Philosophy of Physiology
Abstract
Time is ripe to complement the question 'what is health and disease?' in philosophy of medicine with a 'philosophy of physiology.' Indeed, the actors in this debate share the conviction that a 'foundational' concept dictates to this scientific field what is to be considered healthy or pathological and leaves it to explore only facts and mechanisms. Rejecting this presupposition, philosophy of physiology accepts that biomedical sciences explore and redefine their own object: the healthy, the pathological. Indeed, various theories of disease and health, that philosophers have rarely studied, form the core of biomedical research, too hastily considered as a science 'without theories.' The Element identifies them, and clarifies their content, presuppositions, and scope. Finally, it proposes a new question about the unity of the pathological phenomenon: not 'what do all diseases have in common?' but rather, 'why is the susceptibility to disease a universal and necessary characteristic of living beings?'
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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.
Most philosophers of science do philosophy ‘on’ science. By contrast, others do philosophy ‘in’ science (‘PinS’), i.e., they use philosophical tools to address scientific problems and to provide scientifically useful proposals. Here, we consider the evidence in favour of a trend of this nature. We proceed in two stages. First, we identify relevant authors and articles empirically with bibliometric tools, given that PinS would be likely to infiltrate science and thus to be published in scientific journals (‘intervention’), cited in scientific journals (‘visibility’) and sometimes recognized as a scientific result by scientists (‘contribution’). We show that many central figures in philosophy of science have been involved in PinS, and that some philosophers have even ‘specialized’ in this practice. Second, we propose a conceptual definition of PinS as a process involving three conditions (raising a scientific problem, using philosophical tools to address it, and making a scientific proposal), and we ask whether the articles identified at the first stage fulfil all these conditions. We show that PinS is a distinctive, quantitatively substantial trend within philosophy of science, demonstrating the existence of a methodological continuity from science to philosophy of science.
We situate the well-trodden debate about defining health and disease within the project of a metaphysics of science and its aim to work with and contribute to science. We make use of Guay and Pradeu’s ‘metaphysical box’ to reframe this debate, showing what is at stake in recent attempts to move beyond it, revealing unforeseen points of agreement and disagreement among new and old positions, and producing new questions that may lead to progress. We then discuss the implications of the two-way benefits between medicine and philosophy when the latter is driven and constrained by medical science.
Eukaryogenesis, the origin of the eukaryotes, is still poorly understood. Herein, we show how a detailed all-kingdom phylogenetic analysis overlaid with a map of key biochemical features can provide valuable clues. The photolyase/cryptochrome family of proteins are well known to repair DNA in response to potentially harmful effects of sunlight and to entrain circadian rhythms. Phylogenetic analysis of photolyase/cryptochrome protein sequences from a wide range of prokaryotes and eukaryotes points to a number of horizontal gene transfer events between ancestral bacteria and ancestral eukaryotes. Previous experimental research has characterised patterns of tryptophan residues in these proteins that are important for photoreception, specifically a tryptophan dyad, a canonical tryptophan triad, an alternative tryptophan triad, a tryptophan tetrad and an alternative tetrad. Our results suggest that the spread of the different triad and tetrad motifs across the kingdoms of life accompanied the putative horizontal gene transfers and is consistent with multiple bacterial contributions to eukaryogenesis.
Aging is an elusive property of life, and many important questions about aging depend on its definition. This article proposes to draw a definition from the scientific literature on aging. First, a broad review reveals five features commonly used to define aging: structural damage, functional decline, depletion, typical phenotypic changes or their cause, and increasing probability of death. Anything that can be called ‘aging’ must present one of these features. Then, although many conditions are not consensual instances of aging, aging is consensually described as a process of loss characterized by a rate and resulting from the counteraction of protective mechanisms against mechanisms that limit lifespan. Beyond such an abstract definition, no one has yet succeeded in defining aging by a specific mechanism of aging because of an explanatory gap between such a mechanism and lifespan, a consensual explanandum of a theory of aging. By contrast, a sound theoretical definition can be obtained by revisiting the evolutionary theory of aging. Based on this theory, aging evolves thanks to the impossibility that natural selection eliminates late traits that are neutral mainly due to decreasing selective pressure. Yet, the results of physiological research suggest that this theory should be revised to also account for the small number of different aging pathways and for the existence of mechanisms counteracting these pathways, that must, on the contrary, have been selected. A synthetic, but temporary definition of aging can finally be proposed.
