'...a challenging and useful book, both because it provokes a careful scrutiny of one's own basic ideas regarding evolutionary theory, and because it cuts across so many biological disciplines.' -The Quarterly Review of Biology 'In my view, this work exemplifies Theoretical Biology at its best...here is rampant speculation that is consistently based on cautious reasoning from the available data. Even more refreshing is the absence of sloganeering, grandstanding, and 'isms'.' -Biology and Philosophy 'Epigenetics is fundamental to understanding both development and (...) gene expression, and not surprisingly, evolutionary biologists have long been fascinated with its proper place in evolutionary theory...Enter Jablonka and Lamb, who provide a thoughtful review of the recent molecular literature and suggest a number of potential consequences.' -EvolutionSince first publication of this controversial book, much of the initial opposition to the ideas it contained has been replaced by a general, although often grudging, acceptance of them. Advances in knowledge, especially at the molecular level, have enhanced general awareness and interest in epigenetics and the evolution of systems that store and transmit information and put any of the authors' speculations on a more solid basis. This paperback edition contains a new Preface that sets out the major changes in the scientific world and in the authors' own thinking that have occurred since the book was published. A new Appendix provides a selected bibliography of the many books and articles about epigenetic inheritance and its role in evolution that have appeared since first publication. (shrink)

In recent decades, advances in the life sciences have created an unprecedentedly detailed picture of heredity and the formation of the phenotype where clusters of simplistic reductionist and deterministic views and interpretations have begun to lose ground to more complex and holistic notions. The developments in gene regulation and epigenetics have become a vivid emblem of the ongoing ‘softening’ of heredity. Despite this headway, the outlook and rhetoric widely popular in the twentieth century favoring the ‘gene’ in the ‘genegenetic plasticityphenotypeenvironment’ (...) tetrad have not been successfully tackled but continue to exist in parallel with a new, equally monochromatic, viewpoint championing genetic plasticity. An examination of epigenetics and its presentation in the public sphere, open to a conversation with the social disciplines and philosophy, could address this dichotomy and contribute to the discourse. This article outlines key biological aspects of epigenetics and discusses the language, presentation and wider resonance of this field of life science research. (shrink)

A rich literature in public health has demonstrated that health is strongly influenced by a host of environmental factors that can vary according to social, economic, geographic, cultural or physical contexts. Bioethicists should, we argue, recognize this and – where appropriate – work to integrate environmental concerns into their field of study and their ethical deliberations. In this article, we present an argument grounded in scientific research at the molecular level that will be familiar to – and so hopefully more (...) persuasive for – the biomedically-inclined in the bioethics community. Specifically, we argue that the relatively new field of molecular epigenetics provides novel information that should serve as additional justification for expanding the scope of bioethics to include environmental and public health concerns. We begin by presenting two distinct visions of bioethics: the individualistic and rights-oriented and the communitarian and responsibility-oriented. We follow with a description of biochemical characteristics distinguishing epigenetics from genetics, in order to emphasize the very close relationship that exists between the environment and gene expression. This then leads to a discussion of the importance of the environment in determining individual and population health, which, we argue, should shift bioethics towards a Potterian view that promotes a communitarian-based sense of responsibility for the environment, in order to fully account for justice considerations and improve public health. (shrink)

How epigenetic mechanisms regulate genome output and response to stimuli is a fundamental question in development and disease. Past decades have made tremendous progress in deciphering the regulatory relationships involved by correlating aggregated (epi)genomics profiles with global perturbations. However, the recent development of epigenetic editing technologies now enables researchers to move beyond inferred conclusions, towards explicit causal reasoning, through 'programing’ precise chromatin perturbations in single cells. Here, we first discuss the major unresolved questions in the epigenetics field that (...) can be addressed by programable epigenome editing, including the context‐dependent function and memory of chromatin states. We then describe the epigenetic editing toolkit focusing on CRISPR‐based technologies, and highlight its achievements, drawbacks and promise. Finally, we consider the potential future application of epigenetic editing to the study and treatment of specific disease conditions. (shrink)

To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes (...) in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)

This chapter offers a brief review of theories on mirror neuron development, highlighting different models. These models focus on either the role of genetic mechanisms or the contributions of experience and of learning processes in shaping the brain circuits involved in action–perception coupling. As an alternative, the chapter proposes an epigenetic model for mirror neuron development, explaining how such a model can help to elucidate, within a unifying explanatory framework, the emergence, diversity, and functional reuse of mirror neurons. Lastly, (...) a related evolutionary scenario is sketched in which epigenetic regulation, genetic assimilation/the Baldwin effect, and niche construction play crucial roles in mirror neuron evolution. (shrink)

