Artificial Cell Research As a Field That Connects Chemical, Biological and Philosophical Questions

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Year: 2016

Artificial cell research as a field that connects chemical, biological and philosophical questions

Deplazes-Zemp, Anna

Abstract: This review article discusses the interdisciplinary nature and implications of artificial cell research. It starts from two historical theories: Gánti’s chemoton model and the autopoiesis theory by Maturana and Varela. They both explain the transition from chemical molecules to biological cells. These models exemplify two different ways in which disciplines of chemistry, biology and philosophy canprofit from each other. In the chemoton model, conclusions from one disciplinary approach are relevant for the other disciplines. In contrast, the autopoiesis model itself (rather than its conclusions) is transferred from one discipline to the other. The article closes by underpinning the relevance of artificial cell research for philosophy with reference to the on-going philosophical debates on emergence, biological functions and biocentrism.

DOI: https://doi.org/10.2533/chimia.2016.443

Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-135057 Journal Article Published Version

Originally published at: Deplazes-Zemp, Anna (2016). Artificial cell research as a field that connects chemical, biological and philosophical questions. CHIMIA International Journal for Chemistry, 70(6):443-448. DOI: https://doi.org/10.2533/chimia.2016.443 NCCR MoleCulaR SySteMS eNgiNeeRiNg CHIMIA 2016, 70, No. 6 443 doi:10.2533/chimia.2016.443 Chimia 70 (2016) 443–448 © Swiss Chemical Society Artificial Cell Research as a Field that Connects Chemical, Biological and Philosophical Questions

Anna Deplazes-Zemp*

Abstract: This review article discusses the interdisciplinary nature and implications of artificial cell research. It starts from two historical theories: Gánti’s chemoton model and the autopoiesis theory by Maturana and Varela. They both explain the transition from chemical molecules to biological cells. These models exemplify two different ways in which disciplines of chemistry, biology and philosophy can profit from each other. In the chemoton model, conclusions from one disciplinary approach are relevant for the other disciplines. In contrast, the autopoiesis model itself (rather than its conclusions) is transferred from one discipline to the other. The article closes by underpinning the relevance of artificial cell research for philosophy with reference to the on-going philosophical debates on emergence, biological functions and biocentrism. Keywords: Artificial cell research · Autopoiesis · Chemoton · Interdisciplinary research · Philosophy

With the ambition of producing a sim- alytically, the two material categories and between chemistry and biology in the two ple albeit living cell starting from non-liv- research approaches can still be separated. models and the implications for philosophy ing molecules, scientists move from the Sometimes, studying molecules and stud- that their authors are considering. Finally, I classical domain of chemistry to that of ying living organisms go hand in hand, and will give some examples of philosophical- biology. On the one hand, this transition research findings of one classical disci- ly relevant concepts that profit from find- happens at the level of the research subject, pline are often highly relevant for the oth- ings in artificial cell research. This article which changes from non-living molecules er. This does, however, not invalidate the will not provide a complete history of arti- to a living entity. On the other hand, there analytical difference between the chemical ficial cell research nor will it cover all the is a shift at the conceptual level concern- and biological categories with respect to interactions and influences that take place ing the research approach. Chemists tra- material, research approach and addressed between the discussed disciplines. Rather, ditionally study specific molecules and questions. Chemical as well as biological the aim of this article is to raise the reader’s singular reactions. In contrast, biological results and models in the context of this awareness and interest for the inter- and research concepts, models and questions shift raise interesting questions for philos- trans-disciplinary nature of artificial cell focus on the living entity and biologists ophy. More specifically, they are relevant research, and to use this research field as an are most interested in the function that for the philosophy of science and bioeth- example to illustrate fruitful interactions chemical molecules and reactions fulfil ics. The first field reflects on different and influences between the disciplines of in maintaining the life of such entities. methods, concepts, models and findings chemistry, biology and philosophy. This being said, it must be added that the of the sciences in question, and the latter emergence of disciplines such as molecu- deals with ethical implications related to lar biology or biochemistry, have blurred the discussed scientific research. The Transition from Chemistry to the strict separation between chemistry In this short review article, I would Biology in Artificial Cell Research and biology in practice. Nevertheless, an- like to discuss artificial cell research in the context of the three disciplines of chem- In this article, the phrase ‘artificial cell istry, biology and philosophy. Questions research’ is used for research approaches, about life have been the research subject which aim at producing minimal living not only of scientific disciplines but also cells starting from lipid vesicles. The dif- philosophy, social sciences, humanities, ferent contributions to this special issue arts and religions.[1] It will not be possi- show that research on and with artificial ble to address the relationship between all cells can pursue different research objec- of these approaches in detail within such tives and address different research ques- a review article. I thus decided to address tions. It would be inaccurate to describe the relationship between chemistry, biolo- research on artificial cells as a field driven gy and philosophy in two historical mod- by the unique aim to produce living cells. It els that are repeatedly being consulted and is not likely that this ambitious aim will be quoted by current artificial cell research- achieved in the near future; further, scien- ers. As models that describe and explain tists focus on more specific and often more the transition from chemical molecules to applied research questions. Nevertheless, *Correspondence: Dr. A. Deplazes-Zemp biological cells, they directly relate the lab- at least some artificial cell scientists are in- Institute of Biomedical Ethics and History of Medicine oratory work of artificial researchers to the terested in the very general – and cross-dis- University of Zurich Winterthurerstr. 30, CH-8006 Zurich more general questions about life. After an ciplinary – question about the conditions E-mail: [email protected] introduction, I will compare the relation and basic principles of life as well as the 444 CHIMIA 2016, 70, No. 6 NCCR MoleCulaR SySteMS eNgiNeeRiNg