Debates in fields studying the biological aspects of aging and longevity, such as biogerontology, are often split between ‘anti-aging’ approaches aimed largely at treating diseases and those focusing more on maintaining, promoting, and even enhancing health. However, it is far from clear what this ‘health’ is that would be maintained, promoted, or enhanced. Interestingly, what few have yet to fully reflect on is that there is still no theory of health within the health or aging sciences that would provide an integrative explanatory framework akin to other scientific theories. After clarifying why such a theory could be useful, I discuss five general features of medical theories that could be used to evaluate the utility of a given proposal. With these features in hand, I suggest that philosophers and scientists work together on analyzing actual medical research (experimental analysis), and the ways in which a theoretical construct of ‘health’ is being progressively identified and measured therein. I conclude by suggesting that research fields studying stress and aging might be particularly helpful in developing candidates for theory construction due to their broad scope, increasing specificity, and potential for providing integrative explanations.
‘This is an incredibly audacious book. Derek Bolton and Grant Gillett brilliantly succeed in providing the big picture that was lacking in the defense of the biopsychosocial model promoted by Engel 40 years ago.’
- Steeves Demazeux, Assistant Professor in philosophy, Bordeaux-Montaigne University, France
This open access book is a systematic update of the philosophical and scientific foundations of the biopsychosocial model of health, disease and healthcare. First proposed by George Engel 40 years ago, the Biopsychosocial Model is much cited in healthcare settings worldwide, but has been increasingly criticised for being vague, lacking in content, and in need of reworking in the light of recent developments. The book confronts the rapid changes to psychological science, neuroscience, healthcare, and philosophy that have occurred since the model was first proposed and addresses key issues such as the model’s scientific basis, clinical utility, and philosophical coherence.
The authors conceptualise biology and the psychosocial as in the same ontological space, interlinked by systems of communication-based regulatory control which constitute a new kind of causation. These are distinguished from physical and chemical laws, most clearly because they can break down, thus providing the basis for difference between health and disease. This work offers an urgent update to the model’s scientific and philosophical foundations, providing a new and coherent account of causal interactions between the biological, the psychological and social.
Derek Bolton is Professor of Philosophy and Psychopathology at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, UK. He was awarded a double first in Moral Sciences and a PhD in Philosophy at the University of Cambridge. His subsequent professional career was in clinical psychology and he has published extensively in philosophy of psychiatry as well as basic and clinical health science.
Grant Gillett is Professor of Bioethics at the University of Otago, New Zealand. His professional career was in Neurosurgery, punctuated by a D. Phil. at Oxford University in philosophy of mind and meta-ethics. He has published extensively in neuroethics, philosophy of mind and language, philosophy of medicine (particularly psychiatry), and the philosophy of medical and social sciences.
Human microbiome research makes causal connections between entire microbial communities and a wide array of traits that range from physiological diseases to psychological states. To evaluate these causal claims, we first examine a well-known single-microbe causal explanation: of Helicobacter pylori causing ulcers. This apparently straightforward causal explanation is not so simple, however. It does not achieve a key explanatory standard in microbiology, of Koch’s postulates, which rely on manipulations of single-microorganism cultures to infer causal relationships to disease. When Koch’s postulates are framed by an interventionist causal framework, it is clearer what the H. pylori explanation achieves and where its explanatory strengths lie. After assessing this ‘simple’, single-microbe case, we apply the interventionist framework to two key areas of microbiome research, in which obesity and mental health states are purportedly explained by microbiomes. Despite the experimental data available, interventionist criteria for explanation show that many of the causal claims generated by microbiome research are weak or misleading. We focus on the stability, specificity and proportionality of proposed microbiome causal explanations, and evaluate how effectively these dimensions of causal explanation are achieved in some promising avenues of research. We suggest some conceptual and explanatory strategies to improve how causal claims about microbiomes are made.
