The rapidly changing field of genetics affects society through advances in health-care and through implications of genetic research. This study addresses the impacts of new genetic discoveries and technologies on different segments of today's society. The book begins with a chapter on genetic complexity, and subsequent chapters discuss moral and ethical questions arising from today's genetics from the perspectives of health care professionals, the media, the general public, special interest groups and commercial interests.

Without directly addressing the Demarcation Problem for logic—the problem of distinguishing logical vocabulary from others—we focus on distinctive aspects of logical vocabulary in pursuit of a second goal in the philosophy of logic, namely, proposing criteria for the justification of logical rules. Our preferred approach has three components. Two of these are effectively Belnap’s, but with a twist. We agree with Belnap’s response to Prior’s challenge to inferentialist characterisations of the meanings of logical constants. Belnap argued that for a logical (...) constant to exist, its rules must be conservative over a previously given consequence relation and guarantee the uniqueness of the constant. The twist is that we require logical vocabulary to be provably conservative, not over a previously given formal consequence relation, but over a previously given meaningful vocabulary of a language. Uniqueness is also a feature defined in terms of provability: if two syntactically distinguished expressions are governed by the same rules, then formulas with them as main operators are interderivable. Belnap’s criteria are not only those for the existence of a logical constant, but more: they are what distinguishes logical vocabulary from all other expressions. It is the defining mark of a logical constant that it is provably conservative over the fragment of the language which excludes it and that its rules guarantee its uniqueness. The third component is the topic neutrality of logic. The provable conservativeness of logic over a previously given vocabulary of a language is motivated, in part, by appeal to molecularism in the theory of meaning. Molecularity is a feature endorsed by the theory of meaning as a whole, so it does not distinguish logical constants from other expressions. The same is true for conservativeness. We argue that molecularity, and hence conservativeness, are implicit presuppositions of speakers’ use of language: the addition of new vocabulary to a language is presupposed to be conservative. But this presupposition is one that we should be able reflectively to endorse (such as when attempting a rational reconstruction of the use of the vocabulary). Thus, where conservativeness is found to fail, this defect should be remedied and the use of the vocabulary corrected (as in classical negation) or excised altogether (as in pejoratives). We go on to characterise a notion of topic neutrality, which we argue applies to logical vocabulary. We then note that reflective endorsement of the conservativeness of a topic neutral vocabulary requires a proof that the vocabulary is conservative relative to any base vocabulary. Thus we require that logical vocabulary be demonstrably conservative. Allying this requirement, distinctive of logic, to a general consideration about the commitments of assertion yields a mode of justification for logical constants akin to some conceptions of Harmony, i.e., to the idea that the consequences of assertion of a logical complex need to be warranted by the grounds and ought to be the strongest consequences warranted by the grounds. Intuitionistic logic acquires a somewhat familiar justification but emanating from a new motivation. (shrink)

This chapter contains section titled: The Neutral Theory of Molecular Evolution The Molecular Clock The Neutral Null Model Controversy in Molecular Evolution Acknowledgment References Further Reading.

There is consensus within the chemosciences that olfactory perception is of the molecular structure of chemical compounds, yet within philosophical theories of smell there is little agreement about the nature of smell. The paper critically assesses the current state of debate regarding smells within philosophy in the hopes of setting it upon firm scientific footing. The theories to be covered are: Naïve Realism, Hedonic Theories, Process Theory, Odor Theories, and non-Objectivist Theories. The aforementioned theories will be evaluated based on (...) their explanations of the (a) the olfactory quality of a smell, (b) smells as distal entities, and (c) our experience of smells as intentional objects. The paper concludes with a defense of Molecular Structure Theory that demonstrating its superiority in accounting for each of these three aspects of smell. (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)

Biologists and historians often present natural history and molecular biology as distinct, perhaps conflicting, fields in biological research. Such accounts, although supported by abundant evidence, overlook important areas of overlap between these areas. Focusing upon examples drawn particularly from systematics and molecular evolution, I argue that naturalists and molecular biologists often share questions, methods, and forms of explanation. Acknowledging these interdisciplinary efforts provides a more balanced account of the development of biology during the post-World War II era.

