_Philosophy of Molecular Medicine: Foundational Issues in Theory and Practice_ aims at a systematic investigation of a number of foundational issues in the field of molecular medicine. The volume is organized around four broad modules focusing, respectively, on the following key aspects: What are the nature, scope, and limits of molecular medicine? How does it provide explanations? How does it represent and model phenomena of interest? How does it infer new knowledge from data and experiments? The essays collected here, authored (...) by prominent scientists and philosophers of science, focus on a handful of mainstream topics in the philosophical literature, such as _causation_, _explanation_, _modeling_, and _scientific inference_. These previously unpublished contributions shed new light on these traditional topics by integrating them with problems, methods, and results from three prominent areas of contemporary biomedical science: _basic research_, _translational_ and _clinical research_, and _clinical practice_. (shrink)

During his celebrated 1922 debate with Bergson, Einstein famously proclaimed: “the time of the philosopher does not exist, there remains only a psychological time that differs from the physicist’s.” Einstein’s dictum, I maintain, has been metabolized by the natural sciences, which typically presuppose, more or less explicitly, the existence of a single, univocal, temporal substratum, ultimately determined by physics. This reductionistic assumption pervades much biological and biomedical practice. The chronological age allotted to individuals is conceived as an objective quantity, allowing (...) one to straightforwardly assign and compare the biological age of organisms. This essay argues that the standard practice of assessing the age and aging of organisms against the backdrop of a physical conception of time is problematic. This becomes especially evident in light of recent discoveries of various levels of senescence underlying the development of individual organisms—a phenomenon known as ‘age mosaicism.’ The bottom line is that the study of age and aging requires a biological conception of time, as opposed to a physical one. Einstein clearly wasn’t wrong about his operationalization of time in relativity theory. Still time may be less monolithic than he surmised. (shrink)

Causal relations among components and activities are intentionally misrepresented in mechanistic explanations found routinely across the life sciences. Since several mechanists explicitly advocate accurately representing factors that make a difference to the outcome, these idealizations conflict with the stated rationale for mechanistic explanation. We argue that these idealizations signal an overlooked feature of reasoning in molecular and cell biology—mechanistic explanations do not occur in isolation—and suggest that explanatory practices within the mechanistic tradition share commonalities with model-based approaches prevalent in population (...) biology. (shrink)

Current discussions of hermeneutical injustice, I argue, poorly characterise the cognitive state of victims by failing to account for the communicative success that victims have when they describe their experience to other similarly situated persons. I argue that victims, especially when they suffer moral wrongs that are yet unnamed, are able (1) to grasp certain salient aspects of the wrong they experience and (2) to cultivate the ability to identify instances of the wrong in virtue of moral emotions. By moral (...) emotions I mean emotions like indignation that reflect an agent’s ethical commitments and bear on her ethical assessments. Further, I argue that victims can impart their partial understanding of the wrong they suffer to others who are not similarly situated by eliciting moral emotions such as pity that are tied to broad notions of justice and fairness. (shrink)

This article presents and discusses one of the most prominent inferential strategies currently employed in cognitive neuropsychology, namely, reverse inference. Simply put, this is the practice of inferring, in the context of experimental tasks, the engagement of cognitive processes from locations or patterns of neural activation. This technique is notoriously controversial because, critics argue, it presupposes the problematic assumption that neural areas are functionally selective. We proceed as follows. We begin by introducing the basic structure of traditional “location-based” reverse inference (...) and discuss the influential lack of selectivity objection. Next, we rehearse various ways of responding to this challenge and provide some reasons for cautious optimism. The second part of the essay presents a more recent development: “pattern-decoding reverse inference”. This inferential strategy, we maintain, provides an even more convincing response to the lack of selectivity charge. Due to this and other methodological advantages, it is now a prominent component in the toolbox of cognitive neuropsychology. Finally, we conclude by drawing some implications for philosophy of science and philosophy of mind. (shrink)

