Molecular Biology, Misc

Binding specificity is a centrally important concept in molecular biology, yet it has received little philosophical attention. Here I aim to remedy this by analyzing binding specificity as a causal property. I focus on the concept’s role in drug design, where it is highly prized and hence directly studied. From a causal perspective, understanding why binding specificity is a valuable property of drugs contributes to an understanding of causal selection—of how and why scientists distinguish between causes, not just causes from (...) noncauses. In particular, the specificity of drugs is precisely what underwrites their value as experimental interventions on biological processes. (shrink)

Jacques Monod (1971) argued that certain molecular processes rely critically on the property of chemical arbitrariness, which he claimed allows those processes to “transcend the laws of chemistry”. It seems natural, as some philosophers have done, to interpret this in modal terms: a biological relationship is chemically arbitrary if it is possible, within the constraints of chemical “law”, for that relationship to have been otherwise than it is. But while modality is certainly important for understanding chemical arbitrariness, understanding its biological (...) role also requires an account of the concrete causal-functional features that distinguish arbitrary from non-arbitrary phenomena. In this paper I elaborate on this under-emphasised aspect by offering a general account of these features: arbitrary relations are instantiated by mechanisms that involve molecular adapters, which causally couple two properties or processes which would otherwise be uncorrelated. Additionally, adapters work by acting as intermediate rather than cooperating causes. (shrink)

Mechanistic explanations are often said to explain because they reveal the causal structure of the world. Conversely, dynamical models supposedly lack explanatory power because they do not describe causal structure. The only way for dynamical models to produce causal explanations is via the 3M criterion: the model must be mapped onto a mechanism. This framing of the situation has become the received view around the viability of dynamical explanation. In this paper, I argue against this position and show that dynamical (...) models can themselves reveal causal structure and consequently produce nonmechanistic, dynamical explanations. Taking the example of cell fates from systems biology, I show how dynamical models, and specifically the attractor landscapes they describe, identify the causes of cell differentiation and explain why cells select particular fates. These dynamical features of the system better fit Woodward’s (2010, 2018) criteria of specificity and proportionality and make them the best candidate causes of cell fates than mechanisms. I also show how these causes are irreducible and inaccessible to mechanistic models, making 3M unworkable and counterproductive in this case. Dynamical models can reveal dynamical causes and thereby provide causal explanations. (shrink)

Philosophers have committed sins while studying science, it is said – philosophy of science focused on physics to the detriment of biology, reconstructed idealizations of scientific episodes rather than attending to historical details, and focused on theories and concepts to the detriment of experiments. Recent generations of philosophers of science have tried to atone for these sins, and by the 1980s the exculpation was in full swing. Marcel Weber’s Philosophy of Experimental Biology is a zenith mea culpa for philosophy of (...) science: it carefully describes several historical examples from twentieth century biology to address both ‘old’ philosophical topics, like reductionism, inference, and realism, and ‘new’ topics, like discovery, models, and norms. Biology, experiments, history – at last, philosophy of science, free of sin. (shrink)

n this article the author develops a critique of reductionism in biological sciences from three different points of view. The first is related to the problem of reduction in the context of scientific theories. More specifically, reduction deals with a special form of intertheoretic relationship between molecular biology and the rest of biology. The second meaning of reductionism has to do with the significance of its genetic outfit for the ontogeny of an organism, i.e. its development from zygote to its (...) final or adult structure and function. Third, closely related to this more biological topic are questions about the anthropological consequences of the application of reductionistic methodologies for the explanation and evaluation of human behaviour. (shrink)

Review of: Sophia Roosth, Synthetic: How Life Got Made (University of Chicago Press, 2017); and Andrew S. Balmer, Katie Bulpin, and Susan Molyneux-Hodgson, Synthetic Biology: A Sociology of Changing Practices (Palgrave Macmillan, 2016).

