This article addresses three paradoxes of biomimicry. First of all: how can biomimicry be as old as technology as such and at the same time decidedly innovative and new? Secondly: how can biomimicry both entail a 'naturalisation' of technology and a 'technification' of nature? And finally: how can biomimicry be perceived as nature-friendly but at the same time (potentially at least) as a pervasive biotechnological assault on nature? Contemporary (technoscientific) biomimicry, I will argue, aims to mimic nature at the level (...) of biomolecular processes and structures: contemporary biomimicry as micro-biomimicry. Moreover, building on Aristotle, Delbrück and Schrödinger, I will emphasise that what is mimicked by contemporary (technoscientific) biomimicry, in contrast to traditional (artisanal) instances of biomimicry, is not the morphological form (eidos), but rather the program or formula (logos;) of living systems. Contemporary biomimicry is 'in accordance with nature', but not in the traditional sense. Rather, building on decades of biomolecular research, it strives to reconcile nature and technology against the backdrop of advanced technicity. But biomimetics will only achieve its goals if it is not pursued purely as a technological endeavour, but complemented by an ethos of sustainability and respect for nature. These claims will be elucidated with the help of two case studies: a research project (namely the BaSyC project, launched in 2017 and aimed at producing a synthetic cell) and a science novel (namely Ian McEwan's Solar, which concerns the epistemic and moral challenges involved in artificial photosynthesis). (shrink)

The recent development of RNA replicating protocells and capsules that enclose complex biosynthetic cascade reactions are encouraging signs that we are gradually getting better at mastering the complexity of biological systems. The road to truly cellular compartments is still very long, but concrete progress is being made. Compartmentalization is a crucial natural methodology to enable control over biological processes occurring within the living cell. In fact, compartmentalization has been considered by some theories to be instrumental in the creation of life. (...) With the advancement of chemical biology, artificial compartments that can mimic the cell as a whole, or that can be regarded as cell organelles, have recently received much attention. The membrane between the inner and outer environment of the compartment has to meet specific requirements, such as semi‐permeability, to allow communication and molecular transport over the border. The membrane can either be built from natural constituents or from synthetic polymers, introducing robustness to the capsule. (shrink)

Metaphors allow us to come to terms with abstract and complex information, by comparing it to something which is structured, familiar and concrete. Although modern science is “iconoclastic”, as Gaston Bachelard phrases it, scientists are at the same time prolific producers of metaphoric images themselves. Synthetic biology is an outstanding example of a technoscientific discourse replete with metaphors, including textual metaphors such as the “Morse code” of life, the “barcode” of life and the “book” of life. This paper focuses (...) on a different type of metaphor, however, namely on the archetypal metaphor of the mandala as a symbol of restored unity and wholeness. Notably, mandala images emerge in textual materials related to one of the new “frontiers” of contemporary technoscience, namely the building of a synthetic cell: a laboratory artefact that functions like a cell and is even able to replicate itself. The mandala symbol suggests that, after living systems have been successfully reduced to the elementary building blocks and barcodes of life, the time has now come to put these fragments together again. We can only claim to understand life, synthetic cell experts argue, if we are able to technically reproduce a fully functioning cell. This holistic turn towards the cell as a meaningful whole also requires convergence at the “subject pole”: the building of a synthetic cell as a practice of the self, representing a turn towards integration, of multiple perspectives and various forms of expertise. (shrink)

To construct a synthetic cell we need to understand the rules that permit life. A central idea in modern biology is that in addition to the four entities making reality, matter, energy, space and time, a fifth one, information, plays a central role. As a consequence of this central importance of the management of information, the bacterial cell is organised as a Turing machine, where the machine, with its compartments defining an inside and an outside and its metabolism, reads (...) and expresses the genetic program carried by the genome. This highly abstract organisation is implemented using concrete objects and dynamics, and this is at the cost of repeated incompatibilities (frustration), which need to be sorted out by appropriate «patches». After describing the organisation of the genome into the paleome (sustaining and propagating life) and the cenome (permitting life in context), we describe some chemical hurdles that the cell as to cope with, ending with the specific case of the methionine salvage pathway. (shrink)

