There are two fundamentally distinct kinds of biological theorizing. "Formal biology" focuses on the relations, captured in formal laws, among mathematically abstracted properties of abstract objects. Population genetics and theoretical mathematical ecology, which are cases of formal biology, thus share methods and goals with theoretical physics. "Compositional biology," on the other hand, is concerned with articulating the concrete structure, mechanisms, and function, through developmental and evolutionary time, of material parts and wholes. Molecular genetics, biochemistry, (...) developmental biology, and physiology, which are examples of compositional biology, are in serious need of philosophical attention. For example, the very concept of a "part" is understudied in both philosophy of biology and philosophy of science. ;My dissertation is an attempt to clarify the distinction between formal biology and compositional biology and, in so doing, provide a clear philosophical analysis, with case studies, of compositional biology. Given the social, economic, and medical importance of compositional biology, understanding it is urgent. For my investigation, I draw on the philosophical fields of metaphysics and epistemology, as well as philosophy of biology and philosophy of science. I suggest new ways of thinking about some classic philosophy of science issues, such as modeling, laws of nature, abstraction, explanation, and confirmation. I hint at the relevance of my study of two kinds of biological theorizing to debates concerning the disunity of science. (shrink)

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

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 1926, Haldane published an essay titled 'On Being the Right Size' in which he argued that the structure, function, and behavior of an organism are strongly conditioned by the physical forces that exert the greatest impact at the scale at which it exists. This chapter puts Haldane’s insight to work in the context of contemporary cell and molecular biology. Owing to their minuscule size, cells and molecules are subject to very different forces than macroscopic organisms. In a (...) sense, macroscopic and microscopic entities inhabit different “worlds”: the former is ruled by gravity and inertia, whereas the latter is governed by Brownian motion. One implication is that we should be extremely skeptical of models and analogies that seek to explain properties of microscopic entities by appealing to properties of macroscopic ones. Unfortunately, this is precisely what the appeal to engineering metaphors in molecular biology attempts to do. Molecular biologists routinely resort to such metaphors because they are familiar and intuitively intelligible. But if our machines were the size of molecules it would be impossible for them to function the way they do. It follows that we should avoid distorting biological reality by construing it in engineering terms. In this chapter I examine four key metaphors in molecular biology – “genetic program,” “cellular circuitry,” “molecular machine,” and “molecular motor” – and I argue that their deficiencies derive from their neglect of scale. I also try to explain why many biologists today appear to have forgotten the importance of scale that Haldane drew attention to in his essay. I suggest that the reason has to do with the influence of Schrödinger’s argument in 'What is Life?' regarding the stability of the gene. (shrink)

We characterize a type of functional explanation that addresses why a homologous trait originating deep in the evolutionary history of a group remains widespread and largely unchanged across the group’s lineages. We argue that biologists regularly provide this type of explanation when they attribute conserved functions to phenotypic and genetic traits. The concept of conserved function applies broadly to many biological domains, and we illustrate its importance using examples of molecular sequence alignments at the intersection of evolution and cell (...) biology. We use these examples to show how the study of conserved functions can integrate knowledge of a trait’s causal effects on fitness and its history of natural selection without invoking adaptation. We also show how conserved function provides a novel basis for addressing objections against evolutionary functions raised by Robert Cummins. (shrink)

The philosophical debate around the impact of machine learning in science is often framed in terms of a choice between AI and classical methods as mutually exclusive alternatives involving difficult epistemological trade-offs. A common worry regarding machine learning methods specifically is that they lead to opaque models that make predictions but do not lead to explanation or understanding. Focusing on the field of molecular biology, I argue that in practice machine learning is often used with explanatory aims. (...) More specifically, I argue that machine learning can be tightly integrated with other, more traditional, research methods and in a clear sense can contribute to insight into the causal processes underlying phenomena of interest to biologists. One could even say that machine learning is not the end of theory in important areas of biology, as has been argued, but rather a new beginning. I support these claims with a detailed discussion of a case study involving gene regulation by microRNAs. (shrink)

Denis Nobel looks at four important misinterpretations of molecular biology concerning evolutionary processes and demonstrates that the new synthesis today looks rather outdated. The modern synthesis is nearly 80 years old. The proponents who worked out the modern synthesis had no access to the current knowledge on cell biology, genetics, epigenetics, RNA biology and virology. Therefore this contribution adds several aspects which Nobel’s article does not explicitly mention, providing some examples for a better understanding of (...) evolutionary novelty. (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)

Griffiths and Stotz’s Genetics and Philosophy: An Introduction offers a very good overview of scientific and philosophical issues raised by present-day genetics. Examining, in particular, the questions of how a “gene” should be defined and what a gene does from a causal point of view, the authors explore the different domains of the life sciences in which genetics has come to play a decisive role, from Mendelian genetics to molecular genetics, behavioural genetics, and (...) evolution. In this review, I highlight what I consider as the two main theses of the book, namely: genes are better conceived as tools; genes become causes only in a context. I situate these two theses in the wider perspective of developmental systems theory. This leads me to emphasize that Griffiths and Stotz reflect very well an on going process in genetics, which I call the “epigenetization” of genetics, i.e., the growing interest in the complex processes by which gene activation is regulated. I then make a factual objection, which is that Griffiths and Stotz have almost entirely neglected the perspective of ecological developmental biology, and more precisely recent work on developmental symbioses, and I suggest that this omission is unfortunate in so far as an examination of developmental symbioses would have considerably strengthened Griffiths and Stotz’s own conclusions. (shrink)