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)

Chords are not pure sets of tones or notes. They are mainly characterized by their matrices. A chord matrix is the pattern of all the lengths of intervals given without further context. Chords are well-structured invariants. They show their inner logical form. This opens up the possibility to develop a molecular logic of chords. Chords are our primitive, but, nevertheless, already interrelated expressions. The logical space of internal harmony is our well-known chromatic scale represented by an infinite line of (...) integers. Internal harmony is nothing more than the pure interrelatedness of two or more chords. We consider three cases: chords inferentially related to subchords, pairs of chords in the space of major–minor tonality and arbitrary chords as arguments of unary chord operators in relation to their outputs. One interesting result is that chord negation transforms any pure major chord into its pure minor chord and vice versa. Another one is the fact that the negation of chords with symmetric matrices does not change anything. A molecular logic of chords is mainly characterized by combining general rules for chord operators with the inner logical form of their arguments. (shrink)

Philosophical discussion of molecular and developmental biology began in the late 1960s with the use of genetics as a test case for models of theory reduction. With this exception, the theory of natural selection remained the main focus of philosophy of biology until the late 1970s. It was controversies in evolutionary theory over punctuated equilibrium and adaptationism that first led philosophers to examine the concept of developmental constraint. Developmental biology also gained in prominence in the 1980s as part of (...) a broader interest in the new sciences of self-organization and complexity. The current literature in the philosophy of molecular and developmental biology has grown out of these earlier discussions under the influence of twenty years of rapid and exciting growth of empirical knowledge. Philosophers have examined the concepts of genetic information and genetic program, competing definitions of the gene itself and competing accounts of the role of the gene as a developmental cause. The debate over the relationship between development and evolution has been enriched by theories and results from the new field of 'evolutionary developmental biology'. Future developments seem likely to include an exchange of ideas with the philosophy of psychology, where debates over the concept of innateness have created an interest in genetics and development. (shrink)

Recent work on gene concepts has been influenced by recognition of the extent to which RNA transcripts from a given DNA sequence yield different products in different cellular environments. These transcripts are altered in many ways and yield many products based, somehow, on the sequence of nucleotides in the DNA. I focus on alternative splicing of RNA transcripts (which often yields distinct proteins from the same raw transcript) and on 'gene sharing', in which a single gene produces distinct proteins with (...) the exact same amino acid sequence. These are instances of molecular pleiotropy, in which distinct molecules are derived from a single putative gene. In such cases the cellular and external environments play major roles in determining which protein is produced. Where there is molecular pleiotropy, alternative gene concepts are naturally deployed; molecular epigenesis (revision of sequence-based information by altering molecular conformations or by action of non-informational molecules) plays a major role in orderly development. These results show that gene concepts in molecular biology do, and should, have both structural and functional components. They also show the need for a plurality of gene concepts and reveal fundamental difficulties in stabilizing gene concepts solely by reference to nucleotide sequence. (shrink)

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries (...) to biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science. (shrink)

The paper argues against the central dogma and its interpretation by C. Kenneth Waters and Alex Rosenberg. I argue that certain phenomena in the regulation of gene expression provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. My thesis of 'molecular epigenesis' with its three classes of phenomena, sequence 'activation', 'selection', and 'creation', is exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA editing. It (...) argues that other molecular resources share the causal role of genes; the sequence specificity for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (thesis of distributed causal specificity). I conclude that the central dogma has unnecessarily restricted genetic research to the sequencing of protein-coding genes, unilinear pathway analyses, and the focus on exclusive specificity. (shrink)

