1. Introduction

The fundamental question of what is life is and how it can be defined has occupied mankind for centuries and has recently gained increasing attention in several fields of emerging biotechnologies, especially within synthetic biology (SB) [1–3]. In general, SB is understood as an umbrella term covering a diverse field of scientific practices with different agendas and methodologies. Hence, it combines varied disciplines, such as biology, physics, chemistry, and engineering. SB promises to provide profound new insights about the characteristics, principles, and origins of life and nature [4, 5] as its underlying scientific objective is to gain a deeper and more comprehensive understanding of biological organisms, their features and central organizational principles. This is achieved by conceptualizing and finally constructing novel biological systems consisting of newly modularized components. The vision of generating new forms of life–as well as the related successes postulated by scientists within this field [6]–challenges traditional concepts of life and nature as well as classical distinctions between living and non-living matter [5, 7, 8]. Thus, these (expected) developments urge us to reconsider questions related to the central principles and characteristics of life and living and stimulate both the scientific and the ethical debate on defining life.

The question of what life is and of whether or not it is a meaningful or even possible scientific endeavor to search for a definition of life has a long-reaching history [9]. While Aristotle argued that life has to be understood as a fundamental, irreducible property of nature [10], it was Descartes (among others) who defined life as a universal mechanism [11]. During his engagement with the mechanistic definition of life, Kant responded by defining life as the capacity for self-determination [12]. Thus, in his understanding, life is a form of causality, which itself cannot simply be explained in an empirical-causal way. As a consequence, several scientists built upon this idea of Kant and merged it with Aristotle’s concept. Against the mechanical perspective, they postulated that living organisms contain some non-physical element, which fundamentally distinguishes them from non-living entities. This more or less strict dichotomy between mechanistic and vitalistic definitions of life spilled over into the twentieth century, especially during the time that biochemists were defining their field as a separate discipline from chemistry or physiology. There were several approaches in both the natural sciences as well as philosophy, trying to revive the debate again. Within the natural sciences this was the famous work of Schrödinger [13] and within philosophy the work of Whitehead [14] as well as of Plessner [15].

The current debate has revisited the concepts and theories of life. This is especially the case because natural scientists, as well as philosophers, are facing the question of whether or not it is possible to create novel forms of life from scratch [16–18]. Despite manifold attempts on a definition of life, there is no consensus on the necessary and sufficient conditions for life. This is even true for the attempt to define life in terms of a list of distinctive properties that distinguish living organisms from non-living [19, 20]. Although there is some overlap, there is a set of similar but often not congruent lists, each of them trying to comprehensively define life [21]. Additionally, these lists of criteria seem to function as fuzzy concepts by including or excluding entities, which tend to blur the lines between living and non-living [22]. This applies for instance to viruses, which are not able to reproduce on their own, or crystals which–under some circumstances–seem to be able to grow. One possible solution in dealing with these challenges and the fact that no scientific consensus can be reached may be to reject the assumed need and related attempts to establish a definition of life. This may be due to the notion that life is an irreducible fact about the ‘natural world’ and the related incapability of definitions to mark out natural kinds, or the notion that life is an irreducible, fuzzy, vague and too broad concept [23–26].

In general, there are two distinct kinds and uses of definitions of life that are discussed in the literature most predominantly [3]: Fixed definitions with an ontological claim, which aim at demarcating life by carving out natural kinds and are based on the generalization of characteristics of all forms of living [26] on the one hand and flexible “operational definitions” [3] with an instrumental claim serving as theoretical tools that guide debates and experiments [27] on the other. As Bich and Green (3) argue, the aforementioned critique addresses primarily the first category of definitions of life and assumes that a definition’s basic purpose is to establish a set of universal criteria of living objects. In contrast, they indicate that within the current scientific discourse in emerging biotechnologies, such as SB, the issue of defining life has a more pragmatic utility in the sense of operational definitions that serve as theoretical and epistemic tools in scientific practice. By means of exemplary definitions of life of leading scientists within the field of SB [e.g. 1, 27] they show that these conceptualizations influence the choice of the conducted experiments, the research programs as well as the assessment of scientific results.

While assuming, that there is a fundamental entanglement between the used fundamental concepts on life and the used approaches and pursued goals within SB [28–31], there is only little knowledge about the notions and concepts of life which are used by the scientist themselves. Against this background, this article first scrutinizes the underlying epistemological presumptions of life and living matter. Second, we ask which implications the different epistemological concept of life has on the conducted practices and endeavors within SB. In spite of the widespread assumption on the anticipated scientific advances within SB, there is a lack of empirical research examining the specific perceptions and underlying notions of life and living matter of scientists working in the field of SB. To fill in this research gap, we conducted a qualitative interview study with scientists that addresses the following main questions: 1.) How do researchers in the field of SB conceptualize (synthetic) life and living matter? 2.) Which basic principles, characteristic features, and distinguishing dimensions underlie their approaches to life?

