Since the early nineteenth century a membrane or wall has been central to the cell’s identity as the elementary unit of life. Yet the literally and metaphorically marginal status of the cell membrane made it the site of clashes over the definition of life and the proper way to study it. In this article I show how the modern cell membrane was conceived of by analogy to the first “artificial cell,” invented in 1864 by the chemist Moritz Traube (1826–1894), (...) and reimagined by the plant physiologist Wilhelm Pfeffer (1845–1920) as a precision osmometer. Pfeffer’s artificial cell osmometer became the conceptual and empirical basis for the law of dilute solutions in physical chemistry, but his use of an artificial analogue to theorize the existence of the plasma membrane as distinct from the cell wall prompted debate over whether biology ought to be more closely unified with the physical sciences, or whether it must remain independent as the science of life. By examining how the histories of plant physiology and physical chemistry intertwined through the artificial cell, I argue that modern biology relocated vitality from protoplasmic living matter to nonliving chemical substances—or, in broader cultural terms, that the disenchantment of life was accompanied by the (re)enchantment of ordinary matter. (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)

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)

Human DNA can be cloned as yeast artificial chromosomes (YACs), each of which contains several hundred kilobases of human DNA. This DNA can be manipulated in the yeast host using homologous recombination and yeast selectable markers. In relatively few steps it is possible to make virtually any change in the cloned human DNA from single base pair changes to deletions and insertions. In order to study the function of the cloned DNA and the effects of the changes made in (...) the yeast, the human DNA must be transferred back into mammalian cells. Recent experiments indicate that large genes can be transferred from the yeast host to mammalian cells in tissue culture and that the genes are transferred intact and are expressed. Using the same methods it may soon be possible to transfer YAC DNA into the mouse germ line so that the expression and function of genes cloned in YACs can be studied in developing and adult mammalian animals. (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)

Artificial gametes, derived from stem cells, have the potential to enable in vitro fertilization of embryos. Currently, artificial gametes are only being generated in laboratory animals; however, considerable efforts are underway to develop artificial gametes using human cell sources. These artificial gametes are being proposed as a means to address infertility through assisted reproductive technologies. Nonetheless, the availability of artificial gametes obtained from adult organisms can potentially expand the possibilities of reproduction. Various groups, such (...) as same-sex couples, post-menopausal women, and deceased donors, could potentially utilize artificial gametes to conceive genetically related offspring. The advent of artificial gametes raises significant bioethical questions. Should all these reproductive scenarios be accepted? How can we delineate the range of future reproductive choices? A normative bioethical framework may be necessary to establish a consensus regarding the use of human artificial gametes. This review aims to present the current state of research on the biological roadmap for generating artificial gametes, while also summarizing proposed approaches to establish a normative framework that delineates ethically acceptable paths for reproduction. (shrink)

A number of recent papers have described the successful derivation of egg and sperm precursor cells from mouse embryonic stem cells—so-called “artificial” gametes. Although many scientific questions remain, this research suggests numerous new possibilities for stem cell research and assisted reproductive technology, if a similar breakthrough is achieved with human embryonic stem cells. The novel opportunities raised by artificial gametes also prompt new ethical questions, such as whether same-sex couples should be able to access this (...) technology to have children who are genetically related to them both.THE CREATION OF “ARTIFICIAL” GAMETESOver the past two years, a number of papers have been published detailing the first successful attempts at differentiating mouse embryonic stem cells into egg1 and sperm2 precursor cells. Previously, researchers had used embryonic stem cells to generate tissues such as brain, liver, and pancreatic cells, but not germ cells of any kind. Production of gamete precursor cells was achieved initially through allowing stem cell lines to differentiate more or less randomly, but recent research has focused on identifying the precise ways in which differentiation into gametes can be precipitated and controlled. These breakthroughs make it seem likely that ongoing research on human stem cells will yield similar possibilities,3 raising questions over the practicalities of what might be achieved with such “artificial” gametes. In turn, the novel opportunities presented by artificial gametes raise a number of ethical concerns.The initial breakthrough, namely the obtaining of egg cells from mouse stem cells, was achieved by means of relatively simple science. Rather than coaxing stem cells to develop into eggs using complicated cocktails of growth factors, researchers adopted standard cell culture conditions, but grew the cells at higher density than usual.3–6 Growing the cells in this way led to the formation of ovary-like cell aggregates, which (when separated and stimulated with …. (shrink)

Stem cell banks curating and distributing human embryonic stem cells have been established in a number of countries and by a number of private institutions. This paper identifies and critically discusses a number of arguments that are used to justify the importance of such banks in policy discussions relating to their establishment or maintenance. It is argued (1) that ‘ethical arguments’ are often more important in the establishment phase and ‘efficiency arguments’ more important in the maintenance phase, and (2) (...) that arguments relating to the interests of embryo and gamete donors are curiously absent from the particular stem cell banking policy discourse. This to some extent artificially isolates this discourse from the broader discussions about the flows of reproductive materials and tissues in modern society, and such isolation may lead to the interests of important actors being ignored in the policy making process. (shrink)