Molecular Revolution in BrazilFélix Guattari and Suely Rolniktranslated by KarelClapshow and Brian HolmesYes, I believe that there is a multiple people, a people of mutants, apeople of potentialities that appears and disappears, that is embodied in social, literary, andmusical events.... I think that we're in a period of productivity, proliferation, creation, utterlyfabulous revolutions from the viewpoint of this emergence of a people. That's molecular revolution:it isn't a slogan or a program, it's something that I feel, that I live....--from (...) MolecularRevolution in BrazilFollowing Brazil's first democratic election after two decades of militarydictatorship, French philosopher Félix Guattari traveled through Brazil in 1982 with Brazilianpsychoanalyst Suely Rolnik and discovered an exciting, new political vitality. In the infancy of itsnew republic, Brazil was moving against traditional hierarchies of control and totalitarian regimesand founding a revolution of ideas and politics. Molecular Revolution in Brazil documents theconversations, discussions, and debates that arose during the trip, including a dialogue betweenGuattari and Brazil's future President Luis Ignacia Lula da Silva, then a young gubernatorialcandidate. Through these exchanges, Guattari cuts through to the shadowy practices of globalizationgone awry and boldly charts a revolution in practice.Assembled and edited by Rolnik, MolecularRevolution in Brazil is organized thematically; aphoristic at times, it presents a lesser-known,more overtly political aspect of Guattari's work. Originally published in Brazil in 1986 asMicropolitica: Cartografias do desejo, the book became a crucial reference for political movementsin Brazil in the 1980s and 1990s. It now provides English-speaking readers with an invaluablepicture of the radical thought and optimism that lies at the root of Lula's Brazil. Félix Guattari, post-'68 French psychoanalyst and philosopher, is the author of Anti-Oedipus, The Anti-Oedipus Papers, 2006), and other books. Semiotext haspublished the first two volumes of his complete essays, Chaosophy and Soft Subversions, and will publish the final volume, Chaos and Complexity, in 2008. Suely Rolnik is apsychoanalyst, cultural critic, and curator who lives and works in São Paulo, Brazil. She was aclose collaborator of Guattari during her exile in Paris from the military dictatorship inBrazil. (shrink)

Perhaps the hottest topic in the philosophy of chemistry is that of the relationship between chemistry and physics. The problem finds one of its main manifestations in the debate about the nature of molecular structure, given by the spatial arrangement of the nuclei in a molecule. The traditional strategy to address the problem is to consider chemical cases that challenge the definition of molecular structure in quantum–mechanical terms. Instead of taking that top-down strategy, in this paper we face (...) the problem of the reduction of molecular structure to quantum mechanics from a bottom-up perspective: our aim is to show how the theoretical peculiarities of quantum mechanics stand against the possibility of molecular structure, defined in terms of the spatial relations of the nuclei conceived as individual localized objects. We will argue that, according to the theory, quantum “particles” are not individuals that can be identified as different from others and that can be reidentified through time; therefore, they do not have the ontological stability necessary to maintain the relations that can lead to a spatially definite system with an identifiable shape. On the other hand, although quantum chemists use the resources supplied by quantum mechanics with successful results, this does no mean reduction: their “approximations” add certain assumptions that are not justified in the context of quantum mechanics or are even inconsistent with the very formal structure of the theory. (shrink)

Senior molecular geneticists were interviewed about their perceptions of the ethical and social implications of genetic knowledge. Inductive analysis of these interviews identified a number of strategies through which the scientists negotiated their moral responsibilities as they participated in generating knowledge that presents difficult ethical questions. These strategies included: further analysis and application of scientific method; clarification of multiple roles; negotiation with the public through public debate, institutional processes of funding, ethics committees and legislation; and personal responsibility.

In this fascinating study, the author analyzes the conceptual roots of molecular biology and the social matrix in which it was developed.

Background There are intense discussions about the ethical and societal implications of biomedical engineering, but little data to suggest how scientists think about the ethics of their work. The aim of this study is to describe how scientists frame the ethics of their research, with a focus on the field of molecular systems engineering.Methods Semi-structured qualitative interviews were conducted during 2021–2022, as part of a larger study. This analysis includes a broad question about how participants view ethics as related (...) to their work, with follow up probes about the topics they consider most important. Interviews were transcribed, inductively coded by two researchers to consensus, and analyzed thematically.Results Twenty-four scientists participated in the study. Interviewees hold positions as professors, principal investigators, and senior staff researchers in universities or research institutes in the United States and Europe. Among those scientists who reported reflecting on ethical considerations in their work, many equated ethics with research ethics topics (e.g., safety, replicability), or with regulation and guidelines. Participants expressed the view that ethical issues are primarily relevant for clinical trials of bioengineered products, or for those working with animal or human subjects. Scientists described their research as “too early” or “not examining anything living” with regard to ethical reflection. Finally, many felt that ethics is seen as territory for experts and therefore beyond scientists’ competencies.Conclusions Molecular systems engineering scientists currently focus on regulatory aspects as the framework for their ethical analyses. They describe using a framework to define when life arises, as a means to determine when further ethical engagement is warranted. Further research is needed to investigate how scientists relate to the ethics of their scientific work, and build consensus around concepts of life, autonomous behavior, and physiological relevance of bioengineered systems. (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)

