Abstract Moral status ascribes equal obligations and rights to individuals on the basis of membership in a protected group. Substance change is an event that results in the origin or cessation of individuals who may be members of groups with equal moral status. In this paper, two substance changes that affect the moral status of human embryos are identified. The first substance change begins with fertilization and ends with the formation of the blastocyst, a biological individual with moral status comparable to that ascribed to human organs. The second substance change begins at implantation and ends late in embryological development with the formation of the human body, an organism with moral status as a human being. The bioethical implications of each substance change are explored. The Two Substance Change theory is contrasted with continuity theories, which recognize no substance change in embryological development and with fertilization-only substance change theories. abortion, human embryo, metaphysics, moral status, stem cell research I. INTRODUCTION The moral status of the human embryo in early embryological development is a pressing problem in bioethics because embryonic stem cell research requires the sacrifice of early human embryos in the derivation of pluripotent cell lines and because in vitro fertilization (IVF) techniques in reproductive medicine countenance early embryo sacrifice as a consequence of cryopreservation. In addition, some forms of contraception may on occasion work by preventing implantation. The moral status of the embryo in late embryological development raises other ethical problems, including the moral permissibility of abortion in the first trimester. If human embryos have moral status as human beings, then they have the full panoply of human rights, including the right not to be killed in medical experiments and the right not to be endangered by the reproductive acts of other people. So, it is important to think clearly about this topic. In Section II of this paper, competing accounts of the moral status of the human embryo are examined in the context of alternative theories of embryological development. In Section III, I respond to two objections to substance change theories of embryological development. Section IV presents an argument for an alternative to fertilization-only substance change theories of the moral status of the human embryo. It is argued that fertilization is the first phase of a substance change that transpires over the first week in embryological development. This substance change results in the origin of a biological individual but does not result in the origin of a human being. In Section V, bioethical implications of the first substance change are identified. Section VI makes the case for a second substance change which transpires over eight weeks in late embryological development and which does result in the origin of a human being. In Section VII, bioethical implications of the second substance change are identified. In Section VIII, I argue that continuity theories of embryological development cannot provide an equally explanatory account of the moral status of the embryo. The conclusion summarizes the argument in support of the two substance change theories of the moral status of the human embryo. II. CONTINUITY AND MORAL STATUS In a recent paper published in this journal, Jason Morris contrasts continuity theories with substance ontology theories of embryological development (Morris, 2012). Continuity theorists view stages in early embryological development as pragmatically useful markers in a process of gradual quantitative change. Fertilization, for example, is a process in which the final stage in ovular meiosis overlaps with the pairing of maternal and paternal chromosomes at syngamy, which in turn initiates a series of mitotic cell divisions known as cleavage events at the end of which the newly formed embryonic genome begins to exert influence over the morphology and gene expression profiles of embryonic cell lines (Kiessling and Anderson, 2003; Naikan et al., 2012). On this view, Carnegie Stages and similar rubrics are useful heuristics for tracking smooth transitions in development but should not be mistaken for objectively real breaks in embryological or fetal development (Morris, 2012, 333). For Continuity Theorists such as Jason Morris, fertilization and other stages in embryological and fetal development are pragmatically convenient labels that enable social decisions regarding moral status to be adjudicated in a manner that reflects a reasonable balance between competing interests of individuals and social institutions (Morris, 2012, 331).1 Blastocysts, for example, may be assigned substantially higher moral status than activated ova because in the context of IVF-assisted reproduction they are potential children to gamete donors and potential siblings to one another. Natural embryo mortality rates in excess of 60%, on the other hand, provide strong pragmatic reason not to ascribe full moral status to the blastocyst. To do so would be to generate duties of rescue with which it would be impossible to comply. The moral status of the human embryo, according to continuity theorists, cannot be pegged to objectively real stages in development because those stages do not exist, but this does not mean that the choice to confer moral status is arbitrary. For Morris and other continuity theorists, moral status judgments are subjective only in the sense that they reflect a moral calculus between deeply held values, including the sanctity of human life, autonomy, privacy, and human equality. Social choice in this matter is contentious precisely because these values may not be shared equally by all members of the moral community. “Substance Ontology” is a form of metaphysical realism in which individuals are understood as temporally bounded substances with identities determined by essential properties derived from an ontological category, often a natural kind term, such as Homo sapiens. Among those essential properties are persistence conditions, either identity constituting sufficient conditions, identity destroying necessary conditions, or identity preserving life cycle transitions. A substance change occurs when an individual undergoes a change in essential properties, either at an origin event or at a cessation event. Substance change in this sense is a logical consequence of metaphysical realism with respect to temporally bounded individuals.2 For substance ontologists, discontinuities in embryological development are thought to be objectively real stages; some of which are identity preserving life cycle transitions, whereas others are substance changes. Substance change need not be abrupt or sudden—death, after all, is a substance change which can be extended for days or weeks in a modern Intensive Care Unit—but substance change does culminate in a qualitative change in essential properties. Cessation and origin substance change events also may occur in succession. Patrick Lee, for example, is a substance ontologist who identifies fertilization and relevantly similar cellular reprogramming as substance changes that signal the cessation of gametes or other precursor cells followed by the origin of an embryonic human being (Lee, Tollefsen, and George, 2014).3 Other substance ontologists recognize different developmental stages as substance changes, including gastrulation, organogenesis, and the onset of consciousness (Smith and Brogard, 2003). One might hold, for example, that the aftermath of fertilization is a substance change that results in the origin of a human organism which may be followed in the third trimester by a second substance change which signals origin of a person, understood as an embodied mind (McMahan, 2002). Alternatively, a substance ontologist might recognize fertilization as initiating a substance change that results in the origin of a biological individual that cannot be identified with a human being, followed by a second substance change later in embryological development, which signals the origin of an individual human being.4 This is the position that is defended in this paper. Continuity theorists may object that substance ontology depends on a discredited form of species essentialism. Traditional species essentialism holds that the essence of a species is a set of intrinsic properties held in common by all members of the species and which are individually necessary and jointly sufficient for species membership (Ereshefsky, 2010). Evolutionary theory, in contrast, holds that natural selection and other evolutionary forces operate on natural variability in intrinsic genetic, behavioral, and morphological properties. A common set of essential intrinsic properties would render evolution impossible. Continuity theorists of embryological development argue that the attempt to identify substance change on the basis of species-specific essential properties is out of step with contemporary science (Morris, 2012, 347). Discontinuity Theories can be reformulated within the Homeostatic Property Cluster species concept, a form of species essentialism that is compatible with evolutionary theory.5 A homeostatic property cluster consists in disjunctions of pairs of properties which influence their co-occurrence (Boyd, 1999). One or more underlying homeostatic mechanisms may generate systematic co-instantiation of pairs of properties. These mechanisms provide the causal explanatory basis for inductive generalization with respect to natural kinds such as chemical elements (Magnus, 2014). In biology, homeostatic property clusters may function to sustain dynamic equilibrium at two levels: over the lifetime of organisms and over evolutionary time for species. At the species level, natural kind stability is sustained through homeostatic mechanisms such as reproductive isolation of breeding populations and the constraints coadapted genotypes impose on heritability. Homeostatic property clusters that constitute the essence of a species are disjunctions