A CALL FOR AN INTERNATIONAL GOVERNANCE FRAMEWORK FOR HUMAN GERMLINE GENE EDITING.

• Author: Hess, Melanie

INTRODUCTION

From December 1 to 3, 2015, the First International Summit on Human Gene Editing took place in Washington, D.C. to "discuss the scientific, ethical, and governance issues associated with human gene-editing research." (1) Following the 2015 summit, the National Academy of Sciences (NAS) issued the 2017 Report on Human Genome Editing: Science, Ethics, and Governance. The report recognized that risks involved in the field of human genome editing required the addition of new principles and guidance to existing norms, which include the protection of human dignity, "the need for research having scientific and social value," and the related need to generate knowledge that promotes human health. (2) To support the endeavor responsibly, the report has a chapter dedicated to the state of regulatory and international oversight of the field. (3) Notably, the report identified "transnational cooperation" as critical to developing governance in the field, and stresses the "commitment to collaborative approaches to research and governance while respecting different cultural contexts." (4)

To build on relevant discoveries and research as well as continue the international societal dialogue about gene editing, the Second International Summit on Human Genome Editing convened from November 27 to 29, 2018. (5) During the 2018 summit, varying perspectives emerged surrounding the advisability and ethical implications of moving forward with germline gene editing. Germline gene editing, the topic central to this Note, is the editing of heritable genes that will impact future generations, and as will be discussed, is considered a particularly problematic application of gene editing. One commentator cautiously observed that:

[M]any of the arguments made against germline genome editing, such as consideration of the autonomy of a child, societal equity, and possible misuse, can be applied as well to other medical technologies, but many jurisdictions have nevertheless permitted those technologies to move forward, so long as they are sufficiently beneficial, safe, and effective. (6) More skeptical experts noted that germline editing "could be morally permissible in certain circumstances but those circumstances do not yet exist anywhere in the world." (7)

The 2018 summit was heavily impacted by news of Chinese doctor He Jiankui's research, which leaked just before the summit and then was presented at the summit, that he had created the world's first gene-edited human babies through the use of CRISPR-Cas9 (CRISPR) technology. (8) The reaction to this announcement was swift condemnation from the global community, given the undeveloped stage of the technology, regulation, and lack of consensus regarding the implicated ethical issues. (9) David Baltimore of the California Institute of Technology, the chair of the 2018 Summit Organizing Committee, described the occurrence of Dr. He's experiment "a failure of self-regulation by the scientific community." (10)

The failure of this self-regulation is perhaps a consequence of the fact that there is not currently a stronger international regulatory framework or set of principles guiding this subject. There is scant consensus on how to regulate and what to allow, and this is largely because despite the potential benefits of germline editing, the field is rife with controversy surrounding the "safety concerns, unprecedented informed consent, challenges to human dignity, and the potential for permanent negative impact on future generations, including its abuse for eugenics or enhancement (the parental pursuit of specific traits for non-medical reasons)." (11) There is, however, a general consensus that no clinical applications should proceed until there is "broad societal consensus" involving the opinions of all social groups, perhaps on a global scale. (12)

This Note will argue that human germline editing ought to be subject to a worldwide regulatory initiative contained in an international governance framework. It will touch on the justifications for the call for this agreed upon framework and discuss the current state of regulation of human germline editing, including norms and principles promulgated by international instruments and important statements on the topic. Finally, it will propose suggestions for the substance that an international governance framework should include and acknowledge the challenges in implementing such a framework.

