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

The debate began when Chiapperino and Paneni highlighted a fundamental technical obstacle: epigenetic studies are largely unable to incorporate fine-grained mapping data of an individual’s surrounding social milieu. The same limitation, they noted, afflicts genomics. Zaina accepts this diagnosis and praises the authors for elevating questions of scientific epistemology into public debate. His response, however, goes a step further. He argues that because epigenetic marks are tightly coupled to DNA sequence, epigenetics is structurally doomed to reproduce the very shortcomings of genomics that Chiapperino and Paneni identified. If the sequence sets the stage for most methylation patterns, then no amount of interdisciplinary ingenuity will allow epigenetics to serve as a clean molecular record of social experience.

To understand why, Zaina insists, one must revisit the history of the concept. The term epigenetics traces back to Conrad Waddington’s definition of epigenesis in the 1940s, a description of molecular development that, in Zaina’s view, sits awkwardly with the modern scientific community’s intuition of what the field does. Epigenetics remained poorly understood until genomic imprinting revived it, because DNA methylation offered a mechanism to explain that clearly non-genetic phenomenon. The next breakthrough came with the demonstration that epigenetic marks can be modified by exogenous factors, notably through studies showing that early nutrition could alter methylation of transposable elements. From these milestones emerged the definition now taught in textbooks: a DNA sequence-independent, environmentally sensitive mode of gene regulation, widely adopted as a tool to hunt for markers of non-communicable diseases, particularly in light of genetics’ notorious missing heritability problem.

That definition, Zaina argues, can be dismantled with the field’s own data. The decisive evidence comes from methylation quantitative trait loci, or methylation QTL, first documented by Tycko’s group in 2008. These are genetic variants that predict methylation states at nearby or distant sites, and subsequent surveys show they account for the vast majority of DNA methylation variation in humans. A comprehensive analysis of human tissues found roughly twice as many methylation QTL as expression QTL colocalizing with genetic variants identified by genome-wide association studies. Even a textbook example of sequence dependence has long been available but rarely stated: mammalian CpG islands, the GC-rich regions surrounding many gene promoters, remain generally unmethylated precisely because of their peculiar sequence composition. The genetic grip on epigenetics is further tightened by methodology. Mendelian randomization, which exploits genetic variants as instruments, is currently the best available tool for assessing whether any given DNA methylation profile causally influences a phenotype, a dependence on genetics that Zaina finds telling.

There is also a quantitative prediction that follows from this tight coupling. If methylation is largely sequence-driven, then individual differentially methylated CpG sites should exert comparatively small phenotypic effects, echoing the missing heritability problem that has frustrated geneticists for decades. The available evidence, Zaina notes, suggests that this prediction is correct. He also flags a conceptual confusion at the heart of the field’s self-description: independence from changes in DNA sequence is often cited as the main difference between epigenetics and genetics, yet genetics deals with sequence variation in populations rather than sequence changes, mutations being a relatively minor topic. The distinction, in other words, is less clean than the standard rhetoric implies.

The second pillar of the popular narrative, the idea that the epigenome is an open book on which the environment can freely write, erase, or rewrite information, fares no better in Zaina’s assessment. He points to the controversy surrounding a famous New Yorker article that proposed epigenetics as the mechanism underlying phenotypic divergence between identical twins, an interpretation that drew sharp criticism from prominent epigeneticists. Even more contentious is the hypothesis of epigenetic transgenerational inheritance in humans, the notion that methylation patterns altered by a grandparent’s environment could be transmitted across generations. Reviews of the evidence describe it as highly controversial, with mechanisms in mammals poorly established and human data difficult to disentangle from genetic and cultural confounding.

