Lilian Srour S3127389 [621227]

Human Genome Modification from a Human Rights Perspective Can the Right to Health accommodate novel technologies, such as CRISPR-Cas9? Name: Lilian Srour Student: [anonimizat]: s3127389 Supervisor: Brigit Toebes Word Count: 16,959 Date: 15 June 2020

Lilian Srour S3127389
2 ABBREVIATIONS 3 INTRODUCTION 4 CHAPTER 1 GENETIC TECHNOLOGIES, GENOME MODIFICATION AND HUMAN RIGHTS 9 1. SETTING THE LANDSCAPE 9 2. THE CRISPR REVOLUTION 10 2.1. BUT HOW DOES IT WORK? 10 2.1.1. Somatic v Germline Editing 11 3. CRISPR’S POTENTIAL APPLICATIONS AND CHALLENGES 11 3.1. PROSPECTIVE USES IN MEDICINE 11 3.2. KEY ISSUES 13 3.2.1. The Search for Consensus 13 3.2.2. Is the Law Able to Keep Up? 14 4. THE APPEAL TO HUMAN RIGHTS 16 CHAPTER 2 LEGAL FRAMEWORK SURROUNDING HUMAN GENOME MODIFICATION 18 1. INTERNATIONAL LEVEL 18 1.1. UNESCO DECLARATION ON THE HUMAN GENOME AND HUMAN RIGHTS (1997) 19 1.2. UNESCO DECLARATION ON BIOETHICS AND HUMAN RIGHTS (2005) 20 1.3. INTERNATIONAL HUMAN RIGHTS STANDARDS 22 1.4. CIVIL SOCIETY EFFORTS 23 1. REGIONAL LEVEL 24 1.1. THE CONVENTION FOR THE PROTECTION OF HUMAN RIGHTS AND DIGNITY OF THE HUMAN BEING WITH REGARD TO THE APPLICATION OF BIOLOGY AND MEDICINE: CONVENTION ON HUMAN RIGHTS AND BIOMEDICINE (1999) 24 2. NATIONAL LEVEL 27 2.1. A BIRD’S EYE VIEW OF EUROPE 27 2.1.1. Permissive 28 2.1.2. Somewhere In-between 28 2.1.3. Prohibitionist 29 2.2. ZOOMING OUT: THE UNITED STATES 29 3. FRAGMENTED RESPONSES 30 CHAPTER 3 A NEW BOX FOR CRISPR? 32 1. THE RIGHT TO HEALTH 32 2. THE AAAQ 34 3. THE RIGHT TO HEALTH, THE AAAQ AND CRISPR 36 3.1. AVAILABILITY 37 3.2. ACCESSIBILITY 41 3.3. ACCEPTABILITY 43 3.4. QUALITY 45 CONCLUDING REMARKS 48 BIBLIOGRAPHY 49

Lilian Srour S3127389
3 Abbreviations AAAQ Availability, accessibility, acceptability, quality CESCR Committee on Economic, Social, Cultural Rights CoE Council of Europe CRISPR CRISPR-Cas9 HFEA Human Fertilisation and Embryology Authority ICCPR International Covenant on Civil and Political Rights ICESCR International Covenant on Economic, Social, Cultural Rights Oviedo Convention The Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine UDBHR Universal Declaration on Bioethics and Human Rights UDHGHR Universal Declaration on the Human Genome and Human Rights UDHR Universal Declaration on Human Rights UNESCO United Nations Educational, Scientific, and Cultural Organisation

Lilian Srour S3127389
4 Introduction Genetic engineering and genome modification have recurrently been making the headlines. Whilst several genome modification techniques and tools are well-established in research, it is the development of more advanced tools, such as CRISPR-Cas9 (CRISPR), which have generated wide-spread enthusiasm and pushed genome modification into the spotlight.1 The progress witnessed in the life sciences domain in recent years is remarkable. CRISPR, particularly, has generated wide-spread excitement due to its potential for applications in biotechnology and medicine, among others.2 Scientists, scholars and science fiction writers have long predicted that advanced genetic and medical technologies could alter the genetic build of humans as a means of alleviating human suffering and improving the quality of life.3 Notably, contemporary biotechnological advancements represent the more general characteristics of the current intersection of medicine, state of the art science, technology and law whereby the use of life engineering technologies is being discussed by scientists, philosophers, sociologists, lawyers and politicians alike.4 As with most new technologies, there are differing views with respect to potential applications. There are various fields within which the use of CRISPR could be beneficial, as for instance; utilizing CRISPR to eliminate diseases such as malaria through the modification of the mosquito vector to transmit disease,5 for the improvement of crops in agriculture,6 and more relatedly in human health and medicine.7 In the context of human health, CRISPR operates as both; a tool for discovery and as a solution to fundamental issues related to disease and undesirable mutations.8 CRISPR’s novelty lies in its increased efficiency, specificity, ease of use and accessibility for researchers, when compared to its counterparts, i.e. previous technologies such as zinc-finger nucleases .9 Whilst definitions of genetic modification slightly differ, essentially genetic editing refers to deliberately making changes to a living being’s genetic information that would not occur by 1 PHG Foundation, 'Somatic genome editing: an overview' (2020) <https://www.phgfoundation.org/briefing/somatic-genome-editing-overview> accessed 5 May 2020. 2 These shall be further discussed in Chapter 1. 3 Stephen P. Marks, 'Tying Prometheus Down: The International Law of Human Genetic Manipulation' [2002] 3(1) Chicago Journal of International Law 115, 135. 4 Eva Šlesingerová, 'In Risk We Trust/Editing Embryos and Mirroring Future Risks and Uncertainties' [2019] 22(2) Medicine, Healthcare and Philosophy 191. 5 Deleting a single gene from mosquitoes can make them highly resistant to the malaria parasite and thus much less likely to transmit the parasite to humans; ScienceDaily, 'Gene knockout using new CRISPR tool makes mosquitoes highly resistant to malaria parasite' (8 March 2018), available at: <https://www.sciencedaily.com/releases/2018/03/180308143052.htm> accessed 15 June 2020; Gholamreza Farnoosh et al., 'CRISPR Genome Editing and its Medical Applications' [2018] 32(2) Biotechnology & Biotechnological Equipment 286, 288. 6 The CRISPR technology could potentially revolutionise plant breeding and result in overall crop improvement; Tian Wang et al., 'CRISPR technology is revolutionizing the improvement of tomato and other fruit crops' [2019] 6(77) Horticulture Research <https://www.nature.com/articles/s41438-019-0159-x> accessed 16 June 2020. 7 Friedrich Soltau, ‘CRISPR/Cas9 – gene editing technology takes off’, brief for GSDR (2016) available at: <https://sustainabledevelopment.un.org/content/documents/955511_Soltau_CRISPR-Cas9%20_%20gene-editing%20technology%20takes%20off.pdf> accessed 5 May 2020. 8 Soren H Hough et al, 'The Future of CRISPR Applications in the Lab, the Clinic and Society' in Stephan H Tsang, Precision Medicine, CRISPR and Genome Editing (Springer International Publishing, 2017) 158. 9 Heidi C. Howard et al., 'One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans' [2018] 26(1) European Journal of Human Genetics 1-11,1.

Lilian Srour S3127389
5 natural reproduction.10 Genes are the ‘recipes for the building blocks of life’ and the (human) genome comprises of all the genetic information of an individual.11 CRISPR allows for the modification of genomic DNA in plants, animals and humans with rather high efficiency and ease of use.12 Due to its simplicity, low cost and other appealing qualities, since 2012 CRISPR has become the genetic modification platform of choice for scientists globally.13 Notwithstanding the wide-spread excitement about CRISPR, not all prospective applications have been received with the same enthusiasm. To demonstrate, in 2018 the world was shocked by the news of the birth of the two first genetically modified humans.14 This experiment was largely condemned on numerous grounds, but particularly because at this point in time there is an observable lack of consensus surrounding germline applications utilising CRISPR.15 It remains unclear whether those are acceptable or not. The overall debate, and particularly civil society efforts have revealed that the current regulatory framework surrounding potential CRISPR applications is deficient in various regards.16 Primarily, there is an absence of concrete international guidance on this topical matter. Further, legislation addressing genome modification within national jurisdictions, when there is legislation in place, has been described as vague or inadequate.17 Additionally, the overall lack of consensus surrounding prospective applications of CRISPR, can also be observed through the contradictory reactions to the announcement in 2018. On the one hand, a group of prominent scientists issued global calls for a moratorium on germline applications of CRISPR. On the other hand, national and international bodies called for the development of adequate guidelines and regulations that encompass rigorous safety standards to address aspects of the social and ethical concerns which 10 Personal Genetics Education Project, ‘Genetic Modification, Genome Editing and CRISPR’, available at: <https://pged.org/genetic-modification-genome-editing-and-crispr/> accessed 5 May 2020. 11 Matthijs Gert and Borry Pascal, The Human Recipe: Understanding Your Genes in Today’s Society (Leuven University Press 2016) 9. 12 Stephan Guttinger, 'Trust in Science: CRISPR-Cas9 and the Ban on Human Germline Editing' [2018] 24(4) Science and Engineering Ethics 1077,1078. 13 Michael A. Stramiello, 'CRISPR: The New Frontier of Biotechnology Innovation' (American Bar Association, 2018) available at: <https://www.americanbar.org/groups/intellectual_property_law/publications/landslide/2017-18/january-february/crispr-new-frontier-biotechnology-innovation-digital-feature/#2> accessed 6 May 2020. 14 David Cyranoski and Heidi Ledford, 'Genome-edited baby claim provokes international outcry' (Nature, 28 November 2018) available at: <https://www.nature.com/articles/d41586-018-07545-0> accessed 12 June 2020. 15 For instance, the Chinese Academy of Sciences issued a statement condemning He’s work, Jennifer Doudna stated that the process he utilized was ‘inappropriate on so many levels’ and many in the scientific community faulted He for a lack of transparency and the manner in which he embarked on such a landmark, but risky project, see David Cyranoski, 'CRISPR-baby scientist fails to satisfy critics' (Nature, 28 November 2018) available at: <https://www.nature.com/articles/d41586-018-07573-w> accessed 6 May 2020; Dan Robitzski, ‘Scientists Around the World Condemn That CRISPR Baby Experiment’ (Futurism, 27 November 2018) available at: < https://futurism.com/neoscope/scientists-condemn-crispr-baby-experiment> accessed 6 May 2020; Sharon Begley, ‘Scientists Call for Do-Over for Rules on Creating ‘CRISPR Babies’’ (Scientific American, 12 August 2019) available at: <https://www.scientificamerican.com/article/scientists-call-for-do-over-for-rules-on-creating-crispr-babies/> accessed 16 June 2020. 16 Erin Quick, ‘Addressing International Legal Challenges of Genetic Engineering’ (The Regulatory Review, 2 April 2018) available at: <https://www.theregreview.org/2018/04/02/quick-international-dimensions-genetic-engineering/> accessed 15 June 2020; John Conley, ‘A Lawyer’s Guide to CRISPR Gene Editing’ (The Privacy Report, 28 March 2019) available at: < https://theprivacyreport.com/2019/03/28/a-lawyers-guide-to-crispr-gene-editing/> accessed 16 June 2020. 17 Angela Chen, ‘If someone wants to create gene edited babies, who would stop them?’ (The Verge, 26 November 2018), available at: < https://www.theverge.com/2018/11/26/18112970/crispr-china-babies-embryos-genetic-engineering-bioethics-policy> accessed 16 June 2020; See generally Max Planck Gesellschaft, ‘Discussion paper focusing on the scientific relevance of genome editing and on the ethical, legal and societal issues potentially involved’ (2019) Ethics Council of Max Planck Gesellschaft, <https://www.mpg.de/13811476/DP-Genome-Editing-EN-Web.pdf> accessed 15 June 2020, 17.

Lilian Srour S3127389
6 accompany germline interventions, rather than agreeing with the calls for a moratorium.18 Notably, amidst these efforts to approach the topical matter of human genome modification, there is a shortage of standards for promulgating sound guidelines.19 Human genome modification has tremendous benefits to offer and should not be overshadowed by the difficulties it raises. The future and the use of genetic technologies will be guided by how appropriately the international community and national governments are able to regulate the uses and applications of these technologies so as to ensure the maximization of benefits and minimization of complications.20 With respect to CRISPR, the very rapid uptake of the technology by laboratories world-wide, and its novel features, have added urgency to the need to discuss potential applications so as to ensure effective and responsible regulatory oversight.21 This paper aims to contribute to the conversation by viewing a novel biotechnology, e.g. CRISPR, from a human rights perspective. This particular lens provides the advantage of anchoring efforts to regulate human genome modification within a system of rights that corresponds to state obligations established under international law, whereby States Parties to treaties need to ensure respect for and enjoyment of the rights contained within.22 Notwithstanding the highly complex and novel concerns this type of biotechnology raises, this paper aims to consider the manner in which actual human lives, and human rights, will be impacted. Arguably, the use of CRISPR will have many implications for human health particularly in numerous ways, as for instance; in the context of clinical applications such as through gene therapy or through applications of CRISPR for reproductive purposes.23 Against this backdrop, the main question this paper seeks to answer is whether novel biotechnologies, such as CRISPR, can be accommodated under the international human right to health, as understood under article 12 of the International Covenant on Economic, Social and Cultural Rights (ICESCR).24 To this purpose, the author will rely mostly on an inductive approach. Namely, the initial premise is that CRISPR is a novel biotechnology that has not yet been addressed in a uniform way due to the lack of consensus. Concurrently, this paper will also be based on the premise that there is an existing legal framework (in particular AAAQ) under international human rights law which may be able to address novel biotechnologies, i.e. 18 For instance, several scientists published in nature calling for a moratorium whilst the Organising Committee of the Second International Summit on human genome editing called for an ongoing international forum to foster broad public dialogue; Eric Lander, Francois Baylis et.al., ‘Adopt a moratorium on heritable genome editing’ (Nature, 13 March 2019) < https://www.nature.com/articles/d41586-019-00726-5 > accessed 15 June 2020; ‘Statement by the Organising Committee of the Second International Summit on Human Genome Editing’ (The National Academies of Sciences, Engineering, Medicine, 28 November 2018) < https://www.nationalacademies.org/news/2018/11/statement-by-the-organizing-committee-of-the-second-international-summit-on-human-genome-editing> accessed 15 June 2020. 19 Kevin Doxzen and Jodi Halpern, 'Focusing on Human Rights: a framework for CRISPR germline genome editing ethics and regulation' [2020] 63(1) Perspectives in Biology and Medicine 44-53, . 20 John P. Ryan and Benjamin Hron, ‘The Evolution of Human Rights in the Age of Biotechnology’ [1999] 63(5) Social Education 303, available at: <http://www.socialstudies.org/sites/default/files/publications/se/6305/630505.html> accessed 15 June 2020. 21 Soltau (n7), 1. 22 WHO, ‘A Human Rights-Based Approach To Health’, available at: <https://www.who.int/hhr/news/hrba_to_health2.pdf> accessed 16 June 2020 23 For instance, editing sperm to find new ways to prevent disorders caused by genetic mutations that are passed down from men or to treat forms of female infertility; Rob Stein, ‘Scientists Attempt Controversial Experiment to Edit DNA in Human Sperm Using CRISPR’ (npr, 22 August 2019) available at: <https://www.npr.org/sections/health-shots/2019/08/22/746321083/scientists-attempt-controversial-experiment-to-edit-dna-in-human-sperm-using-cri> accessed 15 June 2020. 24 International Covenant on Economic, Social and Cultural Rights (adopted 16 December 1966, entered into force 3 January 1976) 993 UNTS 3 (ICESCR), article 12.

Lilian Srour S3127389
7 CRISPR. In this endeavour, both soft law and legally binding instruments, namely UNESCO’s Declaration on the Human Genome and Human Rights,25 the Universal Declaration on Bioethics and Human Rights26 and the Oviedo Convention27 will be examined. A limited examination of national jurisdictions will follow in order to identify the main approaches pursued in relation to the implementation of legislation concerning human genome modification. Additionally, article 12 ICESCR and General Comment No. 1428 will represent a central focus in the analysis to determine whether individuals and their right to health would be adequately protected under the existent legal framework. The ‘AAAQ’ framework, developed by the UN Committee on Economic, Social and Cultural Rights (CESCR) entails important principles for the operationalisation and realisation of the right to health.29 This particular human rights indicator is useful for analysing whether clinical applications utilising CRISPR, be they somatic or germline, can be accommodated by the right to health. The AAAQ framework translates international human rights obligations into standards, indicators and benchmarks.30 Moreover, the right to health, and the AAAQ, aid in ensuring that duty bearers meet their obligations and empower rights-holders to claim their rights.31 Mindfully, progress in the field of genetics has been claimed as necessary for a healthier population and for the cure of fatal diseases.32 Furthermore, it has been stated that gene therapy shall become a ‘staple of 21st century medicine’.33 The author is of the view that the right to health is a particularly useful point for discussion as it carries many significant implications for human genome modification, especially in view of the obligations of states who decide to introduce its clinical application. 34 The lack of consensus and the myriad of concerns which accompany potential applications of CRISPR are reminiscent of those which surround contentious issues such as abortion, euthanasia or in vitro fertilisation (IVF), all matters which have been regulated and addressed in varying degrees and forms.35 From this viewpoint, the distinctive features of the right to health may aid in the 25 UNESCO, Universal Declaration on the Human Genome and Human Rights (adopted 11 November 1997) (UDHGHR). 26 UNESCO, Universal Declaration on Bioethics and Human Rights (adopted 19 October 2005, published 2006) SHS/EST/BIO/06/1 (UDBHR). 27 Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (1999) ETS 164 (Oviedo Convention). 28 UN CESCR, General Comment No.14: The Right to the Highest Attainable Standard of Health (11 August 2000) E/C.12/2000/4 (General Comment 14). 29 The availability, accessibility, acceptability and quality (AAAQ) framework is an authoritative human rights framework, mentioned in General Comments 14 and 22 of the CESCR; General Comment 14 (n28); UN CESCR, General comment No. 22 (2016) on the right to sexual and reproductive health (2 May 2016) E/C.12/GC/22 (General Comment 22). 30 Danish Institute For Human Rights, ‘The Availability, Accessibility, Acceptability, Quality (AAAQ) Toolbox’, available at: <http://humanrightseducation.dk/HRBA_Training_Package/HRBA_in_practice/AAAQ%20Toolbox%20concept%20note%20brief.pdf> accessed 16 June 2020. 31 WHO (n22). 32 Elvira Dominguez, 'The Right to Health' (Icelandic Human Rights Center) available at: <http://www.humanrights.is/en/human-rights-education-project/human-rights-concepts-ideas-and-fora/substantive-human-rights/the-right-to-health> accessed 16 June 2020. 33 Jack McCain, 'The Future of Gene Therapy' [2005] 2(3) Biotechnology Healthcare 52. 34 Rumiana Yotova ,‘The Regulation of Genome Editing and Human Reproduction Under International Law, EU Law and Comparative Law’ (Nuffield Council on Bioethics, June 2017) < https://nuffieldbioethics.org/wp-content/uploads/Report-regulation-GEHR-for-web.pdf> accessed 10 June 2020, 18. 35 For instance, IVF and abortion are matters that have been a controversial topic from the outset, with several countries still prohibiting such practices, whilst others have adopted legislation regulating the matter. Euthanasia, similarly, is a contentious matter whereby only several jurisdictions allow for such practices under

Lilian Srour S3127389
8 guidance of regulating novel biotechnologies, e.g. CRISPR, and may also aid in circumventing a deadlock in the decision-making process regarding the regulation of human genome modification.
different terms. E.g. Netherlands allows for euthanasia under a strict set of conditions; see generally Guardian Staff, ‘Euthanasia and assisted suicide laws around the world’ (The Guardian, 17 July 2014) available at: < https://www.theguardian.com/society/2014/jul/17/euthanasia-assisted-suicide-laws-world> accessed 1 May 2020; ‘IVF regulation: ensuring safe and ethical treatment’ (Human Fertilisation and Embryology Authority, 20 December 2018) available at: < https://www.hfea.gov.uk/about-us/news-and-press-releases/2018-news-and-press-releases/ivf-regulation-ensuring-safe-and-ethical-treatment/> accessed 3 May 2020.

Lilian Srour S3127389
9 Chapter 1 Genetic Technologies, Genome Modification and Human Rights 1. Setting the Landscape Since the advent of recombinant DNA technology in the early 1970’s, many multidisciplinary approaches were pursued, ranging from applications in medicine and agriculture, to the environment.36 Such technologies, for the making and manipulating of DNA, have presented themselves as ground-breaking tools from the outset. The last century has witnessed the discovery of the DNA double helix,37 the completion of the Human Genome Project,38 and the increased use of genetic testing, among others.39 Such scientific innovation has fostered a world-wide interest in genetics and directed increasing efforts towards learning more about the genetic build of human beings, as well as the underlying reasons for disease and disability.40 These developments have facilitated technological innovation and allowed for the refinement of genetic technologies and techniques. Therefore, continuing the development of genetic technologies offers the possibility of precision medicine, for instance, which carries the potential of altering healthcare significantly.41 The tools utilised to modify genomes have improved tremendously over the years. Previously, researchers relied on homologous recombination, an approach that has been said to provide a low frequency of correct targeting events in many organisms.42 In an attempt to devise more specific techniques, zinc-finger nucleases (ZFNs) were developed. These did offer improved site-specific gene replacement, however the complexity of their assembly and variable efficacy in vivo somewhat discouraged their wide-spread adoption by the scientific community. In the decade which followed, transcription activator-like effector endonucleases (TALENs) were developed.43 However, ZFNs and TALENs require complete engineering of the enzymes for programming whilst with CRISPR it is sufficient to merely reprogram Cas9 to target the 36 Emannuelle Tuerlings, ‘Background Paper Governance Human Genome Editing’ (WHO, 2019), available at: < http://origin.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Governance-1-paper-March-19.pdf> accessed 25 May 2020, 5. 37 The Francis Crick Papers, 'The Discovery of the Double Helix, 1951-1953' US National Library of Medicine; available at <https://profiles.nlm.nih.gov/spotlight/sc/feature/doublehelix> last accessed 16 June 2020. 38 ‘2003: Human Genome Project Completed’ (National Human Genome Research Institute, last updated 25 November 2014), available at:< https://www.genome.gov/25520492/online-education-kit-2003-human-genome-project-completed> accessed 16 June 2020. 39 See generally, Kathryn A. Phillips et al., ‘Genetic Test Availability and Spending: Where Are We Now? Where Are We Going?’ [2018] 37(5) Health Affairs 710 <https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2017.1427?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=hlthaff> accessed 10 June 2020; Jayshree Pandya, ‘The Rise of Genetic Testing Companies and DNA Data Race’ (Forbes, 1 April 2019) available at: < https://www.forbes.com/sites/cognitiveworld/2019/04/01/the-rise-of-genetic-testing-companies-and-dna-data-race/#7d0a28e32afb> accessed 12 April 2020. 40 Shawna Benston, ‘CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability’ [2016] 5(1) Laws <https://www.mdpi.com/2075-471X/5/1/5> accessed 1 May 2020; Teresa B. Burke, ‘Gene Therapy: A Threat to the Deaf Community?’ (Impact Ethics, 2 March 2017) available at: < https://impactethics.ca/2017/03/02/gene-therapy-a-threat-to-the-deaf-community/> accessed 15 June 2020. 41 See generally Gustavo Rosa Gameiro et al., ‘Precision Medicine: Changing the way we think about healthcare’ [2018] 73 Clinics < https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251254/> accessed 12 May 2020. 42 Minjung Song et al., Genome Engineering in Human Cells Chapter 5 in Jennifer Doudna et al., (eds) The Use of CRISPR/Cas9, ZFNs, and TALENs in Generating Site-Specific Genome Alterations (Elsevier/Academic Press, 2014) 94. 43 Stephane Pelletier, Genome Editing with Targetable Nucleases, in Kursad Turksen (ed), Genome Editing (Springer International Publishing 2016) 2.