Endothelial cells in culture have, in the past, been a valuable but capricious tool to test hypotheses on the role of components of the blood vessel wall in such functions as blood pressure homeostasis, hemostasis, permeability, transport of macromolecules and the processing of circulating biologically active substances. Now techniques are becoming available for raising long‐term, large‐scale cultures that can be maintained reproducibly and without loss of phenotypic characteristics. The outlook for establishing endothelial cell factories invites speculation on some far‐reaching (...) possibilities, such as endothelial cell banks that could be used for seeding autogenous cells on vascular prostheses, artificial kidney tubing, heart valves, or corneas, or for virus production, or for synthesis by endothelial cells of products at present beyond the reach of bacterial cells. (shrink)

Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They (...) may originate as either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication. (shrink)

Nowadays, batteries play an important role in a lot of different applications like energy storage, electro-mobility, consumer electronic and so on. All the battery types have a common factor that is their complexity, independently of its nature. Usually, the batteries have an electrochemical nature. Several different test are accomplished to check the batteries performance, and commonly, it is predictable how they work depending of their technology. The present research describes the hybrid intelligent system created to accomplish fault detection over a (...) Lithium Iron Phosphate—LiFePO4 power cell type, commonly used in electro-mobility applications. The approach is based on the cell temperatures behaviour for voltage and current specific values. Taken into account the operating range of a real system based on a LiFePO4 cell, a large set of points of operation have been used to achieve the dataset. The different behaviour zones have been obtained by clustering as a first step. Then, different regression techniques have been used over each cluster. Polynomial regression, artificial neural networks and support vector regression were the combined techniques to develop the hybrid intelligent model proposed. The intelligent system gives very good results over the operating range, detecting all the faults tested during the validation. (shrink)

Nothing in McKay & Dennett's (M&D's) target article deals with the issue of how the adaptivity, or some other aspect, of beliefs might become a biological adaptation; which is to say, how the functions discussed might be coded in such a way in the brain that their development was also coded in gametes or sex transmission cells.

Artificial genetic constructs that direct the synthesis of self‐replicating RNA molecules are used widely to induce gene silencing, for bioproduction, and for vaccination. Interestingly, one variant of the self‐replicon has not been discussed in the literature: namely, transgenic organisms that synthesise alien replicons. For example, plant cells may be easily genetically modified to produce bacteriophages or insect viruses. Alien replicon‐producing organisms (ARPOs) may serve as a unique tool for biocontrol or to selectively influence the characteristics of a target (...) organism. The ARPO approach would have to meet strict biosafety criteria, and its practical applications are problematic. However, a discussion on ARPO applicability would be valuable to outline the full set of options available in the bioengineering toolbox. In this paper, RNA replicons for bioengineering are reviewed briefly, and the ARPO approach is discussed. (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)

Continuous culture techniques were developed in the early twentieth century to replace cumbersome studies of cell growth in batch cultures. In contrast to batch cultures, they constituted an open concept, as cells are forced to proliferate by adding new medium while cell suspension is constantly removed. During the 1940s and 1950s new devices have been designed—called “automatic syringe mechanism,” “turbidostat,” “chemostat,” “bactogen,” and “microbial auxanometer”—which allowed increasingly accurate quantitative measurements of bacterial growth. With these devices cell growth came under (...) the external control of the experimenters and thus accessible for developing a mathematical theory of growth kinetics—developed mainly by Jacques Monod, Aron Novick and Leo Szilard in the early 1950s and still in use today. The paper explores the development of continuous culture devices and claims that these devices are simulators for standard cells following specific requirements, in particular involving mathematical constraints in the design and setting of the devices as well as experiments. These requirements have led to contemporary designs of continuous culture techniques realizing a specific event-based flow algorithm able to simulate directed evolution and produce artificial cells and microorganisms. This current development is seen as an alternative approach to today’s synthetic biology. (shrink)

Recent results from studies on animals suggest that functional germ cells may be generated from human pluripotent stem cells, giving rise to three possibilities: research with these so‐called artificial gametes, including fertilization experiments in vitro; their use in vivo for therapy for the treatment of human infertility; and their use in assisted reproductive technologies in vitro. While the legal, philosophical, and ethical questions associated with these possibilities have been already discussed intensively in other countries, the debate in (...) Germany is still at its beginning. A systematic and detailed analysis of the legal framework in Germany is provided with regard to the three possibilities, including the applicable statutory laws as well as the constitutional law. The question emerges as to whether the statutory laws as well as the constitution justify a distinction to be made between embryos of artificial and natural origin. This question is subject to philosophical analysis, discussing the distinction between person and thing, dignity and price, personality and property, and nature and technique. As a result, the criterion of naturalness alone may not be sufficient to differentiate between embryos of natural and artificial origin, and other criteria need to be identified. (shrink)

Two reports have shown that mammalian artificial chromosomes (MAC) can be constructed from cloned human centromere DNA and telomere repeats, proving the principle that chromosomes can form from naked DNA molecules transfected into human cells. The MACs were mitotically stable, low copy number and bound antibodies associated with active centromeres. As a step toward second-generation MACs, yeast and bacterial cloning systems will have to be adapted to achieve large MAC constructs having a centromere, two telomeres, and genomic copies (...) of mammalian genes. Available construction techniques are discussed along with a new P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined to other PACs in vitro, avoiding a cloning step during which large repetitive arrays often rearrange. The PAC system can be used as a route to further define the optimal DNA elements required for efficient MAC formation, to investigate the expression of genes on MACs, and possibly to develop efficient MAC-delivery protocols. BioEssays 1999;21:76–83. © 1999 John Wiley & Sons, Inc. (shrink)

