Addressing the current research gap on the ethical evaluation of epigenome editing

By Karla Alex and Eva C. Winkler.

Epigenome editing is a new research tool that has many potential applications in medicine but has not yet received much attention from ethicists. Our new article in Journal of Medical Ethics addresses this gap and proposes criteria for the assessments of risks of genome editing versus epigenome editing. The proposed criteria might even be useful for assessing and comparing the risks of several other new types of gene technologies still to be developed.

Epigenome editing is currently developed for being used in humans for therapeutic purposes (Fine-tuning epigenome editors | Nature Biotechnology). In the article “Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions” we compare epigenome editing with the more widely discussed technology of genome editing.

Both, epigenome and genome editing, can be considered new “gene technologies”. Genome editing is employing “gene scissors”, that is, specific molecules that can “cut” the DNA. Epigenome editing does not use such “scissors”. Epigenome editing instead modifies the DNA at a different level. It is not the genetic sequence, that is, not the specific code of DNA-bases, that is changed, but epigenome editing modifies how the DNA strand is folded. This means that epigenome editing can introduce changes to the density of DNA. In a sense, it untangles the DNA strand a bit and by this makes it possible that specific genes are “switched off” or “switched on”. A gene that is “switched on” can then be, what is called “transcribed” or “read” by other molecules. These mechanisms are explained in the first part of our article, where we also summarize areas of potential future therapeutic applications of epigenome editing. As we show, epigenome editing has many potential uses in the clinic.

The answer to the question how these future clinical applications are to be evaluated ethically depends on the risks associated with epigenome editing. The very few ethical assessments of epigenome editing that have already been published are either focusing more on epigenome editing for enhancement than for therapeutic purposes (see in our article the section “Current ethical debates”), or are portraying epigenome editing as less risky than at least germline genome editing, that is, heritable types of genome editing (News: Exploring the Ethical Puzzle of Epigenome Editing – CRISPR Medicine (crisprmedicinenews.com)). We started out in our research with the open question whether epigenome editing could be preferable to genome editing and ended up learning that this is not always the case and needs more scrutiny.

We soon realized that it is impossible to broadly and generally compare all potential types of epigenome editing with all potential types of genome editing in terms of risks. Therefore, we propose to answer the following three questions to assess how risky any new editing approach (genome editing, epigenome editing, or even other editing approaches, for example, RNA editing) is:

  1. Is the editing done inside a patient’s body or outside the body (in the laboratory), with edited cells later being retransferred to the patient?
  2. When does the editing take place (during which stages of human development, for example, before birth, soon after birth or later in life)? and
  3. Which diseases does the editing target?

In our article, we propose three criteria for risk assessment of new gene technologies that are related to these three questions. It is possible that these criteria proposed in our paper can also be used in future risk assessments of other new gene technologies, besides genome and epigenome editing, which are still to be discussed from an ethical perspective, too, such as RNA editing (Frontiers | RNA Biology Provides New Therapeutic Targets for Human Disease (frontiersin.org)).

Our comparative assessment of risks of genome and epigenome editing is a first step in addressing the research gap about the ethics of epigenome editing. Along the lines of the three questions above, this assessment shows that epigenome editing cannot always be regarded as safer than genome editing.

Our article also includes some suggestions for future debate. Thus, in the final section of the paper, we briefly discuss potentially unique new applications of epigenome editing to “reverse” acquired diseases and point out some of the ethical implications of such applications.

The intention of this paper, which emerged from the research project COMPASS-ELSI, is to stimulate a broader debate about epigenome editing within bioethics.

 

Paper title: Comparative ethical evaluation of epigenome editing and genome editing in medicine: first steps and future directions

Authors: Alex K, Winkler EC

Affiliations: Section Translational Medical Ethics (NCT-EPOC), Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg University, Germany

Competing interests: None declared

Social media accounts of post authors: Twitter account name: Ethics Section Winkler @EthicsWinkler

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