The theory of evolution of complex, including the humans system and algorithm for its constructing are a synthesis of evolutionary epistemology, philosophical anthropology and concrete scientific empirical basis in modern science,. In other words, natural philosophy is regaining the status bar element theoretical science in the era of technology-driven evolution. The co-evolutionary concept of 3-modal stable evolutionary strategy of Homo sapiens is developed. The concept based on the principle of evolutionary complementarity of anthropogenesis: value of evolutionary risk and evolutionary path (...) of human evolution are defined by descriptive (evolutionary efficiency) and creative-teleological (evolutionary correctly) parameters simultaneously, that cannot be instrumental reduced to others ones. Resulting volume of both parameters define the vectors of biological, social, cultural and techno-rationalistic human evolution by two gear mechanism ˗ genetic and cultural co-evolution and techno-humanitarian balance. The resultant each of them can estimated by the ratio of socio-psychological predispositions of humanization/dehumanization in mentality. Explanatory model and methodology of evaluation of creatively teleological evolutionary risk component of NBIC technological complex is proposed. Integral part of the model is evolutionary semantics (time-varying semantic code, the compliance of the biological, socio-cultural and techno-rationalist adaptive modules of human stable evolutionary strategy). (shrink)

In this paper we offer a minimal characterisation of the concept of mechanism in biomedicine, according to which a mechanism is a theoretically described causal pathway. We argue that this conceptionan be drawn from scientific practice, as illustrated by how a central biological and biomedical mechanism, the mechanism of apoptosis, was first identified and characterised. We will use the example of cytological and biochemical theoretical descriptions of the mechanism of apoptosis to draw lessons about the meaning of the concept of (...) mechanism in biomedical contexts and to contrast our preferred account of mechanism with some prominent accounts within the philosophical literature. The main outcome of our discussion will be that commitment to mechanism is first and foremost a methodological stance. (shrink)

A summarizing English version on “Theory of Innovation and the Evolution of General Human Capabilities, such as Cognition-based Empathy” is included in the download. Den biologisch modernen Menschentyp charakterisieren sehr allgemeine Fähigkeiten, wie begriffliche Sprache, strategisches Denken und kognitionsgestützte Empathie. Neurobiologisch kann Empathiefähigkeit als eine Verbindung von Repräsentationen von Mitmenschen mit dem je eigenen Gefühlszentren im Gehirn angesehen werden. In Grundzügen ist sie vor vielleicht 100 000 Jahren als Folge von Mutationen der Erbsubstanz DNA entstanden. Für solche genetische Innovationen spielten (...) wohl nicht nur lokale Veränderungen des Genoms eine Rolle, sondern auch seltene größere Umordnungen, besonders neue Zufallskombinationen von Regelbereichen in der DNA. Dies könnte in seltenen Einzelfällen eine Art Weichenstellung für eine neue Richtung der Evolution bewirken, die dann in vielen kleinen Schritten ausgeprägt wurde. Interessant ist die Analogie solcher biologischer mit technischer Innovation: Auch in ihr, Beispiel Dampfschiff, spielt die (seltene) Neukombination von Grundfähigkeiten eine Initialrolle für die Ausbreitung einer Innovation. (shrink)

Several authors have used the notion of causal specificity in order to defend non-parity about genetic causes (Waters 2007, Woodward 2010, Weber 2017, forthcoming). Non-parity in this context is the idea that DNA and some other biomolecules that are often described as information-bearers by biologists play a unique role in life processes, an idea that has been challenged by Developmental Systems Theory (e.g., Oyama 2000). Indeed, it has proven to be quite difficult to state clearly what the alleged special role (...) of genetic causes consists in. In this paper, I show that the set of biomolecules that are normally considered to be information-bearers (DNA, mRNA) can be shown to be the most specific causes of protein primary structure, provided that causal specificity is measured over a relevant space of biological possibilities, disregarding physical as well as logically possible states of the causal variables. (shrink)

