Second, if synthetic biology does base upon a series of conceptual metaphors, which are not identified as such, then serious epistemological problems exist. All inference from the inductive argument of analogy is to be considered invalid: We might try and understand living beings as machines – that, however, does not impy that they indeed behave as such. Publications we worked with: :[12] Black M (1954): Metaphor. ''Proc Aristo Soc'' 55: 273-294
:[13] Black M (1979): More about Metaphor. In: Ortony A (ed.): ''Metaphor and thought.'' Cambridge University Press, Cambridge. 19-43
:[14] Lakoff G (1993): The contemporary theory of metaphor. In: Ortony A (ed.): ''Metaphor and thought.'' Cambridge University Press, Cambridge. 202-251
'''Fifth meeting - Necessary properties of a ‘living machine’'''
In our firth meeting, we discussed about the necessary properties that a living beings needs to have in order to be considered a ‘living machine’ ([8],[10],[11],[15]). For the following meetings we decided to analyse in detail the properties of ''artificiality'' and ''technical functionality'', as machines are usually understood as physical objects, which were intentionally produced by human beings to achieve certain goals. Only if we can justify why products of synthetic biology are artificial and why do they have a technical function, we can use the expression ‘living machine’ as a proper term. Publications we worked with: :[15] Schark M (2012): Synthetic Biology and the Distinction between Organisms and Machines. ''Environ. Values'' 21: 19-41
'''Sixth meeting - Artificiality'''
Our inquiry of artificiality showed that we ought not to use the adjective ‘artificial’ as an honorary title. Due to the existing continuum between the natural and the artificial (e.g. [16]), we cannot argue that something is simply natural or simply artificial. A bioengineering product is less artificial than Venter’s ''Synthia'', which is respectively less artificial than a product of the protocell approach. All the products of synthetic biology are not simply ‘artificial life’: a bioengineering product has ‘artificial parts’, a synthetic genomics product an ‘artificial genome’ and, according to our argumentation, only the bottom-up protocell approach might be capable of producing entities, which could be meaningfully called as a whole ‘artificial life’ or ‘synthetic life’. Thus, all references to biological systems with the adjectives ‘artificial’ or ‘synthetic’ not being marked as a ''metaphor'' or as a ''future aim'' are therefore not warranted. Publications we worked with: :[16] Sandler R (2012): Is artefactualness a value-relevant property of living beings? ''Synthese'' 185: 89-102
'''Seventh meeting - Technical functionality: the overdetermination problem'''
The following necessary property we examined was the ''technical functionality'', because machines are not only made by humans, they are also supposed to have a useful function: a machine needs to be constructed with the intention to be a helpful mean to some human end. Although many of the scholars who worked on the products of synthetic biology accepted almost unproblematicly that the synthetic entities have technical functions (e.g. [10],[11],[17]), we wanted to examine in detail the idea of a synthetic biological product following a human-set goal. For this, we decided to study the relation between ''technical functions'' and ''biological functions'', as the concept of a ‘living machine’ seems to have both of them. Generally, referring to a function supposes to explain why its correspondent function bearer occurs and why it is there [18]. For example: if someone asks what a knife is, then we usually appeal to its function as cutting and stabbing tool and if someone asks what a heart is, then we answer referring to its function of pumping blood. Hence, functions are good for causal explanations. However, regarding the products of the synthetic biology we have an ''overdetermination problem'', because we can explain what a trait is referring to both, technical functions and biological functions. Imagine following situation:

A synthetic biologist produces modified bacteria which are susceptible to glucose and that assist the treatment of diabetes in human beings. These bioengineered bacteria have a synthetic toggle switch which is activated when blood sugar levels reaches a tolerance threshold and allows the transcription of a substance to help the uptake of glucose from the blood. The decrease of glucose in blood allows the bacteria to live on.

