“It was there all along”: Situated uncertainty and the politics of publication in environmental epigenetics

Abstract

Drawing on two ethnographic examples from a laboratory study of a group conducting environmental epigenetics research on suicide risk, we examine the ways in which researchers go about making credible claims in the face of a range of profound uncertainties. We first explore how a range of factors led to what is now accepted as a fact or discovery being explained away, several years ago, as a combination of technical error and known background noise. To set this first example within a broader context, we turn to a debate that erupted in the lab during a journal club meeting about claims-making and publishing in science. Through these examples, we aim to demonstrate the complex terrain in which scientists manage epistemic uncertainties and produce credibility in environmental epigenetics research. Our goal is to trace uncertainties from the unknowable reasons and internal states that lead people to respond to data in a particular way, through to the technical difficulties in identifying data from noise, through to issues of ethical self-making, as students learn to become certain types of scientists. We argue that the ways in which uncertainty takes on meaning, has effects and is managed also has much to do with its situatedness.

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Notes

  1. 1.

    Other important points of dispute include the precise mechanisms of epigenetics (Herman et al, 2014) and the durability of epigenetic profiles (Bale, 2015; Nagy and Turecki, 2012; Skinner, 2014). Finally, others have pointed to the difficulty of identifying clear correlations, let alone evidence of causation, between complex environmental factors and phenotypic outcomes, particularly when studies are carried out in human populations (Edwards et al, 2013; Lynch and Kemp, 2014; Morange, 2009).

  2. 2.

    We thank one of the anonymous reviewers for pushing us to think about the ways in which issues of uncertainty open up onto questions of credibility in our ethnographic material.

  3. 3.

    This debate must be placed in context of the transitions in the field of genetics in the twentieth-century, from the period of classic genetics from very approximately 1900 to 1940 to the era of molecular genetics from 1940 to approximately 2000 and the transition to our current era of postgenomics (Müller-Wille and Rheinberger, 2012, pp. 135–165). The Modern Evolutionary Synthesis was produced during the middle period of molecular genetics and attempted to reconcile questions of heredity and evolution according to prevailing understandings of genetics and gene functioning and the evolutionary record (see Müller-Wille and Rheinberger, 2012 for further details). The Modern Evolutionary Synthesis finds itself under attack on many fronts in the postgenomic era and in particular from findings emerging from epigenetics research that suggest that acquired traits might be passed transgenerationally, in plants, fungi, and research in C. elegans, with some findings emerging in mammalian studies (Jablonka et al, 2014; Pembrey, 2015). These critiques have profound implications for taken for granted notions of trait transmission and must be situated in over a century of – and ongoing – debates about hard and soft heredity. While some label these positions as Mendelian or Lamarckian, these simplifications cannot do justice to the complexity of the changes to basic hereditary assumptions brought to the fore by epigenetics research. Maurizio Meloni summarizes the situation neatly, “History is a not a pendulum that swings back and forth between other- wise immutable positions” (Meloni, 2016, p. 4).

    It is another criticism of the Modern Evolutionary Synthesis, however, that is perhaps most important to consider in the context of the epigenetics research we focus on in this article. Eva Jablonka and Marion Lamb suggest that the term “epigenetic inheritance” has been used in two overlapping ways (Jablonka and Lamb, 2007). The first of these includes inter- and transgenerational inheritance of developmental traits that do not originate in DNA sequences and which are not induced by a persistent environment. These are the types of inheritance discussed in the previous paragraph. It is the second type of inheritance, that Jablonka and Lamb, refer to as cellular epigenetic inheritance, that is of greatest interest to us. Within this category, they include the transmission of variations of gene expression from mother to daughter cell, in other words, the acquired variations are transmitted mitotically (i.e., persistent across cell division). Jablonka and Lamb also include cell memory in this category, which refers to the “persistence of functional and structural cellular states in non-dividing cells, such as most neurons” (Jablonka and Lamb, 2008, p. 390). Here they cite studies of the apparent long-term effects of early maternal behaviour amongst rats on their offspring’s brain cells via chromatic marks in a key gene (Weaver et al, 2004). The occurrence of these functionally specific – early maltreatment as leading to increased stress responses later in life – rather than stochastic changes are described by Jablonka and Lamb as undermining the Modern Evolutionary Synthesis in two ways. First, while the concept of “epimutations” – a term coined in 1985 to describe heritable changes in gene expression – is not new, epimutations were consistent with the core role attributed to random mutations in the Modern Evolutionary Synthesis (Pembrey, 2015, p. 1113). Functionally specific changes, or “soft inheritance”, “in which heritable variations are the result of environmental effects, use and disuse, and other factors” is considered something entirely different (Jablonka and Lamb, 2008, p. 389). These functionally specific changes run up against another tenet of the Modern Evolutionary Synthesis, namely that hereditary information is passed through DNA and not impacted on by life experiences. In other words, somatic changes should not play a role in heredity. If it is the case that stress can impact the DNA durably – whether across generations of organisms, across cell divisions, or inscribed in cell memory – this is seen as incompatible with the Modern Evolutionary Synthesis (Jablonka and Lamb, 2008, pp. 393–394; Meloni, 2016, p. 390).