The vitality of physiology is currently under debate. Some say that physiology is a dying discipline in the era of molecular medicine and systems biology, whereas others claim that physiology remains a key biological and medical discipline, due in part to its integrative nature. In this conceptual review, we argue that any assessment of the vitality of physiology depends heavily on the definition of this discipline adopted. We examine two main conceptions of physiology, one focusing on its object (what physiology is about), and the other on the methods used (how physiologists study the biological reality). We contend that physiology no longer encompasses all biological disciplines and may no longer be the only synoptic biological science. However, far from indicating a sterility of this discipline, this situation should drive physiology to re-invent its relationship with these other biological domains.
Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term’s historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth.
Several evolutionary processes influence virulence, the amount of damage a parasite causes to its host. For example, parasites are favored to exploit their hosts prudently to prolong infection and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. Thus parasites face a tradeoff between prudent exploitation and rapid reproduction-a life history tradeoff between longevity and fecundity. Other tradeoffs among components of parasite fitness also influence virulence. For example, competition among parasite genotypes favors rapid growth to achieve greater relative success within the host. Rapid growth may, however, lower the total productivity of the local group by overexploiting the host, which is a potentially renewable food supply. This is a problem of kin selection and group selection. I summarize models of parasite virulence with the theoretical tools of life history analysis, kin selection, and epidemiology. I then apply the theory to recent empirical studies and models of virulence. These applications, to nematodes, to the extreme virulence of hospital epidemics, and to bacterial meningitis, show the power of simple life history theory to highlight interesting questions and to provide a rich array of hypotheses. These examples also show the kinds of conceptual mistakes that commonly arise when only a few components of parasite fitness are analysed in isolation. The last part of the article connects standard models of parasite virulence to diverse topics, such as the virulence of bacterial plasmids, the evolution of genomes, and the processes that influenced conflict and cooperation among the earliest replicators near the origin of life.
We generally think of a genetic disease as a disease that is genetically caused or as a disease for which the genetic cause is more important than environmental causes. Diseases like PKU (phenylketonuria) and lactose intolerance, for instance, are classified as genetic, because they are caused by enzyme deficiencies which are due to genetic defects. In both cases the absence of a gene (or the absence of a gene with an adequate structure) leads to the absence of an enzyme that is able to counteract a harmful substance. The substance, phenylalanine or lactose, accumulates and damages the organism.
This new, thoroughly recast Second Edition has been acclaimed as “the most important book written since the beginning of that strange project called bioethics” (Stanley Hauerwas, Duke University). Its philosophical exploration of the foundations of secular bioethics has been substantially expanded. The book challenges the values of much of contemporary bioethics and health care policy by confronting their failure to secure the moral norms they seek to apply. The nature of health and disease, the definition of death, the morality of abortion, infanticide, euthanasia, physician-assisted suicide, germline genetic engineering, triage decisions and distributive justice in health care are all addressed within an integrated reconsideration of bioethics as a whole. New material has been added regarding social justice, health care reform and environmental ethics. The very possibility and meaning of a secular bioethics are re-explored.
The unexpected roles of the microbiota in cancer challenge explanations of carcinogenesis that focus on tumor-intrinsic properties. Most tumors contain bacteria and viruses, and the host’s proximal and distal microbiota influence both cancer incidence and therapeutic responsiveness. Continuing the history of cancer-microbe research, these findings raise a key question: to what extent is the microbiota relevant for clinical oncology? We approach this by critically evaluating three issues: how the microbiota provides a predictive biomarker of cancer growth and therapeutic responsiveness, the microbiota’s causal role(s) in cancer development, and how therapeutic manipulations of the microbiota improve patient outcomes in cancer. Clarifying the conceptual and empirical aspects of the cancer-associated microbiota can orient future research and guide its implementation in clinical oncology.
A PubMed analysis shows that the vast majority of human genes have been studied in the context of cancer. As such, the study of nearly any human gene can be justified based on existing literature by its potential relevance to cancer. Moreover, these results have implications for analyzing and interpreting large-scale analyses.
While aging research and policy aim to promote ‘health’ at all ages, there remains no convincing explanation of what this ‘health’ is. In this paper, I investigate whether we can find, implicit within the sciences of aging, a way to know what health is and how to measure it, i.e. a theory of health. To answer this, I start from scientific descriptions of aging and its modulators and then try to develop some generalizations about ‘health’ implicit within this research. After discussing some of the core aspects of aging and the ways in which certain models describe spatial and temporal features specific to both aging and healthy phenotypes, I then extract, explicate, and evaluate one potential construct of health in these models. This suggests a theory of health based on the landscape of optimized phenotypic trajectories. I conclude by considering why it matters for more candidate theories to be proposed and evaluated by philosophers and scientists alike.