origin of life. In order to be able to produce The chemoton model is an abstraction realistic size and complexity to serve as a an artificial living cell, one needs to start of the minimal living system; it describes source of all other components.[6] What is from a model that outlines the conditions the simplest version of a system that can important with regards to the relation be- and criteria that a minimal cell needs to be called alive. It is present in every liv- tween chemistry, biology and philosophy fulfil in order to be considered as ‘alive’. ing being and absent in non-living entities. in artificial cell research, is the implication The two historical models that I would like Gánti starts from observations of simple of this chemical model for research on life to introduce are being used by influential unicellular organisms and states that all at the other levels. artificial cell researchers as a starting point living cells contain the three subsystems: As previously mentioned, Gánti’s work to develop their model on how a living cytoplasm, membrane and genetic materi- also includes some reflections on the bio- cell could be synthesised from non-living al.[4] For the chemoton model, he reduces logical (rather than chemical) research ap- molecules. The chemoton theory by Tibor these components into the following three proach to study life, which focuses on the Gánti received, for instance, significant at- abstract subsystems (Fig. 1): first, the met- criteria of life. The most inventive aspect tention in the textbook on protocells edited abolic subsystem found in the cytoplasm. of this part of his theory consists in his by Steen Rasmussen and colleagues.[2] The It forms a reaction network that, starting distinction between absolute and poten- second example is the autopoiesis theory from a nutrient X, produces all compo- tial life criteria. The former must apply to by Humberto Maturana and Francisco nents to reproduce itself as well as the other every living organism, while the latter are Varela, which has repetitively been con- two subsystems. Moreover, it releases the not applicable to every individual organism sulted and discussed by Pier Luigi Luisi waste productY. Second, there is the mem- but necessary for the “survival of the living and his collaborators.[3] brane subsystem, which is capable of auto- world”.[4] He lists five absolute life criteria: catalytic growth, and third the information (1) A living organism is an inherent unity Chemoton Model subsystem, a reaction system that can pro- with new qualitative properties compared The chemoton model was developed duce macromolecules by template poly- to its parts; (2) Metabolism provides for by Tibor Gánti, a chemical engineer from condensation. Byproducts of this subsys- transformation of external material and Hungary. He first published this mod- tem are used to form the membrane. Gánti energy by the system; (3) Inherent stability el in his book ‘The principle of life’ in explains that this third subsystem thereby means that the organisation of a living sys- Hungarian in 1971; it was published in is able to control and couple the other two tem remains stable in spite of changes in English in 1987.[4] In this book, Gánti de- subsystems stoichiometrically and to syn- its environment; (4) An information-car- velops the idea that life can be studied at chronise growth.[5] He understands it as the rying subsystem contains the instructions different levels. He speaks of life criteria, abstraction of the genetic material. Modern for origin, function and development of the which fall into the research field of biolo- protocell scientists refer to this model as system; (5) Regulation and control of its gy, the principle of life concerning the laws an early schematic model and honour the processes is characteristic for living sys- behind these criteria that he describes in stoichiometric coupling of the function- tems. The first of the three potential life his chemical chemoton theory, and finally, al elements. However, they also identify criteria is (1) growth and reproduction, an approach to study life as a philosophical limitations of the model, for instance, that which are indispensable for the survival of category.[4] Gánti explicitly discusses and the chemoton model only considers the a species but cannot be found in each or- separates research on life along the three role of metabolism for growth but not for ganism. Gánti’s distinction allows speak- disciplines examined in this article. His maintenance.[5a] Another criticism refers to ing of the controversially discussed feature main focus clearly lies in chemistry, the the feature that the information subsystem of ‘reproduction’ as a life criterion without first level, where he develops his chemo- does not modulate the metabolism, or that being forced to accept the implausible con- ton model. ‘nutrient’ X must be of a practically un- clusion that sterile organisms cannot count as living entities. Capability of hereditary change and evolution is the second poten- Fig. 1. Gánti’s illustra- tial life criterion (2). Again, the possibility tion of his chemoton of potential criteria that concern the living model with its three stoichiometrically world is an elegant solution for the prob- coupled subsystems. lem that heredity and evolution does not A: metabolic subsys- occur at the level of individuals. These tem, T: membrane features can thus not count as criteria to subsystem, V: infor- describe a single organism as living. The mation subsystem. final potential life criterion is (3) mortality. Reproduced with per- As Gánti writes “Non-living systems can- mission from Oxford not die”.[4,p79] On the other hand, death is [4b] University Press. essential for the living world, because it allows for recycling of the organic material. The ‘potential’ nature of this criterion allows counting it as a criterion even though there are living systems, such as singular cells, whose life as an individual ceases by mitosis rather than by death. In this article, the question of how these biological criteria are connected to the chemical chemoton model is of particular interest. On the one hand, the chemoton, as the minimal living system, must satisfy the life criteria, which it clearly does as Gánti describes in detail.[4] On the other hand, Gánti writes that the chemoton theory describes the NCCR MoleCulaR SySteMS eNgiNeeRiNg CHIMIA 2016, 70, No. 6 445