2. Study design

The present interview study is based on 20 semi-structured interviews with scientific experts working as researchers in the field of SB. The research team conducting the study holds expertise in sociology, ethics and biology and has a long-standing expertise on the ethical and philosophical issues with regard to SB. This has played an important role in identifying the scope of this study and helps us to get into touch with the leading figures in the field of SB.

The general focus of our investigation is on the scientific (and not on the more application-oriented, industry-driven) part of SB. This is due to the fact that merely scientific approaches within this field directly address questions of the concept, principles and origins of life following a specific research methodology and agenda [32, 33]. The interview study was conducted from autumn 2017 until the beginning of 2018. The interviewees were selected by a contrasting sampling method in order to obtain a heterogenic sample with wide-ranging structural variation within the field of SB. Such a contrasting case selection during data collection and analysis aims at exploring the heterogeneity of the research field in order to enable a generalization of the reconstructed patterns even on the basis of a relatively small sample [34]. Initially, we predefined contrasting typological sampling criteria in terms of gender, scientific background, professional position and the research approach of the scientists. On the basis of these features, in a first step, we selected and recruited via email leading scientific experts who are internationally recognized for their work within the field of SB (h-index > 19). In a second step, utilizing snowball-sampling [35], we contacted further researchers (mainly postdocs) following the recommendations of the initially interviewed senior scientists, who thus served as multiplicators. In total, we asked 24 researchers to participate in the study. Two of the senior researchers, as well as two of the postdocs, were not able to attend because of time issues. The overall sample provided a range of experts in SB across Germany with different scientific backgrounds and professional positions (see Table 1): it consisted of senior scientists, who were all full professors (n = 11), as well as junior scientists (postdocs) in a mid-level position (n = 9) and included experts being trained as biologists and biochemists (n = 10), physicists and biophysicists (n = 5), chemists (n = 3) and engineers (n = 2).

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Table 1. Sample structure of the interview study.

https://doi.org/10.1371/journal.pone.0235808.t001

The interviews were planned as semi-structured, guideline-based expert interviews [36, 37], using a set of open questions on specific pre-existing topics in a flexible running order. The underlying strategy was to account for both comparability and openness, aimed at maintaining a continuous narrative process of the respondents. The interview guide addressed four main topics: 1.) perspectives on SB and self-conception as a researcher in this area, 2.) approaches to life, 3.) assessment of current research activities and envisioned future prospects of SB, 4.) anticipated ethical and societal implications of SB. Depending on the preferred language of the respective scientist, the interviews have been conducted either in German or English. The interviews lasted between 25 minutes and almost one and a half hours, with an average duration of around 45 minutes. As usual, informed consent for participation in the interview study was obtained in writing from all respondents.

The interviews were audio-recorded and transcribed word-for-word for further analysis. In cases where the interview has been conducted in German, the transcript has been translated by a native speaker and been double-checked by the research team [38]. All personal identifying data of the participants were anonymized. The central aim of the analysis was to go beyond the manifest content of the respondents’ statements by revealing underlying patterns of interpretation and argumentation as rather implicit structures of meaning. For this purpose, we conducted theoretical coding according to central principles of the approach of Grounded Theory [39–41]. The overarching categories and their assigned codes were mainly developed inductively, which means that they are based on findings from the empirical material. Furthermore, the development of the semi-structured interview guide was embedded into an in-depth analysis of the ethical and philosophical literature regarding concepts of (synthetic) life. The reason for this was to develop and proof the interview design against the background of the current state of debate. As a first step, a sequential single-case analysis was carried out by means of open coding in order to reconstruct the different perceptions and conceptualizations of life in detail and to build initial codes. In a second step, following axial coding, the relations between the different cases and codes were explored in-depth, and the most relevant codes were grouped around a few central categories with certain subcategories. All categories and codes were validated internally by an intercoder consensus of three researchers who discussed their interpretative results until a shared understanding was reached. On the basis of minimal and maximal contrast, we identified four basic concepts of life, which all interviewed scientific experts could be assigned to. The crucial subcategories for conceptual differentiation with regard to the underlying patterns of argumentation addressed the following relations, understood here as distinguishing dimensions of life as a border phenomenon: 1.) differentiation between living and non-living, 2.) differentiation between natural/non-synthetic and artificial/synthetic, especially with regard to the assessment of the generation of synthetic organisms, 3.) differentiation between life and living objects.