Health is usually defined as the absence of pathology. Here, we endeavor to define health as a compendium of organizational and dynamic features that maintain physiology. The biological causes or hallmarks of health include features of spatial compartmentalization (integrity of barriers and containment of local perturbations), maintenance of homeostasis over time (recycling and turnover, integration of circuitries, and rhythmic oscillations), and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, and repair and regeneration). Disruption of any of these interlocked features is broadly pathogenic, causing an acute or progressive derailment of the system coupled to the loss of numerous stigmata of health.
Due to rapidly aging populations, the number of people worldwide experiencing dementia is increasing, and the projections are grim. Despite billions of dollars invested in medical research, no effective treatment has been discovered for Alzheimer's disease, the most common form of dementia. This book exposes the predicaments embedded in current efforts to slow down or halt Alzheimer's disease through early detection of pre-symptomatic biological changes in healthy individuals. Based on a meticulous account of the history of Alzheimer's disease and extensive in-depth interviews, the book highlights the limitations and the dissent associated with biomarker detection. It argues that basic research must continue, but should be complemented by a public health approach to prevention that is economically feasible, more humane, and much more effective globally than one exclusively focused on an increasingly harried search for a cure.
This edited volume aims to better understand the multifaceted phenomenon we call health.
Going beyond simple views of health as the absence of disease or as complete well-being, this book unites scientists and philosophers. The contributions clarify the links between health and adaptation, robustness, resilience, or dynamic homeostasis, and discuss how to achieve health and healthy aging through practices such as hormesis.
The book is divided into three parts and a conclusion: the first part explains health from within specific disciplines, the second part explores health from the perspective of a bodily part, system, function, or even the environment in which organisms live, and the final part looks at more clinical or practical perspectives. It thereby gathers, across 30 chapters, diverse perspectives from the broad fields of evolutionary and systems biology, immunology, and biogerontology, more specific areas such as odontology, cardiology, neurology, and public health, as well as philosophical reflections on mental health, sexuality, authenticity and medical theories.
The overarching aim is to inform, inspire and encourage intellectuals from various disciplines to assess whether explanations in these disparate fields and across biological levels can be sufficiently systematized and unified to clarify the complexity of health. It will be particularly useful for medical graduates, philosophy graduates and research professionals in the life sciences and general medicine, as well as for upper-level graduate philosophy of science students. https://www.springer.com/gp/book/9783030526627
A distinction between different notions of “structure” and “function” is suggested for interpreting the overwhelming amount of data on microbiome structure and function. Sequence data, biochemical agents, interaction networks, taxonomic communities, and their dynamics can be linked to potential or actual biochemical activities, causal roles, and selected effects, respectively. This conceptual clarification has important methodological consequences for how to interpret existing data and approach open questions in contemporary microbiome research practice. In particular, the field will have to start thinking about notions of function more directly.
The ability to maintain health, or recover to a healthy state after disease, is an active process involving distinct adaptation mechanisms coordinating interactions between all physiological systems of an organism. Studies over the past several decades have assumed the mechanisms of health and disease are essentially inter-changeable, focusing on the elucidation of the mechanisms of disease pathogenesis to enhance health, treat disease, and increase healthspan. Here, I propose that the evolved mechanisms of health are distinct from disease pathogenesis mechanisms and suggest that we develop an understanding of the biology of physiological health. In this Perspective, I provide a definition of, a conceptual framework for, and proposed mechanisms of physiological health to complement our understanding of disease and its treatment.
