The editorial announcing the section, published as an open-access article in the journal, was written by Luca Chiapperino of the University of Lausanne, Eline Bunnik of Erasmus MC in Rotterdam, and Gerard J. van den Berg of the University of Groningen. Their argument is straightforward but ambitious: epigenetics sits at a crossroads where biology meets the social world so directly that the two cannot be disentangled, and the research community needs a stable venue where life scientists, ethicists, philosophers, historians and social scientists can interrogate the field together. The new section will accept original research, reviews, perspectives and correspondence pieces, and the editors explicitly welcome authors from inside and outside academia. It is an unusual move for a molecular life sciences journal, and it reflects a growing recognition that the questions epigenetics raises are too big for any single discipline to answer alone.

The first pillar of the new section concerns the ethical, legal and social aspects of epigenetic research, often abbreviated to ELSA. The editors point out that this body of scholarship has accumulated for years without settling some of its most fundamental questions. One of the sharpest is the role epigenetics should play in public health promotion. If the science can be read as a molecular account of how social determinants of health, such as deprivation, stress and environmental exposures, become inscribed in our biology and shape disease predispositions, does that strengthen the case for social and community interventions, or does it instead invite a rhetoric of personal responsibility, in which individuals are urged to make positive lifestyle changes to protect their epigenomes? The editorial notes that the ELSA literature remains divided on how public representations of epigenetic knowledge should frame modifiable disease risks, and on what the field implies for the unfair distribution of environmental and transgenerational risks across societies.

Among the most technically provocative issues the section hopes to address is epigenetic editing. Techniques derived from CRISPR-Cas systems can now be repurposed not to cut and rewrite the DNA sequence itself, but to add, remove or reposition the chemical marks that regulate gene expression. Because these marks are, in principle, transient and reversible, epigenetic editing is often assumed to be a safer and less controversial option than genomic editing, which makes permanent, heritable changes to the genetic code. The editors argue that this assumption deserves scrutiny rather than complacency. A decade of debate around genome editing has crystallised a set of ethical intuitions, and the reversible nature of epigenetic modifications challenges them in ways that have not yet been properly dissected. As epigenetic editing approaches clinical translation, the section will seek work that maps the specific concerns and opportunities of the technology on its own terms, rather than treating it as a footnote to the genome editing debate.

The ethical agenda extends to the conduct of research itself. The editors invite contributions on best practices for study design and on the rules of engagement for participants in epigenetic studies, with particular attention to vulnerable populations. This is not an abstract concern. Epigenetic studies increasingly involve refugees, asylum seekers, marginalised communities and people exposed to environmental harms, groups for whom the promise of molecular insight into their suffering carries real risks of stigmatisation, re-identification and exploitation. The section also welcomes ELSA assessments of understudied topics, including the societal concerns attached to the epigenetic engineering of plants, an area where agricultural applications may be outpacing public deliberation. By bringing these questions into a life sciences journal rather than confining them to bioethics periodicals, the editors hope to reach the researchers whose daily decisions actually shape how such studies are designed and communicated.

A second key dimension of the section concerns the clinical promise and peril of epigenetic technologies. The editors are interested in assessments of the utility and limitations of existing and future applications in the diagnosis, stratification and prognosis of disease, along with the risks these applications carry and the models needed for their responsible clinical implementation. Epigenome-wide association studies have proliferated, machine learning approaches are being applied to DNA methylation data to build diagnostic and classification tools, and epigenetic risk-predictive screening for cancers is already being debated. Each of these developments raises questions about validity, interpretability and equity that the editors want examined before, not after, the technologies reach the clinic. The section will serve as a place where the technical literature on biomarkers and screening can be read alongside careful analysis of what these tools mean for patients and health systems.

On a deeper level, the editors encourage submissions that uncover the epigenetic mechanisms and pathways through which socio-economic conditions and life events influence later health outcomes. This is where epigenetics becomes genuinely interdisciplinary in a demanding sense. Epidemiologists and economists have documented transgenerational effects of childhood conditions on the health and education of subsequent generations, and epigenetics offers a candidate molecular substrate for such effects. Studies of this kind, the editorial argues, improve understanding of the long-run implications of social, economic and psychological factors for health and for societal inequality. If adversity leaves molecular traces that shape disease risk decades later, then epigenetics becomes not just a laboratory science but a lens on how inequality is biologically embedded, and potentially reproduced, across lifetimes and generations.

