In The Ethics of Ambiguity (herein the Ethics), Simone de Beauvoir declares that science condemns itself to failure if it takes as its task the total disclosure of being (Beauvoir 1948/1976, 130). I suggest that the Ethics actually parallels the spirit of some scientific programs, specifically those that utilize positive skepticism as method. I draw out connections among the Ethics, Maurice Merleau-Ponty's Phenomenology of Perception (Merleau-Ponty 1945/1962) to which Beauvoir's works show much likeness, and Francis Bacon's The New Organon (Bacon (...) 1620/2000), the latter being at once a scientific and a positive skeptical program. Underscoring the ways in which Beauvoir's method of interrogating the being of beings and reality is compatible with some scientific pictures is important. It complicates the usual thought that existentialism is antiscience, problematizes Beauvoir's overly simplistic depiction of science, and nuances her analysis of the existent's experience of itself. (shrink)

The word “sustainable” débuted in 1987 but has since become a hot topic issue, both for scientific research and wider society. Although sustainability may appear to be a thoroughly twenty-first century goal, sustainability science concepts and goals such as balance, endurance, order and change, reach back at least as far as the proto-scientific investigations of alchemy. Both alchemy and sustainability science can be understood as systems or strategies which individuals and societies can use to organise and manage themselves in a (...) complex world filled with dynamic problems. Alchemy never created a panacea or transmuted base metals into gold because those goals proved to be based on fundamentally flawed theories and premises. Nevertheless, alchemy did succeed in helping adherents manage themselves and their societies in advantageous ways. Alchemy also positively and significantly influenced subsequent scientific development. Likewise, science helps humanity manage itself on multiple scales, from the individual to the international, and will certainly contribute to further scientific research and development. However, it is not yet known whether carbon neutrality, entirely renewable energy and other sustainability goals will be achieved or whether these goals will also come to be seen as based on flawed understandings and theories. For this reason, this article explores key features of alchemy, traces how they persisted through Enlightenment-era science and how they continue to be present and influential within scientific efforts today. The article goes on to reflect on how the history, development and continued use of concepts such as balance, endurance, order and change may be useful portents of how humans and human society will manage themselves in the future. Such reflections may also temper the zeal with which individuals that accept or reject sustainability goals treat each other, thereby offering a way for divergent groups to manage their interactions. Flawed theories prevented alchemy from achieving many of its primary stated goals. However, alchemy was very beneficial, both during its period of use and subsequently through its influence on subsequent development. This article identifies ideas from alchemy that were originally beneficial and that have persisted through Enlightenment-era science and into contemporary science. The article also explores how those ideas continue to influence scientific and sustainability goals today. Understanding and reflecting on alchemy’s successes and failures facilitates reflection on the potential successes and failures of sustainability and the human consequences of trying to manage a sustainable future. (shrink)

Background: The experimental method to acquire knowledge about efficacy and efficiency of medical procedures is well established in evidence-based medicine. A method to attain evidence about the significance of diseases and interventions from the patients' perspectives taking into account their right to self-determination about their lives and bodies has however not been sufficiently characterized.Design: Identification of a method to acquire evidence about the clinical significance of disease and therapeutic options from the patients' perspectives.Arguments: Communication between patient and physician is analyzed (...) as the method to attain evidence about what is at stake for individual patients in disease and therapy. It is the method that enables physicians to directly take into account patients' disease experiences and their aims regarding treatments. These patients' perspectives in turn determine the clinical significance of diagnoses and therapeutic options, if patient-autonomy is taken seriously.Conclusions: A full account of evidence-based medicine needs to include experimentation and communication between physician and patient as equally important methods to attain evidence necessary to practice patient-oriented medicine. The communicative method is especially important for primary physicians as they direct patients within the medical system to have their medical problems most effectively and efficiently addressed. (shrink)

Popper, Polanyi and Duncker represent the widely held position that theoretical and experimental scientific research are motivated by problems to which discoveries are solutions. According to the argument here, their views are unsupported and - in light of counter-instances, anomalous chance discoveries, and the force of curiosity - over-generalized.