Levels of Analysis in Psychopathology - edited by Kenneth S. Kendler April 2020
The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Parental environmental factors including diet, body composition, metabolism and stress affect the health and chronic disease risk of people throughout their lives, as captured in the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. Research across epidemiological, clinical and basic science fields has identified the period around conception as being critical in the processes mediating parental influences on the next generation’s health. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune and neurological morbidities, often termed ‘developmental programming’. We review ‘periconceptional’ induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and from the use of assisted reproductive treatment. Human studies and animal models demonstrate the underlying biological mechanisms, including epigenetic, cellular, physiological and metabolic processes. A novel meta-analysis of mouse paternal and maternal protein undernutrition indicate distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
Classifying Madness examines the conceptual foundations of the D.S.M., the main classification of mental disorders used by psychiatrists world-wide. It will be of interest to both mental health professionals and to philosophers interested in classification in science. The D.S.M. has become extremely controversial, and the possibility that there may be philosophical difficulties with it has become a commonplace in the mental health literature. Classifying Madness offers mental health professionals an opportunity to explore suspicions that there might be conceptual problems with the D.S.M. For philosophers, this book aims to contribute to debates in the philosophy of science concerning natural kinds, the theory-ladenness of classification, and the effect of sociological factors in science. These issues are normally approached via a consideration of the natural sciences and, as will be seen, approaching them via a consideration of psychiatry helps shed new light on old problems.
GENERAL INTRODUCTION This study of the concept of health is an attempt to combine central ideas in modern philosophy of medicine with certain results from analytical action theory. What emerges from the study is a concept 'of health based on an action-theoretic foundation. A person's health is characterized as his ability to achieve his vital goals. The general conception is not new. This study has been inspired by a number of scholars, both ancient and modern. The most important influences from the latter have been those of Georges Canguilhem, H. Tristram Engelhardt Jr. , Caroline Whitbeck and Ingmar Porn. The novel aspect of this book consists of elaborations made to the general conception. First, the action-theoretic platform is analysed in some detail. The nature of the ability involved, as well as the conditions for having that ability, are specified. Second, the vital goals of man are given considerable attention. Some previous attempts to define such vital goals are analysed and criticized. A new characterization is proposed, in which the vital goals are conceptually linked to the notion of happiness. A person's vital goals are such states of affairs as are necessary and together sufficient for his minimal happiness. Third, a number of consequences of this con ception are observed and analysed. One issue which is particularly empha sized is that of whether the concept of health is a theoretical or a normative concept.
In contrast to homeostasis, allostasis refers to the relatively new idea of "viability through change." This book addresses basic physiological regulatory systems, and examines bodily regulation under duress. It integrates the basic concepts of physiological homeostasis with disorders such as depression, stress, anxiety and addiction. It will interest graduate students, medical students, and researchers in physiology, epidemiology, endocrinology, neuroendocrinology, neuroscience, and psychology.
Good bacteria help fight cancer
Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer.
Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32
We defend a view of the distinction between the normal and the pathological according to which that distinction has an objective, biological component. We accept that there is a normative component to the concept of disease, especially as applied to human beings. Nevertheless, an organism cannot be in a pathological state unless something has gone wrong for that organism from a purely biological point of view. Biology, we argue, recognises two sources of biological normativity, which jointly generate four "ways of going wrong" from a biological perspective. These findings show why previous attempts to provide objective criteria for pathology have fallen short: Biological science recognizes a broader range of ways in which living things can do better or worse than has previously been recognized in the philosophy of medicine.
What kind of a thing are chronic diseases? Are they objects, bundles of signs and symptoms, properties, processes, or fictions? Rather than using concept analysis—the standard approach to disease in the philosophy of medicine—to answer this metaphysical question, I use a bottom-up, inductive approach. I argue that chronic diseases are bodily states or properties—often dispositional, but sometimes categorical. I also investigate the nature of related pathological entities: pathogenesis, etiology, and signs and symptoms. Finally, I defend my view against alternate accounts of the nature of disease.
Dysbiosis, an imbalance in the microbiota, has been a major organizing concept in microbiome science. Here, we discuss how the balance concept, a holdover from prescientific thought, is irrelevant to — and may even distract from — useful microbiome research.
Some ‘naturalist’ accounts of disease employ a biostatistical account of dysfunction, whilst others use a ‘selected effect’ account. Several recent authors have argued that the biostatistical account offers the best hope for a naturalist account of disease. We show that the selected effect account survives the criticisms levelled by these authors relatively unscathed, and has significant advantages over the BST. Moreover, unlike the BST, it has a strong theoretical rationale and can provide substantive reasons to decide difficult cases. This is illustrated by showing how life-history theory clarifies the status of so-called diseases of old age. The selected effect account of function deserves a more prominent place in the philosophy of medicine than it currently occupies.