The third pillar of the section addresses the agendas, questions and research practices of epigenetics itself, including how these shape the societal circulation of the knowledge produced. A substantial body of empirical work in Science and Technology Studies has examined the intrinsic biases and limitations of epigenetic research practices, biases that may produce a controversial uptake of the science in public. Scholars in this tradition have analysed, for example, how assumptions about the causal primacy of maternal effects influence research on the developmental origins of health and disease, how gendered imaginaries structure knowledge of epigenetic programming, and how laboratory constructions of early-life adversity frame what counts as an intervention. The editors observe that this work is rarely brought to the attention of life scientists and seldom gains recognition beyond networks of social science collaboration. They are asking Science and Technology Studies scholars to condense their thick socio-anthropological analyses into short perspectives and correspondence articles suitable for a life sciences audience, with the explicit aim of improving the methods, designs and configurations of research that critics have found wanting.

Fourth, the section will serve as an outlet for philosophical, historical and socio-anthropological work on the theoretical and experimental foundations of epigenetics. This literature has interrogated how the field reiterates fundamental questions about life and biology, and how it challenges the established conception of the body as a self-contained entity. Epigenetics straddles disciplinary divides between the life and social sciences, and it straddles research traditions within biology itself, oscillating between mechanism and organicism, reduction and emergence, linear determination and plasticity. The editors argue that these seemingly abstract debates are far from idle. Definitional and methodological disagreements within epigenetics, including disputes over what global methylation measures actually signify and how the epigenetic timeline should be conceptualised, offer a prolific terrain for empirical and conceptual inquiry into foundational notions such as genes, genomes and organisms. They envision the section as a trading zone where theoretical analysis and pragmatic scientific relevance can productively engage with one another.

Underlying the whole enterprise is the notion of the biosocial, a term the editors use to describe a contested experimental space at the crossroads of the social and life sciences, one that captures complex, non-linear social-biological transitions in the shaping of the epigenome and situates biology within its material, social and ecological environments. The section welcomes honest reports on the challenges of interdisciplinary work towards a biosocial science of health, because collaboration, as the editors note, is a loaded practice: the encounter of different research cultures is intricate, power-driven, often frustrating and risky. Extending the journal’s stated openness to negative data beyond molecular biology, they invite accounts of interdisciplinary experimentations that succeeded and those that did not. The editors believe a venue that connects and integrates different communities of researchers may be a major enabler of a thriving epigenetic science, and that the time is ripe for collaborative approaches capable of structuring an effective contribution of epigenetics to societal flourishing.

Subject of Research: The ethical, societal and interdisciplinary appraisal of epigenetics research

Article Title: ‘Epigenetics and Society’: a forum for the theoretical, ethical and societal appraisal of a burgeoning science

Article References: Chiapperino, L., Bunnik, E., & van den Berg, G. J. (2022). ‘Epigenetics and Society’: a forum for the theoretical, ethical and societal appraisal of a burgeoning science. Epigenetics Communications, 2(1), Article 6. https://doi.org/10.1186/s43682-022-00013-x

Image Credits: AI Generated

DOI: 10.1186/s43682-022-00013-x

Keywords: epigenetics, ELSA, bioethics, epigenetic editing, CRISPR, biosocial science, Science and Technology Studies, public health, interdisciplinarity, DNA methylation, social determinants of health, Epigenetics Communications

At the heart of the disagreement lies a deceptively simple question: how much of the variation observed between individual epigenomes is actually driven by genes rather than by environment? Zaina’s reply leaned heavily on evidence that genetic differences between individuals exert a powerful influence on epigenetic patterns, particularly DNA methylation, the chemical modification of cytosine bases that is the most widely studied epigenetic mark. He pointed to studies such as work by Husquin and colleagues, published in Genome Biology, which explored the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation. If, as Zaina contends, the individual characteristics of the epigenome are for the vast majority dependent on interindividual genetic differences, he asks whether the field should really invest so heavily in understanding the social and environmental ramifications of those differences.

