The new mechanistic philosophy is divided into two largely disconnected projects. One deals with a metaphysical inquiry into how mechanisms relate to issues such as causation, capacities and levels of organization, while the other deals with epistemic issues related to the discovery of mechanisms and the intelligibility of mechanistic representations. Tudor Baetu explores and explains these projects, and shows how the gap between them can be bridged. His proposed account is compatible both with the assumptions and practices of experimental design (...) in biological research, and with scientifically accepted interpretations of experimental results. (shrink)

We discuss foundational issues of quantum information biology —one of the most successful applications of the quantum formalism outside of physics. QIB provides a multi-scale model of information processing in bio-systems: from proteins and cells to cognitive and social systems. This theory has to be sharply distinguished from “traditional quantum biophysics”. The latter is about quantum bio-physical processes, e.g., in cells or brains. QIB models the dynamics of information states of bio-systems. We argue that the information interpretation of quantum mechanics (...) is the most natural interpretation of QIB. Biologically QIB is based on two principles: adaptivity; openness. These principles are mathematically represented in the framework of a novel formalism— quantum adaptive dynamics which, in particular, contains the standard theory of open quantum systems. (shrink)

In recent years the number of scholarly publications devoted to Kant's theory of biology has rapidly growing, with particular attention being given to Kant's thoughts about the concepts of teleology, function, organism, and their respective roles in scientific practice. Moving from these recent studies, and distancing itself from their mostly evolutionary background, the main aim of the present paper is to suggest an original "cognitive turn" in the interpretation of Kant's theory of biology. More specifically, the Authors will trace a (...) connection between some Kantian theses about the “peculiar” or special nature of the human mind, advanced in the Critique of the Power of Judgement, and some specific epistemological issues pertaining to the research practice of contemporary molecular biology. (shrink)

Despite the transformation in biological practice and theory brought about by discoveries in molecular biology, until recently philosophy of biology continued to focus on evolutionary biology. When the Human Genome Project got underway in the late 1980s and early 1990s, philosophers of biology -- unlike historians and social scientists -- had little to add to the debate. In this landmark collection of essays, Sahotra Sarkar broadens the scope of current discussions of the philosophy of biology, viewing molecular (...) biology as a unifying perspective on life that complements that of evolutionary biology. His focus is on molecular biology, but the overriding question behind these papers is what molecular biology contributes to all traditional areas of biological research.Molecular biology -- described with some foresight in a 1938 Rockefeller Foundation report as a branch of science in which "delicate modern techniques are being used to investigate ever more minute details" -- and its modeling strategies apparently argue in favor of physical reductionism. Sarkar's first three chapters explore reductionism -- defending it, but cautioning that reduction to molecular interactions is not necessarily a reduction to genetics. The next sections of the book discuss function, exploring how functional explanations pose a problem for reductionism; the informational interpretation of biology and how it interacts with reductionism; and the tension between the unifying framework of molecular biology and the received framework of evolutionary theory. The concluding chapter is an essay in the emerging field of developmental evolution, exploring what molecular biology may contribute to the transformation of evolutionary theory as evolutionary theory takes into account morphogenetic development. (shrink)

The convergence of developmental biology — embryology — and molecular biology was one of the major scientific events of the last decades of the twentieth century. The transformation of developmental biology by the concepts and methods of molecular biology has already been described. Less has been told on the reciprocal transformation of molecular biology on contact with higher organisms. The transformation of molecular biology occurred at the end of a deep crisis which affected this discipline in (...) the sixties and seventies and which led to a cruel criticism of the preexisting models of gene regulation. Numerous new, sometimes heterodox, models were proposed to describe the level at which gene regulation took place and its underlying mechanisms. The crisis resolved itself at the beginning of the eighties with the rapid accumulation of results from genetic engineering techniques and, above all, a displacement of the descriptive level from the molecule to the cell. This displacement gave molecular biologists the 'explanandum' which had been cruelly lacking during their initial study of higher organisms. The new molecular cell biology is an interfield explanation of living phenomena, relating a description and an interpretation localized at different levels of organization. (shrink)

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the 'central dogma', on the socalled 'informational talk'. It is argued that talk of information in the 'central dogma' can be reduced to causal claims. In that respect, the primary (...) aim of the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. (shrink)

An assessment is offered of the recent debate on information in the philosophy of biology, and an analysis is provided of the notion of information as applied in scientific practice in molecular genetics. In particular, this paper deals with the dependence of basic generalizations of molecular biology, above all the ‘central dogma’, on the so-called ‘informational talk’ (Maynard Smith [2000a]). It is argued that talk of information in the ‘central dogma’ can be reduced to causal claims. In that (...) respect, the primary aim of the paper is to consider a solution to the major difficulty of the causal interpretation of genetic information: how to distinguish the privileged causal role assigned to nucleic acids, DNA in particular, in the processes of replication and protein production. A close reading is proposed of Francis H. C. Crick's On Protein Synthesis (1958) and related works, to which we owe the first explicit definition of information within the scientific practice of molecular biology. Introduction 1.1 The basic questions of the information debate 1.2 The causal interpretation (CI) of biological information and Crick's ‘central dogma’ Crick's definitions of genetic information The main requirement for (CI) Types of causation in molecular biology 4.1 Structural causation in molecular biology 4.2 Nucleic acids as correlative causal factors The ‘central dogma’ without the notion of information Concluding remarks This is a new version of this article as there were errors in the abstract and full text in the previous version. (shrink)