This paper argues that nothing that has been discovered in the increasingly complex delails of gene regulation has provided any grounds to retract or qualify Crick's version of the central dogma. In particular it defends the role of the genes as the sole bearers of information, and argues that the mechanism of epigenetic modification of the DNA is but another vindication of Crick's version of the central dogma. The paper shows that arguments of C.K. Waters for the distinctive causual (...) role of the genes are equivalent in important respects to the present ones and concludes with a defense of the informational role of the genes against an argument from trans-actĭng genetic regulation due to Stotz. (shrink)

Recent epidemiological reports of associations between socioeconomic status and epigenetic markers that predict vulnerability to diseases are bringing to light substantial biological effects of social inequalities. Here, we start the discussion of the moral consequences of these findings. We firstly highlight their explanatory importance in the context of the research program on the Developmental Origins of Health and Disease (DOHaD) and the social determinants of health. In the second section, we review some theories of the moral status of health (...) inequalities. Rather than a complete outline of the debate, we single out those theories that rest on the principle of equality of opportunity and analyze the consequences of DOHaD and epigenetics for these particular conceptions of justice. We argue that DOHaD and epigenetics reshape the conceptual distinction between natural and acquired traits on which these theories rely and might provide important policy tools to tackle unjust distributions of health. (shrink)

We hypothesize that heritable epigenetic changes can affect rates of fitness increase as well as patterns of genotypic and phenotypic change during adaptation. In particular, we suggest that when natural selection acts on pure epigenetic variation in addition to genetic variation, populations adapt faster, and adaptive phenotypes can arise before any genetic changes. This may make it difficult to reconcile the timing of adaptive events detected using conventional population genetics tools based on DNA sequence data with environmental drivers (...) of adaptation, such as changes in climate. Epigenetic modifications are frequently associated with somatic cell differentiation, but recently epigenetic changes have been found that can be transmitted over many generations. Here, we show how the interplay of these heritable epigenetic changes with genetic changes can affect adaptive evolution, and how epigenetic changes affect the signature of selection in the genetic record. (shrink)

The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles arrested in meiotic prophase I and is maintained independent of DNA replication and cell proliferation, thereby lacking stem cell‐based maintenance. Largely unknown is how cellular states of the ovarian reserve are established and maintained for decades. Our recent study revealed that a distinct chromatin state is established during ovarian reserve formation in mice, uncovering a novel window of (...) class='Hi'>epigenetic programming in female germline development. We showed that an epigenetic regulator, Polycomb Repressive Complex 1 (PRC1), establishes a repressive chromatin state in perinatal mouse oocytes that is essential for prophase I‐arrested oocytes to form the ovarian reserve. Here we discuss the biological roles and mechanisms underlying epigenetic programming in ovarian reserve formation, highlighting current knowledge gaps and emerging research areas in female reproductive biology. (shrink)

We tend to hold people responsible for their choices, but not for what they can’t control: their nature, genes or biological makeup. This thought-provoking collection redefines the boundaries of moral responsibility. It shows how epigenetics reveals connections between our genetic make-up and our environment. The essays challenge established notions of human nature and the nature/nurture divide and suggest a shift in focus from individual to collective responsibility. Uncovering the links between our genetic makeup, environment and experiences, this is an important (...) contribution to ongoing debates on ethics, genetics and responsibility. (shrink)

Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological (...) variability. An improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine. Epigenetic and transcriptional variability mediate phenotypic plasticity, enabling adaptation to changing environments. In this review, we describe the sources of inter- and intra-individual variability and discuss epigenetic regulators of gene expression variability, including DNA methylation and chromatin structure. Understanding these molecular mechanisms will improve therapeutic approaches and personalized medicine. (shrink)

Robert Sparrow argues that genome editing is unlikely to be person-affecting for the foreseeable future and, as a result, will neither benefit nor harm edited individuals. We regard Sparrow’...

This short paper comments on the connections between epigenetics, responsiveness and embodiment. Epigenetics has solidified a new conception of DNA as “responsive,” and rightfully so. Yet, the discussion too easily falls back to metaphors of agency and can show a tendency to see responsiveness and embodiment as based on epigenetics, which is shown to be wrong.

All animals have evolved solutions to manage their genomes, enabling the efficient organization of meters of DNA strands in the nucleus and allowing for nuanced regulation of gene expression while keeping transposable elements suppressed. Epigenetic modifications are central to accomplishing all these. Recent advances in sequencing technologies and the development of techniques that profile epigenetic marks and chromatin accessibility using reagents that can be used in any species has catapulted epigenomic studies in diverse animal species, shedding light on (...) the multitude of epigenomic mechanisms utilized across the evolutionary tree. Now, comparative epigenomics is a rapidly growing field that is uncovering mechanistic aspects of epigenetic modifications and chromatin organization in non‐model invertebrates, ranging from octopus to sponges. This review puts recent discoveries in the epigenetics of non‐model invertebrates in historical context, and describes new insight into the patterning and functions of DNA methylation and other highly conserved epigenetic modifications. (shrink)

