This paper argues that embryonic development is best understood through the lens of process philosophy rather than traditional substance metaphysics. Drawing on both contemporary developmental biology and process thought, I demonstrate how key phenomena in embryogenesis-including morphogenesis, cellular differentiation, and organismal integration-align naturally with process-philosophical principles. Through critical engagement with major figures in developmental biology and philosophy of biology, including Turing's mathematical theory of morphogenesis and autopoietic approaches to biological organization, I show how persistent difficulties in (...) developmental biology stem from implicit substance-metaphysical assumptions and demonstrate how a process framework better captures the dynamic, relational nature of development. Furthermore, I argue that this perspective provides novel insights into emergence in biological systems while resolving longstanding theoretical difficulties in developmental biology. This theoretical framework has important implications for both biological understanding and experimental practice. (shrink)

Embryonic Stem Cell Research raises ethical issues. In the process of research, embryos may be destroyed and, to some, such an act entails the ‘killing of human life’. Past studies have sought the views of scientists and the general public on the ethics of ESCR. This study, however, explores multi-faith ethical viewpoints, in particular, those of Buddhists, Hindus and Catholics in Malaysia, on ESCR. Responses were gathered via semi-structured, face-to-face interviews. Three main ethical quandaries emerged from the data: (...) sanctity of life, do no harm, and ‘intention’ of the research. Concerns regarding the sanctity of life are directed at particular research protocols which interfere with religious notions of human ensoulment and early consciousness. The principle of ‘do no harm’ which is closely related to ahimsa prohibits all acts of violence. Responses obtained indicate that respondents either discourage research that inflicts harm on living entities or allow ESCR with reservations. ‘Intention’ of the research seems to be an interesting and viable rationale that would permit ESCR for the Buddhists and Hindus. Research that is intended for the purpose of alleviating human suffering is seen as being ethical. This study also notes that Catholics oppose ESCR on the basis of the inviolability of human life. (shrink)

Human embryonic moral status in the embryo debate in the Indian religious school of thoughts is a challenging issue. The paper tries to figure out whether ontological status implies moral status of embryo. Consciousness is an important determinant of animation of human embryo. In this paper an attempt had been made to understand the concept of man and soul in the Hindu philosophical thought. In the process we would also make a critical review of embryology in the Hindu (...) philosophical thought. The study would adopt a conceptual elucidation of morality. The paper made an elaborative study of Puruṣa as found in the Saṃkhya Philosophy and the study of consciousness and animation would try to resolve the related question, when does life begin to have that value? Embryo-protectionist regards embryos as a potential person. The Gita says the human person is individual self-called āttmā, whose nature is of pure consciousness, Brahman/Puruṣa. Consciousness constitutes the essentiality of individual Self. Human embryo developments are elaborately studied in the Yajñavalkya Smṛti, Garbha Upaniṣad, and Suśruta Saṃhitā. The self that remain latent in the embryo gets impetus with the association of consciousness until then it cannot be a human personality. In Hinduism sanctity of life gets combined with autonomy and self-determination. The sanctity of life applies both to the fetus as well as to the overall welfare of the society. The embryo being in an interim stage and the soul not being destroyed upon body annihilation, it may be claimed that since destruction or annihilation of the physical form does not destroy the soul, beneficial embryo research should thus not be abhorrent. The Hindu ethics as examined here precludes the consideration of the situation at hand, and causing the least harm and work according to one’s dharma. (shrink)

The recent success in generating live offspring from embryonic stem cell –derived gametes in mice sparked visions of growing tailor-made sperm for men faced with infertility. However, although this development will almost certainly lead to new insights into the processes underlying spermatogenesis and thus in the possible causes of male infertility, it is less certain if deriving sperm from ES cells, which are in turn derived from a sterile man, can make someone a genetic parent. As the gap between (...) newly envisioned reproductive technologies and natural reproduction widens, the question thus needs to be asked if these possible therapies still lead to genetic parenthood. (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)

The differentiation of mammalian neurons during development is a highly complex process involving regulation and coordination of gene expression at multiple steps. The P19 mouse embryonal carcinoma cell line is a suitable model system with which to analyze regulation of neuronal differentiation. These multipotential cells can be maintained and propagated in tissue culture in an undifferentiated state. Exposure of aggregated P19 cells to retinoic acid results in the differentiation of cells with many fundamental phenotypes of mammalian neurons. Undifferentiated P19 (...) cells are amenable to genetic manipulations such as transfection and establishment of stable clonal cell lines expressing introduced genes. Proteins that play a key role in the neuronal differentiation of P19 cells are beginning to be identified. These include retinoic acid receptors, the epidermal growth factor receptor and the transcription factors Oct‐3 and Brn‐2. The biological and technical advantages of this system should facilitate deeper analysis of the activities of proteins that play a role in neuronal differentiation. (shrink)