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

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with “genomic medicine” nor with “precision medicine”, but with “data medicine”. The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The “transformation” of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision (...) of care. Molecular tumor boards are one response to these changes and are now providing better access to next-generation sequencing and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent documents at all academic medical centers and to introduce dynamic and electronic informed consent. (shrink)

Since the publication of Nikolas Rose’s ‘The Politics of Life Itself’ there has been vivid discussion about how biopolitical governance has changed over the last decades. This article uses what Rose terms ‘molecular politics’, a new socio-technical grip on the human body, as a contrasting background to ask anew his question ‘What, then, of biopolitics today?’ – albeit focusing not on advances in genetics, microbiology, and pharmaceutics, as he does, but on the rapid proliferation of wearables and other sensor-software (...) gadgets. In both cases, new technologies providing information about the individual body are the common ground for governance and optimization, yet for the latter, the target is habits of moving, eating and drinking, sleeping, working and relaxing. The resulting profound differences are carved out along four lines: ‘somatic identities’ and a modified understanding of the body; the role of ‘expert knowledge’ compared to that of networks of peers and self-experimentation; the ‘types of intervention’ by which new technologies become effective in our everyday life; and the ‘post-discipline character’ of molecular biopolitics. It is argued that, taken together, these differences indicate a remarkable shift which could be termed aretaic: its focus is not ‘life itself’ but ‘life as it is lived’, and its modality are new everyday socio-technical entanglements and their more-than-human rationalities of governance. (shrink)

Whether or not quantum physics can account for molecular structure is a matter of considerable controversy. Three of the problems raised in this regard are the problems of molecular structure. We argue that these problems are just special cases of the measurement problem of quantum mechanics: insofar as the measurement problem is solved, the problems of molecular structure are resolved as well. In addition, we explore one consequence of our argument: that claims about the reduction or emergence (...) of molecular structure cannot be settled independently of the choice of a particular resolution to the measurement problem. Specifically, we consider how three standard putative solutions to the measurement problem inform our under- standing of a molecule in isolation, as well as of chemistry’s relation to quantum physics. (shrink)

By their own account, physicalists are committed to the claim that physics is causally complete, or closed. The claim is presented as an empirical one. However, detailed and explicit empirical arguments for the claim are rare. I argue that molecular models are a key source of evidence but that, on closer inspection, they do not support the completeness claim.

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)

The SARS‐CoV‐2 virus is responsible for the COVID‐19 pandemic the world experience since 2019. The protein responsible for the first steps of cell invasion, the spike protein, has probably received the most attention in light of its central role during infection. Computational approaches are among the tools employed by the scientific community in the enormous effort to study this new affliction. One of these methods, namely molecular dynamics (MD), has been used to characterize the function of the spike protein (...) at the atomic level and unveil its structural features from a dynamic perspective. In this review, we focus on these main findings, including spike protein flexibility, rare S protein conformational changes, cryptic epitopes, the role of glycans, drug repurposing, and the effect of spike protein variants. (shrink)

This paper focuses on the consolidation of Molecular Evolution, a field originating in the 1960s at the interface of molecular biology, biochemistry, evolutionary biology, biophysics and studies on the origin of life and exobiology. The claim is made that Molecular Evolution became a discipline by integrating different sorts of scientific traditions: experimental, theoretical and comparative. The author critically incorporates Timothy Lenoir’s treatment of disciplines , as well as ideas developed by Stephen Toulmin on the same subject. On (...) their account disciplines are spaces where the social and epistemic dimensions of science are deeply and complexly interwoven. However, a more detailed account of discipline formation and the dynamics of an emerging disciplinary field is lacking in their analysis. The present essay suggests focusing on the role of scientific concepts in the double configuration of disciplines: the social/political and the epistemic order. In the case of Molecular Evolution the concepts of molecular clock and informational molecules played a central role, both in differentiating molecular from classical evolutionists, and in promoting communication between the different sorts of traditions integrated in Molecular Evolution. The paper finishes with a reflection on the historicity of disciplines, and the historicity of our concepts of disciplines. (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)