How to interpret the “molecular gene” concept is discussed in this paper. I argue that the architecture of biological systems is hierarchical and multi-layered, exhibiting striking similarities to that of modern computers. Multiple layers exist between the genotype and system level property, the phenotype. This architectural complexity gives rise to the intrinsic complexity of the genotype-phenotype relationships. The notion of a gene being for a phenotypic trait or traits lacks adequate consideration of this complexity and has limitations in (...) explaining the genotype-phenotype relationships. I explore ways toward an integrative interpretation of the gene in the context of multi-layered biological systems. A gene, I argue, should be interpreted as a functional unit that is responsible for the trans-generation passage of the capacity to dynamically produce a biochemical activity or biochemical activities. At the molecular level, a gene is a genetic unit, a stretch of DNA sequence, which dictates the behavior and the dynamic production of the encoded cellular component(s). Embedded in a gene’s quadruple DNA code are the regulatory signals, such as those for RNA splicing and/or editing, as well as for transcription factor binding. A regulatory signal can be recognized by the gene expression machinery in one state, but not in another. The confusion caused by RNA splicing, editing, and a gene’s selective tissue distribution pattern is addressed. Instead of a context-dependent definition of the gene, I argue for the view that it is the same gene displaying multiple meanings, subject to differential interpretation by the cellular machinery in different states. In other words, the same gene gives rise to different products and expression levels under different conditions. (shrink)

Ancient DNA has been discovered in many types of preserved biological material, including bones, mummies, museum skins, insects in amber and plant fossils, and has become an important research tool in disciplines as diverse as archaeology, conservation biology and forensic science. In archaeology, ancient DNA can contribute both to the interpretation of individual sites and to the development of hypotheses about past populations. Site interpretation is aided by DNA‐based sex typing of fragmentary human bones, and by the use of (...) genetic techniques to assess the degree of kinship between the remains of different individuals. On a broader scale, population migrations can be traced by studying genetic markers in ancient DNA, as in recent studies of the colonisation of the Pacific islands, while ancient DNA in preserved plant remains can provide information on the development of agriculture. (shrink)

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology (...) and ‘transcends’ its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology (...) and ‘transcends’ its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

1900 was a remarkable year for science. Several ground-breaking events took place, in physics, biology and psychology. Planck introduced the quantum concept, the work of Mendel was rediscovered, and Sigmund Freud published The Interpretation of Dreams . These events heralded the emergence of completely new areas of inquiry, all of which greatly affected the intellectual landscape of the 20 th century, namely quantum physics, genetics and psychoanalysis. What do these developments have in common? Can we discern a family likeness, a (...) basic affinity between them, so that we can use the one to deepen our understanding of the other? One common denominator is that they open up realms of inquiry that are significantly different from the world of everyday experience, namely the realm of elementary particles, of genes and genomes, and of the unconscious. But to what extent can we meaningfully argue, for instance, that the genome is the biological unconscious, and the unconscious the psychic genome? To address these questions, I will build on the work of two key intellectual figures who have explored the affinities of these developments in depth, namely Erwin Schrödinger (a quantum physicist and avid reader of Schopenhauer who initiated molecular biology) and Jacques Lacan (who reframed the specificity of psychoanalysis with the help of 20 th century science: the era of structural linguistics, but also of quantum physics, molecular biology, bioinformatics and DNA). (shrink)

In the debate on causal explanation in biology, in the past two decades largely influenced by the new mechanist approach, the concept of a pathway has recently reemerged as a promising research agenda, 551-572, 2018; The British Journal for the Philosophy of Science, 72, 131-158, 2021). Ross’ account of biological explanation differentiates several autonomous types of causal structures that play explanatory and other roles across the life sciences. NM, however, prioritizes mechanisms as vehicles of biological explanations. According to (...) this program, the causal architecture of biological pathways and other causal structures, such as cascades and processes, can be interpreted with at least one of the NM’s mechanism concepts. In other words, these alternative causal structures are not sufficiently distinctive to merit the explanatory autonomy with regard to the NM corresponding concepts. We examine the explanatory practice of molecular biology and concur with Ross that there are indeed distinct types of causal structures, not all falling under the concept of a mechanism. Nonetheless, we show that the concept of mechanism is referring to a privileged causal structure, at the center of explanatory efforts in molecular biology. Pathways and other causal concepts, while somewhat distinct from mechanisms themselves, are explanatorily relevant to the degree in which they exhibit mechanistic features, are parts of a mechanistic architecture, or may lead to a mechanistic arrangement. What emerges in that manner is a hierarchy of causal structures with mechanisms at the explanatory top, and lower levels differing in the degree in which they contribute to mechanistic arrangements. (shrink)