“principle of life” or the “laws uniting [the ginning and end of human life. Whether There is no difference between producer characteristics of life]”.[4, p74] Indeed, each brain death or cardiac death counts as and product, the producer produces itself. of the absolute and potential life criteria criterion for human death is significant, This autopoietic system is captured within depend in one way or another on the organ- for instance, with respect to organ dona- a determined boundary, which itself is of isation described by the chemoton model. tion. The removal of a vital organ from course produced by the system. The sys- This organisation implies that independ- a brain-dead patient seems to be legally tem thus constitutes an autonomous and ent and stable unities with new properties and morally less problematic if the body clearly defined unity. arise. In the chemoton model, this organ- counts as ‘dead’. At the beginning of life, Maturana and Varela emphasise that isation obviously includes metabolism the question of whether a human embryo their theory gets by without reference to a and the information system and allows for should already count as a full human be- genome. As mentioned above, they claim regulation and control. Moreover, it en- ing is important, for example, for the eth- thatthenotionofanautopoieticorganisation sures the possibility of reproduction and ical assessment of abortion. The biologi- is necessary and sufficient to characterise a heredity and thus evolution. Finally, the cal definition of the beginning and end of living system.[8,9] Some modern supporters organisation can be abolished, which leads life has turned out to be difficult, because, of the autopoiesis theory put this claim for to death of the living system. In this sense, although a brain-dead patient or a human sufficiency into question. Pier Luigi Luisi the chemical model is highly relevant for embryo do not live a typical human life, and collaborators support their argument the understanding of the biological criteria. they doubtlessly show certain signs of life. that autopoiesis is not sufficient to distin- What about the transition from chemis- Gánti’s model may provide an explanation guish living from non-living systems with try/biology to philosophy? Although Gánti for this discrepancy. He argues that brain empirical evidence. In collaboration with explains that he does not discuss life as a death should be the death criterion in the Varela, Luisi started to develop models philosophical category,[4] his final chapter case of human life, because secondary life for experimental production of autopoietic and another essay titled ‘Levels of life and ends, even if certain primary life functions chemical systems,[10] which he and his re- death’ do address certain philosophical continue. Analogously, an oocyte or early search group then elaborated and applied implications of his chemoton theory and embryo do have primary but not second- towards the production of ‘autopoietic ves- life criteria.[7] The final chapter deals with ary life, which starts only with the func- icles’ that are not alive.[11] They described the responsibility of the biologist, which tioning of the brain, the information and such a vesicle as: “a synthetic vesicle that Gánti explains against the background of control subsystem at the secondary level. absorbs a particular molecule from the his chemoton theory and life criteria.[4] However, the ethically relevant question of medium, and by so doing, reproduces it- The irreversible functioning of the infor- why secondary life is the decisive criteri- self via an autocatalytic process“.