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[GeN] Special Issue of GID: Just do it?

This is an article of the special issue on germline editing of GID, the magazine of coalition member Gen-ethisches Netzwerk (Germany).
By Dr. Daniel Papillon, biologist and spokesperson of the International Coalition to Stop Designer Babies

 

Current landscape of the international debates on human genome editing

The invention of CRISPR-Cas has sparked a debate around fundamental questions that should remain separated from the issue of efficiency of the technology. While proponents dream of improving our species, others call for a ban on all research.

Human genetic modification (HGM) is the deliberate manipulation of the DNA of human embryos, with the intention of leading to pregnancy.1  Since the changes affect all the cells of the body, including the future eggs and sperm, the genetic changes are heritable, that is, they are passed on to the next generations. There is a strong international consensus against HGM, backed notably by international treaties such as the European Convention on Human Rights and Biomedicine and the Universal Declaration on the Human Genome and Human Rights, but also by national policies. In fact, of 96 countries that do have relevant policy documents, 70 prohibit the use of genetically modified in vitro embryos to initiate a pregnancy. More interestingly, no country specifically allows HGM.2  Despite this overwhelming social consensus, civil society and human rights organisations, as well as many scientists, are worried about potential future implementation of HGM. Since the advent of CRISPR, a genetic modification technique deemed more powerful, safe, and precise than previous ones, the biotech and assisted reproduction technologies (ARTs) industries, associated with specific parts of the scientific community, are pushing for legalisation of HGM.

From theoretical discussions to practice

The emergence of CRISPR as a genome editing tool in 2012 stimulated an international debate: suddenly gene editing embryos for use in artificial reproduction stopped being science fiction and became a real possibility. Some organisations, ethics societies and concerned scientists reaffirmed that HGM should not be pursued3,4  or that, at the very least, a moratorium should be put in place.5,6  In 2015, the National Academies of Sciences from the USA, the UK, and China organised the first International Summit on Human Genome Editing (ISHGE). Hundreds of scientists from around the world gathered to discuss scientific, ethical, legal, social, and governance issues around human genetic editing. The summit’s report acknowledged that due to technical safety reasons it would be irresponsible to proceed immediately with clinical use of HGM and deemed a “broad societal consensus” necessary to move forward with HGM. However, the proposal of a moratorium with the possibility of a ban put forward by some participants was overruled.7  In 2017, a report by the US National Academy of Sciences concluded that while it was presently unsafe to create a human with a CRISPR-modified genome, it might one day be justified for compelling reasons.8  This report was endorsed by the European Academies Science Advisory Council.9

In 2018, a second ISHGE was held in Hong Kong. While the summit was unfolding, a participating scientist, He Jiankui, revealed that he had used CRISPR to modify the genome of at least three embryos that lead to pregnancies – for medical reasons, he claimed. Interestingly to “He’s ears, it was the [First 2015 ISHGE] report’s fundamental conclusion that mattered. Despite many notes of caution, that report’s message was clear […]: gene-edited children were ultimately permissible if the goal was to treat or prevent serious illnesses.”10  The tepid and ambiguous conclusions of the first ISHGE had served as a justification for He’s experiment on humans. After a few years of debate on the controversial possibilities of HGM using CRISPR, He had brought the issue to a head by implementing its first application. Initially, the science community reacted with an uproar, inside and outside the summit. It was later revealed, however, that He was not a ‘rogue’ scientist but had been in contact with many of the leading CRISPR scientists in the US and China – none of whom raised alarm when He told them of his plans.

It is not surprising, therefore, that the organising committee of the second ISHGE issued a concluding statement that was even more permissive than the previous one: HGM was here to stay, it would be accepted in the future, so a ‘translational pathway to germline editing [HGM]’ should be designed from research to actual clinical use.11  The statement simply mentioned in passing an “attention to societal effects” thus underscoring the shift from the previous demand of a “broad societal consensus” to the much narrower call for a “broad scientific consensus”. The social and scientific conversations about HGM should thus be separated: scientists would keep working while society catches up to their decisions. Of course, not all stakeholders in the debate agreed – in the following I will describe the main positions on HGM that consolidated in the years after these early summits.