of property clusters, no one of which must be instantiated by every member of the species, but at least one of which must be instantiated by any member of the species. In this way, homeostatic property clusters encompass sufficient biological heterogeneity for natural selection, while still functioning as the kind essence for a natural kind such as Homo sapiens. In organisms, homeostatic mechanisms are self-regulating negative feedback circuits through which variations in internal state are kept within parameters compatible with life and development. The hypothalamus in adult human beings, for example, maintains body temperature that fluctuates around 98.6°F through feedback from the bloodstream that initiates compensatory responses in breathing, perspiration, and blood sugar level. The hypothalamus is one component in an integrated network of homeostatic mechanisms in the central nervous system which function as a homeostatic central control system through which dynamic equilibrium is sustained within the body at a particular point in time and over extended periods of time. Specifically, homeostatic mechanisms that constitute the central control systems of organisms regulate transitions between species-specific developmental stages. Since the homeostatic property clusters that determine the species essence of organisms are disjunctive sets of homeostatic mechanisms, it is entirely possible that organic unity could be sustained by different homeostatic mechanisms at different developmental stages.6 Richard Boyd points out that this explains how developmental stages can be recognized as the life cycle of the same organism, even “in organisms whose [juvenile or] larval and adult stages are so dissimilar as to appear contraspecific” (Boyd, 1999, 163). Butterflies undergo metamorphosis without ceasing to be butterflies because alternative pairings of underlying homeostatic mechanisms in their species-specific homeostatic property cluster co-occur with greater frequency at certain points in their life cycle. Different configurations of homeostatic mechanisms function as the internal control system of the organism at different stages of development. In this way, homeostatic property clusters function as identity preserving intrinsic properties throughout development. The life cycle of human beings also can be understood as regulated by a succession of homeostatic mechanisms that constitute homeostatic central control systems that coordinate and integrate life processes. The onset of puberty, for example, is regulated by neurohormonal homoeostatic mechanisms in the pituitary gland, which complement ongoing brain stem and cardiovascular homeostatic mechanisms. Obviously, adolescence is not a substance change. Neither should a change in homeostatic control system in embryological development necessarily be interpreted as a substance change. If, on the other hand, no configuration of the human homeostatic property cluster is instantiated, then either the entity is not a human being or homeostatic collapse has led to the death of a human being. It is important to bear in mind that internal control systems belong to the organism as a whole. It would not be sufficient for the parts of an entity to have their own internal control systems operating in parallel. A flock of geese is not a bird; a tumor is not an organ; and dissociated cells in culture are not an organism. Organic unity presupposes a homeostatic internal control system that belongs to the organism as a whole in the sense that it coordinates and integrates subsystems to sustain the life and serve the interests of the organism. In an adult human being, organic unity in this sense is sustained by the brain stem, which in conjunction with other components of the central nervous system integrates and coordinates vital organ systems. It is for this reason that the Uniform Determination of Death Act defines human death as the irretrievable cessation of the integrative functions of the whole brain or the irretrievable cessation of the integrative functioning of the circulatory system (Bernat, 2006). Respiration and other vital functions may be sustained artificially by a number of medical devices operating in parallel in an Intensive Care Ward. Nonetheless, a cessation substance change is thought to have occurred because there is no proper part of the human body that functions as an internal control system which integrates and coordinates vital functions.7 The distinction between “Continuity Theories of Embryological Development” and “Substance Ontology Theories” leads to a parallel distinction between “Conferred Moral Status Theories” of the type Morris defends and “Intrinsic Moral Status Theories” of the kind Patrick Lee and I defend. In general, moral status ascribes equal rights, duties, and obligations to individuals on the basis of their membership within a group thought to be associated with moral values deserving of protection. Membership in the group may be a matter of social convention or it may be in virtue of an intrinsic property shared equally by all members of the group. Social conventions in the practice of medicine, for example, bestow upon individuals under the care of a physician moral status as a patient, which carries with it certain duties of beneficence that are owed equally to all patients. Intrinsic moral status, in contrast, entitles individuals to equal basic moral rights on the basis of the moral value of intrinsic properties shared by all members of the group. Personhood, understood as the capacity for rational self-consciousness, is commonly viewed as the morally valuable intrinsic property that elevates all persons to full and equal moral status. Intrinsic moral status adheres to individuals in virtue of traits which meet the threshold conditions for membership in a protected group. Moral status in this sense rests on an objective foundation; it cannot be conferred or withdrawn on pragmatic grounds or to serve the interests of third parties. It should now be clear why the distinction between “Continuity Theory” and “Substance Ontology” matters in discussions of the moral status of the human embryo. If, as Morris contends, embryological development is a smoothly continuous process of gradual change, then there are no natural groupings of embryos, all of whom would be entitled to equal protection on the basis of their membership in the group (Morris, 2012, 334). The moral status of embryos, if any, would be a matter of social convention. If substance ontologists correctly identify substance change in embryological development, then embryos, which cross these thresholds, are entitled to the same moral status as any other individual that crosses the threshold. Specifically, embryos that have entered the developmental stage at which they exemplify the essential properties of human beings would be entitled to intrinsic moral status as human beings. This is not to say that human embryos have the same moral status as human persons. At no point in embryological development does the embryo exhibit the neurological foundation for sentience or the higher order consciousness characteristic of personhood. Duties of beneficence to relieve suffering or autonomy rights to participate in medical decision-making cannot be reasonably ascribed to embryos. In this respect, the moral status of embryos who are human beings would be similar to the moral status of human beings who have never been conscious or who have lost the capacity for consciousness, but who in some sense have the potential for consciousness.8 III. TWIN CHALLENGES TO SUBSTANCE ONTOLOGY Jason Morris (2012) presents arguments of two kinds against substance ontology theories of the moral status of the early embryo. According to Morris, cellular reprogramming in induced pluripotent stem cells and in embryonic stem cell research demonstrates that the sequence of events occurring at fertilization consists in a continuous series of modest quantitative changes in cellular gene expression profile (Morris, 2012, 334). Since these molecular pathways can be readily replicated, manipulated, and reversed in settings that do not usher into existence a new human being, the very same processes should not be considered a substance change in the context of fertilization. The second argument Morris presents calls attention to implications of substance ontology with respect to monozygotic twinning, chimeric blastomere association, and similar phenomena that he finds deeply counterintuitive. These phenomena do pose a challenge to substance ontologists such as Patrick Lee, but I will argue that they are no threat to substance ontologists who locate the origin of human beings at a second substance change in late embryological development. In their response to Jason Morris in this journal, Patrick Lee, Christopher Tollefsen, and Robert George considered the first argument in detail, insisting that the crucial difference between fertilization and cellular reprogramming technology is that the latter causes the formation of an organically unified biological individual (Lee, Tollefsen, and George, 2014, 489). I will not challenge Lee, Tollefsen, and George’s claim that fertilization results in the origin of a new biological individual, although I will take issue with their claim that this individual is a human being.9 Lee, Tollefsen, and George may be right that fertilization is a sharp discontinuity that initiates a substance change in which sperm and ova cease to exist and a conceptus comes into existence with sufficient organic unity to be a biological individual in its own right. All by itself, this does not imply that the early embryo is a human being or that it has the moral status to which human beings are entitled. Individuality is a necessary but not a sufficient condition for intrinsic moral status as a human being. If the essential properties of the early embryo are not compatible with the essential properties of human beings, then whatever the early embryo might be, it is not a human being. Even if the early embryo