Historians looking to make history a professional discipline of study in Victorian Britain believed they had to establish firm boundaries demarcating history from other literary disciplines. James Anthony Froude ignored such boundaries. The popularity of his historical narratives was a constant reminder of the continued existence of a supposedly overturned phase of historiography in which the historian was also a man of letters, transcending the boundary separating fact from fiction and literature from history. Just as professionalizing historians were constructing a (...) methodology that called on historians to be inductive empirical workers, Froude refused to accept the new science of history, and suggested instead that history was an individual enterprise, one more concerned with drama and art than with science. E. A. Freeman warned the historical community that they “cannot welcome [Froude] as a partner in their labors, as a fellow-worker in the cause of historic truth.”This article examines the boundary work of a professionalizing history by considering the attempt to exclude Froude from the historian’s discourse, an attempt that involved a communal campaign that sought to represent Froude as “constitutionally inaccurate.” Froude suffered from “an inborn and incurable twist,” argued Freeman, thereby diagnosing “Froude’s disease” as the inability to “make an accurate statement about any matter.” By unpacking the construction of “Froude’s disease,” the article exposes the disciplinary techniques at work in the professionalization of history, techniques that sought to exclude non-scientific modes of thought such as that offered by Froude. (shrink)

Humans accumulate porphyrins in the body mostly during the course of porphyrias, diseases caused by defects in the enzymes of the heme biosynthesis pathway and that produce acute attacks, skin lesions and liver cancer. In contrast, some wild mammals and birds are adapted to accumulate porphyrins without injurious consequences. Here we propose viewing such physiological adaptations as potential solutions to human porphyrias, and suggest certain wild animals as models. Given the enzymatic activity and/or the patterns of porphyrin excretion and (...) accumulation, the fox squirrel, the great bustard and the Eurasian eagle owl may constitute overlooked models for different porphyrias. The Harderian gland of rodents, where large amounts of porphyrins are synthesized, presents an underexplored potential for understanding the carcinogenic/toxic effect of porphyrin accumulation. Investigating how these animals avoid porphyrin pathogenicity may complement the use of laboratory models for porphyrias and provide new insights into the treatment of these disorders. (shrink)

Inborn errors of vitamin B12 (cobalamin) metabolism are associated with homocystinuria and methylmalonic aciduria, either alone or in combination. A number of these disorders have provided the first evidence for the existence of important steps in the transport or metabolism of cobalamin in eukaryotic cells. Eight complementation classes have been defined on the basis of somatic cell hybridization studies. Although the majority of patients present in infancy or early childhood, some are not diagnosed until adolescence or later. For some (...) of these disorders, prenatal diagnosis and therapy with cobalamin during pregnancy has been attempted. Although only males have been described with cblE disease, all of these disorders are presumed to be autosomal recessive in inheritance. The clinical and laboratory aspects of the different complementation classes (cblA–cblG) are reviewed here. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

Eugenics can be defined as the use of science applied to the qualitative and quantitative improvement of the human genome. The subject was initiated by Francis Galton with considerable support from Charles Darwin in the latter half of the 19th century. Its scope has increased enormously since the recent revolution in molecular genetics. Genetic files can be easily obtained for individuals either antenatally or at birth; somatic gene therapy has been introduced for some rare inborn errors of metabolism; and (...) gene manipulation of human germ-line cells will no doubt occur in the near future to generate organs for transplantation. The past history of eugenics has been appalling, with gross abuses in the USA between 1931 and 1945 when compulsory sterilization was practised; and in Germany between 1933 and 1945 when mass extermination and compulsory sterilization were performed. To prevent such abuses in the future statutory bodies, such as a genetics commission, should be established to provide guidance and rules of conduct for use of the new information and technologies as applied to the human genome. (shrink)

