Modern integrative systems biology defines itself by the complexity of the problems it takes on through computational modeling and simulation. However in integrative systems biology computers do not solve problems alone. Problem solving depends as ever on human cognitive resources. Current philosophical accounts hint at their importance, but it remains to be understood what roles human cognition plays in computational modeling. In this paper we focus on practices through which modelers in systems biology use computational simulation and other tools to (...) handle the cognitive complexity of their modeling problems so as to be able to make significant contributions to understanding, intervening in, and controlling complex biological systems. We thus show how cognition, especially processes of simulative mental modeling, is implicated centrally in processes of model-building. At the same time we suggest how the representational choices of what to model in systems biology are limited or constrained as a result. Such constraints help us both understand and rationalize the restricted form that problem solving takes in the field and why its results do not always measure up to expectations. (shrink)

In this article, we provide a case study examining how integrative systems biologists build simulation models in the absence of a theoretical base. Lacking theoretical starting points, integrative systems biology researchers rely cognitively on the model-building process to disentangle and understand complex biochemical systems. They build simulations from the ground up in a nest-like fashion, by pulling together information and techniques from a variety of possible sources and experimenting with different structures in order to discover a stable, robust result. Finally, (...) we analyze the alternative role and meaning theory has in systems biology expressed as canonical template theories like Biochemical Systems Theory. (shrink)

The importation of computational methods into biology is generating novel methodological strategies for managing complexity which philosophers are only just starting to explore and elaborate. This paper aims to enrich our understanding of methodology in integrative systems biology, which is developing novel epistemic and cognitive strategies for managing complex problem-solving tasks. We illustrate this through developing a case study of a bimodal researcher from our ethnographic investigation of two systems biology research labs. The researcher constructed models of metabolic and cell-signaling (...) pathways by conducting her own wet-lab experimentation while building simulation models. We show how this coupling of experiment and simulation enabled her to build and validate her models and also triangulate and localize errors and uncertainties in them. This method can be contrasted with the unimodal modeling strategy in systems biology which relies more on mathematical or algorithmic methods to reduce complexity. We discuss the relative affordances and limitations of these strategies, which represent distinct opinions in the field about how to handle the investigation of complex biological systems. (shrink)

Integrative systems biology is an emerging field that attempts to integrate computation, applied mathematics, engineering concepts and methods, and biological experimentation in order to model large-scale complex biochemical networks. The field is thus an important contemporary instance of an interdisciplinary approach to solving complex problems. Interdisciplinary science is a recent topic in the philosophy of science. Determining what is philosophically important and distinct about interdisciplinary practices requires detailed accounts of problem-solving practices that attempt to understand how specific practices address the (...) challenges and constraints of interdisciplinary research in different contexts. In this paper we draw from our 5-year empirical ethnographic study of two systems biology labs and their collaborations with experimental biologists to analyze a significant problem-solving approach in ISB, which we call adaptive problem solving. ISB lacks much of the methodological and theoretical resources usually found in disciplines in the natural sciences, such as methodological frameworks that prescribe reliable model-building processes. Researchers in our labs compensate for the lack of these and for the complexity of their problems by using a range of heuristics and experimenting with multiple methods and concepts from the background fields available to them. Using these resources researchers search out good techniques and practices for transforming intractable problems into potentially solvable ones. The relative freedom lab directors grant their researchers to explore methodological options and find good practices that suit their problems is not only a response to the complex interdisciplinary nature of the specific problem, but also provides the field itself with an opportunity to discover more general methodological approaches and develop theories of biological systems. Such developments in turn can help to establish the field as an identifiably distinct and successful approach to understanding biological systems. (shrink)

We lay groundwork for applying ethnographic methods in philosophy of science. We frame our analysis in terms of two tasks: to identify the benefits of an ethnographic approach in philosophy of science and to structure an ethnographic approach for philosophical investigation best adapted to provide information relevant to philosophical interests and epistemic values. To this end, we advocate for a purpose-guided form of cognitive ethnography that mediates between the explanatory and normative interests of philosophy of science, while maintaining openness and (...) independence when framing such an investigation to achieve robust unbiased results. (shrink)

