To Edit or Not to Edit? - Regulating CRISPR Transnationally.

• Date: 01 November 2020
• Author: Potter, Ann

TABLE OF CONTENTS I. WHY WE NEED BETTER CRISPR REGULATIONS 1728 II. WHAT IS CRISPR AND WHY SHOULD WE REGULATE IT? 1732 A. Origins of Gene Editing Indicate the Need for Regulation 1733 B. The Discovery of CRISPR 1734 C. The Ethics of CRISPR 1736 III. DIFFERENT APPROACHES TO REGULATING CRISPR 1740 A. Existing Transnational Regulations 1741 1. Universal Declaration on the Human Genome and Human Rights 1741 2. International Summit on Human Gene Editing 1744 3. Oviedo Convention 1745 B. Sample Countries 1746 1. The United States: Innovation Leads to Hesitancy 1747 2. The United Kingdom: Flexible but Strong Intervention 1751 3. Japan: Flourishing under Regulatory Reluctance 1754 VI. THE INTERNATIONAL GENE-EDITING ETHICS COMMISSION 1757 A. The Incentives: Information and Funding 1759 B. The Purpose: Ethical Advancement of Gene Editing 1760 C. Practicality 1762 V. CONCLUSION 1763 I. WHY WE NEED BETTER CRISPR REGULATIONS

In the fall of 2018, Chinese scientist Dr. He Jiankui announced that he edited the genes of human embryonic cells for the first time in history, and that the mother had given birth to the babies already. (1) Dr. He inserted CRISPR/Cas-9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) into germline cells, in order to naturally immunize the babies to human immunodeficiency virus (HIV (7)). (2) Once the embryonic cells received the vector, they were then placed in the mother via in vitro fertilization. (3) Nine months later, Dr. He announced his feat, propelling the global community into the germline-editing era without its permission. (4)

In 2015, before this groundbreaking announcement, the scientific communities of the United States, the United Kingdom, and China decided to meet for the first International Summit on Human Gene Editing in Washington, DC to hash out guiding principles for gene-editing technologies. (5) After several conferences and lengthy discussions among the lawyers, scientific leaders, and other international scholars, the Summit released its first statement on the issue of gene editing in clinical trials. (6) The Summit affirmed the need for meticulous preclinical research, approved clinical trials involving the editing of somatic cells under the existing regulatory framework, and firmly prohibited gene editing on germline cells until further notice. (7) The Committee emphasized that it was crucial to continue meeting to readdress the global scientific standards it had been charged with overseeing. (8)

The second International Summit met in Hong Kong in November of 2018 with quite a different tone. (9) At this summit, Dr. He announced his clinical trial and the birth of the twins. (10) While the Committee did not approve of Dr. He's experiment and he received three years in prison for it, the Committee understood that the gene editing of germline cells was a reality that needed to be addressed quickly and globally. (11)

By way of background, scientists divide gene editing into two broad categories: somatic cell editing and germline cell editing. (12) Somatic, literally meaning "of the body," refers to the living cells of humans, whereas germline cells are reproductive cells. (13) Modifying the somatic cells of a human corrects an inheritable gene in that person only; the modifications will not be inheritable because those cells will not be used in reproduction. (14) Germline cell modification, meaning modifications of the cells used to reproduce, will affect the human genome permanently because changes in those cells are inheritable. (15)

Different ethical issues arise with each type of gene editing. Ethical questions arise in the somatic cell editing context when deciding which purposes are acceptable for justifying its use. Germline cell editing can raise questions about designer babies and consent. (16) Yet some bioethical concerns underpin both types of editing--those questions such as accessibility, regulation, and scientific responsibility. (17) This Note will primarily focus on questions surrounding the regulation of clinical somatic cell editing, though much of its discussion could apply to germline editing in the future. Because CRISPR's minimal off-target effects, cheaper use, and precision distinguish it from other gene-editing technologies, like zinc-finger nucleases and TALENs (transcriptor activator-like effector nucleases), gene editing is more accessible than ever before. (18) Additionally, considering the existing global and national frameworks failed to prevent a scientist from using CRISPR to permanently alter the human genome, the need for an international legal solution is clear.