Imagination and idealism are particularly important creative epistemic virtues for the medical sciences if we hope to improve the health of the world’s ageing population. To date, imagination and idealism within the medical sciences have been dominated by a paradigm of disease control, a paradigm which has realised significant, but also limited, success. Disease control proved particularly successful in mitigating the early-life mortality risks from infectious diseases, but it has proved less successful when applied to the chronic diseases (...) of late life (like cancer). The time is ripe for the emergence and prominence of a supplementary medical research paradigm, the paradigm of ‘healthy ageing’ which prioritises the goal of rate (of ageing) control rather than disease control. This is the difference between extending the human healthspan versus extending survival by managing (or trying to eliminate) the multi-morbidities, frailty and disability currently prevalent in late life. The idealism of the disease control paradigm is myopic because it ignores the health constraints imposed by the inborn ageing process itself, a biological reality which is already inflicting significant economic and disease burdens on the world’s ageing populations. Unless the medical sciences retard the rate of biological ageing, these problems will continue to be amplified as larger numbers of persons survive into late life. (shrink)

Between Sickness and Health is about illness rather than disease, and recovery rather than cure. The book argues that illness is an experience, represented by the feeling that 'I am not myself'. From the book's phenomenological point of view, feelings of illness cannot be 'unreal' or 'fake', whatever their biological basis, nor need they be categorised as 'physical', 'psychosomatic' or 'psychiatric'. The book challenges the disease-centred ethos of medicine and medical education. It demonstrates that a clearer conception of illness, as (...) distinct from disease, is therapeutic. The feeling that 'I am once again myself' can return, in some degree, whatever state the body is in. Resilience becomes more available when it is seen as a set of personal skills that can be developed, rather than as an inborn trait. Possibilities of wellness are enhanced by recognising that medical and other therapies can either support or impede recovery, as can human relationships and the socio-political environment. The book's many clinical examples are drawn from the author's broad experience as a neurologist, rehabilitation physician and systemic family therapist. Between Sickness and Health will be useful for students, practitioners and academics, and also for anyone who has been or might one day be ill. (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic (...) epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

John Davis (_New Methuselahs_: _The Ethics of Life_ _Extension_, The MIT Press, Cambridge, 2018) advances a novel ethical analysis of longevity science that employs a three-fold methodology of examining the impact of life extension technologies on three distinct groups: the “Haves”, the “Have-nots” and the “Will-nots”. In this essay, I critically examine the egalitarian analysis Davis deploys with respect to its ability to help us theorize about the moral significance of an applied gerontological intervention. Rather than focusing on futuristic scenarios (...) of radical life extension, I offer a rival egalitarian analysis that takes seriously (1) the health vulnerabilities of today’s aging populations, (2) the health inequalities of the “aging status quo” and, (3) the prospects for the fair diffusion of an aging intervention over the not-so-distant future. Despite my reservations about Davis’s focus on “life-extension” vs. increasing the human “healthspan”, I agree with his central conclusion that an aging intervention would be, on balance, a good thing and that we should fund such research aggressively. But, I make an even stronger case and conjecture that an intervention that slows down the rate of molecular and cellular decline from the inborn aging process will likely be one of the most important public health advancements of the twenty-first century. This is so because aging is the most prevalent risk factor for chronic disease, frailty and disability, and it is estimated that there will be over 2 billion persons age > 60 by the year 2050. (shrink)