Philosophers have traditionally addressed the issue of scientific unification in terms of theoretical reduction. Reductive models, however, cannot explain the occurrence of unification in areas of science where successful reductions are hard to find. The goal of this essay is to analyse a concrete example of integration in biology—the developmental synthesis—and to generalize it into a model of scientific unification, according to which two fields are in the process of being unified when they become explanatorily relevant to each other. I (...) conclude by suggesting that this methodological conception of unity, which is independent of the debate on the metaphysical foundations of science, is closely connected to the notion of interdisciplinarity. 1 Introduction2 Some Troubles with Theory Reduction3 Interfield and Mechanistic Unification4 Foundations of the Developmental Synthesis5 Explanatory Relevance6 Concluding Remarks. (shrink)

Bricks and boxes -- Between Scylla and Charybdis -- Lessons from the history of science -- Placeholders -- Black-boxing 101 -- History of science 'black-boxing style' -- Diet mechanistic philosophy -- Emergence reframed -- The fuel of scientific progress -- Sailing through the strait.

The aim of this article is to discuss the conditions under which functional neuroimaging can contribute to the study of higher cognition. We begin by presenting two case studies—on moral and economic decision making—which will help us identify and examine one of the main ways in which neuroimaging can help advance the study of higher cognition. We agree with critics that functional magnetic resonance imaging (fMRI) studies seldom “refine” or “confirm” particular psychological hypotheses, or even provide details of the neural (...) implementation of cognitive functions. However, we suggest that neuroimaging can support psychology in a different way—namely, by selecting among competing hypotheses of the cognitive mechanisms underlying some mental function. One of the main ways in which neuroimaging can be used for hypothesis selection is via reverse inferences, which we here examine in detail. Despite frequent claims to the contrary, we argue that successful reverse inferences do not assume any strong or objectionable form of reductionism or functional locationism. Moreover, our discussion illustrates that reverse inferences can be successful at early stages of psychological theorizing, when models of the cognitive mechanisms are only partially developed. (shrink)

Reductionists in biology claim that all biological events can be explained in terms of genes and macromolecules alone, while antireductionists argue that some biological events must be explained at a higher level. The literature, however, does not distinguish between different kinds of molecular explanation. The goal of this article is to identify and analyze three such kinds. The analysis of molecular explanations herein carries an important philosophical implication; in shunning crude reductionism and extreme versions of holism, we can combine the (...) insights of thoughtful reductionists with sophisticated antireductionism. When this is done, the question of explanatory reductionism becomes less substantial than often supposed. (shrink)

This essay is concerned with concentrations of entities, which play an important—albeit often overlooked—role in scientific explanation. First, I discuss an example from molecular biology to show that concentrations can play an irreducible causal role. Second, I provide a preliminary philosophical analysis of this causal role, suggesting some implications for extant theories of causation. I conclude by introducing the concept of causation by concentration, a form of statistical causation whose widespread presence throughout the sciences has been unduly neglected and which (...) deserves to be studied in more depth. 1 Introduction2 Solving Lillie's Paradox: Lysogenic Induction in Phage λ3 Repressor Concentration and the Tuning of the Switch4 Concentration and Causality5 Preemption in Concentrations: Analysis and Implications6 Causation by Concentration: General Definition, Refinements, and Further Applications. (shrink)

The ‘species problem’ can be characterized, to a first approximation, as the task of providing a viable species concept —that is, a functional analysis that picks out the ‘right’ kind of biological entities. After decades of debate and centuries of taxonomic practice, no overarching consensus has been reached. The individuation and definition of the units of evolution and classification, species included, remains controversial. If anything, there now seems to be more disagreement than ever before.

