Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. (...) Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III). (shrink)

Targeted modifications of the human epigenome, epigenome editing (EE), are around the corner. For EE, techniques similar to genome editing (GE) techniques are used. While in GE the genetic information is changed by directly modifying DNA, intervening in the epigenome requires modifying the configuration of DNA, for example, how it is folded. This does not come with alterations in the base sequence (‘genetic code’). To date, there is almost no ethical debate about EE, whereas the discussions about GE are voluminous. (...) Our article introduces EE into bioethics by translating knowledge from science to ethics and by comparing the risks of EE with those of GE. We, first (I), make the case that a broader ethical debate on EE is due, provide scientific background on EE, compile potential use-cases and recap previous debates. We then (II) compare EE and GE and suggest that the severity of risks of novel gene technologies depends on three factors: (i) the choice of an ex vivo versus an in vivo editing approach, (ii) the time of intervention and intervention windows and (iii) the targeted diseases. Moreover, we show why germline EE is not effective and reject the position of strong epigenetic determinism. We conclude that EE is not always ethically preferable to GE in terms of risks, and end with suggestions for next steps in the current ethical debate on EE by briefly introducing ethical challenges of new areas of preventive applications of EE (III). (shrink)

Excerpt: 1. Introduction This chapter provides insight into the diverse ethical debates on genetics and epigenetics. Much controversy surrounds debates about intervening into the germline genome of human embryos, with catchwords such as genome editing, designer baby, and CRISPR/Cas. The idea that it is possible to design a child according to one’s personal preferences is, however, a quite distorted view of what is actually possible with new gene technologies and gene therapies. These are much more limited than the editing and (...) design metaphors suggest. Such metaphors are therefore highly problematic phrases in the context of new gene technologies, for two reasons. On one hand, to design a child of choice by modifying the genome would require modifying any gene of choice, which is more than can be done with current gene technologies, such as CRISPR/Cas. On the other hand, a modification of genes would need to be enough to create any characteristic of choice in the future child. The latter presupposes the assumption of genetic determinism. Moreover, the CRISPR/Cas technology can not only be used in a potentially therapeutic manner at the germline level. In addition, there is the (more likely) scenario of a future clinical therapeutic use of these new gene technologies for modifying the DNA sequence of other cells of the body (somatic genome editing). There is also the option of modifying the epigenome, that is, the spatial configuration of DNA (epigenome editing) (see table 1). Like genetics and genome editing, epigenetics has been at the center of recent popular scientific and ethical discourse as well as scientific debates. The concept of epigenetics has given rise to very different notions of inheritability and responsibility for health, which, however, are oftentimes based on scientifically controversial basic assumptions. That there continues to be covert genetic determinism in the form of epigenetic determinism (see table 2) in debates about epigenetics has been pointed out in ethical analyses of epigenetics. Neither genetic determinism nor epigenetic determinism has been confirmed scientifically. It is therefore important to recognize the concepts that are discussed (and sometimes harshly criticized) in debates about genome editing and epigenetics—for example, concepts about the causal role of DNA for our own life course. This importance is based on the fact that if we understand such controversial concepts, we will be able to remain critical when evaluating scientific knowledge and ethical arguments about genome editing and epigenetics. This chapter, therefore, explains some of these concepts. For an ethical analysis of epigenetics as well as of genome editing, it is necessary to understand and critically reflect upon the underlying concepts of genetic determinism and other, related -isms. The following section offers a detailed introduction to these -isms (section 2; see also table 2). Section 3 provides an ethical analysis of genome editing and epigenetics based on the explanations in section 2. Section 3 focuses on inheritability and responsibility, justice, safety, the problem of consent, and the effects of genome editing and epigenetics on embryos and future generations. This section does not discuss in detail further points that can be found in ethical debates about epigenetics as well as in ethical debates about genome editing. These points include (among others): • fear that the findings of epigenetics and that the methods of genome editing are misused—this also with respect to eugenics and enhancement; • naturalness—an issue we mention in passing a few times in the following analysis; • a possible connection between the genome/epigenome and the concept of human dignity, and the derived danger of instrumentalization and infringement of autonomy when intervening in the genome or epigenome. Since current discourse about ethical issues associated with genome editing focuses mainly on germline interventions, which are, for instance, interventions into a human embryo’s genome, we mainly focus on germline interventions when comparing the debates on genome editing and on epigenetics in section 3. (shrink)

Epigenetic markers could potentially be used for risk assessment in risk-stratified population-based cancer screening programmes. Whereas current screening programmes generally aim to detect existing cancer, epigenetic markers could be used to provide risk estimates for not-yet-existing cancers. Epigenetic risk-predictive tests may thus allow for new opportunities for risk assessment for developing cancer in the future. Since epigenetic changes are presumed to be modifiable, preventive measures, such as lifestyle modification, could be used to reduce the risk of cancer. Moreover, epigenetic markers (...) might be used to monitor the response to risk-reducing interventions. In this article, we address ethical concerns related to personal responsibility raised by epigenetic risk-predictive tests in cancer population screening. Will individuals increasingly be held responsible for their health, that is, will they be held accountable for bad health outcomes? Will they be blamed or subject to moral sanctions? We will illustrate these ethical concerns by means of a Europe-wide research programme that develops an epigenetic risk-predictive test for female cancers. Subsequently, we investigate when we can hold someone responsible for her actions. We argue that the standard conception of personal responsibility does not provide an appropriate framework to address these concerns. A different, prospective account of responsibility meets part of our concerns, that is, concerns about inequality of opportunities, but does not meet all our concerns about personal responsibility. We argue that even if someone is responsible on grounds of a negative and/or prospective account of responsibility, there may be moral and practical reasons to abstain from moral sanctions. (shrink)