Today’s world is one of quick civilization changes, influencing the development of human thought and the understanding of many basic values. Particularly the last decades have posed a concrete question about freedom and its limitations. The value of freedom is still today being reborn and restructured, once suspicious as a source of sin, now a challenge and a responsible task for the human. Similar questions have also arisen as to the ideas of human dignity and mutual respect, as inherent parts (...) of the human condition.The contemporary world, despite being a new era in human history, does not, in fact, differ much from the Europe of the Middle Ages—divided and united by Christianity, paradoxical in that we strive to build solidarity and closeness and at the same time feel lost and helpless against the evil of the world. With that knowledge we may avoid unnecessary tragedies, learning from St. Francis times, where there was everything in that world—wars, fears, diseases on the one hand, asceticism and self-denial on the other—but no joy. A question may arise whether the voice of St. Francis would still be heard and listened to today. Whether his example would teach love, ecumenism and evangelical joy.The word «ecumenism» is and has been widely used, but often without any deeper reflection on its rich history and variety of meanings. Against the divisions and hatred of contemporary world, the idea of ecumenism increases its importance, becoming one of the main areas of Christian concern. Vatican II brought about a new era of ecumenical thinking, not only defining the theological basis for dialogue, but most importantly, showing its value and encouraging active participation of the faithful. Such participation requires, however, a man’s inner change–which cannot occur without appropriate formation and everyday practice of ecumenism. That presupposes respect for the other, pursuance of mutual trust, openness to widely understood cooperation and elimination of prejudice and fears. Such formation and change must encompass everyone without any difference, laymen and clergy, the faithful and the searching, so that the actions show true concern for the human as such. In that sense, ecumenism is an “inner conversion” (as says A. Skowronek), a new attitude towards the other—religion, human, culture.Against the above mentioned background, one can say that St. Francis exceeded whole centuries of ecumenical dialogue. However, to analyze his phenomenon, one must concentrate on the historical picture, leaving aside any strictly legendarymythological images.St. Francis’s popularity seems to be—almost irrationally—growing with the passage of time, despite not offering anything new or revealing. As a matter of fact, St. Francis reappears in all centuries, teaching the Christian message and teaching to love. His humanism is realized in kindness, solidarity, authentic respect and pure love of God and the human. The human is central in St. Francis’s thinking—great, beautiful and dramatic, full of dignity, and full of the conflict of his inborn goodness and threatening evil. The key to understanding him is only love, assuring freedom and spiritual richness. Yet St. Francis claims: Love is not loved. Re-reading the Gospel anew is a way to meet that Love, and oneself.The human always needed love. Love is inextricably connected with goodness and hence a positive relation towards the other. Those qualities, together with respect, acceptance and search for the truth, are also fundamental to ecumenism. Love appears to be the answer. St. Francis loved not only God, not only the human, but he loved and praised the beauty of all of God’s creation, his love being “the most literal realization of the message contained in the Gospel” (K. Starczewska). But as the first step to love and respect is for the human to respect his own dignity in himself. In that way, he shall also discovers his right to freedom and the truth about himself.The conclusion is the following: Undoubtedly, the character of St. Francis is a universal one. He spoke of his love of God—and human—in concrete deeds of love, never in abstract concepts. Tradition and legend have partly made St. Francis to a cheerful, carefree troubadour of love; however, he knew well the modern world, with its disagreements, hatred and half-truths. A simple tool in God’s hand, he made others overcome the prejudice in them and shake hands in reconciliation, practicing good deeds. Whether that still happens today, and the world adopts St. Francis’s humanistic attitude, depends also on us. (shrink)

Comprising eight revised essays and seven new pieces, this work provides a comprehensive resource for students, scientists, bioethicists, physicians, and laypeople to better understand and discuss the ethical issues underlying this technology that has the potential to forever change the world.

Many experts have warned that environmental degradation is increasing the likelihood of future pandemics like COVID-19, as habitat loss and poaching increase close contact between wildlife and people. This fact has been framed as a reason to increase wildlife conservation efforts. We have many good reasons to step up conservation efforts, but arguments for doing so on the basis of pandemic prevention are rhetorically, ethically, and empricially flawed.

This paper examines the characteristics of infectious diseases that raise special medical and social ethical issues, and explores ways of integrating both current bioethical and classical public health ethics concerns. Many of the ethical issues raised by infectious diseases are related to these diseases’ powerful ability to engender fear in individuals and panic in populations. We address the association of some infectious diseases with high morbidity and mortality rates, the sense that infectious diseases are caused (...) by invasion or attack on humans by foreign micro‐organisms, the acute onset and rapid course of many infectious diseases, and, in particular, the communicability of infectious diseases. The individual fear and community panic associated with infectious diseases often leads to rapid, emotionally driven decision making about public health policies needed to protect the community that may be in conflict with current bioethical principles regarding the care of individual patients. The discussion includes recent examples where dialogue between public health practitioners and medical‐ethicists has helped resolve ethical issues that require us to consider the infected patient as both a victim with individual needs and rights and as a potential vector of disease that is of concern to the community. (shrink)

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask “where’s...