What remains, once these assumptions are stripped away? In Zaina’s formulation, epigenetics describes a highly sequence-dependent and comparatively weakly environmentally sensitive mode of transcriptional regulation, functionally closer to the activity of transcription factors or DNA-binding long non-coding RNAs than to a free-floating environmental ledger. He even suggests the field might be more accurately renamed paragenetics. Adding micro-RNAs and non-coding RNAs to the definition, he argues, has only deepened the confusion. The counterfactual he poses is striking: had methylation QTL been documented forty years ago rather than in 2008, the current enthusiasm for epigenetics might never have taken hold. Had the higher affinity of DNA methyltransferases for RNA relative to DNA been appreciated earlier, textbooks might describe those enzymes as RNA-binding proteins that modify DNA chemistry.

The stakes of this conceptual housekeeping extend well beyond taxonomy. Zaina’s central concern is that biosocial epigenetics, the quest to find molecular signatures of adverse social environments, whether politically or economically adverse, is likely to uncover genetics-related phenomena rather than pure environmental imprints. Researchers searching for DNA methylation profiles written exclusively by an adverse milieu to explain how social circumstances create and maintain disadvantaged groups will, on his reading, inevitably bump into sequence-dependent variation. Such findings would be highly controversial if they appeared to clash with dominant views in identity politics or social constructivism. The devils of genetics when applied to social sciences and economics are obvious, he writes, but hidden ones may lurk in epigenetics, precisely because the field’s environmental framing can mask its genetic dependencies.

Zaina is careful not to dismiss the enterprise entirely. Reducing the daylight between epigenetics and fine-grained mapping of the social milieu remains, in his words, a noble and useful pursuit, and he credits Chiapperino and Paneni with correctly identifying the problem and acknowledging its difficulty even for the best interdisciplinary research and technological advances. But he insists that the hurdles will only be overcome after a correct understanding of the essence of epigenetics, however dynamic that essence proves to be. His closing question is deliberately uncomfortable: this territory feels remote from pipettes and tubes, and scientists must decide whether they should walk that far at all. The reply, published open access in Epigenetics Communications, ensures that the debate over whether epigenetics can ever truly bridge biology and society will continue, and that any future biosocial science will have to reckon with the sequence it inherits along with the environment it measures.

Subject of Research: The debate over whether epigenetics can function as a biosocial science given its dependence on DNA sequence

Article Title: Will epigenetics ever be a biosocial science? A reply to Chiapperino and Paneni

Article References: Zaina, S. (2023). Will epigenetics ever be a biosocial science? A reply to Chiapperino and Paneni. Epigenetics Communications, 3(1), Article 2. https://doi.org/10.1186/s43682-023-00018-0

Image Credits: AI Generated

DOI: 10.1186/s43682-023-00018-0

Keywords: epigenetics, DNA methylation, methylation QTL, biosocial science, genomics, social epigenomics, transgenerational inheritance, Mendelian randomization, gene regulation, missing heritability, Waddington, CpG islands

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

Chiapperino and Paneni’s argument was straightforward: the tools, techniques, and habits of mind inaugurated with genomics were repurposed for multi-omics and big data analytics, yet these approaches were never designed to disentangle the complex interactions and looping effects among biological and environmental factors. They called for less reductionism and more holistic methods in epigenetics research. Dupras, who has repeatedly voiced similar concerns about the purely biomedical translation of epigenetic knowledge, nonetheless finds the framing problematic. In his view, conceptualizing the problem of reductionism as a question of whether epigenetics succeeds or fails as a biosocial science invites a series of unexamined assumptions, five of which he systematically dismantles in his commentary.

The first assumption is that genetics is not a biosocial science. Dupras argues this is demonstrably wrong. Our genomes are constantly exposed to and disrupted by ionic radiation, oxidative stress, mutagens, and viruses, all of which can alter the linear sequence of DNA and thereby gene expression. DNA repair mechanisms are highly active but not always successful, and repeated exposure to stressors coupled with imperfect repair can produce permanent mutations that affect gene expression over the long term, in ways not unlike epigenetic modifications. Beyond molecular damage, social factors shape the prevalence of genes within families, communities, and populations: historical events, migrations, niche construction behaviors, and mating patterns all influence the human genome, its diversity, and the distribution of genetic variants over time. Social scientists have also long observed that groups form and are reinforced around shared biological traits, a phenomenon known as biosociality, in which belonging to such groups encourages individuals to adopt or reinforce associated behaviors.

