Problems and Purpose

Mitochondria are present in almost all human cells. For any cell to work properly, the mitochondria need to be healthy. Unhealthy mitochondria can cause genetic disorders known as mitochondrial disease, caused by faults in the DNA within mitochondria, which can cause a range of conditions from mild to severe and life threatening, with no known cure and limited treatment options. Mitochondrial disease can be transmitted from a mother to her children. 

Techniques to modify the DNA of eggs or embryos are currently allowed for research purposes, but are currently illegal for treatment purposes under the Human Fertilisation and Embryology (HFE) Act of 1990. Permitting mitochondrial replacement in treatment would require a change in the law by Parliament, through secondary legislation to introduce regulations. 

The dialogue was commissioned at the request of the Secretary of State for Health, by the Human Fertilisation and Embryology Authority (HFEA) to advise on the public’s views of the ethical issues involved in the techniques. 

The aim of the engagement process was to assist HFEA in understanding: 

• the ethical issues entailed in licensing techniques to avoid mitochondrial disease  
• how people comprehend ethical issues involved in techniques to avoid mitochondrial disease  
• the deliberative process people go through to form views on techniques to avoid mitochondrial disease  
• the difference between informed and uninformed views on techniques to avoid mitochondrial disease 
• interested stakeholders’ arguments for and against techniques to avoid mitochondrial disease. [1]  

Background History and Context

In January 2012, the Wellcome Trust announced funding of £4.4 million for a new Wellcome Centre for Mitochondrial Research at the University of Newcastle, to establish the safety and efficacy of two new medical techniques to avoid inherited mitochondrial disease. The techniques involve removing the nuclear DNA from an egg or embryo with unhealthy mitochondria and transferring it into a donor egg or embryo with healthy mitochondria. If this were allowed in treatment, it would be the first time that modified embryos were used to make a child who would in turn have DNA from its parents and a donor, and who would pass those changes down the maternal line to the next generation. The researchers estimated that these techniques could become treatments within two years. 

These techniques (‘mitochondria replacement’) are currently illegal in treatment in the UK. The Human Fertilisation and Embryology Act (1990), as amended in 2008, governs research and treatment involving human embryos and related clinical practices in the UK. The Act only permits eggs and embryos that have not had their nuclear or mitochondrial DNA altered to be used for treatment. Permitting mitochondrial replacement in treatment would require a change in the law by Parliament, through secondary legislation to introduce regulations. A six-month inquiry by the Nuffield Council on Bioethics into the ethical issues raised by the new techniques was launched in January 2012 and reported in June 2012. 

Also in January 2012, the Secretary of State for Health, and the Secretary of State for Business, Innovation and Skills, asked the HFEA to seek public views on emerging IVF-based techniques to prevent the transmission of mitochondrial disease (with support from Sciencewise). [1]

Organizing, Supporting, and Funding Entities

Total cost of project: £220,000 (Sciencewise contribution: £72, 000)

The Office for Public Management (OPM), in partnership with Forster and Dialogue by Design, was commissioned by the Human Fertilisation and Embryology Authority (HFEA) to deliver the project following an open call. Cardiff University were the evaluators of the project. Sciencewise provided support in the form of expertise and funding. 

Human Fertilisation and Embryology Authority (HFEA)

The commissioning agent for the dialogue, the HFEA licenses and monitors UK fertility clinics and all UK research involving human embryos, while providing impartial and authoritative information to the public.

University of Cardiff

Cardiff University School of Social Sciences was the project evaluator.

OPM

OPM is an independent public interest company that helps public services and communities to improve social outcomes. OPM was responsible for delivery of the public dialogue and other engagement strands of the project. [2]

Sciencewise-ERC

Sciencewise-ERC is a Department for Business, Innovation and Skills funded programme to bring scientists, government and the public together to explore the impact of science and technology in our lives. It helps Government departments and agencies commission and use public dialogue to inform policy making, involving science and technology issues. Its core aim is to develop the capacity of Government to carry out good dialogue, to gather and disseminate good practice, have successful two-way communications with the public and other stakeholders, and to embed the principles of good dialogue into internal Government processes.