The ‘managed-metabolism’ hypothesis suggests that a ‘cooperation barrier’ must be overcome if self-producing chemical organizations are to undergo the transition from non-life to life. This dynamical barrier prevents un-managed autocatalytic networks of molecular species from individuating into complex, cooperative organizations. The barrier arises because molecular species that could otherwise make significant cooperative contributions to the success of an organization will often not be supported within the organization, and because side reactions and other ‘free-riding’ processes will undermine cooperation. As a result, (...) the barrier seriously impedes the emergence of individuality, complex functionality and the transition to life. This barrier is analogous to the cooperation barrier that also impedes the emergence of complex cooperation at all levels of living organization. As has been shown at other levels of organization, the barrier can be overcome comprehensively by appropriate ‘management’. Management implements a system of evolvable constraints that can overcome the cooperation barrier by ensuring that beneficial co-operators are supported within the organization and by suppressing free-riders. In this way, management can control and manipulate the chemical processes of a collectively autocatalytic organization, producing novel processes that serve the interests of the organization as a whole and that could not arise and persist in an un-managed chemical organization. Management self-organizes because it is able to capture some of the benefits that are produced when its interventions promote cooperation, thereby enhancing productivity. Selection will therefore favour the emergence of managers that take over and manage chemical organizations so as to overcome the cooperation barrier. The managed-metabolism hypothesis demonstrates that if management is to overcome the cooperation barrier comprehensively, its interventions must be digitally coded. In this way, the hypothesis accounts for the two-tiered structure of all living cells in which a digitally-coded genetic apparatus manages an analogically-informed metabolism.GraphicalOpen image in new window. (shrink)

The question “What is an organism?”, formerly considered as essential in biology, has now been increasingly replaced by a larger question, “What is a biological individual?”. On the grounds that i) individuation is theory-dependent, and ii) physiology does not offer a theory, biologists and philosophers of biology have claimed that it is the theory of evolution by natural selection which tells us what counts as a biological individual. Here I show that one physiological field, immunology, offers a theory, which makes (...) possible a biological individuation based on physiological grounds. I give a new answer to the question of the individuation of an organism by linking together the evolutionary and the immunological approaches to biological individuation. (shrink)

This paper advances the thesis of methodological mechanism, the claim that to be committed to mechanism is to adopt a certain methodological postulate, i.e. to look for causal pathways for the phenomena of interest. We argue that methodological mechanism incorporates a minimal account of understanding mechanisms, according to which a mechanism just is a causal pathway described in the language of theory. In order to argue for this position we discuss a central example of a biological mechanism, the mechanism of (...) cell death, known as apoptosis. We argue that this example shows that our philosophically deflationary account is sufficient in order to have an illuminating account of mechanisms as the concept is used in biology. (shrink)

The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins. -/- .

This paper examines the adequacy of causal graph theory as a tool for modeling biological phenomena and formalizing biological explanations. I point out that the causal graph approach reaches it limits when it comes to modeling biological phenomena that involve complex spatial and structural relations. Using a case study from molecular biology, DNA-binding and -recognition of proteins, I argue that causal graph models fail to adequately represent and explain causal phenomena in this field. The inadequacy of these models is due (...) to their failure to include relevant spatial and structural information in a way that does not render the model non-explanatory, unmanageable, or inconsistent with basic assumptions of causal graph theory. (shrink)

Molecular biology is a relatively new and very successful branch of science but currently it faces challenges posed by very complex issues that cannot be addressed by a traditional reductionist approach. However, despite its origins in the providential shift of some theoretical physicists to biology, currently molecular biology is immersed in a blind trend in which high-throughput technology, able to generate trillions of data, is becoming the leading edge of a discipline that has traded rational and critical thinking for computer (...) power, data crunching and statistics in hope of finding, once more, its way. However, the complex questions facing MB may only be solved by a paradigm shift in the causal way of thinking, so that complex, emergent, non-linear phenomena may be effectively understood in top-down and not in bottom-up terms. (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration of (...) a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

This chapter discusses several kinds of reduction that are often found in the biomedical sciences, in contrast to reduction in fields such as physics. This includes reduction as a methodological assumption for how to investigate phenomena like complex diseases, and reduction as a conceptual tool for relating distinct models of the same phenomenon. The case of Parkinson’s disease illustrates a wide variety of ways in which reductionism is an important tool in medicine.

