Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico‐chemical properties of cartilage‐specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage‐specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes (...) are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage‐specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints. (shrink)

The recently uncovered role of Fukutin‐related protein (FKRP) in fibronectin glycosylation has challenged our understanding of the basis of disease pathogenesis in the muscular dystrophies. FKRP is a Golgi‐resident glycosyltransferase implicated in a broad spectrum of muscular dystrophy (MD) pathologies that are not fully attributable to the well‐described α‐Dystroglycan hypoglycosylation. By revealing a new role for FKRP in the glycosylation of fibronectin, a modification critical for the development of the muscle basement membrane (MBM) and its associated muscle linkages, new possibilities (...) for understanding clinical phenotype arise. This modification involves an interaction between FKRP and myosin‐10, a protein involved in the Golgi organization and function. These observations suggest a FKRP nexus exists that controls two critical aspects to muscle fibre integrity, both fibre stability at the MBM and its elastic properties. This review explores the new potential disease axis in the context of our current knowledge of muscular dystrophies. (shrink)

The collagen family of extracellular matrix proteins has played a fundamental role in the evolution of multicellular animals. At the present, 28 triple helical proteins have been named as collagens and they can be divided into several subgroups based on their structural and functional properties. In tissues, the cells are anchored to collagenous structures. Often the interaction is indirect and mediated by matrix glycoproteins, but cells also express receptors, which have the ability to directly bind to the triple helical (...) domains in collagens. Some receptors bind to sites that are abundant in all collagens. However, increasing evidence indicates that the coevolution of collagens and cell adhesion mechanisms has given rise to receptors that bind to specific motifs in collagens. These receptors may also recognize the different members of the large collagen family in a selective manner. This review summarizes the present knowledge about the properties of collagen subtypes as cell adhesion proteins. BioEssays 29:1001–1010, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Fibril‐forming (fibrillar) collagens are extracellular matrix proteins conserved in all multicellular animals. Vertebrate members of the fibrillar collagen family are essential for the formation of bone and teeth, tissues that characterise vertebrates. The potential role played by fibrillar collagens in vertebrate evolution has not been considered previously largely because the family has been around since the sponge and it was unclear precisely how and when those particular members now found in vertebrates first arose. We present evidence that the classical (...) vertebrate fibrillar collagens share a single common ancestor that arose at the very dawn of the vertebrate world and prior to the associated genome duplication events. Furthermore, we present a model, ‘molecular incest’, that not only accounts for the characteristics of the modern day vertebrate fibrillar collagen family but demonstrates the specific effects genome or gene duplications may have on the evolution of multimeric proteins in general. BioEssays 25:142–151, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and (...) information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain. (shrink)

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have (...) been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems. (shrink)

Health, Disease, and Illness brings together a sterling list of classic and contemporary thinkers to examine the history, state, and future of ever-changing "concepts" in medicine.

Rare diseases pose a particular priority setting problem. The UK gives rare diseases special priority in healthcare priority setting. Effectively, the National Health Service is willing to pay much more to gain a quality-adjusted life-year related to a very rare disease than one related to a more common condition. But should rare diseases receive priority in the allocation of scarce healthcare resources? This article develops and evaluates four arguments in favour of such a priority. These pertain to (...) public values, luck egalitarian distributive justice the epistemic difficulties of obtaining knowledge about rare diseases and the incentives created by a higher willingness to pay. The first is at odds with our knowledge regarding popular opinion. The three other arguments may provide a reason to fund rare diseases generously. However, they are either overinclusive because they would also justify funding for many non-rare diseases or underinclusive in the sense of justifying priority for only some rare diseases. The arguments thus fail to provide a justification that tracks rareness as such. There are no data in this work. (shrink)

Collagen is the most abundant vertebrate protein and forms a stable fibrous architecture in connective tissues, such as bone, cartilage, skin and tendon. Much recent research has been directed towards an understanding of the molecular and cellular mechanisms involved in the synthesis and degradation of collagen, because a change in the normal balance, or an increased destruction of collagen, can cause loss of function of specialized tissues. This short review attempts to summarize present knowledge about the proteolytic (...) destruction of collagen and the exciting new work on the factors that are emerging as important controlling agents. An understanding of the regulatory processes is yielding some important clues regarding the levels at which they can fail in pathological conditions and we speculate about evolving strategies for preventing uncontrolled resorption. (shrink)