Lilian Srour S3127389
10 desired sequence. In other words, CRISPR’s simplicity, high efficacy and multiplexing capability have propelled it to the forefront of genome modification.44 2. The CRISPR Revolution Genomes comprise of the genetic information that controls the development and physiological functions of all living organisms on our planet, and therefore form a central interest in all facets of biomedical research.45 To further understand the ‘blueprint of life’, scientists have long aspired to read and modify the genome using a promptly growing toolbox.46 To be able to read the genome, state of the art technologies have enabled the sequencing of any single genome in a quick and cheap manner. In spite of everything, methods for the introduction of targeted modifications in the genome, whilst feasible, have long remained inefficient. That was until the adaptation of the bacterial CRISPR system, which has changed the situation dramatically.47 CRISPR is increasingly becoming available to a large number of scientists, who intend to use it for a multitude of reasons across different research domains. When such powerful and potentially disruptive technologies begin to demonstrate a tendency to become utilized on a wide-spread scale, naturally discourse and debate ensues.48 Observably, discussing the possibilities of using CRISPR in a safe and effective manner, whether for somatic or germline applications, is necessary in light of the speed at which the technology is developing and the intensity with which the enthusiasm for realizing the applications is growing. 2.1. But How Does It Work? The CRISPR-Cas9 system is a molecular tool that enables scientists to edit DNA in living organisms with accuracy.49 This system has two fundamental components, namely; a strand of guide RNA and a CRISPR associated nuclease.50 This system is part of a naturally-occurring adaptive immune system in bacteria and archaea.51 CRISPR stands for ‘clustered regularly interspaced palindromic repeats’ and refers to particular sequence motives first discovered in 1987, whereas Cas stands for ‘CRISPR-associated’.52 Together these form a ‘search and snip’ complex, whereby CRISPR acts as a guide for the Cas proteins to target specific parts of the genome. In lay terms, CRISPR effectively resembles a pair of micro scissors that cuts DNA in a precise manner.53 Overall, what has been said to be enticing about the CRISPR-Cas system is the ease with which it can be adapted as a molecular tool in a laboratory setting. When using the Cas9 protein as 44 Ibid. 45 Renjie Jiao et al., ‘The CRISPR/Cas9 Genome Editing Revolution’ [2016] 34(5) Journal of Genetics and Genomics 227-228. 46 Ibid. 47 Ibid. 48 Genetic Home Reference, ‘What are genome editing and CRISPR-Cas9?’ US National Library of Medicine, available at <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839051/> accessed 17 June 2020. 49 Wageningen University and Research, ‘CRISPR-Cas – accurate DNA modification’ available at: < https://www.wur.nl/nl/Dossiers/dossier/CRISPR-Cas-accurate-DNA-modification.htm> accessed 15 June 2020. 50 Stramiello (n13). 51 The two components are a strand of guide RNA (gRNA) and a CRISPR associated endonuclease, e.g. Cas9; Stramiello (n13). 52 Guttinger (n12), 1080. 53 Stramiello (n13).

Lilian Srour S3127389
11 the nuclease of choice, the CRISPR system enables researches to create organisms with an altered genome.54 2.1.1. Somatic v Germline Editing Briefly, when it comes to applications of this technique it is important to differentiate the target populations of cells on which genetic engineering can be performed, which are as follows; somatic cells, pluripotent stem cells and germ cells. In somatic cell applications, genetic modifications are intended for the patients solely and would usually not be transmitted to descendants. Gene editing in the germline, however, results in changes in the individual’s hereditary genetic profile, thus enabling them to transmit such changes to future generations.55 3. CRISPR’s Potential Applications and Challenges Having laid out the scientific landscape, the following sections will address various beneficial applications of CRISPR in relation to human health, as well as some of the challenges and concerns future applications raise. Genome modification sheds a new light on old issues, whereby progress in genetic technologies brings profound challenges and begs the question of whether new regulatory requirements are necessary to protect individuals.56 It has been acknowledged that even though many concerns within the human health sector are similar to those in the ethical literature on human genetic and genome modification, scientific innovations are nevertheless raising significant conceptual queries.57 Therefore, seeing that genome modification methods are currently being pursued in basic research, in several commercial applications and in some industrial efforts, it is important to discuss distinctive features that trigger social concerns over the use of such technologies, and more particularly in the context of human genome modification. This is even more so considering that an effective regulatory framework with an emphasis on human rights should encompass and address features which trigger societal concern over human genome modification.58 3.1. Prospective Uses in Medicine The impacts of scientific advancement are highly visible in the health and related fields, where those have motivated changes in individual and community healthcare. This progress has enabled healthcare to be more predictive, has increased treatment options, and led to the expansion of healthcare programs.59 It goes without saying that genetic advances play a significant role in the scientific developments that affect healthcare. Furthermore, statements have been made claiming that we have reached a stage where we can combine knowledge on the genome with gene therapy technologies, to translate this ‘young academic science into therapeutics’.60 Minding that CRISPR operates as both, a tool for discovery and as a solution 54 Guttinger (n12), 1080. 55 Guido De wert et al., 'Responsible Innovation in Human Germline Gene Editing: Background Document to the Recommendations of ESHG and ESHRE' [2018] 26(4) European Journal of Human Genetics 450-470, 451. 56 Tuerlings (n36), 4. 57 Ibid. 58 Doxzen and Halpern (n19), 45. 59 Shawn H. E. Harmon, 'The Significance of UNESCO’s Universal Declaration on the Human Genome & Human Rights' [2005] 2(1) SCRIPTed 20, 21. 60 Bermingham Nessan et al., 'Realizing the potential of CRISPR' (McKinsey & Company, January 2017) <https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/realizing-the-potential-of-crispr> accessed 5 May 2020.

Lilian Srour S3127389
12 to major issue related to disease, the subsequent paragraphs will outline some prospective uses in medicine. Such applications arguably lie amongst the most significant implications for the right to health and human health in general, and as such merit discussion. In the research domain, CRISPR increases knowledge on human gene functions through the use of human cells, tissues and embryos. This technique also allows for the further understanding of DNA-repair mechanisms and elaborates on the links between genes and diseases.61 It allows researchers to better understand disease and to clarify molecular mechanisms that can be employed to improve therapeutic applications.62 Consequently, an active area of research entails the genetic manipulation of patient-derived stem cells for the creation of models of various diseases such as colon cancer, brain-malformations, cystic fibrosis and numerous more.63 Notably, CRISPR is already being utilized to identify targets in oncology through obtaining a cancer cell and screening every gene in the genome to determine whether it is involved in the cell’s ability to divide continuously.64 In the realm of clinical applications, CRISPR has the potential to affect numerous therapeutic domains and illnesses. Genome modification or editing is viewed as forming part of the gene therapy toolkit by physicians and scientists alike.65 Gene therapy entails the manipulation of DNA or RNA for human disease treatment or prevention.66 Gene therapy strategies are diverse, ranging from rectifying replacing or deleting the culprit genes in genetic diseases to producing disabling mutations in pathogen genomes to combat infectious diseases.67 This form of therapy is promising for a wide range of human illnesses including cancer, AIDS, diabetes, heart failure and neurodegenerative diseases.68 Thus far, there have been over 2000 gene therapy clinical trials world-wide, with some gene therapy products already having been approved by governments, such as Cerepro for malignant brain tumours in Europe.69 It has often been said that for the near future, CRISPR is most likely to be developed and approved for treating monogenic diseases, and for blood-based disorders like beta thalassemia.70 At the current state, the standard treatment for beta thalassemia is regular blood transfusions, and the only cure is a bone-marrow transplant from a donor, which often carries the risk of morbidity and mortality. CRISPR stands to offer a safer and more effective treatment, whereby the clinician takes stem cells from the patient, edits them so as to correct the defect, and then re-administers them to the patient.71 It should be noted that CRISPR is already beginning to translate into the clinic. In 2019, CRISPR Therapeutics and Vertex Pharmaceuticals achieved a landmark by beginning the first dosing of a patient with a CRISPR 61 Ibid. 62 Hongyi Li et al., ‘Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects’ [2020] 5 Signal Transduction and Targeted Therapy 1, <https://www.nature.com/articles/s41392-019-0089-y#citeas> accessed 12 June 2020. 63 Masayuki Fujii et al., ‘Modeling Human Digestive Diseases with CRISPR-Cas9-Modified Organoids’ [2019] Gastroenterology 562 < https://www.gastrojournal.org/article/S0016-5085(18)35296-X/pdf> accessed 15 June 2020. 64 Nessan et al. (n60). 65 See generally; Krishnarao Appasani, Genome Editing and Engineering: From TALENs, ZFNs and CRISPRs to Molecular Surgery (CUP, 2018). 66 Lu Xiao-Jie et al., ‘CRISPR-Cas9: a new and promising player in gene therapy’ [2015] 52(5) Journal of Medical Genetics 289-296, 289. 67 Ibid. 68 Ibid. 69 Ibid. 70 Nessan et al. (n60) 71 Ibid.

Lilian Srour S3127389
13 therapeutic in a Phase I/II trial.72 CTX001, the therapeutic, is being utilized to treat patients with thalassemia. This same trial intended to extend to include patients with sickle-cell anaemia.73 Overall, CRISPR represents a powerful tool for researchers to better understand the relations between genes and disease, and thus stands to revolutionise future treatments for such. Moreover, many see promising applications in diagnostics, therapeutics, genetic research and drug development. In relation to therapeutics, somatic genome editing could be offered to patients whose cancer has failed to respond to conventional treatments, as for instance chemotherapy.74 Furthermore, some germline genome applications of CRISPR could potentially cure genetic disorders, such as thalassemia, in human embryos, or introduce natural resistance to HIV, among others.75 Having noted that CRISPR is already beginning to translate from bench to bedside and discussed some prospective beneficial applications in relation to health, the next section will move to address key related issues in relation to human genome modification. 3.2. Key Issues The dawn of genome modification has challenged, and continues to challenge, scientific communities, ethicists, policy makers and the public to ponder the appropriateness of existing oversight and regulatory as well as ethical frameworks which govern genome modification. Naturally, this has provoked wide-ranging debates about societal, ethical and legal implications of genetic engineering and genome modification technologies. Still further, a concern which accompanies all debates is that the science appears to be progressing faster than public understanding and policy-making.76 3.2.1. The Search for Consensus Prior to the announcement of He Jiankui’s experiment in 2018, genome modification was already the topic of many meetings, workshops and position statements by groups ranging from national funding organizations, to supranational political entities.77 Although many differ in their focus, essentially all reports call for sufficient public engagement in order to establish the trajectory of research and the eventual applications of CRISPR. Nevertheless, it remains difficult to identify how any public consensus should be measured, let alone achieved.78 72 CRISPR Therapeutics, ‘CRISPR Therapeutics and Vertex Announce Progress in Clinical Development Programs for the Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001’ (Press Release, 25 February 2019) available at: < http://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-and-vertex-announce-progress-clinical> accessed 16 June 2020. 73 MaryAnn Labant, ‘CRISPR Jump-Starts Gene Therapy’ (Genetic Engineering & Biotechnology News, 1 April 2019) available at: <https://www.genengnews.com/insights/crispr-jump-starts-gene-therapy/> accessed 17 June 2020. 74 The National Academies of Sciences, Engineering, Medicine, ‘Human Genome Editing: Science, Ethics and Governance’ (2017), available at:<https://www.nationalacademies.org/our-work/human-gene-editing-scientific-medical-and-ethical-considerations> accessed 25 May 2020, 5. 75 Tuerlings (n36), 7. 76 Ibid, 3. 77 See, WHO, ‘Information Resources on Human Genome Editing, available at: < https://www.who.int/ethics/topics/human-genome-editing/resources/en/> accessed 1 May 2020. 78 Michael Morrison and Stevienna de Saille, ‘CRISPR in context: towards a socially responsible debate on embryo editing’ [2019] 5 Palgrave Communications 110, < https://www.nature.com/articles/s41599-019-0319-5> accessed 16 June 2020, 5.

Lilian Srour S3127389
14 To demonstrate, it is recognisable through the discussions surrounding CRISPR that engineering heritable changes in humans brushes on something regarded as central to human existence. Contrastingly, non-heritable genome modification applications appear to generate a rather passive response from the medical and scientific communities and the public.79 For instance, FDA approved clinical trials which aim to edit the CCR5 gene in individuals to treat HIV infection were deemed an important medical advance forward. However, scientists utilising CRISPR on embryos also targeting the CCR5 gene, aiming to prevent HIV infection, are described as taking a step ‘backwards’.80 This already highlights the tension remaining concerning potential germline applications utilising CRISPR. Nevertheless, this is not to say that somatic applications of CRISPR have been accepted without opposition.81 For instance, there are concerns regarding the use of CRISPR to treat deafness, as the deaf communities have seen this as a cultural threat, a disruptive reframing of deafness and as a detriment rather than an advantage.82 Despite increased efforts at public engagement, the concerns accompanying CRISPR are complex, with many not extensively addressed. However, this search for consensus calls for public debate whilst science continues to push the moral boundaries already in place, testing the parameters to determine where pressure may be applied.83 It should be noted that it is highly unlikely that further research and applications of CRISPR should fail to proceed if consensus is lacking. This is reminiscent of assisted reproduction, which has expanded into a cross border industry where parents frequently go to obtain reproductive services that are prohibited in their own country.84 In this pursuit for the impossible, i.e. widespread consensus, the risk that some may take advantage of this unregulated domain may threaten individuals in various regards, but most relatedly with respect to their right to health. 3.2.2. Is the Law Able to Keep Up? The discovery of CRISPR represents one of the most thrilling breakthroughs in biomedical science. Considering its novelty, many commentaries discussing the consequences of human genome modification have emphasised concerns related to, among others, ‘designer babies’.85 However, this may have diverted attention from discussing other pressing issues associated with CRISPR in the context of clinical applications. 86 It should be acknowledged that with respect to genome modification and the concerns it raises, experience has taught us that social 79 Doxzen and Halpern (n19), 45. 80 Ibid. 81 For instance, the risk of emerging discriminatory practices directed against persons with disabilities, that might arise in the context of the use of biotechnology, have been recently addressed by the Special Rapporteur on Persons with Disabilities in one of her latest reports (17 December 2019) UN Doc A/HRC/43/41, para 22, available at: <https://undocs.org/en/A/HRC/43/41?fbclid=IwAR3cmsfm_sOe0TsKCb0N2VJb44Ze3LGPiz3BXtha2A6m7wIAYaM5RO8Wdpg> accessed 10 June 2020. 82 Doxzen and Halpern (n19), 45. 83 Morrison and Saille (n78), 4. 84 Ibid, 5. 85 See generally, Miller Kathleen and Kohm Lynne Marie, 'Designer Babies: Are Test Tubes and Microbes Replacing Romance? Relevant Legal Issues and DNA' [1996] 17(4) The American Journal of Forensic Medicine and Pathology 305-307; Nishith Desi Associates, ‘Are we ready for Designer Babies?’ (2019) Nishith Desai Associates, available at: <http://www.nishithdesai.com/fileadmin/user_upload/pdfs/Research_Papers/Designer_Babies.pdf> accessed 15 June 2020. 86 Dianne Nicol et al., ‘Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic’ [2017] 9 Genome Medicine 85, available at: <https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-017-0475-4> accessed 12 June 2020.

Lilian Srour S3127389
15 and ethical concerns which accompany the application of new technologies are ‘rarely new or unique to that technology’.87 Nevertheless, observably, policy makers are struggling to keep up with the CRISPR revolution, as often happens with disruptive technological breakthroughs.88 An observable trend running through the regulatory recommendations addressing human genome modification suggests that the delineation between treatment and enhancement is a core social concern.89 Surveys have demonstrated that the public is at unease with using human genome modification to enhance an individual, compared to when addressing a medical need.90 This distinction between treatment and enhancement has, been utilized as a ‘permissibility pillar’ when attempting to formulate guidance and legislation on human genome modification. This, however, cannot be utilized to promulgate an effective regulatory framework because the line between treatment and enhancement is ‘blurry at best’.91 Primarily, what is viewed as a treatment or enhancement can be context dependent, considering that some treatment in one culture may be viewed as an enhancement in another. Notably, several reports addressing genetic modification have described the use of human genome modification to treat disease as a therapeutic measure, even though such preventive measures could result in human enhancement itself. Therefore, targeted treatments could potentially result in enhancement, as the concept of disease changes.92 On another note, somatic editing applications are addressed throughout numerous national frameworks. However, these have recently come into question, considering CRISPR’s novelty. For instance, national frameworks addressing gene therapies are often broadly formulated, focusing on the intended purpose rather than the technology used.93 Some have contended that it is not necessary to revise their legislation, however critics have begged to disagree, as demonstrated by the PHG Foundation.94 There is a lack of clarity as to how the technology may develop and therefore they have argued that there is a need to ensure that existing laws and guidelines are sufficient for the purposes of genome modification applications.95 In comparison to traditional gene therapy, this uses different mechanisms, suggesting that different approaches to safety assessment may be required, among others. Moreover, it has been noted that revisions may be necessary for clinical trials protocols, to limit the potential for health tourism.96 This is reminiscent of issues related to reproductive technologies that are prohibited in certain countries, whereby prospective parents travel to jurisdictions where such procedures are allowed.97 In light of the aforementioned, in has been suggested that the case of genome modification could be a learning opportunity as the policies and institutional capacities adopted for the use 87 Tuerlings (n36), 4. 88 Andrea Boggio et al., ‘The Human Right to Science and the Regulation of Human Germline Engineering’ [2019] 2(3) The CRISPR Journal 134, 134. 89 Doxzen and Halpern (n19), 46. 90 Among others, Christine Critchley et al., ‘Predicting Public Attitudes Toward Gene Editing of Germlines: The Impact of Moral and Hereditary Concern in Human and Animal Applications’ (Frontiers in genetics ESL in genetics, 9 January 2019) available at: < https://www.frontiersin.org/articles/10.3389/fgene.2018.00704/full> accessed 18 May 2020. 91 Doxzen and Halpern (n19), 46. 92 Ibid. 93 For instance, in the UK regulations addressing gene therapies are drafted broadly; PHG Foundation (n1). 94 Ibid. 95 Ibid. 96 Ibid. 97 Morrison and Saille (n78), 4.

Lilian Srour S3127389
16 of genome editing could potentially serve as a model for policies in other areas of advanced therapies and emerging technologies for health.98 4. The Appeal to Human Rights Scientific advancements are expanding the scope of human activity. This impact can be observed in the health and related fields, where such advances have contributed to a change in individual and community healthcare.99 Scientific innovation represents the potential to alleviate suffering and increase the quality of life. Its intimate interaction with health raises concerns about the pace of advances, the shortage of applicable legal standards, and the social consequences related to the application of biotechnology within existent healthcare systems.100 Moreover, whilst genetic modification has long been the subject of attention, the advent of novel genome editing techniques such as CRISPR have provoked renewed interest in this area. The comparative efficiency and precision of this technique greatly increases its value for research as well as the potential for its applications. Genome modification, combined with stem cell science, has the potential to offer a new generation gene therapies.101 However, a notable concern is that the increased attention directed to genome editing techniques and their potential applications in therapeutics is likely to enthuse surging demand from patient groups, particularly in the case of conditions for which there is currently no effective treatment, as was the case with stem cell therapies. This, in combination with CRISPR’s novel qualities, creates the real possibility that in the absence of adequate regulation and oversight, clinical treatments utilising CRISPR, whether somatic or germline, may be provided prior to sufficient determination of safety and efficacy. This is also likely to be most problematic in countries within which unlicensed therapies are highly prevalent102 Observably, ethics, and more particularly bioethics, have dominated much of the debate surrounding CRISPR and its potential applications. Whilst very related, and the relationship between bioethics and human rights is strong, the appeal towards human rights, in this regard, is stronger for various reasons. Primarily, the human rights foundation has been described as one that is composed of universally shared notions and cross-cultural perceptions of humanity that also recognizes moral pluralism.103 The human rights discourse has, also, been described as the ‘already accepted language of international ethics’, as such allowing for a framework that addresses universal social problems.104 The moral claims within the human rights framework are embedded in legally binding documents that have been widely ratified by states, which prove to be much more effective than bioethical appeals whose force is mainly derived from the coherency of arguments.105 Under the human rights framework, states parties to international treaties are under legally binding obligations to protect and secure the human rights of their peoples, offering political and legal dimensions that mere moral appeals significantly lack. Human rights treaties impose a series of positive and negative obligations, 98 Tuerlings (n36), 10. 99 Harmon (n59), 21. 100 Ibid. 101 See generally Karim Benabdellah, ‘Genome-edited adult stem cells: Next generation advanced medicinal products’ [2020] 9(6) Stem Cells Translational Medicine 674. 102 Sarah Chan and Maria Medina-Arellano, ‘Genome editing and international [2016] regulatory challenges: Lessons learned from Mexico’ [2016] 2(3) Ethics, Medicine and Public Health 426, 426. 103 Elizabeth Fenton, ‘Genetic enhancement – a threat to human rights’ [2008] 22(1) Bioethics 1, 2. 104 Ibid. 105 Elizabeth Fention and John D. Arras, ‘Bioethics and Human Rights: Curb Your Enthusiasm’ [2010] 19(1) Cambridge Quarterly of Healthcare Ethics 127, 128.