Position 1: Let’s just do it

The first position is one that clearly embraces HGM. Proponents of this position, exemplified by the Nuffield Council On Bioethics in the UK, would not only argue that there is no ethical nor political case against HGM, but that there are “moral reasons to continue with the present lines of research and to secure the conditions under which heritable genome editing interventions would be permissible”.12  This was echoed by another report from the US-American National Academies of Sciences, that clearly set out this ‘translational pathway’ to start implementing HGM in clinical context, i.e., on real people.13  Both reports went beyond its use for therapeutic needs to consider genetic enhancements.14

The scientific enthusiasm for human enhancements shouldn’t come as a surprise. Since the birth of modern biology, scientists have entertained a vision of science finally reigning over the messiness and unpredictability of nature. This is iterated by, Francis Galton, the 19th century British polymath who invented eugenics – “What nature does blindly, slowly, and ruthlessly, man may do providently, quickly, and kindly. As it lies within his power, so it becomes his duty to work in that direction”.15  This view found a more recent formulation by Jennifer Doudna, the Nobel Prize winning scientist for her contribution in the development of CRISPR: “Indeed, we are already supplanting the deaf, dumb, and blind system that has shaped genetic material on our planet for eons and replacing it with a conscious, intentional system of human-directed evolution.”16 On a more militaristic example, British researcher Robin Lovell Badge affirmed: “You could also contemplate altering humans so they could see in the infrared or the ultraviolet range, as some animals can do. Such enhancements would be ideal for troops fighting at night or in other hostile conditions.”17  As Lovell Badge is a key player in the debate as the chair of ISHGE summits and part of British regulatory bodies, this gruesome outlook on the use of HGM on cannot be dismissed as a fringe position.

These proponents find moral support in the work of philosophers like Savulescu and Singer, for whom an ethically justifiable translational pathway to HGM should look like this: “catastrophic single gene disorders (like Tay–Sachs disease), then severe single gene disorders (like Huntington’s disease), then reduction in the genetic contribution to common diseases (like diabetes and cardiovascular disease), then enhanced immunity and perhaps even delaying ageing … Further into the future, gene editing could be used for enhancement of the genetic contribution to general intelligence.”18

Position 2: Let’s do it, but safety first

An intermediate position is embodied by the World Health Organisation (WHO), which adopted an ambiguous stance recognizing that it is still “irresponsible at this time to proceed” with HGM and advised refraining from approving clinical trial application. But it did not call for a moratorium.19,20 A similar ambiguity emerged from the third ISHGE in 2023. Critics like the US-based NGO Alliance for Humane Biotechnology noted an interesting recasting of terminology. What previously was termed ‘Human germline genetic editing’ was split into ‘Heritable human genetic editing’ (HHGE) and ‘Non-heritable human genetic editing’. In other words, there was human genetic engineering ‘for reproduction’ and ‘not for reproduction’. This allowed the germline research and manipulation (such as in vitro gametogenesis and its possibilities) to be recast as “non-heritable”, and therefore, presumably, less ethically controversial and easily bracketed out of the social conversation.21

Planning for the third ISHGE started out with an ostensible effort to be more inclusive and some critics did get the chance to lay out arguments against HGM. But some voices, i.e. from the disability rights movement, were still missing. Despite such exclusions, the criticism of civil society organisations and some scientists was reflected in the concluding statement: “Heritable human genome editing remains unacceptable at this time. Public discussions and policy debates continue and are important for resolving whether this technology should be used”22 (emphasis added). This position was the result of intense efforts to change the framing of the debate from one that tended mostly to be about how to implement HGM, to go back to actually considering whether we wanted it to be implemented at all.

Indeed, focusing narrowly on safety reduces the permissibility of HGM to technical and scientific criteria.23  From such a truncated framing, technologies simply need to be developed further and, presuming that safety will be reached, the ethical and political issues of HGM will therefore fall away. Addressing the question at the root of the issue, however, should not be influenced by the efficiency of a technology: does HGM constitute an ethical and moral human ‘red line’? Do we actually want to go ahead with it? How will the implementation of HGM unfold in our highly unequal societies blighted by racism, sexism, and ableism?