Collagen fibrils are some of the most‐abundant and important extracellular structures in our bodies, yet we are unsure of their shape and size. This is largely due to an inherent difficulty in isolating them from their surrounding tissues. Echinoderms have collagenous tissues that are similar to ours in many ways, yet they can be manipulated to easily relinquish their collagen fibrils, providing an excellent opportunity to study native fibrillar structure. In the early 1990s, they were found to defy (...) the commonly accepted fibrillar model of the time in that they were much shorter, they were shaped like double‐ended spindles, and their centers exhibited a reversal in molecular polarity. Realization of these features helped to reform the questions that were being asked about vertebrate fibrils, shifting the focus toward shape and size. Since then, researchers working with both groups (echinoderms and vertebrates) have worked together to find the structure of native fibrils. This information will be fundamental in understanding what holds collagenous tissues together at the fibrillar level, and could have important implications for people with Ehlers‐Danlos syndrome. BioEssays 29:645–653, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

RECENT PHILOSOPHICAL ATTENTION TO THE LANGUAGE OF DISEASE HAS FOCUSED PRIMARILY ON THE QUESTION OF ITS VALUE-NEUTRALITY OR NON-NEUTRALITY. PROPONENTS OF THE VALUE-NEUTRALITY THESIS SYMBOLICALLY COMBINE POLITICAL AND OTHER CRITICISMS OF MEDICINE IN AN ATTACK ON WHAT THEY SEE AS VALUE-INFECTED USES OF DISEASE LANGUAGE. THE PRESENT ESSAY ARGUES AGAINST TWO THESES ASSOCIATED WITH THIS VIEW: A METHODOLOGICAL THESIS WHICH TENDS TO DIVORCE THE ANALYSIS OF DISEASE LANGUAGE FROM THE CONTEXT OF THE PRACTICE OF MEDICINE AND A SUBSTANTIVE THESIS WHICH (...) HOLDS THAT DISEASE LANGUAGE IS EVALUATIVELY NEUTRAL. IN PARTICULAR, THE ESSAY CRITICALLY FOCUSES ON THE VALUE NEUTRAL POSITION ADOPTED BY CHRISTOPHER BOORSE, WHICH HE TERMS A FUNCTIONAL THEORY OF DISEASE. THE ARGUMENT CONCERNS WHETHER OR NOT ONE CAN HAVE VALUE NEUTRAL DESCRIPTION OF DISEASE STATES OR WHETHER DISEASE LANGUAGE ESSENTIALLY INVOLVES VALUES. (shrink)

Conceptual analysis of health and disease is portrayed as consisting in the confrontation of a set of criteria—a “definition”—with a set of cases, called instances of either “health” or “ disease.” Apart from logical counter-arguments, there is no other way to refute an opponent’s definition than by providing counter-cases. As resorting to intensional stipulation is not forbidden, several contenders can therefore be deemed to have succeeded. This implies that conceptual analysis alone is not likely to decide between naturalism and normativism. (...) An alternative to this approach would be to examine whether the concept of disease can be naturalized. (shrink)

Rare genetic diseases collectively impact millions of individuals in the United States. These patients and their families share many challenges including delayed diagnosis, lack of knowledgeable providers, and limited economic incentives to develop new therapies for small patient groups. As such, rare disease patients and families often must rely on advocacy, including both self-advocacy to access clinical care and public advocacy to advance research. However, these demands raise serious concerns for equity, as both care and research for a given (...) disease can depend on the education, financial resources, and social capital available to the patients in a given community. In this article, we utilize three case examples to illustrate ethical challenges at the intersection of rare diseases, advocacy and justice, including how reliance on advocacy in rare disease may drive unintended consequences for equity. We conclude with a discussion of opportunities for diverse stakeholders to begin to address these challenges. (shrink)

In their Bioessays review ‘Current views of collagen degradation’, Gillian Murphy and John Reynolds gave an outline of the molecular structure of the members of the collagen family and described their traditional role in providing stable tissue frameworks.1 This short review considers the relationship between the different members of that family and what gene structure reveals about their evolution. Mutation of the collagen structural genes has been discovered in patients suffering from brittle‐bone syndrome and other inherited connective (...) tissue disorders, and here I attempt to rationalize these results into an overall concept of collagen gene mutation and evolution. (shrink)

