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Perspectives on Genome Modification

This policy document is the first part of a response submitted by the Progress Educational Trust (PET) to a Call for Evidence (.pdf 228KB) issued by the Nuffield Council on Bioethics, as part of the latter's project Genome Editing.

Is there anything special about the genome that makes intervening in it different from other ways of manipulating nature (eg, selective breeding of plants or animals)?
Broadly speaking, no. The fact that we are in a position to consider intervening purposefully in nature at such a fundamental level as the genome speaks to remarkable scientific advances, but is ultimately still a part of humanity's ongoing trajectory of investigating and manipulating nature to human advantage. In future, we may develop interventions in nature that are more intricate still.
It is also worth remembering that even intervention in nature often draws upon nature, rather than representing a completely alien incursion into the natural domain. The CRISPR approach to genome editing was not invented in complete isolation from the natural world and then introduced into it, but rather was adapted from a naturally occurring mechanism used by bacteria as a defence against invading viruses.

To what extent can the development of genome editing techniques be regarded as distinct from or continuous with existing techniques? In what way are the differences significant?
The development of genome editing techniques is very much a logical part of, rather than being distinct from, the development of other techniques of investigating and manipulating genes. The history of genome editing - successive breakthroughs, over the course of three decades, in the development of targeted gene insertions and knockouts and in the use of various guide molecules and (endo)nucleases to edit gene sequences - cannot be disentangled from wider advances and developments in biomedicine.
If genome editing sometimes appears to represent a radical break with the past, this is due largely to the rapid increases in its accuracy and efficiency - and decreases in its cost and difficulty - brought about by CRISPR, which is proving to be something of a disruptive technology. If CRISPR appears to have become suddenly ubiquitous, imbuing bioethical discussion with a sense of urgency, this state of affairs is the result of developments that can be traced back decades (notwithstanding the fact that the rapid culmination of these developments has caught many people and organisations on the back foot).
With the advances brought about by CRISPR, the range of possible varieties and applications of genome editing is now so wide that distinctions within the field - between somatic and germline, between research and therapy, and between human, animal, plant and microbe - are arguably just as significant as distinctions between genome editing and other areas of biomedicine, if not more so.

What obligations do scientists involved in developing and using genome editing technologies owe to society and what freedoms should society allow to these scientists? Do genome scientists have any special obligations to society that are distinct from those of other scientists?
One of the key obligations that scientists working in this field owe to society is the obligation to explore the potential of genome editing as thoroughly as possible, within the parameters of current regulation. Genetic conditions in particular are not always well understood, and tend to lack effective treatments. Genome scientists should be seeking to improve this situation.
Society, in turn, has an obligation to the scientists - an obligation not to impede their work where the work is lawful, to help with the funding of their work (either by providing public funding or by encouraging private funding), and to understand and help to promulgate their work (by improving the public understanding of science, and by raising the level of ethical and political debate).
Genome editing scientists do not have any special obligations distinct from those of other scientists, except inasmuch as their field can be especially challenging for the layperson to understand. ZFNs, TALENs and CRISPR come atop an already high mountain of genetics-related acronyms and jargon, describing processes which can have a major impact on people's lives.
Scientists need to lighten the burden of comprehension where possible, by explaining their work clearly and engagingly and by fielding questions and criticisms from outside their profession.

To what extent is the development of genome editing valuable as a pure research tool, and to what extent is its value dependent on envisaged practical applications?
Genome editing is extremely valuable as a pure research tool, giving us the ability to ask and answer questions about some of the most fundamental aspects of biology. The ability to conduct unprecedentedly precise and intricate experiments at the molecular level is a game changer, and could add immensely to the sum total of human knowledge. This new knowledge cannot help but bring to our attention new practical possibilities - possibilities which may or may not involve further application of genome editing.
It is important to remember that research using genome editing can yield insights which have practical applications elsewhere. Take the UK's first licensed human embryo research using CRISPR, led by Dr Kathy Niakan at the Francis Crick Institute, which is investigating the genes involved in the first seven days of embryo development. Such research could ultimately lead to improvements in assisted conception techniques, or at the very least an improved understanding (beyond trial and error) of how and why such techniques work, without the techniques themselves necessarily involving any genome editing at all.
The value of genome editing as a pure research tool is not contingent upon its practical applications. Speculation about envisaged practical applications is useful (not to mention exciting!) and has its place, but should not be used as a pretext to restrict pure research.
Practical applications do not have to follow ineluctably from pure research. Rather, pure research leaves us better placed make a well-informed decision about whether or not a specific practical application should be investigated.

What obligations do governments have towards society to ensure 'safe' science or otherwise to shape the scientific research and development?
It is incumbent upon governments and legislators to regulate scientific research and practice, either directly or via specialist regulators, to ensure that well-defined and proportionate standards of safety are met. This applies to genome editing just as it applies to any field of scientific endeavour involving some degree of risk (risk is inevitable, especially in therapeutics).
A narrative is forming around genome editing which suggests that somatic applications of the technology are safer and will be developed first, whereas germline applications of the technology are riskier and will take longer to satisfy the requisite safety standards. There is some truth to this, but it is a position that may change.
For example, editing the genome of a single-celled gamete or embryo may transpire to be considerably safer than editing millions of cells (as typically occurs in somatic cell therapies), because there will be a lower risk of accidental modifications to the gene sequence and a lower risk of mosaicism.