is a biological individual as Lee, Tollefsen, and George argue, the conceptus could have full moral status only after a second substance change gives rise to a biological individual that is essentially human. A change in persistence conditions can result in substance change in two quite different ways: an individual could lose one or more of its essential properties as defined by its kind essence. It could suffer homeostatic collapse and die, for example. If, on the other hand, the persistence conditions that constitute the kind essence of an individual themselves undergo change, an origin substance change has occurred in which a new kind of individual has emerged.10 Specifically, if the persistence conditions of the early embryo are incompatible with the persistence conditions of human beings, then the early embryo and the human being to which it may give rise are not individuals of the same kind. Human beings would persist in accordance with the kind essence determined by the species Homo sapiens, whereas an early embryo might persist under the kind essence “Human blastocyst.” In this case, early embryos could not be identified with a human being at a later stage of development. A human embryo could be a biological individual, just not the same biological individual as a human being. Additionally, early embryos could have moral status of some kind, just not the same moral status as a human being. Two well-established phenomena in early embryological development imply that the early embryo persists under conditions different from adults and infants: monozygotic twinning and embryonic chimeric blastomere association. Identical twinning can occur at any time prior to the onset of gastrulation. This means that under certain conditions—a spontaneous or induced breach in the zona pelucida (the external boundary of the embryo at the cleaving blastomere stage) or a topographical separation of the inner cell mass (ICM) at the blastocyst stage—an early embryo may divide into two or more qualitatively indiscernible embryos, each of which may undergo separate embryological and fetal development. If two embryos come into close proximity at the cleaving blastomere stage, they may undergo a blastomere association fusion event. They merge to form a single embryo that may go on to develop into an adult human being. The result is a human chimera, a single human being whose tissues bear the marks of distinct genotypes. An indeterminate number of people are human chimeras, some with expressed genetic disorders, and others who appear completely healthy and may not even know their genetic history (Kopinski, 2004, 624–26). As a matter of logic, one individual cannot persist as two individuals; nor can two individuals persist as one individual. For this reason, a pre-twin embryo cannot be identified with either of its post-twin successors; nor can either pre-chimeric embryo be identified with its chimeric embryonic successor. It is not just that the logic of individual identity rules out a fertilization-only substance change account in these cases. More fundamentally, individuals capable of originating by fusion or ceasing to exist by division would not be members of the same natural kind as individuals who cannot do so. Lee, Tollefsen, and George suggest that many, perhaps all, cases of monozygotic twinning are forms of budding, in which one twin has substantially greater qualitative similarity with the pre-twin embryo and thus can be identified with it (Lee, Tollefsen, and George, 2014, 496). Budding does occur in nature—in yeast and groves of aspen—although it is unlikely to be the best explanation for monozygotic twinning at the cleaving blastomere stage. Cleavage is a form of mitotic cell division, which in general results in qualitatively indiscernible daughter cells. Perhaps monozygotic twinning due to topographical separation of the ICM at the blastocyst stage could be viewed as a form of budding, but even if plausible in some cases, the possibility that early embryos bud offspring simply reinforces the conclusion that early embryos are not individuals of the same kind as human beings. Reproduction by fission or fusion or budding is compatible with biological individuality—such phenomena are commonplace in microbiology, botany and invertebrate biology—but individuals that reproduce in this way clearly have different persistence conditions than individuals that are not capable of fission or fusion or budding.11 Nor does the fact that most human embryos do not divide or fuse or bud imply that they could be the human beings that emerge from gestation. Recall that persistence conditions are elements of the natural kind Homo sapiens, components of a species-specific homeostatic property cluster. As such, persistence conditions are modal properties that determine identity in all possible situations. Consider a scenario in which upon picking up one’s children from the day care center one was told that one’s daughter had divided into two sisters, one’s sons had fused into a single boy and that one’s eldest had budded off a new member of the family. How could this be possible? Children are not capable of such things, but embryos are. Pre-twin, pre-chimeric, pre-budding embryos are divisible, fusible, and buddible whether or not they actually divide, fuse, or bud. Children cannot divide or fuse or bud; early embryos can. Therefore, early embryos are not children. One might object that the day care center scenario shows that spontaneous division (fusion or budding) is not within the developmental repertoire of human beings, but this does not rule out some form of forced division (or fusion, or budding).12 Thought experiments in which the cerebral hemispheres of one person are surgically divided and transplanted into the skulls of two (brainless) human bodies have convinced some philosophers that personal identity is divisible.13 Could we not imagine something similar to the human body? The answer, I believe, is no, for reasons that are directly relevant to substance change in embryological development. Human beings are vertebrates, with bodies that are bilaterally symmetrical in many respects: two arms, two legs, two cerebral hemispheres, and so forth. Yet beneath the surface symmetries lie deep asymmetries: vital organs such as the heart, liver, and diaphragm are unitary, as are entire organ systems, including the gastrointestinal tract, the endocrine system, the urogenital system, and the spinal cord. Surgical separation along the bilateral axis would result in massive organ failure. Human beings would not survive bisection because the human body follows a vertebrate body plan that is established in late embryological development. It is at this point, the onset of the fetal stage of development at week nine postfertilization, that an indivisible human body makes its first appearance, and it is at this point, I argue, that a second substance change occurs, an event that heralds the origin of a human being. IV. THE FIRST SUBSTANCE CHANGE: FROM FERTILIZATION TO BLASTOCYST The idea that fertilization marks the beginning of human life strikes many people as scientifically informed common sense. It is common knowledge that conception is the immediate reproductive consequence of sexual intercourse; it is received wisdom that modern genetics demonstrates that the DNA formed at conception is the bedrock of biological identity. This view is essentially correct with respect to invertebrate species such as the fruit fly Drosophila (Nüsslein-Volhard, 2006, 45–9; Carlson, 2014, 37). Fertilization occurs rapidly and is followed in quick succession by rapid development of the larval body of the insect. In placental mammals such as Homo sapiens, events unfold in a different way and at a more leisurely pace.14 Before the human body can begin to form, the functional equivalent of a placenta must be in place. Many people are surprised to learn that fertilization of the human oocyte is not a momentary event, but a multiphase process that extends 24 hours or more, and that the DNA taken to be essential to human identity does not fuse until the next day (Nüsslein-Volhard, 2006, 111). They would be more surprised to hear that fertilization initiates a week-long process and that it results not in a baby, but in a protoplacental blastocyst. Embryological development in placental mammals encompasses two substance changes: from gametes to blastocyst and from blastocyst to offspring. Blastocysts are not parts of human beings; they are biological individuals in their own right. They may be generated within human beings, but this is true of other biological individuals, including countless intestinal tract microbiota and parasites. In an IVF clinic, blastocysts are capable of independent existence and follow their own developmental pathway. Their genotype is discordant with the genotype of their maternal hosts, which may recognize a blastocyst as a foreign body, eliciting an immune response a woman may experience as morning sickness. The human blastocyst can be described as a multicellular organism, which functions in accordance with a homeostatic property cluster which sustains dynamic equilibrium at a metabolic level and coordinates development through the brief life cycle of the blastocyst. The blastocyst consists of two epigenetically distinct cell lines organized into three anatomical subsystems. The trophoblast consists of metabolically active cells that encase the other blastocyst components. Prior to blastocystic hatching, the trophoblast is covered by the zona pelucida, a noncellular protein coat deposited on the oocyte at ovulation. The ICM is a mound of pluripotent stem cells from which the embryo proper and the amnion, yolk sac, and other extraembryonic support structures may develop. The third structure is the blastocoele, a fluid-filled cavity consisting primarily of water. The trophoblast is the internal control system that enables the blastocyst to sustain homeostatic dynamic equilibrium. In the fallopian tubes, IVF petri dish, or other suitably permissive