The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult stem cell research will need to (...) be pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Direct Nuclear Reprogramming: Response to Condic, Lee, and GeorgeGerard Magill, Ph.D. and William B. NeavesWe read with great interest the response of Maureen Condic, Patrick Lee, and Robert George (2009) to our essay, “Ontological and Ethical Implications of Direct Nuclear Reprogramming” in the March 2009 issue of the Kennedy Institute of Ethics Journal (Magill and Neaves 2009). Much of their response addressed issues that are (...) not in dispute: somatic cells are not zygotes, neurons and hepatocytes are different, growth-factor signals from the trophoblast influence development of the inner cell mass, membranes derived from the trophectoderm are critically required for embryonic survival, and stem cells cannot produce a fetus “on their own.”The crucial point of disagreement deals with the fact that iPS cells are not totipotent but zygotes are. Zygotes can generate their own placental structures while iPS cells must be given them through tetraploid complementation. Condic, Lee, and George consider totipotency to be crucial to natural potentiality. We present an alternative view in our essay (Magill and Neaves 2009, pp. 28–29). Placental structures make no lasting contribution to the postnatal organism, and the equivalency of iPS cells with the inner cell mass of the blastocyst is apparent from tetraploid complementation experiments.The respondents acknowledge the following:... somatic cells can be “converted” into zygotes by the process of somatic cell nuclear transfer (SCNT) or direct reprogramming in combination with tetraploid complementation—just as sperm and egg cells can be “converted” into a zygote by the process of natural fertilization—....(Condic, Lee, and George 2009, p. 35)As the respondents recognize, different ways of manipulating cells can lead to embryogenesis: sperm and egg cells in the process of natural fertilization, the enucleated egg and an ordinary body cell in the process of somatic cell nuclear transfer, and reprogrammed skin cells and a tetraploid blastocyst in the case of induced pluripotent stem (iPS) cells. In each case, different cells are manipulated—or “converted” in the respondents’ terminology—in a process that alters their biological fate within a supportive environment facilitating embryogenesis.The developmental potential that resides in the human genome does not unfold in isolation, not even in a zygote. In all cases, whether involving a zygote or an iPS cell, interaction with a supportive environment is required to express the developmental program residing in the genome. [End Page 201]This biological reality supports what we have described as “early cellular development along the continuum of natural potentiality that can result in the formation of a fetus” (Magill and Neaves 2009, p. 30), and it presents a significant challenge to the natural potentiality argument.Gerard MagillVernon F. Gallagher Chair for the Integration of Science, Theology, Philosophy, and Law, and Professor, Center for Healthcare Ethics Duquesne University Pittsburgh, PA.William B. NeavesPresident and CEO Stowers Institute for Medical Research and Professor of Basic Medical Science University of Missouri at Kansas City School of Medicine Kansas City, MOReferencesCondic, Maureen L.; Lee, Patrick; and George, Robert P. 2008. Ontological and Ethical Implications of Direct Nuclear Reprogramming: Response to Magill and Neaves. Kennedy Institute of Ethics Journal 19: 33–40. Google ScholarMagill, Gerard, and Neaves William B. 2009. Ontological and Ethical Implications of Direct Nuclear Reprogramming. Kennedy Institute of Ethics Journal 19: 23–32. Google ScholarCopyright © 2009 The Johns Hopkins University Press... (shrink)

Scientific breakthroughs rarely yield the potential to engage a foundational ethical question. Recent studies on direct reprogramming of human skin cells reported by the Yamanaka lab in Japan and the Thomson lab in Wisconsin suggest that scientists may have crossed both a scientific and an ethical threshold. The fascinating science of direct nuclear reprogramming highlights empirical data that may clarify the ontological status of cellular activity in the early stages of what could become a human fetus (...) and justify ethical options for research in this controversial field. The ontological and ethical implications that accrue here are connected with the biological or natural potentiality of these cells. (shrink)

The paper by Magill and Neaves in this issue of the Journal attempts to rebut the "natural potency" position, based on recent advances in direct reprogramming of somatic cells to yield "induced pluripotent stem" (iPS) cells. As stated by the authors, the natural potency position holds that because "a human embryo directs its own integral organismic function from its beginning . . . there is a whole, albeit immature, and distinct human organism that is intrinsically valuable with the (...) status of inviolability and deserving full moral respect" (p. 26). The authors boldly assert that "The recent production of iPS . . . highlights a prima facie absurdity for the natural potentiality argument" (p. 29). Yet the argument against natural potency is both logically flawed and based on a characterization of the scientific evidence that is factually inaccurate. (shrink)