One of the defining features of the classical gene was its position. In molecular genetics, positions are defined instead as nucleotide numbers and there is no clear correspondence with its classical counterpart. However, the classical gene position did not simply disappear with the development of the molecular approach, but survived in the lab associated to different genetic practices. The survival of classical gene position would illustrate Waters’ view about the practical persistence of the (...) genetic approach beyond reductionism and anti-reductionist claims. We show instead that at the level of laboratory practices there are also reductive processes, operating through the rise and fall of different techniques. Molecular markers made the concept of classical gene position practically dispensable, leading us to rethink whether it had any causal role or was just a mere heuristic. (shrink)

The idea that development is the expression of information accumulated during evolution and that heredity is the transmission of this information is surprisingly hard to cash out in strict, scientific terms. This paper seeks to do so using the sense of information introduced by Francis Crick in his sequence hypothesis and central dogma of molecular biology. It focuses on Crick's idea of precise determination. This is analysed using an information-theoretic measure of causal specificity. This allows us to reconstruct (...) some of Crick's claims about information in transcription and translation. Crick's approach to information has natural extensions to non-coding regions of DNA, to epigenetic marks, and to the genetic or environmental upstream causes of those epigenetic marks. Epigenetic information cannot be reduced to genetic information. The existence of biological information in epigenetic and exogenetic factors is relevant to evolution as well as to development. (shrink)

We describe an approach to measuring biological information where ‘information’ is understood in the sense found in Francis Crick’s foundational contributions to molecular biology. Genes contain information in this sense, but so do epigenetic factors, as many biologists have recognized. The term ‘epigenetic’ is ambiguous, and we introduce a distinction between epigenetic and exogenetic inheritance to clarify one aspect of this ambiguity. These three heredity systems play complementary roles in supplying information for development. -/- We then consider the (...) evolutionary significance of the three inheritance systems. Whilst the genetic inheritance system was the key innovation in the evolution of heredity, in modern organisms the three systems each play important and complementary roles in heredity and evolution. -/- Our focus in the earlier part of the paper is on ‘proximate biology’, where information is a substantial causal factor that causes organisms to develop and causes offspring to resemble their parents. But much philosophical work has focused on information in ‘ultimate biology’. Ultimate information is a way of talking about the evolutionary design of the mechanisms of development and inheritance. We conclude by clarifying the relationship between the two. Ultimate information is not a causal factor that acts in development or heredity, but it can help to explain the evolution of proximate information, which is. (shrink)

Within the framework of historical epistemology (G. Canguilhem, M. Foucault, L. Loison) the key concepts of a scientific discipline are considered as historically and culturally contingtent, that is, predetermined by outside factors rather than by the internal logic of the development of science. A fundamental attempt to demonstrate the contingency of the concept of “genetic information” was made in 2000 by Lily Kay, who argues that there was an “epistemic rupture” between this concept and the previous biological discourse of “specificity”. (...) As I. A. Kuzin has recently demonstrated, this work is essential not only for the history of biology, but also for the methodology of history of science and for modern biology as well. This paper contains a critical approach to both works. The sociocultural (externalist) conceptualizations of the history of biology contain serious difficulties and contradictions that internalism can successfully cope with. Being an explanans, “discourse” is not able to explain the key features of the history of deciphering the genetic code. “Discourse”, “concept” and “metaphor” of information are confused; two separated phases of the deciphering the code are separated groundlessly as “formal” and “material” stages; the transition from syntactic aspect of information to semantic one (from the “cipher” metaphor to the “code” metaphor) is at least problematic. The internalist approach preserves the idea of the contingency of the concept of information (in the form of methodological contingency instead of historical and cultural one), and at the same time incorporates it into the internal development of genetics and molecular biology. (shrink)

Two decades ago, Rolf Landauer (1991) argued that “information is physical” and ought to have a role in the scientific analysis of reality comparable to that of matter, energy, space and time. This would also help to bridge the gap between biology and mathematics and physics. Although it can be argued that we are living in the ‘golden age’ of biology, both because of the great challenges posed by medicine and the environment and the significant advances that have (...) been made—especially in genetics and molecular and cell biology—we feel that information as an essential aspect of life has been neglected, or at least misunderstood. We therefore summon Maxwell’s Demon and its distant relative the ratchet, and apply these to biology. (shrink)

