What do we mean by ‘genome editing’?
Genome editing is the alteration of a selected DNA sequence in a living cell by cutting the DNA molecule at a chosen point and either removing existing elements of the genome or deliberately introducing a new sequence.
Genome editing techniques make use of a large family of proteins, first discovered in the 1960s, that are able to cut the genome at specific sites. Since around 2005, new and programmable families of genome-cutting proteins have been described – including Zinc Finger Nucleases, TALENs and RNA- (CRISPR-) guided endonucleases – that allow cuts in the DNA to be targeted to any point in the genome.* After the cut is made, repair mechanisms that exist naturally within every cell rejoin the severed DNA ends, either by pasting them together with small insertions or deletions of genetic information (‘indels’), or by using a different strand of genetic material as a template for repair.**
Among the recent genome editing technologies, CRISPR-based methods are particularly promising owing to their relative efficiency, low cost and ease of use, and the possibility of making edits at multiple places in the genome in a single procedure. This has led to their rapid diffusion and broad uptake across biology. Although most uses of genome editing so far have been in research, the potential applications seem to be unlimited, given that variations of the technique are applicable to all genomes.
We think it is impossible to consider normative questions about research (questions about its value and what research should be pursued, for example) in isolation from questions about the broader context, including the societal conditions under which it is carried out and the possibilities to which it might lead. This is why we think it is important to consider current research together with its potential non-research applications and, at the same time, why these uses should be a matter for public reflection beyond any narrow community of users.
Areas of research and possible application include:
- crops and livestock (e.g. increasing yield, introducing resistance to disease, pests and pesticides, nutritional traits, and tolerance of different environmental conditions)
- industrial biotechnology (e.g. developing ‘third generation’ biofuels)
- ecology (e.g. managing populations of disease vector organisms or even restoring extinct species)
- biomedicine (e.g. pharmaceuticals, xenotransplantation, and gene, cell and regenerative therapies)
- reproduction (e.g. removing hereditary disease traits from future generations)
By ‘genome editing’, therefore, we do not mean to refer to a particular technique or an existing area of research but, rather, to the idea of using molecular approaches to alter genes or gene expression in purposive ways, however imperfectly this may be realised through the techniques currently in use.
The idea of making controlled alterations to the genome is not new, of course, and some may see the techniques now available as new tools, much better in many respects than those available hitherto, but serving a similar range of ambitions. Others, however, may see them as transformative, opening up new horizons of possibility, leading science and technology in directions that were previously unidentified, neglected or forsworn. Either of these points of view, or any that lie between them, may be persuasive but the perspective taken may have significant implications for how genome editing will be developed, applied and controlled.
Why are we seeking evidence?
The Council’s terms of reference charge it “to identify and define ethical questions raised by recent advances in biological and medical research in order to respond to, and to anticipate, public concern.” The Council believes that genome editing raises such questions.
The Council’s mode of working is primarily deliberative: it involves a process of collective reasoning by an informed group of individuals who bring a range of different skills and perspectives to the process. Accordingly, in June 2015, the Council established an interdisciplinary working group to examine questions raised in relation to genome editing. The reasoning and conclusions of this group will be thoroughly tested by the Council itself, through consultation with others, and ultimately in public debate.
As members of the working group we do not have, either individually or collectively, all the available information, nor are we likely to reflect the full range of perspectives, that are relevant to moral deliberation about genome editing. To supplement our own professional knowledge, we are gathering information from those who can offer additional information and insight. This call for evidence is one of the principal ways in which we hope to gather those inputs. Our aim is to open our inquiry as wide as possible in order to draw from sources that other forms of research might miss.
How will the evidence contribute to our work?
This project is being carried out in two stages. The first stage, to which this call for evidence relates, is intended to investigate the proper context for asking more practical questions about genome editing. This part of our project will be guided by questions about how we should think about genome editing, what sort of thing it is and to what sort of ethical questions it gives rise. For example, we will investigate whether genome editing itself raises any distinctively new moral questions or simply casts familiar questions in a new light.
In this first stage, we will not be addressing practical policy questions directly, questions about, for example, under what conditions (if any) a particular use of genome editing would be morally acceptable/ desirable/ required, or about who should decide when genome editing may be used for a particular purpose or in a given set of circumstances. We will move on to these in the second stage, after we have published the findings of our first stage.
We think it will be better to address the conceptual questions first, since our conclusions will inform both our understanding of which questions should have the highest priority and how we might tackle them in stage two.
What sort of evidence are we seeking?
This is an open call for evidence, seeking information, insight and opinion relevant to the ethical reflection on genome editing in both research and application across the full range of uses, from microorganisms through plants and animals, to humans. For the time being we are interested in gathering:
- Information: references, especially recent or unpublished information that may not show up in literature research; information about current or planned research or applications; other sources of information that we should consult
- Insight: what are the relevant perspectives and the issues they foreground? Are any perspectives unfairly marginalised? How are different actions and outcomes valued, and on what basis? Using what frames of reference and systems of values might we understand and respond to genome editing?
- Evaluation: What are the potential benefits and to whom do those benefits accrue? What are the potential risks and adverse effects, and how are those risks and effects likely to be distributed? How are we to identify and evaluate the scale and significance of those benefits and risks in relation to each other?
- Opinion: What are the rates and direction of travel, likely applications and timescales? What is realistic and what is hyperbole? What is on the scientific horizon and what is (currently) science fiction?
The divisions of our inquiry follow a familiar delineation of research subjects (microorganisms, plants, animals, humans) for pragmatic reasons. We recognise there will be much cross-over among these areas and difference within them, and we also raise a number of cross-cutting issues (such as ownership of intellectual property).
The questions are indicative of our current interests. We encourage you to answer as few or as many questions as you wish, and feel free to ignore those that do not relate to your own knowledge or interests. We do not expect anyone responding to address all of them. Please feel free to provide other information that you think may assist the working group and, especially, to indicate other questions that you think we ought to address but may have omitted.
*TALENs stands for ‘transcription activator-like effector nucleases’; CRISPR stands for ‘clustered regularly interspaced short palindromic repeats’ (Cas9 stands for ‘CRISPR associated protein 9’). These systems, and zinc finger nucleases (ZFNs), use endonucleases that operate as ‘molecular scissors’ to cut the DNA molecule at a desired point and exploit cell repair mechanisms to repair the cut using one of two pathways that are naturally present in all cells.
**Where the repair is mediated by the non-homologous end-joining (NHEJ) pathway, the repair will involve the uncontrolled loss or gain of DNA at the cut site. When the pathway is homology-directed repair (HDR), an extra piece of DNA is used to introduce a predictable change at the cut site, which can enable intentional insertions, including, for example, the introduction of new functional genes to the genome or the replacement of a segment of DNA that permits subtle changes to be made to an existing gene.