This paper examines how scientific understanding is enhanced by virtual entities, focusing on the case of the synthetic cell. Comparing it to other virtual entities and environments in science, we argue that the synthetic cell has a virtual dimension, in that it is functionally similar to living cells, though it does not mimic any particular naturally evolved cell (nor is it constructed to do so). In being cell-like at most, the synthetic cell is akin to many (...) other virtual objects as it is selective and only partially implemented. However, there is one important difference: it is constructed by using the same materials and, to some extent, the same kind of processes as its natural counterparts. In contrast to virtual reality, especially to that of digital entities and environments, the details of its implementation is what matters for the scientific understanding generated by the synthetic cell. We conclude by arguing for the close connection between the virtual and the artifactual. (shrink)

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstract, cur- rency of reality. For example proteins age, sometimes very fast. The cell must identify, then get rid of old proteins without destroying young ones. Implementing discrimination in cells leads (...) to the second set of functions, usually ignored. Being abstract, information must nevertheless be embodied into material entities, with unavoidable idiosyncratic properties. This brings about novel unmet needs. Hence, the buildup of cells elicits specific but awkward material implementations, ‘kludges’ that become essential under particular settings, while difficult to identify. Finally, a third functional category char- acterizes the need for growth, with metabolic implementations allowing the cell to put together the growth of its cytoplasm, membranes, and genome, spanning different spatial dimensions. Solving this metabolic quandary, critical for engineering novel synthetic biology chassis, uncovered an unexpected role for CTP synthetase as the coordinator of nonhomothetic growth. Because a significant number of SynBio constructs aim at creating cell factories we expect that they will be attacked by viruses (it is not by chance that the function of the CRISPR system was identified in industrial settings). Substantiating the role of CTP, natural selection has dealt with this hurdle via synthesis of the antimetabolite 30-deoxy-30,40-didehydro- CTP, recruited for antiviral immunity in all domains of life. (shrink)

Synthetic biology aims at reconstructing life to put to the test the limits of our understanding. It is based on premises similar to those which permitted invention of computers, where a machine, which reproduces over time, runs a program, which replicates. The underlying heuristics explored here is that an authentic category of reality, information, must be coupled with the standard categories, matter, energy, space and time to account for what life is. The use of this still elusive category permits (...) us to interact with reality via construction of self-consistent models producing predictions which can be instantiated into experiments. While the present theory of information has much to say about the program, with the creative properties of recursivity at its heart, we almost entirely lack a theory of the information supporting the machine. We suggest that the program of life codes for processes meant to trap information which comes from the context provided by the environment of the machine. (shrink)

Synthetic biology is often seen as the engineering turn in biology. Philosophically speaking, entities created by synthetic biology, from synthetic cells to xenobots, challenge the ontological divide between the organic and inorganic, as well as between the natural and the artificial. Entities such as synthetic cells can be seen as hybrid or transitory objects, or neo–things. However, what has remained philosophically underexplored so far is the impact these hybrid neo–things will have on (our phenomenological (...) experience of) the living world. By extrapolating from Walter Benjamin’s account of how technological reproducibility affects the aura of art, we embark upon an exploratory inquiry that seeks to fathom how the technological reproducibility of life itself may influence our experience and understanding of the living. We conclude that, much as technologies that enabled reproduction corroded the aura of original artworks (as Benjamin argued), so too will the aura of life be under siege in the era of synthetic lifeforms. This article zooms in on a specific case study, namely the research project Building a Synthetic Cell (BaSyC) and its mission to create a synthetic cell–like entity, as autonomous as possible, focusing on the properties that differentiate organic from synthetic cells. (shrink)

The topic of synthetic life has long been a subject for science fiction writers, philosophers, and even scientists. With the announcement in 2010 by renowned biologist J. Craig Venter that he and a team of scientists from the J. Craig Venter Institute (JCVI) had created a bacterial cell with chemically synthesized genome, discussions of synthetic life were no longer just conjecture.Humans had assembled nonliving components to make a living cell (Gibson et al. 2010). I was one of the (...) leaders of that endeavor, and this article will be a first-person account of how we made our cell, along with my conjectures about what will come next in the new fields of synthetic biology and synthetic genomics.Scanning electron .. (shrink)

