Page URL: https://www.progress.org.uk/genomicsgenomeediting

Written evidence submitted to Genomics and Genome Editing in the NHS, an Inquiry by the Science and Technology Select Committee of the UK Parliament's House of Commons

13 October 2017
This policy document is written evidence submitted by the Progress Educational Trust (PET) to Genomics and Genome Editing in the NHS, an Inquiry by the Science and Technology Select Committee of the UK Parliament's House of Commons.

Executive summary
It is important to promote better understanding of what a genome is, alongside public and policy discussion of genomics and genome editing.
Public debate and discussion are vital, if genomics is to be successfully embedded into mainstream healthcare.
Genome sequencing and genome editing should not be conflated, as they are very different genomic technologies.
Genome editing is very important in research and in a small number of experimental treatments, but does not currently form a significant part of the 'genomic medicine' picture (certainly not in the NHS).
Greater priority should be given to explaining the use(s) of genome editing than should be given to explaining the mechanism(s) via which genome editing works. CRISPR and Cas9 should only be referred to when there is a specific reason to do so. Policies and principles concerning genome editing should be applicable beyond the specific technique used.
Policymakers and others should refrain from suggesting that there is a settled consensus on the importance and ethical implications of either the somatic/germline distinction or the treatment/enhancement distinction.

1. Introduction
The Progress Educational Trust (PET) is a registered charity which advances public understanding of science, law, ethics and policy in the fields of human genetics, assisted reproduction, embryology and stem cell research. Its vision is to improve the choices for people affected by genetic conditions and infertility. Its mission is to educate and debate the responsible application of reproductive and genetic science. PET's experience in this field is substantial - the charity was founded in 1992, while its precursor organisation (the Progress Campaign for Research into Human Reproduction) was founded in 1985.
In recent years PET has conducted thoroughgoing public engagement and policy work in the fields of genomics and genome editing, bringing experts together with patients and laypeople to improve scientific understanding and to debate matters of ethics and policy. Most recently, PET conducted a project entitled 'Basic Understanding of Genome Editing' with fellow charity Genetic Alliance UK and with the support of the Wellcome Trust. The findings of the project are published in a report at www.progress.org.uk/genomeediting
Our project explored what patients and laypeople think and know about genome editing and its implications, and developed Recommendations for how best to discuss genome editing in public. Some of these findings are discussed below, but one finding which is worth flagging up at the outset is the importance of making clear distinctions between different areas of genomics. The title and scope of this Committee's Inquiry - Genomics and Genome Editing in the NHS - are so broad as to risk perpetuating the confusion that already exists between very different genomic technologies.
The participants in the 'Basic Understanding of Genome Editing' project were drawn from the (in)fertility, genetic disease and rare disease communities, and yet even participants in the latter two categories - who were more likely than an average member of the public to have encountered and thought about genomics - struggled to distinguish genome sequencing from genome editing. For example, many participants laboured under the misapprehension that genome editing was the research tool behind the government-initiated 100,000 Genomes Project, which involves no use of genome editing at all.
One factor that contributed to participants' confusion is the fact that the term 'genome' is not very well understood - it has not (yet) entered popular use with its meaning intact, not even among those who might be considered likely to encounter and use it. Our participants tended to be familiar with the term 'genome', but unable to explain it. Many were uncertain about whether a genome is bigger or smaller than a gene, and whether a genome is the same or different in different cells of an individual's body. This finding points to the importance of promoting better understanding of what a genome is, alongside public and policy discussion of genomics and genome editing.
'Genomic medicine' - an approach to medicine in which our genomic information plays a central role in understanding, preventing, diagnosing and treating disease - is an increasingly important concept in healthcare and policy. In documents such as the Chief Medical Officer's recent report Generation Genome, the term 'genomic medicine' refers to the new possibilities afforded by sequencing and studying genomes on a large scale. By contrast, the editing of genomes - while very important in research, and in a small number of experimental treatments - does not currently form a significant part of the 'genomic medicine' picture (certainly not in the NHS).
Below, PET presents its views on genome sequencing and genome editing - considered separately - and draws upon its experience organising and promoting public debate about these areas. PET urges this Inquiry to be mindful of, and clear about, the distinctions between these areas.