This essay examines the relation between causation and causal explanation. It distinguishes two prominent roles that causes play within the sciences. On the one hand, causes may work as metaphysical posits. From this standpoint, mainstream in contemporary philosophy, causation provides the ‘raw material’ for explanation. On the other hand, causes may be conceived as explanatory postulates, theoretical hypotheses lacking any substantial ontological commitment. This unduly neglected distinction provides the conceptual resources to revisit longstanding philosophical issues, such as overdetermination and causal (...) pluralism. It also inspires a provocative reframing of Russell’s famous, if notoriously elusive, remarks on the nature of causation. (shrink)

This article explores the complementary strengths and weaknesses of grounded and abstract representations in the domain of early algebra. Abstract representations, such as algebraic symbols, are concise and easy to manipulate but are distanced from any physical referents. Grounded representations, such as verbal descriptions of situations, are more concrete and familiar, and they are more similar to physical objects and everyday experience. The complementary computational characteristics of grounded and abstract representations lead to trade‐offs in problem‐solving performance. In prior research with (...) high school students solving relatively simple problems, Koedinger and Nathan (2004) demonstrated performance benefits of grounded representations over abstract representations—students were better at solving simple story problems than the analogous equations. This article extends this prior work to examine both simple and more complex problems in two samples of college students. On complex problems with two references to the unknown, a “symbolic advantage” emerged, such that students were better at solving equations than analogous story problems. Furthermore, the previously observed “verbal advantage” on simple problems was replicated. We thus provide empirical support for a trade‐off between grounded, verbal representations, which show advantages on simpler problems, and abstract, symbolic representations, which show advantages on more complex problems. (shrink)

The U.S. National Institute of Allergies and Infectious Diseases and the National Institute of Mental Health have a new research priority: inclusion of terminally ill persons living with HIV in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. As end-of-life HIV cure research is relatively new, the scientific community has a timely opportunity to (...) examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable. (shrink)

Some argue against coercive preventive measures on the grounds that they amount to cloaked forms of punishment. Others offer a qualified defence of such measures on the grounds that such measures have substantively different goals and purposes from punishment. Focusing on the case of civil preventive injunctions, I clear the ground and provide reasons for a third logical possibility: that coercive preventive measures are relevantly similar to punishment, but this does not itself give us a reason to oppose them. ‘Punishment’ (...) has a great deal of rhetorical force, and it thereby distracts us from the justificatory work that we need to do to specify proper restrictions on the state’s coercive powers. Whereas many commentators have proposed that legal theory provides grounds for challenging civil preventive orders, I argue for the opposite view. If we understand properly the function of civil preventive orders, we will endorse them at least in principle, and will come to rethink some central ideas in the grounding of the criminal justice processes. (shrink)

We think we know what healers do: they build on patients' irrational beliefs and treat them in a 'symbolic' way. If they get results, it's thanks to their capacity to listen, rather than any influence on a clinical level. At the same time, we also think we know what modern medicine is: a highly technical and rational process, but one that scarcely listens to patients at all. In this book, ethnopsychiatrist Tobie Nathan and philosopher Isabelle Stengers argue that this commonly (...) posed opposition between traditional and modern medicine is misleading. They show instead that healers are interesting precisely because they don't listen to patients, using techniques of 'divination' rather than 'diagnosis'. Healers construct genuine therapeutic strategies by identifying the origins of symptoms in external forces, outside of the mind of the sufferer, and in this regard African healers are virtuosos. Though it may claim otherwise, modern medicine, for its part, is characterised by empiricism rather than rationality. What appears to be the pursuit of rationality is ultimately only a means to dismiss and exclude other forms of treatment. Blurring the distinctions between traditional and modern practices and drawing on perspectives from across the globe, this ethnopsychiatric manifesto encourages us to think in radically new ways about illness, challenging accepted notions on the relationship between sufferer and symptom. It will be of great interest to those working in medicine and healthcare, as well as anthropologists, social scientists and those in the humanities more broadly. (shrink)