Lilian Srour S3127389
17 i.e. duties of action and obligations to refrain from interfering with the full realisation of human rights,106 that states have to adhere to. This is especially reflected through the respect, protect, fulfil (RPF) typology107 and more specifically in the context of the right to health, through the AAAQ framework, which will be discussed in more detail throughout Chapter 3. Nevertheless, a human rights-oriented lens offers the advantage of anchoring efforts to address human genome modification within a system of rights which corresponds to state obligations established under international law.108 Therefore, human rights standards and principles ought to be a focal point in the development of such technologies across all sectors and phases of the process.109 Having established that CRISPR represents a novel biotechnology with tremendous potential for various sectors, but most relatedly for its prospective to treat disease on an unprecedented scale, and that it is accompanied by many concerns, particularly related to the highest attainable standard of health, as for instance but not limited to, access to clinical applications of CRISPR, the next chapter will move to discuss the legal aspects of the matter at hand.
106 ICESCR (n24), article 2(1). 107 See generally, Inter-Parliamentary Union and the UN Office of High Commissioner for Human Rights, ‘Human Rights. Handbook for Parliamentarians No.26’ (2016) available at: <https://www.ohchr.org/Documents/Publications/HandbookParliamentarians.pdf> accessed 13 June 2020. 108 WHO (n22). 109 Ibid.

Lilian Srour S3127389
18 Chapter 2 Legal Framework Surrounding Human Genome Modification 1. International Level The previous chapter sought to lay out the general landscape, i.e. focusing mostly on social, ethical and scientific aspects, and touch on the numerous concerns which accompany human genome modification. In this regard, the current chapter aims to elaborate on the legal dimension of the subject under consideration by identifying relevant legal instruments at the international, regional and national levels. To date, there is no legally binding instrument of general application dedicated to human genome modification under international law. However, as Vogel described, the regulatory landscape surrounding genome editing is fragmented, varied and contingent.110 For long, human genome modification has predominantly been discussed under the umbrella of bioethics, using its concepts, terminology and discourse. Since the beginning of the 20th century, however, bioethics and human genome modification have increasingly become discussed within the broader international human rights framework and within the even wider international law framework.111 There are several international documents,112 inspired by the goal to secure respect for human rights, which address human genome editing throughout various provisions which carry significant relevance for the matter at hand.113 Additionally, in the international sphere, there are several authoritative soft-law instruments which address human genome modification, notably; UNESCO’s Universal Declaration on the Human Genome and Human Rights (UDHGHR),114 and the Universal Declaration on Bioethics and Human Rights (UDBHR).115 Further, minding that the international human rights framework contains numerous relevant provisions within it, due to matters of space, a discussion will follow on only a handful of selected provisions. At the regional level, more particularly within the European legal sphere, there are several Regulations and Directives which address genome modification. The Oviedo Convention, for instance, enshrines state obligations to protect the dignity, identity and human rights of all with respect to applications of biology and medicine through drafting legislation.116 It should be mentioned that currently numerous countries are in the process of evaluating whether and to what extent current regulations accommodate such a novel technology in the context of research and applications.117 Many nations are experiencing difficulties in their assessment of whether genome modification is different from classical gene editing from both 110 Kathleen M. Vogel, 'Crispr goes global: A snapshot of rules, policies, and attitudes' (Bulletin of the Atomic Scientists, 5 June 2018) <https://thebulletin.org/2018/06/crispr-goes-global-a-snapshot-of-rules-policies-and-attitudes/> accessed 23 May 2020. 111 Cesare P. R. Romano et al., ‘The Governance of Human (Germline) Genome Modification at the International and Transnational Level, Chapter 2 in Andrea Boggio, Cesare P. R. Romano, Jessica Almqvist (eds), Human Germline Genome Modification and the Right to Science: A Comparative Study of National Laws and Policies (Cambridge University Press 2019) 22. 112 For instance, see generally Council for International Organizations of Medical Sciences (CIOMS), The Declaration of Inuyama on Genetic Testing and Screening, Gene Therapy (adopted 1990) available at: < https://www.who.int/genomics/elsi/regulatory_data/region/international/032/en/> accessed 15 June 2020. 113 Nuffield Council on Bioethics, ‘Genome Editing and Human Reproduction: Social and Ethical Issues’ (Nuffield Council on Bioethics 2018) 114, available at: <https://www.nuffieldbioethics.org/publications/genome-editing-and-human-reproduction> accessed 23 May 2020, 114. 114 UDHGHR (n25). 115 UDBHR (n26). 116 Oviedo Convention (n27), article 1. 117 Vogel (n110).

Lilian Srour S3127389
19 a research perspective, in the domain of applications and also when viewing it as a product.118 Bearing this in mind, several national jurisdictions will be touched upon towards the end of this Chapter. 1.1. UNESCO Declaration on the Human Genome and Human Rights (1997) UNESCO’s constitutional purposes entail, among others, to advance the objectives of international peace and common welfare of mankind and to contribute to peace and security by promoting educational, scientific and cultural collaboration among states to further universal respect for justice, the rule of law, and human rights.119 UNESCO has also been said to have the authority to negotiate and sponsor the codification and implementation of international instruments aiming to advance technology, public health and human rights.120 In response to significant scientific advancement and the age of genetics, Federico Mayor, former Director General of UNESCO, understood that scientific developments require the coordination of effective legal and ethical responses globally.121 In light of the concerns relating to genetic research and the changing nature of medicine, the need for an instrument that protects human rights in the sphere of genetics whilst promoting bioethics formed the basis for the creation of the UDHGHR. This document was unanimously adopted by the General Conference in 1997, and by the United Nations General Assembly in 1998.122 This Declaration has been said to form the basis of soft law in the governance of the human genome.123 It sets universal ethical standards on human genetic research and practices which balance the freedom of scientists to pursue their work alongside the need to safeguard human rights.124 The Preamble of the Declaration recalls the ideals of UNESCO, identifies the international instruments referred to125 and highlights the risks genetic advancements represent.126 The overarching aim of this instrument is to preserve the human genome from inappropriate modifications which may endanger the identity and physical integrity of future generations.127 The Declaration is comprised of 25 articles in 7 sections which aim to set universal bioethical standards that shall ensure genetic advances are not utilised in a manner contrary to human rights. Article 4 prohibits financial gain from the genome in its natural state,128 article 6 reiterates the anti-discrimination principle extending the prohibited grounds to genetic characteristics,129 article 7 addresses patient privacy rights and first-consent,130 article 8 refers 118 Vogel (n110). 119 UDHGHR (n25), preamble paras 6-7; Constitution of the United Nations Educational, Scientific and Cultural Organization (signed on 16 November 1945, entered into force 4 November 1946) (UNESCO Constitution) available at <http://portal.unesco.org/en/ev.php URL_ID=15244&URL_DO=DO_TOPIC&URL_SECTION=201.html > accessed 15 June 2020, article 1. 120 Harmon (n59), 27. 121 Ibid, 23-24. 122 UDHGHR (n25). 123 Cesare P. R. Romano et al. (n111), 33-34. 124 The American Association for the Advancement of Science (AAAS) and EurekAlert, ‘UNESCO Adopts Universal Declaration On The Human Genome And Human Rights’, available at: < https://www.eurekalert.org/pub_releases/1997-11/U-UAUD-111197.php> accessed 23 May 2020. 125 For example, the UDHR, ICESCR, ICCPR, Convention on the Elimination of All Forms of Racial Discrimination and the Convention on the Elimination of All Forms of Discrimination Against Women; UDHGHR (n26), preamble. 126 Harmon (n59), 35. 127 Cesare P. R. Romano (n111), 33-34. 128 UDHGHR (n25), article 4. 129 Ibid, article 6. 130 Ibid, article 7.

Lilian Srour S3127389
20 to repatriation for individual damage sustained as a result of genome interventions,131 article 9 encourages the adoption of universal thresholds,132 article 10 holds that human rights must take precedence over research,133 article 12 states that research benefits must be made available to all,134 and according to article 24135 the International Bioethics Committee (IBC) and the Intergovernmental Bioethics Committee (IGBC) are to issue recommendations and assist UNESCO in promoting and disseminating the principles set out within the Declaration.136 Whilst this declaration has somewhat been hailed as a success, there is a lot of criticism.137 For instance, the Declaration fails to provide guidance on internationally acceptable standards for acquiring consent and protecting confidentiality.138 Additionally, whilst consent is addressed, the provisions are not entirely relevant to situations with genetic implications. With respect to aspects of non-discrimination, the Declaration has been described as vague considering that much is left at the discretion of domestic law-makers when it comes to defining which acts infringe upon this right.139 There is a lack of guidance concerning what practices could be considered incompatible, and there is no insight as to what requirements must be met to determine equal treatment in the context of one’s genetic circumstances, whilst there are also no suggestions as to the consequences for states or entities which infringe upon non-discrimination rights. Furthermore, it has also been stated that amongst the Declaration’s weaknesses is the inadequacy with which it addresses questions related to the medical context of applications.140 Considering germline interventions specifically, this Convention has been said to suggest that such applications could be contrary to human dignity, however, the IBC has thus far not expressly decided the issue.141 1.2. UNESCO Declaration on Bioethics and Human Rights (2005) The field of bioethics has been growing considerably since the 1970s. Numerous scientific practices have extended beyond national borders, highlighting the need to set universal ethical guidelines addressing issues related to the field of bioethics, and the need to promote the emergence of wide-spread shared values.142 In 2003, at its 32nd session, the General Conference considered that it was desirable ‘to set universal standards in the field of bioethics with due regard for human dignity and human rights and freedoms, in the spirit of cultural pluralism inherent in bioethics’.143 In 2005, after nearly two years of deliberations and negotiations, the 131 Ibid, article 8. 132 Ibid, article 9. 133 Ibid, article 10. 134 Ibid, article 12. 135 Ibid article 24. 136 The IBC and IGBC are permanent committees established within UNESCO; UNESCO, Statutes of the International Bioethics Committee of UNESCO (IBC) (2005) SHS.2005/WS/4 REV, available at: < https://unesdoc.unesco.org/ark:/48223/pf0000138292> accessed 24 May 2020. 137 As stated by Harmon, the Declaration is more of an example of a ‘knee-jerk’ reaction, rather than an example of ‘lengthened foresight’; Harmon(n59), 45. 138 Ibid, 38. 139 Ibid, 40. 140 Ibid, 44. 141 Nuffield Council on Bioethics (n113), 115. 142 UNESCO, ‘Universal Declaration on Bioethics and Human Rights’, available at: < https://en.unesco.org/themes/ethics-science-and-technology/bioethics-and-human-rights> accessed 24 May 2020. 143 UNESCO, Records of the General Conference, 32nd session, Paris, 29 September to 17 October 2003, v. 1: Resolutions (2004) 32 C/Resolutions, available at: < https://unesdoc.unesco.org/ark:/48223/pf0000133171> accessed 24 May 2020, 47.

Lilian Srour S3127389
21 Universal Declaration on Bioethics and Human Rights (UDBHR) was adopted.144 Given its non-binding nature, the Declaration is to be incorporated into the national laws of the members of UNESCO in order to take effect.145 Prior to the adoption of this document international instruments which the UDBHR also refers to in its preamble, such as the Declaration of Helsinki,146 were already well-established in bioethics.147 The UDBHR addresses states primarily, but can also be implemented by individuals, groups, communities, institutions and corporations, where appropriate.148 It covers an extensive range of bioethical principles, some of which had already become customary bioethics; for instance, the principle of informed consent, which also features in previously adopted bioethical instruments.149 Articles 1-17 outline the principles in the Declaration. Article 9 protects the privacy and confidentiality of persons concerned,150 whilst article 11 embodies the principle of non-discrimination whereby no individual or group should be discriminated against or stigmatised on any grounds in violation of human dignity, human rights and fundamental freedoms.151 Article 14 addresses health in the context of promoting health and social development of citizens as a core purpose of governments.152 Article 15 states that benefits resulting from scientific research and its applications should be shared within the international community. This is to be achieved through, inter alia, ensuring access to quality healthcare.153 A recently conducted questionnaire, inquiring about the most pressing challenges related to science and technology which could be considered by the IBC in the coming years (2020-2023), revealed some concerns remaining with respect to the UDBHR.154 Respondents signalled the need for further elaboration on article 16 in light of the technical capabilities to modify the genetic makeup of embryos, and on the ambiguity relating to the protection of future generations to better reflect which interventions in genes are permissible and those which are not.155 In connection to this, it was also noted that climate change and the inequalities in access to healthcare and education are risks which also need to be addressed. Furthermore, in connection to equality, justice and equity, 156 the questionnaire revealed that in the Southern hemisphere the right to health and healthcare, is at risk due to high prevalence of inequality. In this vein, it was emphasised that equality, justice and equity represent important features of primary healthcare, in order to improve healthcare services that are accessible to all individuals and communities.157 144 UDBHR (n26). 145 Ibid, article 22. 146 World Medical Association, Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects (adopted June 1964) as amended by the WMA General Assembly in 2013 (Helsinki Declaration), available at: < https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/> accessed 26 May 2020. 147 UDBHR (n26), preamble. 148 Ibid, article 1(2). 149 Helsinki Declaration (n146), para 22. 150 UDBHR (n26), article 9. 151 Ibid, article 11. 152 Ibid, article 14. 153 Ibid, article 15(b). 154 UNESCO, ‘Summary of the Responses on Possible Work Topics for 2020-2023 of the International Bioethics Committee of UNESCO (IBC) and the World Commission on the Ethics of Scientific Knowledge and Technology of UNESCO (COMEST)’ (11 June 2019) SHS/BIO/IGBC-11/19/2 REV. 155 Ibid, para 9; UDBHR (n26), article 16. 156 UDBHR (n26), article 10. 157 UNESCO (n154), para 16.

Lilian Srour S3127389
22 1.3. International Human Rights Standards There is no internationally binding document particularly addressing human genome modification. Despite the lack of specific legislation, the use of such a biotechnology does not create a legal vacuum. There are several human rights provisions which could be adapted to tackle matters relating to certain aspects of CRISPR. For example, articles 25 and 27 in the Universal Declaration on Human Rights (UDHR).158 Notwithstanding the non-binding nature of the UDHR, these provisions have acquired legally binding force through their inclusion into the International Bill of Rights, comprised of the ICESCR and International Covenant on Civil and Political Rights (ICCPR).159 Therefore, article 12 ICESCR confirms individual rights to healthcare and represents the rights of access to healthcare advances, echoing article 25 UDHR.160 On the other hand, article 15 ICESCR, similarly to article 27 UDHR, provides that everyone has the right to share in scientific advancement, and benefit from resultant applications.161 The aforementioned rights are all logically applicable in the genetic context and the provisions could, for instance, be relied on to demand access to innovative treatments and to share in advances.162 Relatedly, concerning informed consent, article 17 ICCPR is of relevance considering it codifies the right to privacy, thus entailing the right to informed consent.163 Essentially, the human rights framework offers several rights which are invocable in the context of genetics, more relatedly applications of CRISPR, which could be utilized by states as reference points for formulating human rights-sensitive regulations.164 Furthermore, monitoring and enforcement mechanisms of the UN human rights bodies offer individuals the option of filing communications in case of human rights breaches. For instance, the Optional Protocol to the International Covenant on Civil and Politics Rights (ICCPR-OP) could be utilized by individuals to support the respect for first generation rights.165 Notably, in relation to ESC rights, the UN Commission on Human Rights has already invited states and NGOs to inform it of measures pursued to ensure the science develops in a direction that respects human rights.166 Despite the above, with respect to genome modification and clinical applications of CRISPR, the human rights framework does still contain gaps in protection, and leaves dominant health and human rights related concerns unaddressed. For instance, questions remain regarding how we can promote and realise the even distribution of benefits, what appropriate protection and disclosure mechanisms for genetic information should look like, which criteria should be utilized to identify whether genetic research is 158 Universal Declaration on Human Rights (adopted 10 December 1948) UNGA Res 217 A(III) (UDHR), articles 25 and 27. 159 International Covenant on Civil and Political Rights (adopted 16 December 1966, entered into force 23 March 1976) 999 UNTS 171 (ICCPR). 160 ICESCR (n24), article 12; UDHR (n158), article 25. 161 Article 15(b) ICESCR states that everyone has the right to enjoy the benefits of scientific progress and its applications, and article 27(1) UDHR guarantees everyone the right to freely participate in the cultural life of the community, to enjoy the arts and to share in scientific advancements and its benefits; ICESCR (n24), article 15; UDHR (n158), article 27. 162 Harmon (n59), 33. 163 ICCPR (n159), article 17. 164 Harmon (n59), 34. 165 UN Optional Protocol to the International Covenant on Civil and Political Rights (adopted 16 November 1966, entered into force 23 March 1976) 999 UNTS 171. 166 Report on the forty-ninth Session of the Commission on Human Rights (26 April 2001) E/CN.4/1993/122, 268.

Lilian Srour S3127389
23 permissible or guidance on how to combat the rise of science-based discrimination, among others.167 1.4. Civil Society Efforts The richness of other forms of regulation and soft governance, including the role of learned societies and institutions, significantly contributes to fostering public debate and democratic participation. The reach and implications of biomedical and genetic research have extended beyond national borders, thus the necessity to address corresponding ethical, social and legal challenges through international instruments has been acknowledged.168 However, opposing cultural and social sensitivities across nations have made the formulation and implementation of international or universal norms challenging. This lies amongst the main motivations of international organisations to develop frameworks relevant for the conduct of genetic research and interventions in the forms of declarations, guidelines and reports. Such frameworks, alongside civil society efforts overall, are highly relevant for countries that lack national or institutional instruments for regulatory oversight concerning genetic research and applications.169 Learned societies often have strong international links and often participate in frequent international exchanges of information which may aid in the formulation of international or global strategies.170 Several national learned societies and research institutes have made their position on human genome modification, and often on germline interventions, more public. For instance; the German Academy of Sciences171, the French medical research institute INSERM172, COGEM from the Netherlands173, and the Nuffield Council on Bioethics in the UK174 have issued reports addressing human genome modification. The views posited range from positions endorsing only research to aspirations to introduce such applications into the clinic. Furthermore, the US National Academies of Sciences and Medicine produced a consensus report in 2017 which demonstrated that arrangements for basic research and somatic genome interventions are broadly accepted in the US.175 These reports and those issued by other institutions have provided avenues for debate relevant for the development of social understandings and for the establishment of some form of consensus regarding what proficient and adequate oversight of human genome modification entails. Notably, a common trend running through numerous 167 Harmon (n59), 34-35. 168 Nuffield Council on Bioethics (n113), xviii. 169 UNESCO and IBC, ‘Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights’ (2 October 2015) SHS/YES/IBC-22/15/2 REV.2, 7.), 12. 170 Nuffield Council on Bioethics (n113), 128. 171 Leopoldina, ‘Chancen und Grenzen des genome editing’ (2015), available at: < https://www.leopoldina.org/publikationen/detailansicht/publication/chancen-und-grenzen-des-genome-editing-2015/> accessed 25 May 2020. 172 Inserm, ‘Fostering Global Responsible Research with CRISPR-Cas9’ (2016), available at: < https://www.inserm.fr/en/research-inserm/ethics/inserm-ethics-committee-cei/ethics-committee-workshops/fostering-global-responsible-research-with-crispr-cas9> accessed 25 May 2020. 173 COGEM, ‘Editing Human DNA. Moral and social implications of germline genetic modification’ (2017) CGM/170328-01, available at: < https://cogem.net/en/publication/editing-human-dna-moral-and-social-implications-of-germline-genetic-modification-2/> accessed 25 May 2020. 174 Nuffield Council on Bioethics, ‘Genome editing: an ethical review’ (2016), available at: < https://www.nuffieldbioethics.org/publications/genome-editing-an-ethical-review> accessed 15 June 2020; Nuffield Council on Bioethics (n113). 175 The National Academies of Sciences, Engineering, Medicine (NASEM), ‘Human Genome Editing: Science, Ethics and Governance’ (2017), available at:<https://www.nationalacademies.org/our-work/human-gene-editing-scientific-medical-and-ethical-considerations> accessed 25 May 2020.

Lilian Srour S3127389
24 reports is the emphasis placed on the need to consider and respect human rights when promulgating mechanisms for such oversight. It is worth noting that two significant reports addressing human genome modification are expected in 2020, from the Royal Society and from the World Health Organisation (WHO).176 It is also worth noting that in 2019 the WHO announced its plans to set up an international registry for clinical trials, so as to increase transparency globally.177 With respect to the expected reports, there are hopes that these will coordinate all the voices of CRISPR to build a consensual and acceptable framework to ensure the responsible guidance and use of CRISPR.178 1. Regional Level Throughout history, European nations have significantly contributed to wide-spread scientific and technological progress. This influence is still present today, and currently Europe is the only region which has regulatory frameworks for biomedical research.179 Through the European Union (EU), Member States influence the direction of research globally, as research conducted by European institutions often involves non-European researchers.180 Notably, regulations addressing genetic interventions are varied within the region.181 Due to matters of space, the following section addresses the Oviedo Convention only. Whilst it is an international treaty of regional application, it is regarded as authoritative and should be taken into account when considering appropriate guidance relating to human genome modification, given that it incorporates agreed international standards and good practices in the field of biomedicine.182 1.1. The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (1999) The European Convention on Human Rights and Biomedicine, commonly referred to as the Oviedo Convention, is the first internationally binding document in the field of biomedicine and human rights.183 Amongst the manifold reasons for the adoption of this document was the issues Member States were facing related to medicine and connected matters, e.g. in relation to patients’ rights and genetic materials. Concurrently, the growing proximity of European countries enabled the increased movement of patients, health enterprises and researchers, 176 As mentioned in Rodolphe Barrangou, 'Foresight is 2020: Ten Bold Predictions for the New CRISPR Year' [2019] 2(6) The CRISPR Journal 341. 177 ‘WHO launches global registry on human genome editing’, (WHO, 28 August 2019) available at: <https://www.who.int/news-room/detail/29-08-2019-who-launches-global-registry-on-human-genome-editing> accessed 12 May 2020. 178 Barrangou (n148). 179 Jessica Almqvist et al., ‘The Regulation of Human Germline Genome Modification in Europe’ Chapter 6 in Andrea Boggio, Cesare P. R. Romano, Jessica Almqvist (eds) Human Germline Genome Modification and the Right to Science (Cambridge University Press, 2019), 156-157. 180 Ibid. 181 Regarding regulatory oversight of genome editing in the EU, Dr Kessler identified several relevant Directives and Regulations, as for instance; Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products and Regulation (EU) No. 536/2014 on Clinical Trials on Medicinal Products for Human Use; FEAM, ‘Human Genome Editing in the EU’ (2017), available at: <https://www.interacademies.org/publication/feam-human-genome-editing-eu> accessed 25 May 2020, 6. 182 Yotova (n34), 4. 183 Oviedo Convention (n27).