The aim of synthetic biology is to rationally design devices, systems, and organisms with desired innovative and useful functions (Slusarczyk, Lin, and Weiss 2012). To achieve this aim, synthetic biology uses a concept similar to engineering sciences: well-characterized and standardized modular biological building blocks are reassembled in a systematic and rational manner to generate complex devices and systems with a predicted function. In the past, molecular biological research in combination with intense work in new research areas like systems (...) biology and functional genomics revealed a large inventory of multifaceted modular biological parts that are now in the toolboxes of synthetic biologists. Due to .. (shrink)

Lipid vesicles are often used as compartment structures for preparing cell‐like systems and models of protocells, the hypothetical precursor structures of the first cells at the origin of life. Although the various artificially made vesicle systems are already remarkably complex, they are still very different from and much simpler than any known living cell. Nevertheless, the preparation and study of the structure and the dynamics of functionalized vesicle systems may contribute to a better understanding of biological cells, in (...) particular of the essential features of a living cell that are not found in the non‐living form of matter. The study of protocell models may possibly lead to a better understanding of the origin of the first cells. To avoid misunderstanding in this field of research, it would be useful if generally accepted definitions of terms like “artificial cells,” “synthetic cells,” “minimal cells,” “protocells,” and “primitive cells” exist. Editor's suggested further reading in BioEssaysSynthetic cells and organelles: compartmentalization strategies Abstract. (shrink)

Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease‐related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will (...) arise from combining ‘protect and repair’ strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site‐specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long‐term therapies for many brain diseases in human patients. (shrink)

The recent publications reported in 2022 reveal the possibility of obtaining mouse embryos without the need for egg or sperm. These ‘artificial embryos’ can recapitulate some stages of development ex utero – from neurulation to organogenesis – without implantation. Synthetic mouse embryos might serve as a valuable model to gain further insights into early developmental stages. Indeed, it is expected for these models to be replicated by employing human cells. This promising research raises ethical issues and expands the (...) horizon of ethics in regard to the development of the human embryo. From this point of view, we state some of the new open venues for bioethical research. (shrink)

Synthetic biology research is often described in terms of programming cells through the introduction of synthetic genes. Genetic material is seemingly attributed with a high level of causal responsibility. We discuss genetic causation in synthetic biology and distinguish three gene concepts differing in their assumptions of genetic control. We argue that synthetic biology generally employs a difference-making approach to establishing genetic causes, and that this approach does not commit to a specific notion of genetic program (...) or genetic control. Still, we suggest that a strong program concept of genetic material can be used as a successful heuristic in certain areas of synthetic biology. Its application requires control of causal context, and may stand in need of a modular decomposition of the target system. We relate different modularity concepts to the discussion of genetic causation and point to possible advantages of and important limitations to seeking modularity in synthetic biology systems. (shrink)

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie (...) into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (shrink)

Synthetic biology is a dynamic, young, ambitious, attractive, and heterogeneous scientific discipline. It is constantly developing and changing, which makes societal evaluation of this emerging new science a challenging task, prone to misunderstandings. Synthetic biology is difficult to capture, and confusion arises not only regarding which part of synthetic biology the discussion is about, but also with respect to the underlying concepts in use. This book offers a useful toolbox to approach this complex and fragmented field. It (...) provides a biological access to the discussion using a 'layer' model that describes the connectivity of synthetic or semisynthetic organisms and cells to the realm of natural organisms derived by evolution. Instead of directly reviewing the field as a whole, firstly our book addresses the characteristic features of synthetic biology that are relevant to the societal discussion. Some of these features apply only to parts of synthetic biology, whereas others are relevant to synthetic biology as a whole. In the next step, these new features are evaluated with respect to the different areas of synthetic biology. Do we have the right words and categories to talk about these new features? In the third step, traditional concepts like "life" and "artificiality" are scrutinized with regard to their discriminatory power. This approach may help to differentiate the discussion on synthetic biology. Lastly our refined view is utilized for societal evaluation. We have investigated the public views and attitudes to synthetic biology. It also includes the analysis of ethical, risk and legal questions, posed by present and future practices of synthetic biology. This book contains the results of an interdisciplinary research project and presents the authors' main findings and recommendations. They are addressed to science, industry, politics and the general public interested in this upcoming field of biotechnology. (shrink)