Considerable variation exists not only in the kinds of transposable elements (TEs) occurring within the genomes of different species, but also in their abundance and distribution. Noting a similarity to the assortment of organisms among ecosystems, some researchers have called for an ecological approach to the study of transposon dynamics. However, there are several ways to adopt such an approach, and it is sometimes unclear what an ecological perspective will add to the existing co-evolutionary framework for explaining transposon-host interactions. This (...) review aims to clarify the conceptual foundations of transposon ecology in order to evaluate its explanatory prospects. We begin by identifying three unanswered questions regarding the abundance and distribution of TEs that potentially call for an ecological explanation. We then offer an operational distinction between evolutionary and ecological approaches to these questions. By determining the amount of variance in transposon abundance and distribution that is explained by ecological and evolutionary factors, respectively, it is possible empirically to assess the prospects for each of these explanatory frameworks. To illustrate how this methodology applies to a concrete example, we analyzed whole-genome data for one set of distantly related mammals and another more closely related group of arthropods. Our expectation was that ecological factors are most informative for explaining differences among individual TE lineages, rather than TE families, and for explaining their distribution among closely related as opposed to distantly related host genomes. We found that, in these data sets, ecological factors do in fact explain most of the variation in TE abundance and distribution among TE lineages across less distantly related host organisms. Evolutionary factors were not significant at these levels. However, the explanatory roles of evolution and ecology become inverted at the level of TE families or among more distantly related genomes. Not only does this example demonstrate the utility of our distinction between ecological and evolutionary perspectives, it further suggests an appropriate explanatory domain for the burgeoning discipline of transposon ecology. The fact that ecological processes appear to be impacting TE lineages over relatively short time scales further raises the possibility that transposons might serve as useful model systems for testing more general hypotheses in ecology. (shrink)

The Aristotelian axiom that function follows form was beautifully instantiated in molecular biology by the discovery of DNA’s structure that immediately suggested how DNA might work as depository and vehicle for genetic information. However, later on molecular biology became infatuated with the gene that became the center of the universe. This gene-centered viewpoint is an obstacle for the emerging field of evo-devo aiming at finding the causal connections between evolution and biological development. Here it is argued that molecular biology must (...) reject the narrow-minded causality associated with the gene-centered view and so it must recover to the spirit of Aristotelian natural history and its four types of causation in order to foster the evo-devo field of research. (shrink)

Melinda Fagan’s book on the philosophy of stem cell biology is a superb discussion of this exciting field of contemporary science, and the first book-length philosophical treatment of the subject. It contains a detailed and insightful examination of stem cell science, its structure, methods, and challenges.The book does not require any previous knowledge of stem cell biology—all the relevant scientific details and concepts, the central experimental procedures and results, as well as the historical development of the field, are presented in (...) as clear and accessible a way as possible. The presentation of the science starts in Chapter 1, with a general characterisation of stem cell biology, and continues throughout the book, with every chapter deepening and complicating the initial picture. Fagan’s lucid style makes even the more technical and detailed discussions of the research on human embryonic stem cells and on blood stem cells easy to follow.After the first in .. (shrink)

Chemical kinds (e.g. gold) are generally treated as having timelessly fixed identities. Biological kinds (e.g. goldfinches) are generally treated as evolved and/or evolving entities. So what kind of kind is a biochemical kind? This paper defends the thesis that biochemical molecules are clustered chemical kinds, some of which–namely, evolutionarily conserved units–are also biological kinds.On this thesis, a number of difficulties that have recently occupied philosophers concerned with proteins and kinds are shown to be resolved or dissolved.