Lilian Srour S3127389
25 whilst disparities between national legislations remained.184 Since the 1980s, the Council of Europe (CoE) issued several Resolutions and Recommendations on genetic engineering and embryo research.185 In 1983 it created an advisory group tasked with overseeing combined efforts to prepare a convention.186 The Oviedo Convention is an international treaty with regional, rather than general, application considering all its signatories are members of the CoE. It was adopted in 1999, and it draws on the principles of the European Convention on Human Rights (ECHR), 187 and its framework aims to protect the dignity and identity of all human beings. Furthermore, it sets out principles applicable to daily medical practice, and is regarded as the European treaty on patient’s rights.188 Right from the start, the Convention was considered a framework convention, meaning an international legal instrument that contains only broad and general principles, which are intended to be further developed through the adoption of additional protocols on specific issues, nationally, through the implementation of legislation. This document was one that the members of the CoE could opt to ratify or ignore.189 The Convention consists of 28 articles and is organized into 14 chapters. Chapter I outlines the general norms, chapters II to VII entail substantive provisions relating to specific bioethical matters and Chapters VIII to XIV include procedural norms, treaty organs and final clauses. Article 1 of the Convention states that each ratifying state has to take the necessary measures in their internal laws to give effect to the provisions of the Convention’.190 Article 2 assigns the utmost priority to the interests and welfare of the human being whose respect shall ‘prevail over the sole interest of society or science’.191 Article 5, relating to informed consent, has been hailed as a successful feature of the Convention, and is applied in therapeutic interventions, organ and tissue donation, clinical trials and genetic interventions still.192 Chapter IV regulates the human genome. Article 11 addresses non-discrimination whereby any form of discrimination against a person on the basis of genetic heritage is prohibited.193 Article 13, which will be discussed further below, provides that interventions seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes, only if the aim is to not introduce any modifications in the genome of descendants.194 Article 15 provides for the freedom of scientific research in the fields of biology and medicine, subject to the protection of human rights.195 Several provisions contained within the Convention are akin to those found in the UDHGHR, and also in the Helsinki Declaration.196 Despite the Convention’s 184 Vera L. Raposo, ‘The Convention of Human Rights and Biomedicine revisited: Critical Assessment’ [2016] 20(8) The International Journal of Human Rights 1277, 1277. 185 For example, Parliamentary Assembly of the Council of Europe, Resolution 934 (1982) on Genetic Engineering, available at: < https://assembly.coe.int/nw/xml/XRef/Xref-XML2HTML-en.asp?fileid=14968&lang=en> accessed 15 June 2020; Parliamentary Assembly of the Council of Europe, Resolution 1512 (2001) on the Protection of the Human Genome by the Council of Europe, available at: < https://assembly.coe.int/nw/xml/XRef/Xref-XML2HTML-en.asp?fileid=16897&lang=en> accessed 14 June 2020. 186 Raposo (n184), 1277-1278. 187 Convention for the Protection of Human Rights and Fundamental Freedoms (European Convention on Human Rights, as amended) (ECHR) ETS No.005 (Opened for signature 1950, entered into force 1953). 188 Council of Europe, ‘Oviedo Convention and its Protocols’ Bioethics, available at: <https://www.coe.int/en/web/bioethics/oviedo-convention> accessed 15 June 2020. 189 Jessica Almqvist et al. (n179), 160-161. 190 Oviedo Convention (n26), article 1. 191 Ibid, article 2. 192 Ibid, article 5. 193 Ibid, article 11. 194 Ibid, article 13. 195 Ibid, article 15; Observably, this provision resembles numerous other provisions found throughout human rights treaties affirming the freedom of scientific research as a human right. 196 Helsinki Declaration (n146).

Lilian Srour S3127389
26 mandatory nature, it cannot be enforced by the European Court of Human Rights (ECtHR), as its only authority in the matter is to express opinions regarding the interpretation of its norms.197 Furthermore, violations of the Oviedo Convention can only have repercussions in this context when there are violations of the ECHR. Furthermore, the Convention itself also does not include actual sanctions for the violations of norms, making the document rather void of affecting the signatories. It is in fact the responsibility of states to anticipate in their national laws the adequate sanctions for violations of the Oviedo Convention.198 Scientific knowledge has immensely progressed since the drafting of the Oviedo Convention, with the CRISPR system currently being developed and diffused rapidly. Against this backdrop, the CoE Committee responsible for overseeing the Convention, the Committee on Bioethics, issued a statement on genome editing technologies in 2015.199 This statement recognized that there is much potential for genome editing technologies in biomedical research, expressing support for the further understanding of disease and the developments of future treatments. Whilst it has been stated that the values reflected in article 13 remain relevant today and could be referred to in the international debate on questions surrounding technological advancements, these are not the last words on the matter.200 More recently, a Workshop Report conducted by the French Academy of Medicine revealed that delegates at the workshop were rather optimistic regarding the development of an EU-wide consensus regarding the benefits and further development of the clinical applications of genome modification in somatic cells.201 It was contended that regulatory guidance requires ongoing effective dialogue between regulators and researchers. Concerning germline applications, participants considered these necessary to inform basic research about human development and likewise indispensable to improve efficacy and safety of genome modification techniques to better support a potential future with applications in a clinical setting.202 Nevertheless, it was reiterated that the scope of the prohibitions within the Oviedo Convention, concerning some aspects of research and clinical activity in germline editing were rather ambiguous. Interestingly, it was noted that the context in which article 13 of the Convention had been formulated was actually written to deal with somatic gene therapy rather than with germline genetic interventions.203 Another report published in 2017 revealed a divided discussion between several authors concerning human germline therapy and the Oviedo Convention.204 The opposing sides presented arguments as to whether there should be a ban on such technology by the CoE. Arthur Caplan, for instance, considered that no ban should be reaffirmed205 whilst Francoise Baylis 197 Oviedo Convention (n26), article 29. 198 Raposo (n184), 1282. 199 Committee on Bioethics (DH-BIO), ‘Statement on genome editing technologies’ (2015), available at: < https://www.coe.int/en/web/bioethics/emerging-technologies/-/asset_publisher/O6iBP5ISnOh1/content/gene-editing?_101_INSTANCE_O6iBP5ISnOh1_viewMode=view/> accessed 25 May 2020. 200 Peter Mills, ‘Genome editing, human rights and the ‘posthuman’’ (Nuffield Council on Bioethics, 3 October 2017) available at: < https://www.nuffieldbioethics.org/blog/genome-editing-human-rights-posthuman> accessed 15 June 2020. 201 FEAM (n181), 2. 202 Ibid. 203 Ibid, 7. 204 Iñigo De Miguel Beriain et al., 'Human germline editing is not prohibited by the Oviedo Convention: An argument' [2019] 19(2-3) Medical Law International 226, 227. 205 Arthur Caplan and Peter Sykora, ‘The Council of Europe Should Not Reaffirm the Ban on Germline Genome Editing in Humans’ (EMBO Rep, 2017), available at: < https://www.embopress.org/doi/abs/10.15252/embr.201745246> accessed 25 May 2020.

Lilian Srour S3127389
27 insisted on the need for further maintaining a ban.206 The arguments put forth by both sides were interesting, and as some scholars have noted, the common ground observed through both arguments is that initially they are built on the presumption that the Oviedo Convention prohibits germline interventions.207 However, several authors have argued this presumption is a misinterpretation of the Convention, and that it is perfectly possible to adopt an alternative interpretation concerning article 13 and germline interventions. Therefore, it was argued that the new scientific context deserves an updated version of article 13 which allows for clinical applications of germline interventions, as also affirmed by the Nuffield Council of Bioethics.208 2. National Level Considering that the subject matter at hand has implications which cross national borders, it is worthwhile discussing how genome modification is currently addressed throughout several jurisdictions. Generally, the governance of human genome modification falls under the scope of pre-existing regulations developed for gene therapy and for the use of human embryos in research.209 The following paragraphs will briefly discuss several responses within Europe, and beyond. 2.1. A Bird’s Eye View of Europe In Europe, thus far, reports have demonstrated that regulations addressing gene therapy were generally appropriate for oversight of genome editing applications in somatic cells. However, it may be necessary to reconsider several aspects of regulatory oversight in the clinical setting of somatic intervention therapy, specifically where such methods of genome modification differ from those of conventional gene therapy, such as with the case of CRISPR. 210 This approach is not shared when it comes to germline research and interventions. Such applications have been a controversial subject for numerous countries. This has led to the emergence of various governance mechanisms demonstrating the differing national views on the moral and legal status of human embryos, and the acceptability of creating and utilising embryos, whereby public policies range from rather permissive to more prohibitionist.211 On the one end of the spectrum countries such as Germany and Italy forbid all research using human embryos, whilst on the other end countries such as the UK allow for the creation of embryos for research purposes. The Netherlands and France lie somewhere in-between, where under certain requirements, research on embryos may be performed. Overall, within Europe the regulatory regimes which are applicable to human genome modification on germ cells are varied and often ambiguous, reflecting the different national perspectives on the matter.212 This divide amongst nations can also be seen by the fact that not all European States have ratified the Oviedo Convention.213 It has been noted that these 206 Françoise Baylis and Lisa Ikemoto, ‘The Council of Europe and the Prohibition on Human Germline Genome Editing’ (EMBO Rep, 2017), available at: <https://www.embopress.org/doi/full/10.15252/embr.201745343> accessed 25 May 2020. 207 Beriain et al. (n204), 227. 208 Ibid, 232; Nuffield Council on Bioethics (n113), 150,154. 209 Tuerlings (n36), 22. 210 Ibid, 20. 211 Ibid. 212 Ibid. 213 For instance, Italy, the Netherlands, Poland and Sweden have signed the Convention but not ratified it, whilst Bulgaria, Denmark, Greece and Hungary have signed and ratified the Convention. Countries such as Austria, Belgium, Germany and the United Kingdom have neither signed nor ratified the Convention; ‘Chart of

Lilian Srour S3127389
28 variations could potentially challenge the development of a European framework concerning the use of human genome modification, and it can also affect research cooperation amongst Member States of the EU.214 2.1.1. Permissive In the UK, research on human embryos and gametes is regulated under the Human Fertilisation and Embryology Act 1990.215 This Act also installed a new regulator, namely the Human Fertilisation and Embryology Authority (HFEA). The HFEA is an executive non-departmental public body of the Department of Health in the UK.216 In relation to research, the law works through a general prohibition and qualified permission. In other words, no human embryo research may be conducted without a license from the HFEA. The 2008 version of the Act has also clarified many of the conditions for research and that it is not possible to use genome editing techniques on embryos. Notably, since 2015, the UK has permitted mitochondrial donation treatment. There has been much debate on whether the use of mitochondrial replacement techniques (MRT) should be regarded as a form of germline modification. In the UK, legislation prohibits clinical germline applications, but this ban does not apply to MRTs.217 It should be noted that the UK is not a state party to the Oviedo Convention and thus not bound by it. 2.1.2. Somewhere In-between The Netherlands and France are countries that lie somewhere amongst permissive and prohibitionist countries, where research on human embryos may be performed utilising surplus IVF embryos. In France this was made possible through the new 2013 regulatory framework.218 In the Netherlands, the 2002 Dutch Embryo Act is relevant for the regulatory landscape for human genome modification.219 Research involving embryos in gametes is covered under the Embryo Act and must undergo a review every several years by the Central Committee on Research Involving Human Subjects. Notably, under Dutch laws it is prohibited to alter the Signatures and ratifications of Treaty 164’ (Council of Europe, 15 June 2020) available at: <https://www.coe.int/en/web/conventions/full-list/-/conventions/treaty/164/signatures> accessed 15 June 2020. 214 Jeff Kipling, ‘The European Landscape for Human Genome Editing’ (26 April 2016, FEAM) available at: < https://acmedsci.ac.uk/file-download/41517-573f212e2b52a.pdf> accessed 15 June 2020, 1-2. 215 Parliament of the United Kingdom, Human Fertilisation and Embryology Act (1 November 1990) as amended by HFEA Act 2008, available at: <http://www.legislation.gov.uk/ukpga/2008/22/contents?fbclid=IwAR2wUDaYn_JSmAs5H-mn4MRQH2358ugGL2anzTtR67qruu-EL4mltaXY4XA> 216 Non-departmental public bodies are not an integral part of any government department, but rather they conduct their work at ‘an arm’s length’ from ministers, who are ultimately responsible to Parliament for the activities of bodies sponsored by their department; Stephan Rixen, Genome Editing and the Law. in Matthias Braun, Hannah Schickl, Peter Dabrock (eds), Between Moral Hazard and Legal Uncertainty (Springer 2018), 20. 217 Parliament of the United Kingdom, The Human Fertilisation and Embryology (Mitochondrial Donation) Regulation (entered into force 25 October 2015), available at: <https://www.legislation.gov.uk/ukdsi/2015/9780111125816> accessed 26 May 2020. 218 French Parliament, Law no. 2013-715 of August 6, 2013 amending Law no. 2011-814 of July 7, 2011 relating to bioethics by authorizing under certain conditions research on the embryo and embryonic stem cells (1 August 2013), available at: <https://www.legifrance.gouv.fr/affichTexte.do;jsessionid=8DE166F34A25D1129E06625D904FE6B8.tpdjo14v_2?cidTexte=JORFTEXT000027811435&categorieLien=id&fbclid=IwAR1khZrzol5ygkMj4tmzGYaKT7wdRQTGRebXEUIl_4OtEOdJORdehFQaOfk> accessed 26 May 2020. 219 The Dutch Council of State, Embryo Act (20 June 2002), available at: <https://wetten.overheid.nl/BWBR0013797/2013-09-27> accessed 26 May 2020.

Lilian Srour S3127389
29 nuclear DNA of germline cells, which is in line with the Oviedo Convention which the Netherlands has signed but not ratified. Interestingly, legislation was also adapted to accommodate MRT in the Netherlands. This was achieved by limiting the ban on reproductive germline modification in the Embryo Act.220 2.1.3. Prohibitionist In Italy, Law 40 of the 2004 legislation concerning assisted procreation previously regulated much of the research carried out on in vitro fertilisation.221 Over the years, the Italian Constitutional Court gradually removed numerous constraints on research found within the Act, including lifting the ban on pre-implantation genetic diagnosis (PGD) in 2015. Nevertheless, research on embryos, including the use of embryos to derive stem cells, remains prohibited.222 Similarly, in Germany the Embryo Protection Act of 1990 prohibits the generation and use of human embryos for basic research purposes.223 Section 1 of the Act outlines the improper uses of reproduction technologies including the artificial fertilisation of an egg for any purposes other than for pregnancy in the woman from whom the egg was collected. The act also prohibits sex selection except for in cases of serious sex-linked hereditary diseases. Amongst the most significant provisions lies section 5 of the Act, which states that anyone that artificially alters the genetic information of a human germline cell will face up to 5 years of imprisonment or a fine.224 2.2. Zooming Out: The United States Genome modification has also been a topical matter reaching beyond the European region.This section will briefly discuss the United States, currently considered a pioneer in human genome modification,225 and CRISPR more particularly. In the US there is no federal legislation which places limitations on experiments which aim to manipulate human DNA. Nevertheless, federal control exists in terms of: (i) allocating federal funding towards genome editing research projects, (ii) approval to run gene therapy clinical trials on humans and (iii) awarding FDA approval in terms of a marketable product.226 Concerning the allocation of funds, in 1995 an amendment was passed prohibiting the National Institutes of Health (NIH) from funding research involving the manipulation of embryos.227 220 De Wert et al. (n55), 456. 221 Italian Parliament, Law No.40/2004 Rules on Medically Assisted Procreation (19 February 2004), available at: <https://www.ieb-eib.org/ancien-site/pdf/loi-pma-italie-english.pdf?fbclid=IwAR0brK4LJNiKEHR831uHI51CgwlXQVXR1kzoep_vn4hheZgAHTmmIIOGfNw> accessed 26 May 2020. 222 FEAM (n181), 15. 223 German Federal Ministry of Justice and Consumer Protection, Embryo Protection Act (13 December 1990), available at: <http://www.gesetze-im-internet.de/eschg/BJNR027460990.html?fbclid=IwAR2Lyz-SFH5Ve-hGxvuVv-oKRpZ32ReFsjhFErurn5_nY9oJ0mEPFI5Lxg0> accessed 26 May 2020. 224 Ibid, section 5. 225 Jacqueline Martin-Laffon et al., ‘Worldwide CRISPR patent landscape shows strong geographical biases’ [2019] 37(6) Nature Biotechnology <https://www-nature-com.proxy-ub.rug.nl/articles/s41587-019-0138-7> accessed 15 June 2020. 226 Kevin Curran, 'How on Earth Are We Currently Regulating Human Genetic Modification?' (Rising Tide Biology, 23 January 2020) <https://www.risingtidebio.com/human-gene-therapy-regulations-laws/> accessed 25 May 2020. 227 US Congress, Dickey-Wicker Amendment Bill to the Balanced Budget Act I, Public Law no 104-99, Stat.26, p.110 (26 January 1996), available at: <https://www.congress.gov/bill/104th-congress/house-

Lilian Srour S3127389
30 With respect to approving gene therapy trials, Congress issued a provision stating that the FDA must approve any human clinical trials concerning genome modification.228 In response to the recent innovations, particularly CRISPR, the FDA attempted to clarify its position through stating that any use of CRISPR in genome modification will be considered to be gene therapy.229 This is regulated by the FDA’s Center for Biologics Evaluation and Research. Furthermore, clinical studies involving gene therapy in humans require the submission of an investigational new drug application prior to their initiation in the US.230 Additionally, marketing of a gene therapy product requires submission and approval of a biologics license application.231 It is worth mentioning that the US has already issued legislation addressing CRISPR. The first American law passed addressing CRISPR was written by a republican senator in California, and it stated that companies should be prevented from selling CRISPR kits intended to modify human DNA.232 This appears to be motivated by recent actions from Josiah Zayner, who operates a company called ‘The Odin’, which sells genetic engineering supplies online.233 A report on genome modification from the US conducted an in-depth analysis on the adequacy of oversight systems in place to address the specific issues it raises.234 This report revealed that whilst improvements could be implemented, the overall regulatory system within the US is adequate. It also noted that both somatic and germline interventions would eventually be regulated within the framework for research on gene transfer, and once approved, the framework for gene therapy.235 3. Fragmented Responses Broadly speaking, it can be observed that treaties relevant to human genome modification take different approaches to secure similar aims. For instance, whereas the UDHGHR focuses on the integrity of the human genome, the Oviedo Convention focuses on the integrity of the inheritance of genetic features in a manner that reflects a web of relations which links all human bill/2880/text?overview=closed&fbclid=IwAR1nqbW-fMgab40fVtaFMfj5yUy8E0rRd2_iOcdt8SrikAghHEGBseEHJ7I> accessed 26 May 2020. 228 For further information regarding the FDA approval process see <https://www.fda.gov/drugs/development-approval-process-drugs?fbclid=IwAR0brK4LJNiKEHR831uHI51CgwlXQVXR1kzoep_vn4hheZgAHTmmIIOGfNw> last accessed 26 May. 229 FDA, ‘Information About Self-Administration of Gene Therapy’ (FDA, 2017), available at:< https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/information-about-self-administration-gene-therapy> accessed 26 May 2020. 230 US Food and Drug Administration, Code of Federal Regulations, Title 21(5) Food and Drug Administration Department of Health and Human Services (D) Drugs for Human Use (1 April 2019), available at: <https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.2> accessed 26 May 2020. 231 US Food and Drug Administration, Code of Federal Regulations, Title 21(7) Food and Drug Administration Department of Health and Human Services (F) Biologics (1 April 2019), available at: < https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=600&showFR=1> accessed 26 May 2020. 232 Antonio Regalado, ‘Don’t Change your DNA at home, says America’s first CRISPR law’ (MIT Technology Review, 9 August 2019) available at: <https://www.technologyreview.com/2019/08/09/65433/dont-change-your-dna-at-home-says-americas-first-crispr-law/> accessed 15 June 2020. 233 Molly Campbell, ‘Meet Josiah Zayne, the Biohacker Next Door’ (Genomics Research, 21 June 2019) available at: <https://www.technologynetworks.com/genomics/articles/meet-josiah-zayner-the-biohacker-next-door-320964>; The Odin, ‘About Us’ (The Odin,2020) available at: < https://acmedsci.ac.uk/file-download/41517-573f212e2b52a.pdf> accessed 15 June 2020. 234 NASEM (n175). 235 Tuerlings (n36), 22.

Lilian Srour S3127389
31 beings together.236 As put by Inigo de Miguel Beriain, the central concern of the Convention does not revolve around the preservation of genetic immutability, but rather the safety of the procedure.237 At the European level, it has generally been stated that none of the existing regulations by the EU or the CoE in fact pose decisive obstacles to CRISPR.238 On this note, it appears that countries are ‘relaxing’ their laws addressing genome modification to accommodate treatments as for instance with the use of MRT. Considering the dynamics of scientific innovation and medical developments, it is relevant to reflect on the arguments behind legislation that is currently in place and to question whether it is still capable of appropriately accommodating novel technologies, as for instance CRISPR. 239 Overall, human genome modification is not a matter that has been left unaddressed entirely. Scholarly literature, as well as various efforts at the international level and national jurisdictions have begun to move towards discussing a future within which applications of CRISPR would be feasible and how to best ensure that such a future captures the full potential of CRISPR in a responsible and beneficial manner. Nevertheless, as described above, there are various gaps in the legal framework currently surrounding human genome modification. In continuation of the discussion, the next Chapter will move to explore the right to health as understood under article 12 ICESCR, and the ‘AAAQ’ framework, before viewing CRISPR within the respective framework.
236 Nuffield Council on Bioethics (n113), 116. 237 Vera L. Raposo, 'CRISPR-Cas9 and the Promise of a Better Future' [2019] 26(4) European Journal of Health Law 308-329, 326. 238 Ibid. 239 De Wert et al. (n55), 456.