The recent discussion of fictional models has focused on imagination, implicitly considering fictions as something nonconcrete. We present two cases from synthetic biology that can be viewed as concrete fictions. Both minimal cells and alternative genetic systems are modal in nature: they, as well as their abstract cousins, can be used to study unactualized possibilia. We approach these synthetic constructs through Vaihinger’s notion of a semi-fiction and Goodman’s notion of semifactuality. Our study highlights the relative existence of (...) such concrete fictions. Before their realizations neither minimal cells nor alternative genetic systems were any well-defined objects, and the subsequent experimental work has given more content to these originally schematic imaginings. But it is as yet unclear whether individual members of these heterogeneous groups of somewhat functional synthetic constructs will eventually turn out to be fully realizable, remain only partially realizable, or prove outright impossible. (shrink)

Mammalian synthetic biology holds the promise of providing novel therapeutic strategies, and the first success stories are beginning to be reported. Here we focus on the latest generation of mammalian transgene control devices, highlight state‐of‐the‐art synthetic gene network design, and cover prototype therapeutic circuits. These will have an impact on future gene‐ and cell‐based therapies and help bring drug discovery into a new era. The inventory of biological parts that are essential for life on this planet is becoming (...) increasingly complete. The postgenomic era has provided encyclopedic information on gene‐function correlations and systems biology is now delivering comprehensive details on the dynamics of biochemical reaction networks in living organisms. The time has come to reassemble these catalogued items and design new biological devices and systems with novel and useful functionality in a rational and systematic manner. This is the premise of synthetic biology, a constructive systems biology discipline likely to become the life science revolution of the 21st century. (shrink)

The scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their func- tionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adapta- tions, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. (...) In particular, the analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an oppor- tunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would sug- gest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to imple- ment novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engi- neering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engi- neering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (shrink)

Synthetic biology is an emerging technology that aims to design and engineer DNA and molecular structures of single cell organisms. Existing organisms can be altered, novel organisms can be created. In doing so, synthetic biology makes use of specific technoscientific understandings of living beings. This volume sets out to explore and assess synthetic biology and its notions of life from philosophical, ethical, social, and legal perspectives. Contents Concepts, Metaphors, Worldviews.- Public Good and Private Ownership.Social and Legal Ramifications.- (...) Opportunities, Risks, Governance. Target Groups Scholars of sociology, philosophy, theory of science, history of science, biology, engineering Politicians and policymakers The Editor Dr. Joachim Boldt is Deputy Director at the Institut für Ethik und Geschichte der Medizin in Freiburg, Germany. (shrink)

It is increasingly suggested that shortages in the supply chain for human blood could be met by the development of techniques to manufacture human blood ex vivo. These techniques fall broadly under the umbrella of synthetic biology. We examine the biopolitical context surrounding the ex vivo culture of red blood cells through the linked concepts of alienation, immunity, bio-value and biosecuritization. We engage with diverse meanings of synthetic blood, and questions about how the discourses of biosecurity and (...) privatization of risk are linked to claims that the technology will address unmet needs and promote social justice. Through our discussion we contrast communitarian ideas that culturing red blood cells ‘extends the gift’ of adult blood donation with understandings of the immunitary logics that underpin the cord-blood economy. (shrink)