We apply molecular code theory to a rule-based model of the human inner kinetochore and study how complex formation in general can give rise to molecular codes. We analyze 105 reaction networks generated from the rule-based inner kinetochore model in two variants: with and without dissociation of complexes. Interestingly, we found codes only when some but not all complexes are allowed to dissociate. We show that this is due to the fact that in the kinetochore model proteins can (...) only bind at kinetochores by attaching to already attached proteins and cannot form complexes in free solution. Using a generalized linear mixed model we study which centromere protein can take which role in a molecular code . By this, associations between CENPs and code roles are found. We observed that CenpA is a major risk factor while CenpQ is a major protection factor . Finally we show, using an abstract model of copolymer formation, that molecular codes can also be realized solely by the formation of stable complexes, which do not dissociate. For example, with particular dimers as context a molecular code mapping from two different monomers to two particular trimers can be realized just by non-selective complex formation. We conclude that the formation of protein complexes can be utilized by the cell to implement molecular codes. Living cells thus facilitate a subsystem allowing for an enormous flexibility in the realization of mappings, which can be used for specific regulatory processes, e.g. via the context of a mapping. (shrink)

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function (...) as reflected in Christian Anfinsen’s The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling’s identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health had an impact on evolutionary biology. (shrink)

El surgimiento de la biología molecular en la frontera que separa la teoría genética y la bioquímica constituye un buen banco de pruebas para distintas estrategias metacientíficas. El teoreticismo de las revoluciones científicas de Thomas S. Kuhn propende hacia un constructivismo social que no sirve para dar cuenta de la posible verdad y corrección del teorema de la doble hélice. El enfoque semántico (desarrollado por J. Sneed, W. Stegmüller, U Moulines, etc.), aunque pretende adecuar sus análisis a los contenidos (...) estructurales y al significado de los teoremas científicos, acaba disolviendo estos en meras correspondencias formales. La teoría del cierre categorial, en cambio, se adscribe a un constructivismo circularista que permite entender los dogmas sobre la estructura del ADN como si fueran identidades sintéticas materiales sin desdeñar por ello los aspectos pragmáticos, históricos y sociales, que valoran en su justa medida las aportaciones del grupo Fago, de Watson y Crick, de Pauling o de las universidades implicadas. (shrink)

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with “genomic medicine” nor with “precision medicine”, but with “data medicine”. The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The “transformation” of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision (...) of care. Molecular tumor boards are one response to these changes and are now providing better access to next-generation sequencing and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent documents at all academic medical centers and to introduce dynamic and electronic informed consent. (shrink)

Statements about the behavior of biochemical entities (e.g., about the interaction between two proteins) abound in the literature on molecular biology and are increasingly becoming the targets of information extraction and text mining techniques. We show that an accurate analysis of the semantics of such statements reveals a number of ambiguities that have to be taken into account in the practice of biomedical ontology engineering: Such statements can not only be understood as event reporting statements, but also as ascriptions (...) of dispositions or tendencies that may or may not refer to collectives of interacting molecules or even to collectives of interaction events. (shrink)

Much of the recent philosophical debate on causation and causal explanation in the biological and biomedical sciences has focused on the notion of mechanism. Mechanisms, their nature and epistemic roles have been tackled by a range of so-called neo-mechanistic theories, and widely discussed. Without denying the merits of this approach, our paper aims to show how lately it has failed to give proper credit to processes, which are central to the field, especially of contemporary molecular biology. Processes can be (...) summed up in the notion of ‘pathway’, which is far from being just equivalent to that of ‘mechanism’ and has a profound epistemological and explanatory relevance. It is argued that an adequate consideration of pathways impels some rethinking of scientific explanation in molecular biology, namely its functional and contextual features. A number of examples are given to suggest that the focus of philosophical attention in this disciplinary field should shift from the notion of mechanism to the notion of pathway. (shrink)