The article reconciles contentious issues between code biology and biosemiotics. The framework of semantic biology and molecular meaning woven around organic codes by Marcello Barbieri defied classical informational conceptualizations of meaning in the biological realm while the discourse on meaning and agency and their respective (in)dependency on interpretation continues. Whereas the role of codes in agency is often secondary to other aspects, I present here a more consistent picture– integrating codes and artifacts to smoothly transcend from the world (...) of mechanistic molecular meaning to organismic agency. Interpretation is presented as a call-to-action based on intraindividual states, and sense-making as call-to-change based on interindividual communication. (shrink)

Although molecular systematists may use the terminology of cladism, claiming that the reconstruction of phylogenetic relationships is based on shared derived states , the latter is not the case. Rather, molecular systematics is based on the assumption, first clearly articulated by Zuckerkandl and Pauling , that degree of overall similarity reflects degree of relatedness. This assumption derives from interpreting molecular similarity between taxa in the context of a Darwinian model of continual and gradual change. Review of the (...) history of molecular systematics and its claims in the context of molecular biology reveals that there is no basis for the “molecular assumption.”. (shrink)

In the last decades, Systems Biology (including cancer research) has been driven by technology, statistical modelling and bioinformatics. In this paper we try to bring biological and philosophical thinking back. We thus aim at making diferent traditions of thought compatible: (a) causality in epidemiology and in philosophical theorizing—notably, the “sufcient-component-cause framework” and the “mark transmission” approach; (b) new acquisitions about disease pathogenesis, e.g. the “branched model” in cancer, and the role of biomarkers in this process; (c) the burgeoning of (...) omics research, with a large number of “signals” and of associations that need to be interpreted. In the paper we summarize frst the current views on carcinogenesis, and then explore the relevance of current philosophical interpretations of “cancer causes”. We try to ofer a unifying framework to incorporate biomarkers and omic data into causal models, referring to a position called “evidential pluralism”. According to this view, causal reasoning is based on both “evidence of diference-making” (e.g. associations) and on “evidence of underlying biological mechanisms”. We conceptualize the way scientists detect and trace signals in terms of information transmission, which is a generalization of the mark transmission theory developed by philosopher Wesley Salmon. Our approach is capable of helping us conceptualize how heterogeneous factors such as micro and macro-biological and psycho-social—are causally linked. This is important not only to understand cancer etiology, but also to design public health policies that target the right causal factors at the macro-level. (shrink)

I will relate some social and epistemic aspects involved in the conceptual development of the genetic model in the early Molecular Biology. I will use the link between Biology and Physics as a framework, which supports such assumptions, providing new methodologies, but mainly as a framework that provides a model of objectivity developed within Modern Tradition. Finally, I will interpret this relationship from the pragmatist perspective to embrace Rorty’s thesis on «the ontological priority of the social» which implies understanding (...) biology as a part of a general cultural politics. (shrink)

The sequence of nucleotide bases occurring in an organism’s DNA is often regarded as a codescript for its construction. However, information in a DNA sequence can only be regarded as a codescript relative to an operational biochemical machine, which the information constrains in such a way as to direct the process of construction. In reality, any biochemical machine for which a DNA codescript is efficacious is itself produced through the mechanical interpretation of an identical or very similar codescript. In these (...) terms the origin of life can be described as a bootstrap process involving the simultaneous accumulation of genetic information and the generation of a machine that interprets it as instructions for its own construction. This problem is discussed within the theoretical frameworks of thermodynamics, informatics and self-reproducing automata, paying special attention to the physico-chemical origin of genetic coding and the conditions, both thermodynamic and informatic, that a system must fulfil in order for it to sustain semiosis. The origin of life is equated with biosemiosis. (shrink)

This paper explores the epistemology of extrapolation from model organisms to humans in molecular medicine. We take into account two common views on the issue, the homology view and the disanalogy view. In response to both interpretations, we argue that the foundational basis of extrapolations cannot simply be provided by homology and that relevant disanalogies can, thanks to the techniques of molecular biology, be experimentally controlled and exploited to allow useful and reliable extrapolations. The case of "humanised mice" (...) in the context of cancer stem cell research provides evidence of how animal models can be construed to approximate bona fide causal analogue models of human diseases. To supplement this view we show how the epistemology of model organisms needs to take into account the engineering side of molecular medicine. Model organisms are often manipulated to create analogies or remove disanalogies with the target system. We maintain that highlighting this feature is fundamental to explain what warrants extrapolation in the search for the molecular causes of disease. (shrink)

Scientific knowledge production is currently affected by the dissemination of data on an unprecedented scale. Technologies for the automated production and sharing of vast amounts of data have changed the way in which data are handled and interpreted in several scientific domains, most notably molecular biology and biomedicine. In these fields, the activity of data gathering has become increasingly technology-driven, with machines such as next generation genome sequencers and mass spectrometers generating billions of data points within hours, and with (...) little need for human supervision. Given the relative ease and low costs with which datasets can be produced (that is, once a laboratory has been able to afford .. (shrink)

