WMA Statement on Human Genome Editing

Adopted by the 71^st WMA General Assembly (online), Cordoba, Spain, October 2020

PREAMBLE

Genome editing, enabled by recent scientific advances, can generate targeted insertions and deletions in DNA and may even offer enough precision to modify a single base pair within the genome of an organism. Basic science research with genome editing is now underway in laboratories globally.

Human genome editing is also advancing rapidly, with clinical trials now in progress for prevention and treatment of various human diseases. These trials, which are currently in early stages, involve somatic (non-reproductive) cells, and thus are not anticipated to introduce genetic changes that will be passed on to offspring or the germline (reproductive) cells.

While genome editing holds great potential to help improve human lives, the technology raises profound safety, ethical, legal, and social concerns. These concerns are compounded by the fact that regulatory and ethical guidance often lag rapid technological developments.

Safety concerns for genome editing include the risk of unintended or unforeseen pleiotropic effects off-target effects (edits in the wrong place) unwanted on-target modifications (imprecise edits), and mosaicism (when only some cells carry the edit), and abnormal immunological responses.

Ethical issues regarding genome editing include concerns that editing may be used for non-therapeutic and enhancement purposes rather than for therapeutic purposes, i.e. improving health or curing disease. There are also concerns that germline modifications could create classes of individuals defined by the quality of their engineered genome, possibly enabling eugenics, which could exacerbate social inequalities or be used coercively.

The effect of epigenomic changes are unpredictable, and there is disquiet as to how this will affect the existing healthy biological systems, including interactions with other genetic variants, and societal norms. Once introduced into the human population, genetic alterations would be difficult to remove and would not remain within any single community or country. The effects could remain uncertain for many subsequent generations, during which time deleterious modifications could be dispersed throughout the population.

Legal issues include providing clarity for risk management and assignment of duties and liabilities, particularly when modifications can be passed to subsequent generations. There are also risks, both legal and ethical, involved in the proliferation of unvalidated direct-to-consumer CRISPR (clustered regularly interspaced short palindromic repeats) kits that allow individuals to undertake gene editing independently in a home setting.

At a social level, debates revolve around the concerns that access to beneficial genome editing will be inequitable (e.g., only the wealthy will have access) and will increase existing disparities in health and medical care.

The WMA reaffirms principles in the Declaration of Reykjavik on the  ethical considerations regarding the use of genetics in health care, the Declaration of Taipei on Ethical Considerations regarding Health Databases and Biobanks and the Declaration of Helsinki and makes the following recommendations:

RECOMMENDATIONS

1. Human genome-editing, like any other medical intervention, should be implemented according to appropriate evidence that is collected via well-conducted and ethically approved research studies.
2. When contemplating use of germline cells for research purposes, germline editing should be permitted only within a separate ethical and legal framework, distinct from an ethical and legal framework applied to somatic genome editing.
3. Governments should:

• Develop robust and enforceable regulatory frameworks for genome editing in their own countries.
• Urge continued development of an international consensus, grounded in science and ethics, to determine permissible therapeutic applications of germline genome editing.

4. WMA constituent members should:

• Be cognisant of the advances in research in genomic medicine and inform their members on scientific advances in genome
• Advocate for research to understand (i) the benefits and risks of human genome editing, (ii) the socio-political, ethical, and legal aspects of editing the human germline and (iii) the necessity of physician involvement in therapeutic genome editing.
• Develop and promote ethical guidelines for genome editing for their members, taking into consideration societal perspectives, professional consensus, national laws and regulations, and international standards.
• Advocate for the development of appropriate laws and regulations for genome editing in accordance with both international and national norms and standards.
• Where human genome editing is safe and effective, advocate for equal patient access to the technology.

5. Physicians should:

• Educate themselves on the technical, ethical, social, and legal aspects of genome editing.
• Familiarise themselves with the international and local ethical frameworks regulating genome
• Follow all ethical standards for approved research in these areas, including appropriate informed consent.