Human genome editing: unlimited potential or ethical concern?

By L. Sophie Gullino

Genome editing holds the promise of revolutionizing the future of humanity from its very core, by altering the genetic instructions that define us. It is estimated that 10,000 disorders arise from single gene mutations. All these “monogenic” diseases could be eradicated by preventing those genes from being inherited. Nevertheless, this unlimited potential comes with safety concerns and great ethical responsibilities which need to be addressed.

From the 1970s, recombinant DNA technologies have allowed us to edit an organism’s DNA to produce genetic traits of value for scientific research, pharmacology or agriculture. Whilst it gained popularity as a tool for crop breeding, a great success of recombinant DNA was the development of insulin.

In the decades that followed, other gene editing techniques were developed, aiming to modify the genome in a more efficient and cost-effective fashion. In particular CRISPR, stood out for its simplicity, speed, and low cost. In layman’s terms, we can describe CRISPR as a way to quickly find a specific part of DNA inside a cell, subsequently allowing us to alter it in an extremely specific manner. The CRISPR technology is now widely employed in medical research, such as in cancer, AIDS, and even COVID-19 vaccines.

The potential of human gene editing as a tool for improving human health is undeniable, however this technology has radically different implications depending on if the target is a somatic cell or part of the germline. Somatic gene editing involves altering the DNA in a cell of a person’s body, typically for clinical reasons, such as to alleviate a health condition. Gene therapies usually refer to the introduction of a healthy gene into an individual’s DNA, to substitute a gene which causes a genetic disease. Despite being incredibly expensive, gene therapy is becoming increasingly popular thanks to its application to a plethora of conditions, including cystic fibrosis, familial hypercholesterolemia and cancer.

Germline editing, on the contrary, refers to modifications to the DNA of embryos, sperm, or egg cells. Whilst somatic gene editing affects solely the person receiving it, the DNA changes in germline editing can be passed onto the offspring. For this reason, germline gene editing is highly controversial from an ethical point of view and is currently banned in most countries. A few countries (such as Columbia, Panama, Belgium and Italy) have policies that prohibit this technology but with a list of potential exceptions, whist in other nations, like South Africa, these is no kind of gene editing legislation at all. Notably though, no country specifically permits heritable human genome editing.

Due to the abundance of safety, ethical and social concerns, many scientists and policymakers believe that germline editing is a line that should not be crossed. Nonetheless, in 2018 a Chinese scientist He Jiankui reported that he edited the genome of two twins, with the goal of making them resistant to HIV. Jiankui was eventually sentenced to three years in prison, as the safety of human germline editing has not yet been established. This led scientists from all over the world to call for a five-year moratorium of human gene editing, starting March 2019. They asked that human gene editing would temporarily be prohibited to allow for the time to discuss and establish an international framework to regulate it. In response to this an International Commission on the Clinical Use of Human Germline Genome Editing was created, and World Health Organization (WHO) also appointed an interdisciplinary committee to draw recommendations on the topic.

Despite Jianuki’s actions being nearly universally condemned, the incident sparked a wide debate raising a range of important questions. If gene editing can really make an impact to human health, shouldn’t anyone have a voice in this decision? Should this be a debate at a global level? Should we push the technology forward with the goal of curing all genetic diseases? Or will germline gene editing lead to a new form of eugenics, selecting for any desirable trait and removing diversity?

Interdisciplinary committees and organizations all over the world are exploring ways in which germline editing could become politically and ethically acceptable. This would require novel legislations to control this technology both at the national and international level. Many international bodies, like the WHO and the Association for Responsible Research and Innovation in Genome Editing, are attempting to facilitate this discussion.

It is paramount to assess the safety of this technology. Safety concerns include unintended editing, or intended editing having unintended effect, including the cells repairing the cut DNA in an unpredicted way. These uncertainties make apparent that more research in the field is needed, however current and future studies should be conducted in the spirit of open science, valuing transparency and accountability. In line with this, in 2019, the WHO launched the global human genome editing registry, this is a central database collecting information on clinical trials using human genome editing worldwide.

As human gene editing has global public health implications, international cooperation is also essential to provide oversight. This can involve international agreements, institutions and bodies that can be developed following international discussion of the different views on gene editing. Notably, not all countries have committed the necessary resources to ensure appropriate and effective regulations of this technology. This introduces the risk of so-called “ethics dumping” which refers to scientists from strictly regulated countries purposefully choosing to conduct research in countries that lack the relevant domestic policy or oversight. This issue should clearly be addressed and international agencies are aiming to assist countries to create a regulatory framework which prevent the unethical use of this technology.

This global discussion must also involve interdisciplinary dialogue between scientists, ethics committees, and policy makers alike. It is essential to increase the awareness of lay people, so that the values and views of the citizens can be taken into account, for example by creating opportunities for the public to participate in decision-making. Whilst some public engagement is already happening, such as through educational material, media, and documentaries, often these depict Western narratives which are not applicable worldwide. Hence, we should consider that there is not a one-size-fit-all strategy to public engagement, but that it should be tailored to different social and cultural contexts.

Whilst talking into consideration the ethical aspects of genome editing, we should also promote health equality, making sure that access to human gene editing is fair and equitable as opposed to being available only to a select few. Genome editing might provide solutions to genetic diseases and life-threatening conditions, but it can only do so if a detailed regulatory framework is in place, promoting open science, public disclosure, and transparency. The fear of “designer babies” and exclusive treatment available only to a wealthy minority should be fought with a global interdisciplinary effort towards clearer regulation establishing the specific boundaries of this technology.