DNA methylation is a repressive epigenetic mark vital for normal development. Recent studies have uncovered an unexpected role for the DNA methylome in ensuring the correct targeting of the Polycomb repressive complexes throughout the genome. Here, we discuss the implications of these findings for cancer, where DNA methylation patterns are widely reprogrammed. We speculate that cancer‐associated reprogramming of the DNA methylome leads to an altered Polycomb binding landscape, influencing gene expression by multiple modes. As the Polycomb system is responsible (...) for the regulation of genes with key roles in cell fate decisions and cell cycle regulation, DNA methylation induced Polycomb mis‐targeting could directly drive carcinogenesis and disease progression.Editor's suggested further reading in BioEssays Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition Abstract. (shrink)

Direct reprogramming of human skin cells makes available a source of pluripotent stem cells without the perceived evil of embryo destruction, but the advent of such a powerful biotechnology entangles stem cell research in other forms of moral complicity. Induced pluripotent stem cell (iPSC) research had its origins in human embryonic stem cell research and the projected biomedical applications of iPS cells almost certainly will require more embryonic stem cell research. Policies that inhibit iPSC research in order to (...) avoid moral complicity are themselves complicit in preventable harms to patients. Moral complicity may be unavoidable, but a Blue Ribbon Panel charged with assessing the need for additional embryonic stem cell lines may ease a transition from embryonic stem cell research to clinical applications of iPS cells. (shrink)

Graphical AbstractOrganelles are reaction vessels containing metabolic pathways. As in a chemical factory, the size of the reaction vessels limits the rate of product formation. Organelle size is tuned to metabolic needs, hence reprogramming organelle size could be a novel therapeutic strategy as well as a new tool for metabolic engineering.

In the adult mammalian brain, neurogenesis is restricted to few regions, while gliogenesis continues in a wide‐spread manner. Here we discuss our knowledge of extrinsic and intrinsic factors regulating neuro‐ and gliogenesis in the adult brain and propose a model of fate specification identifying the states of easiest transition between glio‐ and neurogenesis, highlighting the unique mechanisms stabilising the neural stem cell state. The model also encompasses the fate alterations achieved by direct reprogramming, and hence addresses a novel (...) avenue for repair, namely eliciting neurogenesis from glial cells outside the neurogenic niches. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Response to Byrnes and FurtonMark T. Brown, Ph.D.In “Moral Complicity in Induced Pluripotent Stem Cell Research” (MCIPS) (Brown 2009), I sketched the moral complicity implications of alternative national stem cell policies with respect to direct reprogramming techniques that appear to result in pluripotent stem cells derived from skin cells, hair cells, and possibly other somatic cells. This aspect of the stem cell debate was considered from the (...) perspective of those who are pro embryo life and who attribute to human embryos a complete set of basic human rights, including a stringent right to life; and from the perspective of advocates of embryonic stem cell research who do not recognize full moral equivalence between human embryos and human children and who do not ascribe to human embryos an inviolable right to life. The moral complicity concerns of embryonic stem cell research advocates focus upon the scope of medical beneficence with respect to patients whose quality of life and personal autonomy are negatively impacted by the interval between the time when they might have gotten effective medical treatment through unimpeded stem cell science and the time at which stem cell science constrained by pro embryo life moral complicity concerns arrives at a similar destination. The moral complicity concerns of embryo life proponents focus upon noncooperation in past and future destruction of human embryos in order to derive in vitro embryonic stem cell lines.Among the policy alternatives considered were proposals that would be responsive to the possibility that induced pluripotent stem cells (iPSC) at some point may provide a source of stem cell lines that would substitute for human embryonic stem [End Page 206] cell (hESC) lines in cell replacement therapy. If functional equivalence between iPSC lines and hESC lines for cell replacement purposes were confirmed, a national stem cell research policy might be crafted that could accommodate the central moral complicity concerns both of persons who are embryo life advocates and of advocates of embryonic stem cell research. Policy alternatives considered in MCIPS included those based upon the assumption that currently existing embryonic stem cell lines are sufficient to conduct iPSC/hESC functional equivalence studies and policy options based upon the assumption that currently existing hESC lines fall short of what would be required for methodologically sound validation studies. The moral complicity implications for those who are embryo life advocates of both sets of policies were outlined, as were the moral complicity implications of alternative policies for embryonic stem cell research advocates. Since moral complicity concerns are one factor that those who formulate national stem cell policy should consider, MCIPS was an attempt to provide some guidance to policymakers with respect to how alternative policies accommodate or fail to accommodate the moral complicity concerns of various constituencies.In a 2008 article, Malcolm Byrnes (2008, p. 286) appears to consider both empirical assumptions regarding the sufficiency of existing stem cell lines for meaningful functional equivalence studies, and for that reason I drew upon his paper to frame the moral complicity implications for advocates of embryo life of national stem cell policy based upon either assumption. In his paper, Byrnes refers both to stem cell scientists who “suggest” that the hESC lines approved by President Bush in 2001 are sufficient and to stem cell scientists who believe that more hESC lines are needed. Based on my reading of his paper, I erroneously included Byrnes in the group who were willing to consider new hESC derivations in order to complete functional equivalence studies. However, my description of the moral complicity implications for advocates of embryo life of policies that enable new hESC derivations was an exercise in contingency planning, and certainly not intended as “a condemnation” of Byrnes (2009, p. 203). Similarly, what Byrnes (2009, p. 204) sees as “ironic” is simply a description later in my paper of policy options based upon an alternative factual assumption.Byrnes’s position seems to be that existing hESC lines are sufficient to conduct iPSC/hESC functional equivalence studies and that no additional hESC lines should be derived. Although it appears that I did mischaracterize Byrnes’s view of the permissibility of deriving additional hESC lines for equivalence studies, I think my interpretation was... (shrink)