Two reports have shown that mammalian artificial chromosomes (MAC) can be constructed from cloned human centromere DNA and telomere repeats, proving the principle that chromosomes can form from naked DNA molecules transfected into human cells. The MACs were mitotically stable, low copy number and bound antibodies associated with active centromeres. As a step toward second-generation MACs, yeast and bacterial cloning systems will have to be adapted to achieve large MAC constructs having a centromere, two telomeres, and genomic copies (...) of mammalian genes. Available construction techniques are discussed along with a new P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined to other PACs in vitro, avoiding a cloning step during which large repetitive arrays often rearrange. The PAC system can be used as a route to further define the optimal DNA elements required for efficient MAC formation, to investigate the expression of genes on MACs, and possibly to develop efficient MAC-delivery protocols. BioEssays 1999;21:76–83. © 1999 John Wiley & Sons, Inc. (shrink)

All species, extant and extinct, from the simplest unicellular prokaryotes to humans, have an existential consciousness. Without sentience, the first cells that emerged some 4 billion years ago would have been evolutionary dead-ends, unable to survive in the chaotic, dangerous environment in which life first appeared and evolved. In this book, Arthur Reber's theory, the Cellular Basis of Consciousness (CBC), is outlined and distinguished from those models that argue that minds could be instantiated on artificial entities and those (...) that maintain consciousness requires a nervous system. The CBC framework takes a novel approach to classic topics such as the origin-of-life, philosophy of mind, the role of genes, the impact of cognition, and how biological information is processed by all species. It also calls for a rethinking of a variety of issues including the moral implications of the sentient capacities of all species, how welfare concerns need to be expanded beyond where they currently are, and critically, how all life is intertwined in a coordinated cognitive ecology. The Sentient Cell explores this revolutionary model, which updates the standard neo-Darwinian framework within which current approaches operate and examines the underlying biomolecular features that are the likely candidates for the "invention" of consciousness and outline their role in cellular life. (shrink)

Background Though artificial intelligence holds great value for healthcare, it may also amplify health inequalities through risks of bias. In this paper, we explore bias risks in targeted medicines manufacturing. Targeted medicines manufacturing refers to the act of making medicines targeted to individual patients or to subpopulations of patients within a general group, which can be achieved, for example, by means of cell and gene therapies. These manufacturing processes are increasingly reliant on digitalised systems which can be controlled by (...) artificial intelligence algorithms. Whether and how bias might turn up in the process, however, is uncertain due to the novelty of the development. Methods Examining stakeholder views across bioethics, precision medicine, and artificial intelligence, we document a range of opinions from eleven semi-structured interviews about the possibility of bias in AI-driven targeted therapies manufacturing. Result Findings show that bias can emerge in upstream (research and development) and downstream (medicine production) processes when manufacturing targeted medicines. However, interviewees emphasized that downstream processes, particularly those not relying on patient or population data, may have lower bias risks. The study also identified a spectrum of bias meanings ranging from negative and ambivalent to positive and productive. Notably, some participants highlighted the potential for certain biases to have productive moral value in correcting health inequalities. This idea of “corrective bias” problematizes the conventional understanding of bias as primarily a negative concept defined by systematic error or unfair outcomes and suggests potential value in capitalizing on biases to help address health inequalities. Our analysis also indicates, however, that the concept of “corrective bias” requires further critical reflection before they can be used to this end. (shrink)

There is considerable enthusiasm about the prospect that artificial intelligence (AI) will help to improve the safety and efficacy of health services and the efficiency of health systems. To realize this potential, however, AI systems will have to overcome structural problems in the culture and practice of medicine and the organization of health systems that impact the data from which AI models are built, the environments into which they will be deployed, and the practices and incentives that structure their (...) development. This perspective elaborates on some of these structural challenges and provides recommendations to address potential shortcomings. (shrink)

In possible scenarios on the origin of life, protocells represent the precursors of the first living cells. To study such hypothetical protocells, giant vesicles are being widely used as a simple model. Lipid vesicles can undergo complex morphological changes enabling self‐reproduction such as growth, fission, and extra‐ and intravesicular budding. These properties of vesicular systems may in some way reflect the mechanism of reproduction used by protocells. Moreover, remarkable similarities exist between the morphological changes observed in giant vesicles and (...) bacterial L‐form cells, which represent bacteria that have lost their rigid cell wall, but retain the ability to reproduce. L‐forms feature a dismantled cellular structure and are unable to carry out classical binary fission. We propose that the striking similarities in morphological transitions of L‐forms and giant lipid vesicles may provide insights into primitive reproductive mechanisms and contribute to a better understanding of the origin and evolution of mechanisms of cell reproduction.Editor's suggested further reading in BioEssays Synthesizing artificial cells from giant unilamellar vesicles: State‐of‐the art in the development of microfluidic technology Abstract. (shrink)