The second assumption flips the question: is epigenetics itself truly biosocial? Dupras points out that many epigenetic traits are almost entirely determined by widely shared components of the human genome, leaving little room for social factors. During embryogenesis and fetal development, cells and tissues differentiate and acquire their specific functions through obligatory epigenetic modifications, largely via DNA methylation programs. These highly conserved, necessary processes are epigenetic, but it is hard to see how they qualify as biosocial. Moreover, thinking of epigenetics as uniformly biosocial downplays the variety of external factors that affect epigenetic mechanisms, including physical rather than social environments such as environmental chemicals and pharmaceutical products, as well as lifestyle factors like tobacco or alcohol consumption, which are shaped by social contingencies but also by individual behavior and decision-making.

Third, Dupras challenges the notion that epigenetics is a homogeneous scientific field. Drawing on a recent international survey of epigenetic researchers, he notes there is currently no consensus on the appropriate definition and scope of the discipline. While most researchers agree that DNA methylation and histone modifications fall within epigenetics, there is disagreement about whether mechanisms such as RNA interference and the regulation of transcription factors should be included. This dissensus creates practical challenges, for instance when assessing whether existing policies against genetic discrimination should extend to epigenetic information. The survey also showed that researchers are spread across many subfields, including disease, functional, developmental, environmental, and inheritance-focused epigenetics. Notably, the International Human Epigenome Consortium has focused from its inception on mapping reference epigenomes for various cell types, a methodologically valuable objective that does not capture how epigenetic variants change under exposure or disease. Some researchers, Dupras adds, do not even identify as epigeneticists, finding the term too broad or too narrow for their work.

Fourth, the assumption that epigenetics and genomics are fundamentally distinct does not survive close scrutiny. Some epigenetic variants are plastic and reversible, but others are remarkably stable and can hardly be affected by environmental or social exposures; some may even be considered innate rather than acquired, persisting from birth to death much like genetic variants. The definitional boundary is also contested. One of the most widely used definitions of modern epigenetics describes it as the study of changes in gene function that are mitotically or meiotically heritable and that do not entail a change in DNA sequence. While histone modifications clearly leave the sequence intact, the case of DNA methylation is murkier. Following Lappé and Landecker, Dupras asks why we take for granted that methylation does not change the sequence: what if cytosine methylated in this way were conceptualized as a distinct molecular entity rather than a modified version of the original base? Taking the conundrum seriously leaves two options: redefine epigenetics, or reconceptualize DNA methylation as a genetic change. Either way, the line between the fields blurs considerably.

Fifth, and perhaps most unsettling, Dupras questions the assumption that epigenetics’ biosocial character will automatically produce socially desirable outcomes. He agrees with Chiapperino and Paneni that research may be skewed toward treating biomarkers as mere targets for molecular and pharmacological intervention. But he wonders why we assume that knowledge of the molecular effects of social phenomena will translate into greater policy recognition and prevention of inequities created by the social determinants of health. The main challenge facing public health, he suggests, may be more biopolitical than scientific. There is a real risk that molecular knowledge will instead favor biomedical interventions that fix the biological consequences of morally questionable social inequalities while leaving the inequalities themselves untouched. There is also the danger of increased stigmatization and discrimination arising from emphasizing correlations between sociocultural factors and biological differences between individuals and groups.

There are practical obstacles as well. Correlating complex social and environmental phenomena with biological marks seems inevitably prey to reductionism, because a large diversity of social stimuli can affect the same epigenetic variants, and a single social stimulus can affect multiple variants, making it extremely challenging to accurately correlate scales that are largely incommensurable. At minimum, Dupras argues, it may not always be relevant or useful to attempt such correlations at the molecular level. While endorsing greater recognition of complexity may look good on paper, specifying and operationalizing that posture in the daily conduct of research is far harder, and it may not account for the many similarities and blurred lines between genetics and epigenetics.