Zaina’s answer is a firm no, and he offers two distinct reasons for it. The first is that he believes there is little to be learnt from studies of environmentally driven variation in epigenetic predispositions to disease, because what he calls the grip of genetics over epigenetics is so strong that the field should, in his view, be renamed paragenetics. The term is deliberately provocative: it suggests that epigenetics is not an autonomous discipline studying environmental regulation of the genome, but essentially a satellite of genetics, a layer of molecular detail whose variation is predetermined by underlying DNA sequence. The second reason is more subtle and more philosophical. Zaina warns that by calling for a complexification of the biosocial tools of epigenetics, researchers run the risk of reifying the social differences under study, converting them into the genetic differences that supposedly have a grip on them. In other words, the very act of tracing social disparities to molecular marks might end up naturalizing those disparities as biological facts.

Chiapperino and Paneni’s response does not dismiss these concerns. They concede that Zaina’s reading of the relationship between genetics and epigenetics contains several elements of truth, and they note that these elements can also be found in a well-established thread of philosophical, historical and sociological scholarship on the subject. Epigenetic differences, they acknowledge, may not simply be the marks, the product, or the biological correlates of one’s unique exposures to ecological, material and social environments. The epigenome is also the result of developmental trajectories, meaning the timing of events during an organism’s development, and of individual genetic differences, meaning variation in DNA sequence. The authors are explicit that they never intended to suggest otherwise, and they credit Zaina for acknowledging that dialogue around the biosocial aspects of epigenetics is worth the community’s effort.

But the authors argue that a wrong conclusion is often drawn from this acknowledgment. Claiming that the presence of genetics’ grip on the epigenome proves either that environmental determinants are unimportant, or that the epigenome is in essence under the control of the genome, is, in their view, just as problematic as the opposite claim that the epigenome sits entirely at the mercy of its environments. The reason, they insist, is that this is not an either/or matter. Drawing on extensive scholarship in developmental epigenetics and on decades of analysis of the nature-nurture debate, they argue that the dichotomous framing itself is the problem. Genetic and non-genetic factors, they write, constitute a dynamic, mutually dependent, relational developmental system within which different components and levels of organization coact to promote the emergence, maintenance, or modification of phenotypic traits. On this view, asking whether genes or environment matter more is a category error, because both are constitutive of the developmental process rather than competing causes of it.

From this diagnosis flows what Chiapperino and Paneni describe as a pragmatic call towards methodological symmetry. Their complaint is not that epigenetics ignores biology, but that the sophistication of its methods, tools and questions is strikingly lopsided. When researchers study biological variables of developmental systems, they deploy elaborate molecular assays, statistical models and experimental designs of considerable complexity. Yet when it comes to socio-environmental variables and their biological ramifications, the same level of methodological rigor is rarely matched. Why, the authors ask, should the measurement of social exposures, life conditions and environmental contexts remain so comparatively crude when the molecular readouts they are supposed to explain have become so refined? This asymmetry, they suggest, is a genuine scientific weakness, not merely a sociological observation, because poorly characterized environmental variables undermine the very inferences that epigenetic studies are designed to support.

The second half of their reply tackles Zaina’s warning about reification more directly. Chiapperino and Paneni state plainly that they do not believe the complexity of the phenotypes and human conditions studied in epigenetics will ever be amenable to genetic differences, let alone be bound to be reframed as genetics-related phenomena. Crucially, their reasoning is not that misinterpretation is impossible. They fully acknowledge that genetic or epigenetic differences can be misread as privileged informational sources, obscuring the deep social, historical and environmental ramifications behind them, and they cite a body of critical scholarship that has repeatedly raised the alarm about risky revivals of sociobiological ideas within epigenetics. Scholars such as Maurizio Meloni, who has written on race in an epigenetic time, and Dupras, Saulnier and Joly, who surveyed the ethical, legal and social dimensions of the field, have hammered this nail on its head, in the authors’ words. The concern that epigenetics could become a vehicle for old biological determinism dressed in new molecular clothing is taken seriously rather than waved away.

Instead, the authors ground their confidence in a different principle: the impossibility of reducing complex phenotypic differences to either one of their components, whether the genome or the environment. There may be specific phenotypes for which a genetic difference is more instructive for understanding the roles and contributions of a given epigenetic difference, including those relating to environmental exposures or developmental trajectories. Yet even these phenotypes, they argue, must ultimately be explained as the product of the biosocial components of the system, that is, of the organism as a whole embedded in its conditions of life. Once this distinction is recognized, the authors write, they cannot share Zaina’s caution about the risk of affirming the primacy of the genome through the epigenome. A risk of misinterpreting the biosocial dimensions of the epigenome certainly exists, but they pose a pointed counter-question: is that risk enough of a reason to give up on what Zaina himself called the noble and useful enterprise of reducing the daylight between epigenetics and fine-grained mapping of the social milieu?