Stem cell research is very promising. The use of human embryos has been confronted with objections based on ethical and religious positions. The recent production of reprogrammed adult (induced pluripotent) cells does not – in the opinion of scientists – reduce the need to continue human embryonic stem cell research. So the debate continues.Islam always encouraged scientific research, particularly research directed toward finding cures for human disease. Based on the expectation of potential benefits, Islamic teachings permit and support human embryonic (...) stem cell research. The majority of Muslim scholars also support therapeutic cloning. This permissibility is conditional on the use of supernumerary early pre-embryos which are obtained during infertility treatment in vitro fertilization (IVF) clinics. The early pre-embryos are considered in Islamic jurisprudence as worthy of respect but do not have the full sanctity offered to the embryo after implantation in the uterus and especially after ensoulment.In this paper the Islamic positions regarding human embryonic stem cell research and therapeutic cloning are reviewed in some detail, whereas positions in other religious traditions are mentioned only briefly.The status of human embryonic stem cell research and therapeutic cloning in different countries, including the USA and especially in Muslim countries, is discussed. (shrink)

This paper analyzes creative practice including virtual music composition by a human and sets of computer programs, improvisation of music and dance in human-robot ensembles, and drawings produced by a human and a robotic arm. In all of these examples, the paper argues that creativity arises from a process of human-robot collaboration. Human influences on the machines involved exist at many levels, from initial creation and programming, via processes of reprogramming and setup of underlying data and parameters, to engagement (...) throughout the process of creative production. The decision to value a machine as a creative other is supported most strongly when collaborating with the machine directly, while witnessing the creative team at work, as opposed simply to seeing the result, is more likely to bring an audience to a similar understanding. The creativity of the human-machine collaborations analyzed in this paper relies on close interaction, within which there is a continual recognition of the otherness of the machine and its nonhuman abilities. Such relations can be theorized by extending Emmanuel Levinas’ conception of the face-to-face encounter within which self and other are brought into proximity, but the alterity of the other is nonetheless retained. The paper’s analysis of creative interactions between humans and robots supports the idea that machines need not be regarded as challenging human artistic practice, but rather enable new ways for creativity to arise through human-machine collaborations within which human and nonhuman creative abilities are combined. (shrink)

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

On Sunday morning, 23 February 1997, the world awoke to a technological advance that shook the foundations of biology and philosophy. On that day, we were introduced to Dolly, a 6-month-old lamb that had been cloned directly from a single cell taken from the breast tissue of an adult donor. Perhaps more astonished by this accomplishment than any of their neighbors were the scientists who actually worked in the field of mammalian genetics and embryology. Outside the lab where the cloning (...) had actually taken place, most of us thought it could never happen. Oh, we would say that perhaps at some point in the distant future, cloning might become feasible through the use of sophisticated biotechnologies far beyond those available to us now. But what many of us really believed, deep in our hearts, was that this was one biological feat we could never master. New lifemust have its origins in an embryo formed through the merger of gametes from a mother and father. It was impossible, we thought, for a cell from an adult mammal to become reprogrammed, to start all over again, to generate another entire animal or person in the image of the one born earlier. (shrink)

