COMParative ASSessment of Genome and Epigenome Editing in Medicine: Ethical, Legal and Social Implications 2.0 (COMPASS-ELSI 2.0)

• Applicants: Professor Dr. Ralf Müller-Terpitz; Professorin Eva Winkler, Ph.D.
• Subject Area: Practical Philosophy ; Public Law
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409799774

• Final Report Year: 2023

Final Report Abstract

A peculiarity of epigenome editing (EE) is that it does not introduce a modification of DNA 'bases' (the 'letters' of the 'genetic code'), but it changes the configuration of DNA and can impact the expression of genes. This might have similar effects as genome editing (GE), where genes, or at least parts of genes, are ‘rewritten.’ The project COMPASS-ELSI studied how GE and EE differ in ethically and legally relevant respects and how use of both technologies should be regulated. The project had an ethical and a legal subproject (ESP, LSP). GE on the somatic and germline level and EE on the somatic level are promising approaches for the development of future therapies. Whereas in some areas their fields of application might overlap, in other areas certain diseases might be targeted with one approach rather than the other. However, both interventional systems still suffer from significant problems of specificity and effectiveness, and risks of unintended effects. The LSP comprehensively assessed EE compared to GE in view of German and European law. The ESP focused on jumpstarting an ethical debate on EE, and on identifying gaps in the broad ethical debate on GE to contribute something to this field of research as well. Our legal analysis revealed that for somatic gene therapies on born humans there are no significant regulatory differences between GE and EE. In both scenarios, the existing regulatory framework, especially the obligation to obtain informed consent, grants sufficient protection. Hence, the patient/research subject, or, in case of children, a legal representative, must consent to the editing procedure based on information about remaining risks, once the technologies are ready for clinical use. The legal analysis of germline applications revealed that under current German law, GE of embryos is prohibited, whereas EE at the germline level is not, although its application might face similar risks. Even though EE does not appear to be technically feasible for germline interventions now, this regulatory gap should be closed. In the ESP, we developed criteria for risk assessment of EE and GE, analyzed inheritability, naturalness, impact on future generations in comparison of EE and GE, and evaluated an important type of argument in the ethical debate on germline GE, based on the so-called "Non-Identity Problem" (NIP). A result of the ethical analysis is that risks of different gene technologies can differ, but severity not always depends on whether EE or GE are employed. A further result is that, whereas EE and some GE approaches differ regarding their impact on future generations, they are to be evaluated similarly not only regarding risks for edited individuals, but also in their presumed (un-)naturalness. With respect to germline GE, the ESP asked: Are existing individuals edited or new human beings created? If the latter is true, a person’s existence might depend on GE, and the NIP would apply. It is then very challenging to argue that 'edited' embryos are harmed. In sum, COMPASS-ELSI has achieved ist main goal: it introduced EE into the ethical as well as the legal debate. That being said, there remains much work to be done to broaden these debates.

Publications

• A philosophical analysis of future generations’ impact on the value of healthcare: the case of genome and epigenome modifying therapy. (International conference for young scholars (BMBF): Defining the value of medical interventions. Normative and empirical challenges, Sept. 18, 2019, Nuremberg/Fürth)
  Alex K & Winkler EC
  
• Panel discussion following the film “Human Nature: Die CRISPR Revolution” (Nov. 11, 2019, Heidelberg, Gloria)
  Alex K., Fischer L., Müller-Terpitz W. & Wittbrodt J.
  
• Panel discussion: “Ethische und rechtliche Fragen der Forscher und Kliniker zum Genom-Editing bei Menschen,“ Tieren und Pflanzen (9. Seminar Medizin auf dem Österberg: Ärztliche Entscheidungen in Grenzsituationen – Nutzen und Risiken der Gentechnik. Nahrungsmittel, Medikamente, Menschen, Oct. 19, 2019, Tübingen)
  Dingermann T, Dederer G, Fehse F, Flügge UI & Winkler EC
  
• Panel discussion: “Wie werden wir in 10 Jahren über Genom-Editierung denken?“ (Genom-Editierung – (fast) natürlich? Dialogkonferenz: Die Genschere im gesellschaftlichen Diskurs, Nov. 19, 2019, Federal Ministry of Education and Research (BMBF), Berlin. Further information)
  Winkler E.C., Wiesemann C., Schleissing S. & Wildermuth V.
  
• Verantwortbarkeit der (Ein-Generation)Keimbahntherapie? (Interdisciplinary Symposium of the German Federal Ministry of Education and Research (BMBF), Oct. 30, 2019, Berlin)
  Schleidgen S., Müller-Terpitz R., Cantz T. & Ott M.
  