Reductionism concerns a set of ontological and epistemological claims, and methodological strictures based on them, about the relationship between two different scientific domains. The critical assumption is that one of these domains is privileged over the other in the sense that the concepts, rules, laws, and other elements of the privileged domain can be used to specify, constitute, or account for those of the other “reduced” domain. This specification often consists of explanation, such that the “reducing” domain is epistemically privileged (...) over the reduced one. Explanations of this type are “reductionist” (or, are “reductions”) and reductionism is then the thesis that such explanations will always be forthcoming or at least are possible in principle. Reductionism is most plausible if the entities of the reduced domain can be interpreted as arising from (e.g., as aggregates of) entities of the reduced domain. This ontological claim is controversial but motivates many reductionist theses and associated scientific research programs. Thus, epistemological and ontological claims about reductionism have the methodological implication that they should govern and guide scientific research. When such research proves to be fruitless over a period of time, the associated reductionist claims themselves become suspect. Although issues connected with reductionism arise in the physical and social sciences, most attention to reductionism in philosophy of science over the last few decades has focused on the biological sciences, especially after the advent of molecular biology made it plausible to believe that biological phenomena can be uniformly explained (in detail) from their physical basis. However, the program of finding such explanations has a long philosophical history often couched in terms of seeking “mechanical,” “mechanistic,” or “materialistic” explanations. The contrast here is with traditional vitalism and various forms of teleology and holism. (shrink)

In this paper, I will reread the history of molecular genetics from a psychoanalytical angle, analysing it as a case history. Building on the developmental theories of Freud and his followers, I will distinguish four stages, namely: (1) oedipal childhood, notably the epoch of model building (1943–1953); (2) the latency period, with a focus on the development of basic skills (1953–1989); (3) adolescence, exemplified by the Human Genome Project, with its fierce conflicts, great expectations and grandiose claims (1989–2003) and (...) (4) adulthood (2003–present) during which revolutionary research areas such as molecular biology and genomics have achieved a certain level of normalcy—have evolved into a normal science. I will indicate how a psychoanalytical assessment conducted in this manner may help us to interpret and address some of the key normative issues that have been raised with regard to molecular genetics over the years, such as ‘relevance’, ‘responsible innovation’ and ‘promise management’. (shrink)

Boltzmann's gas model representing the second law of thermodynamics is based on the improbability of certain molecular distributions in space. Maxwell argued that a hypothetical ‘being’ with the faculty of seeing individual molecules could bring about such improbable distributions, thus violating the law of entropy. However, it appears that to render the molecules visible for any observer would increase the entropy more than the demon could decrease it, hence ‘Maxwell's Demon cannot operate’ . In the study presented here Maxwell's (...) Demon is interpreted in a general way as a biological observer system within systems which can upset thermodynamic probabilities provided that the relative magnitudes between observer system and observed system are appropriate.Maxwell's Demon within Boltzmann's Gas Model thus appears only as a special case of inappropriate, relative magnitude between the two systems. (shrink)

In the advertising discourse of human genetic database projects, of genetic ancestry tracing companies, and in popular books on anthropological genetics, what I refer to as the anthropological gene and genome appear as documents of human history, by far surpassing the written record and oral history in scope and accuracy as archives of our past. How did macromolecules become "documents of human evolutionary history"? Historically, molecular anthropology, a term introduced by Emile Zuckerkandl in 1962 to characterize the study of (...) primate phylogeny and human evolution on the molecular level, asserted its claim to the privilege of interpretation regarding hominoid, hominid, and human phylogeny and evolution vis-à-vis other historical sciences such as evolutionary biology, physical anthropology, and paleoanthropology. This process will be discussed on the basis of three key conferences on primate classification and evolution that brought together exponents of the respective fields and that were held in approximately ten-years intervals between the early 1960s and the 1980s. I show how the anthropological gene and genome gained their status as the most fundamental, clean, and direct records of historical information, and how the prioritizing of these epistemic objects was part of a complex involving the objectivity of numbers, logic, and mathematics, the objectivity of machines and instruments, and the objectivity seen to reside in the epistemic objects themselves. (shrink)

This paper examines the history of animal behavior studies after the synthesis period. Three episodes are considered: the adoption of the theory of natural selection, the mathematization of ideas, and the spread of molecular methods in behavior studies. In these three episodes, students of behavior adopted practices and standards developed in population ecology and population genetics. While they borrowed tools and methods from these fields, they made distinct uses that set them relatively apart and led them to contribute, in (...) their own way, to evolutionary theory. These episodes also highlight some limitations of “conjunction narratives” centered on the relation between a discipline and the modern synthesis. A trend in conjunction narratives is to interpret any development related to evolution in a discipline as an “extension,” an “integration,” or as a “delayed” synthesis. I here suggest that this can lead to underestimate discontinuities in the history of evolutionary biology. (shrink)

The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a (...) strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology. (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)

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed (...) by homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed (...) by homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

