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)

Non-human animal chimeras, containing human neurological cells, have been created in the laboratory. Despite a great deal of debate, the status of such beings has not been resolved. Under normal definitions, such a being could either be unconventionally human or abnormally animal. Practical investigations in animal sentience, artificial intelligence, and now chimera research, suggest that such beings may be assumed to have no legal rights, so philosophy could provide a different answer. In this vein, therefore, we can ask: What would (...) a chimera, if it could think, think about? Thinking is used to capture the phenomena of a novel, chimeric being perceiving its terrible predicament as no more than a laboratory experiment. The creation of a thinking chimera therefore forces us to reconsider our assumptions about what makes human beings (potentially) unique (and other sentient animals different), because, as such, a chimera’s existence bridges our social and legal expectations about definitions of human and animal. Society has often evolved new social norms based on different kinds of (ir)rational contrivances; the imperative of non-contradiction, which is defended here, therefore requires a specific philosophical response to the rights of a thinking chimeric being. (shrink)

… the decision to genome edit will almost certainly be identity affecting, as a couple (or individual) will usually make it before they have created any embryos and the process itself will, at the...

Like all research, embryo research can take a variety of forms, some posing substantially more risks to persons than others. Savulescu et al argue persuasively that regulatory regimes specially designed for sensitive embryo research should differentiate between person-affecting and non-person-affecting embryo research, with substantial scrutiny only warranted for the former.1 Yet if we find Savulescu et al ’s argument persuasive, what practical implications would it have? In this commentary, we focus in particular on how such an argument might apply in (...) Singapore, one of the jurisdictions with special regulations for embryo research. We will summarise the way in which approval for oocyte and embryonic research operates in Singapore, and suggest that Savulesc et al ’s distinction requires specification to be useful in such contexts. We propose adopting a risk-stratified framework similar to that employed with Institutional Review Boards. This requires a wider view of risks than the focus by Savulescu et al on future persons. We then illustrate how such a framework would apply in five scenarios discussed in Savulescu et al. Research with embryos and oocytes is regulated in Singapore under the Human Biomedical Research Act.2 Enacted in 2015, this law sets out requirements for consent, IRB review and research oversight. By definition, all research involving gametes and embryos fall within the remit of the Act. Moreover, such research is defined as ‘restricted’; besides the Act, research involving oocytes and embryos is also subject to control under the Human Biomedical Research …. (shrink)

The paper by Savulescu et al is timely and the concepts illuminated deserve further reflection.1 Reproductive tissue which includes sperm, oocytes and embryos are commonly treated differently to other human tissue, even when the reproductive potential of these has no possibility of being realised. This unnecessary exceptionalism hampers research in human reproduction, disadvantaging patients and delaying life-changing treatments from being incorporated into clinical practice. In jurisdictions where embryo creation is permitted for clinical purposes, such as in vitro fertilisation (IVF), supernumerary (...) embryos are routinely discarded once they are no longer required to attempt pregnancy. We contend that research on such embryos, which will never realise their reproductive potential, is not substantially different to any other human tissue research and should not require any additional ethical or regulatory oversight. The only individuals who can possibly be harmed by such research are the tissue providers and their interests, including confidentiality and informed consent provision, should be protected. This protection once again is no different in its scope to any other type of research involving human cells and tissues. Most Western societies have moved away from the concept that ‘every sperm is sacred’ and it is time that the regulators and scientific community aligned with the prevailing communal norms and stop treating gametes and embryos as somehow holding higher moral value, compared with other human cell/tissue lines, provided that there is no intention to attempt a pregnancy …. (shrink)

Savulescu and colleagues propose a distinction between ‘future person embryo research’ and ‘non-future person embryo research’, which they hold can help decision-makers more efficiently discriminate between higher risk and lower risk embryo research.1 The authors’ proposed distinction does point to an ethically significant difference between different forms of embryo research, which they illustrate in an enlightening manner using a series of detailed case studies. In the following, I wish to comment, first, on the substance of the authors’ distinction, and second, (...) on the possibility of looking beyond the relatively narrow scope of their argument. A first point concerns the authors’ characterisation of FPE research as including ‘anything which is done to an embryo that will be or could be implanted into a woman’s uterus’. Insofar as they also emphasise the idea of research that can ‘affect’ a future person, this formulation might suggest that the key distinction here is between research procedures that causally impact the characteristics of a future person, and those that do not. However, this is not how the authors’ distinction between FPE and NFPE research should be understood. Indeed, they describe ‘observational research’, including the first test case they present, as an exception …. (shrink)