The WHO report on Global Governance and Oversight of Human Genome Engineering

Genetics Otago Magazine, November 2021

Researchers, ethicists and regulators have debated the benefits and risks of genetic engineering for nearly four decades, and some forms of genetic engineering, such as mitochondrial replacement therapy, are already in use. But it wasn’t until the discovery of CRISPR/Cas in the early 2000s that therapeutic human genome editing (HGE) became a feasible – and imminent – possibility. There are currently 47 CRISPR-based clinical trials currently underway according to Clinicaltrials.gov, most of which are ex-vivo therapies that involve inactivating or interfering with gene expression rather than introducing specific sequence modifications. New tools and techniques are likely to increase the efficiency of more fine-grained genomic modification to the point where it is suitable for clinical translation and several pre-clinical studies that have successfully used base and prime editing (eg progeria in mice, heart disease in non-human primates).

Public advisory bodies in countries around the world began to consider social and ethico-legal issues of CRISPR and related technologies in 2015, with the first International Summit on Human Genetic Engineering being held in December of that year. Then, in November 2018, Chinese researcher Jiankui He announced the birth of twin girls carrying genetically modified CCR5, leading to a moritorium on heritable genome editing in most countries around the world ,and recognition of the need for international regulation of human genome engineering.

The WHO Expert Advisory Committee on Developing Global Standards Governance and Oversight on Human Genome Editing was established in December 2018 to develop a framework for local, regional and global governance measures on human genome editing. Composed of scientists, ethicists and legal experts from the Americas, SE Asia, Europe, the Eastern Mediterranean and Western Pacific, the Committee drew on reports and recommendations from a variety of sources (including the New Zealand Society Te Apārangi report on Gene Editing), and consulted with a diverse range of national and international organisations, professional and academic institutions and representatives of business, patient and indigenous groups. A background paper on the scientific, legal, social and ethical challenges associated with somatic and heritable genetic modifications was released in 2019 https://www.who.int/ethics/topics/human-genome-editing/WHO-Commissioned-Governance-1-paper-March-19.pdf) , and the final report, which consists of a framework for and a recommendation paper was released in August of this year.

The Committee defines ‘good governance’ as an active and evolving process guided by principles of caution, fairness, transparency, accountability, inclusivity, non-discrimination, and justice (both social and global), and makes 9 recommendations.

 These include:

• Making the WHO the principal body responsible for outlining the ethical issues associated with HGE and the consequences of failing to address them.
• Formulating common standards and collaborative approaches to governance and regulation, and fostering international agreements on responsible research and medical travel to ensure HGE research and treatment should only take place in countries and territories with (appropriate) domestic policy and oversight.
• Establishing international registers for clinical trials and for basic research. (A pilot project for the former, established in 2019, currently contains 126 trials)
• Ensuring there are processes in place to allow whistle-blowers to safely and confidentially report questionable research such as that carried out by He Jiankui.
• Promoting the adoption of ethical licensing of IP to ensure applications and benefits of HGE research are universally available, and building capacity in resource-constrained countries.
• Encouraging the UN to establish a working group to ensure inclusive dialogue (particularly with under-represented groups) on the future of genome editing.

(https://www.who.int/publications/i/item/9789240030060)

In order to illustrate how their proposed governance framework and the ethical principles underlying it could be applied, the Frameworks report outlines seven hypothetical (but plausible) scenarios that highlight the opportunities and challenges posed by HGE:

• Somatic HGE for sickle cell anaemia and HD
• Unscrupulous entrepreneurs and clinics
• Somatic/epigenetic editing of athletes
• Heritable HGE
• Unscrupulous expansion of Assisted Reproductive Technology
• In-utero editing for CF

(https://www.who.int/publications/i/item/9789240030381 )

One of the Committee’s main concerns is the potential for significant social and global equity, with rich Western countries most likely to benefit without mechanisms to ensure equity of access. Not only may low or middle-income countries also find themselves being used for clinical trials of treatments they will never be able to afford (and potentially redirect money away from other public health measures), there is limited data on genetic variation in non-Caucasian/European populations, meaning that treatments will not target disease variants in other groups. It is also critical to ensure the appropriate use and ownership of biological materials/data from historically exploited or stigmatised communities, or those with different views on the body/privacy.

These case studies highlight the importance of engaging with, educating and empowering patients and marginalised groups, and building capacity (both research and regulatory) in low and middle-income countries. They also address other areas of concern, including the dangers of ‘do-it-yourself’ editing, the sale of HGE technologies to individuals/clinics/companies operating in countries with no oversight, and that the potential for opportunistic marketing – or public pressure for a relaxation of standards – will lead people to pursue unproven and potentially dangerous treatments.

There are undoubtedly those who will question whether the future of HGE should be dictated by an international body or be left to individual countries or institutions (a tension the Committee recognises in its acknowledgement that a number of countries already have governance measures in place, based on their own laws, values and priorities). However research – and its social implications – extend beyond national boundaries. And, by identifying key values and principles to guide policy-making, and drawing attention to the multiple ways in which oversight of HGE can be provided by governmental, professional and social institutions, the WHO has created an important resource for countries and researchers alike, and principles on which this report is based are applicable to areas of health research above and beyond HGE.