If we want to explain why the bacteria have a toggle switch, we can say two things: this toggle switch enables the production of a substance, which decreases the amount of blood sugar and hence helps the treatment of diabetes ''or'' this toggle switch enables the production of a substance which decreases the amount of blood sugar and is therefore beneficial for the bacteria (and the occurrence of this toggle switch in the bacteria is the result of a feedback mechanisms involving the exercise of producing the substance). The bacteria also have a synthetic toggle switch, because it was constructed so or because it helps the whole system to live. If both functional explanations are correct ''in the same context'', then we have a faulty overdetermination (two causes for one effect). Publications we worked with: :[17] Holm S (2011a): Biocentrism and Synthetic Biology. ''App Ethics'' 62-74
:[18] Krohs U, Kroes P (eds) (2009): ''Functions in biological artificial worlds''. MIT press, Cambridge
'''Eighth meeting - Technical functionality: solution'''
We decided to work with two different theories of functions in order to encounter the abovementioned overdetermination problem. On the one hand we studied the ICE-theory for the ascription of technical functions by agents ([19],[20]). On the other hand we studied the organisational account of biological functions ([21],[22],[23]). By the products of synthetic biology both ascriptions of functions are possible – although we noticed that the technical function ascription applies imperfectly. Through the analysis of specific situations and counterexamples we showed that the technical function ascription is neither necessary nor sufficient to explain the products of synthetic biology ''per se''. The explanation based on biological functions makes a closure, due to the circular causality of living systems, which makes every reference to human intentionality dispensable. To make this account clear, we can examine the following example:

'''The hidden entities'''

In a fictive secret part of our world a civilisation of human beings with an impressive scientific knowledge existed. They constructed impressive machine-like entities, which were capable of moving around and do things, but not to (re)produce, maintain and organize themselves. Using artificial organic materials they also constructed some bacteria-like living entities, which were able to absolve self-production, self-maintenance and self-organisation. This civilisation was destroyed without leaving anything but these two kinds of entities. We now find these entities, without knowledge of the past civilisation, and try to explain them.

The explanation of the machine-like entities is ad-hoc not possible at all. One could try to explain them under the terms of their physical structures, but certainly without luck. One would probably make an ‘inference to the best explanation’ and, because these functioning machine-like entities cannot (re)produce, maintain and organise themselves, conclude that they were made by intentional beings. In contrast, no reference to human intentionality is needed by the explanation of the bacteria-like entities. A sufficient explanation of these entities can be given by just referring to the circular causality they own. The ahistorical circular causality makes any external cause unnecessary. These considerations show that in the moment in which we are capable of ascribing biological functions to an entity, all references to an ‘intelligent designer’ to explain this entity in itself is dispensable. Therefore, we conclude that the ascription of technical functions to the products of synthetic biology is only possible regarding a human context, but not if we want to describe what they are in themselves. Thus, it is not warranted to say that the synthetic entities follow a ‘human aim’. Moreover, this analysis allows a clear distinction between machines and living beings, making the expression ‘living machine’ necessarily a metaphor. Publications we worked with:
:[19] Vermaas, PE (2006): The physical connection: Engineering function ascriptions to technical artefacts and their components. ''Stud Hist Philos Sci'' A 37: 62-75
:[20] Vermaas, PE, Houkes, W (2006): Technical functions: A drawbridge between the intentional and structural natures of technical artefacts. ''Stud Hist Philos Sci'' 37: 5-18
:[21] McLaughlin, P (2001): ''What Functions Explain. Functional Explanation and Self-reproducing Systems.'' Cambridge University Press, Cambridge
:[22] Mossio M, Saborido C, Moreno A (2009): An Organizational Account of Biological Functions. ''Br J Philos Sci'' 60(4): 813-841
:[23] Saborido C, Mossio M, Moreno A (2011). Biological organization and cross-generation functions. ''Br J Philos Sc'' 62: 583-606

'''Ninth meeting - Conclusion and ethics'''
Finally, we discussed in our last meeting about the implications of our epistemological analysis for the synthetic biology and for society. In addition we studied different ethical approaches and tried to apply them to the products of synthetic biology ([16],[17],[24],[25]). Many of the approaches failed to justify if the synthesised entities have a moral status or not, revealing the necessity of novel bioethical theories. Some of our team members sympathises with Sune Holm’s biocentric view, because he also refers to the organisational account of biological functions for the foundation of his position ([17],[25]). Some other team members believe that the notion of a ‘natural purpose’ and the naturalisation of teleology and normativity (as the organisational account does) need further examination. Publications we worked with:
:[24] Krebs A (eds) (1997): ''Naturethik. Grundtexte der gegenwärtigen tier- und ökologischen Diskussion.'' Suhrkamp, Frankfurt a.M.
:[25] Holm S (2011b): Biological Interests, Normative Functions and Synthetic Biology. ''Philos Technol'' doi:10.1007/s13347-012-0075-6 [[#top|Back to top]]