What sets someone on a life trajectory? This question is at the heart of studies of 21st-century neurosciences that build on scientific models developed over the last 150 years that attempt to link psychopathology risk and human development. Historically, this research has documented persistent effects of singular, negative life experiences on people’s subsequent development. More recently, studies have documented neuromolecular effects of early life adversity on life trajectories, resulting in models that frame lives as disproportionately affected by early negative experiences. (...) This view is dominant, despite little evidence of the stability of the presumably early-developed molecular traits and their potential effects on phenotypes. We argue that in the context of gaps in knowledge and the need for scientists to reason across molecular and phenotypic scales, as well as time spans that can extend beyond an individual’s life, specific interpretative frameworks shape the ways in which individual scientific findings are assessed. In the process, scientific reasoning oscillates between understandings of cellular homeostasis and organisms’ homeorhesis, or life trajectory. Biologist and historian François Jacob described this framework as the “attitude” that researchers bring to bear on their “objects” of study. Through an analysis of, first, historical and contemporary scientific literature and then ethnographic research with neuroscientists, we consider how early life trauma came to be associated with specific psychological and neurobiological effects grounded in understandings of life trajectories. We conclude with a consideration of the conceptual, ontological, and ethical implications of interpreting life trajectories as the result of the persistence of long-embodied biological traits, persistent life environments, or both. (shrink)

In this dissertation I address three philosophical problems in the philosophy of biology united by the underlying, and interlocking, issues of the explanatory role of teleological, normative, and representational concepts in biology. In the first chapter, I argue that extant accounts of functions have foundered on a problem I dub the Dysfunction Dilemma, and I offer a way to move forward. Functions are of philosophical interest because the concept plays an important explanatory role in biology, and other sciences, but is (...) apparently teleological and normative –an item’s function is its end, purpose, or goal, and a dysfunctional item is one that fails to realize a particular norm, performance of its proper function. Extant accounts of function do not successfully capture both its explanatory import and its normative and teleological character, either painting dysfunction as conceptually incoherent or painting functions as epiphenomenal. I diagnose the source of the dilemma and offer an account of functional explanation which avoids it. In the second chapter, I defend the idea that genes, like words or concepts, have intentionality or representational/semantic content. First, I argue that while the standard motivation for this idea is mechanistic analogies between molecular mechanisms and digital computation, Ernst Mayr, one of the architects of the modern synthesis in biology, has provided an alternative and more defensible justification for taking the idea seriously. Parallel to the standard case for representational and computational theories of cognition, Mayr’s justification rests on the need to invoke representations to explain end-directed processes. I then put Mayr’s argument to work answering three kinds of objection to the idea that genes are representational: 1) Genetic representations are causally or explanatorily inert, 2) Genetic processes are too complex and context sensitive to be captured by representational concepts, and 3) Details of molecular biology undermine representational conceptions of genes. In the final chapter, I develop a historical and philosophical interpretation of Ernst Mayr’s distinction between proximate and ultimate causes and its relation to Niko Tinbergen’s "four questions." Both frameworks have been influential in the biological study of behavior and are typically presented as a single framework, with Mayr’s proximate-ultimate distinction corresponding to one of two axes dividing Tinbergen’s four questions. I argue that this interpretation misrepresents Mayr’s and Tinbergen’s philosophical positions. I offer a positive account of both frameworks and their relation to one another, and I argue that contrary to many critics, Mayr’s proximate-ultimate distinction, when properly interpreted, does not present a barrier to the project of integrating biological work on Tinbergen’s four questions. (shrink)

In this paper we criticize the “Ashbyan interpretation” (Froese & Stewart, 2010) of autopoietic theory by showing that Ashby’s framework and the autopoietic one are based on distinct, often incompatible, assumptions and that they aim at addressing different issues. We also suggest that in order to better understand autopoiesis and its implications, a different and wider set of theoretical contributions, developed previously or at the time autopoiesis was formulated, needs to be taken into consideration: among the others, the works of (...) Rosen, Weiss and Piaget. By analyzing the concepts of organization and closure, the idea of components, and the role of materiality in the theory proposed by Maturana and Varela, we advocate the view that autopoiesis necessarily entails self-production and intrinsic instability and can be realized only in domains characterized by the same transformative and processual properties exhibited by the molecular domain. From this theoretical standpoint it can be demonstrated that autopoietic theory neither commits to a sharp dualism between organization and structure nor to a reflexive view of downward causation, thus avoiding the respective strong criticisms. (shrink)

Advances in molecular biology have generally been taken to support the claim that biology is reducible to chemistry. I argue against that claim by looking in detail at a number of central results from molecular biology and showing that none of them supports reduction because (1) their basic predicates have multiple realizations, (2) their chemical realization is context-sensitive and (3) their explanations often presuppose biological facts rather than eliminate them. I then consider the heuristic and confirmational implications (...) of irreducibility and argue that purely biochemical approaches are likely to be unsound and to be unable to confirm an important range of statements. I conclude by sketching criteria for scientific unity that do not entail reducibility and yet leave an important place for identifying underlying mechanisms. Molecular biology, properly understood, provides an excellent paradigm of non-reductive unity between different explanatory levels. (shrink)