After a long and successful career in tracheal surgery and lung cancer, Paolo Macchiarini became very famous in 2008 with the transplantation of a trachea from a cadaver that then apparently used the patient’s own stem cells to supposedly regenerate new trachea, i.e., tissue-engineered tracheae. Among the nine patients that received this revolutionary treatment, using biological or artificial tracheae, under Macchiarini’s supervision, six have reportedly died. Although several critics had expressed concerns with the procedures, allegations of misconduct against (...) Macchiarini first arose in August of 2014 by four Karolinska Institutet (KI) colleagues, and an independent investigation was called for by KI based on claims made in seven published papers. Among the claims were the fact that the procedure constituted a high risk, information on the patients was incomplete and that there was no or incomplete ethical approval, thus constituting misconduct. His CV was also shown to contain inaccuracies. By September 10, 2016, most of these claims have now proved to be true, and Macchiarini was found guilty of misconduct by KI. This paper looks primarily at earlier published papers by Macchiarini and his collaborators in a search for clues to better understand the evolution of altruism, or narcissism. An assessment of the controversial papers, and of letters written by critics and skeptics like Pierre R. Delaere, indicate that insufficient experimental evidence was presented for several case studies, and that claims made about the success of the procedures exceeded what was shown by the evidence. A domino effect of personal and professional tragedies ensued, in rapid succession, between 2014 and 2016. The effect on the field of stem cell research has been chilling, and the side-effects have taken their toll, with several high-profile resignations, primarily at KI, within the Swedish education system and in the Nobel Committee. This case has mesmerized the bioethics and biomedical communities for years. (shrink)

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 (εi~δος), but rather the program or formula (δóγOς) 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 concept of complexity has become very important in theoretical biology. It is a many faceted concept and too new and ill defined to have a universally accepted meaning. This review examines the development of this concept from the point of view of its usefulness as a criteria for the study of living systems to see what it has to offer as a new approach. In particular, one definition of complexity has been put forth which has the necessary precision and (...) rigor to be considered as a useful categorization of systems, especially as it pertains to those we call living. This definition, due to Robert Rosen, has been developed in a number of works and involves some deep new concepts about the way we view systems. In particular, it focuses on the way we view the world and actually practice science through the use of the modelling relation. This mathematical object models the process by which we assign meaning to the world we perceive. By using the modelling relation, it is possible to identify the subjective nature of our practices and deal with this issue explicitly. By so doing, it becomes clear that our notion of complexity and especially its most popular manifestations, is in large part a product of the historical processes which lead to the present state of scientific epistemology. In particular, it is a reaction to the reductionist/mechanistic view of nature which can be termed the Newtonian Paradigm. This approach to epistemology has dominated for so long that its use as a model has become implicit in most of what we do in and out of science. The alternative to this approach is examined and related to the special definition of complexity given by Rosen. Some historical examples are used to emphasize the dependence of our view of what is complex in a popular sense on the ever changing state of our knowledge. The role of some popular concepts such as chaotic dynamics are examined in this context. The fields of artificial life and related areas are also viewed from the perspective of this rigorous view of complexity and found lacking. The notion that in some way life exists at the edge of chaos is examined from the perspective of the second law of thermodynamics given by Schneider and Kay. Finally, the causal elements in complex systems are explored in relation to complexity. Rosen has shown that a clear difference in causal relations exists between complex and simple systems and that this difference leads to a uniquely useful definition of what we mean by living. Rosen makes it very clear that the class of systems which are complex is a much larger class than those which we call living. For that reason, the focus of this review will be on complexity as a stepping stone towards the deeper question of what makes a system alive. (shrink)

Is life a property of the material structure of a living system or an abstract form of organization that can be realized in other media; artificial as well as natural? One version of the Artificial Life research programme presumes, that one can separate the logical form of an organism from its material basis of construction, and that its capacity to live and reproduce is a property of the form, not the matter (Langton 1989). This seems to oppose the (...) notion of a cell within contemporary molecular biology, according to which "form" and "matter" do not represent separate realms. The information in a living cell is intimately bound to the properties of the material substrate. This condition may represent a restriction on the validity of formal theories of life. (shrink)

Living organisms have long since been a source of inspiration for humans to build artifacts mimicking their behaviour. Usually models used are quite simple by comparison to their natural sources of inspiration. However, on computers, we have the freedom to test approaches both realistic and outnght speculative, from the biological point of view. This article overviews several Artificial Life (ALife) models and their application areas. On the one hand we have models that are currently used as tools in engineeering, (...) especially for optimisation, and on the other hand we have environments and models that exhibit properties alike those observed in bio-organisms, that are useful to study and develop biological theories. Therefore, we will describe computer based models, such as artificial neural networks, evolutionary algonthms, artificial immune systems, swarm based algonthms as bio-inspired tools and artificial life environments and autonomous robots in the perspective of artificial beings. A bnef reference to biochemistry research, with the nickname of wet ALife, especially onented to build artificial cells will complete this review. The paper ends with a discussion on the implications of natural versus artificial life. (shrink)