Paul Griffiths and John Matthewson argue that selected effects play the key role in determining whether a state is pathological. In response, it is argued that a selected effects account faces a number of difficulties in light of modern genomic research. Firstly, a modern history approach to selection is problematic as a basis for assigning function to human traits in light of the small population sizes in the hominin lineage, which imply that selection has played a limited role in shaping (...) these genomes in the evolutionarily recent past. Secondly, determining both the genetic basis of disease and selective histories of the various alleles involved may be experimentally intractable. Thirdly, the existence of “selected disorders” is well supported, and yet on the other hand many other common diseases may not reduce evolutionary fitness. In summary, the biological ends promoted by natural selection, as best modeled in recent research, do not adequately ground a concept of dysfunction that aligns well with the interests of human health. (shrink)

, Lawrie Reznek argues that disease is not a natural kind term. I raise objections to Reznek's two central arguments for establishing that disease is not a natural kind. In criticizing his a priori, conceptual argument against naturalism, I argue that his conclusion rests on a weaker argument that appeals to the empirical diversity in the symptoms and manifestations of disease. I also raise questions about the account of natural kinds which Reznek utilizes and his point that conventions for classification (...) are excluded by there being natural kinds. Keywords: Disease, natural kind, value judgement CiteULike Connotea Del.icio.us What's this? (shrink)

There is a flood of papers being published on new ways to diagnose Alzheimer disease before it is symptomatic, involving a combination of invasive tests , and pen and paper tests. This changes the landscape with respect to genetic tests for risk of AD, making rational suicide a much more feasible option. Before the availability of these presymptomatic tests, even someone with a high risk of developing AD could not know if and when the disease was approaching. One could lose (...) years of good life by committing suicide too soon, or risk waiting until it was too late and dementia had already sapped one of the ability to form and carry out a plan. One can now put together what one knows about one's risk, with continuing surveillance via these clinical tests, and have a good strategy for planning one's suicide before one becomes demented. This has implications for how these genetic and clinical tests are marketed and deployed, and the language one uses to speak about them. The phrase ‘there is nothing one can do’ is insulting and disrespectful of the planned suicide option, as is the language of the Risk Evaluation and Education for Alzheimer's Disease studies and others that conclude that it is ‘safe’ to tell subjects their risk status for AD. Further, the argument put forward by some researchers that presymptomatic testing should remain within research protocols, and the results not shared with subjects until such time as treatments become available, disrespects the autonomy of people at high risk who consider suicide an option. (shrink)

If there is any value in the idea that disease is something other than the mere absence of health then that value must lie in the way that diseases are classified. This paper offers further development of a view advanced previously, the 'contrastive model' of disease: it develops the account to handle asymptomatic disease ; and in doing so it relates the model to a broadly biostatistical view of health. The developments are prompted by considering cancers featuring viruses as (...) prominent causes, since these appear to amount to cases where the prescriptions of the contrastive model could be followed, but aren't. The resulting irrelevance objection claims that the contrastive model is irrelevant to medical science and practice. The paper seeks to rebut the irrelevance objection. (shrink)

This chapter relates the problem of demarcating the pathological from the non-pathological in psychiatry to the general problem of defining ‘disease’ in the philosophy of medicine. Section 2 revisits three prominent debates in medical nosology: naturalism versus normativism, the three dimensions of illness, sickness, and disease, and the demarcation problem. Sections 3–5 reformulate the demarcation problem in terms of semantic vagueness. ‘Disease’ exhibits vagueness of degree by drawing no sharp line in a continuum and is combinatorially vague because there are (...) several criteria for the term’s use that might fall apart. Combinatorial vagueness explains why the other two debates appear hopeless: Should we construe ‘disease’ in a naturalistic or in a normative way? Neither answer is satisfactory. How should we balance the three dimensions of pathology? We do not have to, because illness, sickness and disease (narrowly conceived) are non-competing criteria for the application of the cluster term ‘disease’. (shrink)

The concept of disease remains hotly contested. In light of problems with existing accounts, some theorists argue that the disease concept ought to be eliminated. We answer this skeptical challenge by reframing the discussion in terms of the role that the disease concept plays in the complex network of health-care institutions in which it is deployed. We argue that while prevailing accounts do not suffer from the particular defects that critics have identified, they do suffer from other deficits, and this (...) leads us to propose a new account that satisfies the desiderata for a concept of disease in human medicine. (shrink)