Position 3: We shouldn’t do it

These questions are at the heart of the third position on HGM. It is illustrated by the 2019 call for a moratorium on HGM written by some concerned scientists24 , which was subsequently backed by numerous organisations.25,26,27,28,29  Additionally, public interest advocates, policy experts, bioethicists, and scientists issued the Geneva statement to demand a “course correction” on HGM.30  Several Civil society organisations also backed the idea of a moratorium or even a ban on HGM31,21, as well as some scientists.32  In 2023, various national civil society organisations and initiatives formed the International Coalition to Stop Designer Babies. Right at the start of the third ISHGE, this coalition, which included 44 organisations and over 1600 signatories from around the globe, published the International Declaration Against Legalisation of Human Genetic Modification, calling for an international ban on HGM.33  The Missing Voices Initiative from the US-based organisation Center for Genetics and Society shares a similar position. It aims to amplify “social justice and human rights voices and perspectives in debates about heritable genome editing”.34  There are also some more academic initiatives, which are not necessarily displaying a clear position on the matter, like the Global Observatory for Genome Editing that “seeks to expand the range of questions arising at the frontiers of emerging biotechnologies and explore and encourage alternatives”, a somehow mysterious endeavour.35  The observatory called for a “Democratic Governance of Human Germline Genome Editing” in 2019, with unclear results.36  Other projects like the Global Citizens’ Assembly on Genome Editing, spearheaded by scientists from the University of Canberra in Australia, try to develop methods to reach the “broad societal consensus” the first summit proposed as needed for HGM. Related to this initiative, citizen assemblies and juries were organised in Australia, France, the USA and the UK to discuss issues around HGM, with the aim of organising an eventual world-wide Global Citizen Assembly.37  As the outcomes of these formats are very sensitive to what arguments are presented and whose voices are heard, the result of this process remains to be seen. The outcome of the UK version were used by the media to justify the implementation of HGM.38

Conclusion

Other articles in this issue are making the case against HGM. But from my very summarised picture of the ISHGE process and the various positions regarding HGM in the scientific community and civil society, we can conclude that despite the framing of HGM as only a matter of technical safety in the mainstream debate, much is left in the open. The global legal landscape of the rejection of HGM is often ignored while crucial issues of equity and human rights are not given the importance they deserve.