environment, the trophoblast functions as an external boundary that prevents dissociation of the ICM and the blastocoele and acts as a barrier to toxins, bacteria, viruses, and other xenobiota. It regulates the internal milieu within parameters compatible with life, pumping water into and out of the blastocoele and enabling exchange of signal molecules in the uterine environment. The trophoblast also regulates development in the blastocyst. The trophoblast coordinates hatching, a major life cycle event in the blastocyst, in which it emerges from the zona pelucida in a manner reminiscent of a bird hatching from its shell. Hatching is initiated through rhythmic pulses in the trophoblast followed by corrosive enzyme secretions from trophoblastic projections (Carlson, 2014, 51). This creates an opening in the zona pelucida from which the blastocyst escapes. At this point, the trophoblast secretes immunosuppressant enzymes that inhibit maternal immunological rejection. Cell adhesion molecules form on the trophoblastic projections, which anchor the blastocyst to the uterine wall (Carlson, 2014, 52). The trophoblast flattens to form the trophoblastic plate for the chorion; the trophoblastic projections become primary chorionic villi; together the chorion and villi constitute the mature placenta (Carlson, 2014, 124). Just before implantation, the ICM undergoes a topographical change to become the bilaminar disc (Carlson, 2014, 75). Although not well understood in the human case, this developmental milestone almost certainly is influenced by alterations in the biochemical milieu in the interior of the blastocyst initiated by activity of the trophoblast. Toward the end of its life cycle, the blastocyst either disintegrates as a result of implantation failure or successfully implants in the uterine wall, a result that elicits the decidual reaction in the maternal endometrium (Carlson, 2014, 51–3). The decidual reaction culminates in the fusion of the blastocyst with the maternal decidua, a substance change in which the blastocyst ceases to exist as a distinct individual. This fusion event is different in significant ways from gametic fusion at fertilization, but decidual fusion is similar in that it is a cessation event followed by an origin event. Actually, the decidual reaction signals the emergence of two new biological individuals: a fetomaternal organ, a fully functional placenta, and an organically unified embryo, a biological individual with its own persistence conditions and internal control system. These substance changes are neither sudden nor abrupt. On the contrary, this process transpires throughout late embryological development and ultimately yields a radically new kind of biological individual, a human being. At this point, some may object that if the blastocyst were viewed as a biological individual, it would make more sense to identify it with the ICM, which will develop into the embryo proper and from there into the fetus and newborn.15 The ICM may be in some sense the most important part of the blastocyst, but this does not mean that it or any of its proper parts are biological individuals, much less the same biological individual as the fetus. The ICM falls well short of the organic unity constitutive of a biological individual. Its principal activity is mitotic cell division, which appears to proceed independently in each cell line. No part of the ICM is a plausible candidate for an internal control system that integrates and coordinates the mass of cells as a unified organism. They interact so weakly that mere separation of the cell mass into two heaps in the blastocystic cavity can result in monozygotic twinning (Gilbert, Tyler, and Zacklin, 2005, 15–7). The trophoblast may be the basket, but the ICM is not the baby. Perhaps, one could view each embryonic stem cell in the ICM as a nascent form of human life. If embryonic stem cells are transferred to a host trophoblast through a technique called tetraploid complementation, they may be induced to traverse a developmental pathway leading to live birth.16 On this view, the trophoblast is merely the permissive environment in which offspring develop. It would seem to follow that each of the cells in the ICM is an embryonic human being who may be entitled to the same moral status as anyone else, a result even more strange than the day care center scenario. In any case, embryonic stem cells cannot be identified with human beings because their persistence conditions include a form of division incompatible with being human. Embryonic stem cells transferred to a trophoblastic environment would undergo a cessation substance change at the first mitotic event. The ICM cannot be identified with the embryo proper for another reason: ICM cells are pluripotent in the sense that not only can they generate any of the 200 cell lines that make up the human body, but they are also pluripotent in the sense that they can generate certain extraembryonic support structures, such as the amnion and umbilical vesicle. The bilaminar disc that forms just before implantation consists of the lower layer, the hypoblast, which follows a differentiation pathway to the primary and secondary yolk sac, and an upper layer, the epiblast, which undergoes gastrulation and subsequently develops as the embryo proper. One could not identify the embryo proper with the ICM as a whole since the ICM consists of the hypoblast and epiblast, but one might be tempted to identify the embryo proper with part of the ICM, the epiblast. However, even if one could distinguish hypoblast cells from epiblast cells in the ICM, it still would be logically impermissible to identify the embryo proper with the epiblast cells of the ICM. After implantation, the epiblast itself differentiates along two cell lineage pathways, one terminating in another extraembryonic structure, the amnion, and the other developing as the embryo proper (Carlson, 2014, 75–6). One might describe the epiblast as either the embryo proper or the amnion, but if so, the embryo proper could not be identified with the epiblast. Nor is it possible to identify in the blastocyst the part of the epiblast that will give rise to the embryo proper, because cell line branching occurs after the decidual reaction, when the blastocyst has ceased to exist as a separate individual. The reason for these failures of identity is clear: at the blastocyst stage, the embryo proper has not yet begun to develop. The ICM may be a mere heap of dissociable stem cells, but the blastocyst can be considered a biological individual in its own right. It is sufficiently integrated to meet a minimal threshold of organic unity and traces a life cycle defined by a coherent set of persistence conditions. The emergence of a human being, with its own, quite different, internal control system, is something that occurs later, perhaps much later, in embryological development. Fertilization-only proponents such as Lee, Tollefsen, and George contend that embryos at the zygote and cleaving blastomere stage also are biological individuals. Like blastocysts, they are capable of independent existence and follow a distinctive developmental trajectory; also, like blastocysts, zygotes and multicell embryos cannot reasonably be considered parts of host organisms. The key difference between blastocysts and embryos at the zygote and cleaving blastomeres stage is that the latter does not possess an internal control system that sustains organic unity.17 The genetic and epigenetic properties on which Lee, Tollefsen, and George (2014, 493–95) place such emphasis cannot fulfill this function in the zygote because the embryonic genome does not form in the one-celled zygote. Paternal and maternal pronuclei commingle for the first time in the nucleus of the two cells that result from the first mitotic event (Kiessling and Anderson, 2003, 59; Gilbert, Tyler, and Zacklin, 2005, 63; Nüsslein-Volhard, 2006, 111). The immediate consequence of fertilization is completion of ovular gametogenesis, beginning with re-initiation of meiosis II at the acrosome reaction and culminating in the alignment of pronuclei at syngamy. The oocyte to embryo transition (OET) occurs over three days of blastomere cleavage, in which mitosis results in totipotent, autonomous cells of approximately equal, decreased size. The conceptus is transcriptionally silent at the onset of OET, during which maternal ovular RNA is downregulated and degraded. The first wave of embryonic genome activation (EGA) occurs on the third day postfertilization, at the four- to eight-cell stage. Lineage restriction EGA begins shortly thereafter, at the early blastomere stage, followed by successive waves of EGA throughout development (Naikan et al., 2012). For Lee, Tollefsen, and George (2014, 484), the OET period is better understood as a developmental stage of an embryonic human being. They emphasize the role of regulation at the four- to eight-cell stage, suggesting that this property invests cleaving blastomeres with the organic unity of an organism. The authors write: “It is in this context [the eight cell stage] that the regulative nature of the embryonic system takes on such importance . . . the embryo develops in the same manner—adapts—despite removing or adding cells to the early (preimplantation) embryo . . . with regularity and predictability in a way that contributes to the survival and development of the whole” (italics in original; ellipsis omits references to Jason Morris) (Lee, Tollefsen, and George, 2014, 500–1). “Regulation” is a distinctive property of embryos at the cleaving blastomere stage, but the way Lee, Tollefsen, and George use the term may be misleading. In most contexts, regulation implies a feedback mechanism of some sort, something that aligns internal processes along a narrow causal pathway. In the context of cleaving blastomeres, regulation refers to the ability of a multicell embryo to produce a normal structure even if blastomeres have been removed or replaced (Carlson, 2014, 45). In a procedure known as “Preimplantation Genetic