The Neurological Disease Ontology (ND) is being developed to provide a comprehensive framework for the representation of neurological diseases (Diehl et al., 2013). ND utilizes the model established by the Ontology for General Medical Science (OGMS) for the representation of entities in medicine and disease (Scheuermann et al., 2009). The goal of ND is to include information for each disease concerning its molecular, genetic, and environmental origins, the processes involved in its etiology and realization, as well as its clinical (...) presentation including signs and symptoms. (shrink)

The vagueness or imprecision of ‘the normal’ allows it to be exploited for various purposes and political ends. It is conspicuous in both medicine and athletics; I am going to try to say something about the normal in each of these areas. In medicine the idea of the normal is often deployed in understanding what constitutes disease and hence, as some see it, in determining the role of physicians, in determining what is or ought to be covered by insurance, and (...) in underwriting certain views on social justice. In athletics the use of performance enhancing substances raises different sorts of questions about the normal, especially when it comes to deciding what constitutes an enhancement and which enhancements, if any, are acceptable. (shrink)

Debates about the genuine disease status of controversial diseases rely on intuitions about a range of factors. Adopting tools from experimental philosophy, this paper explores some of the factors that influence judgments about whether low sexual desire should be considered a disease and whether it should be medically treated. Drawing in part on some assumptions underpinning a divide in the literature between viewing low sexual desire as a genuine disease and seeing it as improperly medicalized, we investigate whether health (...) and disease judgments are affected by factors such as an individual’s gender, the cause of the low desire, whether the desire is high or low, and both personal and societal valuations of the condition. Our main findings indicate that (a) the cause of a condition influences whether it is judged a disorder, (b) how the individual values the condition influences whether the condition is seen as a proper target of medical intervention, and (c) perceived dysfunction influences judgments regarding health, disorder classification, medicalization, and medical intervention. Our findings help further illuminate the intricate interplay of factors that influence judgments about health and disease in controversial conditions. (shrink)

In the contemporary biomedical literature, every disease is considered genetic. This extension of the concept of genetic disease is usually interpreted either in a trivial or genocentrist sense, but it is never taken seriously as the expression of a genetic theory of disease. However, a group of French researchers defend the idea of a genetic theory of infectious diseases. By identifying four common genetic mechanisms (Mendelian predisposition to multiple infections, Mendelian predisposition to one infection, and major gene and polygenic (...) predispositions), they attempt to unify infectious diseases from a genetic point of view. In this article, I analyze this explicit example of a genetic theory, which relies on mechanisms and is applied only to a specific category of diseases, what we call “a regional genetic theory.” I have three aims: to prove that a genetic theory of disease can be devoid of genocentrism, to consider the possibility of a genetic theory applied to every disease, and to introduce two hypotheses about the form that such a genetic theory could take by distinguishing between a genetic theory of diseases and a genetic theory of Disease. Finally, I suggest that network medicine could be an interesting framework for a genetic theory of Disease. (shrink)

In 1949, Linus Pauling and collaborators published in Science a paper provocatively titled: 'Sickle cell anemia, a molecular disease'. What was actually meant by 'molecular disease'? We interpret the concept of molecular disease in the frame of the traditional positions about the nature of diseases: the ontological and the physiological positions. We conclude that the physiological does not give an adequate account of what molecular diseases are. The ontological position, when correctly reinterpreted, leads to an understanding of molecular (...) diseases where the macromolecule is seen as a symptom or as a part of a mechanism leading to the symptoms of the disease. We then show that the concept of molecular disease leads to a particular view of therapy, emphasizing eugenics as a way of eliminating disease. On the individual level, this concept leads to an increased power of diagnosis, and especially predictive diagnosis, but has little therapeutic consequence. Lastly, we examine how this concept of disease unifies two contemporary classifications of diseases, one based on the location of the diseases, the other on the cause of the diseases. (shrink)

The following article presents preliminary reflections on a processual theory of health and disease. It does this by steering the discussion more toward an ontology of organisms rather than conceptual analysis of the semantic content of the terms “health” and “disease.” In the first section, four meta-theoretical assumptions of the traditional debate are identified and alternative approaches to the problems are presented. Afterwards, the view that health and disease are constituted by a dynamic relation between demands imposed on an organism (...) and individual presuppositions for adequate response is developed. In the last section, the paper takes stock of three possible objections to and clarifies some implications of this approach to the notions of health and disease. (shrink)