Cancer biology features the ascription of normal functions to parts of cancers. At least some ascriptions of function in cancer biology track local normality of parts within the global abnormality of the aberration to which those parts belong. That is, cancer biologists identify as functions activities that, in some sense, parts of cancers are supposed to perform, despite cancers themselves having no purpose. The present paper provides a theory to accommodate these normal function ascriptions—I call it the Modeling (...) Account of Normal Function (MA). MA comprises two claims. First, normal functions are activities whose performance by the function-bearing part contributes to the self-maintenance of the whole system and, thereby, results in the continued presence of that part. Second, MA holds that models of system-level activities that are (partly) constitutive of self-maintenance are improved by including a representation of the relevant function-bearing part and by making reference to the activity/activities that part performs which contribute(s) to those system-level activities. I contrast MA with two other accounts that seek to explicate the ascription of normal functions in biology, namely, the organizational account and the selected effects account. Both struggle to extend to cancer biology. However, I offer ecumenical readings which allow them to recover some ascriptions of normal function to parts of cancers. So, though I contend that MA excels in this respect, the purpose of this paper is served if it provides materials for bridging the gap between cancer biology, philosophy of cancer, and the literature on function. (shrink)

Conventional methods of genetic engineering and more recent genome editing techniques focus on identifying genetic target sequences for manipulation. This is a result of historical concept of the gene which was also the main assumption of the ENCODE project designed to identify all functional elements in the human genome sequence. However, the theoretical core concept changed dramatically. The old concept of genetic sequences which can be assembled and manipulated like molecular bricks has problems in explaining the natural genome-editing competences (...) of viruses and RNA consortia that are able to insert or delete, combine and recombine genetic sequences more precisely than random-like into cellular host organisms according to adaptational needs or even generate sequences de novo. Increasing knowledge about natural genome editing questions the traditional narrative of mutations (error replications) as essential for generating genetic diversity and genetic content arrangements in biological systems. This may have far-reaching consequences for our understanding of artificial genome editing. (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 this paper, I defend the agent/patient distinction against critics who argue that causal interactions are symmetrical. Specifically, I argue that there is a widespread type of causal interaction between distinct entities, resulting in a type of ontological asymmetry that provides principled grounds for distinguishing agents from patients. The type of interaction where the asymmetry is found is when one of the entities undergoes a change in kind, structure, powers, or intrinsic properties as a result of the interaction while the (...) other does not. Interactions of this type are widespread in molecular biology and chemistry. I focus specifically on (i) the actions of enzymes on substrates and (ii) water molecules breaking the bonds of polarized molecules. Finally, I respond to objections by laying out and to a limited extent defending three commitments of my account: emergent entities and powers, realism about chemical kinds or structures, and the assumption of the agent/patient distinction in functional attributions in biology. (shrink)

This paper examines causal theories of reference with respect to how plausible an account they give of non-physical natural kind terms such as ‘gene’ as well as of the truth of the associated theoretical claims. I first show that reference fixism for ‘gene’ fails. By this, I mean the claim that the reference of ‘gene’ was stable over longer historical periods, for example, since the classical period of transmission genetics. Second, I show that the theory of partial reference (...) does not do justice to some widely held realist intuitions about classical genetics. This result is at loggerheads with the explicit goals usually associated with partial theories of reference, which is to defend a realist semantics for scientific terms. Thirdly, I show that, contrary to received wisdom and perhaps contrary to physics and chemistry, neither reference fixism nor partial reference are necessary in order to hold on to scientific realism about biology. I pinpoint the reasons for this in the nature of biological kinds, which do not even remotely resemble natural kinds (i.e., Lockean real essences) as traditionally conceived. (shrink)

The scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their func- tionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adapta- tions, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. In (...) particular, the analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an oppor- tunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would sug- gest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to imple- ment novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engi- neering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engi- neering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (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 scientific study of living organisms is permeated by machine and design metaphors. Genes are thought of as the ‘‘blueprint’’ of an organism, organisms are ‘‘reverse engineered’’ to discover their functionality, and living cells are compared to biochemical factories, complete with assembly lines, transport systems, messenger circuits, etc. Although the notion of design is indispensable to think about adaptations, and engineering analogies have considerable heuristic value (e.g., optimality assumptions), we argue they are limited in several important respects. In particular, the (...) analogy with human-made machines falters when we move down to the level of molecular biology and genetics. Living organisms are far more messy and less transparent than human-made machines. Notoriously, evolution is an opportunistic tinkerer, blindly stumbling on ‘‘designs’’ that no sensible engineer would come up with. Despite impressive technological innovation, the prospect of artificially designing new life forms from scratch has proven more difficult than the superficial analogy with ‘‘programming’’ the right ‘‘software’’ would suggest. The idea of applying straightforward engineering approaches to living systems and their genomes— isolating functional components, designing new parts from scratch, recombining and assembling them into novel life forms—pushes the analogy with human artifacts beyond its limits. In the absence of a one-to-one correspondence between genotype and phenotype, there is no straightforward way to implement novel biological functions and design new life forms. Both the developmental complexity of gene expression and the multifarious interactions of genes and environments are serious obstacles for ‘‘engineering’’ a particular phenotype. The problem of reverse-engineering a desired phenotype to its genetic ‘‘instructions’’ is probably intractable for any but the most simple phenotypes. Recent developments in the field of bio-engineering and synthetic biology reflect these limitations. Instead of genetically engineering a desired trait from scratch, as the machine/engineering metaphor promises, researchers are making greater strides by co-opting natural selection to ‘‘search’’ for a suitable genotype, or by borrowing and recombining genetic material from extant life forms. (shrink)