Born in 1918 in New York, awarded a doctorate in analytical chemistry (1944), Leonard K. Nash enjoyed a distinguished career at Harvard, holding a chair of chemistry from 1959 to 1986. Conducting research in thermodynamics and statistical mechanics, Nash authored successful textbooks, some of which remain in print (e.g. Elements of Chemical Thermodynamics, and Elements of Statistical Thermodynamics).This essay describes the theory of science that Nash developed in a book he published in 1963, The Nature of the Natural Sciences. The (...) present author is of the view that Nash's neglected theory is worth retrieving, as one that is likely to kindle the interest of historians of metascience on several counts. Part of .. (shrink)

Proponents of evidence-based medicine and some philosophers of science seem to agree that knowledge of mechanisms can help solve the problem of applying results of controlled studies to target populations (‘the problem of extrapolation’). We describe the problem of extrapolation, characterize mechanisms, and outline how mechanistic knowledge might be used to solve the problem. Our main thesis is that there are four often overlooked problems with using mechanistic knowledge to solve the problem of extrapolation. First, our understanding of mechanisms is (...) often (and arguably, likely to remain) incomplete. Secondly, knowledge of mechanisms is not always applicable outside the tightly controlled laboratory conditions in which it is gained. Thirdly, mechanisms can behave paradoxically. Fourthly, as Daniel Steel points out, using mechanistic knowledge faces the problem of the ‘extrapolator’s circle’. At the same time, when the problems with mechanistic knowledge have been addressed, such knowledge can and should be used to mitigate (nothing can entirely solve) the problem of extrapolation. (shrink)

Philosophers of science have insisted that evidence of underlying mechanisms is required to support claims about the effects of medical interventions. Yet evidence about mechanisms does not feature on dominant evidence-based medicine “hierarchies.” After arguing that only inferences from mechanisms (“mechanistic reasoning”)—not mechanisms themselves—count as evidence, I argue for a middle ground. Mechanistic reasoning is not required to establish causation when we have high-quality controlled studies; moreover, mechanistic reasoning is more problematic than has been assumed. Yet where the problems can (...) be overcome, mechanistic reasoning can and should be used as evidence. (shrink)

This paper is concerned with the problem of experimental error. The prevalent view that experimental errors can be dismissed as a tiresome but trivial blemish on the method of experimentation is criticized. It is stressed that the occurrence of errors in experiments constitutes a permanent feature of the attempt to test theories in the physical world, and this feature deserves proper attention. It is suggested that a classification of types of experimental error may be useful as a heuristic device in (...) studying the nature of these errors. However, the standard classification of systematic and random errors is mathematically based does not focus on the causes of the errors, their origins, or the contexts in which they arise. A new typology of experimental errors is therefore proposed whose criterion is epistemological. This typology reflects the various stages that can be discerned in the execution of an experiment, each stage constituting a category of a certain type of experimental error. The proposed classification consists of four categories which are illustrated by historical cases. (shrink)

Science traditionally is taught as a linear process based on logic and carried out by objective researchers following the scientific method. Practice of science is a far more nuanced enterprise, one in which intuition and passion become just as important as objectivity and logic. Whether the activity is committing to study a particular research problem, drawing conclusions about a hypothesis under investigation, choosing whether to count results as data or experimental noise, or deciding what information to present in a research (...) paper, ethical challenges inevitably will arise because of the ambiguities inherent in practice. Unless these ambiguities are acknowledged and their sources understood explicitly, responsible conduct of science education will not adequately prepare the individuals receiving the training for the kinds of decisions essential to research integrity that they will have to make as scientists. (shrink)

Background: The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations.DiscussionWe review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for (...) models in toxicity testing as an example of the problem with using animal models.SummaryWe conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. (shrink)

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has (...) been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights. (shrink)

Claude Bernard (1813–1878) and Emil du Bois-Reymond (1818–1896) rank as two of the most influential scientists of the nineteenth century. Renowned for their experiments, lectures, and writing, Bernard and du Bois-Reymond earned great prestige as professors of physiology in a time when Paris and Berlin reigned as capitals of science. Yet even though they were equals in every way, du Bois-Reymond’s reputation has fallen far more than Bernard’s. This essay compares aspects of the two men’s attitudes to philosophy, history, and (...) biology in an attempt to explain why Bernard remains the better known. The answer lies less in the value of du Bois-Reymond’s contributions than in the way that science is remembered in France and Germany. (shrink)