• 1 Introduction
• 2 Biostatistical and Selected Effect Accounts of Function
• 3 Objections to the Selected Effect Account
• 3.1 Boorse
• 3.2 Kingma
• 3.3 Hausman
• 3.4 Murphy and Woolfolk
• 4 Problems for the Biostatistical Account
• 4.1 Schwartz
• 5 Analysis versus Explication
• 6 Explicating Dysfunction: Life History Theory and Senescence
• 7 Conclusion
In the mucosa, the immune system's T cells and B cells have position-specific phenotypes and functions that are influenced by the microbiota. These cells play pivotal parts in the maintenance of immune homeostasis by suppressing responses to harmless antigens and by enforcing the integrity of the barrier functions of the gut mucosa. Imbalances in the gut microbiota, known as dysbiosis, can trigger several immune disorders through the activity of T cells that are both near to and distant from the site of their induction. Elucidation of the mechanisms that distinguish between homeostatic and pathogenic microbiota-host interactions could identify therapeutic targets for preventing or modulating inflammatory diseases and for boosting the efficacy of cancer immunotherapy.
Christopher Boorse’s biostatistical theory of health and disease (BST) puts forward a naturalistic definition of these two concepts. Indeed, ‘naturalism’ in the philosophy of medicine was initially defined in terms of the BST, and has often been since. This chapter is an attempt to clarify in what sense Boorse does in fact defend a naturalistic definition of health and disease. We identify different theses that make naturalistic claims regarding health and disease and which help analyze the core claims of Boorse’s naturalism. Some of them have mainly to do with the central role physiology plays in medicine. But, as no physiologist has hitherto proposed a satisfactory scientific definition of ‘disease’ and ‘health’, Boorse’s naturalism must at the same time: (i) propose just such a definition; and (ii) prove that it is central to medicine. Our claim is that even if Boorse’s definition possibly succeeds in (i), it merely assumes (ii). We conclude by examining the necessity that a naturalistic definition of health and disease takes into account not only physiology but also other medical sciences.
In this article, I argue that as a theoretical matter, a population's health-level is best quantified via averagism. Averagism asserts that the health of a population is the average of members' health-levels. This model is better because it does not fall prey to a number of objections, including the repugnant conclusion, and because it is not arbitrary. I also argue that as a practical matter, population health-levels are best quantified via totalism. Totalism asserts that the health of a population is the sum of members' health-levels. Totalism is better here because it fits better with cost-benefit analysis and such an analysis is the best practical way to value healthcare outcomes. The two results are compatible because the theoretical and practical need not always align, whether in general or in the context of population health.
Psychiatry and Philosophy of Science explores conceptual issues in psychiatry from the perspective of analytic philosophy of science. Through an examination of those features of psychiatry that distinguish it from other sciences for example, its contested subject matter, its particular modes of explanation, its multiple different theoretical frameworks, and its research links with big business Rachel Cooper explores some of the many conceptual, metaphysical and epistemological issues that arise in psychiatry. She shows how these pose interesting challenges for the philosopher of science while also showing how ideas from the philosophy of science can help to solve conceptual problems within psychiatry. Coopers discussion ranges over such topics as the nature of mental illness, the treatment decisions and diagnostic categories of psychiatry, the case-history as a form of explanation, how psychiatry might be value-laden, the claim that psychiatry is a multi-paradigm science, the distortion of psychiatric research by pharmaceutical industries, as well as engaging with the fundamental question whether the mind is reducible to something at the physical level. Psychiatry and Philosophy of Science demonstrates that cross-disciplinary contact between philosophy of science and psychiatry can be immensely productive for both subjects and it will be required reading for mental health professionals and philosophers alike.
It is now increasingly acknowledged that an evolutionary perspective can give us important new insights into issues central to medical research and practice. This fully revised and updated edition, which consists of roughly 95% new material, contains contributions from leading researchers who provide a fresh summary of this rapidly expanding field. It takes a broad approach to the subject, discussing medically relevant research from evolutionary genetics, evolutionary ecology, evolutionary epidemiology, the evolution of aging, and any other biological disciplines where evolutionary approaches make important contributions. The medical conditions discussed include diabetes, obesity, cardiovascular disease, asthma, allergies and other autoimmune diseases, infectious diseases, emerging diseases, and aging. It also provides insights into the evolutionary responses of pathogens to antibiotics and vaccines. What will happen if we continue to expand our use of antibiotics and vaccines? Why do we respond inappropriately (for example by developing cardiovascular disease) to many modern conditions? How do cancers evolve, particularly in response to chemotherapy? Why must we grow old, and can we do anything about it? This book discusses answers to these and many other questions.