Integrative systems biology is among the most innovative fields of contemporary science, bringing together scientists from a range of diverse backgrounds and disciplines to tackle biological complexity through computational and mathematical modeling. The result is a plethora of problem-solving techniques, theoretical perspectives, lab-structures and organizations, and identity labels that have made it difficult for commentators to pin down precisely what systems biology is, philosophically or sociologically. In this paper, through the ethnographic investigation of two ISB laboratories, we explore the particular (...) structural features of ISB thinking and organization and its relations to other disciplines that necessitate cognitive innovation at all levels from lab PI’s to individual researchers. We find that systems biologists face numerous constraints that make the production of models far from straight-forward, while at the same time they inhabit largely unstructured task environments in comparison to other fields. We refer to these environments as adaptive problem spaces. These environments they handle by relying substantially on the flexibility and affordances of model-based reasoning to integrate these various constraints and find novel adaptive solutions. Ultimately what is driving this innovation is a determination to construct new cognitive niches in the form of functional model building frameworks that integrate systems biology within the biological sciences. The result is an industry of diverse and different innovative practices and solutions to the problem of modeling complex, large-scale biological systems. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

The book prescribes a way to educate ourselves and our young people how to disagree well and lays out a framework for flourishing together in society despite our radical differences.

Property and Practical Reason makes a moral argument for common law property institutions and norms, and challenges the prevailing dichotomy between individual rights and state interests and its assumption that individual preferences and the good of communities must be in conflict. One can understand competing intuitions about private property rights by considering how private property enables owners and their collaborators to exercise practical reason consistent with the requirements of reason, and thereby to become practically reasonable agents of deliberation and choice (...) who promote various aspects of the common good. The plural and mediated domains of property ownership, though imperfect, have moral benefits for all members of the community. They enable communities and institutions of private ordering to pursue plural and incommensurable good ends while specifying the boundaries of property rights consistent with basic moral requirements. (shrink)

This is a response to Macleod 2012's argument that the history of unjust property acquisitions requires rich libertarians to give away everything in excess of equality. At first, problematic questions are raised. How much property is usually inherited or illegitimate? Why should legitimate inheritance be affected? What of the burden of proof and court cases? A counterfactual problem is addressed. Three important cases are considered: great earned wealth; American slavery; land usurpation. All are argued to be problematic for (...) class='Hi'>Macleod 2012's thesis. Various problems are explained concerning using the Nozickian argument to decide the alleged excess that rich libertarians own. The essay's main error is the presupposition that free markets do not help the worst-off. The majority of unjust holdings today are not the result of historical injustices but arise through continuing transfers enabled by taxation and state-regulation. More study of libertarian contributions to the social sciences and philosophy would appear to be desirable "personal behavior" among socialists. (shrink)

This chapter offers an account of the aspect of nineteenth‐century naturalism, by focusing on the work of J. S. Mill and Auguste Comte. Both philosophers have high ambitions for naturalism, aiming to offer a sweeping account of all of human knowledge in naturalistic terms. Mill argued that the metaphysical thinking must already have started to exert an influence in order for monotheistic approaches to take hold, and that Comte's account of the theological stage overstated the extent to which fetishistic or (...) polytheistic understanding of phenomena could exist independently of one another. But these are minor disagreements, framed in terms of a narrative that Mill basically accepts. Mill thought Comte's three stage theory important for understanding the rise our way of conceptualizing the world, and consistent with his own account of the rise of scientific induction. (shrink)

Many of the current comparisons of taxic phylogenetic and biological homology in the context of morphology focus on what are seen as categorical distinctions between the two concepts. The first, it is claimed, identifies historical patterns of conservation and variation relating taxa; the second provides a causal framework for the explanation of this conservation and variation. This leads to the conclusion that the two need not be placed in conflict and are in fact compatible, having non-competing epistemic purposes or mapping (...) the same extensions in the form of monophyletic groupings (see Roth, The biological basis of homology 1–26, 1988; Sluys, J Zool Syst Evol Res 34:145–152, 1996; Abouheif, Trends Ecol Evol 12:405–408, 1997; Brigandt, J Exp Zool 299:9–17, 2003, Biol Philos 22:709–725, 2007; Assis and Brigandt, Evol Biol 36:248–255, 2009). This article argues that moves in this direction miss the essential disagreement between these concepts as they have been developed in the context of the debate concerning the best concept for evolutionary investigation. We should rather see these concepts employing a common fundamental methodological approach to homology, but disagreeing about how to apply the methodology effectively. Both concepts employ class reasoning, which pursues homologies as units of generalization—more precisely, as sources of reliable and relevant group-bound information in the form of shared underlying causes. The dispute can be better understood by two poles that structure such reasoning: the need for a reliable basis for projections about the causal history of shared structures, and the desire to identify homologous characters with more informative and specific causal information relevant to generalizing about evolutionary processes. Judgments in favor of one or the other in turn have affected the scope or extension of these competing homology concepts. (shrink)