One of the earliest and most‐fundamental pattern‐ formation events in embryonic development is endoderm and mesoderm specification. In sea urchin embryos, this process begins with blimp1 and wnt8 gene expression at the vegetal pole as soon as embryonic transcription begins. Shortly afterwards, wnt8/blimp1 expression spreads to the adjacent ring of mesoderm progenitor cells and is extinguished in the vegetal‐most cells. A little later, the ring of wnt8/blimp1 activity moves out of the mesoderm progenitors and into the neighboring (...) endoderm cells. Remarkably, this moving ring of gene expression has now been shown to be controlled entirely by transcriptional cis‐regulatory logic.1. BioEssays 30:412–417, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In mice, dosage compensation of X‐linked gene expression is achieved through the inactivation of one of the two X‐chromosomes in XX female cells. The complex epigenetic process leading to X‐inactivation is largely controlled by Xist and Tsix, two non‐coding genes of opposing function. Xist RNA triggers X‐inactivation by coating the inactive X, while Tsix is critical for the designation of the active X‐chromosome through cis‐repression of Xist RNA accumulation. Recently, a plethora of trans‐acting factors and cis‐regulating elements have been (...) suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X‐linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. (shrink)

During the last decade neurotransplantation has developed into a technique with the possible potential to repair damaged or degenerating human brain. Effective neurotransplantation has so far been based on the use of fetal brain tissue derived from aborted embryos or fetuses. The ethical issues related to this new therapeutic approach therefore not only concern the possible adverse side effects for a neural graft-receiving patient, but also the relationship between the requirements for fetal tissue and the decision-making process for induced (...) abortion. Although for decades human embryos and fetuses have been the subject of biomedical studies, and, in principle, their use has therefore not been seen as ethically objectionable, the above points made it necessary to reconsider the moral issues. The present paper points out several of these issues, both from the donor and acceptor (patient) point of view. The conclusion is that under a series of restrictions intended to prevent the use of grafts from encouraging induced abortions and to maintain high standards of respect for life and human dignity, neurotransplantation using embryonic or fetal brain tissue parts cannot be rejected on moral grounds. (shrink)

The compromise position concerning the moral permissibility of different forms of human embryonic stem cell research has two commitments. The first commitment of this position is that it is morally permissible to derive hESCs from unwanted IVF embryos, despite the fact that this process involves the destruction of these embryos. The second commitment of this position is that it is morally impermissible to create human embryos for the sole purpose of destroying them in order to harvest their hESCs. (...) I argue that this compromise position concerning the moral permissibility of different forms of hESC research is theoretically tenable, but unappealing. In order to do so, I first claim that although it may be morally permissible to destroy embryos insofar as they do not have a right to life, it can still be coherent to view them as deserving moral respect. I then argue that one may plausibly view the practice of deriving hESCs from unwanted IVF embryos as being compatible with affording the embryo proper moral respect, whilst also maintaining that creating embryos for the sole purpose of destroying them in order to harvest their hESCs is incompatible with affording this respect. However, although I argue that one may plausibly adopt the compromise position in view of this moral difference between the two forms of hESC research, I also suggest that the compromise position is unappealing. My justification for this conclusion is that there are good reasons to support the claim that therapeutic cloning is morally permissible, even if we concede that it violates the moral respect due to the embryo. (shrink)

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned (...) and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts arise (...) from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

One of the goals of medicine is to improve well-being, in line with the principle of beneficence. Likewise, scientists claim that the goal of human embryonic stem cell research is to find treatments for diseases. In hESC research, stem cells are harvested from a 5-day-old embryo. Surplus embryos from infertility treatments or embryos created for the sole purpose of harvesting stem cells are used in the research, and in the process the embryos get destroyed. The use of human (...) embryos for research purpose raises ethical concern. In this context, the religious leaders play the role to be the moral compass and “reality check” to engage with the public. In Malaysia, the Ministry of Health has outlined the Guidelines for Stem Cell Research and Therapy, reflecting on Islamic principles. Since there has not been much focus on the viewpoints of other faiths in Malaysia, this study attempts to explore the ethical guiding principles deliberated by religious leaders from the Buddhist, Hindu and Catholic traditions and identify if there is a common ground between the mainstream religious views and principles of medical ethics, in relation to hESC research. Eleven religious leaders representing the Buddhist, Hindu and Catholic traditions were interviewed. Interestingly, though reasoning of religious leaders came from different angles, their underlying concerns revolve around the values of “do no harm” and “intention to save lives”. These values are also the key principles in medical ethics. The findings are applied to answer the question as to whether religious and medical guiding principles can co-exist and complement in ethical decision-making, without compromising the values. (shrink)