Recent evidence of intergenerational epigenetic programming of disease risk broadens the scope of public health preventive interventions to future generations, i.e. non existing people. Due to the transmission of epigenetic predispositions, lifestyles such as smoking or unhealthy diet might affect the health of populations across several generations. While public policy for the health of future generations can be justified through impersonal considerations, such as maximizing aggregate well-being, in this article we explore whether there are rights-based obligations supervening on (...) intergenerational epigenetic programming despite the non-identity argument, which challenges this rationale in case of policies that affect the number and identity of future people. We propose that rights based obligations grounded in the interests of non-existing people might fall upon existing people when generations overlap. In particular, if environmental exposure in F0 will affect the health of F2 through epigenetic programming, then F1 might face increased costs to address F2's condition in the future: this might generate obligations upon F0 from various distributive principles, such as the principle of equal opportunity for well being. (shrink)

From the 1930s through the 1970s, C. H. Waddington attempted to reunite genetics, embryology, and evolution. One of the means to effect this synthesis was his model of the epigenetic landscape. This image originally recast genetic data in terms of embryological diagrams and was used to show the identity of genes and inducers and to suggest the similarities between embryological and genetic approaches to development. Later, the image became more complex and integrated gene activity and mutations. These revised (...) class='Hi'>epigenetic landscapes presented an image of how mutations could alter developmental pathways to yield larger phenotypic changes. These diagrams became less important as the operon became used to model differential gene regulation. (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)

There is increasing evidence for epigenetically mediated transgenerational inheritance across taxa. However, the evolutionary implications of such alternative mechanisms of inheritance remain unclear. Herein, we show that epigenetic mechanisms can serve two fundamentally different functions in transgenerational inheritance: (i) selection-based effects, which carry adaptive information in virtue of selection over many generations of reliable transmission; and (ii) detection-based effects, which are a transgenerational form of adaptive phenotypic plasticity. The two functions interact differently with a third form of epigenetic (...) information transmission, namely information about cell state transmitted for somatic cell heredity in multicellular organisms. Selection-based epigenetic information is more likely to conflict with somatic cell inheritance than is detection-based epigenetic information. Consequently, the evolutionary implications of epigenetic mechanisms are different for unicellular and multicellular organisms, which underscores the conceptual and empirical importance of distinguishing between these two different forms of transgenerational epigenetic effect. (shrink)

Parental effects are a major source of phenotypic plasticity and may influence offspring phenotype in concert with environmental demands. Studies of “environmental epigenetics” suggest that (1) DNA methylation states are variable and that both demethylation and remethylation occur in post‐mitotic cells, and (2) that remodeling of DNA methylation can occur in response to environmentally driven intracellular signaling pathways. Studies of mother‐offspring interactions in rodents suggest that parental signals influence the DNA methylation, leading to stable changes in gene expression. If parental (...) effects do indeed enhance the “match” between prevailing environmental demands and offspring phenotype, then the potential for variation in environmental conditions over time would suggest a mechanism that requires active maintenance across generations through parental signaling. We suggest that parental regulation of DNA methylation states is thus an ideal candidate mechanism for parental effects on phenotypic variation. (shrink)

The purpose of this article is to argue for a position holding that epigenetic responsibility primarily should be a political and not an individual responsibility. Epigenetic is a rapidly growing research field studying regulations of gene expression that do not change the DNA sequence. Knowledge about these mechanisms is still uncertain in many respects, but main presumptions are that they are triggered by environmental factors and life style and, to a certain extent, heritable to subsequent generations, thereby reminding (...) of aspects of Lamarckism. Epigenetic research advances give rise to intriguing challenges for responsibility relations between the society and the individual. Responsibility is commonly understood in a backwards-looking manner, identifying causally responsible actors to blame for a bad outcome. If only a backwards-looking responsibility model is applied, epigenetics might give rise to arduous responsibility ascriptions to individuals for their health and the health of their future descendants. This would put heavy responsibility burdens on actors constrained by unequal social and economic structures. In contrast, a forward-looking responsibility notion takes account of structural conditions and pay attention to who is best placed to do something about conditions contributing to bad outcomes. A forward-looking responsibility notion would partly free disadvantaged individuals from responsibility, and identify actors with power and capacity to do something about structural factors constraining genuine choice. (shrink)

