The appointment of this Commission and the beginning of its deliberations occurred at a time when the reported birth of the “CRISPR babies” in China was fresh in many minds. This event made clear the absence of broad international consensus regarding both the societal acceptability of particular applications of heritable human genome editing (HHGE) and the scientific evidence that would be needed to demonstrate that HHGE could be done safely.

It was recognized that, without evidence of high efficiency and specificity to ensure that only the desired changes were introduced into the genome, there was continuing risk of ad hoc editing efforts that could cause significant harm to individuals. Moreover, given that heritable changes would be introduced that could be passed to subsequent generations, it was clear that careful consideration would need to be given to the specific applications of the editing technology.

During the preparation of this report, pressing issues have intervened. With the emergence of the SARS-CoV-2 coronavirus, the world's attention has been focused on the health, economic, and social consequences of the devastating COVID-19 pandemic, including the social inequalities of its impact in many countries. With intense protests that have taken place in many countries, the world's attention has also been focused on calls for changes to address racial injustice and inequities. These twin upheavals have underscored that we live in an interconnected world, where what happens in one country touches all countries, and that science occurs in a societal context. Although of a very different nature, the potential use of HHGE is an issue that transcends individual countries, deserves wide-ranging global discussions, and entails important issues of equity.

Genetic diseases can impose a major burden on families. For many prospective parents, viable options for having genetically-related, unaffected children are already available; but for others, due to genetics or reduced fertility, current alternatives may never be successful. HHGE might, in the future, provide a reproductive option for such couples.

At the same time, it is important to recognize that the idea of making intentional modifications to the human germline evokes to some the eugenics movements of the late 19th century and first half of the 20th century, which promoted now-discredited theories that led to the persecution of whole groups, based on race, religion, class, and ability. Should any nation decide to permit HHGE, it is vitally important that bias and discrimination be avoided. In addition, there must be constraints that prevent the use of HHGE for cases that are not medically justified interventions and not based on a rigorous understanding of genetics.

Great caution must also be taken in the development of genetic technologies like HHGE, fundamentally because of the personal and social contexts and broader societal and ethical issues that surround their application. Proposed uses of these technologies must reflect the conditions and needs of diverse human populations around the world. They should be deployed in ways that prevent harm and ensure equitable access to their benefits. The technologies themselves and the rigorous oversight structures established to regulate their use should be developed in ways that respect the human rights and inherent dignity of all persons.

The Commission is concerned that both the development and use of HHGE and allied assisted reproductive technologies (ARTs) must be properly regulated and overseen. In particular, it is important to avoid irresponsible practices in the use of HHGE. In making its recommendations, this Commission has taken into account the unfortunate fact that the practice of ART around the world too often lacks appropriate oversight.

Matters of equitable access are of course also raised by other ARTs and by health care in general, but these issues deserve note here. There is no doubt that the economic costs of developing and using the technology will be substantial. Moreover, since there are already viable alternatives for prospective parents to have genetically-related, unaffected offspring in the vast majority of cases, the benefits will accrue to very few prospective parents. Nonetheless, it is possible that HHGE might someday become sufficiently safe, robust, and efficient to be routinely applied in conjunction with ART to provide an improved option that would reduce the burden to women of repeated cycles of ovarian stimulation. Equitable access is the province of national jurisdictions, and the Commission recognizes the cost of development and the breadth of access to be issues that must be considered.

The Commission was specifically tasked with defining a responsible pathway for clinical use of HHGE, should a decision be made by any nation to permit its use. In fulfilling this assignment, we have considered current understanding in the areas of human genetics, genome editing, reproductive technologies, and associated social and ethical issues. This report is the product of our deliberations.

International Commission on the Clinical Use of Human Germline Genome Editing