2. Genome sequencing
The most prominent example of genome sequencing in the NHS is the 100,000 Genomes Project, and NHS England's 13 Genomic Medicine Centres where the Project is being delivered. Building on the 100,000 Genomes Project, the NHS is the first healthcare system in the world seeking to commission routine whole genome testing for rare diseases and cancer.
PET is fortunate to have collaborated with Genomics England on public engagement events and activities in both the early stages and the later stages of the 100,000 Genomes Project, and also to have collaborated with the Chief Medical Officer on the launch of her Generation Genome report earlier this year. That report discusses 'the importance of ethical reflection and patient engagement in the development of the coordinated national and international developments in genomic medicine', and the report's 'Recommendations' include 'extensive public dialogue on the shared social contract between patient, public, clinicians and academics in relation to genomic medicine'.
PET can attest to the vital importance of, and tangible benefits from, such public engagement and public dialogue. Although panels of eminent speakers are featured at PET's free-to-attend public events, their presentations are kept concise, in order to foster dialogue and dynamism. Much of the the running time is dedicated to letting the audience put questions and comments to the speakers.
In 2014, PET collaborated with Genomics England on two public events about the 100,000 Genomes Project - 'Genomic Medicine Needs You' (in Oxford) and 'Genetic Conditions: How Should Your DNA Be Used in the 100' (in London) - and these were attended by 315 people. Of those attendees who completed evaluation forms, 95% stated they were better informed as a result of attending these events, and 73% stated that they would be willing in principle to participate in the 100,000 Genomes Project (assuming they were eligible to do so).
Attendees at both events were asked to suggest questions that they wanted PET to put to the wider public, so that the issues discussed could be explored further and so that this discussion could actually be driven by the public (rather than being foreclosed by our own preconceptions). The questions suggested by attendees were used in a poll on the website of PET's flagship publication BioNews in 2015, and this poll elicited responses from 775 people.
The poll began by asking - again - whether respondents would be willing in principle to participate in the 100,000 Genomes Project. The results were very similar - 74% responded 'Yes', while 16% responded 'No' and 10% responded 'Don't know'.
The poll asked people to give reasons for their response to this question. The majority who responded 'Yes' gave responses whose dominant themes were altruism, duty, curiosity, the project's importance, and improved treatment (of their own diseases or those of their family members). The minority who responded 'No' or 'Don't know' gave responses whose dominant themes were data, trust, commercial interests, ethical objections, and concerns that they might discover something via their genome that they preferred not to know.
The other questions PET asked in this poll were:
What feedback would you want from your clinician if you had your whole genome sequenced?
How confident are you that you understand what your whole genome sequence may tell you?
What do you think might be the benefits of participating in the 100,000 Genomes Project?
Do you think participating in the 100,000 Genomes Project could affect any of the following? Why?
Ability to get health insurance
Ability to get life insurance
Ability to get a mortgage
None of the above
Responses to these questions - explored in detail here and here - suggested that large numbers of people believe there are significant benefits to participating in the 100,000 Genomes Project, and believe that these benefits outweigh any risks. At the same time, there remains a constituency of people who - to a greater or lesser extent, and for a variety of reasons - are not persuaded of this view.
PET held two further public events with Genomics England in 2017, which were attended by 270 people. The first event, 'What Next for Genomics? Providing Answers' (in London), marked the launch of the Generation Genome report. The report's contents and implications were discussed by speakers including the Chief Medical Officer herself, NHS England's Chief Scientific Officer, and two experts who had coauthored chapters of the report.
A film of this event can be watched here. A substantial article about issues raised at the event was published by Prospect magazine here.
Of the attendees at this event who completed evaluation forms, 91% stated they were better informed as a result of attending. PET also asked in evaluation forms 'Do you think genomic medicine is having a transformative effect on UK healthcare?', and the responses were encouraging - 83% responded 'Yes', 11% responded 'No' and 6% responded 'Don't know'.
A follow-up event, 'What Does Consent Mean for Generation Genome?' (in Manchester), focused on the topic of consent as addressed in the Generation Genome report and also the National Data Guardian's recent report Developing a Consensus on Data Sharing to Support NHS Clinical Genetics and Genomics Services. Speakers included an expert who contributed to both of these reports, as well as the Chair of the Participant Panel for the 100,000 Genomes Project (whose child has an undiagnosed genetic condition and is severely disabled) and - once again - NHS England's Chief Scientific Officer.
The Generation Genome report calls for 'a short, simple, understandable and workable consent process for patients to choose how confidential genomic data about them is used'. The National Data Guardian's report says work is needed 'to explore how the consent process might cover both direct and indirect care purposes as genetic and genomic medicine become a more routine part of care for a greater number of NHS patients'.
Of the attendees at this event who completed evaluation forms, 86% stated they were better informed as a result of attending. PET also asked in evaluation forms 'Should consent to participation in genomics research always be taken during a face-to-face discussion with a medical professional?'. This time, opinion was sharply divided - of those who completed forms 47% responded 'Yes', 40% responded 'No', and 13% responded 'Don't know'.
PET's events and initiatives with Genomics England and the Chief Medical Officer have left the charity in no doubt that this sort of public discussion is vital, if genomics is to be successfully embedded into mainstream healthcare.
PET would also like to commend the launch in 2017 of the Understanding Patient Data initiative, which has made sensible proposals for meaningful and consistent language concerning data and privacy.