Purposeful infection of healthy volunteers with a microbial pathogen seems at odds with acceptable ethical standards, but is an important contemporary research avenue used to study infectious diseases and their treatments. Generally termed ‘controlled human infection studies’, this research is particularly useful for fast tracking the development of candidate vaccines and may provide unique insight into disease pathogenesis otherwise unavailable. However, scarce bioethical literature is currently available to assist researchers and research ethics committees in negotiating the distinct issues raised (...) by research involving purposefully infecting healthy volunteers. In this article, we present two separate challenge studies and highlight the ethical issues of human challenge studies as seen through a well-constructed framework. Beyond the same stringent ethical standards seen in other areas of medical research, we conclude that human challenge studies should also include: independent expert reviews, including systematic reviews; a publicly available rationale for the research; implementation of measures to protect the public from spread of infection beyond the research setting; and a new system for compensation for harm. We hope these additions may encourage safer and more ethical research practice and help to safeguard public confidence in this vital research alternative in years to come. (shrink)

Pandemic plans recommend phases of response to an emergent infectious disease outbreak, and are primarily aimed at preventing and mitigating human-to-human transmission. These plans carry presumptive weight and are increasingly being operationalized at the national, regional and international level with the support of the World Health Organization. The conventional focus of pandemic preparedness for EIDs of zoonotic origin has been on public health and human welfare. However, this focus on human populations has resulted in strategically important disciplinary silos. As the (...) risks of zoonotic diseases have implications that reach across many domains outside traditional public health, including anthropological, environmental, and veterinary fora, a more inclusive ecological perspective is paramount for an effective response to future outbreaks. (shrink)

While Quine’s linguistic behaviorism is well-known, his Kant Lectures contain one of his most detailed discussions of behaviorism in psychology and the philosophy of mind. Quine clarifies the nature of his psychological commitments by arguing for a modest view that is against ‘excessively restrictive’ variants of behaviorism while maintaining ‘a good measure of behaviorist discipline…to keep [our mental] terms under control’. In this paper, I use Quine’s Kant Lectures to reconstruct his position. I distinguish three types of behaviorism in psychology (...) and the philosophy of mind: ontological behaviorism, logical behaviorism, and epistemological behaviorism. I then consider Quine’s perspective on each of these views and argue that he does not fully accept any of them. By combining these perspectives we arrive at Quine’s surprisingly subtle view about behaviorism in psychology. (shrink)

During the recent Ebola epidemic, some commentators and stakeholders argued that it would be unethical to carry out a study that withheld a potential treatment from affected individuals with such a serious, untreatable disease. As a result, the initial trials of experimental treatments did not have control arms, despite important scientific reasons for their inclusion. In this paper, we consider whether the duty to rescue entails that it would be unethical to withhold an experimental treatment from patient-participants with serious (...) class='Hi'>diseases for which there are no effective treatments, even when doing so is scientifically necessary to test the effectiveness of the treatment. We argue that the duty to rescue will rarely apply. The context of medical research also throws new light on the content of the duty to rescue, since the interests of future patients—who stand to benefit from the fruits of medical research—are relevant to whether the duty applies. (shrink)

Neurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

It is hard to argue with the proposition that value for money should guide health spending. However, even after decades of development, economic evaluation is still a work in progress. As applied, it deals poorly with issues of social justice, ageing and end of life issues; cases involving small numbers—such as decisions about orphan drugs—are also contested. Unfortunately, differences in incremental cost-effectiveness ratios are presented with a degree of precision which contributes to an ‘illusion of validity’.1 Nobel Laureate Amartya Sen (...) has suggested that ‘when all the requirements of ubiquitous market-centred evaluation have been incorporated into the procedures of cost–benefit analysis, it is not so much a discipline as a daydream’.2 As with any approach to public decision making, the use of economic evaluation rests on an implicit social licence, including that the decision making is fair and reasonable. Many countries have developed special policies for rare, ‘ultrarare’ or ‘orphan’ diseases to moderate the effect of a ubiquitous application of economic evaluation. The threshold for defining ‘small’ or rare is a matter of judgement and ranges between 2 and 80 per 100 000 population.3 Magalhaes challenges the ethical basis of special programmes for low incidence conditions and argues against such provisions. In this commentary, I will argue the contrary: that there are good reasons …. (shrink)