[3a, p170] mation subsystem, which in existing living on to decide whether an action is morally What is the difference between such a ves- organisms is implemented in the genetic legitimate or not cannot be answered with icle and a simple living organism, for in- programme, is the reason that direct or in- reference to the scientific model alone. It stance a bacterium? Bacteria do not take up direct effects on this system cause irrevers- demands some additional ethical argumen- their nutrients as a result of ‘coincidental’ ible changes. Ganti writes: “It is this factor tation, which would go beyond the scope chemical reactions. Their pre-existing me- of irreversibility which makes biological of this article. The purpose of these com- tabolism only processes specific nutrients. manipulation incomparably more dan- ments is to show, how discussions pertain- This is a selective interaction with the en- gerous than manipulations performed on ing to ethics and other branches of philos- vironment. Although Maturana and Varela non-living systems. One can also produce ophy can profit from Gánti’s chemical and did not include this aspect into their theory catastrophes in the non-living world, but biological theory. of autopoiesis, it nevertheless has an im- sooner or later every bad thing comes to an portant place in their work. They discuss end. However, in the living world nothing Autopoiesis Theory this particular interaction that living things really comes to an end, neither good nor The second theory that has been influ- have with their environment as ‘cogni- bad. […] Thus the effect of these events is ential concerning the material transition tion’. The choice of this term was unfor- in practice endless”.[4, p154] This inherent from chemistry to biology in the research tunate, because it is often associated with risk in “biological manipulations” leads to field of artificial cells is the autopoiesis consciousness, which can certainly not be particular responsibilities for the biologist. theory. Two Chilean biologists, Humberto found in simple organisms such as bacte- In the previously mentioned essay, Maturana and Francisco Varela, developed ria. However, the meaning that Maturana Gánti advances his theory to animal life; this theory. Their book ‘Autopoiesis and and Varela give to this term has no connec- he speaks of two different kinds of life: pri- Cognition, The Realization of the Living’ tion to a nervous system or consciousness. mary life that can be found already at the was first published in Spanish in 1972; the Rather, they argue: “A cognitive system prokaryotic level and secondary life, which English version followed in 1980.[8] The is a system whose organization defines only occurs at the level of metazoa (multi- authors start from the question of whether a domain of interactions in which it can cellular animals). Interestingly, secondary there is a necessary and sufficient criteri- act with relevance to the maintenance of life is organised by the same three-sub- on for living organisms. For them, there is itself.”[8, p13] It is thus the organisation of system structure defined by the chemoton such a criterion, namely in the organisation a living organism and therefore its auto- model. Analogous to the membrane sub- of living systems, that allows them to be poiesis that defines the cognitive domain system, there is a subsystem governing the autonomous and self-producing unities. of interaction. However, as the mentioned geometrical structure based on skin and Maturana and Varela introduced the term experiments of Luisi’s group on non-liv- bones. There is a subsystem involving a ‘autopoiesis’ for self-production (ancient ing vesicles showed, not every type of au- digestive tract, secretory organs and blood Greek: auto = self, poiesis = creation, topoietic organisation leads to cognition. circulation that governs the metabolic pro- production). Living organisms constant- Together with the physicist and philos- cesses in the whole animal. Finally, there ly maintain their own organisation; they opher Michel Bitbol, Luisi argues that it is an information and control subsystem in are organised as a network of processes, is the metabolism, which implements the the form of the nervous system. which produces components that, in turn, active and selective interaction with the The distinction between primary and participate in processes that realise and re- environment that is characteristic of living secondary life is interesting for philosoph- generate the network. This is to say that systems.[12] It can thus be concluded that ical and ethical discussions about the be- an autopoietic system is self-referential. autopoiesis alone is not sufficient to char- 446 CHIMIA 2016, 70, No. 6 NCCR MoleCulaR SySteMS eNgiNeeRiNg