3. Basic concepts of life in synthetic biology

Based on the empirical data we reconstructed four basic concepts of life, which can be understood as the interviewees’ experience-based approaches to (synthetic) life. As heuristics they do not operate with predefined, specific criteria that are put into a “set of mutually dependent necessary conditions” [3] which is a crucial aspect of (operational) definitions. Nevertheless, they go beyond the simple collection of “tentative criteria” [42] for life because of their overarching, more abstract, and generalizing character and claims. Hence, the present basic concepts of life can be located at a preliminary stage of operational definitions of life mentioned at the beginning of the paper. Although these concepts are more fundamental and less concrete than definitions, they play an important role in the respective scientific practices.

The reconstructed basic concepts of life are: 1.) life as a stage model based on a list of properties of living matter, 2.) life as a non-definable continuous process starting with the origin of life, 3.) life as a hitherto undiscovered general principle, and 4.) life as a relational, intuitive concept depending on subjective views. In the following sections each conceptualization will first be described in a general manner, and second in terms of the three distinguishing dimensions underlying the patterns of argumentation of the interviewees. To provide a better overview, Table 2 shows all the results in advance.

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Table 2. Overview of the concepts of life and their underlying distinguishing dimensions.

https://doi.org/10.1371/journal.pone.0235808.t002

4. Discussion and conclusion

Individual understandings and implicit definitions of life affect scientific debates and research practices within SB: they have an impact on research agendas and activities related to the respective objectives and distinctive features of possible domains of investigation as well as on the definition and evaluation of forms of synthetic life [3, 49]. Our/The study most importantly shows that there are multiple and diverse underlying concepts of (synthetic-) life in the field of SB. The scientists’ concepts of life range from an understanding that underpins traditional biology and describes life as a list of properties shared by all forms of living matter [e.g. 20, 21, 43, 44, 45] to the perception that life is a non-definable, continuous process, which is in line with contemporary philosophical and scientific suggestions [23, 24, 26]. These concepts also range from a perspective that refers to common biological and philosophical concepts of emergence [2, 46] and conceptualizes life as a hitherto undiscovered general principle, to an understanding that is related to contemporary constructivist approaches within philosophy and social science [47, 48] by defining life as a relational, intuitive concept depending on subjective views. Finally, by comparing the four reconstructed conceptions of (synthetic) life and their underlying patterns of argumentation, it becomes evident that all of them, at least implicitly, refer to the same distinguishing dimensions, namely the differentiation between living and non-living, natural/non-synthetic and artificial/synthetic, and between life and living. Within each of the concepts, these distinctions serve as a basis or starting point to describe the characteristic relations and boundaries of life, although the conceptual approaches outline the respective distinctions in different ways. Thus, on a general level, the three identified distinguishing dimensions can be considered fundamental indicators to define life as a border phenomenon, which is oscillating between certain markers of differentiation, serving as dichotomous or at least distinctive poles.

The identified different basic concepts do not provide a simplified, solely mechanical understanding of life or the image of living matter as a controllable artifact, but rather imply complex conceptual approaches to life and living matter.

Nevertheless, the provided analysis has a limitation: the study is based on interviews with scientific experts working as researchers in the field of SB. Thus, the general focus of our investigation is on the scientific part of SB. However, the understanding of life of synthetic biologists working in more application-oriented, industry-driven fields aiming at developing specific applications (e.g. in medicine, biofuel production, etc.) might differ from the differentiated concepts described above or have a stronger focus on an engineering approach to living organisms. Therefore, further empirical research focusing on application-driven SB has to be done. Moreover, from a socio-ethical point of view, further research should examine the specific links to certain underlying theoretical foundations from which the reconstructed heuristic concepts derive their meaning in more detail. Within this context, an interesting further-reaching question would face the normative understandings and evaluations which underlie the different conceptions of life.

Regarding the influence of the synthetic biologists’ basic concepts of life on their scientific practice, our analysis indicates several implications on the modes of practices within SB, which will be outlined for each conceptualization in the following: within the first analyzed conception, life is defined as a stage model based on a list of biological and physical properties shared by all living matter. This understanding of life addresses the following research questions in particular: what do we have to define as the necessary and sufficient properties or features of life and living matter and how can we construct them synthetically? How simple can an organism be with regard to its properties and still be considered living? Thus, an important scientific task is to identify, examine and (re-)construct the essential features of basic biological systems, to put them together step by step and to implement them in synthetic objects through a mix of imitating nature and constructing from scratch. Accordingly, the future aim is to generate novel living organisms consisting of natural as well as synthetic components understood as building blocks. Regarding the assessment of (envisioned) scientific results, this means that novel objects constructed by means of SB might be labeled as synthetic forms of life or living matter, which would then lead to the ascription of an equal or at least similar normative status compared with non-synthetical organisms.