In this paper, I attempt to address a fundamental challenge for machine intelligence: to understand whether and how a machine’s internal states and external outputs can exhibit original non-derivative intentionality. This question has three aspects. First, what does it take for a machine to exhibit original de dicto intentionality? Second, what does it take to exhibit original de re intentionality? Third, what is required for the machine to defer to the external objective world by respecting the word-to-world direction of fit? (...) I attempt to answer the first challenge by providing a constitutive counts-as understanding of de dicto intentionality. This analysis involves repurposing Kant’s vision of a self-legislating agent as a specification of a machine that reprograms itself. I attempt to answer the second and third challenges by extending Kant’s synchronic model of de dicto intentionality with Brandom’s interpretation of Hegel’s diachronic model of de re intentionality, using Hegel’s notion of recollection to provide an understanding of what is involved in achieving deference to the external world. (shrink)

Recent findings position the eukaryotic translation initiation factor eIF4E as a novel modulator of mRNA splicing, a process that impacts the form and function of resultant proteins. eIF4E physically interacts with the spliceosome and with some intron‐containing transcripts implying a direct role in some splicing events. Moreover, eIF4E drives the production of key components of the splicing machinery underpinning larger scale impacts on splicing. These drive eIF4E‐dependent reprogramming of the splicing signature. This work completes a series of studies (...) demonstrating eIF4E acts in all the major mRNA maturation steps whereby eIF4E drives production of the RNA processing machinery and escorts some transcripts through various maturation steps. In this way, eIF4E couples the mRNA processing‐export‐translation axis linking nuclear mRNA processing to cytoplasmic translation. eIF4E elevation is linked to worse outcomes in acute myeloid leukemia patients where these activities are dysregulated. Understanding these effects provides new insight into post‐transcriptional control and eIF4E‐driven cancers. (shrink)

Genetic intervention is on the near horizon for the treatment of substance abu se. Genetic intervention involves a reprogramming of a person’s own genetic instructions so that that person will no longer have the physical craving for the drug of choice. Unlike pharmacologic intervention, genetic intervention will change the genetic identity of the person, albeit slightly. The legal issue is whether one has a fundamental right to this medical procedure. A fundamental right is one that the government cannot deny (...) without a compelling interest. The case law indicates that the right o f medical necessity applies when the person’s affliction is serious, there are no reasonable or effective alternatives, the person did not intentionally cause the condition, and the treatment is effective for the long term. Unlike the medical marijuana ph enomenon, genetic intervention is per se anti - drug, unrelated to illegal, recreational drug use, and on its face has a medical use. Legal doctrines to date though not directly on point are conceptually compatible with the existence of a fundamental right of medical necessity for genetic intervention. (shrink)

Dignitas personae teaches that before research into certain alternative techniques for deriving human pluripotent stem cells can be licit, it is necessary to have moral certitude that no human embryo is brought into existence by those techniques. This article evaluates three such techniques—human parthenogenesis, ANT-OAR, and direct cellular reprogramming—and asks whether at present such moral certitude is achievable. National Catholic Bioethics Quarterly 10.1 (Spring 2010): 123–142.

This paper comments on Gallagher’s recently published direct perception proposal about social cognition [Gallagher, S.. Direct perception in the intersubjective context. Consciousness and Cognition, 17, 535–543]. I show that direct perception is in danger of being appropriated by the very cognitivist accounts criticised by Gallagher. Then I argue that the experiential directness of perception in social situations can be understood only in the context of the role of the interaction process in social cognition. I elaborate on the (...) role of social interaction with a discussion of participatory sense-making to show that direct perception, rather than being a perception enriched by mainly individual capacities, can be best understood as an interactional phenomenon. (shrink)

What kind of content must visual states have if they are to offer direct (noninferential) justification for our external world beliefs? How must they present that content if the degree of justification they provide is to reflect the nuance of our changing visual experiences? This paper offers an argument for the view that visual states comprise not only a content, but a confidence relation to that content. This confidence relation lets us explain how visual states can offer noninferential perceptual (...) justification of differing degrees for external world beliefs. These confidence relations let visual states justify beliefs in a way that is sensitive to subtle differences in the character of our visual experiences, while still allowing that visual states give us direct access to the external world in virtue of their content. (shrink)

Examines the theses that the postulation of mental processing is unnecessary to account for our perceptual relationship with the world, see turvey etal. for a criticque.