In Escherichia coli, the role of lacA, the third gene of the lactose operon, has remained an enigma. I suggest that its role is the consequence of the need for cells to have safety valves that protect them from the osmotic effect created by their permeases. Safety valves allow them to cope with the buildup of osmotic pressure under accidental transient conditions. Multidrug resistance (MDR) efflux, thus named because of our anthropocentrism, is ubiquitous. Yet, the formation of simple leaks (...) would result in futile influx/efflux cycles. Versatile modification enzymes with low sensitivity solve the problem if the modified metabolite is the one exported by MDR permeases. This may account for the pervasive presence of acetyl-transferases, such as LacA, associated to acetyl-metabolite exporters. This scenario of constraints imposed by efficient influx of metabolites provides us with a model that should be followed when constructing synthetic cells. (shrink)

The scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their functionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adaptations, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. In particular, (...) the analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an opportunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would suggest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to implement novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engineering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engineering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (shrink)

Morphological engineering is an emerging research area in synthetic biology. In 2008 “synthetic morphology” was proposed as a prospective approach to engineering self-constructing anatomies by Jamie A. Davies of the University of Edinburgh. Synthetic morphology can establish a new paradigm, according to Davies, insofar as “cells can be programmed to organize themselves into specific, designed arrangements, structures and tissues.” It is obvious that this new approach will extrapolate morphology into a new realm beyond the traditional logic (...) of morphological research. However, synthetic morphology is a highly idealized vision of morphology which derives its visionary ideas from morphological engineering and mathematical idealizations in order to understand the principles of molecular morphology. Thus, the question is, if this approach will help to understand morphogenesis better or if it will just enable biologists to engineer morphogenesis. The paper investigates the development of synthetic morphology and its relation to synthetic biology as well as its epistemic gains. (shrink)

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural (...) cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more “biology inspired.”. (shrink)

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural (...) cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more “biology inspired.”. (shrink)

Synthetic biology is an increasingly high‐profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA‐based device construction, genome‐driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie (...) into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge‐making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. BioEssays 30:57–65, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

The aim of this article is to investigate the relevance and implications of synthetic models for the study of the interactive dimension of minimal life and cognition, by taking into consideration how the use of artificial systems may contribute to an understanding of the way in which interactions may affect or even contribute to shape biological identities. To do so, this article analyzes experimental work in synthetic biology on different types of interactions between artificial and natural systems, more (...) specifically: between protocells and between biological living cells and protocells. It discusses how concepts such as control, cognition, communication can be used to characterize these interactions from a theoretical point of view, which criteria of relevance and evaluation of synthetic models can be applied to these cases, and what are their limits. (shrink)

The arrival of synthetic organs may mean we need to reconsider principles of ownership of such items. One possible ownership criterion is the boundary between the organ’s being outside or inside the body. What is outside of my body, even if it is a natural organ made of my cells, may belong to a company or research institution. Yet when it is placed in me, it belongs to me. In the future, we should also keep an eye on (...) how the availability of synthetic organs may change our attitudes toward our own bodies. (shrink)

The Presidential Commission for the Study of Bioethical Issues released its first report, New Directions: The Ethics of Synthetic Biology and Emerging Technologies, on December 16, 2010.1 President Barack Obama had requested this report following the announcement last year that the J. Craig Venter Institute had created the world’s first self-replicating bacterial cell with a completely synthetic genome. The Venter group’s announcement marked a significant scientific milestone in synthetic biology, an emerging field of research that aims to (...) combine the knowledge and methods of biology, engineering, and related disciplines in the design of chemically synthesized DNA to create organisms with novel or enhanced .. (shrink)