In 1925, A.J. Balfour, first Earl Balfour and author of the famous ‘Balfour Declaration’, attended the inauguration of the Hebrew University in Jerusalem. His education and experience of foreign policy equipped him to take a prominent role. However, the conditions of strife-torn Palestine weighed heavily upon him, and raised wider interests of imperial concern. This essay recounts the circumstances leading to his visit, and suggests that, whatever the region’s political destiny, Balfour’s vision of science-based economic development would play an essential (...) role in crafting its future. (shrink)

The late Colin Macleod's commentary on Iliad 24 has rightly received praise for its sensitivity to the nuances of Homeric language and its appreciation of the entire poem as a carefully constructed work of art. Although reluctant to accept the more radical solutions proposed by the ‘oral’ school, Macleod showed himself fully aware of the contribution made by the oral theory towards elucidating the history of the epic. Nevertheless, his commentary is concerned principally with the Iliad as we (...) have it: a poem which is at one level a masterly re-telling of saga but at another a sublime tragedy, commiserating the sorrows inseparable from human existence and holding up for our admiration the heroes who nobly confront pain and death. I believe that much, and probably most, of the Iliad can and should be viewed in this light. The last book of all, as Macleod himself has shown, offers especially rich rewards to an interpreter who keeps in the front of his mind the overriding aims of the great poet. Yet Macleod's method, like any other single method, will never yield a fully satisfactory answer on all occasions. However the ‘definitive’ or ‘monumental’ composition of the Iliad was brought about, it formed only one stage in the development of the Greek epic. Our Iliad cannot have been the first or the only treatment, on a large scale, of the matter of Troy. (shrink)

In the Spring of 1944, an informal discussion took place in Cambridge between Mr. R. S. Whipple, Professor Allan Ferguson and Mr. F. H. C. Butler, concerning the formation of a national Society for the History of Science. This is the opening sentence of the inaugural issue of the Bulletin of the British Society for the History of Science, the Society's first official publication. Butler himself was the author of this outline account of the subsequent approach to the Royal Society, (...) the parallel moves to establish a National Committee of the International Academy of the History of Science, the formation of a provisional committee to prepare a draft constitution for a national society, and the proceedings of the first Annual General Meeting in May 1947. Whipple had been in Cambridge to discuss his offer to present his collection of old scientific instruments to the University and the possible foundation of a new museum, and Butler, as Secretary of the History of Science Committee in Cambridge, was the chief mover in both this development and an initiative coupled with it to establish a department of the history of science. (shrink)

As Astronomer Royal from 1835 till 1881, G. B. Airy had a very important influence on nineteenth-century British astronomy. His personal qualities combined with his office to give him a position of great authority within the astronomical and general scientific communities, and his powers of organization and work on instrumentation transformed the Royal Observatory. A feature of Airy's work was an extensive interest in horology—particularly in astronomical regulators, marine chronometers and driving clocks for chronographs and equatorial telescopes. He was also (...) concerned with building important turret clocks, and he established a public time service based at Greenwich. The enormous quantity of surviving material makes a complete review of Airy's career a daunting prospect; but the horology is a microcosm, where we can study on a manageable scale his attitudes to the Observatory, to its relation to society, and to the role of the Astronomer Royal as a public servant. (shrink)

Originally published in 1923, this book had enjoyed constant and wide success, being reprinted fourteen times. In this new and thoroughly revised edition, published in 1964, the author has reconsidered his conclusions in the light of modern psychology of the time, and includes many case histories from his long experience as a psychiatrist. The book was important for its insistence that there is no intrinsic conflict between analytical psychotherapy and ordinary moral behaviour.

In this paper we attempt to sharpen and to provide an answer to the question of when human beings first become conscious. Since it is relatively uncontentious that a capacity for raw sensation precedes and underpins all more sophisticated mental capacities, our question is tantamount to asking when human beings first have experiences with sensational content. Two interconnected features of our argument are crucial. First, we argue that experiences with sensational content are supervenient on facts about electrical activity in the (...) cerebral cortex which can be ascertained through EEG readings. Second, we isolate from other notions of a‘functioning brain’that which is required to underpin the view that a cortex is functioning in a way which could give rise to rudimentary conscious experiences. We investigate the development in the human fetus of the anatomical and chemical pathways which underpin cortical activity and the growth and maturation of the electrical circuitry specifically associated with sensational content in adult experience. We conclude that a fetus becomes conscious at about 30 to 35 weeks after conception; an answer based on a careful analysis of EEG readings at various stages of cortical development. Finally, we survey the possible ethical ramifications of our answer. (shrink)