Since the demise of the Sense-Datum independent objects or events to be objects Theory and Phenomenalism in the last cenof perception; however, unlike Direct Retury, Direct Realism in the philosophy of alists, Indirect Realists take this percepperception has enjoyed a resurgence of tion to be indirect by involving a prior popularity.1 Curiously, however, although awareness of some tertium quid between there have been attempts in the literature the mind and external objects or events.3 to refute some of the (...) arguments against Idealists and Phenomenalists agree with Direct Realism, there has been, as of yet, the Indirect Realists. (shrink)

According to what I will call ‘the disanalogy thesis,’ beliefs differ from actions in at least the following important way: while cognitively healthy people often exhibit direct control over their actions, there is no possible scenario where a cognitively healthy person exhibits direct control over her beliefs. Recent arguments against the disanalogy thesis maintain that, if you find yourself in what I will call a ‘permissive situation’ with respect to p, then you can have direct control over (...) whether you believe p, and you can do so without manifesting any cognitive defect. These arguments focus primarily on the idea that we can have direct doxastic control in permissive situations, but they provide insufficient reason for thinking that permissive situations are actually possible, since they pay inadequate attention to the following worries: permissive situations seem inconsistent with the uniqueness thesis, permissive situations seem inconsistent with natural thoughts about epistemic akrasia, and vagueness threatens even if we push these worries aside. In this paper I argue that, on the understanding of permissive situations that is most useful for evaluating the disanalogy thesis, permissive situations clearly are possible. (shrink)

The replication crisis has caused researchers to distinguish between exact replications, which duplicate all aspects of a study that could potentially affect the results, and direct replications, which duplicate only those aspects of the study that are thought to be theoretically essential to reproduce the original effect. The replication crisis has also prompted researchers to think more carefully about the possibility of making Type I errors when rejecting null hypotheses. In this context, the present article considers the utility of (...) two types of Type I error probability: the Neyman–Pearson long run Type I error rate and the Fisherian sample-specific Type I error probability. It is argued that the Neyman–Pearson Type I error rate is inapplicable in social science because it refers to a long run of exact replications, and social science deals with irreversible units that make exact replications impossible. Instead, the Fisherian sample-specific Type I error probability is recommended as a more meaningful way to conceptualize false positive results in social science because it can be applied to each sample-specific decision about rejecting the same substantive null hypothesis in a series of direct replications. It is concluded that the replication crisis may be partly due to researchers’ unrealistic expectations about replicability based on their consideration of the Neyman–Pearson Type I error rate across a long run of exact replications. (shrink)

Many have accepted that ordinary counterfactuals and might counterfactuals are duals. In this paper, I show that this thesis leads to paradoxical results when combined with a few different unorthodox yet increasingly popular theses, including the thesis that counterfactuals are strict conditionals. Given Duality and several other theses, we can quickly infer the validity of another paradoxical principle, ‘The Counterfactual Direct Argument’, which says that ‘A> ’ entails ‘A> ’. First, I provide a collapse theorem for the ‘counterfactual (...) class='Hi'>direct argument’. The counterfactual direct argument entails the logical equivalence of the subjunctive and material conditional, given a variety of assumptions. Second, I provide a semantics that validates the counterfactual direct argument without collapse. This theory further develops extant dynamic accounts of conditionals. I give a new semantics for disjunction, on which A or B is only true in a context when A and B are both unsettled. The resulting framework validates CDA while invalidating other commonly accepted principles concerning the conditional and disjunction. (shrink)

Working memory (WM) is a fundamental cognitive ability to support complex thought, but it is limited in capacity. WM training has shown the potential to make benefit for those in need. Many studies have shown the potential of transcranial direct current stimulation (tDCS) to transiently enhance WM performance by delivering low current to the brain cortex of interest via electrodes on the scalp. TDCS has also been revealed as a promising intervention to augment WM training in a few studies. (...) However, those few tDCS-paired WM training studies focused more on the effect of tDCS on WM enhancement and its transferability after training but paid less attention to the variation of cognitive performance during the training procedure. The current study attempted to explore the effect of tDCS on the variation of performance during WM training in healthy young adults. All the participant received WM training with the load-adaptive verbal N-back task for five days. During the training procedure, active/sham anodal high-definition tDCS (HD-tDCS) was used to stimulate the left dorsolateral prefrontal cortex (DLPFC). To examine the training effect, pre- and post-test were performed respectively one-day before and after the training sessions respectively. At the beginning of each training session, stable-load WM tasks were performed to examine the performance variation during training. Compared to the sham stimulation, higher learning rates of performance metrics during the training procedure were found when WM training was combined with active anodal HD-tDCS. The performance improvements (post-pre) of the active group were also found to be higher than those of sham group and were transferred to a similar untrained WM task. Further analysis revealed that the negative relation between the training improvements and baseline performance. These findings show the potential that tDCS may be leveraged as an intervention to facilitate WM training for those in need of higher WM ability. (shrink)