Significant progress in the molecular investigation of endogenous bioelectric signals during pattern formation in growing tissues has been enabled by recently developed techniques. Ion flows and voltage gradients produced by ion channels and pumps are key regulators of cell proliferation, migration, and differentiation. Now, instructive roles for bioelectrical gradients in embryogenesis, regeneration, and neoplasm are being revealed through the use of fluorescent voltage reporters and functional experiments using well‐characterized channel mutants. Transmembrane voltage gradients (Vmem) determine anatomical polarity and function (...) as master regulators during appendage regeneration and embryonic left‐right patterning. A state‐of‐the‐art recent study reveals that they can also serve as prepatterns for gene expression domains during craniofacial patterning. Continued development of novel tools and better ways to think about physical controls of cell‐cell interactions will lead to mastery of the morphogenetic information stored in physiological networks. This will enable fundamental advances in basic understanding of growth and form, as well as transformative biomedical applications in regenerative medicine. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate the non‐linear, stochastic (...) dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

A recent literature review of commentaries and ‘state of the art’ articles from researchers in psychiatric genetics (PMG) offers a consensus about progress in the science of genetics, disappointments in the discovery of new and effective treatments, and a general optimism about the future of the field. I argue that optimism for the field of psychiatric molecular genetics (PMG) is overwrought, and consider progress in the field in reference to a sample estimate of US National Institute of Mental Health (...) funding for this paradigm for the years 2008 and 2009. I conclude that the amounts of financial investment in PMG is questionable from an ethical perspective, given other research and clinical needs in the USA. (shrink)

Raunig develops a philosophy of dividuality as a way of addressing contemporary modes of production and forms of life. The animal of the molecular revolution will be neither mole nor snake, but a drone-animal-thing that is solid, liquid, and a gas. —from Dividuum As the philosophical, religious, and historical systems that have produced the “individual” (and its counterparts, society and community) over the years continue to break down, the age of “dividuality” is now upon us. The roots of the (...) concept of the “dividuum” can be traced back to Latin philosophy, when Cicero used the term to translate the “divisible” in the writings of Epicurus and Plato; later, medieval scholars utilized the term in theological discussions on the unity of the trinity. Grounding himself in the writings of the medieval bishop Gilbert de Poitiers and his extensive commentaries on Boethius, Gerald Raunig charts a genealogy of the concept and develops a philosophy of dividuality as a way of addressing contemporary modes of production and forms of life. Through its components of dispersion, subsistence, and similarity, dividuality becomes a hidden principle of obedience and conformity, but it also brings with it the potential to realize disobedience and noncompliant con/dividualities. Raunig's bad news is that dividuality is responsible for much of the intensified exploitation and enslavement taking place under contemporary machinic capitalism. Algorithms, derivatives, big data, and social media technology all contribute to the rampant expansion of divisive management strategies and desires for self-division. The good news, however, is that this same terrain of dividuality presents an opportunity for a new kind of resistance, one that can be realized in the form of con/division. (shrink)

In this article, two issues regarding mechanisms are discussed. The first concerns the relationships between “mechanism description” and “mechanism explanation.” It is proposed that it is rather plausible to think of them as two distinct epistemic acts. The second deals with the different molecular biology explanatory contexts, and it is shown that some of them require physics and its laws.

The study of mental illness by the methods of molecular genetics is still in its infancy, but the use of genetic markers in psychiatry may potentially lead to a Virchowian revolution in the conception of mental illness. Genetic markers may define novel clusters of patients having diverse clinical presentations but sharing a common genetic and mechanistic basis. Such clusters may differ radically from the conventional classification schemes of psychiatric illness. However, the reduction of even relatively simple Mendelian phenomena to (...) molecular genetics has been shown to be a surprisingly complex and problematic enterprise. Mental illnesses exist at many levels of including social, environmental, and developmental interactions. Reductionistic shifts in the classification of such a disease entity will have to address the interlevel dynamics that take place within the structure of theories of mental illness. The question of how molecular analysis of psychiatric disease will impact on the structure of existing theories and classification systems is the central topic of this paper. (shrink)