The exchange closes on a note that is part challenge and part invitation. Experimenting with the epistemic foundations and political undertones of a biosocial epigenetics, the authors concede, is no easy task, and it may carry a controlled and relative risk of discomfort. But they believe there exist few alternatives to walking into this territory, a peregrination metaphor they borrow from Zaina himself, without taking that risk of thinking and writing about these issues with colleagues from different trajectories, if not different worldviews. It may be far from the comfort zone of pipettes and tubes, they write, but it may nonetheless be a productive and exciting stroll. Their closing line, urging scientists to take a walk on the wild side, captures the stakes of the debate: whether epigenetics will retreat into a purely molecular, genetically anchored discipline, or embrace the harder, messier work of integrating rigorous social science into its study of how lives become biology. The correspondence, published as open access in Epigenetics Communications and supported by a Swiss National Science Foundation Ambizione grant, makes clear that this conversation is far from over, and that its outcome will shape how a generation of researchers interprets the molecular traces of human difference.

Subject of Research: The debate over genetic versus environmental influences on epigenetic variation and the biosocial ambitions of epigenetics

Article Title: Walk on the wild side: a response to Zaina

Article References: Chiapperino, L., & Paneni, F. (2023). Walk on the wild side: a response to Zaina. Epigenetics Communications, 3(1), Article 3. https://doi.org/10.1186/s43682-023-00019-z

Image Credits: AI Generated

DOI: 10.1186/s43682-023-00019-z

Keywords: epigenetics, DNA methylation, biosocial science, nature and nurture, developmental epigenetics, genetics, gene-environment interaction, social epigenetics, biological determinism, Epigenetics Communications, Chiapperino, Zaina

The research, led by Marloes Oosterhof and Louis Coussement of the University of Groningen together with colleagues in Belgium, Austria and the Netherlands, focused on the liver, the metabolic command center that manages the fuel switch from glucose to fat oxidation that hibernation demands. Because facultative hibernators like the Syrian hamster enter torpor only in response to environmental cues, shortening days, cold and food scarcity, their bodies must actively reprogram gene expression rather than simply follow a fixed seasonal clock. That flexibility makes epigenetic mechanisms, the chemical systems that switch genes on and off without altering the underlying sequence, prime suspects for orchestrating the transition.

To test this idea, the team induced hibernation in Syrian hamsters by shortening the light-dark cycle and lowering ambient temperature, then collected liver samples at carefully defined phases: summer euthermia, when animals were active and warm; late torpor, more than 72 hours after the animals had settled into a bout; and both early and late arousal, shortly after the animals rewarmed. Using infrared motion detectors, the researchers confirmed each animal’s state before euthanasia, ensuring that the molecular snapshots truly reflected the hibernation phase rather than guesswork about body temperature.

The first layer of analysis examined the expression of 94 genes encoding epigenetic writer and eraser enzymes, the proteins that add or remove chemical marks on histones and DNA. Of the 83 genes that could be reliably measured, 11 shifted significantly between phases. Strikingly, four histone acetyltransferases, KAT6A, KAT6B, KAT7 and KAT13D, better known as the circadian gene CLOCK, were differentially expressed, with most declining during torpor and rebounding during arousal. Three deacetylases, SIRT2, SIRT7 and HDAC11, also changed, along with two histone methyltransferases, one demethylase and the DNA demethylating enzyme TET2.

Notably, several of these enzymes, including PCAF, GCN5L2, HAT1 and CBP, had been flagged in previous work on the thirteen-lined ground squirrel, an obligatory hibernator, but showed no expression changes in the hamster. This divergence suggests that facultative hibernators may deploy a distinct epigenetic toolkit, one tailored to switching hibernation on and off in response to the environment rather than to an internal circannual rhythm. The downregulation of CLOCK in the hamster liver is particularly intriguing, since recent work indicates that the liver pauses its circadian rhythms during hibernation while the brain retains them.