Recent philosophical attention to the language of disease has focused primarily on the question of its value-neutrality or non-neutrality. Proponents of the value-neutrality thesis symbolically combine political and other criticisms of medicine in an attack on what they see as value-infected uses of disease language. The present essay argues against two theses associated with this view: a methodological thesis which tends to divorce the analysis of disease language from the context of the practice of medicine and a substantive thesis which (...) holds that disease language is evaluatively neutral. In particular, the essay critically focuses on the value neutral position adopted by Christopher Boorse, which he terms a functional theory of disease. The argument concerns whether or not one can have value neutral description of disease states or whether disease language essentially involves values. (shrink)

Philosophical debates about the concept of disease, particularly of mental disease, might benefit from reconsideration and a closer look at the established terminology and conceptual structure of contemporary medical pathology and clinical nosology. The concepts and principles of medicine differ, to a considerable extent, from the ideas and notions of philosophical theories of disease. In medical theory, the concepts of disease entity and pathologicity are, besides the concept of disease itself, of fundamental importance, and they are essentially connected to the (...) concepts cause of disease or etiological factor, natural course or natural history of disease, and pathological disposition. It is the concept of disease entity that is of key importance for understanding medical pathology and theory of disease. Its central role is shown by a short reconstruction of its main features and its intrinsic connection to the concept of pathologicity. The meaning of pathologicity is elucidated by explicating the underlying criteria. (shrink)

The New Testament, while rejecting any superficial connection between illness and sin, does not reject a possible connection between illness and a person's relationship with God. An example can be seen in the story of the young blind man who was healed. His blindness does not result from any fault he or his parents had committed but apparently from God's wish to reveal his own healing power. The inner blindness of the Pharisees is a different type of blindness far more (...) difficult to heal. The blind young man was actually healed, not only in body but also in soul. Such miraculous healings are rare nowadays. However, if one takes a closer look at modern genetics and psycho-neuro-immunological findings, one may come to a better understanding of how miracle healings are linked to man's inner life and therefore also to his religiousness. Many diseases have genetic backgrounds. Defective genes, however, do not necessarily lead to subsequent illness. Genes have to be switched on or off. Only activated genes trigger pathological change. The human brain and all of man's thinking and feeling are intimately connected with such activations. We may thus conclude that both inner life and religious outlook on life are relevant to the origin and development of diseases. (shrink)

코로나 전염병에 관한 담론을 주제로 한 본 연구는 이중적 목적을 갖고 있다. 첫째 방역정책에 있어 개인의 행동에 초점을 두는 미시적 담론에서 가장 논란이 되는 “신체주권(bodily Sovereignty)”이란 개념을 전염병 현실과 관련하여 분석한다. 이 개념의 원조인 J.S. 밀의 저작에서 신체주권이 무엇을 의미하는지 파악하고, 이를 코로나 현실 상황에 적용하여 신체주권에 기반한 주장의 타당성을 검토한다. 둘째 이렇게 미시적으로 분석된 내용을 사회-정치체계의 장기적 방향을 논의하는 거시적 담론과 연결시켜 논쟁의 향방을 ‘가늠’해보려고 시도한다. 아감벤과 지젝이 서로 대척점에 선거시논쟁에서 본 연구는 미시담론적 분석이 지젝쪽의 주장에 좀 더 무게를 (...) 실어주지 않나 어림잡아 본다. 미시와 거시라는 두 수준에서 각기 분석하여 연결을 이와 같이 시도하는 것은 코로나 전염병에 관한 담론의 전반적 구도를 드러내어 이 주제에 관한 향후 논의에 담론적 개요를 제공할 수 있기를 기대하기 때문이다. (shrink)

Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield’s hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, (...) I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield’s etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield’s theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs. (shrink)

The Infectious Disease Ontology (IDO) is a suite of interoperable ontology modules that aims to provide coverage of all aspects of the infectious disease domain, including biomedical research, clinical care, and public health. IDO Core is designed to be a disease and pathogen neutral ontology, covering just those types of entities and relations that are relevant to infectious diseases generally. IDO Core is then extended by a collection of ontology modules focusing on specific diseases and pathogens. In this (...) paper we present applications of IDO Core within various areas of infectious disease research, together with an overview of all IDO extension ontologies and the methodology on the basis of which they are built. We also survey recent developments involving IDO, including the creation of IDO Virus; the Coronaviruses Infectious Disease Ontology (CIDO); and an extension of CIDO focused on COVID-19 (IDO-CovID-19).We also discuss how these ontologies might assist in information-driven efforts to deal with the ongoing COVID-19 pandemic, to accelerate data discovery in the early stages of future pandemics, and to promote reproducibility of infectious disease research. (shrink)

