What is Life? This is the question asked by Denis Noble in this very personal and at times deeply lyrical book. Noble is a renowned physiologist and systems biologist, and he argues that the genome is not life itself: to understand what life is, we must view it at a variety of different levels, all interacting with each other in a complex web. It is that emergent web, full of feedback between levels, from the gene to the (...) wider environment, that is life. (shrink)

What is Life? To answer this question, Denis Noble argues that we must look beyond the gene's eye view. For modern 'systems biology' considers life on a variety of levels, as an intricate web of feedback between gene, cell, organ, body, and environment. He shows how it is both a biologically rigorous and richly rewarding way of understanding life.

The Modern Synthesis has dominated biology for 80 years. It was formulated in 1942, a decade before the major achievements of molecular biology, including the Double Helix and the Central Dogma. When first formulated in the 1950s these discoveries and concepts seemed initially to completely justify the central genetic assumptions of the Modern Synthesis. The Double Helix provided the basis for highly accurate DNA replication, while the Central Dogma was viewed as supporting the Weismann Barrier, so excluding the inheritance of (...) acquired characteristics. This article examines the language of the Modern Synthesis and reveals that it is based on four important misinterpretations of what molecular biology had shown, so forming the basis of the four Illusions: 1. Natural Selection; 2. The Weismann Barrier; 3. The Rejection of Darwin’s Gemmules; 4. The Central Dogma. A multi-level organisation view of biology avoids these illusions through the principle of biological relativity. Molecular biology does not therefore confirm the assumptions of the Modern Synthesis. (shrink)

Conscious Agency is a major driver of evolution. Artificial Selection (i.e. Conscious Selection by human breeders) was the foil against which Charles Darwin defined Natural Selection. In later work, he extended Artificial Selection to other species. That ability for social (e.g. sexual) selection must have evolved. Jablonka and Ginsburg identify markers of conscious agency, such as Unlimited Associative Learning (UAL), and show that it must have existed at the time of the Cambrian Explosion. To their insights, my commentary argues that (...) the harnessing of stochasticity was also involved in the evolution of the faculty of choice in organisms. (shrink)

The extensive range and depth of the twenty commentaries on my target article confirms that something has gone deeply wrong in biology. A wide range of biologists has more than met my invitation for “others to pitch in and develop or counter my arguments.” The commentaries greatly develop those arguments. Also remarkably, none raise issues I would seriously disagree with. I will focus first on the more critical comments, summarise the other comments, and then point the way forward on what (...) I view as a necessary and long-overdue transition in the foundations of biology. (shrink)

In this paper, we demonstrate (1) how harnessing stochasticity can be the basis of creative agency; (2) that such harnessing can resolve the apparent conflict between reductionist (micro-level) accounts of behaviour and behaviour as the outcome of rational and value-driven (macro-level) decisions; (3) how neurophysiological processes can instantiate such behaviour; (4) The processes involved depend on three features of living organisms: (a) they are necessarily open systems; (b) micro-level systems therefore nest within higher-level systems; (c) causal interactions must occur across (...) all the boundaries between the levels of organization. The higher levels constrain the dynamics of lower levels. The experimental evidence and theoretical arguments are shown to be consistent with previous research on the neuronal mechanisms of conscious choice, and with the interconnected multi-level processes by which organisms harness stochasticity, whether conscious or unconscious. (shrink)

Mathematical models of the heart have developed over a period of about 40 years. Cell types in all regions of the heart have been modelled and they are now being incorporated into anatomically detailed models of the whole organ. This combination is leading to the creation of the first ‘virtual organ,’ which is being used in drug discovery and testing, and in simulating the action of devices, such as cardiac defibrillators. Simulation is a necessary tool of analysis in attempting to (...) understand biological complexity. We often learn as much from the failures as from the successes of mathematical models. It is the iterative interaction between experiment and simulation that is important. Examples are given where this process has been instrumental in some of the major advances in the field. BioEssays 24:1155–1163, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Kathy Wilkes contributed to two books on Goal-directed Behaviour and Modelling the Mind based on interdisciplinary graduate classes at Oxford during the 1980s. In this article, I assess her contributions to those discussions. She championed the school of philosophers who prefer problem dissolution to problem-solution. She also addressed the problem of realism in psychology. But the contribution that has turned out to be most relevant to subsequent work was her idea that in modelling the mind, we might need to “use (...) as structural elements synthetic cells, or things that behaved very like neurones.” I show how this idea has been developed in my own recent work with zoologist and neuroscientist, Raymond Noble, to become a possible physiological basis for the ability of organisms to choose between alternative actions, and so become active agents. I consider that this insight became her seminal contribution in this field. (shrink)