Lilian Srour S3127389
32 Chapter 3 A New Box for CRISPR? In the pursuit of finding an adequate framework for CRISPR, at the core of the analysis of this paper lies the international human right to health, or the right to the highest attainable standard of health, as understood under article 12 ICESCR.240 This is a fundamental right, set out in numerous universal, regional and specialized human rights treaties, making it binding not only under treaty law but arguably also under customary international law.241 Prospective CRISPR applications, arguably those discussed in Chapter 1, stand to impact the health of individuals in particular and the healthcare system overall. As such, viewing CRISPR from the lens of the right to health, and in light of the AAAQ framework, is highly useful in light of the fast-pacing developments aimed at translating potential applications to actual practice. The human right to health has frequently provoked sceptical reactions. Nevertheless, human rights distinguish themselves from moral postulates because they impose legally binding obligations on governments, whereby the State is seen as the formal guarantor of rights for those living under its jurisdiction in accordance with international law.242 As emphasised by Bielefeldt et. al., some critics of the right to health suggested that the semantics of this right may weaken the validity of international human rights claims generally. 243 Whilst this matter falls outside of the scope of this thesis, a brief word is needed. Such criticism is not new and often reflects the juxtaposition of civil and political rights and economic, social and cultural (ESC) rights. Civil and political rights, e.g. the freedom of religion or the freedom of expression244 ‘claim unconditionality’, whilst ESC rights, such as the right to food or the right to adequate housing,245 remain conditional on the basis of available resources.246 Nevertheless, when considering such criticism it is important to recall the nature of human rights, namely; that they are intended to be universal, inalienable and indivisible.247 At this point in time it is safe to assume that the interdependence and indivisibility of ESC rights and civil and political rights has generally been accepted.248 Relatedly, the Committee on Economic, Social and Cultural Rights (CESCR) has offered further explanation on the content of ESC rights through the adoption of a framework underpinned by concepts of availability, acceptability, accessibility and quality, also referred to as the ‘AAAQ framework’.249 This framework is central to the analysis in this paper and will be addressed in detail in the subsequent sections. Recalling that the right to health carries manifold implications for genome modification, particularly for States that opt to introduce clinical CRISPR applications, the following paragraphs will begin by elaborating on the right to health, before moving to discuss the AAAQ framework. 1. The Right to Health 240 ICESCR (n24), article 12. 241 Formulations of the right to health can be found, inter alia, in article 25 UDHR, article 5(e) CERD, articles 11.1,12 CEDAW, and article 24 CRC. 242 Sabine Klotz et al. (eds), Healthcare as a Human Rights Issue (4th Volume, Transcript 2017) 9-10. 243 Ibid. 244 ICCPR (n159), article 18(2) and 19. 245 ICESCR (n24), article 11. 246 Klotz et al. (n242), 10. 247 Vienna Declaration and Programme of Action (adopted on 25 June 1993) A/CONF.157/23, para 5. 248 Alicia E. Yamin, 'The Right to Health Under International Law and Its Relevance to the United States' [2005] 95(7) American Journal of Public Health 1156-1161, 1157. 249 General Comment 14 (n28), para 12.

Lilian Srour S3127389
33 The first expressions of the right to health can be found under article 25 UDHR. It was not expressly guaranteed as a distinct right, but rather combined with the right to an adequate standard of living for health and well-being of all.250 However, the significance of this provision lies in the fact that the UDHR recognised that health has wider reaching implications than medical care. It included preconditions for health deemed central to achieve an adequate standard of living.251 Nevertheless, Article 12 in the ICESCR has been said to represent the ‘fullest and most definitive conception of the right to health’.252 Under the first paragraph of this provision, everyone is entitled to the enjoyment of the highest attainable standard of physical and mental health. Similar formulations are to be found within the other international documents.253 In 2000 the CESCR issued General Comment No.14, an explanatory note on the necessary elements for the fulfillment of the highest attainable standard of health.254 Accordingly, the right to health does not entail a right to be healthy but rather the freedoms to control one’s own body, including sexual and reproductive freedoms and the entitlements to a system of health protection which provides equal opportunity for people to enjoy the highest attainable standard of health.255 As stated by the CESCR, the scope of the right to the highest attainable standard of health is not confined to the right to healthcare. Rather, it extends to appropriate and timely healthcare and to the underlying determinants of health, i.e. access to safe and potable water or access to health-related education and information.256 On the one hand, there is an individual entitlement of access to healthcare including preventive and curative healthcare. This entitles individuals to a system of health protection that provides equality of opportunities for people to enjoy the highest attainable standard of health.257 Notably, the prevention, treatment and control of diseases and injury is crucial to achieving the right to health and recognised under article 12(2)(c), whereby states are to undertake necessary measures for the prevention, treatment and control of diseases.258 On the other hand, there is a list of social and economic factors that influence the exercise of the right to health. In other words, the enjoyment of a variety of facilities, goods and services directly connected with the realisation of the highest attainable standard of health.259 The CESCR has also emphasised that essential elements of the right to health include their scientific and medical quality and their accessibility to everyone without discrimination.260 Within the Comment, the close relations of the right to health with other fundamental human rights was recognized.261 The Comment is comprised of five sections, beginning with an elaboration on key terms and concepts relating to the notion of health. Furthermore, state 250 UDHR (n158), article 25. 251 Manisuli Ssenyonjo, Economic, Social and Cultural Rights in International Law (1st edn, Hart Publishing, 2009) 313. 252 Ibid, 319. 253 Convention on the Rights of the Child (adopted 20 November 1989, entered into force 2 September 1990) 1577 UNTS 3, article 24; African Charter on Human and Peoples' Rights (adopted on 01 June 1981, entered into force 21 October 1986) OAU CAB/LEG/67/3 rev. 5 (ACHPR), article 16. 254 General Comment 14 (n28). 255 Ibid, para 8. 256 Ibid, paras 4 and 11. 257 Ibid, para 8, 17. 258 ICESCR (n24), article 12(2)(c). 259 General Comment 14 (n28), para 9. 260 Ibid, para 12. 261 Ibid, para 3.

Lilian Srour S3127389
34 obligations, implementation at the national level and the obligations of non-state actors are described. Generally, the rights and obligations under article 12 ICESCR are two-fold. Article 12(1) frames health as an individual right and 12(2) imposes specific obligations on States to realise the right to health.262 It should be mentioned, that under international law, States Parties to treaties assume tripartite obligations to respect, protect and fulfil (RPF) the rights of those under their jurisdiction.263 In this context, States parties are to, i.e. respect the right to health through refraining from engaging in acts which would negatively impact the right to health, to protect the right to health through protecting individuals from interference with their rights and the obligation to fulfil the right to health by adopting deliberate measures aimed at achieving access to care and to the underlying determinants of health.264 Notably, the highest attainable standard of health concerns both an individual’s ‘biological and socio-economic preconditions and a State’s available resources’.265 Notwithstanding, there is a minimum standard under which no state should fall.266 For instance, to comply with the obligation to respect the right to health, state’s must undergo steps immediately towards the progressive achievement of the full realisation of the right. Under article 12(2), the ICESCR provides a non-exhaustive list of the steps States are obliged to undertake. Furthermore, the CESCR has introduced core obligations so as to limit the risk of governments unjustifiably invoking the principle of progressive realization to deny health care or to avoid taking action. The Committee has stated that states must ensure minimum core obligations that are not subject to progressive realization, which ensures the fulfillment of minimum essential levels of each right.267 Lastly, with respect to the monitoring of the fulfilment of obligations under the right to health, States must indicate whether they have a national health policy and whether the national health system with universal access to primary health care is available. Moreover, states must indicate what measures have been taken to ensure the realisation of the highest attainable standard of health.268 Overall, this General Comment has received some praise as it was described to have deviated from a substantive notion of core obligations, as for instance essential primary healthcare, to a more procedural and structural approach that encompasses equitable distribution, non-discrimination and a participatory national plan of action.269 2. The AAAQ The ‘AAAQ’ framework has been described as a ‘ground-breaking hands on approach to economic, social and cultural rights’, and it aims to support the operationalisation of numerous rights, as for instance the rights to water, food, sanitation, housing, education and health.270 This authoritative human rights framework, as outlined in the General Comments to the ICESCR, breaks down the obligations of states in relation to human rights into four criteria271 and offers a framework that translates the general provisions of international human rights 262 ICESCR (n24), article 12. 263 See Inter-Parliamentary Union and the UN Office of High Commissioner for Human Rights (n107). 264 Yamin (n248),1157. 265 General Comment 14 (n28), para 9. 266 Ssenyonjo (n251), 65-69,322. 267 UN CESCR, General Comment No.3: The Nature of States Parties Obligations (Art.2, Para.1, of the Covenant (14 December 1990) E/1991/23 (General Comment 3), para 10. 268 Ssenyonjo (n251), 323. 269 Lisa Forman et al., ‘What Do Core Obligations Under the Right to Health Bring to Universal Health Coverage?’ (Health and Human Rights Journal, 5 December 2016) < https://www.hhrjournal.org/2016/12/what-do-core-obligations-under-the-right-to-health-bring-to-universal-health-coverage/#_edn30> accessed 15 June 2020. 270 The Danish Institute for Human Rights, ‘AAAQ’ available at: <https://www.humanrights.dk/what-we-do/sustainability/implementing-economic-social-cultural-rights/aaaq> accessed 13 May 2020. 271 Danish Institute for Human Rights (n30), 2.

Lilian Srour S3127389
35 instruments into indicators and benchmarks for realising ESC rights. In relation to the right to health, States parties, in line with their RPF obligations, are to guarantee the right to health by addressing the elements of AAAQ whilst ensuring non-discrimination.272 Furthermore, it provides a meaningful framework for assessing, among others, health care services as it reflects the idea that health services, facilities and goods are to be available in sufficient quantities, accessible physically, economically, and without discrimination, acceptable in terms of medical, ethical and cultural standards, and they must be of good quality.273 These will be elaborated on in detail below. • Availability: entails the provision of a sufficient quantity of public health and health-care facilities, goods, services and programs. Furthermore, it requires states to ensure that the underlying determinants of health are available in sufficient quantity as necessary for the whole population within a state.274 • Accessibility: this criterion relating to the right to health has four overlapping dimensions, namely; non-discrimination, physical accessibility, economic accessibility and information accessibility. Health facilities, goods and services have to be accessible in accordance with all the mentioned aspects. This includes, inter alia, hospitals, clinics, medical and professional personnel, drugs and other equipment.275 o Non-discrimination: a fundamental element of the right to health entails equal access and non-discrimination. The UN Commission on Human Rights has emphasized that non-discrimination in the field of health is to apply to all people under all circumstances.276 Essentially, states are under the obligation to eliminate de jure and de facto discrimination in access to healthcare and to underlying determinants, as well as access to means and entitlements for their realization. This serves to ensure that all individuals have access, including marginalized groups as for instance persons with disabilities, older persons or asylum seekers.277 o Physical Accessibility: this dimension requires health services and the determinants of health to be within safe physical reach for all parts of the population, including rural areas. This is especially important for those vulnerable or marginalized groups, as mentioned previously, particularly for persons with disabilities, as they must have access to all buildings as well.278 o Economic Accessibility: requires that payments for healthcare services and services related to the underlying determinants of health have to be based on the 272 End FGM European Network, UN Committee on Economic, Social and Cultural Rights – General Comment No. 14: The Right to the Highest Attainable Standard of Health (2000) (16 August 2016) available at <https://www.endfgm.eu/resources/health/un-committee-on-economic-social-and-cultural-rights-general-comment-no.-14-the-right-to-the-highest-attainable-standard-of-health-2000/> accessed 15 June 2020. 273 Forman (n269). 274 General Comment 14 (n28), para 12(a). 275 Ibid, para 12(b). 276 See generally, UN Commission on Human Rights, Resolution 1989/11 on Non-discrimination in the field of health (adopted 2 March 1989) UN Doc E/CN.4/RES/1989/11. 277 General Comment 14 (n28), para 12(b)(i). 278 Ibid, para 12(b)(ii).

Lilian Srour S3127389
36 principle of equity, ensuring that these services, regardless of whether they are provided by public or private entities, are practically affordable for all.279 o Informational Accessibility: the freedom of information has long been hailed as a fundamental human right and has been described as the ‘touchstone of all the freedoms to which the UN is consecrated’.280 This freedom includes the right to seek, receive and impart information and ideas concerning, inter alia, health issues.281 • Acceptability: signifies that healthcare services and facilities must be culturally appropriate, in other words respectful of individual’s culture, sensitive to gender and to life-style requirements. These must also be designed to respect confidentiality and improve the health status of those concerned. 282 • Quality: implies that the available health care and services must be scientifically and medically appropriate and of good quality. This requires, inter alia, skilled medical personnel and scientifically approved drug and hospital equipment.283 3. The Right to Health, the AAAQ and CRISPR Whilst CRISPR and its potential applications have been discussed in terms of human dignity and the right to life,284 viewing this matter in light of the right to health may be more practical. Therefore, rather than solely centering on the ethical concerns and the differences in perspectives surrounding CRISPR, this paper aims to contribute to the conversation by viewing CRISPR in light of the right to health and more particularly the AAAQ framework, in an attempt to discern the attributes of human genome modification that are significant for policy makers and stakeholders, and whether those are appropriately addressed under existent frameworks. Arguably, the right to health possesses distinctive characteristics which stand to provide guidance on what effective oversight would look like, as this right in particular carries many implications for human genome modification, in the form of applications utilising CRISPR. To emphasise, as stated by Paul Hunt, former Special Rapporteur, the right to health offers the conceptional and operational potential to make a significant contribution relating to the implementation of long-term health interventions,285 as for instance with gene therapy. Whilst this paper attempts to put this framework to practice, a few brief remarks are in order. With some exceptions, the practical application of the AAAQ seems to be lacking in the scholarly literature, often fleetingly mentioned when describing the right to health, or for instance more recently by the Danish Institute of Human Rights when discussing sexual and reproductive health rights as well as the right to water.286 Furthermore, it has received little 279 Ibid, para 12(b)(iii). 280 UN General Assembly, Resolution 59(I): Calling of an International Conference on Freedom of Information (adopted 14 December 1946) UN Doc A/RES/59(I). 281 General Comment 14(n28) para 12(b)(iv); ICCPR (159), article 19(2). 282 Ibid, para 12(c). 283 Ibid, para 12 (d). 284 See generally Iñigo De Miguel Beriain, ‘Human dignity and gene editing’ (EMBO Reports, 21 September 2018) < https://www.embopress.org/doi/10.15252/embr.201846789> accessed 14 May 2020. 285 Paul Hunt, ‘Interpreting the International Right to Health in a Human Rights-Based Approach to Health’ (Health and Human Rights Journal, 3 December 2016) < https://www.hhrjournal.org/2016/12/interpreting-the-international-right-to-health-in-a-human-rights-based-approach-to-health/> accessed 15 June 2020. 286 See generally Mads H. Jensen et al., ‘The AAAQ Framework and the Right to Water – international indicators’ (The Danish Institute for Human Rights, 2014) <

Lilian Srour S3127389
37 attention in actual policy practice. Minding that UN agencies have increasingly adopted guidance on how to operationalize human rights, as for example in relation to maternal mortality or HIV/AIDS,287 increased guidance on the practical implementation of the AAAQ framework could be inherently useful in this regard, particularly when determining whether novel biotechnologies can be appropriately accommodated under the current understanding of the what the right to health entails. It should be acknowledged that it remains unclear whether the AAAQ framework was meant to be understood differently in light of different rights and services,288 but with respect to the right to health and potential genome modification applications, further discussion and elaboration may prove to be rather beneficial. Nevertheless, the following sections will discuss potential applications of CRISPR under the AAAQ to determine whether this framework can accommodate the novel features of this biotechnology. Additionally, the author seeks to explore whether this indicator has the potential to contribute to the formulation of an effective legal response that ensures respect for human rights standards, particularly the right to health. The instruments and legal approaches surveyed in Chapter 2 shall provide points of reference. 3.1. Availability Primarily, viewing CRISPR in terms of availability would entail that it is available in a sufficient quantity in the form of a future health service. Relating to CRISPR, this is essential so as to ensure that future services related to this biotechnology are facilitated for those who require it. When discussing availability, clarification as to what a sufficient quantity constitutes has to be established. However, there is yet not mention of what this entails, as there is no universal applicable quantity available mentioned under the AAAQ in relation to health services. This is problematic when attempting to determine availability in the context of CRISPR. There are many uncertainties regarding which factors contribute to availability in this regard. Nevertheless, it can be assumed that this availability would be directly connected to the particular features specific to each country, as for instance available funding directed towards CRISPR applications, and the number of patients in need of such applications in the treatment of certain conditions, i.e. sickle-cell anemia or cancer. Furthermore, availability may also be influenced by predisposition to certain diseases that can be treated or ameliorated by utilizing CRISPR reported to the number of people in respective jurisdictions who are suffering of the corresponding conditions; i.e. cancer or beta thalassemia. Following this rationale, availability will be discussed in light of the instruments and legal approaches discussed in Chapter 2. Amongst the instruments surveyed, the UDHGHR addresses availability in terms of benefiting from advances in biology, genetics and medicine, whereby under article 12 it is stated that those shall be made available to all.289 Furthermore, under the second paragraph of this provision, applications in genetics and medicine concerning the human genome shall seek to offer relief from suffering and improve the health of not just individuals but humankind as a https://www.humanrights.dk/sites/humanrights.dk/files/media/dokumenter/udgivelser/aaaq/aaaq_international_indicators_2014.pdf> accessed 10 May 2020; Lena Kähler et al., ‘AAAQ & Sexual and Reproductive Health and Rights’ (The Danish Institute for Human Rights, 2017) <https://www.humanrights.dk/sites/humanrights.dk/files/media/dokumenter/udgivelser/aaaq/aaaq-srhr_issue_paper_dihr_2017_english.pdf> accessed 12 May 2020. 287 Paul Hunt (n285). 288 Marlies Hesselman et al., ‘International guideposts for essential public services provision and socio-economic human rights’ Chapter 16 in Marlies Hesselman et al. (eds), Socio-Economic Human Rights in Essential Public Services Provision (Routledge, 2017) 303. 289 UDHGHR (n25), article 12.

Lilian Srour S3127389
38 whole. Implying that such advances are to benefit humankind overall arguably, under the right to health, translates into ensuring availability of CRISPR applications for those individuals in need. Under the UDBHR availability is not expressly addressed, however article 14 states that the promotion of health and social development is a central purpose for all States Parties and that quality healthcare must be considered a social and human good.290 Arguably, in relation to the right to health, this could read to imply that potential medical applications of CRISPR should be promoted for those in need, and as such made available. The Oviedo Convention echoes similar aims whereby under article 3 equitable access to healthcare is addressed. The provision reads that States Parties are to take into account health needs and availability of resources to ensure equitable access to healthcare within their jurisdiction.291 Amongst the previously discussed approaches, the UK pursues a more permissive attitude towards human genome modification where, as emphasized by Bakewell, genetic procedures are becoming more common in modern medicine.292 For instance, pre-implementation genetic diagnosis is approved in the UK by the HFEA, and further in 2015 the mitochondrial donation regulations have allowed for the legalization of MRT. Existing legislation in the UK seems to permit for limited genome modification in human reproduction, and it seems highly likely that in the future potential applications of CRISPR will be employed to prevent the transmission of serious diseases, through the application of germline procedures. Bakewell has also emphasized that novel features of biotechnologies, as is the case with CRISPR, are likely to contribute to their availability around the world. She stated that when CRISPR was first announced the acronym received ‘19 million hits on google, 5.000 articles were written, 28.000 patents were taken out, and as we know, two babies were born’.293 The prospects of CRISPR applications in medicine are grand. Considering that about 8 million babies with genetic defects are born each year, the potential for doing good is enormous, with talk about potentially being able to eliminate sickle cell entirely.294 Remarkably, in the UK a national genomic healthcare strategy was set up to improve existing services for those with rare diseases, whereby the NHS offered genome sequencing as part of its service.295 Considering that 6% of UK’s population will be affected by a rare disease throughout their lives, and 30 million people across Europe, it is important to confront the broader dilemmas that come with the application of novel techniques such as CRISPR. On this note, Bakewell reiterated that, since 2003, numerous gene therapy treatments have been approved to treat cancers and other disorders, increasingly demonstrating that the technology holds the promise for innumerable cures.296 Notably, the UK was the first in Europe to make CAR-T therapy available to cancer patients.297 Furthermore, Baroness Bottomley of Nettlestone has stated that a prime focus during her NHS work was to bring together research universities and teaching hospitals so as to protect, enhance and develop scientific and medical research, which she characterized as a great strength in the UK, where it can be seen as a global leader.298 Lastly, to further depict the overall attitude towards CRISPR applications within the UK, universities, such as the University of Manchester, have adopted the use of CRISPR in research whereby 99% of 290 UDBHR (n26), article 14. 291 Oviedo Convention (n27), article 3. 292 HL Deb 30 January 2020, vol 801, col 1521. 293 Ibid. 294 Ibid. 295 Ibid. 296 Ibid, col 1523. 297 Ibid, col 1524. 298 Ibid, col 1525.

Lilian Srour S3127389
39 transgenic experiments are conducted utilizing CRISPR.299 From this permissive attitude it can be observed that aspirations directed at ensuring future availability of CRISPR applications are strong. Furthermore, there appears to be no concrete evidence suggesting that if these developments were to stay their course, that future applications of CRISPR would be prohibited, and largely unavailable. Nevertheless, considering the novel features of CRISPR, there are distinguished other concerns that accompany availability in this context. For instance, as voiced by Bakewell, one of these concerns is who will stop rogue operators or biohackers seeking to undertake genome modification applications with the technique being so cheap and available, to which she has noted that a WHO report is expected that hopefully addresses such worries. Similarly, Lord Bishop of Carlisle noted that prior to exploring genome modification in the realm of a widespread clinical reality, availability-related concerns need to be addressed, e.g. if such applications were to become primarily available through the private sector, as was the case with IVF, would this uphold availability requirements?300 Notably, this also relates to accessibility, and will be elaborated on further below. The present author agrees with the position that the principle of availability is rather open-ended, but it nevertheless carries value in relation to CRISPR. Whilst at first it would seem that a prohibitionist approach towards human genome modification would mean potential applications of CRISPR are under-funded and under-developed, this is not entirely true. For instance, in Germany three pharmaceutical giants have invested millions in CRISPR technology to find revolutionary treatments for various human diseases. Furthermore, the Intellectual Property Office in Singapore has awarded Merck,301 a German pharmaceutical company, a patent to perform CRISPR research.302 However, as previously noted, with respect to regulation of CRISPR and the use of embryos, there are limitations in place as the Embryo Protection Act states that embryos cannot be utilized for any purposes other than pregnancy.303 With respect to somatic applications, however, there is a general spirit of encouraging development and further research.304 Nevertheless, as noted by Vogel, private sector funding for gene editing research is regarded as a way for scientists to commence research without having to struggle with bureaucracy involved in federal funding or university sponsored research.305 The manner in which this will impact availability is not yet clear, however this may potentially lead to applications of CRISPR being provided primarily through the private sector. Overall, Professor Winnaker has noted that it is unsurprising that many inconsistencies remain in the relevant German legislation306 as it is outdated when dealing with recent technological advances. He further noted that it was difficult 299 David Brough, ‘CRISPR – the future of genetic research at Manchester?’ (Faculty of Biology, Medicine and Health University of Manchester) available at: <https://www.bmh.manchester.ac.uk/stories/crispr/> accessed 10 June 2020; Communications Team, ‘Largest study of CRISPR-Cas9 mutations creates prediction tool for gene editing’ (Wellcome Sanger Institute, 27 November 2018) available at: <https://www.sanger.ac.uk/news_item/largest-study-crispr-cas9-mutations-creates-prediction-tool-gene-editing/> accessed 15 May 2020. 300 HL Deb (n292), col 1528. 301 Merck, ‘The Potential of CRISPR Technology’ available at: <https://www.merckgroup.com/en/expertise/pharmaceutical-research/crispr.html> accessed 14 May 2020. 302 Asian Scientist Newsroom, ‘Merck Granted CRISPR Patent in Singapore’ (Asian Scientist, 22 December 2017) available at: <https://www.asianscientist.com/2017/12/pharma/merck-singapore-crispr-patent/> accessed 18 May 2020. 303 As noted in section 3.1.3. Chapter 2 of this paper. 304 FEAM (n181), 2. 305 Vogel (n110). 306 For instance, the Embryo Protection Act 1990 prohibits the generation and use of embryos for basic research. However, the Embryo Protection Act does not explicitly protect embryos that are not viable. As stated by Vogel, the legal scope of non-viable embryos in genome editing experiments remains unclear; Vogel (n110).