What conventional moral principles, if any, do genome editing challenge?
Genome editing does not pose a particular challenge to conventional moral principles. Those whose principles leave them well-disposed towards humans intervening in nature to improve their lot will feel less challenged by genome editing than those whose principles leave them ill-disposed towards humans intervening in nature.
This disposition will in turn shape perceptions of the technology's possible benefits and risks. When lauding or damning the technology, it is important to try to distinguish between arguments that rest on scientific grounds and arguments that rest on moral grounds (even though these two domains cannot be completely decoupled, science being a moral endeavour in many people's view).
The use of genome editing to modify early human embryos for research purposes, without any intention of establishing a pregnancy, fits comfortably under the auspices of the moral principles that apply to all embryo research. This fact is well reflected in UK legislation, where the relevant regulator - the Human Fertilisation and Embryology Authority (HFEA) - is already empowered by statute to grant licences for such research on early human embryos and indeed has already done so, granting a licence (.pdf 309KB) for Dr Kathy Niakan's research at the Francis Crick Institute.
The prospect that we may in future edit the genomes of gametes or embryos, to ensure or to prevent the presence of selected characteristics in a child, has provoked the same expressivist concern as earlier reproductive technologies - the concern that use of the technology will encourage stigmatisation of, or prejudice against, people with disabilities or with other deprecated characteristics. A related criticism is that by proactively choosing one possible future child over another, prospective parents commit the morally abhorrent act of negating the life of the child who was not chosen.
We do not agree with these perspectives. We believe that having the latitude to choose between hypothetical future people is innocuous, and is not tantamount to impugning or ending the existence of an actually existing person (which would indeed be morally abhorrent).
We also believe that the best way to assuage expressivist concerns is to enter into open and honest discussion with those who harbour such concerns, rather than seeking to restrict the choices available to prospective parents.

To what extent can the moral questions raised by genome editing be addressed using existing moral frameworks or approaches?
The UK has a well-established set of approaches and institutions for considering moral questions in biomedicine (including exercises such as the very consultation to which we are responding), and there is no reason to doubt the adequacy of these approaches in addressing the moral questions raised by genome editing.
One possibility raised by genome editing, which some people find morally challenging and which the UK is particularly well placed to address, is the possibility of changing the human germline - of making changes in the course of assisted conception which will affect not only the child born, but also subsequent generations.
Both assisted conception and its regulation are fields that were pioneered in the UK, with the first IVF baby born in the UK in 1978 and with the Warnock Report (769KB) of 1984 leading to the establishment of the HFEA in 1990. Until IVF babies grew up and started having babies of their own - including Louise Brown's son, who was conceived naturally only a decade ago - the impact of IVF on successive generations was necessarily a matter of some uncertainty.
Now that the UK is the first country to legislate for the use of an IVF technique that purposefully changes the germline (mitochondrial donation), the country's clinicians and regulators are leading the way in devising appropriate protocols for clinical follow-up and longer-term research.

To what extent are laws and legal frameworks necessary or desirable in seeking to ensure adherence to the moral principles that should inform genome editing?
Laws, even if they are drafted with moral principles in mind, do not actually ensure adherence to moral principles. Rather, they provide clarity by defining what it is and is not legally permissible to do in a given jurisdiction. Whether or not it is morally permissible to do something is a question on which there is far greater scope for legitimate differences of opinion.
By establishing clearly what is and is not permissible, legal frameworks promote confidence on the part of both people working within a particular framework (in this case researchers and clinicians) and people looking on from outside (the general public and people in other jurisdictions).
Legal frameworks lend coherence and transparency to scientific developments, and to the way the public relates to such developments. By contrast, in a poorly regulated environment, work that pushes back the frontiers of what is knowable and what is doable can seem disconcertingly haphazard and opaque. We have a responsibility to ensure that genome editing is developed in the former environment, rather than being left to the latter.

What other issues do you feel need to be discussed in the context of genome editing? What do you consider to be the issues of greatest moral concern raised by genome editing?
We think it is important to discuss the distinction (or rather lack of one) between therapy and human enhancement. 'Human enhancement' is often discussed as though it is self-evidently a step beyond therapy and more frivolous than therapy, but this is misleading.
All manner of improvements to human health can be considered enhancements, especially when they have the cumulative effect of steadily increasing average human longevity. Vaccinations conferring immunity to disease are a good example of enhancement. Unlike the difference between somatic and germline applications to genome editing, where a clear and important distinction can be made, we are not persuaded that there can always be a meaningful distinction between therapy and enhancement.
We are reassured by the fact that with or without an edited genome, children will - by virtue of being human - continue to grow into autonomous people whose personality is unforeseeable, and whose destiny is in their own hands.