“Exercise starts and ends in the brain”: this was the title of a review article authored by Dr. Bengt Kayser back in 2003. In this piece of work, the author highlights that pioneer studies have primarily focused on the cardiorespiratory-muscle axis to set the human limits to whole-body exercise tolerance. In some circumstances, however, exercise cessation may not be solely attributable to these players: the central nervous system is thought to hold a relevant role as the ultimate site of exercise (...) termination. In fact, there has been a growing interest relative to the “brain” response to exercise in chronic cardiorespiratory diseases, and its potential implication in limiting the tolerance to physical exertion in patients. To reach these overarching goals, non-invasive techniques, such as near-infrared spectroscopy and transcranial magnetic stimulation, have been successfully applied to get insights into the underlying mechanisms of exercise limitation in clinical populations. This review provides an up-to-date outline of the rationale for the “brain” as the organ limiting the tolerance to physical exertion in patients with cardiorespiratory diseases. We first outline some key methodological aspects of neuromuscular function and cerebral hemodynamics assessment in response to different exercise paradigms. We then review the most prominent studies, which explored the influence of major cardiorespiratory diseases on these outcomes. After a balanced summary of existing evidence, we finalize by detailing the rationale for investigating the “brain” contribution to exercise limitation in hitherto unexplored cardiorespiratory diseases, an endeavor that might lead to innovative lines of applied physiological research. (shrink)

Research and clinical trial development for rare diseases pose unique bioethical challenges. Much of the literature on rare diseases focuses on patient advocacy and drug development to manage or cu...

"The largest Ebola outbreak to date—first detected in December 2013 and still ongoing as of April 2015—has cast new light on the shortfalls of international public health systems.1 As in previous health crises, scrutiny has reemerged over the pharmaceutical industry’s ability and willingness to innovate new medicines for underserved disease areas. The public debate has intensified following revelations that promising drug candidates to treat Ebola had gone undeveloped despite compelling preclinical results.2 This lack of development is especially troubling because it (...) occurred after a recently implemented U.S. incentive scheme—the Food and Drug Administration’s (FDA) tropical disease priority review voucher program—designed to counteract exactly this problem. Taking Ebola as a case in point, it is useful to examine the short history and ongoing refinement of this voucher program, since it represents one of the most significant legislative efforts to systematically address the relative absence of com- mercial rewards for drugs targeting tropical diseases. This analysis evaluates the voucher program’s effectiveness for both stimulating private sector innovation and achieving positive health impacts among populations most severely burdened by tropical diseases. It then proposes specific recommendations for how law- makers can improve the program’s legislation to better achieve these objectives. ". (shrink)

The authors suggest creating a scheme that offers new incentives for research on diseases disproportionately affecting the poor, with the goal of making development of neglected disease vaccines a lucrative endeavor for pharmaceutical companies.

: The main contribution of this paper to current philosophical and sociological studies on modeling is to analyze modeling as an object-oriented interdisciplinary activity and thus to bring new insights into the wide, heterogeneous discourse on tools, forms and organization of interdisciplinary research. A detailed analysis of interdisciplinarity in the making of models is presented, focusing on long-standing interdisciplinary collaboration between specialists in infectious diseases, mathematicians and computer scientists. The analysis introduces a novel way of studying the elements of (...) the models as carriers of interdisciplinarity. These elements, being functionally interdependent building blocks, evolve during the modeling work and carry the disciplinary tensions in the process. This shows how the long and challenging process of defining and reformulating the object of research is crucial for understanding the dynamics of interdisciplinarity in the making. (shrink)