Recently, concerns have been raised about the phenomenon of ‘overdiagnosis’, the diagnosis of a condition that is not causing harm, and will not come to cause harm. Along with practical, ethical, and scientific questions, overdiagnosis raises questions about our concept of disease. In this paper, we analyse overdiagnosis as an epistemic problem and show how it challenges many existing accounts of disease. In particular, it raises ques- tions about conceptual links drawn between disease and dysfunction, harm, and risk. We argue (...) that ‘disease’ should be considered a vague concept with a non-classical structure. On this view, overdiagnosed cases are ‘borderline’ cases of disease, falling in the zone between cases that are clearly disease, and cases that are clearly not disease. We then develop a pre ́cising definition of disease designed to provide practical help in preventing and limiting overdiagnosis. We argue that for this purpose, we can define disease as dysfunction that has a significant risk of causing severe harm to the patient. (shrink)

Despite several decades of debate, the concept of disease remains hotly contested. The debate is typically cast as one between naturalism and normativism, with a hybrid view that combines elements of each staked out in between. In light of a number of widely discussed problems with existing accounts, some theorists argue that the concept of disease is beyond repair and thus recommend eliminating it in a wide range of practical medical contexts. Any attempt to reframe the ‘disease’ discussion should answer (...) the more basic sceptical challenge, and should include a meta-methodological critique guided by our pragmatic expectations of what the disease concept ought to do given that medical diagnosis is woven into a complex network of healthcare institutions. In this paper, we attempt such a reframing, arguing that while prevailing accounts do not suffer from the particular defects that prominent critics have identified, they do suffer from other deficits—and this leads us to propose an amended hybrid view that places objectivist approaches to disease on stronger theoretical footing, and satisfies the institutional-ethicaldesiderataof a concept of disease in human medicine. Nevertheless, we do not advocate a procrustean approach to ‘disease’. Instead, we recommend disease concept pluralism between medical and biological sciences to allow the concept to serve the different epistemic and institutional goals of these respective disciplines. (shrink)

The philosophy of medicine and psychiatry has considered the defining of disease, illness, and disorder an important project for over three decades. Within this literature, accounts based on adaptive "functions" have been prominent, particularly in the DSM nosology. In response to this trend, Jerome Wakefield has presented a view of mental disorder as "harmful dysfunction." In this view, "harm" contributes the value-element to disorder concepts, while "dysfunction" implies a value-free foundation as long as the latter is grounded in evolutionary biology. (...) In a critical review of Wakefield's and others' functionalist arguments for disorder concepts, we make four major points. We recommend a shift away from the definition of value-free disorder concepts, instead emphasizing the analysis of the logical features and the value commitments in nosological categories. (shrink)

The concepts of health and disease play pivotal roles in medicine and the health professions This volume brings together the requisite literature for understanding current discussions and debates these concepts. The selections in the volume attempt to present a wide range of views concerning the nature of the concepts of health and issues using both historical and contemporary sources -- Back cover.

This article concerns the metaphysics of disease. Is disease a fixed feature of the world or a social value or preference? I argue that disease is not a value-laden concept and thus debates concerning it differ fundamentally from debates concerning health, harm, or suffering where evaluative judgements are central. I show how the so-called social constructionist view of disease has been motivated both by ethical concerns with medical practices and general theoretical doubts about scientific naturalism. If I can show that (...) ethical concerns about medical treatment can be answered without adopting social constructionism, that leaves only the broader theoretical question of naturalism. I cannot completely answer those theoretical doubts, but I show that the theoretical motivation is less convincing when it is separated from the moral challenge often accompanying it. I conclude that a convincing defense of the non-naturalistic conception of disease is rarely attempted and proves more difficult and counter-intuitive than its proponents assume. (shrink)