This chapter describes the origin of the principle of biological relativity and its development since 2012. It was first formulated by distinguishing between the causal properties of initial and boundary conditions, regarded as a formal cause, compared to the dynamics of the differential functions themselves, regarded as an efficient cause. The concept of organisational level, and of boundaries between levels and environmental factors are also central to the principle. Work on the properties of boundaries reveals two important features: the nature (...) of causation differs significantly between different levels of organisation, and the top-down and bottom-up forms must act simultaneously. These developments of the principle are used to clarify the reasons why bottom-up causation alone is inadequate in multi-level biology. (shrink)

The Weismann Barrier and the Central Dogma do not protect the assumptions of The Modern Synthesis.

Papers from a seminar held in Paris, Sept. 1995, organized by the International Union of Physiological Sciences and UNESCO.

The Language of Symmetry is a re-assessment of the structure and reach of symmetry, by an interdisciplinary group of specialists from the arts, humanities, and sciences at Oxford University. It explores, amongst other topics order and chaos in the formation of planetary systems entropy and symmetry in particle physics group theory, fractals and self-similarity symmetrical structures in western classical music, and how biological systems harness disorder to create order. This book aims to open up the scope of interdisciplinary work in (...) the study of symmetry and is intended for scholars of any background - whether it be science, arts or philosophy. (shrink)

Systems Biology is the study of the interactions between the elements (genes, proteins and other molecules) of living systems. Genes do not act in isolation either from each other or from the environment, and so I replace the metaphor of the selfish gene with metaphors that emphasise the processes involved rather than the molecular biological components. This may seem a simple shift of viewpoint. In fact it is revolutionary. Nothing remains the same. There is no 'book of life', nor are (...) there 'genetic programs'. The consequences for the study of the brain and the nature of the self are profound. They lead naturally to the concept of anātman, no-self, and to a better understanding of the relation between the microscopic and macroscopic views of the world. Organisms are viewed as variable open systems, rather than as determinate closed systems. (shrink)

Athlete after athlete in this book found discipline, hope, and inspiration on the playing field, rising above their circumstances. Filled with first-hand accounts from stars who exemplify the idea of enduring at all costs, Rising Above will serve as a must-read source of inspiration for kids and sports fans of all ages.

Stimulation of airway myocytes by contractile agents such as acetylcholine (ACh) activates a Ca2+-activated Cl– current (IClCa) which may play a key role in calcium homeostasis of airway myocytes and hence in airway reactivity. The aim of the present study was to model IClCa in airway smooth muscle cells using a computerised model previously designed for simulation of cardiac myocyte functioning. Modelling was based on a simple resistor-battery permeation model combined with multiple binding site activation by calcium. In order to (...) validate the model, a combination of equations, used to mimic [Ca2+]i response to ACh stimulation, were incorporated into the model. The results indicate that the model developed in this article accounts for experimental recordings and electrophysiological characteristics of this current in airway smooth muscle cells, with parameter values consistent with those calculated from experimental data. Such a model may thus be used to predict IClCa functioning, though additional experimental data from airway myocytes would be useful to more accurately determine some parameter values of the model. (shrink)

With scale relativity theory, Laurent Nottale has provided a powerful conceptual and mathematical framework with numerous validated predictions that has fundamental implications and applications for all sciences. We discuss how this extended framework reviewed in Nottale (Found Sci 152 (3):101–152, 2010a ) may help facilitating integration across multiple size and time frames in systems biology, and the development of a scale relative biology with increased explanatory power.

The is the Editorial of the 2015 JPBMB Special Issue on Integral Biomathics: Life Sciences, Mathematics and Phenomenological Philosophy.

This is the editorial to the special edition of Progress in Biophysics and Molecular Biology on the role engagement with Eastern traditions of thought could play in the advancement of science generally and biology and the science of mind in particular.

