Illustration of a scientist editing a DNA strand

Establishing Standards for Gene Editing: Initial Steps from Private and Public Actors

By Phebe Hong

Nine months have passed since the startling news broke in November 2018 that Chinese researcher He Jiankui had used CRISPR/Cas9 to genetically modify the embryos of twin girls. The controversial news spurred the scientific and regulatory community into action. In late August 2019, two influential organizations — one from the private sector and one from the public sector — independently released statements announcing their efforts to establish standards for the nascent field of gene editing.

First, the Alliance for Regenerative Medicine (ARM), the advocacy organization representing cell and gene therapy companies, released its “Therapeutic Developers’ Statement of Principles,” offering an industry perspective on the use of gene editing technologies. Shortly thereafter, the World Health Organization (WHO) announced its plans to build a new registry and governance framework to track and regulate human gene editing trials. The statements symbolize an initial step by both private and public organizations to build consensus around responsible stewardship principles to prevent future scientific and ethical transgressions. It remains to be seen how such statements and plans will be implemented and how they will influence the field of genome editing research going forward.

Private Sector: A Statement of Principles

On August 27th, the ARM released a statement of five key principles on the use of gene editing and its commitment to safeguard from misuse. The principles include: an endorsement of somatic gene editing, support for the development of standards by regulatory organizations, a call for evolving national and regional regulatory frameworks, an assertion against the use of germline editing, and a commitment to focus R&D only on somatic cell approaches to treatments for disease.

The statement serves as a clear industry endorsement of somatic cell gene editing therapies, which several ARM-affiliated companies are in the midst of developing. Importantly, the statement defines somatic cells to include pluripotent stem cells, which are cells that have the capacity to self-renew and give rise to all cell types. The statement, however, staunchly opposes germline editing, given the technical and ethical uncertainties associated with creating heritable modifications.

The ARM statement was written and signed by 13 biopharmaceutical companies developing gene therapies. Among the list of companies is CRISPR Therapeutics (currently running a Phase I/II clinical study of a CRISPR/Cas9 gene-edited hematopoietic stem cell therapy for transfusion-dependent beta thalassemia and sickle cell disease), Editas Medicine (conducting a Phase I/II study of a CRISPR/Cas9-based therapy for Leber’s congenital amaurosis, a form of inherited blindness), and bluebirdbio (developing Zynteglo, a gene therapy for beta thalassemia that was approved by the EMA earlier this year). The joint statement seems to be an intentional effort to distinguish the efforts of the collective biopharmaceutical industry from the activities of rogue scientists abroad.

Public Sector: A Global Trials Registry

Two days later, on August 29th, the WHO announced its plans to launch a new registry for human gene editing trials. Building off the International Clinical Trials Registry Platform (ICTRP), the registry is intended to track both somatic and germline clinical trials. Since international attitudes vary significantly on the matter, the WHO proposed the trial registry as a way to monitor planned and ongoing gene editing research, thereby increasing transparency and accountability. To build such a registry, the WHO plans to engage with stakeholders through “online consultations and in-person engagement” to develop a global governance framework. Similar to the ARM, the WHO expert advisory committee maintains that germline editing — at least for the time being — should remain banned in all countries until further technical and ethical discussions take place.

It remains to be seen how the registry will be enforced in practice. Assuming researchers are asked to voluntarily register their trials, if a researcher fails to report her gene editing trial to the established registry, what consequence will result? What enforcement mechanisms exist to ensure registry compliance?

Preliminary interviews suggest that the WHO may choose to rely on publishers of scientific journals and research funders to require trial registration for research they accept or support. In fact, the International Committee of Medical Journal Editors (ICMJE) in 2005 adopted a mandatory requirement of trial registration as a prerequisite for publication in any of its member journals, which includes notable journals such as the New England Journal of Medicine, the Journal of the American Medical Association, and the Lancet. Such a mechanism, however, would not work to enforce compliance among independently-funded scientists who are uninterested in publication. Even imposing legal requirements for clinical trial reporting has been historically difficult to enforce, as exemplified in the United States.

Even if researchers register their gene editing trials, the data may lack in quality. The ICTRP was established in August 2005 with the purpose of ensuring “a single point of access and the unambiguous identification of trials.” It combines data from more than 15 national and regional trial registries, and a minimum dataset of 20 pieces of information for each trial entry is required in order to be considered “compliant” with WHO standards. Even though clinical trial registration is now widely considered an ethical responsibility, trial registries still suffer from poor quality of data and missing information (e.g., protocols, participant-level data). Studies have shown that individual registry entries remain mostly incomplete. The ability to monitor ongoing gene editing trials will be hindered if the public cannot discern the right details about trials.

Increased reporting of clinical trials holds many important advantages, including access to information, prevention of publication bias and selective reporting, and increased accountability. Both private and public actors have staunchly pledged their commitment to prevent germline editing research (for now). The WHO will need to develop a robust registry framework in order to effectively enforce compliance and accountability across all actors.

Phebe Hong

Phebe Hong is a 2L at Harvard Law School. She graduated from Harvard College with a degree in Human Developmental and Regenerative Biology. Prior to law school, she worked as a consultant advising pharmaceutical and biotechnology companies. She is a Research Assistant at the Program on Regulation, Therapeutics, and Law (PORTAL) and an Articles Editor for the Journal of Law and Technology. Her research interests include FDA regulation of biologics and pharmaceutical patent law.

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