We draw on Short’s work on Peirce’s theory of signs to propose a new general definition of interpretation. Short argues that Peirce’s semiotics rests on his naturalised teleology. Our proposal extends Short’s work by modifying his definition of interpretation so as to make it more generally applicable to putatively interpretative processes in biological systems. We use our definition as the basis of an account of different kinds of misinterpretation and we discuss some questions raised by the definition by reference (...) to parallel problems in the field of teleosemantics. We propose that interpretative responses fulfilling the criteria of our definition may be made by relatively simple molecular entities and we suggest two specific empirical applications of the definition to experimental work in the field of origin of life research. Our wider aim is to suggest that a well formulated naturalistic definition of interpretation will allow a re-evaluation of the role of semiotic phenomena in biological systems, including the generation of empirically testable hypotheses. (shrink)

Causal complexities involved in biological phenomena often generate ambiguous experimental results that may create epistemic niches for new approaches and interpretations. The exploration for new approaches may foment momentum of larger epistemological shifts, and thereby introduce the possibilities of adopting new technologies. This paper describes British molecular biologist Robin Holliday’s cell aging research from 1963 to the 1980s that transformed from simple hypothesis testing to working on various alternative and integrative approaches designed to deal with complex data. In (...) the 1960s, hoping to use biochemical investigations of cells to settle a debate about whether DNA mutations or protein errors caused aging, Holliday carried out a series of experiments with fruit flies, fungi, and human fibroblast cells. The results seemed to demonstrate that cytoplasmic protein errors caused cell aging. However, other scientists obtained contradictory results and raised issues about potential flaws in Holliday’s experiments. In the 1970s, working as the director of the Genetics Division of the National Institute for Medical Research in Mill Hill, United Kingdom, Holliday relied on available talents of his associates, including computational expertise, to explore alternative hypotheses and approaches. By the early 1980s, they had worked out an epigenetic explanation and had established integrative, evolutionary models of cell aging that incorporated both DNA mutations and protein errors as critical factors. By delineating Holliday’s research path from simply testing hypotheses to integrating multiple factors involved in aging, this paper offers an account of the difficulties in targeting molecular cause in cell aging around the 1970s, whose failures nevertheless opened up an epistemic niche for integration. (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)

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome‐wide association studies map to non‐protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non‐coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the (...) in‐depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome‐editing techniques including CRISPR/Cas9. These approaches are also applicable to low‐frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. (shrink)

In light of scientific advances such as genomics, predictive diagnostics, genetically engineered agriculture, nuclear transfer cloning, and the manipulation of stem cells, the idea that genes carry predetermined molecular programs or blueprints is pervasive. Yet new scientific discoveries—such as rna transcripts of single genes that can lead to the production of different compounds from the same pieces of dna—challenge the concept of the gene alone as the dominant factor in biological development. Increasingly aware of the tension between certain (...) empirical results and interpretations of those results based on the orthodox view of genetic determinism, a growing number of scientists urge a rethinking of what a gene is and how it works. In this collection, a group of internationally renowned scientists present some prominent alternative approaches to understanding the role of dna in the construction and function of biological organisms. Contributors discuss alternatives to the programmatic view of dna, including the developmental systems approach, methodical culturalism, the molecular process concept of the gene, the hermeneutic theory of description, and process structuralist biology. None of the approaches cast doubt on the notion that dna is tremendously important to biological life on earth; rather, contributors examine different ideas of how dna should be represented, evaluated, and explained. Just as ideas about genetic codes have reached far beyond the realm of science, the reconceptualizations of genetic theory in this volume have broad implications for ethics, philosophy, and the social sciences. Contributors. Thomas Bürglin, Brian C. Goodwin, James Griesemer, Paul Griffiths, Jesper Hoffmeyer, Evelyn Fox Keller, Gerd B. Müller, Eva M. Neumann-Held, Stuart A. Newman, Susan Oyama, Christoph Rehmann-Sutter, Sahotra Sarkar, Jackie Leach Scully, Gerry Webster, Ulrich Wolf. (shrink)

This article looks at Deleuze and Guattari's understanding of molecular biology, focusing particularly on their reading of two highly influential works by the eminent French molecular biologists François Jacob and Jacques Monod, La logique du vivant and Le hasard et la nécessité. In these two works, Jacob and Monod present the significance of molecular biology in broadly reductionist terms. What is more, the lac operon model of gene regulation that they propose serves to reinforce the so-called Central (...) Dogma of molecular biology, according to which information passes from DNA to RNA to proteins, with no reverse route. However, Deleuze and Guattari discover intensive potentials within the descriptions of molecular biology offered by both writers. It is argued that Jacob's work in particular, as it has developed in the years since the publication of La logique du vivant in 1970, has itself developed these intensive potentials. (shrink)