Recent findings in epigenetics have been attracting much attention from social scientists and bioethicists because they reveal the molecular mechanisms by which exposure to socioenvironmental factors, such as pollutants and social adversity, can influence the expression of genes throughout life. Most surprisingly, some epigenetic modifications may also be heritable via germ cells across generations. Epigenetics may be the missing molecular evidence of the importance of using preventive strategies at the policy level to reduce the incidence and prevalence of common (...) diseases. But while this “policy translation” of epigenetics introduces new arguments in favor of public health strategies and policy-making, a more “clinical translation” of epigenetics is also emerging. It focuses on the biochemical mechanisms and epigenetic variants at the origin of disease, leading to novel biomedical means of assessing epigenetic susceptibility and reversing detrimental epigenetic variants. In this paper, we argue that the impetus to create new biomedical interventions to manipulate and reverse epigenetic variants is likely to garner more attention than effective social and public health interventions and therefore also to garner a greater share of limited public resources. This is likely to happen because of the current biopolitical context in which scientific findings are translated. This contemporary neoliberal “regime of truth,” to use a term from Michel Foucault, greatly influences the ways in which knowledge is being interpreted and implemented. Building on sociologist Thomas Lemke's Foucauldian “analytics of biopolitics” and on literature from the field of science and technology studies, we present two sociological trends that may impede the policy translation of epigenetics: molecularization and biomedicalization. These trends, we argue, are likely to favor the clinical translation of epigenetics—in other words, the development of new clinical tools fostering what has been called “personalized” or “precision” medicine. In addition, we argue that an overemphasized clinical translation of epigenetics may further reinforce this biopolitical landscape through four processes closely related to neoliberal pathways of thinking: the internalization and isolation of socioenvironmental determinants of health and increased opportunities for commodification and technologicalization of health care interventions. (shrink)

It seems that the reception of Conrad Hal Waddington’s work never really gathered speed in mainstream biology. This paper, offering a transdisciplinary survey of approaches using his epigenetic landscape images, argues that (i) Waddington’s legacy is much broader than is usually recognized—it is widespread across the life sciences (e.g. stem cell biology, developmental psychology and cultural anthropology). In addition, I will show that (ii) there exist as yet unrecognized heuristic roles, especially in model building and theory formation, which Waddington’s (...) images play within his work. These different methodological facets envisioned by Waddington are used as a natural framework to analyze and classify the manners of usage of epigenetic landscape images in post-Waddingtonian ‘landscape approaches’. This evaluation of Waddington’s pictorial legacy reveals that there are highly diverse lines of traditions in the life sciences, which are deeply rooted in Waddington’s methodological work. (shrink)

Our view of heredity can potentially be distorted by the ease of introducing heritable changes in the replicating gene sequences but not in the cycling assembly of regulators around gene sequences. Here, key experiments that have informed the understanding of heredity are reinterpreted to highlight this distortion and the possible variety of heritable changes are considered. Unlike heritable genetic changes, which are always associated with mutations in gene sequence, heritable epigenetic changes can be associated with physical or chemical changes (...) in molecules or only changes in the system. The transmission of cycling stores along the continuous lineage of cells that connects successive generations creates waves of activity and localization of the molecules that together form the cell code for development in each generation. As a result, heritable epigenetic changes can include any that can alter a wave such as changes in form, midline, frequency, amplitude, or phase. Testing this integrated view of all heritable information will require the concerted application of multiple experimental approaches across generations. (shrink)

Epigenetic changes are implicated in aging and cancer. Sometimes, it is clear whether the causing agent of the condition is a genetic factor or epigenetic. In other cases, the causative factor is unclear, and could be either genetic or epigenetic. Is there a general role for epigenetic changes in cancer and aging? Here, I present the paradigm of causative roles executed by epigenetic changes. I discuss cases with clear roles of the epigenome in cancer and (...) aging, and other cases showing involvement of other factors. I also present the possibility that sometimes causality is difficult to assign because of the presence of self‐reinforcing loops in epigenetic regulation. Such loops hinder the identification of the causative factor. I provide an experimental framework by which the role of the epigenome can be examined in a better setting and where the presence of such loops could be investigated in more detail. (shrink)

This chapter analyses the implications of findings in epigenetics for the ascription of moral responsibility for children. It contrasts shared understandings of procreative responsibility and discusses its extension to include all (individual or collective) actors who influence a child’s gene expression. It also problematizes the focus on biology in this process, using the example of epigenetics as a crossover between social and biological factors that contribute to a child’s life. Epigenetics blurs the boundary between biology and the environment, and thus (...) allows an analysis of contributions to children’s lives that goes beyond classical dualistic categories such as genetic versus environmental or biological versus social. The analysis is undertaken against the broader background of the determination of moral responsibility for children. (shrink)

Everyone has heard of ‘epigenetics’, but the term means different things to different researchers. Four important contemporary meanings are outlined in this paper. Epigenetics in its various senses has implications for development, heredity, and evolution, and also for medicine. Concerning development, it cements the vision of a reactive genome strongly coupled to its environment. Concerning heredity, both narrowly epigenetic and broader ‘exogenetic’ systems of inheritance play important roles in the construction of phenotypes. A thoroughly epigenetic model of development (...) and evolution was Waddington’s aim when he introduced the term ‘epigenetics’ in the 1940s, but it has taken the modern development of molecular epigenetics to realize this aim. In the final sections of the paper we briefly outline some further implications of epigenetics for medicine and for the nature/nurture debate. (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)