Common monogenic genetic diseases, ones that have unexpectedly high frequencies in certain populations, have attracted a great number of conflicting evolutionary explanations. This paper will attempt to explain the mystery of why two particularly extensively studied common genetic diseases, Tay Sachs disease and cystic fibrosis, remain evolutionary mysteries despite decades of research. I review the most commonly cited evolutionary processes used to explain common genetic diseases: reproductive compensation, random genetic drift (in the context of founder effect), and (...) especially heterozygote advantage. The latter process has drawn a particularly large amount of attention, having so successfully explained the elevated frequency of sickle cell anemia in malaria-endemic areas. However, the empirical evidence for heterozygote advantage in other common genetic diseases is quite weak. I introduce and illustrate the significance of a hierarchy of genetic disease phenomena found within the genetic disease explanations, which include the phenomena: single mutation variants of a common genetic disease, single genetic diseases, and classes of diseases with related phenotypic effects. I demonstrate that some of the confusion over the explanations of common genetic diseases can be traced back to confusions over which phenomena are being explained. I proceed to briefly evaluate the existing evidence for two common human genetic diseases: Tay Sachs disease and cystic fibrosis. The above considerations will ultimately shed light on why these diseases’ evolutionary explanations remain so deeply unresolved after so such a great volume of research. (shrink)

Experiments carried out on different tumor cell lines showed a significative growth reduction of all treated lines due to the administration of zebrafish embryo extracts withdrawn at different stem cells differentiation stages. Research conducted in order to establish which molecular events were involved in control and downregulation of cancer cell lines demonstrated a transcriptional regulation of the key cell cycle onco-supressor gene, like p53 and a post-translational modification of molecules, like pRb. Research on apoptosis and differentiation processes showed that stem (...) cells differentiating factors induce caspase-3 activation, mainly through E2F-1 gene regulation, thus hyper expressing c-Myc and activating a p73-dependent apoptotic pathway. Moreover, we demonstrated a concurrent and significative normalization of the e-cadherin/β-catenin expression, with an e-cadherin rise. Administration of SCDF in an open clinical randomized clinical trail conducted on 179 patients affected by interme... (shrink)

This paper addresses the views of R.G. Collingwood and Theodor Adorno on the role of amusement and art in what each of them saw as the crisis of contemporary Western civilization. We will begin by showing how the aesthetic theories of Collingwood and Adorno develop out of their shared concerns about the harmful effects of amusement and bad art on the consciousness of human beings. We will argue that a productive dialogue between these two figures clarifies that the value of (...) art consists in its ability to remedy the corruption of the mental and emotional lives of human beings and in helping to fashion a different social and political order. As part of this, we will show how, despite appearances, Adorno's aesthetic cognitivism and Collingwood's expression theory of art agree with and complement one another in significant ways. In establishing this point, this work will leave us with an understanding of art that is more comprehensive and better equipped to address the crisis of contemporary Western society. (shrink)

How is a disease contracted, and how does it progress through the body? Answers to these questions are fundamental to understanding both basic biology and medicine. Advances in the biomedical sciences continue to provide more tools to address these fundamental questions and to uncover questions that have not been thought of before. Despite these major advances, we are still facing conceptual and technical challenges when learning about the etiology of disease, especially for genetic diseases. In this review, we illustrate (...) this point by discussing the causal links between molecular mechanisms and systems-level phenotypes in molecular diseases. We begin with an examination of sickle cell anemia, and how mechanisms of the disease have been comprehended over the last century. While sickle cell anemia involves a mutation in a single protein in a single cell type, other diseases involve mutations in networks with many protein interactions and in diverse cell types. We introduce the challenges that result from these differences and illustrate the current obstacles by discussing the RASopathies, a recently discovered class of developmental syndromes that result from mutations in signaling networks. Methods to study mutant genotypes that lead to mutant phenotypes are discussed, particularly the use of model organisms and mutant proteins to study protein interactions that may be important for development of disease. These studies will point toward the future of diagnosing and treating genetic disease. (shrink)

The study of rare diseases has long been an area of challenge for medical researchers, with agonizingly slow movement towards improved understanding of pathophysiology and treatments compared with more common illnesses. The push towards evidence-based medicine (EBM), which prioritizes certain types of evidence over others, poses a particular issue when mapped onto rare diseases, which may not be feasibly investigated using the methodologies endorsed by EBM, due to a number of constraints. While other trial designs have been suggested (...) to overcome these limitations (with varying success), perhaps the most recent and enthusiastically adopted is the application of artificial intelligence to rare disease data. This paper critically examines the pitfalls of EBM (and its trial design offshoots) as it pertains to rare diseases, exploring the current landscape of AI as a potential solution to these challenges. This discussion is also taken a step further, providing philosophical commentary on the weaknesses and dangers of AI algorithms applied to rare disease research. While not proposing a singular solution, this article does provide a thoughtful reminder that no ‘one-size-fits-all’ approach exists in the complex world of rare diseases. We must balance cautious optimism with critical evaluation of new research paradigms and technology, while at the same time not neglecting the ever-important aspect of patient values and preferences, which may be challenging to incorporate into computer-driven models. (shrink)