Over the last decades, network-based approaches have become highly popular in diverse fields of biology, including neuroscience, ecology, molecular biology and genetics. While these approaches continue to grow very rapidly, some of their conceptual and methodological aspects still require a programmatic foundation. This challenge particularly concerns the question of whether a generalized account of explanatory, organisational and descriptive levels of networks can be applied universally across biological sciences. To this end, this highly interdisciplinary theme issue focuses (...) on the definition, motivation and application of key concepts in biological network science, such as explanatory power of distinctively network explanations, network levels, and network hierarchies. (shrink)

Most models of generational succession in sexually reproducing populations necessarily move back and forth between genic and genotypic spaces. We show that transitions between and within these spaces are usually hidden by unstated assumptions about processes in these spaces. We also examine a widely endorsed claim regarding the mathematical equivalence of kin-, group-, individual-, and allelic-selection models made by Lee Dugatkin and Kern Reeve. We show that the claimed mathematical equivalence of the models does not hold. *Received January 2007; revised (...) April 2008. †To contact the authors, please write to: Elisabeth Lloyd, Department of History and Philosophy of Science, 130 Goodbody Hall, Indiana University, Bloomington, IN 47405; e-mail: [email protected]; Richard Lewontin, Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge, MA 02138; Marcus Feldman, Department of Biological Sciences, Stanford University, Stanford, CA 94305; e-mail: [email protected]. (shrink)

Symmetries play a major role in physics, in particular since the work by E. Noether and H. Weyl in the first half of last century. Herein, we briefly review their role by recalling how symmetry changes allow to conceptually move from classical to relativistic and quantum physics. We then introduce our ongoing theoretical analysis in biology and show that symmetries play a radically different role in this discipline, when compared to those in current physics. By this comparison, we (...) stress that symmetries must be understood in relation to conservation and stability properties, as represented in the theories. We posit that the dynamics of biological organisms, in their various levels of organization, are not just processes, but permanent (extended, in our terminology) critical transitions and, thus, symmetry changes. Within the limits of a relative structural stability (or interval of viability), variability is at the core of these transitions. (shrink)

The article proposes to further develop the ideas of the Extended Evolutionary Synthesis by including into evolutionary research an analysis of phenomena that occur above the organismal level. We demonstrate that the current Extended Synthesis is focused more on individual traits (genetically or non-genetically inherited) and less on community system traits (synergetic/organizational traits) that characterize transgenerational biological, ecological, social, and cultural systems. In this regard, we will consider various communities that are made up of interacting populations, and for which the (...) individual members can belong to the same or to different species. Examples of communities include biofilms, ant colonies, symbiotic associations resulting in holobiont formation, and human societies. The proposed model of evolution at the level of communities revises classic theorizing on the major transitions in evolution by analyzing the interplay between community/social traits and individual traits, and how this brings forth ideas of top-down regulations of bottom-up evolutionary processes (collaboration of downward and upward causation). The work demonstrates that such interplay also includes reticulate interactions and reticulate causation. In this regard, we exemplify how community systems provide various non-genetic ‘scaffoldings’, ‘constraints’, and ‘affordances’ for individual and sociocultural evolutionary development. Such research complements prevailing models that focus on the vertical transmission of heritable information, from parent to offspring, with research that instead focusses on horizontal, oblique and even reverse information transmission, going from offspring to parent. We call this reversed information transfer the ‘offspring effect’ to contrast it from the ‘parental effect’. We argue that the proposed approach to inheritance is effective for modelling cumulative and distributed developmental process and for explaining the biological origins and evolution of language. (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)

While many different mechanisms contribute to the generation of spatial order in biological development, the formation of morphogenetic fields which in turn direct cell responses giving rise to pattern and form are of major importance and essential for embryogenesis and regeneration. Most likely the fields represent concentration patterns of substances produced by molecular kinetics. Short range autocatalytic activation in conjunction with longer range “lateral” inhibition or depletion effects is capable of generating such patterns (Gierer and Meinhardt, 1972). Non-linear reactions (...) are required, and mathematical criteria were derived to design molecular models capable of pattern generation. The classical embryological feature of proportion regulation can be incorporated into the models. The conditions are mathematically necessary for the simplest two-factor case, and are likely to be a fair approximation in multi-component systems in which activation and inhibition are systems parameters subsuming the action of several agents. Gradients, symmetric and periodic patterns, in one or two dimensions, stable or pulsing in time, can be generated on this basis. Our basic concept of autocatalysis in conjunction with lateral inhibition accounts for self-regulatory biological features, including the reproducible formation of structures from near-uniform initial conditions as required by the logic of the generation cycle. Real tissue form, for instance that of budding Hydra, may often be traced back to local curvature arising within an initially relatively flat cell sheet, the position of evagination being determined by morphogenetic fields. Shell theory developed for architecture may also be applied to such biological processes. (shrink)

