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