Beyond the international summits discussed above, international legal communities are working together to begin addressing the issues surrounding gene editing. Because the scientific community is truly a global one, international legal communities aim to harmonize regulation of technological advancement. (19) In 1998, the United Nations published the Universal Declaration of the Human Genome and Human Rights. Among other things, it emphasized the dignity of the human genome; the rights of patients; the goals of promoting respectful, cooperative, and innovative research; the need for national regulations of gene-editing technologies; and the need for international solidarity on each of these topics. (20) In 2015, the International Summit on Human Gene Editing, referenced above, prompted a conversation between the world's scientific scholars and bioethicists concerning the use of gene editing in clinical trials. (21) The World Health Organization's Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing met for the first time in 2019 to discuss plans for the next twelve to eighteen months. (22) But Dr. He's permanent alteration of the human genome calls the practicality and effectiveness of such vague international guidance into question. (23)

On a national scale, countries like the United States, the United Kingdom, and Japan have hashed out the details of regulating clinical somatic cell editing in their respective countries. (24) Each of these countries attempt to balance retaining pre- and post-market control of gene-editing technologies with too strict regulations that may stifle scientific innovation altogether. (25) The United States established a complex regulatory framework for policing mainly pre-market gene-editing technologies via guidelines for research funding. (26) While this has appeared to effectively control research and pre-market practices, these regulations are relatively weak once an item is in the market. The regulations fail to control who can use the technology, in what conditions they can use the technology, and how often they may use the technology. (27) The United Kingdom regulates both the pre-market and post-market research and treatment of gene-editing technologies at length, while still complying with the European Union's framework. (28) Finally, in Japan, the regulations of gene editing classify each product by degree of risk and apply a regulatory process based on that determination. (29) Though Japan's science, technology, and biotechnology market ranks second-most advanced in the world, the bureaucratic process through which scientists must venture in order to receive funding for gene therapy research and clinical trials has substantially slowed growth in that area. (30)

Even assuming domestic governments are in the best position to regulate scientific technology, an issue as fundamental and global as the future of the human genome requires an international, legally binding solution. (31) Part II details the history of gene editing with CRISPR and its journey to becoming an accepted tool in somatic cell clinical trials. Part III will analyze the existing international and national frameworks regulating clinical trials of somatic cell gene editing in the United States, the United Kingdom, and Japan, with an eye towards the possibility of germline editing. Finally, Part IV of this Note will propose the International Gene-Editing Ethics Commission to create and enforce a binding whistle-blower framework in the global scientific community. This whistle-blower framework would provide qualifications to become a member of the commission and standards for clinical trial approval that emphasize transparency and consensus. It would then provide a way for scientists to blow the whistle on questionable experiments, and issue penalties for those who violate standards.

2. WHAT IS CRISPR AND WHY SHOULD WE REGULATE IT?

   Ideas about changing the human race biologically dramatically pre-date gene-editing technology itself. (32) This Part briefly outlines the historical origins of the ideas that underpin gene editing, explains what CRISPR actually does, and highlights bioethical concerns implicated by CRISPR that affect its governance.

   1. Origins of Gene Editing Indicate the Need for Regulation

      Gene editing originated, at least partially, in eugenics. (33) The definition of eugenics is subjective--generally, it is the idea that one can control reproduction in a way that "improves" future generations. The danger of eugenic thought lies in the decision of what "improves" a future generation. Gene-editing technologies are inherently eugenic because a current generation decides what would genetically improve the next generation. Given this intertwining of gene editing and eugenics, the following chronological history of gene editing and eugenics exemplifies the gravity of the need for regulation of gene-editing technologies. Gregor Mendel's discovery of inheritable traits that could not be changed throughout life laid a foundational concept in the minds of scientists when it was translated in the early twentieth century: our genes cannot be changed by behavior or environment. (34)

      Francis Galton aimed to apply Mendel's findings to human reproduction, and the eugenics...