In 1968, Motoo Kimura submitted a note to Nature entitled “Evolutionary Rate at the Molecular Level,” in which he proposed what has since become known as the neutral theory of molecular evolution. This is the view that the majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral or nearly neutral alleles. Kimura was not proposing that random drift explains all evolutionary change. He does not challenge the view that natural selection explains adaptive evolution, (...) or, that the vertebrate eye or the tetrapod limb are products of natural selection. Rather, his objection is to “panselectionism’s intrusion into the realm of molecular evolutionary studies”. According to Kimura, most changes at the molecular level from one generation to the next do not affect the fitness of organisms possessing them. King and Jukes (1969) published an article defending the same view in Science, with the radical title, “Non- Darwinian Evolution,” at which point, “the fat was in the fire” (Crow, 1985b). The neutral theory was one of the most controversial theories in biology in the late twentieth century. This chapter will review the debate over the netural theory subsequent to Kimura. (shrink)

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about (...) causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

A classic analytic approach to biological phenomena seeks to refine definitions until classes are sufficiently homogenous to support prediction and explanation, but this approach founders on cases where a single process produces objects with similar forms but heterogeneous behaviors. I introduce object spaces as a tool to tackle this challenging diversity of biological objects in terms of causal processes with well-defined formal properties. Object spaces have three primary components: (1) a combinatorial biological process such as protein synthesis that generates objects (...) with parts that are modular, independent, and organized according to an invariant syntax; (2) a notion of “distance” that relates the objects according to rules of change over time as found in nature or useful for algorithms; (3) mapping functions defined on the space that map its objects to other spaces or apply an evaluative criterion to measure an important quality, such as parsimony or biochemical function. Once defined, an object space can be used to represent and simulate the dynamics of phenomena on multiple scales; it can also be used as a tool for predicting higher-order properties of the objects, including stitching together series of causal processes. Object spaces are the basis for a strategy of theorizing, discovery, and analysis in biology: as heuristic idealizations of biology, they help us transform inchoate, intractable problems into articulated, well-structured ones. Developing an object space is a research strategy with a long, successful history under many other names, and it offers a unifying but not overreaching approach to biological theory. (shrink)

Apparency and actuality are discussed with respect to science, genetics, evolution, cognition and perception. Rules for a (sub)set of actual/allowable sets of entities and objects from a total set that is based on differences and contrasts extracted from perceptual experience of the world elucidate tenable combinations/recombinations from a total of the transparent(history/past dependant) and the apparent as they can be construed to comprise the actual/real faces of perception. The elements of dreams, language, symbolisms, abstractions are proposed to encompass to encompass (...) a total set of plausible apparencies. Nature from which both internal and external life is mirrored at the simplest structural level is propose to be constructed similarly-to physically possess also concepts and abstractions as states that reflect differences/combinations/recombinations parametrically that are emerged from the parameters associated with particular circumstances. This view is dependant upon, for its' conceptual soundness, a total construction of the world that descends, rather than ascends, in structural complexity and diversity and which is innately divided and compartmentalized in sequence from a more complex uniquely existing state describable singularly as a place of force and proximities form which all processes ensue. Integration of sound, light, into sensory experience and language is proposed to be a natural process of the accomplishment of new proximities/states from total apparent plausibility’s (past and actual combined) verses the actually(past and present) existing. Two potential important aspects of this scheme exist with regards to evolution theory: 1) a very relative dynamic state of change and emergence is plausible 2) a consistent identity of objects and entities is resolvable that is not based on apparent observations or partial history of events but on a set of total states and processes occurred during the progression to an actual condition. This is suggested to be unique for each and every actual situation as an identifier and is proposed to account for allowances with respect to new potentials. "Self" in this sense can assume more involved relations with self more than with the more distant, hence alien, otherwise arrived at proximal components, components of the environment, inert or otherwise. An example is presented with respect to solar energies and their toxicity to cause disturbances/disease upon internal exposure-as an unnaturally arrived imbalance/proximity between the transparent (history dependant) and the apparent-together comprising, in this situation, a disturbed actual state that can encompass also distortions in the perception of time. Time is proposed to be delineated as a contrast of proximal and distal factors mutually involved with both transparent (genealogically) oriented parameters, and empirically apparent factors that together comprise the actual, as well as those more immediate proximal and distal components(e.g. solar radiation, light-the less structured ambient verse those elements that comprise visual perceptions) as they influence the senses. Each entity species in this scheme possesses its’ own characteristic sense of time along with contemporary factors that influence the perception of time state, state of health and disturbance. (shrink)