A new analysis of the Best Interests Standard is given and applied to the controversy about testing children for untreatable, severe late-onset genetic diseases, such as Huntington's disease or Alzheimer's disease. A professional consensus recommends against such predictive testing, because it is not in children's best interest. Critics disagree. The Best Interests Standard can be a powerful way to resolve such disputes. This paper begins by analyzing its meaning into three necessary and jointly sufficient conditions showing it: is an (...) "umbrella" standard, used differently in different contexts, has objective and subjective features, is more than people's intuitions about how to rank potential benefits and risks in deciding for others but also includes evidence, established rights, duties and thresholds of acceptable care, and can have different professional, medical, moral and legal uses, as in this dispute. Using this standard, support is given for the professional consensus based on concerns about discrimination, analogies to adult choices, consistency with clinical judgments for adults, and desires to preserve of an open future for children. Support is also given for parents' legal authority to decide what genetic tests to do. (shrink)

The discursive approach to psychiatry, taking as it does an ethological approach to the human organism, directs us to rules and story lines that structure our ways of dealing with the challenges thrown up by particular situated positions in our discursive world. For human beings this means engaging with the sense they are making of the world and the words they use to try and communicate that. Doing things with words is behavior that draws on certain skills attuned to prompts, (...) cues, expectations, and so on, all of which can go seriously awry in any setting where certain features are unfamiliar or where one of the participants is "impaired" or out of step with prevailing norms and assumptions. Discursive competence and the reality of the human psyche as a mode of being-in-relation-with others crucially depends on intact neural function and brain pathways slowly and cumulatively developed throughout life and is vulnerable to disruption of that substrate. Hysteria and dementia represent two very different situations in which the discursive mismatch between an individual and his or her context of being causes the voice of a person to be "lost in translation" so that understanding what is happening and then care and restoration demand a great deal of us not just as biomedical scientists but also as human beings who are reaching out to those who suffer and try to endure so as to help hold them in being. (shrink)

This paper examines the characteristics of infectious diseases that raise special medical and social ethical issues, and explores ways of integrating both current bioethical and classical public health ethics concerns. Many of the ethical issues raised by infectious diseases are related to these diseases' powerful ability to engender fear in individuals and panic in populations. We address the association of some infectious diseases with high morbidity and mortality rates, the sense that infectious diseases are caused (...) by invasion or attack on humans by foreign micro-organisms, the acute onset and rapid course of many infectious diseases, and, in particular, the communicability of infectious diseases. The individual fear and community panic associated with infectious diseases often leads to rapid, emotionally driven decision making about public health policies needed to protect the community that may be in conflict with current bioethical principles regarding the care of individual patients. The discussion includes recent examples where dialogue between public health practitioners and medical-ethicists has helped resolve ethical issues that require us to consider the infected patient as both a victim with individual needs and rights and as a potential vector of disease that is of concern to the community. (shrink)

One of the central arguments given to resist testing currently healthy, asymptomatic children for adult-onset diseases is that they may be psychologically harmed by the knowledge gained from such tests. In this discussion I examine two of the most serious arguments: children who are tested may face limited futures, and that testing may result in damage to the child’s self esteem . I claim that these arguments do not stand up to critical evaluation. In conclusion, whilst I do not (...) suggest that all at-risk children should be tested for adult-onset diseases we ought to listen carefully to some parental requests for such testing because the putative psychological harms may not be as significant or likely as initially thought. This is because parents generally have the best interests of their children at heart and if they are properly supported and educated about predictive genetic testing and the possible consequences, then the risk of psychological harms occurring may be ameliorated. (shrink)