In this paper, we argue that Plotinus denies deliberative forethought about the physical cosmos to the demiurge on the basis of certain basic and widely shared Platonic and Aristotelian assumptions about the character of divine thought. We then discuss how Plotinus can nonetheless maintain that the cosmos is «providentially» ordered.

In Ennead 3.6, Plotinus maintains that the soul is unaffectable. This thesis is widely taken to imply that his soul is exempt from change and free from emotional ‘affections’. Yet these claims are difficult to reconcile with evidence that Plotinian souls acquire dispositional states, such as virtues, and are subjects of emotional ‘affections’, such as anger. This paper offers an alternative account that aims to address these difficulties. In denying affections to soul, Plotinus is offering a distinction between the soul’s (...) self-actuated motions (or "activities") and the passive motions (or "affections") of bodies. But this distinction does not imply the soul’s changelessness, since Plotinus regards psychic motions that culminate in the soul’s acquisition of new dispositional states as changes. As for emotional ‘affections’, these (as activities) are merely homonymous with the affections denied to soul, and so do not violate the ban on the soul’s affectability. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy and Literature 27.1 (2003) 241-254 [Access article in PDF] Darwin and Political Theory Denis Dutton [Erratum]IN THE 1970s, during the oil crisis, B. F. Skinner suggested a way that the United States's energy shortage could be alleviated. People should be rewarded, he argued, for coming together to eat in large communal dining halls, rather than cooking and eating at home with their families. His reasoning was irresistible: (...) large cooking pots have a lower ratio of surface area to volume. There would be therefore a considerable saving in energy in massive public kitchens, compared with numberless small individual pots cooking in private kitchen stoves across the nation.Of course, Skinner must have known his idea would have to overcome objections based on ingrained middle-class prejudices. Some parents would feel aggrieved: placing children before big communal pots would rob mothers of the pleasures of preparing foods and feeding their own offspring. Others might object that the only foods adequate to a big, round energy-efficient vessels are stews or soups; they might complain about endless boiled fare. Families of one ethnic background or another might dislike the relatively uniform diet, despite the hearty, nutritious goodness of stew. I can imagine Skinner's frustration: Why are people so stubborn? Why can't they look beyond minor details and see the sheer reasonableness of the proposal?The story is cited by Steven Pinker in The Blank Slate as yet another dream of a better-engineered world shattered by the ornery persistence of human nature. Based on his work with rats and pigeons, Skinner was sure that the proper conditioning applied to human beings could eliminate aggression, overpopulation, pollution, and inequality. In Skinner's utopia, Pinker wisecracks, "The noble savage became the noble pigeon." [End Page 241]B. F. Skinner was just another daft step on a long utopian road that stretches back through Marx, Rousseau, Hobbes, and St. Thomas to Plato. These political philosophers, as well as those who, like Aristotle, are skeptical of utopianism, base their visions on some understanding, argued or merely implied, of human nature. All political systems—free or totalitarian, monarchist or republican—tend to posit some notion of the natural human being. In recent generations many thinkers have been inclined to regard competing conceptions of human nature as stuck in eternal conflict, embodying basic commitments about the human condition that are independent of evidence, originating instead in the religion, culture, or individual temperament of the political philosopher.Evolutionary psychology gives hope against this pessimism. Political philosophers are right to posit a natural background that underlies construction of political systems, evolutionary psychologists say, but it required Darwin finally to explain that background to us. A lucid attempt to spell out the implications evolution for politics has now been published by Paul H. Rubin, a professor of economics and law at Emory University, in the form of Darwinian Politics: The Evolutionary Origin of Freedom (Rutgers University Press, $25.00, paperback). Some of his conclusions are what anyone familiar with evolutionary psychology might suppose even without picking up the book. Others come as a surprise, and were unexpected even by Rubin himself. The book is both fascinating and unpredictable.The scene of evolution is the Environment of Evolutionary Adaptedness, the EEA, essentially the Pleistocene, the whole, long period lasting from 1.6 million years ago up until the shift to the Holocene with the invention of agriculture and large settlements 10,000 years ago. Our present intellectual constitution was achieved by about 50,000 years ago, or 40,000 before the Holocene. Keep in mind the immensity of this time scale: calculating at twenty years for a generation, there were 800,000 generations of humans and proto-humans in the Pleistocene, while there have been a mere 500 generations since agriculture and the first cities. It was in the earlier, much longer period that selective pressures created genetically modern humans. These pressures might have pushed only very slightly in one direction over another. But a slight pressure over hundreds of thousands of generations—toward a taste for sweet, say, or a wariness of snakes—... (shrink)