The development of the CRISPR gene editing technique has been hyped as a technique that could fundamentally change scientific research and its clinical application. Unrecognized is the fact that it joins other technologies that have tried and failed under the same discourse of scientific hype. These technologies, like gene therapy and stem cell research, have moved quickly passed basic research into clinical application with dire consequences. Before hastily moving to clinical applications, it is necessary to consider basic research and determine (...) how CRISPR/Cas systems should be applied. In the case of single gene diseases, that application is expected to have positive impacts, but as we shift to more complex diseases, the impact could be unintentionally negative. In the context of common disabilities, the level of genetic complexity may render this technology useless but potentially toxic, aggravating a social discourse that devalues those with disabilities. This paper intends to define the issues related to disability that are associated with using the CRIPSR/Cas system in basic research. It also aims to provide a decision tree to help determine whether the technology should be utilized or if alternative approaches beyond scientific research could lead to a better use of limited funding resources. (shrink)

Recently, ethicists have posited that consideration of epigenetic mechanisms presents novel challenges to concepts of justice and equality of opportunity, such as elevating the importance of environments in bioethics and providing a counterpoint to gross genetic determinism. We argue that new findings in epigenetic sciences, including those regarding intergenerational health effects, do not necessitate reconceptualization of theories of justice or the environment. To the contrary, such claims reflect a flawed understanding of epigenetics and its relation to genetics that may unintentionally (...) undermine appeals to social justice. We provide a brief summary of epigenetic sciences, focusing on phenomena central to the current ethical discourse. We identify three fallacious modes of reasoning arising from the emergent literature on the ethical and policy implications of epigenetics, including mischaracterization, undue extrapolation, and exceptionalism. We end by discussing how these issues may work against mobilizing health equity policies and present a more modest claim regarding the value of new epigenetic knowledge to health justice by setting this discourse within the context of known themes in biomedical ethics and health policy. (shrink)

While the accumulation and increased circulation of genomic data have captured much attention over the past decade, privacy risks raised by the diversification and integration of omics have been la...

What do we mean when we talk about epigenetic harm? This paper presents a multidimensional view of epigenetic harm. It is a plea to take a step back from discussions of epigenetic responsibility distributions prevalent in ELSA literature on epigenetics. Instead, it urges researchers to take a closer look at the normative role played by the concept of epigenetic harm. It starts out by showing that the ways in which the object of epigenetic responsibility has already been conceptualized are all (...) related to ‘epigenetic harm’: something negative that happens in which epigenetic mechanisms play a role, or rather something that needs to be avoided. Epigenetic harm is then characterized as a bridging concept between relatively neutral findings on epigenetics on the one side, and potential ethical and societal implications of those findings, primarily in terms of responsibility ascriptions and distributions, on the other. The paper proposes that a sufficiently nuanced account of epigenetic harm should include at least three dimensions. The dimension of causation alone leads to an overly narrow understanding of harm, and a wrong understanding of this dimension might prompt researchers to support an excessively simplistic epigenetic determinism. It is argued that a multidimensional analysis of epigenetic harm is less vulnerable to this threat and more reflective of the various kinds of harm that may be experienced by the subjects of epigenetic alterations. The paper applies insights from disability studies and feminist philosophy to draw attention to two other dimensions of epigenetic harm, namely lived experiences and relationality. The paper concludes by exploring what a shift towards a multidimensional approach to epigenetic harm might mean for epigenetic research and responsibility ascriptions by formulating some concrete implications. (shrink)

There has been a spurt in both fundamental and translational research that examines the underlying mechanisms of the human microbiome in psychiatric disorders. The personalized and dynamic features of the human microbiome suggest the potential of its manipulation for precision psychiatry in ways to improve mental health and avoid disease. However, findings in the field of microbiome also raise philosophical and ethical questions. From a philosophical point of view, they may yet be another attempt at providing a biological cause for (...) phenomena that ultimately cannot be so easily localized. From an ethical point of view, it is relevant that the human gut microbiome comprises data on the individual’s lifestyle, disease history, previous medications, and mental health. Massive datasets of microbiome sequences are collected to facilitate comparative studies to identify specific links between the microbiome and mental health. Although this emerging research domain may show promise for psychiatric patients, it is surrounded by ethical challenges regarding patient privacy, health risks, effects on personal identity, and concerns about responsibility. This narrative overview displays the roles and advances of microbiome research in psychiatry and discusses the philosophical and ethical implications of microbiome big data and microbiome-based interventions for psychiatric patients. We also investigate whether these issues are really “new,” or “old wine in new bottles.”. (shrink)