This chapter presents various aspects of different theories and models in medicine. Bolie's model of Insulin-Glucose Regulation assumes only three entities — glucose, insulin, and extracellular fluid — and identifies nine variables. The menstrual cycle is not restricted to humans but medical science has provided the most in-depth and physiologically embedded advances in understanding the cycle — its hormonal, biochemical, physiological, and evolutionary dynamics. An example of a unifying model in medicine is the construction of models of self-regulating systems (homeostatic systems) which, in endocrinology for example, subsumes the insulin–glucose system as well as the menstrual cycle and many other hormonal systems such as the TSH–thyroxin system. An example of a unifying model in medicine is the construction of models of self-regulating systems (homeostatic systems) which, in endocrinology, for example, subsumes the insulin–glucose system as well as the menstrual cycle and many other hormonal systems such as the TSH–thyroxin system. It is suggested that the vast majority of medical science is deeply connected to the rest of science and shares the theoretical depth, sophistication, and explanatory power of those sciences.
Trade-offs between reproduction and maintenance can compromise health. Male hormones such as testosterone regulate energy allocation between reproductive effort and survival; this is made evident when immunological challenges cause changes in reproductive hormones. Female hormones adjust energy allocation between investment in ovarian function, somatic investment, and present offspring (lactation), implementing trade-offs between present and future reproduction. Metabolic hormones respond to environmental cues to sequester or liberate energetic resources such as glucose and fat. Mismatch between environmental conditions and the expression of metabolic hormones are likely to underlie variation in obesity and diabetes. Lifetime variation in endogenous reproductive hormones suggests a trade-off between early benefits for reproduction and later costs against survivorship expressed in population differences in the incidence of reproductive tumors, such as breast and prostate cancer.
Two decades of studies in multiple model organisms have established the Hippo pathway as a key regulator of organ size and tissue homeostasis. By inhibiting YAP and TAZ transcription co-activators, the Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein-coupled receptors, and cellular energy status. Dysregulation of the Hippo pathway exerts a significant impact on cancer development. Further investigation of the functions and regulatory mechanisms of this pathway will help uncovering the mystery of organ size control and identify new targets for cancer treatment.
The brain is the central organ involved in perceiving and adapting to social and physical stressors via multiple interacting mediators, from the cell surface to the cytoskeleton to epigenetic regulation and nongenomic mechanisms. A key result of stress is structural remodeling of neural architecture, which may be a sign of successful adaptation, whereas persistence of these changes when stress ends indicates failed resilience. Excitatory amino acids and glucocorticoids have key roles in these processes, along with a growing list of extra- and intracellular mediators that includes endocannabinoids and brain-derived neurotrophic factor (BDNF). The result is a continually changing pattern of gene expression mediated by epigenetic mechanisms involving histone modifications and CpG methylation and hydroxymethylation as well as by the activity of retrotransposons that may alter genomic stability. Elucidation of the underlying mechanisms of plasticity and vulnerability of the brain provides a basis for understanding the efficacy of interventions for anxiety and depressive disorders as well as age-related cognitive decline.
Twenty years ago, in four papers,1 I offered a unified descriptive analysis of health, disease, and function. In recent philosophy of medicine, these papers are often treated as a standard defense of one pole on the spectrum of views about health: the extreme view that, at least at the theoretical foundation ofmodern Western medicine, health and disease are value-free scientific concepts. Theoretical health, I argued, is the absence of disease; disease is only statistically species-subnormal biological part-function; therefore, the classification of human states as healthy or diseased is an objective matter, to be read off the biological facts of nature without need of value judgments. Let us refer to this general position as “naturalism”—the opposite of normativism, the view that health judgments are or include value judgments. Following Nordenfelt (1987), let me call my specific naturalist theory the “biostatistical theory (BST),” a name emphasizing that the analysis rests on the concepts of biological function and statistical normality.2