Embryogenesis involves biochemical patterning as well as mechanical morphogenetic movements, both regulated by the expression of the regulatory genes of development. The reciprocal interplay of morphogenetic movements with developmental gene expression is becoming an increasingly intense subject of investigation. The molecular processes through which differentiation patterning closely regulates the development of morphogenetic movements are today becoming well understood. Conversely, experimental evidence recently revealed the involvement of mechanical cues due to morphogenetic movements in activating mechano-transduction pathways that control both the differentiation (...) and the active morphogenesis of fundamental events in embryonic tissue development. Here I will first focus on the central role the shape of biological structures of the molecular and mesoscopic cell scales plays in mechano-transduction. Then, after a short description of the genetic regulation of the Drosophila embryo mesoderm invagination at gastrulation—one of the best-understood morphogenetic movement of embryogenesis—I will detail the processes of differentiation and of active morphogenesis of Drosophila embryo gastrulation, which require mechano-transduction. Finally, I will explore the putative consequences in evolution of these mechano-transduction events. I speculate that the first ancient multicellular organisms might have emerged from primary morphological and differentiation patterns induced by primitive mechano-sensation effects allowed by mechano-transduction in response to their physical environment, such as touch by gravity or water flows, which might have acted as primitive motor–sensorial systems, thus conditioning the emergence of our primary animal ancestors. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts arise (...) from the ectoderm in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

In October 2015 the UK enacted legislation to permit the clinical use of two cutting edge germline-altering, IVF-based embryonic techniques: pronuclear transfer and maternal spindle transfer. The aim is to use these techniques to prevent the maternal transmission of serious mitochondrial diseases. Major claims have been made about the quality of the debates that preceded this legislation and the significance of those debates for UK decision-making on other biotechnologies, as well as for other countries considering similar legislation. In this (...) article we conduct a systematic analysis of those UK debates and suggest that claims about their quality are over-stated. We identify, and analyse in detail, ten areas where greater clarity, depth and nuance would have produced sharper understandings of the contributions, limitations and wider social impacts of these mitochondrial interventions. We explore the implications of these additional considerations for the protection of all parties involved, should the techniques transfer to clinical applications; the legitimacy of focussing on short-term gains for individuals over public health considerations, and the maintenance and improvement of public trust in medical biotechnologies. We conclude that a more measured evaluation of the content and quality of the UK debates is important and timely: such a critique provides a clearer understanding of the possible, but specific, contributions of these interventions, both in the UK and elsewhere; also, these additional insights can now inform the emerging processes of implementation, regulation and practice of mitochondrial interventions. (shrink)

Skene and Parker1 raise a number of concerns about religious doctrine unduly influencing law and public policy through amicus curiae contributions to civil litigations or direct lobbying of politicians. Oakley2 picks this up in the same issue with an emphasis on the Roman Catholic Church’s interest in preventing the destruction of embryos for embryonic stem cell research. Skene, Parker, and Oakley seem to be concerned mostly with religious views having undue influence on public policy. My concern is the negative (...) effect that such Church influenced public policy may have on the progress of the biomedical research that is itself foundational to the debate. Oakley seems to be particularly incensed that, as he puts it: “Those who support a total ban on embryonic stem cell research sometimes talk as if theirs are the only views based on moral principle”.2 What seems to be at issue here though are not the moral principles of the sanctity and dignity of human life, but the application of those moral principles to biomedical research.The Roman Catholic Church has historically defended the sanctity and dignity of human life to varying degrees at different times. Human life for much of the past 2000 years was defined by the Church as the presence of the soul, which was thought at different times to appear at various different stages during development. Only recently, with the advent of modern biology, has the Roman Catholic Church shifted its position to claim that the fertilised egg also qualifies as the right sort of human life.3 It should be noted that this doctrinal change was fundamentally driven by developments in our understanding of embryology and not the process of ensoulment.The Church’s current position on the embryo is thus based not solely on Church doctrine but also on …. (shrink)

The precocious induction in vivo and in culture of insect and amphibian metamorphosis by exogenous ecdysteroids and thyroid hormones, and its retardation or inhibition by juvenile hormone and prolactin, respectively, has allowed the analysis of such diverse processes of post‐embryonic development as morphogenesis, tissue remodelling, functional reorganization, and programmed cell death. Metamorphosis in vertebrates also shares many similarities with mammalian development in the late foetal and perinatal period. This review describes the regulation of expression of some of the ‘adult’ (...) gene products during metamorphosis in invertebrates and vertebrates. Recent studies on metamorphosis have revealed the important role played by auto‐induction of hormone receptor genes, based on which a model will be presented to explain the activation of ‘downstream’ genes which give rise to the adult phenotype. It will also be argued that metamorphosis is an ideal model for analyzing some of the major mechanisms governing post‐embryonic development. (shrink)