Participant Recruitment and Selection

• Total public participants in project: 1, 070
• 979 public representative survey
• 90 deliberative workshops
• Total stakeholders: 1,935
• 92 across two open consultation meetings
• 1,836 responded to open consultation questionnaire

An independent Oversight Group was established, comprising a diverse range of experts with different perspectives, to oversee the process and advise on and check materials  

An expert panel of stakeholders was convened and met once to consider the deliberative workshop design and input materials [1]  

Three deliberative workshops, each involving around 30 people, were held in July 2012 in Newcastle, Cardiff and London. Each group met twice. Participants were recruited to represent a broad spectrum of age, gender, socio-economic status and family circumstances. Scientists attended the first series of these workshops to provide specialist input; bio-ethicists attended the second set of workshops.

A focus group was conducted in London in December 2012 with six participants, all of whom had been affected by mitochondrial disease in different ways. One telephone interview was also conducted by the dialogue delivery contractors, in January 2013, with a participant who was unable to attend the focus group. The evaluation report observed limited information on the recruitment of members of the focus group with people affected by mitochondrial disease. [3]

Methods and Tools Used

The project included a wide range of engagement activities. All five consultation strands are described below.  

Deliberative workshops

This element comprised six events: two run in each of three locations: London, Cardiff and Newcastle. The first set of events were largely concerned with providing participants the rudimentary knowledge needed to engage with the mitochondrial disease issue; the second (reconvened with the same participants from the first series) were concerned with debating the social and ethical aspects of this issue. These five-hour events involved the use of videos; presentations from experts; facilitated small group discussions among tables of participants (chosen to be broadly representative of the population); plenary discussions, quizzes, information sheets, and some voting processes (in the second series of events).

In August 2012, an opinion poll survey was carried out, involving 979 face-to-face interviews with a representative sample of the public across 175 random locations.  

In November 2012, two public meetings were held for around two hours in London and Manchester (53 and 39 self-selecting attendees respectively). A panel of speakers, reflecting a range of perspectives, provided input and there was discussion in small groups, and between and across the panel and the floor.  

Between September and December 2012, a consultation website and questionnaire was open to self-selecting respondents.  

Finally, a focus group was held of seven people affected by mitochondrial disease, directly or indirectly. [1]  

What Went On: Process, Interaction, and Participation

Deliberative Workshops

The first series of workshops was largely concerned with providing the scientific background to the issue of mitochondrial disease and novel potential treatments - that is, to provide participants with the knowledge necessary to allow them to consider the merits or otherwise of the proposed innovations. Participants attending the workshops were seated at three tables (pre-designated). Some of the events during the day (which went from 10a.m. to 3p.m.) occurred in plenary, though many took place in three smaller groups (of up to 10). Each table had a professional facilitator. Information was provided to participants through a number of means: handouts, posters, videos, and thorough presentations and responses from a scientific expert. 

The first workshops essentially followed a similar schedule. Between 9.30 and 10.00, participants arrived, registered, and completed an initial questionnaire. Coffee was available. Participants then sat around three tables. The events began with plenary presentations, during which there were introductions to the parties involved; the aims of the day were described; and ‘housekeeping’ issues were raised (by the organisers). The context of the issue was then presented by an HFEA representative. 

Then, a short session followed, in which the groups at separate tables discussed their initial views and knowledge. This session varied in specifics according to event and facilitator (all tables having one facilitator). In some cases, some sort of introductory task took place (e.g. individuals being asked to chat with their neighbour and then introduce them to the group), while in others, the facilitator stood beside a flip chart and simply asked the group what they knew about assisted reproduction. A coffee break followed. 

There were four more elements to the rest of the morning: first, there was a small group ‘discovery session’ called by the organisers ‘bluff your way in biology’. During this, each participant was given 15-20 minutes to answer a short quiz on the basic biology associated with mitochondrial replacement, drawing on information posters that were placed around the room (there were also handouts, and the expert was around as a resource to be quizzed). Participants were split into small groups for this. The answers subsequently emerged on a handout and were discussed at the tables. 

Next, there was a video describing mitochondrial disease. This used cartoon-style animation to give a simple explanation of the problem and potential solutions (this was shown more than once at one event). The experts (scientist and HFEA person) were available to answer any questions following the video, and there were slides showing the two different proposed options for dealing with mitochondrial disease. Some group discussion followed on mitochondrial disease and the ways of avoiding/dealing with it. 

