More Nurture, Less Nature?

What if genes weren’t the perfect blueprint we’ve been led to believe they are? What if your body was constantly being shaped by its environment? What if your children’s ...

What if genes weren’t the perfect blueprint we’ve been led to believe they are? What if your body was constantly being shaped by its environment? What if your children’s biology could be influenced by the anxiety you feel or the trauma you endure? How would this knowledge change our relationship to our external environment and our responsibility to it and future generations?

For most of the 20th century, the gene held an iconic status, and the genetic code was considered a secular version of the “book of life.” Genes were consistently seen as the key biological factor in determining health, development, behavior, and biological heredity, culminating in the completion of the Human Genome Project in 2003. Since the turn of the 21st century, however, the centrality of genes has been challenged by a number of epigenetic findings.

Epigenetics is usually defined today as molecular changes to gene regulation that are not dependent on DNA sequences. These changes—DNA methylation and histone modifications among others—result in the activation or silencing of gene expression. They may be driven by genetic signals or environmental cues originating in the individual body or in society. The rise of epigenetics has brought wider environmental factors to the forefront of molecular biology. Factors like toxins, stress, food, and socioeconomic status have been found to directly affect gene expression, with complex and lasting consequences on present and future health trajectories. If this is the “book of life,” then it is one that is constantly being rewritten.

Epigenetics research increasingly focuses on the transmission of these environmental effects across generations, not only in plants or lower animals but also in mammals, including humans. The best evidence for this, according to some epigenetics researchers, comes from epidemiologic studies that have shown, for example, the long-term health implications for individuals who were prenatally exposed to famine during the Nazi blockade of West Holland (known as the Dutch Hunger Winter). The claims of such effects between or across generations remain controversial and the generalizability and frequency of epigenetic effects questioned.1 Nonetheless, it is socially significant that the NIH is nowadays funding cutting-edge research on the link between paternal diet and offspring metabolism, that is, how epigenetic inheritance through mammalian sperm may “carry information about the environment between generations.”2

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Epigenetic arguments have potentially paradigmatic implications for the understanding of human health, development, and policy. They signal a shift from notions of biological fixedness to ideas of the plasticity and “impressionability” of biological material—notions seemingly forgotten during most of the 20th century.

This shift is much more than just a biological one, however. Epigenetics and programs in Developmental Origins of Health and Disease (DOHaD) are contributing to the rewriting of the human body as permeable down to its genomic core, leaving it, therefore, vulnerable to new risks and new forms of intervention. As the first social analyses of epigenetics argue, what is at stake are the ways in which we understand the management of bodies and the reproduction of social norms.3

How will such ideas—that, say, a future parent’s diet or lifestyle impacts their offspring’s well-being—change notions of responsibility and risk or normality and pathology? If cheap saliva testing can offer epigenetic markers to distinguish between chronological and biological age, who is going to use this knowledge and to what ends?4 At the level of population, social management questions with deep political implications are also being asked: What about groups exposed to famine or violence? Are they “damaged forever before birth,” as one sensationalist headline claimed when reporting on a pioneering study on epigenetic differences between the richest and poorest areas of Glasgow?5 If so, do they need some special form of help, or might their acquired harm make them unresponsive to future intervention?

These questions, though speculative, highlight the potential of epigenetic debates to challenge some established coordinates in 20th-century biology/society debates: namely, that there is a clear distinction between biological and social causes, genetic and environmental factors.

 

A Historical Roadmap to Our Epigenetic Present

There are many ways to explore the potential and significance of such epigenetic debates, one of which is historical. Genetics, as a whole, has a somewhat problematic history. Rather than a progression of scientific successes, the history of genetics can be seen as a continuous process of branching, which, at each juncture, left several possible lines open and several others forgotten, likely to be rediscovered in more propitious times.

Epigenetics is one such forgotten line of knowledge. In fact, the notion of epigenetics precedes the idea of genetics itself and even the discovery of DNA. It was coined from epigenesis, in the 1940s, by embryologist and polymath Conrad Hal Waddington (1905–75) to define in a broader, nonmolecular sense—again, without our contemporary sense of molecular modifications to DNA expression—the “whole complex of developmental processes” that connects genotype and phenotype, the processes that connect the original potential of an organism to its eventual, living expression. Rather than looking at development as the simplistic unfolding of a genetic program, Waddington’s epigenetics described the interaction between organisms, genes, and the environment, “the causal interactions between genes and their products which bring the phenotype into being.”