This paper proposes a classification of hESC research regulation by shifting from the statutory content of relevant national Laws to the method of decision-making process, in order to verify whether it is possible to identify a connection between the concrete characters of that process and its outcome. A set of procedural indexes are identified and applied to the analysed legal systems. According to an increasing fulfilment of indexes, we may individuate two main regulatory families: the ‘value oriented’ and (...) the ‘procedure oriented’ ones. The latter is developing an increasing impact within European context: it is characterised by a mix of regulatory sources, each developing a specific function. Within this model, statutory law cannot infringe a regulatory space reserved to expertise and selfregulation, developing a subsidiary function; furthermore, it has to recognise the integrative role of expertise within statutory-making process. (shrink)

ABSTRACT Recent developments allow for the creation of human stem cells without the creation of human embryos, a process called alternate nuclear transfer (‘ANT’). Pursuing this method of stem cell research makes sense for pro‐lifers if arguments for the sanctity of the human embryo do not apply to ANT. However, the technology that makes ANT possible undermines the erstwhile technical barrier between human embryos and somatic cell DNA. These advances bring home the force of hypothetical arguments about the potential (...) of the DNA in somatic cells, showing that there is not a morally relevant difference between the potential of an embryo and the potential of the DNA in a somatic cell. Therefore, the supposed distinction between entities that are potential human life and entities that are human life does not give any support to arguments for the sanctity of the human embryo because those arguments extend value to too many entities. (shrink)

Amphibian metamorphosis is a post‐embryonic process that systematically transforms different tissues in a tadpole. Thyroid hormone plays a causative role in this complex process by inducing a cascade of gene regulation. While natural metamorphosis does not occur until endogenous thyroid hormone has been synthesized, tadpoles are competent to respond to exogenous thyroid hormone shortly after hatching. In addition, even though the metamorphic transitions of individual organs are all controlled by thyroid hormone, each occurs at distinct developmental stages. (...) Recent molecular studies suggest that this competence of premetamorphic tadpoles to respond to the hormone and the developmental stage‐dependent regulation of tissue‐specific transformations are determined in part by the levels of thyroid hormone receptors and the concentrations of cellular free thyroid hormone. In addition, at least two genes, encoding a cytosolic thyroid hormone binding protein and a 5‐deiodinase, respectively, are likely to be critical players in regulating cellular free thyroid hormone concentrations. This review discusses how all of these molecuar components coordinate to induce amphibian metamorphosis in a correct spatial and temporal manner. These studies provde us with general clues as to how and why tissues become competent to respond to hormonal signals. (shrink)

Embryonic development and ontogeny occupy whatis often depicted as the black box betweengenes – the genotype – and the features(structures, functions, behaviors) of organisms– the phenotype; the phenotype is not merelya one-to-one readout of the genotype. Thegenes home, context, and locus of operation isthe cell. Initially, in ontogeny, that cell isthe single-celled zygote. As developmentensues, multicellular assemblages of like cells(modules) progressively organized as germlayers, embryonic fields, anlage,condensations, or blastemata, enable genes toplay their roles in development and evolution.As modules, (...) condensations are fundamentaldevelopmental and selectable units ofmorphology (morphogenetic units) that mediateinteractions between genotype and phenotype viaevolutionary developmental mechanisms. In ahierarchy of emergent processes, gene networksand gene cascades (genetic modules) link thegenotype with morphogenetic units such ascondensations, while epigenetic processes suchas embryonic inductions, tissue interactionsand functional integration, link morphogeneticunits to the phenotype. To support theseconclusions I distinguish units of heredityfrom units of transmission and discussepigenetic inheritance by tracing the historyof relationship between embryology andevolution, especially the role(s) assigned tocells or to cellular components in generatingtheories of morphological change in evolution.The concept of cells as modular morphogeneticunits is modeled and illustrated using themammalian dentary bone. (shrink)

Emerging evidence suggests that microRNA (miRNA)‐mediated post‐transcriptional gene regulation plays an essential role in modulating embryonic stem (ES) cell pluripotency maintenance, differentiation, and reprogramming of somatic cells to an ES cell‐like state. Investigations from ES cell‐enriched miRNAs, such as mouse miR‐290 cluster and human miR‐302 cluster, and ES cell‐depleted miRNAs such as let‐7 family miRNAs, revealed a common theme that miRNAs target diverse cellular processes including cell cycle regulators, signaling pathway effectors, transcription factors, and epigenetic modifiers and shape their (...) protein output. The combinatorial effects downstream of miRNA action allow miRNAs to modulate cell‐fate decisions effectively. Furthermore, the transcription and biogenesis of miRNAs are also tightly regulated. Thus, elucidating the interplay between miRNAs and other modes of gene regulation will shed new light on the biology of pluripotent stem cells and somatic cell reprogramming. (shrink)