Ever since Darwin a great deal of the conceptual history of biology may be read as a struggle between two philosophical positions: reductionism and holism. On the one hand, we have the reductionist claim that evolution has to be understood in terms of changes at the fundamental causal level of the gene. As Richard Dawkins famously put it, organisms are just ‘lumbering robots’ in the service of their genetic masters. On the other hand, there is a long holistic tradition (...) that focuses on the complexity of developmental systems, on the non-linearity of gene– environment interactions, and on multi-level selective processes to argue that the full story of biology is a bit more complicated than that. Reductionism can marshal on its behalf the spectacular successes of genetics and molecular biology throughout the 20th and 21st centuries. Holism has built on the development of entirely new disciplines and conceptual frameworks over the past few decades, including evo-devo and phenotypic plasticity. Yet, a number of biologists are still actively looking for a way out of the reductionism–holism counterposition, often mentioning the word ‘emergence’ as a way to deal with the conundrum. This paper briefly examines the philosophical history of the concept of emergence, distinguishes between epistemic and ontological accounts of it, and comments on conceptions of emergence that can actually be useful for practising evolutionary biologists. (shrink)

I go deep into the biology of the human organism to argue that the psychological features and functions of persons are realized by cellular and molecular parallel distributed processing networks dispersed throughout the whole body. Persons supervene on the computational processes of nervous, endocrine, immune, and genetic networks. Persons do not go with brains.

Although molecular biology, genetics, and related special disciplines represent a large amount of empirical data, a practical method for the evaluation and overview of current knowledge is far from being realized. The main concepts and narratives in these fields have remained nearly the same for decades and the more recent empirical data concerning the role of noncoding RNAs and persistent viruses and their defectives do not fit into this scenario. A more innovative approach such as applied biocommunication (...) theory could translate empirical data into a coherent perspective on the functions within and between biological organisms and arguably lead to a sustainable integrative biology. (shrink)

Evolutionary biology is a field currently animated by much discussion concerning its conceptual foundations. On the one hand, we have supporters of a classical view of evolutionary theory, whose backbone is provided by population genetics and the so-called Modern Synthesis (MS). On the other hand, a number of researchers are calling for an Extended Synthe- sis (ES) that takes seriously both the limitations of the MS (such as its inability to incorporate developmental biology) and recent empirical (...) and theoretical research on issues such as evolvability, modularity, and self-organization. In this article, I engage in an in-depth commentary of an influential paper by population geneticist Michael Lynch, which I take to be the best defense of the MS-population genetics position published so far. I show why I think that Lynch’s arguments are wanting and propose a modification of evolutionary theory that retains but greatly expands on population genetics. (shrink)

An exploration of the nexus between ecology, evolutionary biology and molecular biology, via the concept of phenotypic plasticity.

Unlike in physics, the category of thought experiment is not very common in biology. At least there are no classic examples that are as important and as well-known as the most famous thought experiments in physics, such as Galileo’s, Maxwell’s or Einstein’s. The reasons for this are far from obvious; maybe it has to do with the fact that modern biology for the most part sees itself as a thoroughly empirical discipline that engages either in real natural history (...) or in experimenting on real organisms rather than fictive ones. While theoretical biology does exist and is recognized as part of biology, its role within biology appears to be more marginal than the role of theoretical physics within physics. It could be that this marginality of theory also affects thought experiments as sources of theoretical knowledge. Of course, none of this provides a sufficient reason for thinking that thought experiments are really unimportant in biology. It is quite possible that the common perception of this matter is wrong and that there are important theoretical considerations in biology, past or present, that deserve the title of thought experiment just as much as the standard examples from physics. Some such considerations may even be widely known and considered to be important, but were not recognized as thought experiments. In fact, as we shall see, there are reasons for thinking that what is arguably the single most important biological work ever, Charles Darwin’s On the Origin of Species, contains a number of thought experiments. There are also more recent examples both in evolutionary and non-evolutionary biology, as we will show. Part of the problem in identifying positive examples in the history of biology is the lack of agreement as to what exactly a thought experiment is. Even worse, there may not be more than a family resemblance that unifies this epistemic category. We take it that classical thought experiments show the following characteristics: They serve directly or indirectly in the non-empirical epistemic evaluation of theoretical propositions, explanations or hypotheses. Thought experiments somehow appeal to the imagination. They involve hypothetical scenarios, which may or may not be fictive. In other words, thought experiments suppose that certain states of affairs hold and then try to intuit what would happen in a world where these suppositions are true. We want to examine in the following sections if there are episodes in the history of biology that satisfy these criteria. As we will show, there are a few episodes that might satisfy all three of these criteria, and many more if the imagination criterion is dropped or understood in a lose sense. In any case, this criterion is somewhat vague in the first place, unless a specific account of the imagination is presupposed. There will also be issues as to what exactly “non-empirical” means. In general, for the sake of discussion we propose to understand the term “thought experiment” here in a broad rather than a narrow sense here. We would rather be guilty of having too wide a conception of thought experiment than of missing a whole range of really interesting examples. (shrink)