During early embryonic development in several metazoans, accurate DNA replication is ensured by high number of replication origins. This guarantees rapid genome duplication coordinated with fast cell divisions. In Xenopus laevis embryos this program switches to one with a lower number of origins at a developmental stage known as mid‐blastula transition (MBT) when cell cycle length increases and gene transcription starts. Consistent with this regulation, somatic nuclei replicate poorly when transferred to eggs, suggesting the existence of an epigenetic memory (...) suppressing replication assembly origins at all available sites. Recently, it was shown that histone H1 imposes a non‐permissive chromatin configuration preventing replication origin assembly on somatic nuclei. This somatic state can be erased by SSRP1, a subunit of the FACT complex. Here, we further develop the hypothesis that this novel form of epigenetic memory might impact on different areas of vertebrate biology going from nuclear reprogramming to cancer development. (shrink)

Plasmodium falciparum is the most deadly human malarial parasite, responsible for an estimated 207 million cases of disease and 627,000 deaths in 2012. Recent studies reveal that the parasite actively regulates a large fraction of its genes throughout its replicative cycle inside human red blood cells and that epigenetics plays an important role in this precise gene regulation. Here, we discuss recent advances in our understanding of three aspects of epigenetic regulation in P. falciparum: changes in histone modifications, nucleosome (...) occupancy and the three‐dimensional genome structure. We compare these three aspects of the P. falciparum epigenome to those of other eukaryotes, and show that large‐scale compartmentalization is particularly important in determining histone decomposition and gene regulation in P. falciparum. We conclude by presenting a gene regulation model for P. falciparum that combines the described epigenetic factors, and by discussing the implications of this model for the future of malaria research. (shrink)

This article takes Catherine Malabou’s provocative insistence on an alliance between plasticity and feminism to initiate an exploration of gestation and its representation in the context of the postgenomic age. I argue that Malabou’s attention to epigenetic schemas of life and becoming can inform and, in turn, be enriched by feminist film-philosophy which locates the maternal as an alternative schema of embodied subjectivity – simultaneously displacing essentialising over-reliance on gender/sex binaries without entirely metaphorising or abstracting the material processes which (...) subtend bodies and their openness to difference. Drawing on recent feminist scholarship, including Ann Carruthers’s Fertile Visions and Sophie Lewis’s Full Surrogacy Now, I turn to Lucile Hadžihalilović’s Evolution (2015) in order to approach gestational bodies as a central site for both the violent subjugation of embodied life and a feminist ethics and aesthetics of affective relationality. Part science-fiction, fairy-tale and body horror, Hadžihalilović’s film responds to contemporary bio-genetic innovations: Malabou’s elaboration of the “phylogenetic remains” and “cellular potentials” that epigenetic plasticity reactivates guides my reading of its seething maternal waters, multiply directed gestational bodies and various forms of plastic co-becoming. As well as being exemplary of new epigenetic imaginaries, Hadžihalilović’s complex foetal/fertile visions illuminate how feminist-philosophical-artistic practices may elaborate an epigenet(h)ics of life – informed by past forms, present configurations, and open to future bio-possibilities. (shrink)

Epigenetic modifications, such as DNA methylation and post‐translation modifications of histones, have been shown to play an important role in chromatin structure, promoter activity, and cellular reprogramming. Large protein complexes, such as Polycomb and trithorax, often harbor multiple activities which affect histone tail modification. Nevertheless, the mechanisms underlying the deposition of these marks, their propagation during cell replication, and the alteration on their distribution during transformation still require further study. Here we review recent data on those processes in both (...) normal and cancer cells, and we propose that the unscheduled expression of oncogenic transcription factors causes reprogramming of normal cells into cancer stem cells. (shrink)

Bourdieu suggested that the habitus contains the ‘genetic information’ which both allows and disposes successive generations to reproduce the world they inherit from their parents’ generation. While his writings on habitus are concerned with embodied dispositions, biological processes are not a feature of the practical reason of habitus. Recent critiques of the separate worlds of biology and culture, and the rise in epigenetics, provide new opportunities for expanding theoretical concepts like habitus. Using obesity science as a case study we attempt (...) to conceptualise the enfolding of biological and social processes (via a Deleuzian metaphor) to develop a concept of biohabitus – reconfiguring how social and biological environments interact across the life course, and may be transmitted and transformed intergenerationally. In conclusion we suggest that the enfolding and reproduction of social life that Bourdieu articulated as habitus is a useful theoretical frame that can be enhanced to critically develop epigenetic understandings of obesity, and vice versa. (shrink)