Silencing of tumor suppressor genes (TSGs), by DNA methylation, is well known in adult cancers. However, based on the “stem cell” theory of tumorigenesis, the early epigenetic events arising in malignant precursors remain unknown. A recent report1 demonstrates that, while pluripotent embryonic stem cells lack DNA methylation and possess a “bivalent” pattern of activating and repressive histone marks in numerous TSGs, analogous multipotent malignant cells derived from germ cell tumors (embryonic carcinoma cells) gain additional silencing modifications to those (...) same genes. These results suggest a possible mechanism by which aberrant differentiation, mediated by histone and DNA methylation, instigates tumor progression. BioEssays 29:842–845, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Colonial ascidians offer opportunities to investigate how developmental events are integrated to generate the animal form, since they can develop similar individuals (oozooids from eggs, blastozooids from pluripotent somatic cells) through very different reproductive processes, i.e. embryogenesis and blastogenesis. Moreover, thanks to their key phylogenetic position, they can help in the understanding of the molecular mechanisms of morphogenesis and their evolution in chordates. We review organogenesis of the ascidian neural complex comparing embryos and buds in terms of topology, developmental mechanisms (...) and terminology. We propose a new interpretation of bud territories, and reconsider nervous system development based on recent results suggesting that ascidians have vertebrate placodal and neural‐crest‐like cells. Comparing embryonic and blastogenic development in Botryllus schlosseri, we propose that the bud has territories with a placodal potentiality, suggesting that chordate ancestors possessed neurogenic placodes, and that the genetic pathways regulating neurogenic placode formation were co‐opted for new developmental processes, such as blastogenesis. BioEssays 28: 902–912, 2006. © 2006 Wiley periodicals, Inc. (shrink)

In one of his earlier essays he offered a sketch of what a philosophy ought to accomplish. It includes elements which have remained constant throughout thirty years of philosophical activity. He wrote then that the task of philosophy remains what it has always been: to "explain, not explain away, the world we all in some sense know." Prodded by the irritant of science and helped with the newly powerful instrument of modern logic, philosophy must build a system of explanation without (...) reduction. His later philosophy vigorously defends non-scientific ways of understanding and resists any capitulation of philosophy to science or logic, but both remain important for an adequate philosophy. The history of philosophy becomes perhaps even more important as time passes. PIP is taken up with long and intricate reflections on philosophers of every time and sort. In his early sketch, nevertheless, the history of philosophy is said to be valuable for avoiding past mistakes. The five errors he singles out have as their counterpart the embryonic concerns of the modal philosophy. (shrink)

Localized mRNA translation is a biological process that allows mRNA to be translated on‐site, which is proposed to provide fine control in protein regulation, both spatially and temporally within a cell. We recently reported that Vasa, an RNA‐helicase, is a promising factor that appears to regulate this process on the spindle during the embryonic development of the sea urchin, yet the detailed roles and functional mechanisms of Vasa in this process are still largely unknown. In this (...) review article, to elucidate these remaining questions, we first summarize the prior knowledge and our recent findings in the area of Vasa research and further discuss how Vasa may function in localized mRNA translation, contributing to efficient protein regulation during rapid embryogenesis and cancer cell regulation. (shrink)

Embryonic stem cell research is morally and politically controversial because the process of deriving the embryonic stem cells kills embryos. If embryos are, as some would claim, human beings like you and me, then ES cell research is clearly impermissible. If, on the other hand, the blastocysts from which embryonic stem cells are derived are not yet human beings, but rather microscopic balls of undifferentiated cells, as others maintain, then ES cell research is probably morally permissible. (...) Whether the research can be justified depends on such issues as its cost, chance of success, and numbers likely to benefit. But this is an issue for any research project, not just ES cell research. What makes the debate over ES cell research controversial is that it, like the debate over abortion, raises “questions that politicians cannot settle: when does human life begin, and what is the moral status of the human embryo?” This paper looks at several theories of moral status and their implications for embryo research. (shrink)