Diagnosis,” for example, a blastomere may be removed from an eight-cell embryo for biopsy without affecting the development of the embryo. It simply continues to cleave until blastomeres are sufficiently compacted to initiate formation of the blastocystic trophoblast. Monozygotic twinning at the cleaving blastomere stage is another illustration of regulation in this sense: one or more blastomeres separate from the multicell without any discernible effect on the development of the twins or triplets. The regulatory nature to which Lee, Tollefsen, and George draw attention is a consequence of epigenetic silence prior to the first wave of EGA. Regulation in this sense actually implies the absence of an internal control system in the three days of OET. The zona pelucida is the remaining candidate for an internal control system in the preblastocyst embryo. Lee, Tollefsen, and George rightly emphasize its unifying role: the zona pelucida hardens after fertilization, preventing polyspermy; it prevents disaggregation of blastomeres; and it protects the embryo from toxins (Lee, Tollefsen, and George, 2014, 498–99). The zona pelucida also is a permeable membrane, permitting small molecule exchange between embryo and maternal environment. Nonetheless, the zona pelucida is a poor candidate for an embryonic internal control system. The zona pelucida is a noncellular protein coat deposited on the oocyte at ovulation. Since it is not part of the embryo, it cannot be the unifying part of the embryo. Even if it were stipulatively defined as part of the early embryo, the zona pelucida is metabolically inactive, rendering it causally inert as a homeostatic mechanism. In the absence of a plausible source of organic unity in the multicell embryo, it is reasonable to conclude that blastomere cleavage is a stage in the OET, an extended substance change that begins with fertilization and culminates in the formation of the blastocyst. The first substance change transpires over five days in early embryological development and gives rise to a new biological individual. The blastocyst may not be an individual human being, but it is a form of human life and, as such, may well be entitled to moral status of some kind. V. BIOETHICAL IMPLICATIONS OF THE FIRST SUBSTANCE CHANGE A full account is beyond the scope of this paper, but a brief overview may help to reframe the debate on the moral status of the early embryo. If the early embryo is a protoplacental blastocyst, then its moral status would be comparable in certain respects to transplantable human organs and tissue. This is not to say that the blastocyst is an organ. Organs are parts of an organism; the human blastocyst is a biological individual. Nonetheless, the moral status of the human blastocyst is analogous in certain respects to the moral status of human organs.18 Transplantable human hearts and kidneys do not have intrinsic moral status because the intrinsic properties that make them hearts and kidneys do not have intrinsic moral value, but there is good reason to confer on them a form of moral status that protects them from commodification in the market, distributes them in a fair process to individuals in need of a transplant, and expresses respect for human dignity. Conferred moral status at this level would imply that blastocysts should not be bought, sold, procured, or produced for market transactions; they should not be considered property in the disposition of an estate on the death of progenitors, nor should they be awarded to litigants in the division of assets in a divorce decree (Crockin and Howard, 2010). Policies governing the disposition of blastocysts created for reproductive purposes but no longer needed for reproductive purposes by their progenitors should be formulated in a process similar to that through which United Network of Organ Sharing allocation protocols were developed (Childress, 1997). Clearly, there are important differences here—progenitors of early embryos have interests different from organ donors, for example—but in both cases distribution decisions should be transparent, fair, and bioethically justified. Conferred moral status comparable to that bestowed on human organs would lend itself to a generally permissive regulatory regime in embryonic stem cell research, IVF-embryo transfer assisted reproduction and forms of contraception that may act by preventing implantation. It is also compatible with the creation and sacrifice of early embryos for legitimate biomedical research, for the treatment of infertility, or for embryonic stem cell-derived cell transplantation therapy, should this technology prove to be safe and effective. Since blastocysts are in no sense human beings, they do not have a right to life or a right not to be used merely as a means to an end. Reasonable complicity avoidance provisions may be built into public policy out of respect for the sensibilities of those who believe on religious or philosophical grounds that early embryos actually are human beings, but these restrictions should not prevent those who choose to accept the medical benefits of embryo research from doing so.19 The analogy between early human embryos and human organs explains why progenitors of surplus IVF embryos in reproductive medicine are entitled to donate them to other patients or for scientific research. Hundreds of thousands of cryopreserved embryos have been effectively abandoned by their progenitors, something these motivated parents would never dream of doing to their children, but something that they may well have done with tissues and organs removed in medical procedures. On this view, cryopreserved embryos are neither possible children nor potential children. They are blastocysts that may give a child the gift of a nurturing environment in which to grow. The analogy between transplantable human organs and transferrable human embryos fails in one important respect. Blastocysts created for reproductive purposes have the intrinsic potential to become particular people with a quite specific repertoire of genetic traits and dispositions. This is the moral relevance of the ICM: at a minimum, IVF blastocysts selected for transfer have intrinsic moral status that entitles them to a maternal environment as free from teratogenic disruption as possible. They also may be entitled to screening of adoptive families to identify those willing and able to nurture their genetic endowment. Other moral protections may flow from the intrinsic potential of blastocysts in the context of reproductive medicine. Both the transplantable organ analogy and the intrinsic potential moral status proposal are intended to be suggestive. Obviously, much more argument would be needed to persuade those not already inclined to accept these moral conclusions. It is worth noting that the “Two Substance Theory” bypasses certain counterintuitive ethical implications with which fertilization-only advocates struggle (George and Tollefsen, 2008, 135–42). Identical twinning and chimeric fusion are not tragic events in which children met an untimely end; implantation failure is not a natural disaster on a monumental scale; and there should be no question that one should save a toddler at a fire in a fertility clinic before rescuing vials of frozen embryos. These events are no more occasions for remorse over the loss of human life than failure to conceive is a misfortune to an imagined child.20 VI. THE SECOND SUBSTANCE CHANGE: FROM BLASTOCYST TO HUMAN BEING The blastocyst comes into existence at approximately five days postfertilization; implantation results in its cessation by fusion by the end of the third week. Implantation also triggers gastrulation, the first differentiation event in the development of the human body. By the end of the second week, the epiblast consists of a trilaminar disc, with three somatic cell lineages: ectoderm, endoderm, and mesoderm (Moore, Persaud, and Torchia, 2013, 77–9). This structure is sufficiently complex to foreclose the possibility of embryonic twinning, fusion, or budding. This discontinuity in embryological development has convinced some bioethicists to identify gastrulation as the substance change that signals the beginning of human life. In part for this reason, policy makers in the United Kingdom and other parts of the world have enacted regulatory regimes that sharply restrict embryo research after 14 days.21 I believe that this is a mistake. For asymmetrical vertebrates such as human beings, individuation is a necessary condition for an origin substance change, but it is not sufficient. The entity that emerges from gastrulation also must exhibit the organic unity characteristic of an animal life form. It must have an identifiable internal control system that belongs to the organism as a whole. Here, as elsewhere, it is critically important to bear in mind the distinction between unrealized potential and functional capacity: otic pits are not ears; optic cups are not eyes; and, more to the point, the primitive streak is not a spinal cord. The primitive streak is an indentation in the trilaminar disc that forms in the immediate aftermath of gastrulation; it often is taken as the marker that individuation has occurred. The primitive streak also establishes the top-bottom and left-right axes of the human body, but by the end of the fourth week (Carlson, 2014, 80), the primitive streak regresses and eventually disappears entirely, replaced by the neural plate, the first phase of neurulation. The primitive streak might be considered a potential spinal cord in the sense that it traces the axes for a functional autonomic nervous system, but it does not function as the internal control system of the postgastrulation embryo. How could it, if it disappears? Nor is any other site a plausible candidate for internal control system in the third week of development. During the brief lifespan of the blastocyst, the trophoblast functions as both a homeostatic and developmental central control system, but it ceases to exist at the decidual fusion event in the aftermath of