ABSTRACT Recent developments in generating gametes via in vitro gametogenesis (IVG) from induced pluripotent stem cells (iPSCs) and their successful use for reproductive purposes in animals strongly suggest that soon these methods could also be used in human reproduction. At least two questions emerge in this context: (a) if a legislator should permit their use and (b) if ethical claims emerge that support their provision, e.g., by public health care systems. This urges an ethical reflection of the new reproductive (...) options this technique might offer. Since the concept of reproductive freedom is a key aspect for the ethical evaluation of artificial reproductive technologies (ARTs), it is necessary to analyze if the new possibilities emerging from IVG fall within the scope of this concept. The results may constitute a morally relevant difference between different imaginable applications of IVG and potentially justify differences in claims to access this technology. (shrink)

Transplantation is becoming an increasingly more common approach to treatment of diseases of organ failure, making organ donation an important means of saving lives. Most world religions find organ donation for the purpose of transplantation to be acceptable, and some even encourage members to donate their organs as a gift of love to others. Recent developments, including artificial organs, transplants from nonhuman species, use of stem cells, and cloning, are impacting the field of transplantation. These new approaches should (...) be discussed with bioethical considerations in mind, particularly the notion of human beings as a unity of body and spirit. (shrink)

An item that stands out (is isolated) from its context is better remembered than an item consistent with the context. This isolation effect cannot be accounted for by increased attention, because it occurs when the isolated item is presented as the first item, or by impoverished memory of nonisolated items, because the isolated item is better remembered than a control list consisting of equally different items. The isolation effect is seldom experimentally or theoretically related to the primacy or the recency (...) effects—that is, the improved performance on the first few and last items, respectively, on the serial position curve. The primacy effect cannot easily be accounted for by rehearsal in short‐term memory because it occurs when rehearsal is eliminated. This article suggests that the primacy, the recency, and the isolation effects can be accounted for by experience‐dependent synaptic plasticity in neural cells. Neurological empirical data suggest that the threshold that determines whether cells will show long‐term potentiation (LTP) or long‐term depression (LTD) varies as a function of recent postsynaptic activity and that synaptic plasticity is bounded. By implementing an adaptive LTP‐LTD threshold in an artificial neural network, the various aspects of the isolation, the primacy, and the recency effects are accounted for, whereas none of these phenomena are accounted for if the threshold is constant. This theory suggests a possible link between the cognitive and the neurological levels. (shrink)

Ownership of Human Tissues and Cells, Office of Technology Assessment, Congress of the United StatesDeputy Chairman New South Wales Law Reform Commision.

Internet of thing building sensors can capture several types of building operations, performances, and conditions and send them to a central dashboard to analyze data to support decision-making. Traditionally, laptops and cell phones are the majority of Internet-connected devices. IoT tracking allows customers to close the distance between devices and enterprises by collecting and analyzing various IoT data through connected devices, customers, and applications on the network. There is a lack of requirements for IoT edge applications security and approval. There (...) are no best practices regarding operations focused on IoT incidents. IoT elements are not covered by audit and logging requirements. In this article, a big data analytics-based customer operation system analyzes the operation. With the exponential rise in data usage, the explosive development in the IoT devices reflects the ideal overlap of big data growth with IoT. Big data analytics continuously evolving network raises trivial questions about the performance, distribution of data, analysis, and protection of data collection. IoT modifies almost all the construction industry characteristics. Human-centered artificial intelligence is described as systems that always improve because of human input while also delivering an effective experience between the human and the robotic. The IoT is the key factor that ensures greater building performance. It was the first evolution of technology in a long time to turn genuine inventions into an industry that depended heavily on paper and manual processes. The benefits of the IoT in construction are now quite obviously much heavier than those of current manual processes. As a result, more construction companies explore and incorporate IoT strategies to address their productivity challenges, increasing efficiencies and profits. The simulation analysis shows that the proposed BDA-CO model enhances the trust score of 98.5%, accuracy detection ratio of 93.4%, probability ratio of 97.6%, and security ratio of 98.7% and reduces the false negative ratio of 21.3%, response time of 10.5%, delay rate of 19.9%, and packet loss ratio of 15.4% when compared to other existing techniques. (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

Unlike eggs and diatoms, most single cells in nature do not have structured shells to provide extensive protection. It is a challenge to artificially confer shell structures on living cells to improve their inherent properties and functions. We discuss four different types of cellular shellizations: man‐made hydrogels, sol‐gels, polyelectrolytes, and mineral shells. We also explore potential applications, such as cell storage, protection, delivery, and therapy. We suggest that shellization could provide another means to regulate and functionalize cells. (...) Specifically, the integration of living cells and non‐living functional shells may be developed as a novel strategy to create “super” or intelligent cells. Unlike biological approaches, this material‐based bio‐interface regulation is inexpensive, effective, and convenient, opening up a novel avenue for cell‐based technologies and practices. (shrink)

Modern life sciences research is increasingly relying on artificial intelligence (AI) approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet (...) it is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research – protein structure prediction and single cell RNA-sequencing – we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems. (shrink)