Lilian Srour S3127389
40 to influence the process towards ensuring that legislation shall be amended to reflect the changing nature of science.307 In comparison, it seems Italy is not as actively engaged in CRISPR research and funding as the UK or Germany. Whilst some funding is directed at CRISPR research,308 it remains unclear how genome modification will be further developed in Italy. For instance, it has been claimed that CRISPR studies conducted in China were omitted from publication in any national scientific paper in Italy.309 In France, the government adopted a plan called ‘Médicine France génomique 2025’ which aims to establish a wide-ranging platform across the country for sharing genome information and technology, as for instance CRISPR research, and ultimately for helping those suffering from cancer or rare diseases.310 Notably, France has ratified the Oviedo Convention, and as such is suffering restrictions on gene editing research due to article 13 which has been interpreted to read that germline interventions are not permitted. However, as discussed in Chapter 2 there are varying interpretations applicable to this article that would not prohibit germline applications. Regardless, there appears to be some movement towards facilitating primarily somatic applications, whilst discussing the manner with which to approach germline interventions. Furthermore, the plan devised by the French government is rather all-encompassing as it aims to address concerns, as for instance, whether medical gene editing technologies will be covered through insurance and national health care programs.311 In terms of availability, it would appear that France is moving towards addressing the practical realities of facilitating clinical applications of CRISPR, even if currently those primarily address somatic applications. Such course of action can serve as guidance for the practical facilitation of germline applications in the future also. Whilst somewhat beyond the scope of this thesis, a brief word on an emerging attitude regarding the European regulatory landscape will follow. In Europe, more and more voices are requesting a revision of the current European GMO Directive.312 Thus far, the number of CRISPR patents originating from the European region is lagging behind those originating from China or the US. As emphasized by Narin, Europe is far behind the US in the production of ‘important, highly cited research’.313 Furthermore, it was emphasized that there is a weakening of European science, which can be attributed to the funding systems. GMO bans in Europe have been said to have a negative impact on the future of biotechnology, including in relation to health aspects, within the region.314 This could arguably impact the availability of CRISPR applications, and as such a way to ensure adequate availability would require addressing such matters. To contrast, the US is not only a pioneer in 307 FEAM (n181), 14. 308 ‘ERC grants to researchers from the Italian Institute of Technology (Research Italy, 21 December 2016) available at: <https://www.researchitaly.it/en/success-stories/erc-grants-to-researchers-from-the-italian-institute-of-technology/ accessed 19 May 2020. 309 FEAM (n181), 15. 310 INSERM Press Office, ‘Presentation of the French Plan For Genomic Medicine 2025’ (Inserm, 23 June 2016) available at: < https://presse.inserm.fr/en/presentation-of-the-french-plan-for-genomic-medicine-2025/24328/> accessed 14 May 2020. 311 Vogel (n110). 312 Matt Ridley, ‘Why Brexit could jump start UK GMO, CRISPR research – once stifled by ‘dead hand’ of EU regulation’ (Genetic Literacy Project, 18 March 2020) available at: <https://geneticliteracyproject.org/2020/03/18/viewpoint-brexit-could-jump-start-uk-gmo-crispr-research-once-stifled-by-dead-hand-of-eu-regulation/> accessed 15 May 2020; see generally, European Parliament and Council Directive 2001/18/EC of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC [2001] OJ L106/01. 313 See generally Alonso Rodriguez-Navarro and Francis Narin, ‘European Paradox or Delusion – Are European Science and Economy Outdated?’ [2018] 45(1) Science and Public Policy 14. 314 Martin-Laffon et al. (n225).

Lilian Srour S3127389
41 gene editing using CRISPR, but it is currently regarded as a leader for improvements in the development of the technology.315 Lastly, CRISPR’s recent availability via online marketing lies amongst its novel features and will be addressed in the following section. 3.2. Accessibility CRISPR in terms of accessibility would imply the provision of applications whilst ensuring non-discrimination, physical accessibility, affordability, and information accessibility. Viewing CRISPR in the context of non-discrimination raises numerous questions. Primarily, it remains unclear what constitutes discrimination in relation to potential CRISPR applications. For instance, recalling that certain communities, i.e. the deaf community, have voiced that such practices stand to threaten them.316 In this regard, it has been voiced that future CRISPR applications may potentially discriminate against the disabled through the reframing of the concepts of disease and health.317 Amongst the instruments surveyed, non-discrimination is addressed through the prohibition of discrimination on the basis of genetic inheritance. However, as discussed in Chapter 2, under the UDHGHR, article 6 leaves much at the discretion of domestic law-makers and does not provide guidance on which practices would constitute discrimination. Under the UDBHR, non-discrimination or stigmatization in violation of human dignity, human rights and fundamental freedoms is prohibited, whereas under the Oviedo convention, article 11 extends grounds of non-discrimination to include those on the basis of genetic heritage. It is yet to be determined, possibly by the international community or other concerned stake-holders, whether applications of CRISPR comply with this dimension, and what non-compliance would entail. Concerning physical accessibility, this would read to imply that applications of CRISPR should be within safe physical reach for all parts of the population. Considering that currently the manner which and to what extent CRISPR applications will be incorporated into the provision of health services, and through which medium this will be facilitated, remains unclear, assessing this dimension is difficult. Regardless, once governments pursue a similar approach, as to that of France, i.e. addressing more practical matters, these questions will become clearer as the answers concerning how to best operationalize CRISPR within national jurisdictions will arguably be highly influenced by the particular attributes of each country. Ideally this should be accompanied by concrete international guidance on how to operationalize the practicalities of human genome modification concerning potential CRISPR uses. However, a matter that should be addressed is that CRISPR kits have recently been marketed online. This provokes thought as to firstly, whether this is an alternative that increases accessibility, and secondly, if this is a form of accessibility that we want to facilitate. For instance, Josiah Zayner, former NASA biochemist and founder of Odin,318 believes that the public should have more access to 315 Ibid; as pointed out by Jacqueline Martin-Laffon et al., the United States not only has been a pioneer in gene editing using CRISPR but is still a leader for improvements of this technical development, with 479 patents compiled in this category. 316 See generally Benston (n40); Teresa B. Burke, ‘Gene Therapy: A Threat to the Deaf Community?’ (Impact Ethics, 2 March 2017) available at: < https://impactethics.ca/2017/03/02/gene-therapy-a-threat-to-the-deaf-community/> accessed 15 June 2020. 317 Doxzen and Halpern (n19), 47. 318 Odin’s webpage reads ‘we believe the future is going to be dominated by genetic engineering and consumer genetic design will be a big part of it. We are making that happen by creating kits and tools that allow anyone to make unique and usable organisms at home or in a lab or anywhere’; The Odin (n233).

Lilian Srour S3127389
42 cutting edge treatments whereby he stated that ‘people are dying’ because the US government refuses people access to such treatment. He is currently under investigation for practicing medicine without a license but nevertheless,319 Odin offered genetic editing supplies online to amateurs. California has introduced the first law to directly regulate CRISPR, whereby it will be prohibited to sell gene therapy kits unless they carry a warning stating that it is not to be used on yourself.320 If one could purchase CRISPR kits online to introduce genetic modifications at home, that would certainly increase accessibility. However, whether and to what extent this form of accessibility is desirable remains questionable, as it also influences other factors such as quality.321 If such kits were to be provided online, questions remain as to who would ensure that those are of a standard that ensures adequate quality and safety of the procedure, and how this shall be done. This aspect must be addressed in future discussions when considering accessibility, and CRISPR overall, by policy-makers and concerned actors. With respect to economic accessibility, CRISPR applications would have to be based on the principle of equity, ensuring that such services are practically affordable for all, regardless of whether they are provided through the public or private sector. To uphold this requirement, national governments will have to primarily determine how to incorporate potential CRISPR applications in the form of a future health service within their health care systems, depending on their approach to the issue.322 The optimal method in which this is to be done will largely depend on the respective countries. Considering that the technology is inexpensive itself, this could contribute to devising affordable treatments. Information accessibility would require the freedom to seek, receive and impart information concerning CRISPR and its potential applications. In light of this, several questions arise. Primarily, would facilitating information accessibility be reached through an obligation on governments to inform their citizens concerning such applications, or would this be achieved through facilitating access to information. If the latter option is considered, how wide-spread is this access, what form shall it take and how will the information be construed so as to ensure sufficient understanding by the lay public. Furthermore, should there be a duty on health practitioners to ensure that you are fully informed concerning potential applications? The author of this thesis is of the opinion that health practitioners should be under the obligation to ensure that patients are fully aware of the procedure, the purposes and the potential outcomes. Furthermore, if eventually CRISPR were to be marketed online, producers and sellers should have duties to provide thorough information as to the specifics of the kits. Perhaps, this can be compared with online sales of pharmaceuticals or other medicinal products which are usually regulated by national law. 323 319 Antonio Regalado, ‘Celebrity biohacker Josiah Zayner is under investigation for practicing medicine without a license’ (MIT Technology Review, 15 May 2019) available at: <https://www.technologyreview.com/2019/05/15/239116/celebrity-biohacker-josiah-zayner-is-under-investigation-for-practicing-medicine-without-a/> accessed 29 May 2020; Tom Ireland ‘I want to help humans genetically modify themselves’ (The Guardian, 24 December 2017) available at: <https://www.theguardian.com/science/2017/dec/24/josiah-zayner-diy-gene-editing-therapy-crispr-interview> accessed 29 May 2020. 320 Regalado (n232). 321 Ibid. 322 See Section 3 Chapter 2 of this paper. 323 See, for example, the Government of Netherlands, ‘Monitoring the quality and safety of medicines’ available at: < https://www.government.nl/topics/medicines/monitoring-the-quality-and-safety-of-medicines> accessed 8 June 2020.

Lilian Srour S3127389
43 3.3. Acceptability In light of acceptability, CRISPR applications must be culturally appropriate, in terms of confidentiality standards and other social determinants (e.g. religion), with the aim of improving the health status of those concerned.324 Therefore, in relation to potential applications of CRISPR, in several countries there is a certain level of opposition in the form of, inter alia, religious opposition. It can be presumed that general public attitudes and concerns can be seen to reflect the level of acceptability of CRISPR applications, and as such will provide a point of reference for discussion. Relating to acceptability and confidentiality standards, the UDHGHR addresses patient privacy rights and first-consent under article 7 but fails to provide guidance on acceptable standards for obtaining consent and protecting confidentiality.325 Furthermore, there are no mechanisms described to respond to such infringements. Similarly, the UDBHR protects privacy and confidentiality under article 9, however concerns have been voiced considering the challenges which accompany issues related to the right to privacy in the context of health data. Stake-holders have suggested that this article requires further elaboration, and mechanisms which are capable of integrating legal norms aimed at securing protection of personal data under international law.326 Under the Oviedo Convention, matters relating to privacy are addressed under article 10 whereby everyone has the right to respect for private life in matters related to health.327 It can be observed that all these provisions aim to secure respect for privacy and confidentiality as required in terms of acceptability. However, as has become clear, the novelty of the biotechnology at hand merits provisions which encompass such features so as to ensure adequate protection of individuals and the upholding of acceptability standards. Relatedly, under the Oviedo Convention acceptability is mentioned in connection with protection of persons undergoing research, whereby research projects must uphold ethically accepted standards.328 Overall, whilst acceptability is addressed in terms of privacy and confidentiality, there is no mention of it relating to culture, gender and life-style requirements, criteria introduced by the CESCR under the AAAQ.329 Considering that acceptability standards are necessary to ensure effective protection of individuals, perhaps the CESCR could provide a revised version of the General Comment addressing the right to health in a manner that better reflects the application of the AAAQ to new technological developments within the realm of healthcare; e.g. human genome modification.330 Human genome modification is a topical matter that has sparked wide-spread debate, including within religious communities. Arguably, the general attitude of the public within a country will influence the regulatory oversight within the borders of a state. These perspectives, as has become clear, are varied whereby some positions pursue more permissive and practical approaches, e.g. the UK and the US, as opposed to those that sanctify all human life, embryos inclusive, e.g. Germany.331 Relatedly, this section seeks to determine whether this influences acceptability. 324 In terms of General Comment 14 para 12(d). 325 UDHGHR (n25), article 7. 326 UNESCO (n154), para 10. 327 Oviedo Convention (n27), article 9. 328 Ibid, article 16. 329 General Comment 14 (n28), para 12 (c). 330 Similar to General 22 that addresses sexual, reproductive and health rights in connection to the AAAQ; General Comment 22 (n29). 331 Kipling (n214), 3.

Lilian Srour S3127389
44 As has become evident from the discussion on availability, the UK appears to be taking progressive steps towards facilitating future CRISPR applications. Furthermore, a survey in the UK revealed that 76% were in favor of correcting genetic diseases in human embryos even if those were heritable changes. 332 Notably, the UK also enjoys the support of the Church of England whereby it has been stated that thus far the attitude to ongoing developments has been positive.333 Generally, it would appear that the future of CRISPR practices are considered widely acceptable, so long as the practices uphold safety and confidentiality requirements. Similarly, in the US polls revealed that 3 in 10 adults were both enthusiastic and worried in relation to prospects of genome modification.334 However, those that were more familiar with gene editing demonstrated to be more inclined to want such applications for their baby. This survey also asked respondents whether the idea of interfering with nature crosses a line that should not be crossed, where 51% stated that such interventions are no different than other methods humans utilize to better themselves and 46% were of the opinion that such meddling does cross the line.335 Conclusively, in the permissive approach it is noticeable that increased information accessibility and wide-spread public discourse have contributed towards acceptability. Whilst initially one would assume that an approach that lies somewhere in-between prohibitionist and permissive would reflect a more balanced sense of acceptability, this is not entirely so. Often those who are against genome modification in embryos believe that it is unnatural and unethical, and that it entails altering a human life without consent. In France, a politically active religious organization has launched a petition that calls for a ban on gene editing and a moratorium on genetic modification.336 Furthermore, the campaign called ‘Stop GMO babies’ aims to hinder scientists from genetically modifying human embryos. 337 A poll in France revealed that more than 65% of respondents were concerned about the acceleration of human genome research with 68% being in favour of international regulation. However, this poll also revealed that 91% of respondents did not know what CRISPR was. 338 Interestingly, even though the legal attitudes of the Netherlands and France are comparable, the public attitude seems to differ. To demonstrate, within the Netherlands, genome modification has been debated for several years in relation applications in humans and in other domains, such as agriculture.339 Numerous articles discussing human genome modification are available, with 332 Vogel (n110). 333 HL Deb (n292), col 1527. 334 Cary Funk et al., ‘U.S public opinion on the future use of gene editing’ (Pew Research Center, 26 July 2016) available at: <https://www.pewresearch.org/science/2016/07/26/u-s-public-opinion-on-the-future-use-of-gene-editing/> accessed 17 May 2020. 335 Ibid. 336 Vogel (n110). 337 Elliot Hosman, ‘French activists protesting ‘GMO babies’ could derail CRISPR on humans debate’ (Genetic Literacy Project, 5 July 2016) available at: <https://geneticliteracyproject.org/2016/07/05/fears-mount-french-activists-protesting-gmo-babies-will-derail-crispr-humans-debate/> accessed 15 May 2020. 338 See generally ‘CRISPR-Cas9: 76% French citizens against genetic modifications of human embryos (Poll) (alliance VITA, 25 May 2016) available at: <https://www.alliancevita.org/en/2016/05/76-french-citizens-against-the-use-of-crispr-cas9-technology-to-perform-in-vitro-modifications-on-human-embryos-poll/> accessed 12 June 2020. 339 For instance, the Netherlands believes new plant breeding techniques should not come under the GMO legislation so long as they are as safe as traditional breeding; Sarantis Michalopoulos, ‘Netherlands wants CRISPR gene-edited crops exempt from Europe’s GMO laws’ (Genetic Literacy Project, 13 September 2017) available at: < https://geneticliteracyproject.org/2017/09/13/netherlands-wants-crispr-gene-edited-crops-exempt-europes-gmo-laws/#:~:text=Netherlands%20wants%20CRISPR%20gene%2Dedited%20crops%20exempt%20from%20Europe's%20GMO%20laws,-

Lilian Srour S3127389
45 the National Institute of Public Health (RIVM) offering information specifically related to CRISPR.340 Furthermore, a survey of the Dutch general public revealed that 85% of participants would use genome modification to cure their own neuromuscular disease and 66% stated that they would undertake germline modification to prevent from passing it on.341 Thus, it can be observed that the overall public attitude remains rather accepting, whereby concerns related to safety, rather than ethics, prevail.342 Therefore, to uphold standards of acceptability, the concerns of the public need to be addressed. In order to integrate effective mechanisms for satisfactory oversight of future CRISPR applications, the protection of individuals and respect for their health must be ensured. Lastly, Germany has supported public dialogue about gene editing and has organized several meetings to discuss the ethical, safety and regulatory concerns surrounding CRISPR.343 A Report in 2019 discussed the German position on human genome modification overall, but particularly germline applications.344 Many members of the ethics council that released this report were concerned about whether developing genome modification applications carries more downsides than benefits.345 Ultimately, however, the members agreed that the human germline is not inviolable, and that they are of the position that germline modifications are not ethically out of the question.346 Thus, whilst disparities remain within the current legislation, it would appear that the overall discussion is moving towards a direction where human genome applications are not solely discussed in the ethical context, but also in terms of benefits and risks and the acceptability of those. Germany’s overall hesitant and rather prohibitionist legal approach towards genome modification, and more particularly germline applications, can, arguably, be traced back to eugenic practices in WWII. Nevertheless, it can be observed Germany is engaging in public discourse in an attempt to identify concerns which affect acceptability towards potential CRISPR practices. Similar to France, those concerns need to be sufficiently addressed so as to incorporate effective oversight that ensures the safeguarding of individuals and their rights. 3.4. Quality When it comes to quality, future CRISPR practices must be scientifically and medically appropriate, and of a good quality. Furthermore, it would imply that healthcare personnel are skilled and trained accordingly, and that medicine and health equipment is scientifically approved. In this regard, it should be acknowledged that CRISPR applications are not entirely Sarantis%20Michalopoulos%20%7C%20EurActiv&text=The%20Netherlands%20believes%20the%20new,as%20safe%20as%20traditional%20breeding.> accessed 10 June 2020. 340 RIVM, ‘CRISPR-technologie’ available at: <https://biotechnologie.rivm.nl/CRISPR-Cas> accessed 10 June 2020. 341 Saskia Hendriks et al., ‘Reasons for being in favour of or against genome modification: a survey of the Dutch general public’ [2018] 3 Human Reproduction Open <https://academic.oup.com/hropen/article/2018/3/hoy008/4996571> accessed 17 May 2020. 342 For instance, Annelien Bredenoord has been said to be amongst the most significant public educators on CRISPR, and has stated that germline interventions could potentially be feasible as soon as the safety of the procedure is well established; Lotte Scholten, ‘Dutch Designer Babies. The Dutch public debate from pre-war eugenics to present-day biotechnology’ (MPhil thesis, Utrecht University, 2019), 60. 343 Vogel (n110). 344 ‘Ethics Council: germline interventions currently too risky, but not ethically out of the question’ (Deutscher Ethikrat, March 2019) available at: <https://www.ethikrat.org/en/press-releases/2019/ethics-council-germline-interventions-currently-too-risky-but-not-ethically-out-of-the-question/> accessed 3 June 2020. 345 Siobhan Dunphy, ‘German Ethics Council: Germline editing ‘not ethically out of question’’ (European Scientist, 15 May 2019) available at: <https://www.europeanscientist.com/en/public-health/germline-editing-not-ethically-out-of-the-question/> accessed 14 May 2020. 346 Ibid.

Lilian Srour S3127389
46 risk free. There is a chance of mosaicism in embryos, and the possibility of ‘off-target’ edits.347 To ensure that the quality requirement is respected, ideally the regulatory landscape surrounding CRISPR would have to keep such concerns in mind when assessing whether the applications are appropriate and of good quality. The science is still in its early stages, hence why applications are discussed in the context of future therapeutic practices. For now, it is important to differentiate between using CRISPR in research and in future therapeutic applications. Primarily, research holds the key to understanding the benefits and risks of such interventions for health and disease and should be pursued to support the further development and justification for implementing these practices. Arguably, the more extensive the research, the higher the likelihood that the quality of applications will be more appropriate. Following this rationale, this section seeks to determine whether the discussed instruments address aspects of quality, and if the legal approaches identified amongst countries stand to impact the quality of future CRISPR practices. Amongst the instruments surveyed, the UDBHR and the Oviedo Convention address aspects of quality in terms of ‘ensuring access to quality healthcare’,348 and guaranteeing that ‘healthcare is of an appropriate quality’.349 Furthermore, under articles 8 UDHGHR and 24 Oviedo Convention, individuals have the right to reparation of damages arising due to, inter alia, genome modification applications.350 Thus, quality is addressed to a certain extent, and one could argue that the right to reparation would suggest that future CRISPR applications have to be of an adequate quality so as to ensure that individuals are not harmed or damaged in any sense. Restrictions on research in permissive countries, e.g. UK, are rather limited and allow, among others, for research to be performed on viable human embryos.351 Arguably, this enables scientists to pursue more extensive research, compared to countries with more limitations in place, e.g. Germany. The manner in which this affects quality is not clear yet. However, as noted previously, such restrictions can interfere with research resulting in stagnation in terms of further developments in countries that pursue a prohibitionist attitude; i.e. in comparison to the US. Nevertheless, the approach in the US is not ideal as, in the view of the author of this paper, the ongoing race for patents could presumably threaten the quality of future CRISPR-related services.352 In the event of the dissemination of patents solely for commercial purposes, this may result in the incentive for profit prevailing over upholding sufficient quality standards. It should be noted that in relation to research and the sharing of scientific advances, whilst addressed within the previously discussed instruments,353 this may not be respected if there are dominant commercial purposes that motivate the development and up-take of such biotechnologies. This is largely so because research would be encouraged and imparted for 347 See generally Xiao-Hui Zang et al., ‘Off-target Effects in CRISPR/Cas9-mediated Genome Engineering’ [2015] 4 Molecular Therapy Nucleic Acids <https://www.sciencedirect.com/science/article/pii/S216225311630049X> accessed 12 June 2020. 348 UDBHR (n26), articles 14,15. 349 Oviedo Convention (n27), article 3. 350 UDHGHR (n25), article 8; Oviedo Convention (n27), article 24. 351 See section 3.1.1. Chapter 2. 352 The US is awarding patents both within the US and Europe; see generally ‘Eleventh U.S CRIPR-Cas9 Patent Awarded to University of California, U.Vienna, Charpentier’ (Genetic Engineering and Biotechnology News, 23 August 2019) available at: < https://www.genengnews.com/news/eleventh-u-s-crispr-cas9-patent-awarded-to-university-of-california-u-vienna-charpentier/> accessed 10 June 2020; Public Affairs UC Berkley, ‘UC now holds largest CRISPR-Cas9 patent potfolio’ (Berkeley News, 1 October 2019) available at: < https://news.berkeley.edu/2019/10/01/uc-now-holds-largest-crispr-cas9-patent-portfolio/> accessed 10 June 2020. 353 UDHGHR (n25), article 18; UDBHR (n26), article 15.