Dupras suggests there may be sociohistorical reasons for our reductionist reflexes. Modern epigenetics is still a burgeoning field, welcomed with open arms by those rightly displeased with decades of genetic reductionism and the persistent belief that the DNA blueprint will solve the mysteries of biological identity. Consequently, epigenetics has been mobilized most vigorously for its differences from genetics. Instead of this polarization, he proposes, following Meloni, that epigenetics be understood as a boundary object, a study object whose nature and significance can be appreciated from multiple epistemological standpoints. Such an approach could promote dialogue and reflexivity between biology and the social sciences, and it is through that dialogue, Dupras concludes, that science will best confront the determinism, essentialism, and exceptionalism that have long shadowed genetics and now threaten to distort epigenetics as well.

Subject of Research: Critique of reductionism and biosocial framing in epigenetics research

Article Title: Being against reductionism regarding epigenetics

Article References: Dupras, C. (2023). Being against reductionism regarding epigenetics. Epigenetics Communications, 3(1), Article 4. https://doi.org/10.1186/s43682-023-00020-6

Image Credits: AI Generated

DOI: 10.1186/s43682-023-00020-6

Keywords: epigenetics, reductionism, biosocial science, genetics, DNA methylation, bioethics, genetic determinism, social determinants of health, epigenetic discrimination, International Human Epigenome Consortium, boundary object, interdisciplinarity

The dispute began with Chiapperino and Paneni’s earlier paper, Why epigenetics is (not) a biosocial science and why that matters, which examined whether and how epigenetic research can genuinely capture the entanglement of biological and social processes in health and disease. Dupras responded with a critical assessment, reading their argument as a call for less reductionism and more holistic methods in the field. That reading, the two authors now insist, misrepresents their intent. They never claimed that epigenetics should be assimilated to nurture while genetics stands for nature, nor did they seek to draw a sharp line between biosocial epigenetics and a supposedly non-biosocial genetics.

At the heart of the reply is a reframing of the central question. The authors argue that the problem is not whether the processes of development, health differentiation, and evolution are either natural or social, either biosocial or not. Instead, they ask to what extent the methods, tools, and study designs of epigenetics can capture the interactions that necessarily occur between nature and nurture, between biological and social processes. This developmental version of epigenetics, which they align with work by researchers such as Robert Lickliter and David Witherington, is explicitly designed to move beyond the inherited dichotomies of the nature-nurture debate rather than reproduce them under a new molecular vocabulary.

The authors also reject the charge that they are demanding a wholesale turn to holism. They acknowledge that the full complexity of biosocial processes may be incommensurable with the methods of the biomedical sciences, yet they explicitly disavow any foundational endeavor toward an all-encompassing holistic biosocial science. Drawing on the history, philosophy, and social anthropology of science, including the work of Hans-Jörg Rheinberger, John Law, and Annemarie Mol, they contend that the reductionism-holism dichotomy is itself inadequate for understanding postgenomic scientific practice. The point, they write, is not whether epigenetic methods are reductionist, since they plainly are, but how they operate most prolifically at the fuzzy boundary between the trivial and the complex.

To make this abstract argument concrete, Chiapperino and Paneni turn to the measurement tools that dominate epigenetic studies of psychosocial environments: stress scales and allostatic load indices. These instruments, widely used to link adversity to molecular change, have drawn sustained criticism for lacking definition, standardization, and fidelity, and for what anthropologist Jörg Niewöhner has called the molecularization of biography and milieu. The authors concede that such methods are certainly reductionist. But they ask whether reductionism necessarily dooms these tools to a poor picture of the environmental embeddedness of health, and their answer is a qualified no.