Because the term ‘epigenetics’ has been used in a wide array of inquires within the life-sciences, it has come to bear a significant number of meanings. And just as biologists cannot come to an univocal understanding on what epigenetics connotes, the effect that its study has had in challenging contemporary neo-Darwinian, genecentred paradigms is also unclear. Some scientists and philosophers go as far as to say epigenetics has eroded dichotomies central to modern western thought, such as nature and nurture, or (...) genotype and phenotype – but the matter ignites a great deal of controversy. What seems unquestionable, however, is that the notion that genetic material is a ‘programme’ that simply manifests itself in an external correlative, thus accounting for the development of a living organism, seems to have – at the very least – shifted. Rather than attempting to pinpoint the implications of epigenetics in contemporary biology, this article focuses on the ‘literary’ dimension of scientific debate: instability of meaning, metaphorical shifts, a redrawing of margins and limits. Furthermore, it will be argued that metaphor does not merely have a pedagogical value in the field but rather works proactively throughout the genesis, development and morphology of science and theory. By outlining a ‘literary’ dimension in discussions around genetics one can identify what Squier refers to as ‘the epistemological value of the imprecise’, which in the case of epigenetics seems to have jeopardized not only the boundaries between genes and their external correlatives, but even challenged the frontiers of traditional disciplinary discourse. (shrink)

Ideas about heredity and evolution are undergoing a revolutionary change. New findings in molecular biology challenge the gene-centered version of Darwinian theory according to which adaptation occurs only through natural selection of chance DNA variations. In Evolution in Four Dimensions, Eva Jablonka and Marion Lamb argue that there is more to heredity than genes. They trace four "dimensions" in evolution -- four inheritance systems that play a role in evolution: genetic, epigenetic, behavioral, and symbolic. These systems, they argue, can (...) all provide variations on which natural selection can act. Evolution in Four Dimensions offers a richer, more complex view of evolution than the gene-based, one-dimensional view held by many today. The new synthesis advanced by Jablonka and Lamb makes clear that induced and acquired changes also play a role in evolution.After discussing each of the four inheritance systems in detail, Jablonka and Lamb "put Humpty Dumpty together again" by showing how all of these systems interact. They consider how each may have originated and guided evolutionary history and they discuss the social and philosophical implications of the four-dimensional view of evolution. Each chapter ends with a dialogue in which the authors engage the contrarieties of the fictional "I.M.," or Ifcha Mistabra -- Aramaic for "the opposite conjecture" -- refining their arguments against I.M.'s vigorous counterarguments. The lucid and accessible text is accompanied by artist-physician Anna Zeligowski's lively drawings, which humorously and effectively illustrate the authors' points. (shrink)

Over the past few years several drugs that target epigenetic modifications have shown clinical benefits, thus seemingly validating epigenetic cancer therapy. More recently, however, it has become clear that these drugs are either characterized by low specificity or that their target enzymes have low substrate specificity. As such, clinical proof‐of‐concept for epigenetic cancer therapies remains to be established. Human cancers are characterized by widespread changes in their genomic DNA methylation and histone modification patterns. Epigenetic cancer therapy (...) aims to restore normal epigenetic modification patterns through the inhibition of epigenetic modifier enzymes. In this review, we provide an overview about the known functional roles of DNA methyltransferases, histone deacetylases, histone methyltransferases, and demethylases in cancer development. The available data identify several examples that warrant further consideration as drug targets. Future research should be directed toward targeted enzyme inhibition and toward exploring interactions between epigenetic pathways to maximize cancer specificity. (shrink)

Emerging evidence that intrauterine exposures to environmental stressors can ‘programme’ epigenetic modifications in offspring, leading to long-lasting health risks, has generated debate about whether prospective mothers have a specific ‘epigenetic’ moral responsibility. However, to date, proposals for maternal epigenetic responsibility have failed to grapple adequately with the uncertainty of scientific evidence, and specifically, whether the causal basis for intrauterine epigenetic effects is sufficiently established to ground claims of moral responsibility. Causality is widely considered a necessary condition (...) for the attribution of moral responsibility. In this paper, we show that much foetal programming science in humans has yet to establish a causal epigenetic connection between intrauterine exposures and subsequent offspring health impacts. This research struggles to establish that the relationship between such exposures and offspring health risks is in fact causal, neither has it been able to evince the causal significance of exposures during pregnancy to such outcomes. We argue that these two challenges to establishing causality in foetal programming research seriously undercut the idea that prospective mothers may have a moral responsibility to ensure the epigenetics of their offspring. (shrink)

Environmental epigenetics is increasingly employed to understand the health outcomes of communities who have experienced historical trauma and structural violence. Epigenetics provides a way to think about traumatic events and sustained deprivation as biological “exposures” that contribute to ill-health across generations. In Australia, some Indigenous researchers and clinicians are embracing epigenetic science as a framework for theorising the slow violence of colonialism as it plays out in intergenerational legacies of trauma and illness. However, there is dispute, contention, and caution (...) as well as enthusiasm among these research communities.In this article, we trace strategies of “refusal” (Simpson, 2014) in response to epigenetics in Indigenous contexts. Drawing on ethnographic fieldwork conducted in Australia with researchers and clinicians in Indigenous health, we explore how some construct epigenetics as useless knowledge and a distraction from implementing anti-colonial change, rather than a tool with which to enact change. Secondly, we explore how epigenetics narrows definitions of colonial harm through the optic of molecular trauma, reproducing conditions in which Indigenous people are made intelligible through a lens of “damaged” bodies. Faced with these two concerns, many turn away from epigenetics altogether, refusing its novelty and supposed benefit for Indigenous health equity and resisting the pull of postgenomics. (shrink)