acterise life, but together with the condi- view was part of a “Zeitgeist”, which led Luisi identifies another divergence be- tion of cognition the sufficiency criterion to the simultaneous development of these tween the two theories in terms of their seems to be fulfilled. similar theories in two entirely different aim and purpose.[3a, pp178–179] Although The autopoiesis theory has been highly environments.[3a, pp177–179] Gánti himself did not experimentally work influential in social sciences and related A closer look at the content of the two on artificial cells, he explicitly observed branches of philosophy. De facto it has re- theories reveals more detailed similarities that his theory “involves the strategy of ceived much more attention in these fields underneath the holistic approach that both the synthesis of living systems”[3a, pp132ff] than in the biological context where it was theories share. Not surprisingly, for both and can be consulted to explain the origin developed. Probably the best-known ex- of them, the compartment or membrane of life.[3a, pp140ff] The aim of Maturana and ample is Niklas Luhmann’s development plays a central role. This certainly is one Varela, in contrast, was to develop a theory of systems theory. He starts from the idea reason why these are the theories used by to describe what life is. In the context of that social systems consist only of commu- artificial cell researchers. The metabolism, this review article, this difference can be nication. He further applies the idea of au- too, plays a key role in both theories. This related to the different disciplinary back- topoiesis to these systems. This means that is true, at least, if one compares the chem- grounds of the authors. The central aspect social systems are constituted and differen- oton model with Luisi’s version of the au- of Gánti’s theory is driven by a chemical tiate from their environment by generating topoiesis theory, which includes cognition approach even though he also touches on their own elements (communication) and (implemented in the metabolism) as a nec- biological questions with his life criteria. maintain themselves strictly by internal essary element for life. His main interest concerns the biochemical operations.[13] Luhmann writes: “Social With respect to Gánti’s third require- reactions that must take place in a mini- systems use communication as their par- ment – the information subsystem – the mal living system and how these reactions ticular mode of autopoietic reproduction. two theories differ. Although, as stated by are coupled. He supports his model with Their elements are communications which Luisi, neither of the theories sets its prima- various chemical equations. Maturana and are recursively produced and reproduced ry focus on nucleic acids, Gánti’s informa- Varela, on the other hand, are biologists by a network of communications and tional subsystem does refer to the genetic interested in the phenomenon of life, in which cannot exist outside of such a net- system as carrying out a function that is what distinguishes living from non-living work.”[14, p174] In contrast to the biological necessary for life. Several of Gánti’s life things. Therefore, the phenomenological context, the material aspects of societies, criteria are conceptualised as depending on description was more central than the pro- such as human bodies, are thus part of the an informational system in the form of a he- cesses that implement this organisation. environment, which itself is not usually reditary programme. In contrast, Maturana However, as discussed, both theories have autopoietic. and Varela emphasise that reference to a far-reaching implications that go beyond The original authors of the autopoie- programme or information system is not their discipline of origin. Interestingly, the sis theory had different opinions about the requested for the characterisation of life. transfer from one discipline to the other(s) applicability of their theory to social sys- The development of the genetic system works differently in the two theories. tems. Maturana was in favour of the idea of is, for proponents of the autopoiesis the- Gánti’s ‘chemical’ chemoton model autopoiesis for social systems. In contrast, ory, one way to implement autopoiesis or serves as an explanation for the biological Varela believed that talking about auto- maybe even an evolutionary consequence criteria of life. These criteria are a con- poiesis in social systems was an “abuse of of autopoiesis. Reproduction and evolu- tinuation and further development of the language” because the notion of “bounda- tion depend on autopoietic units and are chemical theory. They are derived from ry” as it was understood in autopoiesis did therefore secondary to the feature of au- the chemoton model. Moreover, this mod- not apply to social systems.[3a, p176] topoiesis. A kind of Lamarckian evolution el serves as an explanation for primary and already acts on very simple autopoietic en- secondary life, which explains certain phil- tities. If self-reproductive autopoietic enti- osophical and ethical implications as dis- Comparison and Discussion of ties are able to adapt to their environment cussed above. In the case of autopoiesis, the Chemoton and Autopoiesis and reproduce in an adapted way, they will it is the model and not its conclusions that Theories be more successful than non-adapted en- is transferred to the different disciplines. tities. In that sense, Maturana and Varela Luisi, as a chemist, tried to implement the If one sets out to compare these two write: “In autopoietic systems evolution is biological model towards the chemical theories with regards to the transition from a consequence of self-reproduction.”[8, p104] construction of artificial cells. This direct chemical molecules to biological cells, one In the course of evolution as it happened transfer is even more evident in the shift is first struck by some marginal similarities on earth, the nucleic acid system became to social sciences and philosophy, where in the circumstances of their origin. Both the key-feature of the self-reproduction again, it is the model of organisation that theories were developed independently of living entities. However, theoretical- is applied to social systems. So, these two from each other in countries outside the ly other models that involve the two key theories give two different examples of scientific centres in the early 1970s, and processes of evolution – namely self-re- how different academic disciplines can they were both first published in languages production and variation – are conceivable profit from each other’s research. In the that were not influential in sciences. This for autopoietic entities.[8, pp102–106] From first example, the results and conclusions background may, to some extent, explain the perspective of Gánti’s theory, one may of one discipline are used to address re- why neither of the theories received much question how reproduction of a membrane search questions arising in other disci- attention in the mainstream biochemical subsystem and a metabolism (as required plines. In the second case, an explanatory community. Luisi sees other reasons for this for cognition) could practically be coordi- model in one discipline is used to develop neglect in the fact that neither of the theo- nated, if not by a type of information sub- explanations to questions arising in other ries focused on nucleic acids as the main system. However, even if an information disciplines. players, and that they provided systemic system was requested for complex forms Finally, there is another ‘external’ dif- models rather than focusing on the impor- of life as we know them on earth, it could ference that does not pertain to the content tance of singular reactions. Nevertheless, be argued that it is secondary to the feature of the two theories. It concerns how they Luisi explains that the idea to look at cel- of autopoiesis, since it ‘evolved’ as a con- have been received within philosophy. In lular life from a holistic, systemic point of sequence of autopoiesis. contrast to the autopoiesis theory, which NCCR MoleCulaR SySteMS eNgiNeeRiNg CHIMIA 2016, 70, No. 6 447