Certain interventions now permit the derivation of mammalian gametes from stem cells cultivated from either somatic cells or embryos. These gametes can be used in an indefinite cycle of conception in vitro, gamete derivation, conception in vitro, and so on, producing genetic generations that live only in vitro. One commentator has described this prospect for human beings as eugenics, insofar as it would allow for the selection and development of certain traits in human beings. This commentary not only (...) offers this topic for discussion, it also wades into the ethical fray over the practice. Several possible lines of objection can be raised against this practice, but these accounts are by and large insufficient as an ethical analysis of this possible, future way of conceiving human children. (shrink)

Dans cet article, nous interrogeons la désuétude du projet initial de l’intelligence artificielle, fondé conjointement avec la science cognitive, et partageant avec elle ce qu’on appela plus tard l’hypothèse computationnelle de l’esprit, c’est-à-dire l’idée que la pensée intelligente peut être décrite sous la forme de programmes informatiques. Si cette désuétude reflète en partie notre éloignement d’une période très particulière du xxe siècle, celle des années 1950 marquées par les angoisses de la guerre froide, nous souhaitons montrer qu’elle est sous-tendue par (...) une désuétude plus profonde encore, celle d’une conception hétérodoxe, voire « alchimique », de la science. Malgré son abandon au cours des années 1980, nous explorons l’idée que cette hypothèse reste tout de même vivace comme tentation congénitale au projet même de la science cognitive, en examinant les thèses récentes de Gualtiero Piccinini qui considère les mécanismes neuronaux comme une forme élargie de calcul. (shrink)

A new design principle is discussed for making a sufficiently complex cell for the creation of the first wet artificial life in the laboratory. The current approach is to attempt a minimal cell, which consists of a liposome that contains a minimal metabolic cycle for self-maintenance and self-replication. Given the lack of success with the minimal cell to date, the authors suggest it is possible to take an alternative approach to building the first wet artificial life form that (...) they have called the first cell. In this article, the concept of the first cell versus the minimal cell is discussed. The new design principle is supported by the following observations that are examined and developed from an Origins of Life perspective: That human development shows a U-shaped curve where the skills and developmental patterns of human infants are proficient at the first phase then decline and subsequently recover to a qualitatively better level. A review of spatial temporal dynamics using cellular automata studies shows that complexity generated at both the initial states and the time evolution dynamics can synthesize rich evolutionary processes. A chemical experiment exhibiting self-organizing dynamics results in the emergence of a self-propelling oil droplet that demonstrates the self-sustaining properties of a non-equilibrium state. Finally, the important design question Is life a contingent or deterministic phenomenon? is examined which asks whether a life form is a dynamic product of its surroundings or whether it is the inevitable outcome of prior events, and is discussed making reference to the characteristics of an art installation The Way Things Go. This contemporary masterpiece, which exhibits a long-lasting chain of unrelated causal events, serves as a theoretical model for discussion of evolutionary processes, suggesting that when it comes to designing wet artificial life forms in the laboratory, both contingent and deterministic processes should be taken into account. (shrink)

In this paper we challenge the notion of ‘normativity’ used by some enactive approaches to cognition. We define some varieties of enactivism and their assumptions and make explicit the reasoning behind the co-emergence of individuality and normativity. Then we argue that appealing to dispositions for explaining some living processes can be more illuminating than claiming that all such processes are normative. For this purpose, we will present some considerations, inspired by Wittgenstein, regarding norm-establishing and norm-following and show that attributions of (...) normativity to non-social agents are deeply paradoxical. The main conclusions of our discussion are: (1) circular and internal explanations centred on the stability of living systems are insufficient to account for processes where the environment plays an important role, such as adaptation. Enactivism is not an explanatory alternative to evolutionary biology but needs it as a complement to accounts focused on the internal self-assembly of organisms; (2) though we share enactivism’s anti-representational spirit, we argue that ecological psychology can offer a better account of perception. (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)

Recent breakthroughs in stem cell differentiation and reprogramming suggest that functional human gametes could soon be created in vitro. While the ethical debate on the uses of in vitro generated gametes (IVG) was originally constrained by the fact that they could be derived only from embryonic stem cell lines, the advent of somatic cell reprogramming, with the possibility to easily derive human induced pluripotent stem cells from any individual, affords now a major leap in the feasibility of IVG derivation (...) and in the scope of their potential applications. In this paper we develop an ethical framework, rooted in recent scientific evidence, to support a robust experimental pipeline that could enable the first-in-human use of IVG. We then apply this framework to the following objectives: (1) a clarification of the genetic parenting options afforded by IVG, along with their ethical underpinnings; (2) a defence of the use of IVG to remedy infertility, broadening their scope to same-sex couples; (3) an assessment of the most far-reaching implications of IVG for multiplex parenting. These include, first, the liberation of parenting roles from the constraints of biological generations in vivo, allowing multiple individuals to engage in genetic parenting together, thus blurring the distinction between biological and social generations. Second, we discuss the conflation of IVG with sequencing technology and its implications for the possibility that prospective parents may choose among a hitherto unprecedented number of potential children. In view of these perspectives, we argue that, contrary to the exhausted paradigm according to which society lags behind science, IVG may represent instead a salient and most visible instance where biotechnological ingenuity could be used in pursuit of social experimentation. (shrink)