In this paper, we argue that Plotinus denies deliberative forethought about the physical cosmos to the demiurge on the basis of certain basic and widely shared Platonic and Aristotelian assumptions about the character of divine thought. We then discuss how Plotinus can nonetheless maintain that the cosmos is «providentially» ordered. -/- [Note: This paper is a French translation (prepared by Mathilde Brémond) of a paper that appears in A. Marmodoro and B. Prince (eds.), Causation and Creation in Late Antiquity (Cambridge, (...) 2015).]. (shrink)

The Modern Synthesis was based on Darwin’s gradualist view of evolution and early twentieth Century Mendelian and population genetics. Although early results in microbial and molecular genetics seemed to solidify MS views through the Central Dogma of Molecular Biology, accepting their basic concepts as permanent truths blinded MS proponents to the importance of incompatible discoveries in the second half of the 20th and early 21st Centuries. Discoveries based largely on the DNA record have provided a radically different view of genome (...) complexity and biologically-mediated evolutionary change. (shrink)

Denis Noble suggests that biologists who created the Modern Synthesis were taken in by conceptual traps and illusions hidden in the language they used. Rather than blame language itself, my response counters that all writers are responsible for careful attention to the implications of the metaphors they use, and that Richard Dawkins deliberately chose “the selfish gene.” Noble’s concept of biological relativity restores Darwin’s fuller and more nuanced definition of natural selection and shows how it also accounts (...) for Lamarck’s assertion that acquired characteristics can be inherited. Biological relativity is supported by Maurice Merleau- Ponty’s chiasmic ontology. (shrink)

In this commentary on Denis Noble’s “The Illusions of the Modern Synthesis,” I discuss three illusions he argues exist within the Modern Synthesis. These illusions have the common theme of attempting to identify the correct way of understanding and describing biological systems. I agree with much of Noble’s claims, but offer the language of developmental systems theory as a friendly tool for moving the project forward.

Nietzsche implicitly endorses a positive value system grounded in his concept of the will to power, a “noble” alternative to the “slavish” and life-denying values that he believes characterize modern European morality. His own power-affirming value system is usually presented amorally: as an alternative to morality, rather than as a competing morality. Most commentators believe this is necessarily so: because Nietzsche founds his values in the affirmation of power, they are incompatible with the concern for the well-being of others (...) that is characteristic of any authentic morality. This paper argues, on the contrary, that Nietzsche’s noble, power-affirming values are fully compatible with morality. It defends this view by rejecting two common misconceptions about Nietzsche’s philosophy: 1) the view that Nietzsche’s concept of the will to power is inseparable from domination, and 2) the view that noble values require and actively promote social hierarchy. (shrink)

Hume scholars have been anxious to point out that when Hume calls Justice, chastity and so on artificial virtues, he is in no way denying that they are real virtues. I shall argue that they are mistaken, and that anyone who wants to understand Hume's account of Justice and his category of artificial virtues must take seriously his choice of the word ‘artifice,’ recognizing that it means not only ‘Skill in designing and employing expedients,’ but also ‘address, cunning, trickery.'My suggestion (...) will seem strange given Hume's own repeated plea that we not take the term ‘artifice’ too seriously. Yet while it is generally good policy to take people - at least philosophers - at their word, this is a Justified exception, Justified not only by Hume's known proclivities to irony and subtlety, but also by the implications of hearkening to his plea. To see the implications of not taking the terms ‘artificial’ and ‘artifice’ seriously, one can read either Duncan Forbes’ or Barry Stroud's criticisms of Hume's account of Justice. (shrink)