Lilian Srour S3127389
47 motivations that may not take due regard of potential patients or applications. Furthermore, it is highly likely that there would be discrepancies in quality standards amongst different countries, which may encourage health tourism. This phenomenon, whilst not arising due to patents, has already been a topic of debate in relation to plastic surgery, whereby several efforts have attempted to establish the relationship between quality and health tourism in the realm of cosmetic surgery.354 In light of this, to ensure quality standards are upheld, safe-guarding measures aimed at encouraging financial incentives for investment in biotechnologies, e.g. CRISPR, must be put in place. However, it is not for the author of the present paper to determine what measures would fit best into each model (i.e. prohibitionist, permissive or middle-ground) as such endeavors would also be dependent on the national specifics of each country.
354 See generally, Lauren Franzblau et al., ‘Impact of Medical Tourism on Cosmetic Surgery in the United States’ [2013] 1(7) Plastic and Reconstructive Surgery – Global Open 63.

Lilian Srour S3127389
48 Concluding Remarks The enthusiasm for applications of the CRISPR platform for genome editing is pervasive. Furthermore, emerging science and technologies, e.g. human genome modification and CRISPR, could offer new solutions to health concerns. Therefore, it is, not entirely, far-fetched to say that we are embarking on a new era in the history of life on earth, whereby we have unprecedented abilities for the control over the genetic build of living beings that inhabit this planet, humans included.355 The first Chapter aimed to provide context by discussing the scientific and social dimension of the subject matter at hand, namely the future of CRISPR applications in relation to human genome modification. Moreover, highly beneficial therapeutic purposes were discussed, emphasizing that applications in this domain stand to affect healthcare significantly. Further on, the second Chapter addressed the legal dimensions of the matter, whereby several authoritative international instruments, of binding and non-binding nature, were discussed in an attempt to discern whether the current legal framework upholds the requirements enshrined within the AAAQ, which are intended to secure and protect the right to health of individuals. Considering that disparities remain within national jurisdictions, discussing internal laws was considered useful for providing a point of reference when determining whether the current legal framework adequately addresses human genome modification, more particularly CRISPR, in a manner that upholds human rights standards. Finally, the last Chapter sought to contribute to the important ongoing debate we are having by viewing human genome modification, particularly CRISPR, in light of the right to health and the AAAQ. The right to health perspective offers the advantage of commencing debate in a forum that anchors efforts to address potential CRISPR applications in a realistic and practical matter, as opposed to focusing on a search for consensus or exploring the ethical boundaries of future applications. Overall, whilst highly under-discussed, the AAAQ provided a relatively useful illustration of the concerns that need to be better defined and addressed by the current international human rights framework. In this vein, this author is of the opinion that perhaps an elaboration on the practical implementation of the AAAQ in relation to biotechnology could be explored in a future General Comment of the CESCR, as was done in relation to sexual and reproductive health rights.356 Thus, the current human rights framework has a high potential to address emerging issues as a consequence of the use of biotechnologies. However, there is still a stringent need for guidance when it comes to upholding the right to health in this context. In light of CESCR’s role in interpreting the provisions of the Covenant, the applications of scientific discoveries in the field of biomedicine, e.g. CRISPR, shall be clarified and incorporated within the ambit of article 12. This could provide a stepping stone for the formulation of an adequate regulatory framework for biotechnologies, CRISPR included. 355 Martin Stanley, ‘CRISPR and Gene Editing’ (Understanding Regulation) available at: <https://www.regulation.org.uk/specifics-gene_editing.html> accessed 15 June 2020. 356 General Comment 22 (n29).

Lilian Srour S3127389
49 Bibliography I. International Documents a. Treaties Constitution of the United Nations Educational, Scientific and Cultural Organization (signed on 16 November 1945, entered into force 4 November 1946) <http://portal.unesco.org/en/ev.php URL_ID=15244&URL_DO=DO_TOPIC&URL_SECTION=201.html > accessed 15 June 2020 Convention on the Rights of the Child (adopted 20 November 1989, entered into force 2 September 1990) 1577 UNTS 3 International Covenant on Civil and Political Rights (adopted 16 December 1966, entered into force 23 March 1976) 999 UNTS 171 International Covenant on Economic, Social and Cultural Rights (adopted 16 December 1966, entered into force 3 January 1976) 993 UNTS 3 UN Optional Protocol to the International Covenant on Civil and Political Rights (adopted 16 November 1966, entered into force 23 March 1976) 999 UNTS 171 b. Declarations Council for International Organizations of Medical Sciences (CIOMS), The Declaration of Inuyama on Genetic Testing and Screening, Gene Therapy (adopted 1990) available at: < https://www.who.int/genomics/elsi/regulatory_data/region/international/032/en/> accessed 15 June 2020 UNESCO, Universal Declaration on Bioethics and Human Rights (adopted 19 October 2005, published 2006) SHS/EST/BIO/06/1 UNESCO, Universal Declaration on the Human Genome and Human Rights (adopted 11 November 1997) Universal Declaration on Human Rights (adopted 10 December 1948) UNGA Res 217 A(III) Vienna Declaration and Programme of Action (adopted on 25 June 1993) A/CONF.157/23 World Medical Association, Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects (adopted June 1964) as amended by the WMA General Assembly in 2013 (Helsinki Declaration), available at: < https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/> accessed 26 May 2020 c. General Comments UN CESCR, General comment No. 22 (2016) on the right to sexual and reproductive health (2 May 2016) E/C.12/GC/22 UN CESCR, General Comment No.14: The Right to the Highest Attainable Standard of Health (11 August 2000) E/C.12/2000/4 UN CESCR, General Comment No.3: The Nature of States Parties Obligations (Art.2, Para.1, of the Covenant (14 December 1990) E/1991/23 (General Comment 3) d. Resolutions

Lilian Srour S3127389
50 UN General Assembly, Resolution 59(I): Calling of an International Conference on Freedom of Information (adopted 14 December 1946) UN Doc A/RES/59(I) UN Commission on Human Rights, Resolution 1989/11 on Non-discrimination in the field of health (adopted 2 March 1989) UN Doc E/CN.4/RES/1989/11 e. UNESCO Documents Report on the forty-ninth Session of the Commission on Human Rights (26 April 2001) E/CN.4/1993/122 Statutes of the International Bioethics Committee of UNESCO (IBC) (2005) SHS.2005/WS/4 REV, available at: < https://unesdoc.unesco.org/ark:/48223/pf0000138292> accessed 24 May 2020 UNESCO and IBC, ‘Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights’ (2 October 2015) SHS/YES/IBC-22/15/2 REV.2, 7.) UNESCO, ‘Summary of the Responses on Possible Work Topics for 2020-2023 of the International Bioethics Committee of UNESCO (IBC) and the World Commission on the Ethics of Scientific Knowledge and Technology of UNESCO (COMEST)’ (11 June 2019) SHS/BIO/IGBC-11/19/2 REV. UNESCO, Records of the General Conference, 32nd session, Paris, 29 September to 17 October 2003, v. 1: Resolutions (2004) 32 C/Resolutions, available at: < https://unesdoc.unesco.org/ark:/48223/pf0000133171> accessed 24 May 2020 f. UN Documents Special Rapporteur on Persons with Disabilities in one of her latest reports (17 December 2019) UN Doc A/HRC/43/41, para 22, available at: <https://undocs.org/en/A/HRC/43/41?fbclid=IwAR3cmsfm_sOe0TsKCb0N2VJb44Ze3LGPiz3BXtha2A6m7wIAYaM5RO8Wdpg> accessed 10 June 2020 II. Regional a. Treaties African Charter on Human and Peoples' Rights (adopted on 01 June 1981, entered into force 21 October 1986) OAU CAB/LEG/67/3 rev. 5 Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (1999) ETS 164 Convention for the Protection of Human Rights and Fundamental Freedoms (European Convention on Human Rights, as amended) ETS No.005 (Opened for signature 1950, entered into force 1953) b. Directives European Parliament and Council Directive 2001/18/EC of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC [2001] OJ L106/01. c. Resolutions

Lilian Srour S3127389
51 Parliamentary Assembly of the Council of Europe, Resolution 1512 (2001) on the Protection of the Human Genome by the Council of Europe, available at: < https://assembly.coe.int/nw/xml/XRef/Xref-XML2HTML-en.asp?fileid=16897&lang=en> accessed 14 June 2020 Parliamentary Assembly of the Council of Europe, Resolution 934 (1982) on Genetic Engineering, available at: < https://assembly.coe.int/nw/xml/XRef/Xref-XML2HTML-en.asp?fileid=14968&lang=en> accessed 15 June 2020 III. National Documents FDA, ‘Information About Self-Administration of Gene Therapy’ (FDA, 2017), available at:< https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/information-about-self-administration-gene-therapy> accessed 26 May 2020 French Parliament, Law no. 2013-715 of August 6, 2013 amending Law no. 2011-814 of July 7, 2011 relating to bioethics by authorizing under certain conditions research on the embryo and embryonic stem cells (1 August 2013), available at: <https://www.legifrance.gouv.fr/affichTexte.do;jsessionid=8DE166F34A25D1129E06625D904FE6B8.tpdjo14v_2?cidTexte=JORFTEXT000027811435&categorieLien=id&fbclid=IwAR1khZrzol5ygkMj4tmzGYaKT7wdRQTGRebXEUIl_4OtEOdJORdehFQaOfk> accessed 26 May 2020 German Federal Ministry of Justice and Consumer Protection, Embryo Protection Act (13 December 1990), available at: <http://www.gesetze-im-internet.de/eschg/BJNR027460990.html?fbclid=IwAR2Lyz-SFH5Ve-hGxvuVv-oKRpZ32ReFsjhFErurn5_nY9oJ0mEPFI5Lxg0> accessed 26 May 2020 Italian Parliament, Law No.40/2004 Rules on Medically Assisted Procreation (19 February 2004), available at: <https://www.ieb-eib.org/ancien-site/pdf/loi-pma-italie-english.pdf?fbclid=IwAR0brK4LJNiKEHR831uHI51CgwlXQVXR1kzoep_vn4hheZgAHTmmIIOGfNw> accessed 26 May 2020 Parliament of the United Kingdom, Human Fertilisation and Embryology Act (1 November 1990) as amended by HFEA Act 2008, available at: <http://www.legislation.gov.uk/ukpga/2008/22/contents?fbclid=IwAR2wUDaYn_JSmAs5H-mn4MRQH2358ugGL2anzTtR67qruu-EL4mltaXY4XA> accessed 3 June 2020 Parliament of the United Kingdom, The Human Fertilisation and Embryology (Mitochondrial Donation) Regulation (entered into force 25 October 2015), available at: <https://www.legislation.gov.uk/ukdsi/2015/9780111125816> accessed 26 May 2020 The Dutch Council of State, Embryo Act (20 June 2002), available at: <https://wetten.overheid.nl/BWBR0013797/2013-09-27> accessed 26 May 2020 US Congress, Dickey-Wicker Amendment Bill to the Balanced Budget Act I, Public Law no 104-99, Stat.26, p.110 (26 January 1996), available at: <https://www.congress.gov/bill/104th-congress/house-bill/2880/text?overview=closed&fbclid=IwAR1nqbW-fMgab40fVtaFMfj5yUy8E0rRd2_iOcdt8SrikAghHEGBseEHJ7I> accessed 26 May 2020 US Food and Drug Administration, Code of Federal Regulations, Title 21(5) Food and Drug Administration Department of Health and Human Services (D) Drugs for Human Use (1 April 2019), available at:

Lilian Srour S3127389
52 <https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.2> accessed 26 May 2020 US Food and Drug Administration, Code of Federal Regulations, Title 21(7) Food and Drug Administration Department of Health and Human Services (F) Biologics (1 April 2019), available at: < https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=600&showFR=1> accessed 26 May 2020 IV. Books and Contributions Cesare P. R. Romano et al., ‘The Governance of Human (Germline) Genome Modification at the International and Transnational Level, Chapter 2 in Andrea Boggio, Cesare P. R. Romano, Jessica Almqvist (eds), Human Germline Genome Modification and the Right to Science: A Comparative Study of National Laws and Policies (Cambridge University Press 2019) Jessica Almqvist et al., ‘The Regulation of Human Germline Genome Modification in Europe’ Chapter 6 in Andrea Boggio, Cesare P. R. Romano, Jessica Almqvist (eds) Human Germline Genome Modification and the Right to Science (Cambridge University Press, 2019) Krishnarao Appasani, Genome Editing and Engineering: From TALENs, ZFNs and CRISPRs to Molecular Surgery (CUP, 2018) Manisuli Ssenyonjo, Economic, Social and Cultural Rights in International Law (1st edn, Hart Publishing, 2009) Marlies Hesselman et al., ‘International guideposts for essential public services provision and socio-economic human rights’ Chapter 16 in Marlies Hesselman et al. (eds), Socio-Economic Human Rights in Essential Public Services Provision (Routledge, 2017) Matthijs Gert and Borry Pascal, The Human Recipe: Understanding Your Genes in Today’s Society (Leuven University Press 2016) Minjung Song et al., Genome Engineering in Human Cells Chapter 5 in Jennifer Doudna et al., (eds) The Use of CRISPR/Cas9, ZFNs, and TALENs in Generating Site-Specific Genome Alterations (Elsevier/Academic Press, 2014) Sabine Klotz et al. (eds), Healthcare as a Human Rights Issue (4th Volume, Transcript 2017) Soren H Hough et al, 'The Future of CRISPR Applications in the Lab, the Clinic and Society' in Stephan H Tsang, Precision Medicine, CRISPR and Genome Editing (Springer International Publishing, 2017) Stephan Rixen, Genome Editing and the Law. in Matthias Braun, Hannah Schickl, Peter Dabrock (eds), Between Moral Hazard and Legal Uncertainty (Springer 2018) Stephane Pelletier, Genome Editing with Targetable Nucleases, in Kursad Turksen (ed), Genome Editing (Springer International Publishing 2016) V. Journal Articles Alicia E. Yamin, 'The Right to Health Under International Law and Its Relevance to the United States' [2005] 95(7) American Journal of Public Health 1156

Lilian Srour S3127389
53 Alonso Rodriguez-Navarro and Francis Narin, ‘European Paradox or Delusion – Are European Science and Economy Outdated?’ [2018] 45(1) Science and Public Policy 14 Andrea Boggio et al., ‘The Human Right to Science and the Regulation of Human Germline Engineering’ [2019] 2(3) The CRISPR Journal 134 Dianne Nicol et al., ‘Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic’ [2017] 9 Genome Medicine 85, available at: <https://genomemedicine.biomedcentral.com/track/pdf/10.1186/s13073-017-0475-4> accessed 12 June 2020 Elizabeth Fention and John D. Arras, ‘Bioethics and Human Rights: Curb Your Enthusiasm’ [2010] 19(1) Cambridge Quarterly of Healthcare Ethics 127 Elizabeth Fenton, ‘Genetic enhancement – a threat to human rights’ [2008] 22(1) Bioethics 1 Eva Šlesingerová, 'In Risk We Trust/Editing Embryos and Mirroring Future Risks and Uncertainties' [2019] 22(2) Medicine, Healthcare and Philosophy 191 Gholamreza Farnoosh et al., 'CRISPR Genome Editing and its Medical Applications' [2018] 32(2) Biotechnology & Biotechnological Equipment 286 Guido De wert et al., 'Responsible Innovation in Human Germline Gene Editing: Background Document to the Recommendations of ESHG and ESHRE' [2018] 26(4) European Journal of Human Genetics 450-470 Gustavo Rosa Gameiro et al., ‘Precision Medicine: Changing the way we think about healthcare’ [2018] 73 Clinics < https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251254/> accessed 12 May 2020 Heidi C. Howard et al., 'One small edit for humans, one giant edit for humankind? Points and questions to consider for a responsible way forward for gene editing in humans' [2018] 26(1) European Journal of Human Genetics 1 Hongyi Li et al., ‘Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects’ [2020] 5 Signal Transduction and Targeted Therapy 1, <https://www.nature.com/articles/s41392-019-0089-y#citeas> accessed 12 June 2020 Iñigo De Miguel Beriain et al., 'Human germline editing is not prohibited by the Oviedo Convention: An argument' [2019] 19(2-3) Medical Law International 226 Jack McCain, 'The Future of Gene Therapy' [2005] 2(3) Biotechnology Healthcare 52 Jacqueline Martin-Laffon et al., ‘Worldwide CRISPR patent landscape shows strong geographical biases’ [2019] 37(6) Nature Biotechnology <https://www-nature-com.proxy-ub.rug.nl/articles/s41587-019-0138-7> accessed 15 June 2020 John P. Ryan and Benjamin Hron, ‘The Evolution of Human Rights in the Age of Biotechnology’ [1999] 63(5) Social Education 303, available at: <http://www.socialstudies.org/sites/default/files/publications/se/6305/630505.html> accessed 15 June 2020 Karim Benabdellah, ‘Genome-edited adult stem cells: Next generation advanced medicinal products’ [2020] 9(6) Stem Cells Translational Medicine 674

Lilian Srour S3127389
54 Kathryn A. Phillips et al., ‘Genetic Test Availability and Spending: Where Are We Now? Where Are We Going?’ [2018] 37(5) Health Affairs 710 <https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2017.1427?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=hlthaff> accessed 10 June 2020 Kevin Doxzen and Jodi Halpern, 'Focusing on Human Rights: a framework for CRISPR germline genome editing ethics and regulation' [2020] 63(1) Perspectives in Biology and Medicine 44 Lauren Franzblau et al., ‘Impact of Medical Tourism on Cosmetic Surgery in the United States’ [2013] 1(7) Plastic and Reconstructive Surgery – Global Open 63 Lisa Forman et al., ‘What Do Core Obligations Under the Right to Health Bring to Universal Health Coverage?’ (Health and Human Rights Journal, 5 December 2016) < https://www.hhrjournal.org/2016/12/what-do-core-obligations-under-the-right-to-health-bring-to-universal-health-coverage/#_edn30> accessed 15 June 2020 Lu Xiao-Jie et al., ‘CRISPR-Cas9: a new and promising player in gene therapy’ [2015] 52(5) Journal of Medical Genetics 289 Masayuki Fujii et al., ‘Modeling Human Digestive Diseases with CRISPR-Cas9-Modified Organoids’ [2019] Gastroenterology 562 < https://www.gastrojournal.org/article/S0016-5085(18)35296-X/pdf> accessed 15 June 2020 Michael Morrison and Stevienna de Saille, ‘CRISPR in context: towards a socially responsible debate on embryo editing’ [2019] 5 Palgrave Communications 110, < https://www.nature.com/articles/s41599-019-0319-5> accessed 16 June 2020 Miller Kathleen and Kohm Lynne Marie, 'Designer Babies: Are Test Tubes and Microbes Replacing Romance? Relevant Legal Issues and DNA' [1996] 17(4) The American Journal of Forensic Medicine and Pathology 305 Paul Hunt, ‘Interpreting the International Right to Health in a Human Rights-Based Approach to Health’ (Health and Human Rights Journal, 3 December 2016) < https://www.hhrjournal.org/2016/12/interpreting-the-international-right-to-health-in-a-human-rights-based-approach-to-health/> accessed 15 June 2020 Renjie Jiao et al., ‘The CRISPR/Cas9 Genome Editing Revolution’ [2016] 34(5) Journal of Genetics and Genomics 227 Rodolphe Barrangou, 'Foresight is 2020: Ten Bold Predictions for the New CRISPR Year' [2019] 2(6) The CRISPR Journal 341 Sarah Chan and Maria Medina-Arellano, ‘Genome editing and international [2016] regulatory challenges: Lessons learned from Mexico’ [2016] 2(3) Ethics, Medicine and Public Health 426 Saskia Hendriks et al., ‘Reasons for being in favour of or against genome modification: a survey of the Dutch general public’ [2018] 3 Human Reproduction Open <https://academic.oup.com/hropen/article/2018/3/hoy008/4996571> accessed 17 May 2020 Shawn H. E. Harmon, 'The Significance of UNESCO’s Universal Declaration on the Human Genome & Human Rights' [2005] 2(1) SCRIPTed 20 Shawna Benston, ‘CRISPR, a Crossroads in Genetic Intervention: Pitting the Right to Health against the Right to Disability’ [2016] 5(1) Laws <https://www.mdpi.com/2075-471X/5/1/5> accessed 1 May 2020