Darwinian evolutionary theory has two key terms, variations and biological selection, which finally lead to survival of the fittest variant. With the rise of molecular genetics, variations were explained as results of error replications out of the genetic master templates. For more than half a century, it has been accepted that new genetic information is mostly derived from random error-based events. But the error replication narrative has problems explaining the sudden emergence of new species, new phenotypic traits, and (...) genome innovations as a sudden single event. Meanwhile, it is recognized that errors cannot explain the evolution of genetic information, genetic novelty, and complexity. Now, empirical evidence establishes the crucial role of non-random genetic content editors, such as viruses, diversity generating retroelements, and other RNA networks, to produce new genetic information, complex regulatory control, inheritance vectors, genetic identity, immunity, new sequence space, evolution of complex organisms, and evolutionary transitions. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have (...) only sharpened the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

The role of the body in cognition is acknowledged across a variety of disciplines, even if the precise nature and scope of that contribution remain contentious. As a result, most philosophers working on embodiment—e.g. those in embodied cognition, enactivism, and ‘4e’ cognition—interact with the life sciences as part of their interdisciplinary agenda. Despite this, a detailed engagement with emerging findings in epigenetics and post-genomic biology has been missing from proponents of this embodied turn. Surveying this research provides an opportunity (...) to rethink the relationship between embodiment and genetics, and we argue that the balance of current epigenetic research favours the extension of an enactivist approach to mind and life, rather than the extended functionalist view of embodied cognition associated with Andy Clark and Mike Wheeler, which is more substrate neutral. (shrink)

The term “Complex Systems Biology” was introduced a few years ago [Kaneko, 2006] and, although not yet of widespread use, it seems particularly well suited to indicate an approach to biology which is well rooted in complex systems science. Although broad generalizations are always dangerous, it is safe to state that mainstream biology has been largely dominated by a gene-centric view in the last decades, due to the success of molecular biology. So the one gene (...) - one trait approch, which has often proved to be effective, has been extended to cover even complex traits. This simplifying view has been appropriately criticized, and the movement called systems biology has taken off. Systems biology [Noble, 2006] emphasizes the presence of several feedback loops in biological systems, which severely limit the range of validity of explanations based upon linear causal chains (e.g. gene → behaviour). Mathematical modelling is one the favourite tools of systems biologists to analyze the possible effects of competing negative and positive feedback loops which can be observed at several levels (from molecules to organelles, cells, tissues, organs, organisms, ecosystems). Systems biology is by now a well-established field, as it can be inferred by the rapid growth in number of conferences and journals devoted to it, as well as by the existence of several grants and funded projects.Systems biology is mainly focused upon the description of specific biological items, like for example specific organisms, or specific organs in a class of animals, or specific genetic-metabolic circuits. It therefore leaves open the issue of the search for general principles of biological organization, which apply to all living beings or to at least to broad classes. We know indeed that there are some principles of this kind, biological evolution being the most famous one. The theory of cellular organization also qualifies as a general principle. But the main focus of biological research has been that of studying specific cases, with some reluctance to accept (and perhaps a limited interest for) broad generalizations. This may however change, and this is indeed the challenge of complex systems biology: looking for general principles in biological systems, in the spirit of complex systems science which searches for similar features and behaviours in various kinds of systems. The hope to find such general principles appears well founded, and I will show in Section 2 that there are indeed data which provide support to this claim. Besides data, there are also general ideas and models concerning the way in which biological systems work. The strategy, in this case, is that of introducing simplified models of biological organisms or processes, and to look for their generic properties: this term, borrowed from statistical physics, is used for those properties which are shared by a wide class of systems. In order to model these properties, the most effective approach has been so far that of using ensembles of systems, where each member can be different from another one, and to look for those properties which are widespread. This approach was introduced many years ago [Kauffman, 1971] in modelling gene regulatory networks. At that time one had very few information about the way in which the expression of a given gene affects that of other genes, apart from the fact that this influence is real and can be studied in few selected cases (like e.g. the lactose metabolism in E. coli). Today, after many years of triumphs of molecular biology, much more has been discovered, however the possibility of describing a complete map of gene-gene interactions in a moderately complex organism is still out of reach. Therefore the goal of fully describing a network of interacting genes in a real organism could not be (and still cannot be) achieved. But a different approach has proven very fruitful, that of asking what are the typical properties of such a set of interacting genes. Making some plausible hypotheses and introducing some simplifying assumptions, Kauffman was able to address some important problems. In particular, he drew attention to the fact that a dynamical system of interacting genes displays selforganizing properties which explain some key aspects of life, most notably the existence of a limited number of cellular types in every multicellular organism (these numbers are of the order of a few hundreds, while the number of theoretically possible types, absent interactions, would be much much larger than the number of protons in the universe). In section 3 I will describe the ensemble based approach in the context of gene regulatory networks, and I will show that it can describe some important experimental data. Finally, in section 4 I will discuss some methodological aspects. (shrink)