InThe Education of the Human Race, G. E. Lessing helps his readers understand why the propositions of the Old Testament are pseudo-propositions, or why they do not resemble the significant propositions of natural science but thetautologicalpropositions of mathematics and of logic. That is, the so-called propositions of the Old Testament do not teach readers whether what actually happens is this or that; rather what they teach us is to imagine expressions by substitution in such a way as to throw their (...) structure into relief. One of Lessing's most attentive readers was Wittgenstein. Or perhaps only Wittgenstein would have been able to grasp so immediately Lessing's insight that the tautological or pseudo-propositions of the Old Testament invite thinkingonlywhen readers use them to understand ‘what is the case’ in the pictures the propositions have – logically – constructed. Thus in this essay I use Wittgenstein's reading of Lessing to throw light on his work in theTractatus. Rather than take up the new logician's interest in completely analyzing expressions, Wittgenstein insists in theTractatusthat the expressions we use, even those that seem to be propositions or that contain assertions, are in fact designed to be elucidatorywithoutsaying anything about the nature of the subjects that figure in them. Wittgenstein's great insight was to see that the propositional signs of our language are able to bring something to mindwithoutsaying what is a representation of what. (shrink)

In 1948 Ludwik Fleck published a paper in Polish discussing the use of humans in medical experiments, thereby addressing his peers. Though the paper has so far not been translated or studied, it has been taken to indicate Fleck’s deep commitment to ethical questions, notably the question of informed consent. In being written by a former victim of the Nazi policy and a survivor of the Holocaust also acting as an expert witness in the trial of the IG Farben in (...) Nuremberg, the paper is of interest. A scrutiny of Fleck’s text and related sources discloses, however, not only the complexity of the issue at the centre of the Nuremberg trial, but also Fleck’s unexpected stance in seemingly adducing his arguments from both the German defendants and the prosecution, heavily informed by US scientists. Further, the contentious discussion of the past in Fleck’s paper reveals its links to modern bioethical discussion. Though sometimes oblivious of that past, it still faces the same questions. (shrink)

Nietzsche assesses values, moralities, religions, cultures, and persons in terms of health. He argues that we should reject those that are unhealthy and develop healthier alternatives. But what is Nietzsche’s conception of health, and why should it carry such normative force? In this paper I argue for reading Nietzsche’s concept of health as the overall ability to meet the demands of one’s motivational landscape. I show that, unlike other interpretations, this reading accounts for his rejection of particular features of a (...) prevailing, then as now, model of health; for his association of health with strength and with psychic unity; and for his claim that health is compatible with, and can even be enhanced by, functional impairments such as those from which he personally suffered. Throughout I draw connections to recent literature on health and disability. (shrink)

It is a matter of some irony that psychiatry's most trenchant critic for over four decades is himself a psychiatrist. I refer to Thomas S. Szasz. Szasz's core thesis may be succinctly rendered: mental illness is a “myth”, a “metaphor” which serves only to obscure the social and ethical “problems in living” we face as human beings. This paper reconsiders the conceptual bases of Szasz's assault on psychiatry and assesses recent counter-arguments of his critical interlocutors. It presents a defence of (...) the Szaszian conception and emphasises the continuing relevance of his earliest work. Additionally, the paper discusses Szasz's thesis in light of the work of the influential French philosopher of medicine, Georges Canguilhem. (shrink)