• Die gentechnologische Intervention in die genetische Ausstattung des Menschen – Eine ethische und rechtliche Kontextualisierung und Bewertung der Genom- und Epigenomeditierung (doctoral colloquium of the Department of Law, University of Mannheim, May 5, 2020)
  Güneş A.
  
• Ethische Fragen der Epigenom-Editierung: Kein Designerbaby, aber eine neu zu 'designende' ethische Debatte (Jahrestagung der Akademie für Ethik in der Medizin 2020, Sept. 25, 2020, online)
  Alex K & Winkler EC
  
• 13. Ethischer Diskurs zu Epigenetik und Genomeditierung: die Gefahr eines (epi-)genetischen Determinismus und naturwissenschaftlich strittiger Grundannahmen. Fünfter Gentechnologiebericht, 299–323.
  Alex, Karla & Winkler, Eva C.
  
• Ethical aspects of genome and epigenome editing (Workshop organized by the project group on Epigenome Editing in medicine – preferable to Genome Editing?, April 4, 2021, online)
  Alex K.
  
• Ethical conceptualization of a sustainable right to health(care). In: Schildmann J et al. (eds.), Defining the value of medical interventions: Normative and empirical challenges. Stuttgart, Kohlhammer, 28–48
  Alex K.
  
• Ethische Konzeptualisierung eines nachhaltigen Rechts auf Gesundheit und Gesundheitsversorgung (Jahrestagung der Akademie für Ethik in der Medizin 2021, Sept. 24, 2021, online)
  Alex K.
  
• Genet(h)ik – ohne „Strangbruch kein Dammbruch“? Eine vergleichende Bewertung der Genom- und Epigenom-Editierung aus naturwissenschaftlicher, ethischer und juristischer Sicht (Jahrestagung der Akademie für Ethik in der Medizin 2021, Sept. 24, 2021, online)
  Güneş A, Alex K, Müller-Terpitz R & Winkler EC
  
• Genforschung und Gentherapie im Zeitalter der Genom- und Epigenom-Editierung. Wissenschaftsrecht, 54(2), 225-253.
  Müller-Terpitz, Ralf
  
• Is Dupras and Bunnik’s Framework for Assessing Privacy Risks in Multi-Omic Research and Databases Still Too Exceptionalist?. The American Journal of Bioethics, 21(12), 80-82.
  Alex, Karla & Winkler, Eva C.
  
• Normative Methodik der Medizin- und Forschungsethik (Mini-presentation during a meeting of the Junge Medizinethik [JMED] of the German Academy of Ethics in Medicine, March 08, 2021, online)
  Alex K.
  
• Normative Methodik der Medizin- und Forschungsethik (Mini-presentation during a meeting of the Junge Medizinethik [JMED] of the German Academy of Ethics in Medicine, March 8, 2021, online)
  Alex K.
  
• Regulatory aspects of genome and epigenome editing (Workshop organized by the project group on Epigenome Editing in medicine – preferable to Genome Editing?, April 4, 2021, online)
  Güneş A.
  
• Vorschlag eines Modells zur ethischen Analyse von Epigenome Editing im Vergleich mit Genome Editing: Kernfragen und erste Antworten (Leopoldina-Symposium Geschichte, Theorie und Ethik der Humangenetik, Oct. 7, 2021, Universität Düsseldorf)
  Alex K & Winkler EC
  
• Aktuelle Entwicklungen im Recht der Reproduktionsmedizin (Arbeitsgruppe Ethische Fragen am Lebensanfang, AEM, March 10, 2022, online)
  Müller-Terpitz R.
  
• Ausgewählte ethische Herausforderungen des Einsatzes der Genomeditierung am Menschen – mit einem Seitenblick auf das Recht der Reproduktionsmedizin (talk at Regionale Lehrerfortbildung Gymnasium Baden-Württemberg, Biologie “CRISPR-Cas – ein neues Zeitalter der gezielten Genomveränderung,“ May 23, 2022, Heidelberg)
  Alex K.
  
• Das Sterben überzähliger Embryonen – Überlegungen zu aktuellen Entwicklungen aus Sicht der Philosophie (Transmortale XI: Neue Forschungen zum Thema Tod, March 26, 2022, online)
  Alex K.
  
• Does epigenome editing deserve similar consideration as genome editing within bioethics? (GAP.11: Philosophie & Öffentlichkeit, Sept. 13, 2022, Humboldt-Universität Berlin)
  Alex K & Winkler EC
  
• Does epigenome editing deserve similar ethical consideration as genome editing? (Society for Applied Philosophy Annual Conference 2022, July 2, 2022, Edinburgh (UK)
  Alex K & Winkler EC
  
• Fortpflanzungsmedizinrecht – quo vadis? Verfassungsrechtliche Anmerkung zu aktuellen Reformdiskussionen (Tagung der deutschsprachigen Medizinrechtlerinnen und Medizinrechtler 2022: Medizinrecht zwischen Unter- und Überregulierung, May 13, 2022, online)
  Müller-Terpitz R.
  