3. Genome editing
Genome editing has a vast range of current and possible future uses, but has prompted especially high-profile publicity and debate when it has been used in research on human embryos.
In 2017 alone, the genomes of human embryos have been edited by researchers:
In the UK, in order to study gene function (the first time genome editing has ever been used on human embryos for this purpose).
In the USA, in order to correct a mutation that causes hypertrophic cardiomyopathy (other researchers have questioned the findings of this research).
In China, in order to correct a mutation that causes beta thalassemia.
The first two examples listed above employed the CRISPR approach to genome editing, which has increasingly become standard. However, the third example (in China) employed an alternative approach known as 'base editing'.
This bears out one of the key Recommendations of our 'Basic Understanding of Genome Editing' report, namely that greater priority should be given to explaining the use(s) of genome editing than should be given to explaining the mechanism(s) via which genome editing works. By way of analogy with the previous section of this submission, public discussion of genome sequencing does not tend to involve discussion of the method of sequencing or other such detailed mechanics.
Participants in our 'Basic Understanding of Genome Editing' project were confused by the tendency to use CRISPR as a synonym for genome editing per se. They found this especially confusing in relation to one of the most celebrated uses of genome editing in the UK, to reverse advanced leukaemia in a one-year-old baby in 2015, because this treatment did not actually involve CRISPR at all. Rather, it employed the TALENs approach to genome editing which was developed before the CRISPR approach. Policymakers, and the wider public, should be aware that CRISPR was not the first approach to genome editing ever to be devised and it will not be the last.
The term 'CRISPR/Cas9' - which is often used interchangeably with 'CRISPR' and 'genome editing' alike - left our participants even more confused as to where the relevant distinctions lie. 'Cas9' is the nuclease most commonly used in the CRISPR approach to genome editing, but it is not the only nuclease that can be used (for example, work is ongoing with the alternative nuclease Cpf1) and it may yet be superseded in future.
It would be helpful to take a step back and question whether and when CRISPR and Cas9 need to be mentioned in discussions of genome editing, referring to them only when there is a specific reason to do so. Policies and principles concerning genome editing should be applicable beyond the specific technique used.
Confusion also arises from a proliferation of near-synonyms for the term 'genome editing'. Use of the similar terms 'gene editing', 'genomic editing', 'genome engineering', and so on lowered the confidence of our participants (as they could not be certain whether these terms referred to the same technology or to different technologies), and could result in (avoidable) confusion in policy contexts.
The term 'genetic modification' is especially misleading in relation to genome editing, as it has traditionally implied the introduction of foreign (transgenic) DNA into an organism (as in 'GM crops' and 'GM food'), whereas editing the genome of an organism does not necessarily involve introducing any foreign DNA.
Using the term 'genome editing' consistently is the best way to achieve clear discussion of this area, and PET would recommend that this term is adhered to wherever possible. A major advantage of this term is that it has wide scientific applicability - even an edit to a single gene (or part of a gene) in an organism can be said to change an entire genome, and can still involve an entire genome being searched by a guide molecule.
Our participants wished for and benefited from clear, broad distinctions between the following uses of genome editing.
Human and other uses.
Current and future uses.
Research and treatment.
Uses that are currently permitted and uses which would require regulatory change.
When we consider genome editing in humans, one of the most important distinctions - in policy, law, science and ethics - is between somatic genome editing (which results in changes that are not heritable by the next generation) and germline genome editing (which results in changes that are heritable by the next generation). But despite the importance of this distinction to specialists, our participants had difficulty grasping it.
To the extent that our participants did grasp this distinction, they did not ascribe as much importance to it as we might have expected. Recent research into public attitudes to genome editing in the USA found much the same thing, with no significant difference between public support for somatic and germline genome editing .
Another distinction that is often made, when considering clinical uses of genome editing in humans, is between treatment and enhancement. Here, we found a significant difference in attitudes - a majority (but not all) of our participants thought that treatment was more ethically acceptable than enhancement. Again, research into public attitudes to genome editing in the USA has found much the same thing.
However, there is a further nuance that must be taken into account. While it is the case that many of our participants thought that treatment was morally acceptable whereas enhancement was morally dubious, there was significant disagreement over how to distinguish between these two categories.
We explored this disagreement with an applied ethics exercise, where participants were presented with different hypothetical applications of genome editing and asked to place them on a grid which had a treatment/enhancement axis, and an (im)morality axis. There was not always a consensus on how particular applications should be categorised.
Participants found it particularly challenging to categorise the hypothetical use of genome editing to confer resistance to infectious disease. Such an application might have a similar outcome to use of a vaccine, but achieved via radically different means. Would this constitute treatment, or enhancement?
In conclusion, policymakers and others should refrain from suggesting that there is a settled consensus on the importance and ethical implications of either the somatic/germline distinction or the treatment/enhancement distinction.