received more attention in social sciences processes.[18] Emergent properties cannot something can be good or bad for the liv- and philosophy than in biology, the impli- be predicted from the non-relational prop- ing system or in other words, it can support cations of Gánti’s model for philosophy, erties of the components of the system. In or go against the interest[25] of the living has hardly been discussed within this dis- that sense, Bedau suggests that the state of organism. Another condition for having cipline. Thus, there would have been po- the system can only be derived from the interests in this sense is related to the auto- tential for an even more fruitful interaction state and dynamics of its parts by simula- poiesis and chemoton theories. In order to between the disciplines with respect to the tion.[18] These ‘emergentist’ positions do be able to have interests, living organisms implications of the chemoton model.[15] not refer to any non-scientific metaphysi- must be autonomous and able to maintain cal explanations for emergent phenomena themselves, otherwise, their maintenance or properties. They simply suggest that at would not be in their own interest, but in Further Philosophical Questions a certain level of complexity, we need new that of their maintainer. The biocentric Raised by Research on Artificial types of scientific explanations, which – at statement that having interest is the criteri- Cells least at the moment – cannot be derived on for being morally considerable, because from explanations at lower levels. something can be against the interest for As mentioned in the outset of this re- these entities, is certainly controversial. view article, the material transition from Functions Nevertheless, it is a good example for how chemical molecules to biological cells ac- The observation that living entities scientific conclusions can be informative cording to the previously described mod- have different subsystems and elements for a philosophical subdiscipline. els goes along with a conceptual shift in that contribute to maintaining this unity, research questions and approaches. The is the starting point for another debate in focus on singular chemical reactions and the philosophy of biology. This is the dis- Conclusions players shifts to the effects that these re- cussion about biological functions. One actions have for the new biological unity. can distinguish between roughly two ap- In the emergence of disciplines such This latter transition has various impli- proaches to define biological functions. as synthetic biology, systems biology or cations for philosophical research, as the The first approach addresses what Justin various engineering disciplines (for in- third discipline discussed in this article. Garson called “etiological theories of stance molecular systems engineering) the The artificial cell has first been discussed functions”.[19] In a simplified description boundaries between the classic disciplines with respect to its chemical construction of these theories, it can be said that they are often blurred. One could speak of new and its biological criteria; now I will ad- try to give an answer to the question “why transdisciplinary research fields. This de- dress some of its philosophical character- is this function there?”, for instance, why velopment is explicitly not the focus of the istics. I already mentioned some implica- do animals have eyes?[20] Modern answers review article at hand. Here, it was my aim tions and applications that resulted directly to this question refer to evolutionary ex- to discuss how the three different approach- from the discussed scientific theories for planations. Studies in evolution biology es of chemistry, biology and philosophy philosophy and theoretical social sciences. are thus more informative for this approach can profit from each other (summarised in In this section, I would like to briefly in- than research on artificial cells. The second Fig. 2). It may be difficult to assign artifi- troduce three other concepts in philosophy approach deals with consequentialist theo- cial cell research to one classic discipline, that occur with the material transition from ries of function in Garson’s sense. These but it is clearly driven by different research chemical molecules to a biological cell as theories roughly understand functions as questions, approaches and interpretations a unity and the associated conceptual shift contributions to something, for instance to typical for the individual disciplines. I in research questions and approaches. I the survival of the living organisms.[21] The have tried to show how these approaches only refer to these discussions at the level discussion of functions in the context of ar- were combined and how they influenced of simple unicellular forms of life. Most tificial cells primarily supports consequen- each other. Two different sources for the of these questions are then further extend- tialist theories. If one understood functions fruitful nature of this interaction have been ed to what Gánti would call ‘secondary exclusively etiologically with reference to described. First, there is inspiration by an life’ in animals and humans, however, this evolution, one would need to conclude that exchange of research results: The notion of raises many more issues that cannot be ad- at the level of artificial cells, there cannot the chemoton model as a minimal living dressed here. be any biological functions, because they system supported and explained Gánti’s do not have any evolutionary history.[22] life criteria, and served as an explanation Emergence for the ethically relevant distinction be- The philosophical discussion, to which Interests tween primary and secondary life. The em- the transition from chemistry to biology The last point that I will briefly intro- pirical observations of emergent proper- probably contributes most directly, con- duce concerns a much smaller debate than ties, the functions of different subsystems cerns the topic of emergence.[16] How can the two previous topics. Biocentrism is a and the implications of these observations we understand or explain the relation be- position in environmental ethics, which ar- for the new biological unity was the start- tween the chemical basis of living systems gues that all living organisms are morally ing point for studies in philosophy of biol- and the novel properties that they have as considerable.[23] This means that to harm ogy and bioethics, such as those on emer- living unities?[17] This difficulty not only living organisms can morally only be justi- gence, functions and biocentrism. Second, arises at the transition from chemistry to fied, if one can give good reasons, why it is the exchange of an explanatory model can biology.A classic example to discuss emer- necessary to do so. But why should this be be stimulating. The model of autopoietic gent properties is water, whose properties true specifically for living organisms? For self-organisation has been understood as a of being transparent and liquid cannot be the answer to this question, at least some criterion for life by Maturana and Varela as explained with respect to the properties of authors directly refer to the previously an instruction for chemical synthesis of the [24] singular H2O molecules. Marc Bedau de- mentioned discussion on functions. cell by Luisi, and as a model for societal fines emergent phenomena as phenomena External events can support or interfere interactions by Luhmann. It can be hoped, that are, on the one hand, generated by un- with these functions and thereby with the that other emerging transdisciplinary fields derlying processes, and on the other hand, maintenance of a living organism. This is will be open for an equally stimulating in- are autonomous from these very same morally relevant, because it means that teraction between the involved disciplines. 448 CHIMIA 2016, 70, No. 6 NCCR MoleCulaR SySteMS eNgiNeeRiNg