If the genetic code is the “book of life,” then it is one that is constantly being rewritten.

In Waddington’s view, epigenetics was designed to bridge heredity and development—that is, “nature” and “nurture”—and avoid the subsequent erasure of the organism’s development from genetic investigations.

In the 1940s, however, there was little interest in this line of research. In Waddington’s time, molecular biology was taking a different direction, with the discovery of DNA as the hereditary substance and the deciphering of its double helix structure by James Watson and Francis Crick in 1953. Mainstream molecular geneticists saw little to gain from Waddington’s work: Crick judged the complexity described by epigenetic models as a metaphysical waste of time that covered ground already successfully covered by DNA mutations and translation errors—that is, by what he and Watson had discovered. In thinking they had discovered the “book of life,” these mainstream geneticists were unable to see how the book had been written and how often it had been rewritten.

Major institutions that heavily funded mainstream molecular genetics were skeptical of epigenetics. Waddington’s application for funding advanced from the Rockefeller Foundation to explore the “no-man’s-land” between genotype and phenotype—that is, epigenetics—was eventually rejected.

 

The Image of Epigenetics

Perhaps the issue was one of comprehension, of figuring out how to wrap our minds around a “no-man’s-land” between nature and nurture. What exactly does that look like?

A landscape drawing was the image often used by Waddington, the “central figure for the scientific field of epigenetics,” according to Susan Merrill Squier. In her recent Epigenetic Landscapes: Drawings as Metaphor, Squier covers this wider aesthetic dimension of epigenetics research, addressing the question of how to visualize this curious middle ground.

Waddington originally commissioned British painter John Piper to do this landscape drawing, which was the first landscape image used in the former’s book Organisers and Genes (1940). The drawing came in a number of versions from 1940 to the late 1950s: first, a realistic landscape with a river flowing from a mountain, then an abstract landscape with a ball rolling downhill toward a number of branching valleys (possibly simplified for a scientific audience), and finally an empty landscape with a complex number of strings anchored to pegs at the bottom. These pegs represented genes, whose role was highlighted in this last iteration. The landscape was meant to offer, as Squier writes, “a broad and flexible representation of development,” describing the fate of a cell as it moves downhill—from its initial capacity to become any kind of tissue to cellular differentiation, through a number of branching alternatives represented by different valleys.

A key concept to frame this cellular trajectory is canalization, the channeling of the original potentiality of the cell through a stable pathway (a “chreode”—a neologism from the Greek for “necessary path”) that buffers it from external perturbations. Canalization—and the whole developmental repertoire of the landscape—is not just about a cell’s fate, however. As Squire notices, in Waddington’s reading, it is a multidimensional device that can be applied to several scales of biological time that are often simultaneous and continuous: the time of “embryonic development,” of an “organism’s life span,” and ultimately the overall scale of “evolutionary time.”

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Canalization, for instance, has an obvious implication at the level of population and, hence, of human population. As Squire observes, it “was the evolutionary principle central to epigenetics that explained why, over the course of generations, a population tended to remain consistent. This same principle could also explain evolutionary changes: if the environmental perturbations were sufficiently great, they could push a population out of the canalized course of its development into a wholly new trajectory.”

Squier avoids making an overt connection to how this metaphor of canalization sheds light on human development and historical trauma. This is a pity, because a number of epidemiological models of epigenetic plasticity, implicitly following Waddington, have introduced a subtle but significant transformation into the current notion of plasticity and biological temporality, one that contrasts with some contemporary views that emphasize the potential of cells to reverse their fate or of the brain to endlessly repair itself.

Waddington’s landscape is not about fixity, obviously, but neither is it a simplistic celebration of fluidity and endless change, as in some postmodernist takes on plasticity. Waddington’s landscape points to a model of temporality based not on timeless genetic influences on the body but rather on several contingent events that—particularly in some critical windows of development—push the developmental trajectory toward alternative pathways. Once a pathway has been entered, the cell is “‘buffered’ such that it would be difficult to get out of the channel once into it … Cell fate was rigidly fixed if the pathway were sufficiently canalized.” The social implications of this model are not difficult to see.