1. WHAT IS GERMLINE EDITING?

   1. Gene Editing

      Gene editing, or genome editing, (13) is a form of genetic engineering that allows scientists to modify genes, thereby changing an organism's DNA. Gene editing itself is not a new concept or technology: the first successful gene editing technique was created in 1972 by scientists who discovered how to recombine pieces of DNA to create hybrid sequences. (14) This technique, called recombinant DNA, formed the basis of gene therapy, an experimental treatment that attempts to alleviate or cure diseases by inserting healthy genes into DNA sequences to compensate for problematic ones. (15) Gene therapy as a treatment is currently being researched and developed in clinical trials worldwide, and in certain situations is available for patients seeking clinical treatments. (16)

      Despite progress, the recombinant DNA technique was not always consistent or reliable, and could be described as "more of a patch kit than a repair shop." (17) Thus, the advent of CRISPR as a gene-editing tool in 2012 promised to be a game changer for gene editing because of its efficiency and precision in altering, deleting, and adding bits of DNA in living organisms. (18) The protein Cas9 works like "a pair of molecular scissors, capable of cutting strands of DNA" to remove a desired portion of the strand and replace it with a strand that is either healthy or altered in some way. (19)

      CRISPR promises to fulfill many different purposes, ranging from food and agricultural applications to human gene editing. With regard to the latter, laboratory and animal studies have demonstrated CRISPR's potential to correct genetic defects, similar to current applications of gene therapies. (20) Another potential application is to use CRISPR to make gene drives. (21) For contextual purposes, an important distinction must be made between gene therapies, which involve somatic cell gene editing, and gene drives, which involve germline editing. Somatic cells are live but nonreproductive cells that inform the genetics of a single individual organism. Somatic cell editing would address a genetic problem affecting only that individual. (22) As will be described in Part III, clinical trials and applications of somatic cell editing have existed in the United States since the 1980s with extensive oversight from regulatory bodies. (23) According to a recent report, over 2600 clinical trials of gene therapies have been approved, in progress, or completed in 38 countries to date. (24)

      Germline editing, on the other hand, is the editing of cells which are heritable; thus, the modification made in a germline gene will be inherited by successive generations. Gene drives are an application of germline editing that bias inheritance of a gene in future generations by editing heritable germline cells. As will be briefly discussed in the following Section, research has been conducted on nonhuman applications of gene drives, such as engineering malaria-carrying mosquitos to pass on genes that result in predominantly male offspring, thereby reducing the population, but even this research has not yet resulted in widespread testing. (25) Until Dr. He's experiment, research on human germline editing had been limited to petri dishes or banned, either effectively or directly, in all instances. (26) Furthermore, the summits of 2015 and 2018 both resulted in calls for moratoriums on research involving clinical applications (i.e., where a modified embryo was used to establish a pregnancy) until certain criteria are met. (27) In research and discussions of ethics, the two applications--somatic and germline--are viewed very differently: somatic cell editing, which generally involve gene therapies, broadly has the support of the global scientific and policymaker communities and is on the forefront of medicine. (28) Such applications of gene editing do not pose the same controversies as germline editing, largely because they involve individuals who are already sick, will affect only that consenting patient, and have been more extensively researched. In contrast, there is a general consensus that clinical applications of human germline editing should be "off limits" for now. (29) While somatic gene editing and gene therapies are not central to this Note, they are relevant where their governing regulatory regimes overlap or provide guidance for discussions of the regulation around germline editing.

   2. General Applications of Gene Drives and Germline Gene Editing

      Gene editing currently occupies a unique space in international headlines, with fears of dystopian worlds ruled by "designer bab[ies]" on the horizon, hopes for the promise of eradication of terrible genetic diseases and disorders, and confusion about how best to proceed with research and clinical applications. (30) However, while the discussion looms large on the topic of human germline editing, nonhuman applications have been in academic, scientific, and policy-based discussions for many years, particularly around the use of gene drives to engineer solutions to environmental and agricultural problems.

      A gene drive, which is an application of germline editing, is a method of biasing the likelihood that a certain gene or trait will be inherited by a future generation. (31) Applications of gene drives have thus far been discussed seriously in the context of altering populations of plant and animal species, such as "reprogramming mosquito genomes to eliminate malaria, reversing the development of pesticide and herbicide...