Embryonic development and adult tissue homeostasis are controlled through activation of intracellular signal transduction pathways by extracellular growth factors. In the past, signal transduction has largely been regarded as a linear process. However, more recent data from large‐scale and high‐throughput experiments indicate that there is extensive cross‐talk between individual signaling cascades leading to the notion of a signaling network. The behavior of such complex networks cannot be predicted by simple intuitive approaches but requires sophisticated models and computational simulations. (...) The purpose of such models is to generate experimentally testable hypotheses and to find explanations for unexpected experimental results. Here, we discuss the need for, and the future impact of, mathematical models for exploring signal transduction in different biological contexts such as for example development. BioEssays 30:1110–1125, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Embryonic development in Drosophila melanogaster begins with a rapid series of mitotic nuclear divisions, unaccompanied by cytokinesis, to produce a multi‐nucleated single cell embryo, the syncytial blastoderm. The syncytium then undergoes a process of cell formation, in which the individual nuclei become enclosed in individual cells. This process of cellularization involves integrating mechanisms of cell polarity, cell–cell adhesion and a specialized form of cytokinesis. The detailed molecular mechanism, however, is highly complex and, despite extensive analysis, remains poorly (...) understood. Nevertheless, new insights are emerging from recent studies on aspects of membrane polarization and insertion, which show that membrane components from intracellular organelles are involved. In addition, actin and actin‐associated proteins have been heavily implicated while new evidence shows that microtubule cytoskeletal elements are mechanistically involved in all aspects of cellularization. This review will draw on both the traditional models and the new data to provide a current perspective on the nature of cellular blastoderm formation in Drosophila melanogaster. BioEssays 24:1012–1022, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Embryonic development in a given species is orchestrated by genes regulating growth and differentiation in a stereotyped and conserved manner, resulting in embryos of consistent size and shape. Several signaling pathways, including that of Sonic Hedgehog (SHH), have been implicated in these processes. Recent experiments with Gas1 indicate that it may act as a growth-inducing gene, challenging its previous function as a gene specifically involved in growth arrest. Moreover, GAS1, a GPI-linked membrane protein, can bind SHH, suggesting an interacting (...) link between growth and patterning through SHH and GAS1.(1-4) BioEssays 24:22–26, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

The author demonstrates that professional bioethics is culturally very risk averse when it comes to evaluating the possible ethical consequences of new technologies such as genetic testing, human embryonic stem cells, and reproductive cloning. Deeper involvement in the Federal regulatory process by bioethicists will exacerbate this tendency toward risk aversion. This cultural bias toward caution will tempt many bioethicists to look to the so-called precautionary principle for policy guidance. Adopting the precautionary principle would harm patients by slowing the (...) development of new therapies. The author argues that bioethicists should reject the precautionary principle and instead rely on conscientious trial and error as a superior way to approach implementing new biomedical technologies ethically. (shrink)

Principles and processes of stakeholder management are still conceptually at an embryonic stage. This article analyzes several principles and processes important to understanding strategic management and business ethics. Using an inductive approach with empirical data from a Norwegian insurance company, the article contributes to a description of manipulation and power dimensions of stakeholder management. The capacity of the management of large companies to circumvent control and thus accountability is illustrated. New analytic insights are presented, such as the distinction drawn (...) between movement, multimatum, and manipulation. (shrink)

How is the embryonic bipotential gonad regulated to produce either an ovary or a testis? In males, transient early activation of the Y chromosome Sry gene makes both germ cells and soma male. However, in females, available evidence suggests that the process of ovary sex determination may take place independently in the germline and somatic lineages. In addition, in contrast to testis, in ovary somatic cells, female‐to‐male gonadal sex reversal can occur at times throughout ovary development and maturation. (...) We suggest that a single gene pathway, likely hinging on the Foxl2 transcription factor, both initiates and maintains sex differentiation in somatic cells of the mammalian ovary. BioEssays 29: 15–25, 2007. Published 2006 Wiley Periodicals, Inc. (shrink)

X inactivation is the process that brings about the dosage equivalence of X‐linked genes in females to that of males. This complex process initiated at a very early stage of female embryonic development is orchestrated by long non‐coding RNAs transcribed in both sense and antisense orientation. Recent studies present contradicting evidence for the role of small RNAs and RNase III enzyme Dicer in the X inactivation process. In this review, I discuss these results in the overall (...) perspective of X inactivation and gene silencing. (shrink)

After a tortuous legal process that resembled nothing so much as a game of chutes and ladders, on August 24, 2012, the United States Court of Appeals for the District of Columbia Circuit decided in favor of the Department of Health and Human Services' position that human embryonic stem cell research is not research that harms embryos, and therefore is not a violation of the Dickey‐Wicker Amendment. Bioethicists have been following this case because of our interest in the (...) ethics and politics of embryonic stem cell research, but the final decision hinged largely on a series of rather arcane points of law and procedure. (shrink)

Chondrogenesis is a key process in skeletogenesis since endochondral ossification requires the formation of a cartilaginous template. Knowledge of molecular mechanisms regulating chondrogenesis is extremely valuable not only to understand many human disorders but also in regenerative medicine. Embryonic skeletogenesis is an excellent model to study this mechanism. Most cartilages share the cellular basis underlying chondrogenesis but the high heterogeneity in morphologies of the different skeletal elements appears to be generated by differential participation of a variety of chondrogenic (...) signals. Here we overview the regulatory factors responsible for chondrogenesis concluding that early chondrogenic signals for the digit cartilages differ from those implicated in the formation of other axial and appendicular skeletal components. BioEssays 29:725–737, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The Principle of Procreative Beneficence (PB) holds that when a couple plans to have a child, they have significant moral reason to select, of the possible children they could have, the child who is most likely to experience the greatest wellbeing – that is, the most advantaged child, the child with the best chance at the best life.1 PB captures the common sense intuitions of many about reproductive decisions. PB does not posit an absolute moral obligation – it does not (...) dictate what people must do. Instead it holds that there is a significant moral reason to select the best child, but one that must be weighed against other reasons.Recent research suggests that it may become possible to derive gametes (eggs and sperm) from human stem cells in vitro, a process which we will term in vitro gametogenesis (IVG). The ability to create large numbers of eggs or sperm through IVG greatly increases our capacity to select the best child possible. (shrink)