The afternoon session started with an expert question-and-answer session or the re-showing of the video (at one event). There were table discussions focusing on ‘What is new about these techniques? How are they different from assisted reproduction techniques that are currently permitted?’ There were then further table discussions on the issues: ‘What have you discovered today and what more do you need to know? What will you tell your friends and family about today?’ Questions were collected for the expert to answer. 

There was then a plenary summing up of the day and looking forward to the next event, with the issue of ethics introduced. There was also a quiz and a chance to win a box of chocolates. Finally, the event closed; participants were thanked, and asked to complete a short evaluation questionnaire. After this, as they were leaving, participants got ‘thank you’ payments. Close time was officially 3p.m. 

The second series of events was somewhat different in emphasis. These broadly followed a similar process (some events were conducted in plenary, some conducted at three facilitated tables with up to 10 persons at each – generally in the same groups as before, though some effort was made in one of the events to mix the groups up). Again, an HFEA representative was present to cover regulatory (etc.) issues, as was an expert. On this occasion, however, the experts involved were bioethicists, since the workshops now moved on (after initial re-familiarisation of participants with the science) to discuss the ethical issues of allowing (or not) the novel treatments being discussed. Additionally during these workshops, participants’ views on the desirability of allowing the new approaches were collected at three times during the day. 

The groups considered scenarios and deliberated on two specific issues: DNA from 3 people, and the issues of germ line therapy. After discussing the first scenario (with again, variation between events – from group discussions in general, to discussions in pairs, writing on post-its), there was another video – this about the nature of ‘identity’. This was followed by a presentation by the bioethicist. Discussion followed in groups and plenary (a chance for the ethicist to answer questions).

Then the groups considered the second (‘germline’) scenario. A second round of voting (using the stickers) took place. Then there was another segment of video, in which various experts discussed the germline problem, and then the bioethicist spoke again. (The sequence of these events did vary somewhat across the three events.) 

Next there were small table discussions reviewing the issues, and thinking about ‘What’s most important?’ and further ‘What messages do we want to give to the Secretaries of State?’ A third round of voting took place, with discussions in the groups. The event then concluded with a plenary debriefing, discussing what would be done with the participants’ contributions and how they might stay involved. Once more, the event ended with the distribution of the participant evaluation questionnaire and the honorarium payment. [3]

Open Consultation Meetings

The public meetings, one held in London and the other in Manchester, were designed to expose participants to the full gamut of possible views about mitochondria replacement techniques. They established a forum for informed debate about the issues. These two-hour events involved the use of an explanatory video; statements from panel members in plenary; self-facilitated discussions among tables of participants; and plenary answering of questions by the panel members. 

The event began with one of the organising team (from OPM) welcoming participants. This presenter introduced himself and described to participants how this event was one of several strands being used by HFEA to address the mitochondrial disease issue that was being discussed. He continued by explaining the contractor’s role, and then outlined a rough agenda for the evening, notably, that there would be a video, brief presentations from the panellists who were sat on the stage, ’30 minutes’ of table discussions in which they would be asked to ‘facilitate themselves’ and write answers to the questions on the A3 sheets (doing the top sheet first), and then they would open up into ‘public debate’ with free-ranging questions from the floor. 

After these introductions, the video was shown. This was an animated/ cartoon-like video explaining the issue of mitochondrial disease and the nature of the new treatments that might address this. The video was the same one as was shown in the previous public dialogue events held in London, Newcastle and Cardiff 

Following this, the Chair invited the four panellists, in turn, to speak for ‘3-5 minutes maximum’ on the issue. While the first two speakers had generally kept to describing the science issues in a generally neutral manner, the third speaker was more direct in opposition, using ‘blunt’ language and deliberately eschewing ‘euphemisms’. They used emotive terms: ‘harvesting’; ‘kills embryos’; ‘spare parts’. The fourth presentation was also somewhat emotive, with the representative of a patient charity, who had lost a daughter to the disease, giving a description of the progress and effects of the disease. In short, this presentation provided an emotive plea for the new approaches in counter- point to the emotive negative advocacy of the third speaker. 