ABSTRACT:In a series of reports the United Nations Special Representative on the issue of Human Rights and Transnational Corporations has emphasized a tripartite framework regarding business and human rights that includes the state “duty to protect,” the TNC “responsibility to respect,” and “appropriate remedies” for human rights violations. This article examines the recent history of UN initiatives regarding business and human rights and places the tripartite framework in historical context. Three approaches to human rights are distinguished: moral, political, and legal. (...) It is argued that the tripartite framework’s grounding of the responsibility of TNCs to respect human rights is properly understood as moral and not merely as a political or legal duty. A moral account of the duty of TNCs to respect basic human rights is defended and contrasted with a merely strategic approach. The main conclusion of the article is that only a moral account of the basic human rights duties of TNCs provides a sufficiently deep justification of “the corporate responsibility to respect human rights” feature of the tripartite framework. (shrink)

Plotinus, following certain Platonic cues, maintains that ‘we’ and ‘the true human being’ correspond to the rational part of the embodied human soul. This view is counterintuitive because it is natural to see ourselves and our humanity as including parts of the human organism additional to reason. In this paper, I propose that Plotinus’ view that we are our rational part is best understood as expressing a teleological claim. Since our proper end is an activity of the rational part of (...) soul, it is appropriate to identify our nature with that part of the organism alone. (shrink)

Cet ouvrage vise à délimiter le champ d'investigation de la philosophie de l'esprit. Il comprend huit chapitres. Le premier, le plus général, se veut une première délimitation du champ d'investigation de la philosophie de l'esprit à l'aide de ses trois concepts clés: l'intentionnalité, la rationalité et la conscience. Le chapitre suivant se veut une réflexion plus générale sur les motivations philosophiques qui commandent des jugements si opposés sur le statut ontologique et épistémologique de la psychologie du sens commun. Le chapitre (...) IV dresse un tableau de ces différents programmes et des grands courants de la philosophie de l'esprit, en commençant par le behaviorisme, le physicalisme, le fonctionnalisme et le connexionnisme. Les trois chapitres suivants porteront sur les problèmes et débats liés à la naturalisation des trois propriétés principales de l'esprit, des trois problèmes principaux de la philosophie de l'esprit, soit les concepts d'intentionnalité, de rationalité et de conscience. Le chapitre V porte, d'une part, sur la nature de l'intentionnalité et les différents concepts de directionnalité (aboutness) que l'on retrouve actuellement en philosophie de l'esprit ; d'autre part, il s'agira pour nous de décrire et de classer les différents programmes de naturalisation de l'intentionnalité. Le chapitre six est ouvre de nouvelles perpectives en ce qu'il porte sur la nature de la rationalité et sur les différentes tentatives et arguments en faveur de sa naturalisation. Le chapitre VII s'attaque au problème central de la philosophie de l'esprit, à savoir la conscience. (shrink)

This article applies the Kantian doctrine of respect for persons to the problem of sweatshops. We argue that multinational enterprises are properly regarded as responsible for the practices of their subcontractors and suppliers. We then argue that multinationalenterprises have the following duties in their off-shore manufacturing facilities: to ensure that local labor laws are followed; to refrain from coercion; to meet minimum safety standards; and to provide a living wage for employees. Finally, we consider and reply to the objection that (...) improving health and safety conditions and providing a living wage will cause greater harm than good. (shrink)

Le suicide collectif apparaît comme une aberration sociale, une extrême anomalie de la culture. Et si c'était au contraire l'aboutissement de toute collectivisation achevée? Si c'était la destinée cachée - sectaire et mystique - de toute histoire commune, de toute pensée unique? Admettons-le, ne serait-ce qu'un moment. Nous sommes alors contraints de bouleverser notre perception de la vie sociale et politique. Celle-ci ne devrait pas sa survie à la recherche d'unité bien-gérée, mais aux " trous " dans le collectif ; (...) à la résistance des corps vivants, et non à l'Esprit qui tente de les fondre en une mortelle idéalité commune. La théorie freudienne du " lien de masse " rend compte de cette dérive fatale des collectifs idéalisés. Sous- estimée par les sciences sociales, elle permet de lire ce qu'il advient aujourd'hui de nos sociétés saisies dans l'imago d'une " secte-monde ", et du péril majeur qui les y guette. Elle permet aussi, rétroactivement, d'analyser l'histoire occidentale comme une suite d'oscillations entre la capture fatale par l'Idéal et le retour à la pluralité vivante des Corps. Est-ce dans ce balancement, cette danse entre Corps et Esprit, que la culture humaine résiste au cours des temps à la fascination narcissique? (shrink)