Background Biomedicine, i.e. the application of basic sciences to medicine, has become the cornerstone for the study of etiopathogenesis and treatment of diseases. Biomedicine has enormously contributed to the progress of medicine and healthcare and has become the preferred approach to medical problems in the West. The developments in statistical inference and machine learning techniques have provided the foundation for personalised medicine where clinical management can be fully informed by biomedicine. The deployment of precision medicine may impact the autonomy and (...) self-normativity of the patients. Understanding the relationship between biomedicine and medical practice can help navigate the benefits and challenges offered by precision medicine. Methods Conventional content analysis was applied to “Le Normal and le Pathologique” (Canguilhem G. The Normal and the Pathological. Princeton: Princeton University Press; 1991) and further investigated with respect to its relationship with techne and precision medicine using PubMed and Google Scholar and the Standford Encyclopedia of Philosophy to search for the following keywords singularly or in combination: “Canguilhem”, “techne”, “episteme”, “precision medicine”, “machine learning AND medicine”. Results The Hippocratic concept of techne accounts for many characteristics of medical knowledge and practice. The advances of biomedicine, experimental medicine and, more recently, machine learning offer, in contrast, the model of a medicine based purely on episteme. I argue that Canguilhem medical epistemology establishes a framework where episteme and data-driven medicine is compatible with the promotion of patient’s autonomy and self-normativity. Conclusions Canguilhem’s medical epistemology orders the relationship of applied medicine with experimental sciences, ethics and social sciences. It provides guidance to define the scope of medicine and the boundaries of medicalization of healthy life. Finally, it sets an agenda for a safe implementation of machine learning in medicine. (shrink)

Evidence-based medicine (EBM) makes use of explicit procedures for grading evidence for causal claims. Normally, these procedures categorise evidence of correlation produced by statistical trials as better evidence for a causal claim than evidence of mechanisms produced by other methods. We argue, in contrast, that evidence of mechanisms needs to be viewed as complementary to, rather than inferior to, evidence of correlation. In this paper we first set out the case for treating evidence of mechanisms alongside evidence of correlation in (...) explicit protocols for evaluating evidence. Next we provide case studies which exemplify the ways in which evidence of mechanisms complements evidence of correlation in practice. Finally, we put forward some general considerations as to how the two sorts of evidence can be more closely integrated by EBM. (shrink)

Although best known as a nineteenth-century neurologist and creator of the rest cure, S. Weir Mitchell was one of the first Americans to engage in large-scale animal experimentation. In 1860 he published Researches Upon the Venom of the Rattlesnake, and in 1886, in collaboration with Dr. Edward T. Reichert, he published Researches Upon the Venoms of Poisonous Serpents. Yet, Mitchell’s pioneering work in scientific medicine remains a little known aspect of his career. This essay, based mainly on primary source material, (...) tells the story of Mitchell’s medical education and research on venomous snakes in order to reveal the ways myth and metaphor influenced medicine as it was becoming a science. (shrink)

Despite the practical knowledge throughout the nineteenth century that citrus fruit cured scurvy, and that rickets and beriberi were diseases caused by poor diet, it was not until 1901 that animal feeding experiments led one investigator to propose the existence of 'accessory food factors,' a lack of which was determined to be the cause of some illnesses (Hopkins, 1949. In Joseph Needham and E. Baldwin (eds.), Hopkins and Biochemistry, 1861-1947: Papers Concerning Sir Frederick Gowland Hopkins, O.M., P.R.S., with a Selection (...) of His Addresses and a Bibliography of His Publications. Cambridge: W. Heifer and Sons Ltd). The discovery of vitamins has long been considered as a delayed discovery. This delay has been attributed to the power of the germ theory in physiology at the time. While the germ theory and theories of autointoxication certainly played a role in delaying the discovery of vitamins, I argue further that it is important to consider the difference made to physiology by understanding the vitamins’ catalytic function. The profound difference made to physiology by the vitamins’ catalytic function suggests that a vitamin concept had previously been systematically inaccessible to researchers working within the conceptual framework of Bernardian physiology. (shrink)

The article reevaluates the reception of Mendelism in France, and more generally considers the complex relationship between Mendelism and plant breeding in the first half on the 20th century. It shows on the one side that agricultural research and higher education institutions have played a key role in the development and institutionalization of genetics in France, whereas university biologists remained reluctant to accept this approach on heredity. But on the other side, plant breeders, and agricultural researchers, despite an interest in (...) Mendelism, never came to see it as the breeders' panacea, and regarded it instead as of only limited value for plant breeding. I account for this judgment in showing that the plant breeders and Mendelism designed two contrasting kinds of experimental systems and inhabited distinct experimental cultures. While Mendelian geneticists designed experimental systems that allowed the production of definite ratios of different forms that varied in relation to a few characters, plant breeders' experimental systems produced a wide range of variation, featuring combinations between hundreds of traits. Rather than breaking this multiple variation down into simple elements, breeders designed and monitored a genetic lottery. The gene was a unit in a Mendelian experimental culture, an "epistemic thing" as Rheinberger put it, that could be grasped by means of statistical regularities, but it remained of secondary importance for French plant breeders, for whom the strain or the variety -- not the gene -- was the fundamental unit of analysis and manipulation. (shrink)

Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents and have (...) been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units. Ó 2010 Elsevier Ltd. All rights reserved. (shrink)

Explaining the complex dynamics exhibited in many biological mechanisms requires extending the recent philosophical treatment of mechanisms that emphasizes sequences of operations. To understand how nonsequentially organized mechanisms will behave, scientists often advance what we call dynamic mechanistic explanations. These begin with a decomposition of the mechanism into component parts and operations, using a variety of laboratory-based strategies. Crucially, the mechanism is then recomposed by means of computational models in which variables or terms in differential equations correspond to properties of (...) its parts and operations. We provide two illustrations drawn from research on circadian rhythms. Once biologists identified some of the components of the molecular mechanism thought to be responsible for circadian rhythms, computational models were used to determine whether the proposed mechanisms could generate sustained oscillations. Modeling has become even more important as researchers have recognized that the oscillations generated in individual neurons are synchronized within networks; we describe models being employed to assess how different possible network architectures could produce the observed synchronized activity. (shrink)

This article argues that the basic account of mechanism and mechanistic explanation, involving sequential execution of qualitatively characterized operations, is itself insufficient to explain biological phenomena such as the capacity of living organisms to maintain themselves as systems distinct from their environment. This capacity depends on cyclic organization, including positive and negative feedback loops, which can generate complex dynamics. Understanding cyclically organized mechanisms with complex dynamics requires coordinating research directed at decomposing mechanisms into parts and operations with research using computational (...) models to recompose mechanisms and determine their dynamic behavior. This coordinated endeavor yields dynamic mechanistic explanations. (shrink)

Common folks “have” emotions and talk to others; and sometimes they make “their” emotions the topic of such talk. The emotions seem to be “theirs,” since they can be conceived of as private states ; and they can be topicalized, because we seem to be able to attribute or lend a conventionalized public form to some inner state or event. This is the way much of our folk-talk and folk-thinking about emotions, the expression thereof, the role of language in these (...) expressions, and communication in general are organized. However, as we have shown, such talk serves the purpose of communicating effectively and reaching mutual understanding. (shrink)

Since its introduction in 1987, Benjamin Freedman’s principle of clinical equipoise has enjoyed widespread uptake in bioethics discourse. Recent years, however, have witnessed a growing consensus that the principle is fundamentally flawed. One of the most vocal critics has undoubtedly been Franklin Miller. In a 2008 paper, Steven Joffe and Miller build on this critical work, offering a new conception of clinical research ethics based on science, taking what they call a “scientific orientation” toward the ethics of clinical research. Though (...) there is much to recommend Joffe and Miller’s scientifically oriented conception of clinical research ethics, I believe that both the critical and constructive projects suffer from the same basic mistake: inattention to context. The internal norms of science cannot be fully specified, let alone satisfied, independently of contextual (external) factors that only come into view when we are attentive to the particular context of that form of inquiry. (shrink)

Defenders of evolutionary medicine claim that medical professionals and public health officials would do well to consider the role of evolutionary biology with respect to the teaching, research, and judgments pertaining to medical theory and practice. An integral part of their argument is that the human body should be understood as a bundle of evolutionary compromises. Such an appreciation, which includes a proper understanding of biological function and physiological homeostasis, would provide a crucial perspective regarding the understanding and securing of (...) human health needs currently lacking in the medical arena. (shrink)

The German pioneer of electrophysiology, Emil du Bois-Reymond (1818–1896), is generally assumed to have remained silent on the subject of the brain. However, the archive of his papers in Berlin contains manuscript notes to a lecture on “The Seat of the Soul” that he delivered to popular audiences in 1884 and 1885. These notes demonstrate that cerebral localization and brain function in general had been concerns of his for quite some time, and that he did not shy away from these (...) subjects. (shrink)