Many sensory processing regions of the central brain undergo critical periods of experience‐dependent plasticity. During this time ethologically relevant information shapes circuit structure and function. The mechanisms that control critical period timing and duration are poorly understood, and this is of special importance for those later periods of development, which often give rise to complex cognitive functions such as social behavior. Here, we review recent findings in Drosophila, an organism that has some unique experimental advantages, and introduce novel views for (...) manipulating plasticity in the post‐embryonic brain. Critical periods in larval and young adult flies resemble classic vertebrate models with distinct onset and termination, display clear connections with complex behaviors, and provide opportunities to control the time course of plasticity. These findings may extend our knowledge about mechanisms underlying extension and reopening of critical periods, a concept that has great relevance to many human neurodevelopmental disorders. (shrink)

Challenging the posthumanist canon which celebrates the pre-eminence of matter, Ruth Miller, inFlourishingThoughtargues that what nonhuman systems contribute to democracy is thought. Drawing on recent feminist theories of nonhuman life and politics, Miller shows that reproduction and flourishing are not antithetical to contemplation and sensitivity. After demonstrating processes of life and processes of thought are indistinguishable, Miller finds that four menacing accumulations of matter and information--global surveillance, stored embryos, human clones, and reproductive trash--are politically productive rather than threats to democratic (...) politics. As a consequence, she questions the usefulness of individual rights such as privacy and dignity, contests the value of the rational metaphysics underlying human-centered political participation, and re-evaluates the gender relations that derive from this type of participation. Ultimately, in place of these human-centered structures, Miller posits a more meditative mode of democratic engagement. Miller's argument has shattering implications for the debates over the proper use and disposal of embryonic tissue, alarms about data gathering by the state and corporations, and other major ethical, social, and security issues. (shrink)

These two short, influential books, which grew out of Dewey’s hands-on experience in administering the laboratory school at the University of Chicago, represent the earliest authoritative statement of his revolutionary emphasis on education as an experimental, child-centered process. In The School and Society, he declares that we must “make each one of our schools an embryonic community life, active with types of occupations that reflect the life of the larger society and permeated with the spirit of art, history, (...) and science.” In The Child and the Curriculum he stresses the importance of the curriculum as a means of determining the environment of the child, and allowing the teacher to guide children in asserting themselves, exercising their capacities, and fulfilling their own nature. 8 black-and-white illustrations. (shrink)

The vertebrate spleen has important functions in immunity and haematopoiesis, many of which have been well studied. In contrast, we know much less about the mechanisms governing its early embryonic development. However, as a result of work over the past decade‐mostly using knockout mice–‐significant progress has been made in unravelling the genetic processes governing the spleen's early development. Key genetic regulators, such as Tlx1 and Pbx1, have been identified, and we know some of the early transcriptional hierarchies that control (...) the early patterning and proliferation of the splenic primordium. In mouse and humans, asplenia can arise as a result of laterality defects, or the spleen can be absent with no other discernible abnormalities. Surprisingly, given the spleen's diverse functions, asplenic individuals suffer no major haematopoietic or immune defects apart from a susceptibility to infection with encapsulated bacteria. Recent evidence has shed light on a previously unknown role of the spleen in the development and maintenance of specific B cell populations that are involved in the initial response to infection caused by encapsulated bacteria. The lack of these populations in asplenic mice and humans may go some way to explaining this susceptibility. BioEssays 29: 166–177, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The paper investigates Aristotle's simulation of the embryo (zygote) by a gear wheel mechanism. By this technical simulation of a natural thing Aristotle pursues an epistemic end, viz. to gain information on the efficient cause of embryonal development. Aristotle verifies the conjectured, yet unknown efficient cause of this natural process by means of a distinctive mapping of the artifact onto the embryo. The paper aims to show that Aristotle, to achieve this verification, tackles a calculus of relations with a (...) semantics of causal content, providing logicocausal deductions, an ancient causal analogue of the truth-preserving calculus of relations. The elements of this Aristotelian causal calculus are those relations among the components of composite things that Aristotle holds to be causal. To these causal relations he applies various operations, set extension and set restriction, substitution, generalization and particularization, in such a way that the causal content of the relations transformed is preserved, thus affording deductions of relations from relations that are valid in respect to their causal content. The paper finally aims to show that causal calculus, working well when applied to the gear wheel mechanism and the embryo, is not sound in every application. (shrink)