Abstract:Research into the development of stem cell-derived (SCD) gametes in humans, otherwise known asin vitrogametogenesis (IVG), is largely motivated by reproductive aims. Especially, the goal of establishing genetic parenthood by means of SCD-gametes is considered an important aim. However, like other applications in the field of assisted reproduction, this technology evokes worries about the possibility of creating so-called ‘designer babies.’ In this paper, we investigate various ways in which SCD-gametes could be used to create such preference-matched offspring, and what this (...) would mean for the acceptability of IVG, if it is premised that it is morally problematic to ‘design’ offspring. We argue that IVG might facilitate the creation of preference-matched offspring, but conclude that this should not undermine the moral acceptability of IVG altogether—even if one concedes the premise that creating ‘designer babies’ is morally problematic. In the light of this, we also point at a possible inconsistency for a position that condemns the creation of ‘designer offspring,’ while accepting the various endeavors to have genetically related offspring. (shrink)

Systems evolve in order to adjust and survive. The paper’s contribution is that this evolvement is inadequate without an evolutionary telos. It is argued that without the presence of self-destruction in multiple levels of our existence and surroundings, our survival would have been impossible. This paper recognises an appreciation of auto-catastrophe at the cell level, in human attitudes (both as an individual and in societies), and extended to Earth and out to galaxies. Auto-Catastrophic Theory combines evolution with auto-catastrophic behaviours and (...) innovative machinery by offering new themes of understanding their merging such as (a) protogenic and deuterogenic auto-catastrophic processes, (b) protogenic and deuterogenic survival processes, and (c) ‘alive’, partially ‘alive’, and non-‘alive’ systems. The value of self-destruction relies on a numerical stability within a system and correlational relationships between systems. Auto-Catastrophic Theory provides novel justifications why artificial intelligence: (a) is crucial to overcome the extinction of humanity (via H+), (b) is crucial to offer indirect survival of humanity (by saving its history), and (c) is at the same time a threat for humanity. These novel justifications and themes, developed by combining evolution with catastrophe as well as innovative machinery, expand our knowledge of how best to handle fresh challenges ahead. (shrink)

When posing the question "is artificial life possible?", our immediate answer is that on the one hand : of course it is - people make it, and indeed very interesting and even breathtaking structures have already been constructed, such as `aminats', self-reproducing patterns and the other things, we have seen already. In this sense we are forced to take artificial life as a fact (at least as a fact about a new branch of research), nearly in the same (...) way that the philosopher Kant took the theoretical physics of his days, Newtonian physics, as a matter of fact, and then asked: What are the conditions of possibility for this kind of theoretical science? On the other hand: The situation differs from Kant's. Artificial Life does not confront us with an analogy of theoretical mechanics within the field of biology. We face a curious situation: It is not obvious to the majority of biologists that Artificial Life is possible at all, at least in the purely computational sense of `software life'. Probably, most biologists would never call these artificial constructs `living'. Why not? Because the intuitive notions of life and living systems within biology implies, among other things, that living beings are a result of a long, ongoing evolutionary process that have created autonomous organisms, single-celled and multi-celled, that are highly organized, open (non-equilibrium), material thermodynamic systems based on metabolism and some kind of genetic information supported by macromolecules, that only metaphorically resemble a computer program. It is not that.. (shrink)

The emerging field of synthetic biology aims to engineer novel biological entities. The envisioned future bio-based economy builds largely on “cell factories”: organisms that have been metabolically engineered to sustainably produce substances for human ends. In this paper, we argue that synthetic biology’s goal of creating efficient production vessels for industrial applications implies a set of ontological assumptions according to which living organisms are machines. Traditionally, a machine is understood as a technological, isolated and controllable production unit consisting of parts. (...) But modified organisms, or hybrids, require us to think beyond the machine paradigm and its associated dichotomies between artificial and natural, organisms and artefacts. We ask: How may we conceptualise hybrids beyond limiting ontological categories? Our main claim is that the hybrids created by synthetic biology should be considered not as machines but as metabolic systems. We shall show how the philosophical account of metabolism can inform an ontology of hybrids that moves beyond what we call the “machine ontology”, considering that metabolism enables thinking beyond the dominant dichotomies and allows us to understand and design lifeforms in a bio-based economy. Thus, the aim of this paper is twofold: first, to develop the philosophical ontology of hybrids, and second, to move synthetic biology beyond the problematically limiting view of hybrids. (shrink)

All information results from a process, intrinsic to living beings, of info-autopoiesis or information self-production; a sensory commensurable, self-referential feedback process immanent to Bateson’s ‘difference which makes a difference’. To highlight and illustrate the fundamental nature of the info-autopoietic process, initially, two simulations based on one-parameter feedback are presented. The first, simulates a homeostatic control mechanism (thermostat) which is representative of a mechanistic, cybernetic system with very predictable dynamics, fully dependent on an external referent. The second, simulates a homeorhetic process, (...) inherent to biological systems, illustrating a self-referenced, autonomous system. Further, the active incorporation/interference of viral particles by prokaryotic cells and the activation of CRISPR-Cas can be understood as info-autopoiesis at the most fundamental cellular level, as well as constituting a planetary network of self-referenced information. Moreover, other examples of the info-autopoietic nature of information are presented to show the generality of its applicability. In short, info-autopoiesis is a recursive process that is sufficiently generic to be the only basis for information in nature: from the single cell, to multi-cellular organisms, to consideration of all types of natural and non-natural phenomena, including tools and artificial constructions. (shrink)