This essay considers the reliability and proper role of authorial intention in the interpretation of figurative language and argues that, even in cases of metaphor and irony, the meaning of a text must remain logically independent of the intent of its historical author. Irony and metaphor have been broadly considered to be the most problematic cases for the anti-intentionalist approach to interpretation. The arguments in this essay address standard intentionalist arguments and, in the end, defend a sort of hypothetical intentionalism (...) that is, in all significant respects, anti-intentionalist. (shrink)

While philosophers tend to consider a single type of causal history, biologists distinguish between two kinds of causal history: evolutionary history and developmental history. This essay studies the peculiarity of development as a criterion for the individuation of biological traits and its relation to form, function, and evolution. By focusing on examples involving serial homologies and genetic reprogramming, we argue that morphology (form) and function, even when supplemented with evolutionary history, are sometimes insufficient to individuate traits. Developmental mechanisms bring in (...) a novel aspect to the business of classification—identity of process-type—according to which entities are type-identical across individuals and natural kinds in virtue of the fact that they form and develop through similar processes. These considerations bear important metaphysical implications and have potential applications in several areas of philosophy. (shrink)

Recent advancements in the brain sciences have enabled researchers to determine, with increasing accuracy, patterns and locations of neural activation associated with various psychological functions. These techniques have revived a longstanding debate regarding the relation between the mind and the brain: while many authors claim that neuroscientific data can be employed to advance theories of higher cognition, others defend the so-called ‘autonomy’ of psychology. Settling this significant issue requires understanding the nature of the bridge laws used at the psycho-neural interface. (...) While these laws have been the topic of extensive discussion, such debates have mostly focused on a particular type of link: reductive laws. Reductive laws are problematic: they face notorious philosophical objections and they are too scarce to substantiate current research at the intersection of psychology and neuroscience. The aim of this article is to provide a systematic analysis of a different kind of bridge laws—associative laws—which play a central, albeit overlooked role in scientific practice. (shrink)

There is an apparent problem in identifying a basis for equality. This problem vanishes if what I call the ‘intuited response’ is successful. According to this response, there is no further explanation of the significance of the feature in virtue of which an individual matters, beyond the bare fact that it is the feature in virtue of which an individual matters. I argue against this claim, and conclude that if the problem of identifying a basis for equality is to be (...) resolved, it is necessary to defend a substantive account of the independent significance of some feature. (shrink)

Does undercover police work inevitably wrong its targets? Or are undercover activities justified by a general security benefit? In this article I argue that people can make themselves liable to deception and manipulation. The debate on undercover policing will proceed more fruitfully if the tactic can be conceptualised along those lines, rather than as essentially ‘dirty hands’ activity, in which people are wronged in pursuit of a necessary good, or in instrumentalist terms, according to which the harms of undercover work (...) are straightforwardly overcome by its benefits. This article motivates the ‘liability view’ and describes its attractions, challenges, and implications. (shrink)

The philosophy of mechanisms has developed rapidly during the last 30 years. As mechanisms-based explanations are often seen as an alternative to nomological, law-based explanations, MBEs could be relevant in IS. We begin by offering a short history of mechanistic philosophy and set out to clarify the contemporary landscape. We then suggest that mechanistic models provide an alternative to variance and process models in IS. Finally, we highlight how MBEs typically contain deliberate misrepresentations. Although MBEs have recently been advocated as (...) critical realist accounts in IS, idealizations seem to violate some fundamental tenets of CR and research method principles for CR. Idealizations in MBEs, therefore, may risk being regarded as flawed in IS. If it turns out that CR cannot account for idealizations, naturalism can, and it does so without extra-philosophical baggage. (shrink)

This essay presents a model-theoretic account of dispositional properties, according to which dispositions are not ordinary properties of real entities; dispositions capture the behavior of abstract, idealized models. This account has several payoffs. First, it saves the simple conditional analysis of dispositions. Second, it preserves the general connection between dispositions and regularities, despite the fact that some dispositions are not grounded in actual regularities. Finally, it brings together the analysis and the explanation of dispositions under a unified framework.