Thomas Sebeok and Noam Chomsky are the acknowledged founding fathers of two research fields which are known respectively as Biosemiotics and Biolinguistics and which have been developed in parallel during the past 50 years. Both fields claim that language has biological roots and must be studied as a natural phenomenon, thus bringing to an end the old divide between nature and culture. In addition to this common goal, there are many other important similarities between them. Their definitions of language, for (...) example, have much in common, despite the use of different terminologies. They both regard language as a faculty, or a modelling system, that appeared rapidly in the history of life and probably evolved as an exaptation from previous animal systems. Both accept that the fundamental characteristic of language is recursion, the ability to generate an unlimited number of structures from a finite set of elements (the property of ‘discrete infinity’). Both accept that human beings are born with a predisposition to acquire language in a few years and without apparent efforts (the innate component of language). In addition to similarities, however, there are also substantial differences between the two fields, and it is an historical fact that Sebeok and Chomsky made no attempt at resolving them. Biosemiotics and Biolinguistics have become two separate disciplines, and yet in the case of language they are studying the same phenomenon, so it should be possible to bring them together. Here it is shown that this is indeed the case. A convergence of the two fields does require a few basic readjustments in each of them, but leads to a unified framework that keeps the best of both disciplines and is in agreement with the experimental evidence. What is particularly important is that such a framework suggests immediately a new approach to the origin of language. More precisely, it suggests that the brain wiring processes that take place in all phases of human ontogenesis (embryonic, foetal, infant and child development) are based on organic codes, and it is the step-by-step appearance of these brain-wiring codes, in a condition that is referred to as cerebra bifida, that holds the key to the origin of language. (shrink)

Organoids and specifically human cerebral organoids (HCOs) are one of the most relevant novelties in the field of biomedical research. Grown either from embryonic or induced pluripotent stem cells, HCOs can be used as in vitro three-dimensional models, mimicking the developmental process and organization of the developing human brain. Based on that, and despite their current limitations, it cannot be assumed that they will never at any stage of development manifest some rudimentary form of consciousness. In the absence (...) of behavioral indicators of consciousness, the theoretical neurobiology of consciousness being applied to unresponsive brain-injured patients can be considered with respect to HCOs. In clinical neurology, it is difficult to discern a capacity for consciousness in unresponsive brain-injured patients who provide no behavioral indicators of consciousness. In such scenarios, a validated neurobiological theory of consciousness, which tells us what the neural mechanisms of consciousness are, could be used to identify a capacity for consciousness. Like the unresponsive patients that provide a diagnostic difficulty for neurologists, HCOs provide no behavioral indicators of consciousness. Therefore, this article discusses how three prominent neurobiological theories of consciousness apply to human cerebral organoids. From the perspective of the Temporal Circuit Hypothesis, the Global Neuronal Workspace Theory, and the Integrated Information Theory, we discuss what neuronal structures and functions might indicate that cerebral organoids have a neurobiological capacity to be conscious. (shrink)

Recently, Intelligent Tutoring Systems (ITS) got much attention from researchers even though ITS educational technology began in the late 1960s and ITS is just embryonic from laboratories into the field. In this paper we outline an intelligent tutoring system for teaching basics of the databases system called (MDB). The MDB was built as education system by using the authoring tool (ITSB). MDB contains learning materials as a group of lessons for beginner level which include relational database system and lessons (...) in the process to install and set up a database. MDB system has exams for each level of the Lessons. An evaluation was done to see the effectiveness the MDB among learners and instructors. The outcome of the evaluation was promising. (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)

Biological evolution is often viewed narrowly as a change of morphology or allele frequency in a sequence of generations. Here I pursue an alternative informational concept of evolution, as preservation, advance, and emergence of functional information in natural agents. Functional information is a network of signs that are used by agents to preserve and regulate their functions. Functional information is preserved in evolution via complex interplay of copying and construction processes: the digital components are copied, whereas interpreting subagents together with (...) scaffolds, tools, and resources, are constructed. Some of these processes are simple and invariant, whereas others are complex and contextual. Advance of functional information includes improvement and modification of already existing functions. Although the genome information may change passively and randomly, the interpretation is active and guided by the logic of agent behavior and embryonic development. Emergence of new functions is based on the reinterpretation of already existing information, when old tools, resources, and control algorithms are adopted for novel functions. Evolution of functional information progressed from protosemiosis, where signs correspond directly to actions, to eusemiosis, where agents associate signs with objects. Language is the most advanced form of eusemiosis, where the knowledge of objects and models is communicated between agents. (shrink)

Evolution exploits the physics of non‐neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear “developmental pathways” are often inadequate explanations for dynamic large‐scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but (...) also for the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system‐level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering. (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)