This book is divided in two parts, the first of which shows how, beyond paleontology and systematics, macroevolutionary theories apply key insights from ecology and biogeography, developmental biology, biophysics, molecular phylogenetics, and even the sociocultural sciences to explain evolution in deep time. In the second part, the phenomenon of macroevolution is examined with the help of real life-history case studies on the evolution of eukaryotic sex, the formation of anatomical form and body-plans, extinction and speciation events of marine invertebrates, (...) hominin evolution and species conservation ethics. The book brings together leading experts, who explain pivotal concepts such as Punctuated Equilibria, Stasis, Developmental Constraints, Adaptive Radiations, Habitat Tracking, Turnovers, (Mass) Extinctions, Species Sorting, Major Transitions, Trends, and Hierarchies – key premises that allow macroevolutionary epistemic frameworks to transcend microevolutionary theories that focus on genetic variation, selection, migration and fitness. Along the way, the contributing authors review ongoing debates and current scientific challenges; detail new and fascinating scientific tools and techniques that allow us to cross the classic borders between disciplines; demonstrate how their theories make it possible to extend the Modern Synthesis; present guidelines on how the macroevolutionary field could be further developed; and provide a rich view of just how it was that life evolved across time and space. In short, this book is a must-read for active scholars and, because the technical aspects are fully explained, it is also accessible for non-specialists. Understanding evolution requires a solid grasp of above-population phenomena. Species are real biological individuals, and abiotic factors impact the future course of evolution. Beyond observation, when the explanation of macroevolution is the goal, we need both evidence and theory that enable us to explain and interpret how life evolves at the grand scale. (shrink)

The emphasis on the organization of entities and their activities and interactions has been labeled one of the most distinct contributions of mechanistic philosophy. In this paper I discuss the manner in which the organization of entities and their activities and interactions participates in bringing about phenomena. I present a well-known example from molecular biology—the functioning of the genetic switch in phage lambda—and discuss Marco J. Nathan’s notion of causation by concentration. Nathan introduces causation by concentration to account for (...) the irreducible causal role that the concentration ratio between two kinds of proteins possesses in the genetic switch mechanism in phage lambda. I discuss what the irreducibility of this causal role amounts to and provide a mechanistic interpretation of Nathan’s causation by concentration; that is, I explain this irreducible causal role as one organizational feature of this mechanism. The paper concludes that biological mechanisms need a causal pluralist framework [similar to Glennan’s account in, and but slightly modified] where organizational features such as the concentration ratio have a causally relevant role, yet all the causally productive relations occur at the level of entities or individuals. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims of data science (...) (machine learning in particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

I offer a defense, albeit a qualified one, of machine analogies in biology, focusing on molecular contexts. The defense is rooted in my prior work (Levy in Philosopher’s Imprint 14(6), 2014), which construes the machine machine-likeness of a system as a matter of the extent to which it exhibits an internal division of labor. A concrete aim is to shore up the notion of molecular biological machines, paying special attention to processive molecular motors, such as Kinesin. (...) But I will also try to show how the division of labor account gives us guidance more broadly, both about where and why machine analogies can be expected to prove helpful and about their limitations. (shrink)

Systems biology is the rapidly growing and heavily funded successor science to genomics. Its mission is to integrate extensive bodies of molecular data into a detailed mathematical understanding of all life processes, with an ultimate view to their prediction and control. Despite its high profile and widespread practice, there has so far been almost no bioethical attention paid to systems biology and its potential social consequences. We outline some of systems biology's most important socioethical issues by contrasting the concept (...) of systems as dynamic processes against the common static interpretation of genomes. New issues arise around systems biology's capacities for in silico testing, changing cultural understandings of life, synthetic biology, and commercialization. We advocate an interdisciplinary and interactive approach that integrates social and philosophical analysis and engages closely with the science. Overall, we argue that systems biology socioethics could stimulate new ways of thinking about socioethical studies of life sciences. (shrink)

The idea that the world is made of particles — little discrete, interacting objects that compose the material bodies of everyday experience — is a durable one. Following the advent of quantum theory, the idea was revised but not abandoned. It remains manifest in the explanatory language of physics, chemistry, and molecular biology. Aside from its durability, there is good reason for the scientific realist to embrace the particle interpretation: such a view can account for the prominent epistemic fact (...) that only limited knowledge of a portion of the material universe is needed in order to make reliable predictions about that portion. Thus, particle interpretations can support an abductive argument from the epistemic facts in favor of a realist reading of physical theory. However, any particle interpretation with this property is untenable. The empirical adequacy of modern particle theories requires adoption of a postulate known as permutation invariance — the claim that interchanging the role of two particles of the same kind in a dynamical state description results in a description of the identical state. It is the central claim of this essay that PI is incompatible with any particle interpretation strong enough to account for the epistemic facts. This incompatibility extends across all physical theories. To frame and motivate the inconsistency argument, I begin by fixing the relevant notion of particle. To single out those accounts of greatest appeal to the realist, I develop the logically weakest particle ontology that entails the epistemic fact that the world is piecewise predictable, an ontology I call ‘minimal atomism’. The entire series of scientific conceptions of the particle, from Newton’s mechanically interacting corpuscles to the ‘centers of force’ in classical field theories, all comport with MA. As long as PI is left out, even quantum mechanics can be viewed this way. To assess the impact of PI on this picture, I present a framework for rigorously connecting interpretations to physical theories. In particular, I represent MA as a set of formal conditions on the models of physical theories, the mathematical structures taken to represent states of the world. I also formulate PI — originally introduced as a postulate of non-relativistic quantum mechanics — in theory independent terms. With all of these pieces in hand, I am then able to present a proof of the inconsistency of PI and MA. In the second part of the essay, I survey responses to the inconsistency result open to the scientific realist. The two most plausible approaches involve abandoning particles in one way or another. The first alternative interpretation considered takes the property bearing objects of the world to be regions of space rather than particles. In this view, the properties once attributed to particles in quantum states are attributed instead to one or more regions of space. PI no longer obtains in this case, at least not as a statement about the permutation symmetry of property bearers. Rather, the new interpretation naturally imposes an analogous constraint on quantum states. The second major approach to evading the inconsistency result is to dispense with objects altogether. This is the recommendation of so-called ‘Ontic Structural Realism’. The central OSR thesis is that structure rather than entities are the basic ontological components of the world. OSR is intended to embrace the ‘miracle’ argument in favor of scientific realism while avoiding the pessimistic meta-induction. I demonstrate that one principal motivation for OSR based on the under-determination of interpretations in QM is actually dissolved by the incompatibility result. At the same time, I suggest reasons to think that OSR fares no better with respect to the pessimistic meta-induction than traditional realism does. Thus, while PI and MA may be incompatible, object ontologies remain the best option for the realist. (shrink)