Synthetic biology (SynBio) covers two main areas: application engineering, exemplified by metabolic engi- neering, and the design of life from artificial building blocks. As the general public is often reluctant to embrace synthetic approaches, preferring nature to artifice, its immediate future will depend very much on the public’s reaction to the unmet needs created by the pervasive demands of sustainability. On the other hand, this reluctance should not have a negative impact on research that will now take into (...) account the existence of the multiple transitions that cells face over time. The ages of life—birth, development, maturation, senescence and death—reflect specific key transitions and have, until now, rarely been taken into account in SynBio designs. This results in a mismatch between novelty and the very long evolutionary time that led to the existing chassis [remember that this is the common term used to describe the cellular framework as seen by synthetic biologists (de Lorenzo & Danchin, 2008)]. It also implies that, in general, transitions between growth stages will be taken into account with the appro- priate embodiment of highly specific processes. This is particularly important when adapting new models to their host, whether natural or artificial. Adaptation fol- lows two stages, short-term accommodation of new entities and long-term assimilation into the cell as a whole. This requires discrimination between classes of entities. We suggest that proteins playing the essential role of Maxwell’ demons, here named Maxwell’s dis- criminators (MxDs) to refer to their original function, will permit the assimilation and accommodation of artificial constructs. As a consequence, we can foresee that class discrimination, beyond mere recognition, will be implemented in SynBio 2.0, leading to an authentic par- adigm shift (Kuhn, 1996), based on conceptions that embody information as a genuine currency of reality. (shrink)

Top-down synthetic biology makes partly synthetic cells by redesigning simple natural forms of life, and bottom-up synthetic biology aims to make fully synthetic cells using only entirely nonliving components. Within synthetic biology the notions of complexity and emergence are quite controversial, but the imprecision of key notions makes the discussion inconclusive. I employ a precise notion of weak emergent property, which is a robust characteristic of the behavior of complex bottom-up causal webs, where (...) a complex causal web is one that is incompressible and its behavior cannot be derived except by crawling through all of the gory details of the interactions in the web. The central thesis of this article is that synthetic biology centrally is the activity of engineering the desired weak emergent properties of synthetic cells. Synthetic biology has many different ways to engineer desired weak emergent properties of synthetic cells, including Edisonian trial and error, standardized parts, refactoring, and reprogramming synthetic genomes. The article ends by noting two philosophical consequences of engineering weak emergence. One is epistemological: synthesis is crucial for discovering weak emergent properties. The other is metaphysical: simple life forms are nothing but complex chemical mechanisms. (shrink)

Microfluidic technology – the manipulation of fluids at micrometer scales – has revolutionized many areas of synthetic biology. The bottom‐up synthesis of “minimal” cell models has traditionally suffered from poor control of assembly conditions. Giant unilamellar vesicles (GUVs) are good models of living cells on account of their size and unilamellar membrane structure. In recent years, a number of microfluidic approaches for constructing GUVs has emerged. These provide control over traditionally elusive parameters of vesicular structure, such as size, (...) lamellarity, membrane composition, and internal contents. They also address sophisticated cellular functions such as division and protein synthesis. Microfluidic techniques for GUV synthesis can broadly be categorized as continuous‐flow based approaches and droplet‐based approaches. This review presents the state‐of‐the‐art of microfluidic technology, a robust platform for recapitulating complex cellular structure and function in synthetic models of biological cells. (shrink)

This volume launches a new series of contemporary conversations about scientific classification. Most philosophical conversations about kinds have focused centrally or solely on natural kinds, that is, kinds whose existence is not dependent on the scientific process of synthesis. This volume refocuses conversations about classification on unnatural, or synthetic, kinds via extensive study of three paradigm cases of unnatural kinds: nanomaterials, stem cells, and synthetic biology.

Some religious believers may see synthetic biology as usurping God's creative role. The Catholic Church has yet to issue a formal teaching on the field (though it has issued some informal statements in response to Craig Venter's development of a ‘synthetic’ cell). In this paper I examine the likely reaction of the Catholic Magisterium to synthetic biology in its entirety. I begin by examining the Church's teaching role, from its own viewpoint, to set the necessary backround and (...) context for the discussion that follows. I then describe the Church's attitude to science, and particularly to biotechnology. From this I derive a likely Catholic theology of synthetic biology.The Church's teachings on scientific and biotech research show that it is likely to have a generally positive disposition to synbio, if it and its products can be acceptably safe. Proper evaluation of, and protection against, risk will be a significant factor in determining the morality of the research. If the risks can be minimized through regulation or other means, then the Church is likely to be supportive. The Church will also critique the social and legal environment in which the research is done, evaluating issues such as the patenting of scientific discoveries and of life. (shrink)

Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the “gastruloid,” which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos. But fitting an ambiguous object into an existing category with well-worn pathways in research ethics, like the embryo, is only (...) a temporary fix. The bigger problem is that we no longer know what an embryo is. We haven’t had a non-absurd definition of ‘embryo’ for several decades and without a well-defined comparison class, asking whether gastruloids belong to the morally relevant class of things we call embryos is to ask a question without an answer. What’s the alternative? A better approach needs to avoid what I’ll refer to as “the potentiality trap” and, instead, rely on the emergence of morally salient facts about gastruloids and other synthetic embryos. (shrink)

In the case of synthetic biology, the responsibility of humanity for the creation of new technologies that interfere with the processes of natural selection and evolution of species can be invoked, thus annihilating the complex ecological balances and possibly leading to uncontrollable genetic mutations. The big ethical questions are raised by the fact that viral genetic material is hybridized with synthetic genetic material, as well as with the genetic material that underlies the DNA of various living cells, (...) that might interfere with synthetic genetic material - either due to errors in the handling of genetic content or the inability to predict the evolution of synthetic biological systems, an evolution beyond any mathematical modeling that would allow the estimation of biological risks given by the appearance of new species - partially or totally synthetic - and especially by their spread in ecosystems. In this article we will plead for an ethical modeling of technology and a wider communication between ethicist and bio-engineers in order to estimate the directions of technological evolution, especially in the case of synthetic biology. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived (...) gamete of the opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived (...) gamete of the opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

The recent in vitro derivation of gamete‐like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete‐like (sperm‐like or oocyte‐like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived (...) gamete of the opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells. (shrink)

This paper explores the functional role of noise in synthetic biology and its relation to the concept of randomness. Ongoing developments in the field of synthetic biology are pursuing the re-organisation and control of biological components to make functional devices. This paper addresses the distinction between noise and randomness in reference to the functional relationships that each may play in the evolution of living and/or synthetic systems. The differentiation between noise and randomness in its constructive role, that (...) is, between noise as a perturbation in routine behaviours and noise as a source of variability that cells may exploit, indicates the need for a clarification and rectification of the conflicting uses of the notion of noise in the studies of the so-called noise biology. (shrink)

With the development of new procedures in the production of synthetic human gametes it has become important to re-examine the manner in which reproductive cells, taking part in the generation of children, can be understood. Though this can be attempted from many different perspectives, the present study will examine the possibility of considering gametes as representing the persons from whom they originated. From this perspective, it is possible to suggest that, in procreation, the entirety of each human sperm (...) cell may represent and reveal the man from whom it was produced and the entirety of each human egg cell may represent and reveal the woman from whom it was produced. The possible ethical consequences of using synthetic gametes for those who hold this perspective together with their understanding of relational identity will also be examined. (shrink)

Often the only treatment available for patients suffering from diseased and injured organs is whole organ transplant. However, there is a severe shortage of donor organs for transplantation. The goal of organ engineering is to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Recent progress in stem cell biology, biomaterials, and processes such as organ decellularization and electrospinning has resulted in the generation of bioengineered blood vessels, heart valves, livers, kidneys, bladders, and airways. (...) Future advances that may have a significant impact for the field include safe methods to reprogram a patient's own cells to directly differentiate into functional replacement cell types. The subsequent combination of these cells with natural, synthetic and/or decellularized organ materials to generate functional tissue substitutes is a real possibility. This essay reviews the current progress, developments, and challenges facing researchers in their goal to create replacement tissues and organs for patients. (shrink)

Synthetic genomics is a new field of research in which small DNA pieces are assembled in a series of steps into whole genomes. The highly reduced genomes of host‐associated bacteria are now being used as models for de novo synthesis of small genomes in the laboratory. Bacteria with the smallest genomes identified in nature provide nutrients to their hosts, such as amino acids, co‐factors and vitamins. Comparative genomics of these bacteria enables predictions to be made about the gene sets (...) required for core cellular functions and the associated metabolic network for the biosynthesis of host‐selected compounds. Synthetic biology may ultimately enable researchers to make customized cell‐specific organelles for the production and delivery of drugs to humans and domestic animals. Synthetic genomics may also become the method of choice for functional analyses of genes and genomes from bacteria that cannot be cultivated in the laboratory. (shrink)