Scientists assigned to the second conception understand life as a non-definable, continuous process starting with the origin of life. They focus on such research questions as: where are the origins of life? How can the fluent transitions between non-living and living matter and the processuality of life be mapped and described? Therefore, within this conceptual framework, it is not a matter of identifying the essential properties of all living matter, since the differentiation between living and non-living is perceived as being not possible or meaningful. But in spite of this, the suggested research approach is similar to that of the first conception: the task is to build (partially) new objects by composing (single features within) compartments one by one. However, the objective is not to construct life itself but merely to reproduce single life-like features and processes of existing living objects synthetically. This implies that synthetic objects will still resort to natural processes and classifies the research activities within SB as imitating and manipulating nature. Regarding the evaluation of (envisioned) scientific results, this means that constructing synthetic life from scratch is not considered to be possible and, thus, partially synthetically generated objects would not be considered and treated as life or living matter.

Within the third conception, life is defined as a hitherto undiscovered general principle emerging from the interactions between the different properties of living organisms. This concept addresses the following research questions in particular: how can we describe the overarching, structuring principle determining all forms of living matter (by means of a formula)? At what point or state of interaction(s) between certain properties does the assumed specific increase of complexity from which all forms of living necessarily result happen? Hence, the task is not primarily to (re-)construct single biological and physical properties, but rather to examine how they interact with each other in order to discover the emerging basic physical law underlying all forms of living matter and thereby generate synthetic forms of living from scratch. This implies the evaluation that research activities within SB are going beyond manipulating nature and will provide far-reaching new insights about the characteristics and principles of all existing forms of living matter and life itself, enabling the generation of synthetic life as a future research aim. In line with that, future objects constructed by means of SB are considered to be living matter, implying the ascription of an equal normative status compared with non-synthetical organisms.

Researchers grouped under the fourth conception formulate life as a relational, intuitive concept depending on subjective and societally shaped views. They focus on research questions from a very fundamental perspective, asking e.g.: what are possible forms and modes of living matter (even beyond the already known)? How do relational, subjective and social perceptions shape our understanding of living matter and limit our perspective on life as a universal category? Accordingly, there are various possible domains and manners to realize the construction of synthetic forms of living matter, implying that the first general task for synthetic biologists is to distance themselves from common perceptions of life and traditional research practices. The underlying research aim is neither to provide an explanation of the principles of life by means of a formula (as within the third conception) nor to identify the properties shared by all forms of living (as within the first conception) but rather to provide insights about characteristics of specific existing as well as novel forms of living. Research activities within SB are thus labeled as a mix of imitating nature and constructing from scratch, with both based upon subjective judgements. However, developments within SB might modify familiar understandings of living matter and life itself by evoking new subjective as well as socially shaped ascriptions, which also applies with regard to the prospective normative evaluation of novel beings.

These reflections on the practical implications of scientists’ basic concepts of life show that conceptual approaches to life and living matter provide a fundamental framework for current and further scientific research within SB: they have implications for research questions, objectives, and suggested approaches as well as for the assessment of scientific results. Hence, in line with the analyzed contributions of operational definitions [3], it can be stated that the reconstructed heuristics of life have a pragmatic utility in guiding research practices within SB on a general level. As they all imply contrasting explicit or implicit assumptions on the differentiation between living and non-living matter, naturalness and artificiality with regard to the assessment of the generation of synthetic organisms, and between life and living objects the questions arises of whether and to what extent the different conceptual approaches are compatible with each other. Concerning this, we assume that there are some controversies between the different groups of scientists with respect to their very fundamental research questions and final aims, the envisioned manners and perceived general possibilities of constructing forms of synthetic life from scratch and the related evaluation of future scientific results. Nevertheless, a common current starting point for research of all groups is the (re-) construction of basic biological and physical properties as initial tools for generating novel forms of living matter. Within the present state of research in SB it can thus be expected that the distinctive understandings of life should not negatively affect cooperation between researchers with different views. However, with regard to future research activities–after reconstructing and implementing some properties synthetically–it can be expected that the controversies might lead to epistemological and practical differentiations implying different further research strategies, approaches and domains of realization. Further ethical and socio-scientific research should examine this in more detail.

Moreover, the basic issues of defining life and living matter have to be addressed within both fields of debate on SB: the rapidly developing life and bio-sciences as well as within bio-philosophy and science and technology studies. Afterwards, regulative and governance issues concerning the societal handling of (potential) novel forms of synthetic living matter could be addressed, aimed at stimulating a broad public discussion on regulatory principles of SB in particular and biotechnology in general with regard to socially acceptable forms of the modification of life and nature.