[15] The article mentioned in ref. [7] is an exception, which does provide a thorough analysis of important philosophical implications of Gánti’s model. It does, however, not address any ethical issues and thus does not take up the issues that Gánti raised himself. [16] For a multifaceted introduction and discussion of this topic, which includes the scientific perspective, see M. A. Bedau, P. Humphreys, ‘Emergence’, The MIT Press, 2008. [17] As this guiding question indicates, I discuss ‘emergentism’ here as an epistemological theory that captures how we explain and understand the world rather than an ontological theory that explains how the world is constituted. This reflects the approach to emergence taken by many contemporary authors, whereas historical theories often were understood in the latter sense. T. O’Connor, H. Y. Wong, in ‘The Stanford Encyclopedia of Philosophy’, Ed. E. N. Zalta, Stanford University, http://plato. stanford.edu/entries/properties-emergent/, Stanford, 2012, accessed January 2016. Fig. 2. Influences and inspiration between different disciplines in artificial cell research, the chem- [18] M. A. Bedau, Philosophical Perspectives: oton theory and the autopoiesis theory. The arrowheads illustrate how one discipline has influ- Mind, Causation, and World 1997, 11, 375. enced the others, as discussed in the text. Additional interactions are possible and likely. Artificial [19] J. Garson, in ‘A Companion to the Philosophy of cell researchers have referred to the chemoton- and the autopoiesis theory as historical models Biology’,Eds.S.Sarkar,A.Plutynsky, Blackwell that have influenced their research (1,2). Gánti writes of research on life at three different levels. Publishing, Blackwell Reference Online, http:// The chemoton model describes the principle of life, which explains absolute and potential life cri- www.blackwellreference.com/subscriber/ tocnode.html?id=g9781405125727_chunk_ teria (3). These life criteria support, for instance, particular responsibilities of scientists (4) and the g978140512572730 2008, accessed January principle of life constitutes the differences and parallels between primary and secondary life (5). In 2016. artificial cell research, the chemical composition of cells informs biological questions on the origin [20] Besides Garson[19], another informative review and minimal conditions of life (6). The production of a living cell goes along with the appearance on the functions debate is provided by Mark of emergent properties, biological functions and – biocentrists argue – moral considerability (7). Perlman: M. Perlman, The Monist 2004, 87, 3. The autopoiesis model, which was developed in the biological context, has inspired artificial cell [21] Examples for representatives of the two chemists (8) as well as social scientists and philosophers (9). theories are Robert Cummins as a supporter of a consequentialist theory: R. Cummins, in ‘Philosophy of Biology, an Anthology’, Eds. A. Rosenberg, R. Arp, Wiley-Blackwell, Malden, 2010, p. 164. and Ruth Milikan as Acknowledgements [6] S. Rasmussen, M. A. Bedau, J. S. McCaskill, N. a representative of etiological theories: R. I would like to thank Sebastian Wäscher H. Packard, in ‘Protocells, Bridging Nonliving G. Milikan, ‘Language, Thought, and Other and Daniel Gregorowius for their valuable and Living Matter’, Eds. S. Rasmussen, M. Biological Categories’, Bradford