Traditional theorists about free will and moral responsibility endorse the principle of alternative possibilities (PAP): an agent is morally responsible for an action that she performs only if she can do or could have done otherwise. According to source theorists, PAP is false and an agent is morally responsible for her action only if she is the source of that action. Source incompatibilists accept the source theory but also endorse INC: if determinism is true, then no one is morally responsible (...) for any action. This paper is a critique of a kind of source incompatibilism, namely, direct source incompatibilism. Direct source incompatibilists reject PAP on the basis of Frankfurt-style examples. Since PAP is one of two premises in the traditional argument for INC, direct source incompatibilists opt for a version of the direct argument, which argues for INC with the aid of some non-responsibility transfer principle. I demonstrate that this option is not available, for there is a tension between the following two claims. (shrink)

Some argue that humans should enhance their moral capacities by adopting institutions that facilitate morally good motives and behaviour. I have defended a parallel claim: that we could permissibly use biomedical technologies to enhance our moral capacities, for example by attenuating certain counter-moral emotions. John Harris has recently responded to my argument by raising three concerns about the direct modulation of emotions as a means to moral enhancement. He argues that such means will be relatively ineffective in bringing about (...) moral improvements, that direct modulation of emotions would invariably come at an unacceptable cost to our freedom, and that we might end up modulating emotions in ways that actually lead to moral decline. In this article I outline some counter-intuitive potential implications of Harris' claims. I then respond individually to his three concerns, arguing that they license only the very weak conclusion that moral enhancement via direct emotion modulation is sometimes impermissible. However I acknowledge that his third concern might, with further argument, be developed into a more troubling objection to such enhancements. (shrink)

Book II of the Treatise minutely anatomizes the passions Hume dubbed “indirect.” As the account of pride, humility, love, and hatred unfolds, principles are uncovered, causes are exhaustively examined, experiments carried out, difficulties presented and solved. The barrage of detailed description and theorizing threatens to overwhelm even the most devoted of readers. By contrast, Hume’s explicit treatment of the direct passions appears perfunctory. Indeed, Hume states: “None of the direct affections seem to merit our particular attention except hope (...) and fear.” Desire and aversion, though usually mentioned first as examples of the direct passions, receive no separate analysis. (shrink)

Private firms are uniquely positioned to provide significant relief to the misery that pervades the developing world. Global misery has persisted due to a variety of failures in the provision of relief by nation-states and non-governmental organizations, including corruption and the absence of strong background institutions in the countries in need of aid. In many situations, private firms have a comparative advantage over these entities in the provision of aid. Examples such as Merck and the cure for river blindness show (...) how firms can use their specific competencies and knowledge to relieve misery through Direct Corporate Humanitarian Investment (DCHI). DCHI is legitimized by marketplace morality and is consistent with the role of business within society, including legal dimensions. Shareholders may formally approve a corporation’s DCHI strategy and all stakeholders may act in support of their moral desires with respect to the firm and its DCHI strategy. (shrink)

Direct reference theory faces serious prima facie counterexamples which must be explained away (e.g., that it is possible to know a priori that Hesperus = Phosphorus). This is done by means of various forms of pragmatic explanation. But when those explanations that provisionally succeed are generalized to deal with analogous prima facie counterexamples concerning the identity of propositions, a fatal dilemma results. Either identity must be treated as a four-place relation (contradicting what just about everyone, including direct reference (...) theorists, takes to be essential to identity). Or direct reference theorists must incorporate a view that was rejected in pretty much our first lesson about identity—namely, that Hesperus at twilight is not identical to Hesperus at dawn. One way of the other, the direct reference theory is thus inconsistent with basic principles concerning the logic of identity, which nearly everyone, including direct reference theorists, take as starting points. (shrink)