Six recently discussed problems in discrete probabilistic sample space, which have been found puzzling and even paradoxical, are reexamined. The importance is stressed of a sharp distinction between the formalization of mathematical problems and their formal solution that, applied to probability theory, must lead through the explicit partitioning of a sample space. If this approach is consistently followed, such problems reveal themselves to be either inherently ambiguous, and therefore without solution, or quite straightforward. In both cases nothing remains of any (...) sense of paradox. (shrink)

When do two mental items belong to the same life? We could be content with the answer -just when they have certain volitional qualities in common. An affinity is noted between that theory and Berkeley's early doctrine of the self. Some rivals of the volitional theory invoke a spiritual or physical owner of mental items. They run a risk either of empty formality or of causal superstition. Other rivals postulate a non-transitive and symmetrical relation in the set of mental items. (...) They must allow in consequence either for joint ownership of one and the same mental item, or for incompatible simultaneous decisions by one and the same person, or for new forms of death. This makes them disquieting. Another rival invokes a transitive and symmetrical relation defined in terms of co-consciousness. Even that allows for incongruous simultaneities. The volitional theory is free from such disadvantages. (shrink)

Biologists employ a suggestive metaphor to describe the complexities of molecular interactions within cells and embryos: cytological components are said to be part of “ecosystems” that integrate them in a complex network of relations with many other entities. The aim of this essay is to scrutinize the molecular ecosystem, a metaphor that, despite its longstanding history, has seldom be articulated in detail. I begin by analyzing some relevant analogies between the cellular environment and the biosphere. Next, I discuss the applicability (...) of the molecular ecosystem concept in actual scientific practice. (shrink)

I argue that intentionalism in aesthetics and in legal interpretation is vulnerable to a different sort of criticism than is found in the voluminous literature on the topic. Specifically, a kind of paradox arises for the intentionalist out of recognition of a second-order intention embedded in the social practices that characterize both art and law. The paper shows how this second-order intention manifests itself in each of the two enterprises, and argues that its presence entails the overriding centrality of the (...) public text, and hence a rejection of the interpretive stance distinctive of intentionalism itself. (shrink)

Jaynes contends that in many statistical problems a seemingly indeterminate probability distribution is made unique by the transformation group of necessarily implied invariance properties, thereby justifying the principle of indifference. To illustrate and substantiate his claims he considers Bertrand's Paradox. These assertions are here refuted and the traditional attitude is vindicated.

This note studies the 1650 edition of Hugo Grotius’s De iure belli ac pacis. Using online and card catalogues, we have located eighty-nine copies, thirty-seven of which we examined in person, with an additional six fully digitised copies online. We hope that this research note on the preliminary results will generate greater interest in this unduly neglected edition. The note shows how, despite the connection established in the history of seventeenth-century politics that emphasized the ties between Grotius and the Peace (...) of Westphalia, the reception of Grotius’s 1650 edition bore no relation to the debates at Osnabrück and Münster. However, this is an influential edition, cherished by collectors and authors. According to our findings, it would be reproduced in a number of later reprints. (shrink)

This article argues that two words in line 8.612 of the Aeneid, promissa and perfecta, have been transposed since the poem's composition, and that the restoration of their correct order yields a preferable sense. This corruption would have happened at an early stage in the poem's transmission, but there is some reason to believe that Servius’ comment on the verse reflects its original state.

Much problem solving and learning research in math and science has focused on formal representations. Recently researchers have documented the use of unschooled strategies for solving daily problems -- informal strategies which can be as effective, and sometimes as sophisticated, as school-taught formalisms. Our research focuses on how formal and informal strategies interact in the process of doing and learning mathematics. We found that combining informal and formal strategies is more effective than single strategies. We provide a theoretical account of (...) this multiple strategy effect and have begun to formulate this theory in an ACT-R computer model. We show why students may reach common impasses in the use of written algebra, and how subsequent or concurrent use of informal strategies leads to better problem-solving performance. Formal strategies facilitate computation because of their abstract and syntactic nature; however, abstraction can lead to nonsensical interpretations and conceptual errors. Reapplying the formal strategy will not repair such errors; switching to an informal one may. We explain the multiple strategy effect as a complementary relationship between the computational efficiency of formal strategies and the sense-making function of informal strategies. (shrink)