A question and answer session followed and a summing up process. [3]

Public Representative Survey

A survey comprised of 10 questions took place, involving 979 face to face interviews took place alongside the dialogues. Full details of the questions can be found in the Evaluation Report (see [3])

Open Consultation Questionnaire

An open written consultation: ‘Medical Frontiers: debating mitochondria replacement’ ran from 17th September 2012 to 7th December 2012. Respondents were asked to engage with information presented online within the consultation website and provide answers to seven questions. 

Focus Group with People affected by Mitochondrial Disease

The evaluation report notes limited information on this element of the engagement process [3]. It observes that this was a relatively minor – though important – element of the overall process, deliberately engaging with people with a very direct stake in the problem, i.e. sufferers. The only possibly negative issue here is that there was just a single focus group – and more groups might have uncovered other issues (i.e. data saturation cannot be confirmed). However, other views from this important group were also collected through the consultation and expressed by panel members (who were sufferers) in the two public meetings. [3]

Key Messages from the Public

The deliberative public workshops broadly agreed support for the techniques, with caveats and conditions including: 

• Individual choice is important and parents should be able to choose to use these techniques.  
• Individuals need to be provided with all the relevant information they need to make an informed choice. This includes information on the potential risks, any uncertainties, and the pros and cons of the techniques.
• The techniques must be introduced in a regulated environment. 
• Parents who choose to use these techniques should be offered counselling.
• Donors’ identity should be protected – although different views remained about whether some information should be available to the child.
• Fair access to these techniques is essential and they should be available on the NHS, to all who might benefit from them, free of charge.
• The techniques are to be used to produce a healthy child and for no other purpose.

The deliberative public workshops also broadly took the view that certain requirements needed to be in place before support could be given to the use of the techniques:  

• A more comprehensive scientific assessment of safety and efficacy must be done.
• There needs to be more information about how individuals will be able to access the techniques, with an emphasis on the importance of fair, equitable and affordable access.  
• There needs to be more information about mitochondrial disease provided to the public, along with information on testing and diagnosis. 

Most people across all consultation strands believed the two new techniques offer the potential of significant improvements on the reproductive options currently available for women with unhealthy mitochondria. Across the different dialogue strands, most participants were positive about the techniques with the exception of respondents to the open consultation questionnaire (a self-selecting sample), of which a slight majority were opposed. 

The prevailing view of a majority of participants across all five strands of the consultation was that the outcome of the techniques – a healthy child, free of faulty mitochondria and a potentially serious disease – outweighs the possible consequences of changing the germline, even though these might not be apparent until sometime in the future. 

Some participants questioned the implications mitochondria replacement might have on a child’s sense of identity. While most participants seemed to be comfortable with the idea of DNA from three people, others felt that this is not acceptable as our understanding of the role of mitochondrial DNA remains limited in some respects and we should be cautious about introducing these techniques into clinical practice. 

Views on the status of the mitochondrial donor were mixed. While some felt very strongly that the anonymity of the donor should be protected and have the same status as for example blood donors, others, however, felt strongly that children should have the opportunity to know the identity of the donor, should they request it. 

In all the consultation strands participants argued that strong regulation is essential if the techniques are licensed for clinical use. Clinics themselves would need to be licensed, and access to and use of the techniques should be regulated by a body such as the HFEA. 

Most of those involved in other strands of the consultation apart from the open consultation questionnaire would support a change in the law that will allow these techniques to be used in a clinical setting. Those opposing the techniques in the open consultation questionnaire were often arguing that the use of the techniques would amount to inappropriate interference with the natural or spiritual aspect of reproduction, or that any artificial or in vitro manipulation of embryos is unethical. [1] 

Influence, Outcomes, and Effects

There have been significant direct impacts on policy development. The dialogue findings were fed directly into HFEA advice on the public view, which contributed to Government considerations on whether to change the law to allow clinical practice of mitochondria replacement. 

The HFEA agreed its advice to Government on 20 March 2013, concluding that the results of the consultation showed broad support for mitochondria replacement being made available to families at risk of passing on a serious mitochondrial disease. The HFEA advice specifically identified a series of safeguards that reflected the three conditions identified in the results from the public dialogue and drew extensively on all the results from the consultation. The finalised public dialogue and scientific update reports were sent to Government on 28 March 2013. 

