Discussing the modification of heritable DNA in embryos

Summary

Advances in biomedical science and technology allow us to diagnose, treat or prevent a growing number of disorders. The expanding knowledge of the genetic basis of human traits and disorders and new technologies for modifying genes could in time make it possible to alter the building blocks of our lives: human DNA. That could have a variety of social repercussions – changes that affect us all and which, as we show in this report, we need to discuss.

We speak of germline genome editing when the DNA in the cells of a human embryo, or in cells that could grow into reproductive cells, or in a recently fertilised human egg cell (the very early stage of an embryo) is modified in de lab. If such a genetically modified embryo grows into a child after being transferred to the womb, the DNA of that child’s offspring will also contain these modifications. In the Netherlands, making these types of alterations in human germline cells with the intention of creating a viable foetus and pregnancy is prohibited by Article 24(g) of the Embryo Act. This ban is based not only on the uncertainty surrounding the safety and effectiveness of the technology but also on ethical and societal considerations. In the coalition agreement, the current government stated that there should first be a public dialogue on the issue of research with human embryos and the modification of heritable DNA before any decision was made on whether to amend the Embryo Act.

In 2012, a new technology was discovered for modifying DNA: CRISPR-Cas9. In contrast to earlier genome-editing technologies, CRISPR is often referred to as a ‘molecular scissors’. Scientists regard the technology as ‘easy to use, precise and relatively inexpensive’. The discovery appears to create new possibilities for preventing heritable diseases by making targeted genetic modifications in human embryos before they are transferred to the womb. This development has reopened the discussion about the modification of heritable DNA.

Guidelines for a broad public dialogue
In 2018, eleven organisations in the Netherlands, including the Rathenau Institute, took the initiative to organise a broad public dialogue – a process of collective opinion formation –to ascertain the views of Dutch society towards the modification of heritable DNA in the early development of human embryos. The Ministry of Health, Welfare and Sport welcomed this initiative and has, therefore, financed the project entitled ‘A public dialogue on germline genome editing’.

This report provides guidelines (‘lessons’) and instruments (scenarios) for conducting a national dialogue on the subject. In the first part of the report, we describe the debate that has been conducted up to now in the Netherlands – mainly in the media. We review what is already known regarding public opinion on the subject and present an analysis of the reasons for the existing regulation. We also describe the ethical and social issues that play (or could play) a role in the dialogue on the question of whether targeted modification of the genome of future persons is acceptable, and if so, for what purposes and under what conditions. To that end, we examined reports on the subject by national and international advisory bodies and ethics councils and conducted fourteen interviews with representatives of groups and parties with an interest in the dialogue.

Future scenarios
Techno-moral future scenarios can help thinking about and discussing possible futures. In the second part of this report, we, therefore, describe four techno-moral scenarios or foresight studies. These were produced based on the findings from the analyses, a scenario workshop with experts, and two focus groups with non-experts organised by the National Institute for Health and the Environment (RIVM). Based on the scenarios, NEMO Kennislink has produced techno-moral vignettes (in this case, animations) to facilitate a discussion on the social implications of the use of germline genome editing.
Four future scenarios have been formulated based on two key uncertainties (the culture surrounding reproduction and pregnancy and advances in technology):

1. Disease prevention by germline genome editing
2. Modification of heritable human DNA in a free reproduction market
3. Genetically-related children for everyone
4. No modification of the heritable DNA in embryos as a precautionary measure

The debate in the Netherlands
In the media in the last few years, various experts have advocated reopening the debate about the acceptability and desirability of human genome editing. We discern two approaches in that discussion. In the first, the emphasis is on the direct consequences (‘usefulness and necessity’) of the technologies, and manipulation of the DNA of future persons is seen as a potentially valuable medical intervention for preventing heritable disorders. The alternative approach focuses on the wider implications of the targeted modification of the human genome for individuals, society, and mankind.

There have been a few surveys of public attitudes towards human genome editing in the Netherlands and abroad. They often reveal a similar pattern. Modification of the genetic characteristics of offspring is regarded as controversial and acceptance of it depends on the proposed application. Preventing heritable disorders is regarded as acceptable more often than enhancing human traits. Although insights from articles and public surveys could contribute to a dialogue, no broad public debate is yet being conducted on the subject in the Netherlands.

Dialogue with different levels and dimensions
There is still a lot of uncertainty surrounding scientific and technological developments that enable the modification of heritable human DNA, including its safety and the consequences for individuals and society as a whole. These uncertainties will not be easily resolved and need to be thoroughly explored.

To provide a systematic overview of the social and ethical issues involved, we have divided them into three domains: research in the laboratory, research with humans and application in practice. It is important to cover the issues arising in each of these domains in the dialogue. In turn, different questions, considerations and issues can arise at different levels within each domain: the instrumental, the societal and the global (international) level. The time dimension is also relevant: these issues not only concern the here and now, but also future generations and future societies.