Gene expression, however, is only an indirect readout. The team therefore measured histone acetylation directly, first by Western blot and then by quantitative mass spectrometry, a technique that can determine exactly how many acetyl groups sit on specific lysine residues of histones H3 and H4. The results were consistent and telling. Overall acetylation of histone H3 dropped during late torpor, with the acetylation of lysines 18 and 23 falling by roughly 5 and 14 percent respectively, and rising again during arousal. H3K27ac, a mark classically associated with active enhancers and open chromatin, was lowest in torpor and recovered as animals rewarmed, a pattern that fits the idea of chromatin condensing, and transcription shutting down, while the animal is cold and metabolically dormant.

Histone H4 told a subtler story. Unlike H3, whose acetylation largely rebounded during arousal, the H4 peptide spanning lysines 5, 8, 12 and 16 remained under-acetylated even after the animals had rewarmed. The single most heavily used site, H4K16, a modification with the unusual ability to both promote and repress transcription depending on context, was significantly less acetylated in late arousal than in summer-active animals. The researchers point to SIRT2 and SIRT7, both of which target H4K16 and both of which were upregulated during arousal, as plausible culprits, noting that these sirtuins can translocate into the nucleus during cell-cycle transitions and stress, both of which accompany the metabolic turbulence of rewarming.

On the enzyme-activity side, histone acetyltransferase activity stayed flat across all phases, but histone deacetylase activity peaked in late torpor. Inhibitor profiling revealed that a single enzyme, HDAC6, accounted for roughly 71 percent of total hepatic HDAC activity. Yet here the plot thickened: although HDAC6 activity was high and histone acetylation low during torpor, the acetylation of alpha-tubulin, HDAC6’s best-known cytosolic target, actually increased. The authors suggest that HDAC6 may relocate to the nucleus during torpor, deacetylating histones there while leaving tubulin untouched, and note that the enzyme is also tied to hepatic gluconeogenesis and to protective responses in ischemic liver injury, processes highly relevant to both hibernation and, potentially, human organ preservation.

Perhaps the most surprising negative result concerned DNA methylation. Using both the Luminometric Methylation Assay and whole-genome bisulfite sequencing, the team found no significant differences in global cytosine methylation at CpG or non-CpG sites across any hibernation phase, and promoter methylation of the differentially expressed genes was likewise unchanged. This stability mirrored the near-absence of changes in the expression of DNA methyltransferases and demethylating enzymes, and it contrasts with reports of methylation shifts in ground squirrels and horseshoe bats. In the Syrian hamster, at least, the epigenetic levers of hibernation appear to be pulled at the histone level rather than at the DNA level.

The broader implications reach well beyond rodent physiology. Because facultative hibernators can trigger hypometabolic, cytoprotective states essentially on command, understanding their epigenetic switches could inform strategies to protect organs during transplantation, to limit ischemic damage, and even to slow aging, given recent evidence that epigenetic aging is effectively stalled during hibernation in yellow-bellied marmots. The authors caution that their bulk liver measurements largely reflect hepatocytes and that single-cell follow-up work will be needed to resolve contributions from rarer cell types, and that the expression changes, though modest in fold change, match the magnitude of the measured histone modifications. Still, the message is clear: when a hamster decides to hibernate, it does not rewrite its DNA. It retunes the packaging, loosening and tightening the spools of chromatin to silence the genome through the cold and swing it back open for the warmth of arousal.

Subject of Research: Epigenetic regulation of gene expression, specifically histone acetylation and DNA methylation, in the liver of facultatively hibernating Syrian hamsters

Article Title: Changes in histone lysine acetylation, but not DNA methylation during facultative hibernation in Syrian hamster liver

Article References: Oosterhof, M. M., Coussement, L., van Pijkeren, A., Kwiatkowski, M., Zwinderman, M. R. H., Dekker, F. J., de Meyer, T., Reitsema, V. A., Bischoff, R., Guryev, V., Bouma, H. R., Henning, R. H., & Rots, M. G. (2024). Changes in histone lysine acetylation, but not DNA methylation during facultative hibernation in Syrian hamster liver. Epigenetics Communications, 4(1), Article 1. https://doi.org/10.1186/s43682-023-00024-2

Image Credits: AI Generated

DOI: 10.1186/s43682-023-00024-2

Keywords: hibernation, Syrian hamster, epigenetics, histone acetylation, DNA methylation, HDAC6, sirtuins, liver metabolism, torpor, chromatin, KAT6A, epigenetics communications