implantation. In the postgastrulation embryo, a number of signaling centers appear to operate in parallel, with the primitive node organizing the notochord, the prechordal plate coordinating formation of the head, and somites forming at multiple sites (Carlson, 2014, 89). The embryo is in the midst of the second substance change, from blastocyst to human being. By the end of embryological development, parallel developmental processes converge on an organically unified human body. In retrospect, one may be tempted to interpret these events as coordinated development directed by the organism that eventually emerges. The teleological temptation should be resisted. In the absence of a functional central control system that sustains physiological homoeostasis and coordinates development, the human body has not yet come to life. Neurulation may seem a more promising candidate for the emergence of an internal control system in embryological development. The neural plate invaginates, closes at head and tail, partitions the neural crest, and segments in a manner that foreshadows the gross anatomy of the human brain. The neural tube is in some sense a potential central nervous system (Carlson, 2014, 92–7). However, neither the neural tube nor the central nervous system to which it gives rise have the capacity to function as the internal control system of the body until late in fetal development. In general, neural fibers become functional when myelin sheaths form on the axonal arms of neurons (Moore, Persaud, and Torchia, 2013, 253). Without myelination, neither the motor neurons nor the sensory neurons of the central nervous system can send and receive signals through which it could integrate the fetal body as a whole. By 26 weeks, the central nervous system has matured to the point where it can direct rhythmic breathing, control body temperature, and coordinate the function of major organ systems (Moore, Persaud, and Torchia, 2013, 67). From this point until brain death, it will function as the central control system of the human body. Some philosophers are tempted to identify the onset of central nervous system function as the substance change that heralds the true origin of individual human life. Just as brain death, understood as the irretrievable loss of the capacity of the central nervous system to integrate major organ systems, is the death of a human being, the beginning of human life may be identified with brain life, the onset of the capacity of the central nervous system to integrate major organ systems (Burgess, 2010, 37). There is a pleasing symmetry here, but theoretical elegance is not an argument. It is entirely possible that organic unity in the late embryo and early fetus is founded on an internal control system different from that which serves this function in later life.22 Myelination of the central nervous system occurs within a fetal body that already exhibits organic unity through an internal control system that was fully functional in late embryological development: the human heart. The cardiovascular system is the first functional organ system in human development. By the fourth week postfertilization, the embryonic body is growing rapidly. Simple diffusion is no longer sufficient to resupply nutrients and dispose of waste through the maternal bloodstream. The embryo needs actively to transport oxygen and calories and remove carbon dioxide and metabolic waste. By the end of the fourth week, the embryo has a functioning two-chambered heart, although the cardinal veins of the circulatory system have not yet formed (Carlson, 2014, 420–22). By the end of embryological development at week eight, a fully functional four-chambered heart is pumping fetal blood through two circulatory arcs, one that serves the emerging fetal body, the other that nourishes placental structures through the umbilical cord (Carlson, 2014, 104–7). The embryonic cardiovascular system functions both as transport system for the embryo as a whole and as carrier of signal molecules that coordinate the integrated development of other tissues and organ systems, all of which have been established at eight weeks postfertilization (Moore, Persaud, and Torchia, 2013, 40–5). Fetal development is largely a matter of growth in size of the embryonic body plan and growth in the functional capacity of organs, tissues, and fluids established at organogenesis. At nine weeks postfertilization, the cardiovascular system is a plausible candidate for the internal control system for an organically unified human body. The kind essence of “human being” is determined by the homeostatic property cluster that constitutes the species essence of Homo sapiens. As the Uniform Determination of Death Act makes clear, cardiovascular integration of vital systems may be considered a sufficient condition for human life.23 The late embryo thus may be considered a human being, numerically identical to the fetus and to infant, child, and adult. Recall that homeostatic property clusters are disjunctive sets of identity preserving properties. At different developmental stages, different homeostatic mechanisms contribute to the internal control system through which a human being lives and grows. Indeed, the internal control system through which the fetal body sustains organic unity undergoes a transition from cardiovascular-based regulation to central nervous system control late in fetal development. Cardiovascular homeostatic mechanisms and central nervous system homeostatic mechanisms are equally properties in the homeostatic cluster through which organic unity is sustained at different stages of human development. Similar transitions occur at birth as the fetal alimentary and respiratory systems take on functions performed by subsystems in the maternal body. Transitions of this kind do not signal substance change because they are consistent with the homeostatic property cluster that regulates the human life cycle. In contrast, the emergence of a functioning cardiovascular system late in embryological development signals an origin substance change because at this point a human body has begun to function as an organism. The substance change from blastocyst to human being appears to transpire over an entire month. While neither sudden nor abrupt, the late embryological substance change occurs rapidly relative to the seven-month fetal stage; relative to the 70-year life cycle of human beings, the second substance change is a brief interlude between protoplacenta and living human body. The notion that a substance change resulting in an entity as complex and interconnected as a human being could be a momentary event always did carry with it a whiff of the miraculous. VII. BIOETHICAL IMPLICATIONS OF THE SECOND SUBSTANCE CHANGE Here, as with the first substance change, a full account is beyond the scope of this paper. The thesis that human life begins at eight weeks postfertilization has implications for the morality of abortion and other bioethical issues that have generated a vast literature. The most that can be done at this point is to identify ways that this thesis may reframe the debate. The first point to acknowledge is that one could accept a cardiovascular standard for the substance change that generates a human being, but argue that the onset of cardiovascular function occurs somewhat earlier, say, six weeks postfertilization. In either case, the second substance change transpires over approximately a month after implantation, during which time the embryo has not yet met the organic unity criterion for biological individuality as a human being. Until this standard is met, the late embryo would continue to have moral status similar to that of human organs. The cardiovascular standard for organic unity thus implies that it may be possible to justify ethically a substantially more permissive regulatory environment for embryonic stem cell research and developmental biology. In principle, cell lineages derived from late embryos would be available for both clinical biomedicine and basic research. Multipotent neural, pancreatic, cardiac, and other biomedically important tissue types derived from late embryos could be available for cell transplantation therapy or for research into the mechanisms that direct stem cell lines along specific differentiation pathways. Access to these cell lines could dramatically accelerate translation of embryonic stem cell research into a clinical setting. Controlled experiments and observation of cell lines derived from late embryos also could lead to more rapid progress in replicating differentiation pathways in induced pluripotent stem cells and related reprogramming technologies. Clinical applications of the bioscience of the late embryo, as well as the research itself, should be protected from commodification and other market forces, preferably through public funding and regulatory side constraints that are transparent, fair, and respectful of the symbolic value of the human embryo (Steinbock, 2001). In some jurisdictions, considerations of public civility may render such an expansion of embryo research politically unattainable. The implications of a cardiovascular standard of organic unity in reproductive medicine are also far-reaching. Pregnancy termination by dilation and extraction prior to fetal development and abortifacients such as RU 486 that act late in embryological development would be treated as routine medical care, subject to beneficence, non-maleficence, and autonomy constraints on maternal care. On this view, there is no individual who has a future like ours that is deprived of a life that has independent moral value.24 Abortion in the fetal period would be a much more serious matter. The interests of an individual with moral status as a human being now are at stake, an individual whom the woman may reasonably regard as her son or daughter. The fetus would have moral status as a patient in the context of obstetric and pediatric medicine. A woman who intended at eight weeks to bring the pregnancy to term may reasonably be expected to