Nerve cells - neurons - are arguably the most complex of all cells. From the action of these cells comes movement, thought and consciousness. It is a challenging task to understand what molecules direct the various diverse aspects of their function. This has produced an ever-increasing amount of molecular information about neurons, and only in Molecular Biology of the Neuron can a large part of this information be found in one source. In this book, a non-specialist can learn (...) about the molecules that control information flow in the brain or the progress of brain disease in an approachable format, while the expert has access to a wealth of detailed information from a wide range of topics impacting on his or her field of endeavour. The text is designed to achieve a balance of accessibility and broad coverage with up-to-date molecular detail. In the six years since the first edition of Molecular Biology of the Neuron there has been an explosion in the molecular information about neurons that has been discovered, and this information is incorporated into this second edition. Entirely new chapters have been introduced where recent advances have made a new aspect of neuronal function more comprehensible at the molecular level. Written by leading researchers in the field, the book provides an essential overview of the molecular structure and function of neurons, and will be an invaluable tool to students and researchers alike. (shrink)

Neurons are arguably the most complex of all cells. From the action of these cells comes movement, thought and consciousness. It is a challenging task to understand what molecules direct the various diverse aspects of their function. This has produced an ever-increasing amount of molecular information about neurons, and only in Molecular Biology of the Neuron can a large part of this information be found in one source. In this book, a non-specialist can learn about the molecules that (...) control information flow in the brain or the progress of brain disease in an approachable format, while the expert has access to a wealth of detailed information from a wide range of topics impacting on his or her field of endeavour. The text is designed to achieve a balance of accessibility and broad coverage with up-to-date molecular detail. In the six years since the first edition of Molecular Biology of the Neuron there has been an explosion in the molecular information about neurons that has been discovered, and this information is incorporated into this second edition. Entirely new chapters have been introduced where recent advances have made a new aspect of neuronal function more comprehensible at the molecular level. Written by leading researchers in the field, the book provides an essential overview of the molecular structure and function of neurons, and will be an invaluable tool to students and researchers alike. (shrink)

The first part of this paper has shown that the development of regulatory genetics and the lactose operon model stemmed from laboratory cultures rooted in local traditions. A "physiological" culture may be recognized in the Pasteurian context. The institutional continuity provided the basis for a tenuous link between Pasteur, Lwoff, and Monod. My claim is that the "national" value of regulatory and physiological genetics is an artifact produced in the course of the legitimization process accompanying the institutionalisation of the discipline. (...) In the 1960s, the lactose operon model was turned into a "flag-object," a symbol of the new culture. The work done by the Pasteurian group became therefore the most important, if not the only, exemplar of molecular biology in France.The second part o f the paper described the origins of general patterns that dominated the building of molecular biology in France. The study of the relationships between molecular biologists and biochemists or immunologists revealed the existence of alternatives to the development of operon research, or to the convergence with molecular biology. Both examples uncover specific paths leading to achievements that might be viewed as international trends: the expansion of RNA and translation studies, and the development of cellular immunology. They illustrate two possible patterns of linking local settings and disciplinary traditions: an oligopolistic situation where a few groups or one institution dominate an entire field, and the emergence of "collective" trends through collaboration networks or schools. (shrink)

The intellectual origins of molecular biology are usually traced back to the 1930s. By contrast, molecular biology acquired a social reality only around 1960. To understand how it came to designate a community of researchers and a professional identity, I examine the creation of the first institutes of molecular biology, which took place around 1960, in four European countries: Germany, the United Kingdom, France, and Switzerland. This paper shows how the creation of these institutes was linked to (...) the results of post-war economic reconstruction. Then, it compares how the promoters of these different institutional projects delimited the goals of their discipline, reflected on its history, and suggested how research should be organised. I show how they carefully positioned their new discipline within the emerging national science policy discourse of the 1950s, and aligned it with the current vision of scientific modernity. In particular, I discuss how they articulated the meaning of molecular biology with respect to five common themes: the role of physics in the atomic age, the relations between fundamental research and medical applications, the 'Americanisation' of scientific research, the value of science in the reconstruction of national identities, and the drive towards interdisciplinary research. This paper thus demonstrates that beyond the local and national accounts there is a European history of molecular biology. (shrink)