On 25 June 2013, there was a debate in the House of Commons during which the Parliamentary Under-Secretary of State for Health (Anna Soubry) referred to the consultation on mitochondria “In collaboration with Sciencewise, which has a key role in helping the public to understand complex scientific issues, the HFEA took many different approaches to ensure that it gathered public views on the issue”, and the HFEA report included “the outcome of its public dialogue”. She reported that the HFEA had advised the Government that “there was broad support for mitochondrial replacement being made available to families at risk of passing on a serious mitochondrial disease” and that it also advised that “if treatment were to be authorised by Parliament, it should be under certain conditions such as its being available only in licensed clinics”. 

On 28 June 2013, the Chief Medical Officer (Dame Sally Davies) announced that the Government (Department of Health) had decided that “Innovative IVF-based techniques could be made available to patients to help prevent serious mitochondrial disease in the UK”. The announcement included specific reference to the public consultation and its conclusion of support, “subject to strict safeguards and careful regulation”. 

On 1 July 2013, Anna Soubry made a further statement in Parliament that the Government “largely accept the advice contained in the HFEA’s report of 28 March. We therefore propose moving forward towards laying regulations ... to allow mitochondria replacement techniques to prevent the transmission of serious mitochondrial disease, subject to strict safeguards ... We therefore intend to publish draft regulations for consultation in autumn 2013 with the intention that, subject to the views received, these would be laid before Parliament next year.” As well as enabling women “who carry mitochondrial disease the choice to have genetically related children without risk of serious and life-threatening conditions. It would also keep the UK in the forefront in scientific development in this area”. 

Draft regulations were issued for consultation in February 2014, and are expected to be followed by the introduction of a final version of the regulations for debate in Parliament later in 2014. 

There was extensive media interest and coverage of the consultation throughout, including the issue being the top news story in June 2013 when the Government announced its decision to go ahead and produce draft regulations. The HFEA issued press releases throughout the consultation [1]  

Analysis and Lessons Learned

What Worked Well

Overall, the evaluation concluded that consultation was seen as “a perfect example of how to pull together various methodological strands successfully and relatively seamlessly into an overarching consultation” and “manage (if not altogether reconcile) various, polar and antithetical opinions”.

The multiple methods worked well together; the various dialogue components were individually successful and collectively more so. The deliberative public dialogue events were seen to be especially revealing. These were seen as reflecting the views of ‘proper public’, people who didn’t have a stake. Reconvening the workshops was important to show how attitudes changed after people had gone away and thought about it. In addition, information materials, created with diverse stakeholder input, provided an example of how to communicate complex science to an inexpert audience in accurate and unbiased ways. The animated video to explain the techniques to the public at the workshops worked very well, together with the handouts, posters, presentations with Q & A from specialists and quizzes. 

The Oversight Group was a very important aspect in the overall design of the project. Members contributed an expert steer, commentary and advice drawn from their own diverse professional contexts. The evaluation report described the Group as “as near as possible a universal spectrum in critiquing aspects of the project from scientific, theological, journalistic, secular, scholarly and patient perspectives and providing a core component of quality assurance”. 

Holding the final HFEA decision-making meeting in public (as is HFEA normal practice) was significant for demonstrating transparency of process and, to a degree, public accountability. 

What Worked Less Well 

There was a scientist present at the first set of workshops, which worked well, but not at the second where bio-ethicists attended. This was felt to be a gap as questions on the science still remained. In addition, the time lapse between the consultation and Government action could lessen the perceived impacts in informing policy, which could blur lines of causality. [1]

See Also

Sciencewise

References

[1] Sciencewise (2014) “Case Study: Mitochondria Replacement” Sciencewise, April 2014

[2] Sciencewise (2017) “Mitochondria Replacement” [ONLINE] Available at: https://webarchive.nationalarchives.gov.uk/20170110132751/http://www.sciencewise-erc.org.uk/cms/mitochondria-replacement/

[3] Watermeyer, R and Rowe, G (2013) “Evaluation of Project: Mitochondria Replacement Consultation”, Cardiff University, Gene Rowe Evaluations, July 2013

External Links

 https://sciencewise.org.uk/ 

Notes