The problem, they argue, lies less in the instruments than in the study designs that house them. Much epigenetic research reproduces a simplistic linearity: exposures, objectified through stress or allostatic load measurements, produce biological differences readable in the epigenome, which are in turn linked to disease through mechanistic or statistical associations. A different configuration employing the very same reductionist tools could avoid this pitfall. Repeated longitudinal measures of psychological and physiological scales, for example, could reveal the multidirectional effects of stress, its biological embodiment over time, and the biopsychosocial looping effects through which people respond to and reshape their own conditions. Such designs would leave the reductionist qualities of the methods untouched while dramatically complexifying the account of the phenomenon they can offer.

The reply also addresses Dupras’s defense of ambitious large-scale initiatives such as the International Human Epigenome Consortium. Chiapperino and Paneni are careful to state that they do not question the consortium’s importance for advancing standards, methods, reference knowledge, and a sense of global community among epigeneticists. Nor do they deny that the boundary between epigenetics and genetics is blurred, a definitional controversy that continues to occupy commentators such as Bernhard Horsthemke. Yet they maintain that a theoretically modest point remains highly relevant for any endeavor seeking to build reference epigenomes for the understanding of health and disease.

That point comes into sharp focus around ethnicity and DNA methylation. Few researchers hold that interindividual differences in the epigenome can be fully recapitulated by genetic variation, including variation across so-called genetic ancestry groups. The authors cite a study by James Galanter and colleagues showing that, across the genome, genetic ancestry accounts for roughly three-quarters of the association between ethnicity and methylation differences, with the remaining quarter attributed to shared environmental, social, and cultural factors within groups. In that residual quarter lies evidence that both ancestry and the social construction of ethnic difference shape epigenetically measurable disparities in disease prevalence and health trajectories. This finding, they argue, validates ongoing calls to diversify reference epigenomic maps and epigenome-wide association studies beyond their current overrepresentation of participants of European ancestry, but it also demands more than genetic imputation alone.

Here the authors pose a pointed question to the global epigenetics community: what is currently on the agenda to account for the share of health disparities across social groups that stems from differences in social and environmental exposures rather than genetic ancestry? They suggest that the biosocial dimensions of ethnic differences in the epigenome likely lack a fixed ontology, being neither purely biological nor purely social. For some traits, reference epigenomes may prove highly sensitive to genetic differences across ancestry groups; for others, they may be more open to varied developmental trajectories, local contexts, and culturally situated practices. They caution, following Maurizio Meloni and colleagues, that even simplistic cause-effect models can constitute a problematic form of biosocial determinism around epigenetic differences.

Ultimately, Chiapperino and Paneni frame their reply as a call to symmetry: a demand that the development of epigenetic tools, methods, and study designs refrain from overlooking either side of the biosocial continuum. They do not claim to offer a unique path, nor to certify whether epigenetics is or is not a holistic biosocial science. The simplistic stance, they suggest, belongs to those who feel compelled to pick a side in what is ultimately a fabricated dichotomy between the biological and social origins of epigenetic differences. In a field increasingly asked to explain how poverty, discrimination, and stress become embodied, that insistence on balance may prove more consequential than any single methodological prescription, reminding researchers that the most rigorous science of the epigenome may be the one that refuses to let nature and nurture compete for exclusive ownership of it.

Subject of Research: The role of reductionist and holistic methods in capturing biosocial interactions in epigenetic research

Article Title: In medio stat virtus? A reply to Dupras

Article References: Chiapperino, L., & Paneni, F. (2023). In medio stat virtus? A reply to Dupras. Epigenetics Communications, 3(1), Article 5. https://doi.org/10.1186/s43682-023-00017-1

Image Credits: AI Generated

DOI: 10.1186/s43682-023-00017-1

Keywords: epigenetics, biosocial science, reductionism, holism, DNA methylation, allostatic load, genetic ancestry, health disparities, International Human Epigenome Consortium, nature and nurture, study design, philosophy of science