Research on natural and artificial brains is proceeding at a rapid pace. However, the understanding of the essence of consciousness has changed slightly over the millennia, and only the last decade has brought some progress to the area. Scientific ideas emerged that the soul could be a product of the material body and that calculating machines could imitate brain processes. However, the authors of this book reject the previously common dualism—the view that the material and spiritual-psychic processes are separate (...) and require a completely different substance as their foundation. -/- Reductive Model of the Conscious Mind is a forward-thinking book wherein the authors identify processes that are the essence of conscious thinking and place them in the imagined, simplified structure of cells able to memorize and transmit information in the form of impulses, which they call neurons. The purpose of the study is to explain the essence of consciousness to the degree of development of natural sciences, because only the latter can find a way to embed the concept of the conscious mind in material brains. The book is divided into three parts. Part 1 works to convince readers that the emergence of consciousness does not require detailed knowledge of the structure and morphology of the brain, with the exception of some specific properties of the neural network structure that the authors attempt to point out. Part 2 proves that the biological structure of many natural brains fulfills the necessary conditions for consciousness and intelligent thinking. Similarly, Part 3 shows the ways in which artificial creatures imitating natural brains can meet these conditions, which gives great hopes for building artificially intelligent beings endowed with consciousness. Covering topics that include cognitive architecture, the embodied mind, and machine learning, this book is ideal for cognitive scientists, philosophers of mind, neuroscientists, psychologists, researchers, academicians, and advanced-level students. The book can also help to focus the research of linguists, neurologists, and biophysicists on the biophysical basis of postulated information processing into knowledge structures. (shrink)

Should we do whatever science lets us do? This short introduction in the 'All That Matters' series shows how developments in biotechnology, such as genetics, stem cell research and artificial reproduction, arouse both our greatest hopes and our greatest fears. Many people invest the new biotechnology with all the aspirations and faith once accorded to religious salvation. But does everyone benefit equally from scientific progress? This book argues that although we've entered new scientific territory, there is no need to (...) jettison our existing moral sense. By discussing a range of real-life cases, it equips readers to make up their own minds on these important questions. Good science and good ethics needn't be contradictory. (shrink)

The complexity of the human brain creates a spectrum of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning, and consciousness. Understanding how the human brain achieves that has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition and disease states. Human pluripotent stem cells could differentiate into specialized cell types and tissues in vitro. From this pluripotent state, it is possible to generate models of the human brain, (...) such as brain organoids. The recent observation that brain organoids can spontaneously develop complex neural network activity in a dish can help one understand how neural network oscillations evolve and vary between normal and disease states. Moreover, this finding can be leveraged to other applications outside medicine, including engineering and artificial intelligence. However, as the brain model technology becomes more complex, it raises a series of ethical and moral dilemmas. This article discusses the status of this technology, some of its current limitations, and a vision of the future. (shrink)

Reinvention of the form of expression is a conceptual approach characteristic for the evolution of all arts. This research study provides one such step forward in the advancement of scientific paper, a standard form of expression in natural sciences, toward more progressive terrains. The paper adopts the form of a theatrical play where a scientific family of four attempts to find the way around a writer’s block (Act I). Their idealess sense of confinement is overcome through arts or, more specifically, (...) through scientific research implementing the aesthetics of music as its key element. The characters record compositions differing in the degrees of consonance, rhythmicity and tonality, and play them to birds to observe their vocal and behavioral responses (Act II). They note that the birdsong volume drops significantly when the piano tunes, especially the compositionally complex ones, are played to the birds and increases signifcantly when the white noise of ocean waves is played. The bird count experiment proves indirectly that the birdsong volume reduction is an auditory response of the birds to music rather than the effect of their migrating to or away from the sound source. This science with the flavor of art elevates the characters beyond the limits of their confinement and they, exalted and uplifted, gain ideas for creative research in their own disciplines of biomedical science (Act III). They relinquish the newly gained freedom in favor of embracing love for humanity that underlies medical research and return to their confinement, where they conduct, in the coda of the paper, a series of experiments that venture beyond musicology and ornithology and fall in the domains of tissue engineering and drug delivery, but also psychology (Act III). First, sparrow nests are used as templates for tissue engineering constructs, which facilitate the growth of human fibroblastic cells better than their artificial, gridded replicas. Next, the shell of an Easter egg, predominantly calcite in composition, is used with success as a drug delivery carrier. Lastly, the bird nest drawing experiment demonstrates a greater mental health of children than that of the adults, correlating with one of the overarching points of the paper, which is to present children as a model for grownups to follow rather than the other way around. Over the course of the play, the characters discuss the value of the various fusions between art and science, question the limits of human language and repeatedly go off-topic to celebrate the freeness of the creative thinking process. The play reports on real-life research methods and scientific results through a narrative, without diminishing their empirical rigor and analytical accuracy. (shrink)