Social Constructivism about the disease concept has generally been taken to ignore the fundamental biological reality underlying diseases, as well as to fall foul of several apparently compelling objections. In this paper, I explain how the metaphysical relation of grounding can be used to tie a socially constructed account of diseases and their classification to their underlying biological and behavioural states. I then generalize the position by disambiguating several varieties of normativism, including a particularly strong ‘placeholder’ version of (...) social constructivism, and showing that the grounding approach is available to each. I go on to provide what I believe to be the first attempt at a full semantics for disease-talk and disagreement, before using the placeholder to demonstrate on that basis that the most troublesome objections to normativism can be avoided even by very strong versions of the position. (shrink)

Terminally ill patients in 10 states plus Washington, D.C. have the right to take prescribed medications to end their lives (medical aid in dying). But otherwise-eligible patients with neuromuscular disabilities (ALS and other illnesses) are excluded if they are physically unable to “self-administer” the medications without assistance. This exclusion is incompatible with disability rights laws that mandate assistance to provide equal access to health care. This contradiction between aid-in-dying laws and disability rights laws can force patients and clinicians into violating (...) one or the other, potentially creating an underclass of patients denied medical care that is available to those with other (less physically disabling) terminal illnesses. The immediacy of this issue is demonstrated by a lawsuit in Federal court filed in August 2021, requesting assistance in self-administration for terminally ill patients with neuromuscular diseases. This paper discusses the background of this conflict, the ethical issues at the heart of the dilemma, and recommends potential remedies. (shrink)

Stigma has become an important concept in public health law. It is widely accepted that certain diseases are disfavored in society, leading to discrimination against people identified with them, which in turn has the tendency to drive an epidemic underground—i.e., to make it more difficult for voluntary public health programs to reach and succeed among populations bent on concealing their disease or risk status. The need to reduce stigma and its effects has been used to justify the passage of (...) privacy and antidiscrimination law to protect people with HIV. More recently, stigma has been part of the arsenal of justification for special genetic antidiscrimination and privacy law. Despite its importance, however, there is no single widely accepted definition of stigma in social science, and its relationship to law has been generally under-theorized and unsupported by data, reducing our ability to effectively deploy law and other tools in the anti-stigma cause. (shrink)

Alzheimer’s Disease (AD) provides an excellent case study to investigate emerging conceptions of health, disease, pre-disease, and risk. Two scientific working groups have recently reconceptualized AD and created a new category of asymptomatic biomarker positive persons, who are either said to have preclinical AD, or to be at risk for AD. This article examines how prominent theories of health and disease would classify this condition: healthy or diseased? Next, the notion of being “at risk”—a state somewhere in-between health and disease—is (...) considered from various angles. It is concluded that medical-scientific developments urge us to let go of dichotomous ways of understanding disease, that the notion of “risk,” conceptualized as an increased chance of getting a symptomatic disease, might be a useful addition to our conceptual framework, and that we should pay more attention to the practical usefulness and implications of the ways in which we draw lines and define concepts. (shrink)

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in (...) the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. (shrink)

Response to commentary. We are grateful to Crockett and Craigie for their interesting remarks on our paper. We accept Crockett’s claim that there is a need for caution in drawing inferences about patient groups from work on healthy volunteers in the laboratory. However, we believe that the evidence we cited established a strong presumption that many of the patients who are routinely taking a medication, including many people properly prescribed the medication for a medical condition, have morally significant aspects of (...) their cognition and behavior modified in a way that is unintended and may sometimes be unwelcome. Crockett notes that in some cases the effects of long-term drug use may differ, sometimes markedly, from the effects of short-term use. However, if acute use of a drug affects a neural system involved in mediating moral cognition or behavior, this nevertheless provides some evidence that chronic use of the drug may affect that same system and thus have morally significant effects. It is also plausible, in some cases, that an acute moral effect would give rise to a chronic moral effect via cognitive mechanisms. ... (shrink)

It is argued that alcoholism, and substance addiction generally, is a disease. It is not of its nature chronic or progressive, although it is in serious cases. It is better viewed as a psychological disease than a neurological one. It is argued that each time an alcoholic takes a drink, this is the result of choice; however, in cases of serious affliction, such choices are compulsive and may be called 'involuntary' in that they are made against the subject's will, motivated (...) by an overwhelmingly powerful desire that he wishes he did not have and not to act on. Alternative accounts in terms social learning theory and behavioral economics are critiqued. The conception of alcoholism as a tripartite disease composed of a 'physical allergy,' a mental obsession, and a 'spiritual malady' is defended from a contemporary scientific point of view. (shrink)