 

The Politics of Epigenetics

Epigenetics is often sold to the public—at least some publics in the Global North—as a rosy message of individual control and optimization of function. It highlights how we can “train” and regenerate not only our bodies and brains but now also our genomic expression through meditation, a healthy diet, or exercise. It is sold as having only upsides: the constant ability to change for the better, while removing any concerns that some might be negatively affected forever. An individual can constantly remake themselves for the good, but a historically traumatized population need not fear their far-from-permanent epigenetic inheritance.

However, the pattern of biological temporality that emerges from Waddington’s landscape is more complex. Its view of assimilation of environmental inputs into long-term biological trajectories emphasizes restriction of potentialities at each branching, rather than self-renewal and reversibility, which largely comports with today’s understanding. “Alternative fates remain present somewhere on the landscape,” but they remain inaccessible. This does not deny that a hidden genetic potential can be reactivated by environmental exposures, as Waddington believed, but the capacity to change was limited at each bifurcation and temporality across the landscape seen as irreversible.

Squier’s book focuses too intensely on the aesthetics of Waddington’s ideas and in so doing neglects the wider political significance of epigenetics as a whole. What seems missing in Squier’s analysis is that this new “landscape of thought” goes well beyond sophisticated academic debates on visualization, complexity, and the nonlinearity of effects held in cozy conferences on the shores of Lake Como, as happened in the late 1960s and to which Squier devotes a number of pages and anecdotes.

Epigenetics is often sold to the public—at least some publics in the Global North—as a rosy message of individual control and optimization of function.

Across seven chapters, Squier focuses on Waddington’s visual representation of development as an evocative meditation at the intersection of science, art, and technology. She highlights the contribution of visual images to producing scientific meaning and leading to “productive engagements with the unknown.” Squier mobilizes a number of resources to expand the epigenetic imagination beyond its contemporary reduction to a molecular tag on DNA strings, as happens today: the role of comics in health care, landscape architecture theory, miniature landforms, catastrophe theory, bioArt, and feminist debates on “what counts as nature” are all used to reclaim a wider and more “expansive” meaning of epigenetics.

While the book’s attempt to expand the boundaries of science is laudable, its view of the public significance and breadth of epigenetic reasoning in a number of medical and societal iterations is ultimately limited. It reflects an elitist model of science and technology studies that, in my view, fails to appreciate the ongoing penetration of epigenetic reasoning into a number of disciplinary fields and how it serves as an increasingly attractive platform for the biopolitical management of vulnerable populations. Its focus on art is important but misses the transformative role that epigenetics could play around the world and its implications for notions of responsibility and risk, normality and pathology, and particularly how epigenetics may reiterate discourses of blame, responsibility, and control especially for vulnerable groups.

What Squier seems to miss is that while Waddington’s epigenetic elaborations remained rather speculative at the time, they have since assumed a different meaning. With the burgeoning interest in the molecular mechanisms between genotype and phenotype, Waddington’s developmental model is being taken up by research programs in social and environmental epigenetics and DOHaD. The scale of analysis, level of integration, and societal significance of such programs was unheard of in Waddington’s time. This shows the importance of Waddington’s model well beyond the narrow space of academic debates, not in the abstract but in its possible social incarnations and implementations.

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An epigenetic view of plasticity, based on the inertial power of environmentally induced effects, has become an exemplar for a number of nongenetic models of health and racial disparities that emphasize biological embedding and the perpetuation of environmental cues.6

Applied to models of human health and population dynamics, this view of plasticity can have a number of implications. It is significant, for instance, that some biologically based models of historical trauma (slavery, war, famine)—with their cumulative and stabilization effect in downward pathways—resemble a transgenerational version of the Waddingtonian landscape. Here, current health disparities are explained not based on genetic endowment but rather as the accumulation of a number of shocks via epigenetic mechanisms. The inertial impact of these induced environmental effects may be difficult to alter or eliminate. At the same time, the porosity of the body—down to its genomic core—generates new forms of vigilance and responsibility.

A body shaped from and traversed by outside matter—as in epigenetic models of corporeal plasticity—is also one that is vulnerable to a number of disciplinary practices and forces.

 

The Future of Epigenetics

In her attempt to explore the “vital role the epigenetic landscape plays in fields beyond the life sciences,” Squier refers only very marginally to the potential incorporation and expansion of epigenetic models into wider policy debates on health inequalities, which are becoming increasingly visible in the Global South and for vulnerable populations in the North.