Since Aristotle the central question in biology was the origin of organic form; a question put in the backyard by neo-Darwinism that considers organic form as a side effect of the interactions between genes and their products. On the other hand, the fashionable notion of self-organization also fails to provide a true causal explanation for organic form. For Aristotle form is both a cause and the principle of intelligibility and this coupled to the classical concepts of potentiality and (...) actuality provides a rational framework,currently embodied in the contemporary concept of ‘attractor’, for understanding the origin of organic form. (shrink)

Most molecular biological concepts derive from physical chemical assumptions about the genetic code that are basically more than 40 years old. Additionally, systems biology, another quantitative approach, investigates the sum of interrelations to obtain a more holistic picture of nucleotide sequence order. Recent empirical data on genetic code compositions and rearrangements by mobile genetic elements and non-coding RNAs, together with results of virus research and their role in evolution, does not really fit into these concepts and compel a (...) re-examination. In this review we try to find an alternate hypothesis. It seems plausible now that if we look at the abundance of regulatory RNAs and persistent viruses in host genomes, we will find more and more evidence that the key players that edit the genetic codes of host genomes are consortia of RNA agents and viruses that drive evolutionary novelty and regulation of cellular processes in all steps of development. This agent-based approach may lead to a qualitative RNA sociology that investigates and identifies relevant behavioural motifs of cooperative RNA consortia. In addition to molecular biological perspectives this may lead to a better understanding of genetic code evolution and dynamics. (shrink)

Phenotypic integration refers to the study of complex patterns of covariation among functionally related traits in a given organism. It has been investigated throughout the 20th century, but has only recently risen to the forefront of evolutionary ecological research. In this essay, I identify the reasons for this late flourishing of studies on integration, and discuss some of the major areas of current endeavour: the interplay of adaptation and constraints, the genetic and molecular bases of integration, the role of (...) phenotypic plasticity, macroevolutionary studies of integration, and statistical and conceptual issues in the study of the evolution of complex phenotypes. I then conclude with a brief discussion of what I see as the major future directions of research on phenotypic integration and how they relate to our more general quest for the understanding of phenotypic evolution within the neo-Darwinian framework. I suggest that studying integration provides a particularly stimulating and truly interdisciplinary convergence of researchers from fields as disparate as molecular genetics, developmental biology, evolutionary ecology, palaeontology and even philosophy of science. (shrink)

All the central assumptions of the Modern Synthesis (Neo-Darwinism) have been disproven. [1, 2] An article with the title, "Rocking the foundations of molecular genetics,” appearing in the prestigious Proceedings of the National Academy of Sciences at the end of 2012 [3] would have not been possible a decade ago. Groundbreaking experimental evidence of epigenetic maternal inheritance over several generations was published in the same journal, throwing the whole foundation of 21st century molecular genetics into question. (...) Neo-Darwinism attributed genetic change to random events, in which physiology was assumed to play little role. "The germ line was thought to be isolated from any influence by the rest of the organism and its response to the environment. [3] The fundamental concepts that constitute the foundations of contemporary systems biology include holism, emergentism, and robustness, compared to the concepts of reductionism, mechanism, and homeostasis, that form the foundations of molecular biology. [18] Holism is to be contrasted with reductionism which considers a system as merely composed of a sum of parts. Emergentism, the appearance of hierarchical levels of organization, is contrasted with mechanism of independent linear events. Robustness refers to the preservation of the functionality of a system to a certain degree despite external or internal changes, while homeostasis refers to maintaining the stability of the state of a system. The Vedantic view also proposes viewing life from the Organic Whole perspective, in which consciousness forms the supporting basis. The conscious agent is an important part of that view, but the absolute conception of a unifying center is not to be omitted if a proper conception is to be achieved. (shrink)

A phenome occurs through the many pathways of the complex net of interaction between the phenome and its environment; therefore researching and understanding how it arises requires investigation into many possible causes that are in constant interaction with each other. The most comprehensive investigations in biology are the ones in which many biologists from different sub-areas—evolutionary biology, developmental biology, molecular biology, physiology, genetics, epigenetics, ecology—have collaborated. Still, biologists do not always need to collaborate or (...) look for the most comprehensive explanations. A more standard investigation in biology occurs within a single subarea, and uses well-defined experiments with very specific conditions. This paper is about causation and related explanation in plant phenome research and its relevance to Aristotle’s Theory of Four Causes. I argue that there are causes which resemble Aristotle’s formal, material, and efficient causes in phenotype explanation and occurrence; but causes which resemble Aristotle’s final causes occur in phenotype explanation only, not in the occurrence. (shrink)