• Fortpflanzungsmedizinrecht – quo vadis?. Medizinrecht, 40(10), 794-801.
  Müller-Terpitz, Ralf
  
• Gibt es einen therapeutischen Imperativ zum genome editing in der menschlichen Keimbahn?. Human reproduction. Seismo Verlag AG.
  Alex, Karla & Rehmann-Sutter, Christoph
  
• Nicht-Identität und die Unsicherheit, wie Keimbahneingriffe ethisch und rechtlich zu bewerten sind oder Was kann aus dem nicht-personenbezogenen Verständnis der Keimbahn- Genom-Editierung für den ethisch-rechtlichen Diskurs abgeleitet werden und was nicht (Arbeitsgruppe Ethische Fragen am Lebensanfang, AEM, March 10, 2022, online)
  Alex K.
  
• Non-human primates, human embryos and genome editing research – A case study defining tasks for risk-benefit assessment in international animal research ethics. (Interdisciplinary European research retreat for young scholars (BMBF): Animal research ethics as interaction of research ethics, animal ethics and [animal protection] law. International perspectives on theoretical and cultural differences, Sept. 8, 2022, Hannover)
  Alex K.
  
• The Mutual Benefit of the Integration of Philosophy and Bioethics – Our Experience from an Interdisciplinary Research Project on (Epi-)Genome Editing. The American Journal of Bioethics, 22(12), 61-63.
  Alex, Karla Karoline Sonne Kalinka & Winkler, Eva C.
  
• Vergleichende ethische Bewertung von Genom- und Epigenomeditierung als experimentelle reproduktionsmedizinische Technologien: Natürlichkeit, Personenbezogenheit, Vererbbarkeit (Research retreat for early career researchers (BMBF): In-vitro-Gametogenese (IVG) und artifizieller Uterus (AU) – Problemauslöser oder Problemlöser? – Ethische, soziale und rechtliche Aspekte zukünftiger reproduktionsmedizinischer Verfahren, Sept. 22, 2022, Regensburg
  Alex K & Winkler EC
  
• Did He Jiankui harm Lulu and Nana and do stem cell researchers violate human dignity – bioethical debates (Lecture as part of Core Competencies Week 2022 for M.Sc. Molecular Biosciences, Jan, 12, 2023, Universität Heidelberg, Heidelberg)
  Winkler E.C., Alex K. & Herrmann M.
  
• Epigenetik – Die Sprache der Gene. Mit neuem Wissen gegen Erkrankung und Trauma? (Panel discussion Berlin, Nov. 18, 2021, Futurium)
  Mansuy I, Walter J & Winkler EC
  
• Ethical conceptualization of a sustainable right to health(care). (Understanding Value IX: Sheffield Postgraduate Philosophy Conference, Dec. 9, 2020
  Alex K.
  
• Ethical Discourse on Epigenetics and Genome Editing: The Risk of (Epi!)Genetic Determinism and Scientifically Controversial Basic Assumptions. The Impact of Health Care, 77-100. Evangelische Verlagsanstalt.
  Alex, Karla & Winkler, Eva C.
  
• Ethisches Argumentieren im Biologieunterricht? Beispiel: Chancen und Risiken der Genomeditierung in der menschlichen Keimbahn (Regionale Lehrerfortbildung Gymnasium Baden-Württemberg, Biologie “CRISPR-Cas (II) – Schwerpunkt Bewertungskompetenz am Beispiel der Genomeditierung der Keimbahn;“ March 1, 2023, and July 5, 2023, Heidelberg) – contribution to the conception of this course
  Alex K.
  
• Evaluating Human Epigenome Editing: Methods for Risk Assessment and Methodological Challenges for Bioethics (35th European Conference on Philosophy of Medicine & Health Care: Methods in Bioethics and Philosophy of Medicine, Aug. 2023, Riga (Latvia))
  Alex K & Winkler EC
  
• Interdisciplinary uncertainties: Comparative ethical analysis of genome and epigenome editing (Futures Ahead – Translations and collaborations between medicine, social science and the humanities, Conference at the Centre for Medical Humanities and Bioethics, Linköping University, June 6, 2022, Linköping (Sweden)Interdisciplinary uncertainties: Comparative ethical analysis of genome and epigenome editing (Futures Ahead – Translations and collaborations between medicine, social science and the humanities, Conference at the Centre for Medical Humanities and Bioethics, Linköping University, June 6, 2022, Linköping (Sweden)
  Alex K & Winkler EC