assume some responsibility and risk for the sake of her fetus (McCullough and Chervenak, 2008). Therapeutic abortion still may be justified in the fetal period if termination is in the best interests of the woman or the fetus. VIII. THE INCOMPLETENESS OF CONTINUITY THEORIES OF MORAL STATUS Jason Morris claims that the continuities revealed in developmental biology show that it is not possible to “determine when in development a being transits from non-human to human” (Morris, 2012, 331). Attempts by substance ontologists to “draw clear lines between humans and non-humans introduces . . . a false dichotomy between developmental stages” (Morris, 2012, 348) which “should not be used to assign moral status to different developmental stages” (Morris, 2012, 334). Morris is primarily concerned with continuities in early embryological development, but he does not hesitate to extend his analysis to stages in late embryological and fetal development. He dismisses as “rationalizations” proposals by philosophers that identify gastrulation, neurulation, sentience, viability, and birth as objective markers for the transition from nonhuman precursor to human being (Morris, 2012, 347). Human development is said to be continuous from beginning to end; any attempt by philosophers to identify a substance change will result only in an illusion of objectivity (Morris, 2012, 348). Moral status as a human being, according to Morris, is acquired through an unavoidably subjective process in which individuals attempt to reach a consensus that reflects their values (Morris, 2012, 349). If continuity theorists are right about this, then the social decision to confer or withhold moral status on embryos and fetuses extends to all stages of human development. Infancy, childhood, and adolescence are stages in human development no less continuous than zygote, embryo, and fetus. This would seem to imply that the human rights of infants, children, and adolescents could be revoked at any time. Indeed, the individuals who are privileged to express their subjective values in moral status judgments do not themselves have an objective claim to moral status as human beings. Competent adult is just one more stage in a continuous process of human development within which no objective markers of the transit from nonhuman to human can be found. The human rights of men and women would rest on the same subjective foundation as the rights of human beings at other developmental stages. I do not for a minute believe that Morris and other continuity theorists think that infants, children, adolescents, and adults do not have moral status that is independent of social convention. Continuity theorists may take it as obvious that some people have moral status as human beings, but if so, they need to say when and how the transition from nonhuman to human occurs; that is, they need to identify a substance change somewhere in human development. That is tantamount to abandoning continuity theory as Morris and others have defended it. Continuity theorists may reply that even though no discrete event can be identified as a substance change in human development, there nonetheless is an objective difference between human precursors early in development and human beings in the prime of life. Perhaps the entirety of gestation is a gradual, continuous transition from nonhuman cells to complete human being. Recall, however, that nothing in the concept of substance change requires it to be sudden or abrupt. Substance change could take a day, or a week, or a month, or an entire pregnancy. It still would be necessary to indicate when in gestation the transition to human being with moral status has come to a close. The transitional stage, however long it lasts, would be a period in which the individual did not meet the criteria for moral status as a human being. If, for example, continuity theorists wish to preserve moral status as a human being for premature infants, then they would need to identify some milestone in fetal development that would mark the end of the gestational substance change. Morris could find himself enmeshed in the debate about the moral status of the late fetus that he dismissed as a series of thinly veiled rationalizations. When it comes to the determination of moral status as a human being, substance ontology may be unavoidable. IX. CONCLUSION Moral status is a binary relation: individuals who satisfy the criteria for membership in a morally significant group are ascribed an equal set of rights and duties, and individuals who fall below the threshold do not have the same moral status. Moral status judgments carve continuous processes in biology and other spheres of life at points of maximum discontinuity in morally significant properties. Many people believe that the difference between human beings and the rest of the natural and social world is one such point of maximum discontinuity. Some philosophers have challenged the claim that membership in the species Homo sapiens has intrinsic moral value of this kind.25 For the purposes of this paper, I assumed that this challenge could be met.26 Since this assumption is widely shared, exploring its implications in bioethics may be of some interest. On the view defended in this paper, human beings come into existence when the human body begins to function as an organism; human beings go out of existence when the human body ceases to function as an organism. The human body functions as an organism when a cluster of species-specific homeostatic mechanisms function in concert as the central control system that regulates metabolic and developmental processes. There is no doubt that the onset of human life in this sense occurs prior to full-term gestation. A viable premature infant is no less a living human being than a full-term baby. Neonatal Intensive Care Medicine could not operate on any other assumption. It was argued that the earliest point in gestation at which a human body could be said to be an organism in this sense is the onset of cardiovascular system function. This occurs at the threshold between embryological development and fetal development, approximately nine weeks postfertilization. Throughout fetal development and beyond, the fetus has intrinsic moral status as a human being, although prior to delivery the interests of fetal human beings must be balanced with the interests of the woman within whose body the fetus is sheltered. The conceptus passes through a series of developmental stages in the first eight weeks, each of which can make some claim to conferred moral status. Continuity theorists such as Morris and Green rightly call attention to the role of social convention in making these choices, but they mistakenly conclude that at no point in human development can intrinsic moral status be ascribed. This analysis led to the following conclusions: fertilization is the first phase in a week-long process that encompasses the zygote and cleaving blastomere stages and that culminates in the emergence of the human blastocyst, an entity with sufficient organic unity to be a biological individual. Since human beings cease to exist by homeostatic collapse and blastocysts may cease to exist by fission, fusion, or budding, the persistence conditions of blastocysts are incompatible with the kind essence of human beings. For this reason, blastocysts are best understood as precursors to human beings, not developmental stages in the life of human beings. Blastocysts may have conferred moral status in biomedical contexts analogous in some respects to the moral status of human organs. Implantation is the first phase of a process that results in cessation by fusion of the blastocyst and encompasses gastrulation, neurulation, and organogenesis. Since the metabolic and developmental processes in the late embryo are not coordinated or integrated by a central control system that belongs to the embryo, the conceptus at this stage of development also should be considered a human precursor, not a juvenile human being. Moral status may be conferred on the late embryo in virtue of its developmental potential, the interests of other persons and society at large, or the similarity between the placental-embryonic complex and human organs. At the onset of the fetal period, and for the rest of his or her life, the fetus is a human being, with all the rights and duties that entails. NOTES 1. The position taken by Morris (2012) in his recent Journal of Medicine and Philosophy paper will be taken as representative of continuity theories of the moral status of the human embryo. Morris cites Robert Green (2001) as a continuity theorist who shares his views on moral status. In Chapter 2 of The Human Embryo Research Debates, Green presents an extended argument in support of the social construction of moral status. References to Continuity Theorists and to conferred moral status are intended to include the position articulated by Robert Green. 2. “Substance Ontology” is a particularly robust form of metaphysical realism, but realism in some form with respect to temporally bounded individuals is presupposed by virtually all social practices, including ascriptions of moral status in bioethics. Eternal entities, such as God, Platonic Forms, or the Brahman of the Upanishads, might be considered temporally unbounded individuals with special forms of moral status; given Stephen Hawking’s “No Boundary Proposal,” the physical universe might be finite but temporally unbounded; but these exceptional cases do not obviate the need for a theoretical account of some kind for temporally bounded individuals. Any such account would need to demarcate points or origin and cessation. 