  1. This also concerns the direct genetic modification human gametes, the eggs (ovules) and sperm (spermatozoa), as well as the development of “in vitro gametogenesis”, the artificial production of human gametes from somatic (i.e., body) cells. HGM could also be implemented directly at this gamete stage, before fertilization. The term “modification” is preferred to “editing” as the latter, drawing from the “copy and paste” function of text editing software, has been used to convey a dangerous and false idea of perfect accuracy and safety.
  2. Baylis, F. et al (2020): “Human Germline and Heritable Genome Editing: The Global Policy Landscape.” In: The CRISPR Journal, 5 pp.365–77.
  3. Council of Europe (2015): Statement on Genome Editing Technologies – Human Rights and Biomedicine. Online: www.kurzelinks.de/HHGE-01.
  4. International Bioethics Committee, UNESCO (2015): Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights. Online: www.kurzelinks.de/HHGE-02.
  5. Lanphier, E. (2015): Don’t Edit the Human Germ Line. In: Nature, 519, 7544, pp.410-411.
  6. Deutsche Akademie der Naturforscher Leopoldina, and Union der Deutschen Akademien der Wissenschaften (2015): The opportunities and limits of genome editing. Online: www.kurzelinks.de/HHGE-03.
  7. National Academies of Sciences, Engineering, and Medicine (2016): International Summit on Human Gene Editing: A Global Discussion.” National Academies Press.
  8. NASEM, National Academy of Medicine, National Academies of Sciences, Engineering, and Medicine (2017): Human Genome Editing: Science, Ethics, and Governance. National Academies Press.
  9. EASAC (2017): Genome Editing: Scientific Opportunities, Public Interests and Policy Options in the European Union. Online: www.easac.eu.
  10. Regalado, A (2018): Rogue Chinese CRISPR Scientist Cited US Report as His Green Light. In: MIT Technology Review. Online: https://kurzelinks.de/HHGE-05.
  11. Second International Summit on Human Genome Editing (2019): Continuing the Global Discussion: Proceedings of a Workshop in Brief. National Academies Press.
  12. Nuffield Council On Bioethics (2019): Genome Editing and Human Reproduction: Social and Ethical Issues. In: Jahrbuch für Wissenschaft und Ethik.
  13. National Academy of Medicine, National Academy of Sciences, The Royal Society, and International Commission on the Clinical Use of Human Germline Genome Editing (2020): Heritable Human Genome Editing. National Academies Press.
  14. The dichotomy between medical needs and enhancements is itself controversial. Its main function in the recent years has been to legitimate the use of biotechnologies and ARTs for medical reasons (arguing that as long as it was not for enhancement it was ethically ok), without ever defining clearly these two categories, nor questioning who had the legitimacy to formulate these definitions.
  15. Galton, F. (1904): Eugenics: Its Definition, Scope, and Aims. In: American Journal of Sociology 10, 1, pp.1-25.
  16. Doudna, J.A., Sternberg, S.H. (2017): A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. Houghton Mifflin Harcourt.
  17. McKie, R. (05.02.2023): How Far Should We Go with Gene Editing in Pursuit of the ‘Perfect’ Human? In: The Observer. Online: www.kurzelinks.de/HHGE-06.
  18. Savulescu, J./Singer, P. (2019): An Ethical Pathway for Gene Editing.In: Bioethics 33, 2 pp.221-222.
  19. World Health Organisation (2019): Statement on Governance and Oversight of Human Genome Editing. Online: www.kurzelinks.de/HHGE-07.
  20. World Health Organisation (2021): Human Genome Editing: Recommendations. Online: www.kurzelinks.de/HHGE-08.
  21. Alliance for Humane Biotechnology (2022): White Paper: Opposing Human Genetic Engineering. Online: www.humanebiotech.org/white-paper.
  22. Third International Summit on Human Genome Editing (2023): Expanding Capabilities, Participation, and Access: Proceedings of a Workshop—in Brief. National Academies Press. Online: www.ncbi.nlm.nih.gov/books/NBK593530.
  23. Almeida, M., Ranisch, R. (2022): Beyond Safety: Mapping the Ethical Debate on Heritable Genome Editing Interventions. In: Humanities and Social Sciences Communications, 9, 1, pp.1-14.
  24. Lander, E.S. et al. (2019): Adopt a Moratorium on Heritable Genome Editing. In: Nature, 567, 7747, pp.165-68.
  25. American Society of Gene & Cell Therapy (2019): Scientific Leaders Call For Global Moratorium on Germline Gene Editing. Online: www.kurzelinks.de/HHGE-09.
  26. The European Society of Human Genetics (27.03.2019): Response to ‘Adopt a Moratorium on Heritable Gene Editing. Online: www.kurzelinks.de/HHGE-10.
  27. European Society of Human Reproduction and Embryology (22.03.2019): Gene Editing in Human Embryos. Moratorium on Gene Editing in Human Embryos. Online: www.kurzelinks.de/HHGE-11.
  28. International Rare Diseases Research Consortium (17.03.2019): IRDiRC Supports the Call for a Moratorium on Hereditary Genome Editing. Online: www.kurzelinks.de/HHGE-12.
  29. Wolinetz, C.D, Collins, F.S. and National Institute for Health (2019): NIH Supports Call for Moratorium on Clinical Uses of Germline Gene Editing. In: Nature, 567, 7747, p.175.
  30. Andorno, R. et al. (2020): Geneva Statement on Heritable Human Genome Editing: The Need for Course Correction. In: Trends in Biotechnology, 38, 4, pp.351-354.
  31. e.g., Gen-ethisches Netzwerk e.V. 2019. Precise Technology? Report on Genome Editing and Medicine. Online: www.kurzelinks.de/HHGE-13.
  32. Botkin, J.R. (2020): The Case for Banning Heritable Genome Editing. In: Genetics in Medicine 22, 3, pp.487-489.
  33. International Coalition to Stop Designer Babies, Online: www.coalitionstopdesignerbabies.net
  34. Gender Justice and Disability Rights Coalition, Online: www.kurzelinks.de/gender-justice.
  35. Global Observatory for Genome Editing. Online: www.global-observatory.org.
  36. Jasanoff, S, Hurlbut, B., Saha, K. (2019): Democratic Governance of Human Germline Genome Editing. In: The CRISPR Journal, 2, 5, pp.266-271.
  37. Dryzek, J.S. et al. (2020): Global citizen deliberation on genome editing. In: Science, 369, pp.1435-1437.
  38. McKie, R. (04.03.2023): UK Government Urged to Consider Changing Law to Allow Gene Editing of Embryos. In: The Guardian. Online: www.kurzelinks.de/HHGE-14.