  4. 4.

    Martine Lappé and Hannah Landecker point to the “puzzlement” of philosopher Jim Griesemer that certain molecular phenomena are designated as epigenetic based on the assumption that they do not affect DNA sequence (Griesemer, 2002 cited in Lappé and Landecker, 2015). However, they continue, methylation (considered one of the key epigenetic mechanisms) “is a process that changes cytosine to methylated cytosine, changing the character of the nucleotide base. Indeed, methylated cytosine is sometimes referred to as ‘the fifth base’ in this context” (Lappé and Landecker, 2015, p. 169). Attempts to completely disentangle the influence of DNA sequence from acquired methylation variation are increasingly described as “futile” (Pembrey, 2015, p. 1114). Lappé and Landecker argue that more important than focusing on the irrationality of these definitions, is attending to the social functions of these distinctions. Through the emphasis and re-emphasis on the distinction between genetics and epigenetics, important political and social work is being accomplished. “Paying attention to uses of the distinction between the epigenetic and the genetic” allowed “the genome to remain invariant while the epigenome varied above it and around it. In a sense, the separation allowed investigators to hold the genome still (which was not hard, because it had been conceptualized as such) while opening shop just next door” (Lappé and Landecker, 2015, pp. 169–170). In other words, genetic explanations are able to avoid being questioned while researchers develop epigenetic explanations to fill the explanatory gap left by genetics. Scientists maintain the stable backbone of their research, while at the same time being able to work with relative liberty in a new experimental space, despite the ongoing production of data that contradict this distinction. Yet research on environmental exposures and other impacts on the body is increasingly calling into question the nature (temporal, amongst others) of epigenetic marks. How epigenetic and genetic factors are “narratively ordered and experimentally formalized is increasingly coming to matter beyond the laboratory, as medical and policy decisions build upon these findings (Gorelick, 2004; Halfon et al, 2014)” (Lappé and Landecker, 2015: 171). In the process of this research certain experiences and phases of life are imbued with particular importance, while others are obscured. The decision– and implications of these decisions – about where to draw these lines is central to our argument in this text.

  5. 5.

    One of the authors is a principal investigator in the MGSS.

  6. 6.

    Our interest in the epigenetic aspects of the MGSS’s research agenda over others stems from a broader set of concerns, that fall somewhat beyond the frame of this article. Suffice it to say that it was both the relative novelty of environmental epigenetics’ emergent style of reasoning and its centrality to claims about biosocial research being made lately in the social sciences, which led us to focus on this area.

  7. 7.

    Based on Google Scholar statistics.

  8. 8.

    All names, except those of principal investigators, have been changed and identifying traits changed.

  9. 9.

    References to the “gene of interest” are purposefully vague to provide a degree of anonymity to Nicole.

  10. 10.

    Star and Gerson define “anomaly” broadly as any “interruption to routine” (1987, p. 147).

  11. 11.

    For Rheinberger epistemic things are by definition underdetermined; they “are epistemic by virtue of their preliminarity, of what we do not yet know about them, not by virtue of what we already know about them” (Rheinberger, 2005, p. 407). Moreover, it is only through technical objects that these “objects of investigation become entrenched and articulate themselves in a wider field of epistemic practices and material cultures, including instruments, inscription devices, model organisms, and the floating theorems or boundary concepts attached to them” (p. 29). This distinction is materialized in research papers (technical objects appear in the “materials and methods” section, epistemic things in the “discussion”), as well as in laboratory arrangements.

  12. 12.

    Another way to refer to CG methylation where the “p” in CpG refers to a phosphate that links the two nucleosides.

  13. 13.

    This quote and all others related to the journal club meeting are based on field notes rather than recordings.

  14. 14.

    Details of the article have been purposefully left vague in order to render it unidentifiable.

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Acknowledgements

This manuscript is comprised of original material that is not under review elsewhere. The study on which the research is based has been subject to appropriate ethical review. Neither of the authors have any competing interests – intellectual or financial – in the research detailed in the manuscript.

Funding

This work was supported by the Institute of Neurosciences, Mental Health and Addiction, Canadian Institutes of Health Research (273500).

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Lloyd, S., Raikhel, E. “It was there all along”: Situated uncertainty and the politics of publication in environmental epigenetics. BioSocieties 13, 737–760 (2018). https://doi.org/10.1057/s41292-017-0092-x

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Keywords

  • uncertainty
  • environmental epigenetics
  • controversies
  • credibility
  • ethnography
  • anomaly