The guide explains the basic concepts of natural, social and evolutionary components and methods of risk management and control of modern biotechnologies stemming from the general theory of human evolution. A a transdisciplinary approach is a feature of the presentation of the material The risk is considered from the point of view of evolutionary anthropology, as a basic element of a stable evolutionary strategy of our biological species and the basis of a combination of natural-scientific and humanitarian forms of presentation (...) and interpretation of the material. CONTENT BIOSAFETY AND BIOETHICS IN BIOTECHNOLOGY (Introduction). Part 1. BIOTECHNOLOGY AS A FACTOR OF EVOLUTION AND A SOURCE OF TECHNOGENIC RISK. Chapter 1. GENERAL THEORY OF TECHNOLOGICAL RISK. Chapter 2. RISK AS AN ATTRIBUTE OF STABLE HUMAN EVOLUTIONARY STRATEGY. Chapter 3. BIOTECHNOLOGY AS A SOURCE OF BIORISKS Chapter 4. COMPONENTS OF THE "BIOLOGICAL FACTOR" OF RISK. Chapter 5. BIOLOGICAL WEAPONS and BIOTERRORISM. Part 2. BIOLOGICAL, SOCIAL AND EVOLUTIONARY COMPONENTS OF THE RISK OF MODERN BIOTECHNOLOGIES Chapter 6. RISK MANAGEMENT DURING BIOTECHNOLOGICAL RESEARCH.. Chapter 7. BIOTECHNOLOGY AS A SOURCE OF SOCIAL INSTABILITY. Chapter 8. BIOTECHNOLOGY AS A SOURCE OF CIVILIZATIONAL RISK. -/- . (shrink)

Natural selection [Darwin 1859] is perhaps the most important component of evolutionary theory, since it is the only known process that can bring about the adaptation of living organisms to their environments [Gould 2002]. And yet, its study is conceptually and methodologically complex, and much attention needs to be paid to a variety of phenomena that can limit the efficacy of selection [Antonovics 1976; Pigliucci and Kaplan 2000]. In this essay, I will use examples of recent work carried out in (...) my laboratory to illustrate basic research on natural selection as conducted using a variety of approaches, including field work, laboratory experiments, and molecular genetics. I also discuss the application of this array of tools to questions pertinent to conservation biology, and in particular to the all-important problem of what makes invasive species so good at creating the sort of problems they are infamous for [Lee 2002]. (shrink)

Manfred Eigen extended Erwin Schroedinger’s concept of “life is physics and chemistry” through the introduction of information theory and cybernetic systems theory into “life is physics and chemistry and information.” Based on this assumption, Eigen developed the concepts of quasispecies and hypercycles, which have been dominant in molecular biology and virology ever since. He insisted that the genetic code is not just used metaphorically: it represents a real natural language.However, the basics of scientific knowledge changed dramatically within the (...) second half of the 20th century.Unfortunately, Eigen ignored the results of the philosophy of science discourse on essential features of natural languages and codes: a natural language or code emerges from populations of living agents that communicate. This contribution will look at some of the highlights of this historical development and the results relevant for biological theories about life. (shrink)

This essay moves along broad lines from molecular biology to evolutionary biology and ecology to theology. Its objectives are to: 1) present some recent scientific findings in the emerging field of epigenetics that indicate that it is “the genome in context,” not genes per se, that are important in biological development and evolution; 2) show that this weakens the gene-centric neo-Darwinist explanation of evolution which, in fact, shares a certain preformationist orientation with intelligent design theory; 3) argue (...) that the evidence against a gene-centric view in no way negates Darwin’s central idea of “descent with modification”; 4) argue that an embrace of the evolutionary story, with all of its contingency and apparent lack of directionality, is not only consistent with Christianity, but actually resonates with the notion of the self-emptying love of God in Jesus Christ; and finally 5) suggest that we are called through an ecological imperative to embrace our evolutionary story, to listen to our “genetic coding,” and to reclaim our grounding as a species in the natural world. Corrigendum (published in later issue of journal): There was an error in the paragraph describing the mode of action of the small temporally-expressed RNAs (stRNAs) lin-4 and let-7 from Caenorhabditis elegans. Instead of reading "These two stRNAs act by binding to the tails of their target messenger RNAs (mRNAs); this results in destruction of the target and an overall drop in the level of production of protein from agouti mRNA" [note that agouti mRNA is not a target of these stRNAs], the sentence should have read, "These two stRNAs act by binding to the tails of target messenger RNAs (mRNAs); this leads to inhibition of translation of the mRNAs into protein and a consequent drop in the levels of the corresponding target protein.". (shrink)

The question of the holistic structure of an organism is a recurring theme in the philosophy of biology and has been increasingly discussed again in recent years. Organisms have recently been described as complex systems that autonomously create, maintain and reproduce themselves while constantly interacting with their environment. Key focal points include their autopoiesis, autonomy, agency and teleological structure. This perspective marks a significant advancement from the 20th-century viewpoint, which predominantly saw organisms as genetically programmed, randomly generated and blindly (...) selected survival-machines. However, crucial questions about the shape and development of organisms still lack answers. Shape and development are deeply interconnected and seem to require a holistic approach. Here, I will briefly outline a phenomenological perspective which could provide a framework for seeking answers to these fundamental questions. In particular, I propose a common four-fold phenomenal structure of the developing organism and the cognising consciousness, which makes it possible to observe the agential and teleological structure of the organism "from within". This fourfold structure also describes the molecular level and thus provides a general organismic concept. It furthermore corresponds to the four Aristotelian "causes" (conditions). (shrink)