The molecular genetic age can be said to have begun with the letter in Nature in 1953 by Watson and Crick, describing the helical structure of DNA. Some outstanding scientific work preceded that discovery, including especially the recognition by Chargaff of base-pair complementarity, but no discovery quite captured the imagination of the biomedical world as a few understated words by Watson and Crick in their famous one-page paper: "It has not escaped our notice that the specific pairing we have (...) postulated immediately suggests a possible copying mechanism for the genetic material". The manner in which genetic material was passed on from generation to generation had been decoded.That discovery was... (shrink)

We provide an introduction to network theory, evidence to support a connection between molecular network structure and neuropsychiatric disease, and examples of how network approaches can expand our knowledge of the molecular bases of these diseases. Without systematic methods to derive their biological meanings and inter‐relatedness, the many molecular changes associated with neuropsychiatric disease, including genetic variants, gene expression changes, and protein differences, present an impenetrably complex set of findings. Network approaches can potentially help integrate and reconcile (...) these findings, as well as provide new insights into the molecular architecture of neuropsychiatric diseases. Network approaches to neuropsychiatric disease are still in their infancy, and we discuss what might be done to improve their prospects. (shrink)

Molecular Revolution in BrazilFélix Guattari and Suely Rolniktranslated by Karel Clapshow and Brian HolmesYes, I believe that there is a multiple people, a people of mutants, a people of potentialities that appears and disappears, that is embodied in social, literary, and musical events.... I think that we're in a period of productivity, proliferation, creation, utterly fabulous revolutions from the viewpoint of this emergence of a people. That's molecular revolution: it isn't a slogan or a program, it's something that (...) I feel, that I live....--from Molecular Revolution in BrazilFollowing Brazil's first democratic election after two decades of military dictatorship, French philosopher Félix Guattari traveled through Brazil in 1982 with Brazilian psychoanalyst Suely Rolnik and discovered an exciting, new political vitality. In the infancy of its new republic, Brazil was moving against traditional hierarchies of control and totalitarian regimes and founding a revolution of ideas and politics. Molecular Revolution in Brazil documents the conversations, discussions, and debates that arose during the trip, including a dialogue between Guattari and Brazil's future President Luis Ignacia Lula da Silva, then a young gubernatorial candidate. Through these exchanges, Guattari cuts through to the shadowy practices of globalization gone awry and boldly charts a revolution in practice.Assembled and edited by Rolnik, Molecular Revolution in Brazil is organized thematically; aphoristic at times, it presents a lesser-known, more overtly political aspect of Guattari's work. Originally published in Brazil in 1986 as Micropolitica: Cartografias do desejo, the book became a crucial reference for political movements in Brazil in the 1980s and 1990s. It now provides English-speaking readers with an invaluable picture of the radical thought and optimism that lies at the root of Lula's Brazil. Félix Guattari, post-'68 French psychoanalyst and philosopher, is the author of Anti-Oedipus, The Anti-Oedipus Papers, 2006), and other books. Semiotext has published the first two volumes of his complete essays, Chaosophy and Soft Subversions, and will publish the final volume, Chaos and Complexity, in 2008. Suely Rolnik is a psychoanalyst, cultural critic, and curator who lives and works in São Paulo, Brazil. She was a close collaborator of Guattari during her exile in Paris from the military dictatorship in Brazil. (shrink)

The molecular components of complement are a major part of the armoury of the mammalian immune system, being required for the lysis of antibody‐targeted cells. Several of the complement proteins are known to be encoded by genes within the major histocompatibility complex (MHC). Molecular analysis of these genes is providing new information on the basis of complement action and the possible roles of this system in autoimmune disease.

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a (...) complex mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double‐strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation. BioEssays 24:439–448, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Protistology, and evolutionary protistology in particular, is experiencing a golden research era. It is an extended one that can be dated back to the 1970s, which is when the molecular rebirth of microbial phylogeny began in earnest. John Archibald, a professor of evolutionary microbiology at Dalhousie University, focuses on the beautiful story of endosymbiosis in his book, John Archibald, One Plus One Equals One: Symbiosis and the Origin of Complex Life. However, this historical narrative could be treated as synecdochal (...) of how the molecular revolution has changed evolutionary biology forever, and that is how Archibald has structured his book. I will address the encompassing theme of molecular methods in detail, but also pay careful attention to the endosymbiosis thread in its own right. (shrink)

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy‐related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory (...) pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. (shrink)

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