This research note is the eighth instalment in our series of preliminary findings on the census and study of the reception of De iure belli ac pacis. The note presents a bibliographical description of Laurentius’ 1647 re-issue of the 1631 edition by Blaeu, considers Laurentius’ motivation and methods of production, lists and maps the currently known twenty-three surviving copies, and briefly describes two notable exemplars.

A systematic study of rational or justified belief, which throws fresh light on current debates about foundations and coherence theories of knowledge, the validation of induction and moral scepticism. Dr Nathan focuses attention on the largely unsatisfiable desires for active and self-conscious assurance of truth liable to be engendered by philosophical reflection about total belief-systems and the sources of knowledge. He extracts a kernel of truth from the doctrine that a regress of justification is both necessary and impossible, contrasts the (...) resultant scepticism with more familiar complaints about the inapplicability of supposedly essential cognitive concepts and explores the feasibility of non-Humean modes of consolation. This is an original and carefully constructed book, which will interest professional philosophers and advanced students of epistemology. (shrink)

Beneath metaphysical problems there often lies a conflict between what we want to be true and what we believe to be true. Nathan provides a general account of the resolution of this conflict as a philosophical objective, showing that there are ways of thinking it through systematically with a view to resolving or alleviating it. The author also studies in detail a set of interrelated conflicts about the freedom and the reality of the will. He shows how difficult it is (...) to find a freedom either of decision or of action which is both an object of reflective desire and an object of rational belief. He also examines conflicts about volition as such, contending that the veridicality of volitional experience is no less easy to doubt than the veridicality of our experience of colors. In this context, arguments emerge for a voluntarist theory of the self. Nathan's important book will be essential reading for all philosophers interested in free will, volition, the self, and the methodology of metaphysics. (shrink)

The form of the Good in Plato’s Phaedo and Republic seems, by our standards, to do too much: it is presented as the metaphysical princi­ple, the epistemological principle and the principle of ethics. Yet this seemingly chimerical object makes good sense in the broader context of Plato’s philosophical project. He sought certain knowledge of neces­sary truths (in sharp contrast to the contingent truth of modern science). Thus, to be knowable the cosmos must be informed by timeless princi­ples; and this leads (...) to teleology and the Good. The form of the Good, it is argued, is what makes the world knowable insofar as it is knowable. This interpretation plugs a significant gap in the scholarship on the Good and draws attention to a deep connection between Plato’s episte­mology and his teleological understanding of the cosmos. (shrink)

[Colour is king in our innate quality space, but undistinguished in cosmic circles.] Most philosophers would agree with at least the second half of Quine's dictum. It is indeed on the general view wrong to believe that, as qualities, colours are extra-mentally actual in even the humblest role. Mind-independent material things have on the general view powers to cause sensations of red or blue, but if, in [sensations of red or blue], [red] and [blue] name qualities, we are not to (...) believe that these qualities are possessed by things causing the sensations. My first thesis, defended in section 2, is that partly because we do count colours as eminent among qualities, we would on reflection want it to be true that some things have such qualities when they are not perceived. It would therefore be sad subsequently to discover the wrongness of believing that this is how things are. My second thesis, defended in sections 3 and 4, is that there is in fact no danger as yet of this kind of disappointment. So far, the philosophers have not shown that, if we believe that colour qualities exist as contents of experience, we ought not also to believe that things have these qualities when they are not perceived. One might of course deny that colour qualities exist even as contents of experience, so that the desire for them to be mind-independently exemplified evaporates on the realization that it lacks an intelligible object. Our pre-scientific concept of red, according to Armstrong, is, apart from being the concept of something falling under a determinable, [all blank or gap]. (shrink)