Human chromosome 11p15 comprises two imprinted domains important in the control of fetal and postnatal growth. Novel studies1-3 establish that imprinting at one of these, the IGF2-H19 domain, is epigenetically deregulated (with loss of DNA methylation) in Silver-Russell Syndrome (SRS), a congenital disease of growth retardation and asymmetry. Previously, the exact opposite epigenetic alteration (gain of DNA methylation) had been detected at the domain's ‘imprinting control region’ (ICR) in patients with Beckwith-Wiedemann Syndrome (BWS), a complex disorder of fetal overgrowth. (...) However, more frequently, BWS is caused by loss of DNA methylation at the ICR that regulates the second imprinted domain at 11p15. Interestingly, a similar epigenetic alteration (with loss of methylation) at a putative ICR on human chromosome 6q24, is involved in transient neonatal diabetes mellitus (TNDM), a congenital disease with intrauterine growth retardation and a transient lack of insulin. Thus, fetal and postnatal growth is epigenetically controlled by different ICRs, at 11p15 and other chromosomal regions. BioEssays 28: 453–459, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Every cell, tissue, organ and organism is competent to use signs to exchange information reaching common coordinations and organisations of both single cell and group behavior. These sign-mediated interactions we term biological communication. The regulatory system that works in development, morphology, cell fate and identity, physiology, genetic instructions, immunity, memory/learning, physical and mental disease depends on epigenetic marks. The communication of cells, persistent viruses and their defectives such as mobile genetic elements and RNA networks ensures both the transport of (...) regulatory instructions and the reprogramming of these instructions. But how are the different states of the epigenome orchestrated? The epigenetic pathways respond to various signaling cues such as DNA methylation, histone variants, histone modifications, chromatin structure, nucleosome remodeling, and epigenetic interactions. Epigenetic signals are responsible for the establishment, maintenance and reversal of transcriptional states that are fundamental for the cell's ability to memorize past events, such as changes in the external environment, socio-sphere or developmental cues. External signals trigger changes in the epigenome, allowing cells to respond dynamically. Internal signals direct activities that are necessary for body maintenance, and repairing damaged tissues and organs. With the emergence of epigenetic memory, organisms can fix historical and context dependent impressive experiences. Evolution from now on learnt to learn. Learning means organisms can avoid reproduction of always the same. This is key to adaptation. However, inheritance of acquired characteristics is only one of the many examples of the explanatory power of epigenetics. Behavioral epigenetics demonstrates the way in which environmental and social experiences produce individual differences in behaviour, cognition, personality, and mental health. This book assembles experts to outline the various motifs of all kinds of epigenetic regulation of cells throughout their lives. (shrink)

In this paper, I investigate the relation of Kant's theory of biology to epigenetic accounts of organic generation and development. In the literature, a dispute about similarities between Blumenbach's epigenetic account and Kant dominated the debate for many years (see Lenoir 1980, 1981, and 1982, 17–34, Richards 2000; 2002, 207–37; Look 2006, and van den Berg 2009). Some more recent interpreters claim that Wolff's, more than Blumenbach's account plays the pivotal role in the development of a vitalistic conception (...) of epigenesis in Kant (see Dupont 2007 and Huneman 2007). Although I myself hold the view that Kant's position contains preformistic and epigenetic characteristics, in the current paper I focus solely on an investigation of epigenetic elements in Kant's account and compare them to the corresponding epigenetic elements in Wolff's theory. Section I of the paper is devoted to an analysis of Wolff's most important epigenetic theorems: the notion of the essential power (vis essentialis) and the conception of the part-whole composition of organized matter. Although Wolff describes the essential power vitalisticly, as a principle of life, he understands it as the cause of mechanical motions explaining the generation, nourishment, and the growth of an organism. Wolff's model of the part-whole composition of organic matter is subtle, but committed to fundamental mechanistic assumptions, such as that the organism as a whole is composed of inorganic parts. In section II, I analyze the corresponding elements in Kant's theory: the notion of the formative power and the conception of the whole-part composition of organized materials. Kant describes the formative power as a principle that causes the purposive form of an organized being such that matter and mechanism are the means to the purpose of the being as their end. The purpose of the whole is a functional unit which is in principle superior to the form and matter of the subordinate parts. The parts are combined into such a whole in being mutually cause and effect of each other and in being related to the superior whole. In section III, I respond to the debate in the literature. Against Dupont (2007) and Huneman (2007) I argue that, according to Wolff, the vis essentialis accounts for mechanic effects in matter, whereas, according to Kant, the formative power explains the intentional order (form, end, purpose) of an individual organized being, its parts, and its species. Since this view is closer to Blumenbach than to Wolff, the ongoing comparison between Kant and Blumenbach in the literature is justified. However, the emphasis on the specific part-whole composition that Kant considers to be the determining feature of an organized being can be found only in Wolff and not in Blumenbach—though Wolff and Kant describe it in opposing ways. This increases the systematic importance of Wolff for Kant. Thus, a fresh look on the historical debate is required. (shrink)

