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