Lilian Srour S3127389
55 Stephan Guttinger, 'Trust in Science: CRISPR-Cas9 and the Ban on Human Germline Editing' [2018] 24(4) Science and Engineering Ethics 1077 Stephen P. Marks, 'Tying Prometheus Down: The International Law of Human Genetic Manipulation' [2002] 3(1) Chicago Journal of International Law 115 Tian Wang et al., 'CRISPR technology is revolutionizing the improvement of tomato and other fruit crops' [2019] 6(77) Horticulture Research <https://www.nature.com/articles/s41438-019-0159-x> accessed 16 June 2020 Vera L. Raposo, 'CRISPR-Cas9 and the Promise of a Better Future' [2019] 26(4) European Journal of Health Law 308-329 Vera L. Raposo, ‘The Convention of Human Rights and Biomedicine revisited: Critical Assessment’ [2016] 20(8) The International Journal of Human Rights 1277 Xiao-Hui Zang et al., ‘Off-target Effects in CRISPR/Cas9-mediated Genome Engineering’ [2015] 4 Molecular Therapy Nucleic Acids <https://www.sciencedirect.com/science/article/pii/S216225311630049X> accessed 12 June 2020 VI. Discussion Papers/Reports ‘Ethics Council: germline interventions currently too risky, but not ethically out of the question’ (Deutscher Ethikrat, March 2019) available at: <https://www.ethikrat.org/en/press-releases/2019/ethics-council-germline-interventions-currently-too-risky-but-not-ethically-out-of-the-question/> accessed 3 June 2020 Arthur Caplan and Peter Sykora, ‘The Council of Europe Should Not Reaffirm the Ban on Germline Genome Editing in Humans’ (EMBO Rep, 2017), available at: < https://www.embopress.org/doi/abs/10.15252/embr.201745246> accessed 25 May 2020 COGEM, ‘Editing Human DNA. Moral and social implications of germline genetic modification’ (2017) CGM/170328-01, available at: < https://cogem.net/en/publication/editing-human-dna-moral-and-social-implications-of-germline-genetic-modification-2/> accessed 25 May 2020 Committee on Bioethics (DH-BIO), ‘Statement on genome editing technologies’ (2015), available at: < https://www.coe.int/en/web/bioethics/emerging-technologies/-/asset_publisher/O6iBP5ISnOh1/content/gene-editing?_101_INSTANCE_O6iBP5ISnOh1_viewMode=view/> accessed 25 May 2020 Emannuelle Tuerlings, ‘Background Paper Governance Human Genome Editing’ (WHO, 2019), available at: < http://origin.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Governance-1-paper-March-19.pdf> accessed 25 May 2020 FEAM, ‘Human Genome Editing in the EU’ (2017), available at: <https://www.interacademies.org/publication/feam-human-genome-editing-eu> accessed 25 May 2020 Françoise Baylis and Lisa Ikemoto, ‘The Council of Europe and the Prohibition on Human Germline Genome Editing’ (EMBO Rep, 2017), available at: <https://www.embopress.org/doi/full/10.15252/embr.201745343> accessed 25 May 2020

Lilian Srour S3127389
56 Friedrich Soltau, ‘CRISPR/Cas9 – gene editing technology takes off’, brief for GSDR (2016) available at: <https://sustainabledevelopment.un.org/content/documents/955511_Soltau_CRISPR-Cas9%20_%20gene-editing%20technology%20takes%20off.pdf> accessed 5 May 2020 Iñigo De Miguel Beriain, ‘Human dignity and gene editing’ (EMBO Reports, 21 September 2018) < https://www.embopress.org/doi/10.15252/embr.201846789> accessed 14 May 2020 Inserm, ‘Fostering Global Responsible Research with CRISPR-Cas9’ (2016), available at: < https://www.inserm.fr/en/research-inserm/ethics/inserm-ethics-committee-cei/ethics-committee-workshops/fostering-global-responsible-research-with-crispr-cas9> accessed 25 May 2020 Inter-Parliamentary Union and the UN Office of High Commissioner for Human Rights, ‘Human Rights. Handbook for Parliamentarians No.26’ (2016) available at: <https://www.ohchr.org/Documents/Publications/HandbookParliamentarians.pdf> accessed 13 June 2020 Jeff Kipling, ‘The European Landscape for Human Genome Editing’ (26 April 2016, FEAM) available at: < https://acmedsci.ac.uk/file-download/41517-573f212e2b52a.pdf> accessed 15 June 2020 Lena Kähler et al., ‘AAAQ & Sexual and Reproductive Health and Rights’ (The Danish Institute for Human Rights, 2017) <https://www.humanrights.dk/sites/humanrights.dk/files/media/dokumenter/udgivelser/aaaq/aaaq-srhr_issue_paper_dihr_2017_english.pdf> accessed 12 May 2020 Leopoldina, ‘Chancen und Grenzen des genome editing’ (2015), available at: < https://www.leopoldina.org/publikationen/detailansicht/publication/chancen-und-grenzen-des-genome-editing-2015/> accessed 25 May 2020 Mads H. Jensen et al., ‘The AAAQ Framework and the Right to Water – international indicators’ (The Danish Institute for Human Rights, 2014) < https://www.humanrights.dk/sites/humanrights.dk/files/media/dokumenter/udgivelser/aaaq/aaaq_international_indicators_2014.pdf> accessed 10 May 2020 Max Planck Gesellschaft, ‘Discussion paper focusing on the scientific relevance of genome editing and on the ethical, legal and societal issues potentially involved’ (2019) Ethics Council of Max Planck Gesellschaft, <https://www.mpg.de/13811476/DP-Genome-Editing-EN-Web.pdf> accessed 15 June 2020 Nishith Desi Associates, ‘Are we ready for Designer Babies?’ (2019) Nishith Desai Associates, available at: <http://www.nishithdesai.com/fileadmin/user_upload/pdfs/Research_Papers/Designer_Babies.pdf> accessed 15 June 2020 Nuffield Council on Bioethics, ‘Genome Editing and Human Reproduction: Social and Ethical Issues’ (Nuffield Council on Bioethics 2018) 114, available at: <https://www.nuffieldbioethics.org/publications/genome-editing-and-human-reproduction> accessed 23 May 2020 Nuffield Council on Bioethics, ‘Genome editing: an ethical review’ (2016), available at: < https://www.nuffieldbioethics.org/publications/genome-editing-an-ethical-review> accessed 15 June 2020 Rumiana Yotova ,‘The Regulation of Genome Editing and Human Reproduction Under International Law, EU Law and Comparative Law’ (Nuffield Council on Bioethics, June 2017) <

Lilian Srour S3127389
57 https://nuffieldbioethics.org/wp-content/uploads/Report-regulation-GEHR-for-web.pdf> accessed 10 June 2020 The National Academies of Sciences, Engineering, Medicine (NASEM), ‘Human Genome Editing: Science, Ethics and Governance’ (2017), available at:<https://www.nationalacademies.org/our-work/human-gene-editing-scientific-medical-and-ethical-considerations> accessed 25 May 2020 The National Academies of Sciences, Engineering, Medicine, ‘Human Genome Editing: Science, Ethics and Governance’ (2017), available at:<https://www.nationalacademies.org/our-work/human-gene-editing-scientific-medical-and-ethical-considerations> accessed 25 May 2020 WHO, ‘Information Resources on Human Genome Editing, available at: < https://www.who.int/ethics/topics/human-genome-editing/resources/en/> accessed 1 May 2020 VII. Websites Asian Scientist Newsroom, ‘Merck Granted CRISPR Patent in Singapore’ (Asian Scientist, 22 December 2017) available at: <https://www.asianscientist.com/2017/12/pharma/merck-singapore-crispr-patent/> accessed 18 May 2020 ‘2003: Human Genome Project Completed’ (National Human Genome Research Institute, last updated 25 November 2014), available at:< https://www.genome.gov/25520492/online-education-kit-2003-human-genome-project-completed> accessed 16 June 2020 ‘Chart of Signatures and ratifications of Treaty 164’ (Council of Europe, 15 June 2020) available at: <https://www.coe.int/en/web/conventions/full-list/-/conventions/treaty/164/signatures> accessed 15 June 2020 ‘CRISPR-Cas9: 76% French citizens against genetic modifications of human embryos (Poll) (alliance VITA, 25 May 2016) available at: <https://www.alliancevita.org/en/2016/05/76-french-citizens-against-the-use-of-crispr-cas9-technology-to-perform-in-vitro-modifications-on-human-embryos-poll/> accessed 12 June 2020 ‘Eleventh U.S CRIPR-Cas9 Patent Awarded to University of California, U.Vienna, Charpentier’ (Genetic Engineering and Biotechnology News, 23 August 2019) available at: < https://www.genengnews.com/news/eleventh-u-s-crispr-cas9-patent-awarded-to-university-of-california-u-vienna-charpentier/> accessed 10 June 2020 ‘ERC grants to researchers from the Italian Institute of Technology (Research Italy, 21 December 2016) available at: <https://www.researchitaly.it/en/success-stories/erc-grants-to-researchers-from-the-italian-institute-of-technology/ accessed 19 May 2020 ‘IVF regulation: ensuring safe and ethical treatment’ (Human Fertilisation and Embryology Authority, 20 December 2018) available at: < https://www.hfea.gov.uk/about-us/news-and-press-releases/2018-news-and-press-releases/ivf-regulation-ensuring-safe-and-ethical-treatment/> accessed 3 May 2020 ‘Statement by the Organising Committee of the Second International Summit on Human Genome Editing’ (The National Academies of Sciences, Engineering, Medicine, 28 November 2018) < https://www.nationalacademies.org/news/2018/11/statement-by-the-organizing-committee-of-the-second-international-summit-on-human-genome-editing> accessed 15 June 2020 ‘WHO launches global registry on human genome editing’, (WHO, 28 August 2019) available at: <https://www.who.int/news-room/detail/29-08-2019-who-launches-global-registry-on-human-genome-editing> accessed 12 May 2020

Lilian Srour S3127389
58 Angela Chen, ‘If someone wants to create gene edited babies, who would stop them?’ (The Verge, 26 November 2018), available at: < https://www.theverge.com/2018/11/26/18112970/crispr-china-babies-embryos-genetic-engineering-bioethics-policy> accessed 16 June 2020 Antonio Regalado, ‘Celebrity biohacker Josiah Zayner is under investigation for practicing medicine without a license’ (MIT Technology Review, 15 May 2019) available at: <https://www.technologyreview.com/2019/05/15/239116/celebrity-biohacker-josiah-zayner-is-under-investigation-for-practicing-medicine-without-a/> accessed 29 May 2020 Antonio Regalado, ‘Don’t Change your DNA at home, says America’s first CRISPR law’ (MIT Technology Review, 9 August 2019) available at: <https://www.technologyreview.com/2019/08/09/65433/dont-change-your-dna-at-home-says-americas-first-crispr-law/> accessed 15 June 2020 Bermingham Nessan et al., 'Realizing the potential of CRISPR' (McKinsey & Company, January 2017) <https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/realizing-the-potential-of-crispr> accessed 5 May 2020 Cary Funk et al., ‘U.S public opinion on the future use of gene editing’ (Pew Research Center, 26 July 2016) available at: <https://www.pewresearch.org/science/2016/07/26/u-s-public-opinion-on-the-future-use-of-gene-editing/> accessed 17 May 2020 Christine Critchley et al., ‘Predicting Public Attitudes Toward Gene Editing of Germlines: The Impact of Moral and Hereditary Concern in Human and Animal Applications’ (Frontiers in genetics ESL in genetics, 9 January 2019) available at: < https://www.frontiersin.org/articles/10.3389/fgene.2018.00704/full> accessed 18 May 2020 Communications Team, ‘Largest study of CRISPR-Cas9 mutations creates prediction tool for gene editing’ (Wellcome Sanger Institute, 27 November 2018) available at: <https://www.sanger.ac.uk/news_item/largest-study-crispr-cas9-mutations-creates-prediction-tool-gene-editing/> accessed 15 May 2020 Council of Europe, ‘Oviedo Convention and its Protocols’ Bioethics, available at: <https://www.coe.int/en/web/bioethics/oviedo-convention> accessed 15 June 2020 CRISPR Therapeutics, ‘CRISPR Therapeutics and Vertex Announce Progress in Clinical Development Programs for the Investigational CRISPR/Cas9 Gene-Editing Therapy CTX001’ (Press Release, 25 February 2019) available at: < http://ir.crisprtx.com/news-releases/news-release-details/crispr-therapeutics-and-vertex-announce-progress-clinical> accessed 16 June 2020 Dan Robitzski, ‘Scientists Around the World Condemn That CRISPR Baby Experiment’ (Futurism, 27 November 2018) available at: < https://futurism.com/neoscope/scientists-condemn-crispr-baby-experiment> accessed 6 May 2020 Danish Institute For Human Rights, ‘The Availability, Accessibility, Acceptability, Quality (AAAQ) Toolbox’, available at: <http://humanrightseducation.dk/HRBA_Training_Package/HRBA_in_practice/AAAQ%20Toolbox%20concept%20note%20brief.pdf> accessed 16 June 2020 David Brough, ‘CRISPR – the future of genetic research at Manchester?’ (Faculty of Biology, Medicine and Health University of Manchester) available at: <https://www.bmh.manchester.ac.uk/stories/crispr/> accessed 10 June 2020

Lilian Srour S3127389
59 David Cyranoski and Heidi Ledford, 'Genome-edited baby claim provokes international outcry' (Nature, 28 November 2018) available at: <https://www.nature.com/articles/d41586-018-07545-0> accessed 12 June 2020 David Cyranoski, 'CRISPR-baby scientist fails to satisfy critics' (Nature, 28 November 2018) available at: <https://www.nature.com/articles/d41586-018-07573-w> accessed 6 May 2020 Elliot Hosman, ‘French activists protesting ‘GMO babies’ could derail CRISPR on humans debate’ (Genetic Literacy Project, 5 July 2016) available at: <https://geneticliteracyproject.org/2016/07/05/fears-mount-french-activists-protesting-gmo-babies-will-derail-crispr-humans-debate/> accessed 15 May 2020 Elvira Dominguez, 'The Right to Health' (Icelandic Human Rights Center) available at: <http://www.humanrights.is/en/human-rights-education-project/human-rights-concepts-ideas-and-fora/substantive-human-rights/the-right-to-health> accessed 16 June 2020 End FGM European Network, UN Committee on Economic, Social and Cultural Rights – General Comment No. 14: The Right to the Highest Attainable Standard of Health (2000) (16 August 2016) available at <https://www.endfgm.eu/resources/health/un-committee-on-economic-social-and-cultural-rights-general-comment-no.-14-the-right-to-the-highest-attainable-standard-of-health-2000/> accessed 15 June 2020 Eric Lander, Francois Baylis et.al., ‘Adopt a moratorium on heritable genome editing’ (Nature, 13 March 2019) < https://www.nature.com/articles/d41586-019-00726-5 > accessed 15 June 2020 Erin Quick, ‘Addressing International Legal Challenges of Genetic Engineering’ (The Regulatory Review, 2 April 2018) available at: <https://www.theregreview.org/2018/04/02/quick-international-dimensions-genetic-engineering/> accessed 15 June 2020 Genetic Home Reference, ‘What are genome editing and CRISPR-Cas9?’ US National Library of Medicine, available at <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839051/> accessed 17 June 2020 Guardian Staff, ‘Euthanasia and assisted suicide laws around the world’ (The Guardian, 17 July 2014) available at: < https://www.theguardian.com/society/2014/jul/17/euthanasia-assisted-suicide-laws-world> accessed 1 May 2020 INSERM Press Office, ‘Presentation of the French Plan For Genomic Medicine 2025’ (Inserm, 23 June 2016) available at: < https://presse.inserm.fr/en/presentation-of-the-french-plan-for-genomic-medicine-2025/24328/> accessed 14 May 2020 Jayshree Pandya, ‘The Rise of Genetic Testing Companies and DNA Data Race’ (Forbes, 1 April 2019) available at: < https://www.forbes.com/sites/cognitiveworld/2019/04/01/the-rise-of-genetic-testing-companies-and-dna-data-race/#7d0a28e32afb> accessed 12 April 2020 John Conley, ‘A Lawyer’s Guide to CRISPR Gene Editing’ (The Privacy Report, 28 March 2019) available at: < https://theprivacyreport.com/2019/03/28/a-lawyers-guide-to-crispr-gene-editing/> accessed 16 June 2020 Kathleen M. Vogel, 'Crispr goes global: A snapshot of rules, policies, and attitudes' (Bulletin of the Atomic Scientists, 5 June 2018) <https://thebulletin.org/2018/06/crispr-goes-global-a-snapshot-of-rules-policies-and-attitudes/> accessed 23 May 2020 Kevin Curran, 'How on Earth Are We Currently Regulating Human Genetic Modification?' (Rising Tide Biology, 23 January 2020) <https://www.risingtidebio.com/human-gene-therapy-regulations-laws/> accessed 25 May 2020

Lilian Srour S3127389
60 Martin Stanley, ‘CRISPR and Gene Editing’ (Understanding Regulation) available at: <https://www.regulation.org.uk/specifics-gene_editing.html> accessed 15 June 2020 MaryAnn Labant, ‘CRISPR Jump-Starts Gene Therapy’ (Genetic Engineering & Biotechnology News, 1 April 2019) available at: <https://www.genengnews.com/insights/crispr-jump-starts-gene-therapy/> accessed 17 June 2020 Matt Ridley, ‘Why Brexit could jump start UK GMO, CRISPR research – once stifled by ‘dead hand’ of EU regulation’ (Genetic Literacy Project, 18 March 2020) available at: <https://geneticliteracyproject.org/2020/03/18/viewpoint-brexit-could-jump-start-uk-gmo-crispr-research-once-stifled-by-dead-hand-of-eu-regulation/> accessed 15 May 2020 Merck, ‘The Potential of CRISPR Technology’ available at: <https://www.merckgroup.com/en/expertise/pharmaceutical-research/crispr.html> accessed 14 May 2020 Michael A. Stramiello, 'CRISPR: The New Frontier of Biotechnology Innovation' (American Bar Association, 2018) available at: <https://www.americanbar.org/groups/intellectual_property_law/publications/landslide/2017-18/january-february/crispr-new-frontier-biotechnology-innovation-digital-feature/#2> accessed 6 May 2020 Molly Campbell, ‘Meet Josiah Zayne, the Biohacker Next Door’ (Genomics Research, 21 June 2019) available at: <https://www.technologynetworks.com/genomics/articles/meet-josiah-zayner-the-biohacker-next-door-320964> accessed 15 June 2020 Personal Genetics Education Project, ‘Genetic Modification, Genome Editing and CRISPR’, available at: <https://pged.org/genetic-modification-genome-editing-and-crispr/> accessed 5 May 2020 Peter Mills, ‘Genome editing, human rights and the ‘posthuman’’ (Nuffield Council on Bioethics, 3 October 2017) available at: < https://www.nuffieldbioethics.org/blog/genome-editing-human-rights-posthuman> accessed 15 June 2020 PHG Foundation, 'Somatic genome editing: an overview' (2020) <https://www.phgfoundation.org/briefing/somatic-genome-editing-overview> accessed 5 May 2020 Public Affairs UC Berkley, ‘UC now holds largest CRISPR-Cas9 patent portfolio’ (Berkeley News, 1 October 2019) available at: < https://news.berkeley.edu/2019/10/01/uc-now-holds-largest-crispr-cas9-patent-portfolio/> accessed 10 June 2020 RIVM, ‘CRISPR-technologie’ available at: <https://biotechnologie.rivm.nl/CRISPR-Cas> accessed 10 June 2020 Rob Stein, ‘Scientists Attempt Controversial Experiment to Edit DNA in Human Sperm Using CRISPR’ (npr, 22 August 2019) available at: <https://www.npr.org/sections/health-shots/2019/08/22/746321083/scientists-attempt-controversial-experiment-to-edit-dna-in-human-sperm-using-cri> accessed 15 June 2020 Sarantis Michalopoulos, ‘Netherlands wants CRISPR gene-edited crops exempt from Europe’s GMO laws’ (Genetic Literacy Project, 13 September 2017) available at: < https://geneticliteracyproject.org/2017/09/13/netherlands-wants-crispr-gene-edited-crops-exempt-europes-gmo-laws/#:~:text=Netherlands%20wants%20CRISPR%20gene%2Dedited%20crops%20exempt%20from%20Europe's%20GMO%20laws,-

Lilian Srour S3127389
61 Sarantis%20Michalopoulos%20%7C%20EurActiv&text=The%20Netherlands%20believes%20the%20new,as%20safe%20as%20traditional%20breeding.> accessed 10 June 2020 ScienceDaily, 'Gene knockout using new CRISPR tool makes mosquitoes highly resistant to malaria parasite' (8 March 2018), available at: <https://www.sciencedaily.com/releases/2018/03/180308143052.htm> accessed 15 June 2020 Sharon Begley, ‘Scientists Call for Do-Over for Rules on Creating ‘CRISPR Babies’’ (Scientific American, 12 August 2019) available at: <https://www.scientificamerican.com/article/scientists-call-for-do-over-for-rules-on-creating-crispr-babies/> accessed 16 June 2020 Siobhan Dunphy, ‘German Ethics Council: Germline editing ‘not ethically out of question’’ (European Scientist, 15 May 2019) available at: <https://www.europeanscientist.com/en/public-health/germline-editing-not-ethically-out-of-the-question/> accessed 14 May 2020 Teresa B. Burke, ‘Gene Therapy: A Threat to the Deaf Community?’ (Impact Ethics, 2 March 2017) available at: < https://impactethics.ca/2017/03/02/gene-therapy-a-threat-to-the-deaf-community/> accessed 15 June 2020 The American Association for the Advancement of Science (AAAS) and EurekAlert, ‘UNESCO Adopts Universal Declaration On The Human Genome And Human Rights’, available at: < https://www.eurekalert.org/pub_releases/1997-11/U-UAUD-111197.php> accessed 23 May 2020 The Danish Institute for Human Rights, ‘AAAQ’ available at: <https://www.humanrights.dk/what-we-do/sustainability/implementing-economic-social-cultural-rights/aaaq> accessed 13 May 2020 The Francis Crick Papers, 'The Discovery of the Double Helix, 1951-1953' US National Library of Medicine; available at <https://profiles.nlm.nih.gov/spotlight/sc/feature/doublehelix> last accessed 16 June 2020 The Government of Netherlands, ‘Monitoring the quality and safety of medicines’ available at: < https://www.government.nl/topics/medicines/monitoring-the-quality-and-safety-of-medicines> accessed 8 June 2020 The Odin, ‘About Us’ (The Odin,2020) available at: < https://acmedsci.ac.uk/file-download/41517-573f212e2b52a.pdf> accessed 15 June 2020 Tom Ireland ‘I want to help humans genetically modify themselves’ (The Guardian, 24 December 2017) available at: <https://www.theguardian.com/science/2017/dec/24/josiah-zayner-diy-gene-editing-therapy-crispr-interview> accessed 29 May 2020 UNESCO, ‘Universal Declaration on Bioethics and Human Rights’, available at: < https://en.unesco.org/themes/ethics-science-and-technology/bioethics-and-human-rights> accessed 24 May 2020 Wageningen University and Research, ‘CRISPR-Cas – accurate DNA modification’ available at: < https://www.wur.nl/nl/Dossiers/dossier/CRISPR-Cas-accurate-DNA-modification.htm> accessed 15 June 2020 WHO, ‘A Human Rights-Based Approach To Health’, available at: <https://www.who.int/hhr/news/hrba_to_health2.pdf> accessed 16 June 2020 Other

Lilian Srour S3127389
62 Lotte Scholten, ‘Dutch Designer Babies. The Dutch public debate from pre-war eugenics to present-day biotechnology’ (MPhil thesis, Utrecht University, 2019)