3. Patrick Lee, along with his coauthors Richard George and Christopher Tollefsen in their 2014 Journal of Medicine and Philosophy paper and in a number of other publications, argues that the intrinsic potential of the embryo should be considered “a basic natural capacity.” The early embryo is said to have unexercised natural capacities in the same sense that a child who has not yet learned to speak has the natural capacity to do so. On this basis, it is claimed that the zygote and its successors already are rational agents who are entitled to full moral status as human persons. Since “intrinsic potential” and “basic natural capacity” both refer to the genetic and epigenetic properties of the early embryo, this effectively collapses the distinction between potential and capacity in this context (Lee, Tollefsen, and George, 2014). I argued at length against this conflation in Brown (2007). I will not rehearse those arguments here. 4. This also is the position defended in somewhat different terms in Brown (2007), the paper to which Morris refers in his discussion of my view. 5. Richard Boyd first articulated the homeostatic property cluster theory of natural kinds in biology in Boyd (1999). A number of other philosophers of biology have endorsed this view, in whole or in part (see Griffiths, 1999; Wilson, 1999); it is widely recognized as one of the principal alternatives in the species concept debate in philosophy of biology (Ereshefsky, 2010). The claim that the homeostatic property cluster concept of species is a form of intrinsic property essentialism is made most explicitly by Wilson (1999, 196–202). 6. “Imperfect homeostasis is nomologically possible or actual: something may display some but not all of the properties in [the homeostatic property cluster]; some but not all of the underlying homeostatic mechanisms may be present” (Boyd, 1999, 143). 7 The Uniform Determination of Death Act reads: “An individual who has sustained either (1) the irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessations of the entire brain, including the brain stem, is dead” (President’s Commission, 1981, 73). Note that the Uniform Determination of Death Act is disjunctive, as one would expect if the kind essence of human beings consisted in a cluster of homeostatic properties. 8. The morally significant difference between embryos and profound neurological impairment in children and adults is that in the case of embryos the natural course of development would lead to sentience and self-awareness. For example, most embryonic human beings are potential persons while most human beings in a confirmed persistent vegetative state are not. Potential personhood in this sense may itself be an entitlement to enhanced moral status. This is an issue I discussed in some detail in Brown (2007). 9. Lee, Tollefsen, and George rightly point out that in many cases substance change is caused by relatively small quantitative changes in a complex system which result in qualitative ontological change (Lee, Tollefsen, and George, 2014, 486). In the case of human origins, Lee, Tollefsen, and George suggest that substance change occurs within the first few minutes of fertilization, although they recognize that one may reasonably believe that the transition occurs later in embryological development (Lee, Tollefsen, and George, 2014, 487). Their point is that the process that culminates in substance change need not be abrupt. It could take minutes, hours, days, or, as I argue, weeks before the origin of a new human being is complete. 10. On a fertilization-only account, for example, the zygote is a new biological individual in part because zygotes have identity preserving essential properties different from gametes, for example, zygotes do not undergo meiotic cell division. 11. Bacterial mitosis is a ubiquitous form of microbial fission; starfish can regenerate from a single limb; the life cycle of Portuguese Man of War Jellyfish includes a sequence of fusion events in which separable “persons” are incorporated within the colonial organism; flatworms survive being cut in half as two flatworms, and as any gardener knows, hostas and other plants can be split and grafted almost at will. These and other instances of asexual reproduction can be found in any standard zoology textbook or in more accessible form in Parson (2004). 12. I wish to thank an anonymous reviewer for bringing this point to my attention. 13. The classic source for divided consciousness thought experiments is in Derek Parfit’s (1984)Reasons and Persons, although virtually every contemporary account of personal identity considers this possibility in some form. 14. Lee and his collaborators appear not to recognize that fertilization may play a role in placental mammals different from what it does in other animal life forms: “It is clear that a new organism is generated at fertilization with fish and amphibians; it is more economical, and certainly more reasonable, to conclude that a new organism is generated at fertilization with mammals” (Lee, Tollefsen, and George, 2014, 491). This is precisely the claim I wish to contest at this point. Since some fish and amphibians, along with Drosophila, “skip” the blastocyst stage in which the placenta develops, their life cycle sequence differs from that of a placental mammal such as Homo sapiens. 15. I wish to thank an anonymous reviewer for bringing this point to my attention. 16. Tetraploid complementation has resulted in live birth in mice (Kang et al., 2011). The technique involves fusing the cells in a two-celled embryo, and then transferring one or more murine pluripotent stem cells. The lineage of fetal cells is from the stem cells; the lineage of placental and other extraembryonic cells is from the tetraploid cells. 17. The homeostatic property cluster theory of species-specific organic unity is compatible with different homeostatic mechanisms sustaining organic unity at different stages of development. The argument presented here is that there is no such homeostatic mechanism at either the zygote or cleaving blastomere stage. 18. Human embryonic stem cells also could be ascribed moral status similar to the moral status of human organs, although in this case existing patent law may permit a degree of commodification (Cohen, 2007, 189–95). 19. I discuss complicity avoidance policies in some detail in two previously published papers: see Brown (2009, 2013). Crafting noncomplicity schemes without foreclosing access to the benefits of embryo research requires a good faith effort at moral compromise on all sides. The intricacies of these policies are beyond the scope of this paper. 20. Monozygotic twins account for less than 1% of live births, which would seem to imply that the “tragedy” of the loss of an embryonic human being through division is relatively rare, but recent studies suggest that the mortality rate of embryonic monozygotic twins is much higher. Carlson reports that “As many as one in eight live births is a surviving member of a twin pair” (2014, 48). To my knowledge, fertilization-only proponents have not addressed the question of whether 12% of people should feel remorse for absorbing their brother or sister. 21. Twelve countries have laws that restrict research on human embryos to within the first 14 days, including the United Kingdom, South Korea, Canada, Spain, Australia, and Sweden; five countries observe regulatory guidelines that specify a 14-day limit, including the United States, Japan, China, and India (Hyun, Wilkerson, and Johnston, 2016). 22. The Uniform Determination of Death Act implicitly recognizes this: “An individual who has sustained either (1) the irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessations of the entire brain, including the brain stem, is dead” (President’s Commission, 1981, 73). 23. The Uniform Determination of Death Act is intended to be compatible with a cardiopulmonary standard of human life: “people who believe that the continued flow of fluids in such [brain dead] patients means they are alive would not be forced by the statute to abandon those beliefs” (President’s Commission, 1981, 43). It is disjunctive with respect to the determination of death—one may be considered dead if either the whole brain or the circulatory systems cease to function; it also is disjunctive with respect to the determination of life—one may be considered alive if either the brain stem or the circulatory systems continue to function. The statute is thus compatible with a cardiovascular life/cardiovascular death parallelism. Defense of this thesis is beyond the scope of this paper. 24. This is the view recently adopted by Donald Marquis with respect to the early embryo: “a necessary condition for an individual to have a future of value is that the latter stage of the very same individual that is (or would) then value its life . . . human beings and human embryos are both substances. They are different individuals who succeed one another” [italics in original] (Marquis, 2007, 65). Marquis arrives at this conclusion on the basis of a persistence conditions argument similar to that presented in this paper. It is not clear whether or not he would endorse the same conclusion with respect to the late embryo, but if the late embryo is not an individual, as I have argued, then it would seem to follow that abortion prior to eight-week gestation would not deprive it of a future like ours. 25. Peter Singer has argued in a number of publications and contexts that treating being human as morally relevant is a form of invidious discrimination he labels “speciesist.” He makes the point with respect to the moral status of the embryo in Singer and Kuhse (1990). 26. I addressed the moral relevance objection to human rights in this context at length in Brown (2007). ACKNOWLEDGMENTS I am indebted to Professor Douglas Hosler, my colleague in the Philosophy Department at the University of Wisconsin, for his insights on the metaphysics of individual identity and the social construction of ethical judgment. The comments of an anonymous reviewer of an earlier draft of this manuscript prompted me to write a much more substantive paper. REFERENCES Bernat, J. 2006. The whole brain concept of death remains optimum public policy. The Journal of Law, Medicine and Ethics 34 (1): 35– 43. Google Scholar CrossRef Search ADS Boyd, R. 1999. Homeostasis, species and higher taxa. 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