Books /MIT A. Bedau, L. Chen, D. Deamer, K. D. C., N. comments on an earlier version of the man- Press, 1984. H. Packard, P. F. Stadler, The MIT Press, [22] Alternatively, I have suggested an adaptation of uscript. This publication is supported by the Cambridge, MA London, 2009, p. 71. GaryVarner’s etiological definition of biological Swiss National Science Foundation as part of [7] For a more detailed discussion of the functions to deal with synthetic organisms. G. the NCCR Molecular Systems Engineering. philospohical implications of Ganti’s work, for E. Varner, The Southern Journal of Philosophy instance, of his notion of ‘cycle stoichiometry’ 1990, 28, 251; A. Deplazes-Zemp, Environ. Received: March 22, 2016 or for a discussion about the ‘unit of evolution Values 2012, 21, 63. This adaptation would see: J. Griesmer, in ‘The Principles of Life’, allow for the characterisation of biological [1] a) A. Deplazes-Zemp, N. Biller-Andorno, Eds. T. Gánti, E. Zsathmary, J. Griesmer, functions not exclusively by their evolutionary EMBO Rep. 2012, 13, 959; b) A. Deplazes- Oxford University Press, Oxford, 2003. history but also by the fact that they can be Zemp, D. Gregorowius, N. Biller-Andorno, [8] H. R. Maturana, F. G. Varela, ‘Autopoiesis and adapted through evolution in the future. Nanoethics 2015, 9, 179. Cognition, The Realization of the Living’, D. [23] K. Goodpaster, J. Philosophy 1978, 75, 308. [2] S. Rasmussen, M. A. Bedau, L. Chen, D. Reidel Publishing Company, Dordrecht, 1980. [24] For instance, the biocentrist, Gary Varner, Deamer, K. D. C., N. H. Packard, P. F. Stadler, [9] F. G. Varela, H. R. Maturana, R. Uribe, refers to his etiological definition of biological ‘Protocells, Bridging Nonliving and Living BioSystems 1974, 5, 187. functions in order to explain (morally relevant) Matter’, The MIT Press, Cambridge, MA [10] P. L. Luisi, F. G. Varela, Orig. Life Evol. Biosph. interests in living organism.[22] London, 2009. 1989, 19, 633. [25] Importantly, by arguing that living organisms [3] a) P. L. Luisi, ‘The Emergence of Life, From [11] H. H. Zepik, E. Blochliger, P. L. Luisi, Angew. have interests, biocentrists are not claiming Chemical Origins to Synthetic Biology’, Chem. Int. Ed. 2001, 40, 199. that simple living organisms have desires or Cambridge University Press, Cambridge, 2006; [12] a) M. Bitbol, P. L. Luisi, J. R. Soc. Interface intentions, but only that something can be good b) P. Stano, P. L. Luisi, Chem. Commun. 2010, 2004, 1, 99; b) L. Damiano, P. L. Luisi, Orig. or bad for them. 46, 3639. Life Evol. Biosph. 2010, 40, 145. [4] T. Gánti, in ‘The Principles of Life’, Eds. [13] A. Ryan, J. Bohman, in ‘Routledge Encyclo- T. Gánti, E. Zsathmary, J. Griesmer, Oxford pedia of Philosophy’, https://www.rep. University Press, Oxford, 2003, p. 55. routledge.com/articles/systems-theory-in- [5] a) J. Griesmer, E. Szathmary, in ‘Protocells, social-science/niklas-luhmanns-systems- Bridging Nonliving and Living Matter’, Eds. S. theory, 1998, accessed, January 2016. Rasmussen, M. A. Bedau, L. Chen, D. Deamer, [14] N. Luhmann, in ‘Sociocybernetic Paradoxes, K. D. C., N. H. Packard, P. F. Stadler, The MIT Observation, Control and Evolution of Self- Press, Cambridge, MA London, 2009, p. 481; steering Systems’, Eds. F. Geyer, J. van der b) T. Gánti, ‘The Principles of Life’, Oxford Zouwen, SAGE Publications, London, 1986, University Press, Oxford, 2003. p. 172.