Conditions for conducting a public dialogue
Based on the analysis of the public debate in the Netherlands up to now, the relevant ethical and social issues and the Rathenau Institute’s years of experience with conducting public dialogues on (emerging) technologies, we start by formulating some general requirements for a national public dialogue:

• Public engagement. It is essential to devote a lot of attention to reaching and engaging members of the public so that they can inform themselves, form an opinion and discuss different perspectives and arguments.
• Information about the wider consequences for individuals, society, and humanity.
  A mix of methods will need to be used to achieve the goal of public dialogue. Scientific public surveys provide insight into the attitudes and considerations of only a small number of participants. Other activities and initiatives are needed to reach a wider audience.The dialogue must promote deep, joint consideration of the wider social consequences of the introduction of new technologies. Members of the public must also be informed of potential consequences, for themselves and others, for society as a whole and for current and future generations.
• Clarity about the subject matter of the dialogue.There is no consensus on what precisely is being discussed in a debate on the modification of hereditary DNA of future persons: the development of new medical treatments that could prevent a lot of suffering, or the future, dignity, and identity of individuals and humanity. Consequently, there is also (implicit) disagreement on what the central issues of the dialogue should be. Members of the public need to be able and enabled to speak out on both the desirability of germline genome editing and the conditions under which it can be permitted.
• Involvement of related themes. Because the theme of human genome editing is closely related to other themes, such as scientific research with human embryos, embryo selection, prenatal diagnosis, and genetic screening, issues relating to these connected themes could also arise in the dialogue.
• Different participants, different roles. These points call for a different role in the dialogue for experts in medical science and for input from experts from other fields, in addition to the input of parties that are directly or indirectly involved.
• Combination of methods. A mix of methods will need to be used to achieve the goal of public dialogue. Scientific public surveys provide insight into the attitudes and considerations of only a small number of participants. Other activities and initiatives are needed to reach a wider audience.

Ten lessons for the dialogue on germline genome editing
Organising a successful dialogue on germline genome editing presents challenges in terms of both its content and its form. The general conditions set out above lead to the ten following lessons conducting the dialogue on the modification of heritable DNA in human embryos.
Lessons for the content:

1. The questions of ‘whether’ and ‘how’ are interlinked – the dialogue should, therefore, not be limited to one or the other.
2. Include the question of what is at stake in the dialogue.
3. Clearly explain what is needed to make use of human germline genome editing (the research trajectory and basic conditions for the use of the technology in practice).
4. Discuss the broader implications of the targeted editing of the human genome for the individual, society, and humanity.
5. Discussing the modification of heritable DNA in embryos 8
6. Turn it around: think about the society of the future – what its core values should be and what role modification of heritable DNA in humans could play in that respect.

Lessons for the form:

1. Organise a dialogue not only between groups of stakeholders and interested parties, but also amongst themselves.
2. Actively seek ways of reaching and informing less accessible groups and engaging them in the dialogue.
3. A dialogue is not a platform for exchanging fixed views.
4. Involve and instruct appropriate experts and people with practical experience.
5. Think carefully about the themes, the material, the terminology and the subject matter that will be discussed during the sessions.

This report includes four future scenarios which are accompanied by videos.
Please click on the links to watch them. Note: the language is in Dutch.

Scenario 1: What if a society puts the prevention of diseases first?

Scenario 2: What is perfection becomes the norm?

Scenario 3: What if equality within society becomes our main goal?

Scenario 4: What will our society look like if avoidance in the health care prevails?

Ten lessons for the dialogue on germline genome editing

Organising a successful dialogue on germline genome editing presents challenges in terms of both its content and its form. The general conditions set out above lead to the ten following lessons conducting the dialogue on the modification of heritable DNA in human embryos.
Lessons for the content:

1. The questions of ‘whether’ and ‘how’ are interlinked – the dialogue should, therefore, not be limited to one or the other.
2. Include the question of what is at stake in the dialogue.
3. Clearly explain what is needed to make use of human germline genome editing (the research trajectory and basic conditions for the use of the technology in practice).
4. Discuss the broader implications of the targeted editing of the human genome for the individual, society, and humanity.
5. Discussing the modification of heritable DNA in embryos 8
6. Turn it around: think about the society of the future – what its core values should be and what role modification of heritable DNA in humans could play in that respect.

Lessons for the form:

1. Organise a dialogue not only between groups of stakeholders and interested parties, but also amongst themselves.
2. Actively seek ways of reaching and informing less accessible groups and engaging them in the dialogue.
3. A dialogue is not a platform for exchanging fixed views.
4. Involve and instruct appropriate experts and people with practical experience.
5. Think carefully about the themes, the material, the terminology and the subject matter that will be discussed during the sessions.