How fast? How strong? How many? So what? Why do numbers matter in biology? Chromatin binding proteins are forever in motion, exchanging rapidly between bound and free pools. How do regulatory systems whose components are in constant flux ensure stability and flexibility? This review explores the application of quantitative and mathematical approaches to mechanisms of epigenetic regulation. We discuss methods for measuring kinetic parameters and protein quantities in living cells, and explore the insights that have been gained by quantifying (...) and modelling dynamics of chromatin binding proteins. (shrink)

This paper examines the construction of maternal responsibility in transgenerational epigenetics and its implications for pregnant women. Transgenerational epigenetics is suggesting a link between maternal behaviour and lifestyle during pregnancy and the subsequent well-being of their children. For example, poor prenatal diet and exposure to maternal distress during pregnancy are linked to epigenetic changes, which may cause health problems in the offspring. In this field, the uterus is seen as a micro-environment in which new generations can take shape. Because (...) epigenetics concerns how gene expression is influenced by the social realm, including a range of environmental conditions such as stress, diet, smoking, exercise, exposure to chemicals, pollution, and environmental hazards, the research findings in this area have direct policy relevance. For policy makers, rather than controlling this complex range of determinants of health, isolating and targeting maternal body and responsibilising mothers for the control of this micro-environment might seem feasible. Yet, examining the maternal body in isolation as a powerful environment to shape the health of next generations not only responsibilises women for the environment that they cannot control but also makes them a target for intrusive and potentially exploitative biomedical interventions. Even though ‘social factors’ are increasingly considered in epigenetics writing, the phrase is usually taken as self-explanatory without much elaboration. Drawing on the Covid-19 pandemic, this paper moves the current debate forward by providing consolidated examples of how individuals, including pregnant women, have little control over their environment and lifestyle. As evidenced by the pandemic’s disproportionate effects on people with low socioeconomic or poor health status, some pregnant women bore considerable physical and psychological stress which combined with other stress factors such as domestic violence. (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)

This article develops a biosemiotic ´hyper-narrative model´ for the purposes of investigating emergent motor behaviors. It proposes to understand such behaviors in terms of the following associations: the organization of information acquired from the environment, focusing on narrative; the organizational dynamics of epigenetic mechanisms that underly the neural processes facilitating the processing of information; and the evolution of emergent motor behaviors that enable the informational acquisition. The article describes and explains these associations as part of a multi-ordered and multi-causal (...) generative principle of biological phenotype emergence that supersedes the theory of the arbitrary coding of life. Preceeding from narrative’s operations in a biological dimension, the article presents scientific research dealing with the associations of action-oriented organization of narrative information and underlying psychological and physiological dynamics and depicts the relations with a distributed multi-directional mapping dynamic. The article presents the explanatory implications of such a hyper-narrative dynamic model on an example of emergent motor behaviors – bruxism. Central to this discussion is the exploration of the possible mechanisms of emergence and etiopathogenesis of bruxism, based on its neurobiology. The article takes the perspective that complex systems dynamics themselves with a tendency to narrative form are found not to be underlain merely by arbitrary coded mechanisms but, rather, biological neural networks (e.g. neuro-epigenetic network) that render context-dependent bio-informational mapping analogous to that of the narrative possible. (shrink)

Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age‐associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age‐associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de‐differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti‐ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure to reprogramming (...) factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed. (shrink)

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed (...) with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables. (shrink)

Transcriptome sequencing has identified more than a thousand potentially imprinted genes in the mouse brain. This comes as a revelation to someone who cut his teeth on the identification of imprinted genes when only a handful was known. Genomic imprinting, an epigenetic mechanism that determines expression of alleles according to sex of transmitting parent, was discovered over 25 years ago in mice but remains an enigmatic phenomenon. Why do these genes disobey the normal Mendelian logic of inheritance, do they (...) function in specific processes, and how is their imprinting conferred? Next generation sequencing technologies are providing an unprecedented opportunity to survey the whole genome for imprinted genes and are beginning to reveal that imprinting may be more pervasive than we had come to believe. Such advances should lay the foundation for a definitive account of imprinting, but may also challenge accepted views on what it means to be imprinted.Editor's suggested further reading in BioEssays RNA as the substrate for epigenome‐environment interactions Abstract. (shrink)