At the beginning of her book, she dismisses as sensationalist many claims being made in epigenetics on the long-term effects of trauma, war, and stress on the biology of certain individuals or groups. “These hyperbolic hopes,” she claims, “may obscure the reality: there is significant uncertainty about the field of epigenetics.”

This may be a good academic objection but it sounds sociologically and historically naive. Many public health translations of epigenetics and related disciplines like DOHaD remain speculative, but uncertainty has never stopped scientific findings from being translated into policy under the right economic and political circumstances. Much of the science behind early 20th-century eugenics (the unit of character hypothesis, for instance) was, to say the least, as premature and controversial at the time (and ultimately wrong) as some of the claims on transgenerational effects in epigenetics are today. A change in the conditions of “law and sentiment,” as Francis Galton would have put it, turned speculative science into a plausible political platform within only the first few years of the 20th century.

Epigenetic models of human plasticity are always immediately caught in the process of producing social identities.

The present conditions of law and sentiment that are making epigenetics so appealing in a number of fields are elided by Squier’s analysis. She is constantly trying to distinguish good epigenetic knowledge from the way this science “is being narrowed and redirected away from its potential for feminist resistance,” whether by sensationalist or reductionist models. This strategy of purifying science from its contemporary “distortions,” however, runs the risk of perpetuating the illusion of a pure epigenetic kernel—conceived in some refined academic context and full of liberatory potential—that can only be contaminated after the fact by social misuse.

This, however, obscures a much more interesting reality: how epigenetic models of human plasticity—no matter how sophisticated or simplified—are always immediately caught in, and prompted by, the process of producing social identities (gender, class, and race). For instance, a new biopolitics of vulnerable populations, drawing on epigenetic plasticity rather than genetic fixedness, is emerging in macroeconomic analyses that recommend investing during critical windows of plasticity (pregnancy and early childhood), particularly for “developing countries.”

In debates on race, plasticity has historically been used to promote post-racial views that get rid of racial essences or arguments that once again lock people to a place, time, and burden of experience or memories. Similarly, in debates on gender, the permeability of the maternal body has been used as an element of domination and stigmatization (the impressionable womb), but also as a resource for empowerment in shaping heredity and generation.

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This means that epigenetic plasticity is less a promising idea that is later spoiled by social misuse than a complex double-edged sword that simultaneously produces and undermines stable social identities. This inherent duality and unavoidable situatedness of epigenetic knowledge, no matter how simplified or sophisticated, is missing in this book. Excavating the ambiguity of the epigenetic landscape would have helped the reader to see that not only is science never pure, but that there is never a one-to-one relationship between scientific views and social values.

This is what is fascinating about the politics of epigenetics in this turbulent embryonic phase known as postgenomics—that we still don’t know which bifurcation the ball waiting uphill is going to enter and where in the landscape a stable association with social values will be formed.

 

This article was commissioned by Caitlin Zaloom. icon

  1. See Edith Heard and Robert A. Martienssen, “Transgenerational Epigenetic Inheritance: Myths and Mechanisms,” Cell, vol. 157, no. 1 (2014), and Anastasiya Kazachenka et al.,“Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance,” Cell, vol. 175, no. 5 (2018).
  2. Oliver J. Rando, “Dietary Effects on the Sperm Epigenome” (2014–).
  3. Maurizio Meloni and Giuseppe Testa, “Scrutinizing the Epigenetics Revolution,” Biosocieties, vol. 9, no. 4 (2014).
  4. Steve Horvath, “DNA Methylation Age of Human Tissues and Cell Types,” Genome Biology, vol. 14, no. 10 (2013), p. 3156.
  5. Dagmara McGuinness et al., “Socio-economic Status Is Associated with Epigenetic Differences in the pSoBid Cohort,” International Journal of Epidemiology, vol. 41, no.1 (2012).
  6. See, for instance, Christopher W. Kuzawa and Elizabeth Sweet, “Epigenetics and the Embodiment of Race: Developmental Origins of US Racial Disparities in Cardiovascular Health,” American Journal of Human Biology, vol. 21, no. 1 (2009).
Featured image: Nature & Nurture (Genetic Holism) (2017). Drawing and photograph by Daniel Friedman / Flickr