At the beginning of this special issue of Acta Biotheoretica carrying the above title, we present a brief overview on currently important topics that have been brought up during the last “European Conference on Mathematical and Theoretical Biology” in Edinburgh. After emphasizing the need for a “synthetic biology” also from the side of theory, model building and analysis, we survey most plenary talks of this Conference and a selected series of eigth review articles, which are mainly related to corresponding (...) minisymposia, reflecting the current state of the art and the lively discussion within this interdisciplinary field. (shrink)

Synthetic biology is a broad term covering multiple scientific methodologies, technologies, and practices. Pairing biology with engineering, synbio seeks to design and build biological systems, either through improving living cells by adding in new functions, or creating new structures by combining natural and synthetic components. As with all new technologies, synthetic biology raises a number of ethical considerations. In order to understand what these issues might be, and how they relate to those covered in ethics literature (...) on synbio, we conducted an interview study with practicing synthetic biologists affiliated with a synthetic biology centre in Australia. Scientists identified a range of ethical challenges germane to the field, including precarious employment, pressures from industry, gender inequity, and the negative effects of the hyping of synbio. These challenges differed markedly from those identified in the ethics literature, whose treatment of the harms and benefits of synbio remains largely speculative and abstract. In our discussion of the pragmatic, every day ethical issues synthetic biologists face, we illustrate how issues of waste or research integrity play pivotal roles in everything from lived experiences in the laboratory, to long-term research trajectories guiding the field. In a confirmation of the ethical relevance of our participant’s views on the field, we argue that the subjects they raise must be included in any ethical analysis of synbio as a field. (shrink)

In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related (...) international agreements which underlines the work of the Australia Group Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals. (shrink)

The ArgumentIn Germany during the 1870s and 1880s a number of important scientific innovations in chemistry and biology emerged that were linked to advances in the new technology of synthetic dyestuffs. In particular, the rapid development of classical organic chemistry was a consequence of programs in which chemists devised new theories and experimental strategies that were applicable to the processes and products of the burgeoning dye factories. Thereafter, the novel products became the means to examine and measure biological systems. (...) This took place as a result of two trends. The first was a move toward diversification in the dye industry – made possible by the extensive range of products – which in turn was stimulated by economic and political conditions. The second was the increasing availability of techniques, substances, and processes used in industry. This made possible a concrete program of introducing the qualitative and quantitative methods of chemistry into the domain of laboratory experimentation on biological materials, thereby realizing the abstract desire to transform cell biology into an exact science.Moreover, the conceptualization of biological systems that emerged from this endeavor leaned heavily on a theory of dye chemistry that indicated which particular arrangements of atoms performed specific functions. This biological modeling used the imagery of chemical structural formulae to transform chemical nuclei and their side chains into adequate representations of protoplasmic structure. (shrink)

Recent research shows that a faulty or sub‐optimally operating metabolic network can often be rescued by the targeted removal of enzyme‐coding genes – the exact opposite of what traditional gene therapy would suggest. Predictions go as far as to assert that certain gene knockouts can restore the growth of otherwise nonviable gene‐deficient cells. Many questions follow from this discovery: What are the underlying mechanisms? How generalizable is this effect? What are the potential applications? Here, I approach these questions from (...) the perspective of compensatory perturbations on networks. Relations are drawn between such synthetic rescues and naturally occurring cascades of reaction inactivation, as well as their analogs in physical and other biological networks. I specially discuss how rescue interactions can lead to the rational design of antagonistic drug combinations that select against resistance and how they can illuminate medical research on cancer, antibiotics, and metabolic diseases. Editor's suggested further reading in BioEssaysThe evolutionary context of robust and redundant cell biological mechanisms AbstractReprogramming cell fates: reconciling rarity with robustness Abstract. (shrink)