Although this note is prompted by the recent exchange between Gellner [2], [3] and Needham [4], I shall ignore the issues raised by Gellner's specification for an ideal language. I am concerned here only with Needham's statement that ‘biology is one matter and descent is quite another, of a different order’ which, it will be remembered, Gellner treats as Needham's first error. I write under a sense of obligation, for I discussed this matter with Gellner in 1955 while he was (...) preparing his first article and my arguments then were phrased similarly to those advanced by Needham. It appears that I did not make myself clear to Gellner and I shall try again. I do not wish to attack or defend either protagonist; each is quite able to look after himself. Therefore I propose neither to examine where they have misunderstood each other, nor to discuss the difference between kinship and descent, but simply to state the connexion, as I see it, between physical and social kinship. (shrink)

This essay examines the concept of "truth" from empiricist and pragmatist perspectives. This not without reference to other theories. The concern is to see how the ascendancy of pragmatism has affected humanity and may continue to affect humanity, the so-called objectivity in the practice of science and philosophy and the relationships between the diverse peoples of the world. An analysis of the pragmatist's preference for usefulness, rather than truth, it is argued, accounts for the deleterious consequences of pragmatism for humankind (...) in its almost irrational substitution of usefulness for truth. (shrink)

The classical Feferman–Vaught Theorem for First Order Logic explains how to compute the truth value of a first order sentence in a generalized product of first order structures by reducing this computation to the computation of truth values of other first order sentences in the factors and evaluation of a monadic second order sentence in the index structure. This technique was later extended by Läuchli, Shelah and Gurevich to monadic second order logic. The technique has wide applications in decidability and (...) definability theory. Here we give a unified presentation, including some new results, of how to use the Feferman–Vaught Theorem, and some new variations thereof, algorithmically in the case of Monadic Second Order Logic MSOL . We then extend the technique to graph polynomials where the range of the summation of the monomials is definable in MSOL . Here the Feferman–Vaught Theorem for these polynomials generalizes well known splitting theorems for graph polynomials. Again, these can be used algorithmically. Finally, we discuss extensions of MSOL for which the Feferman–Vaught Theorem holds as well. (shrink)

The paper explores the distinction between two doctrines, both of which inform theory construction in much of modern cognitive psychology: the representational theory of mind and the computational theory of mind. According to the former, propositional attitudes are to be construed as relations that organisms bear to mental representations. According to the latter, mental processes have access only to formal (nonsemantic) properties of the mental representations over which they are defined.The following claims are defended: (1) That the traditional dispute between (...) “rational” and “naturalistic” psychology is plausibly viewed as an argument about the status of the computational theory of mind. Rational psychologists accept a formality condition on the specification of mental processes; naturalists do not. (2) That to accept the formality condition is to endorse a version of methodological solipsism. (3) That the acceptance of some such condition is warranted, at least for that part of psychology which concerns itself with theories of the mental causation of behavior. This is because: (4) such theories require nontransparent taxonomies of mental states; and (5) nontransparent taxonomies individuate mental states without reference to their semantic properties. Equivalently, (6) nontransparent taxonomies respect the way that the organism represents the object of its propositional attitudes toitself, and it is this representation which functions in the causation of behavior.The final section of the paper considers the prospect for a naturalistic psychology: one which defines its generalizations over relations between mental representations and their environmental causes, thus seeking to account for the semantic properties of propositional attitudes. Two related arguments are proposed, both leading to the conclusion that no such research strategy is likely to prove fruitful. (shrink)

We investigate the expressive power of second-order logic over finite structures, when two limitations are imposed. Let SAA ) be the set of second-order formulas such that the arity of the relation variables is bounded by k and the number of alternations of second-order quantification is bounded by n . We show that this imposes a proper hierarchy on second-order logic, i.e. for every k , n there are problems not definable in AA but definable in AA for some c (...) 1 , d 1 . The method to show this is to introduce the set AUTOSAT of formulas in F which satisfy themselves. We study the complexity of this set for various fragments of second-order loeic. For first-order logic FOL with unbounded alternation of quantifiers AUTOSAT is PSpace complete. For first-order logic FOL n with alternation of quantifiers bounded by n , AUTOSAT is definable in AA . AUTOSAT) is definable in AA for some c 1 , d 1. (shrink)