Cracking the Code: Unpacking the Ethics of Genetic Editing

In the realm of scientific breakthroughs, few hold as much promise and controversy as gene editing. As a revolutionary technology, gene editing has the potential to transform the landscape of medicine, offering unprecedented opportunities to treat genetic diseases and enhance human health.

With the advent of techniques like CRISPR-Cas9, scientists now possess the ability to screen, modify, and manipulate DNA with remarkable precision, bringing hope for targeted therapies, personalised medicine, and even the eradication of hereditary conditions.

However, as this power becomes increasingly attainable, profound ethical considerations emerge. The immense potential of gene editing necessitates a thoughtful exploration of its promises, limitations, and the ethical constraints that must accompany its use.

Genetic Editing and Preimplantation Genetic Screening

Preimplantation genetic screening (PGS) is a reproductive technology used during in vitro fertilisation (IVF) to assess the genetic health of embryos before implantation. It involves the analysis of embryos to detect chromosomal abnormalities and genetic disorders. By examining the genetic material of the embryos, PGS helps identify embryos with a higher likelihood of implantation success and reduces the risk of implanting embryos with chromosomal abnormalities or genetic disorders.

Genetic editing offers significant potential benefits for the treatment of single-gene diseases. By precisely targeting and modifying specific genes associated with these monogenic diseases, such as sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT), genetic editing techniques hold the promise of correcting or eliminating disease-causing mutations at their source.

By correcting the underlying genetic abnormalities, genetic editing could help restore normal cellular function, halt disease progression, and alleviate the symptoms and complications associated with these conditions. This holds enormous promise for improving the quality of life for affected individuals and their families, potentially offering new avenues for treatment and prevention of previously untreatable or incurable single-gene diseases. However, any march towards medical advances is inextricably entangled with the attendant ethical issues that we must confront.

Genetic Editing: Ethical and the Social Issues

Genetic editing, with its potential to modify the fundamental building blocks of life, raises profound ethical concerns. One primary concern is the potential for unintended consequences and unforeseen long-term effects. The precision and efficiency of editing techniques like CRISPR-Cas9 are improving, but there is still a risk of off-target mutations or other genetic abnormalities that could lead to unforeseen health issues.

‘Designer babies’

One of the first concerns that comes to most people's minds when discussing genetic editing is the concept of ‘designer babies.’ This describes the use of PGS for non-medical purposes, such as enhancing traits like intelligence or physical appearance. This raises concerns about the potential for creating a society that values certain genetic characteristics over others and the potential for discrimination or marginalisation based on unattainable genetic standards.

The concept of saviour siblings, which follows the discussion of designer babies, raises important ethical considerations and highlights the impact of advancing technology. Saviour siblings refer to children born to parents who have a child with a life-threatening disease to serve as a donor of biological materials such as blood and stem cells. The selected embryo must be free of the disease and a suitable match for human leukocyte antigen (HLA).

While this approach may bring benefits for some individuals, it also introduces ethical concerns related to preimplantation genetic diagnosis (PGD) and genetic editing, with additional ethical considerations regarding the well-being of the saviour sibling.

PGS is not a new practice. It has existed long before CRISPR-Cas9 was developed and it has been debated by ethicists, geneticists, patients, and advocates alike for a number of years. Boyle & Savulescu, in a 2001 paper published in the BMJ, take an approach that may leave some queasy:

Who is harmed by allowing PGD [preimplantation genetic diagnosis] to be performed solely for the benefit of a relative? Not the couple who wish to produce an embryo. Nor the child who would not otherwise have existed. Nor the person who receives the stem cell transplant that might save his or her life.

This is a fairly staunch utilitarian position and not one that everyone would be comfortable with. It certainly doesn’t take into account the feelings that the little brother or sister may experience later in life when they discover they were merely a means to an end. This is not to say parents wouldn’t cherish and appreciate this child as they would their ailing one, but the thought is definitely worth bearing in mind as part of the ethical calculus when considering these decisions.

Does the ‘disease’ need a cure`?

One major question surrounding genetic screening and editing is who decides what a disease is? And following on from that, who decides that a disease necessarily needs to be cured? One example of this controversy is deafness.

A 2022 study investigated the use of CRISPR/CasRx-based RNA editing to treat autosomal-dominant hearing loss in mice, paving the way for such research in humans. However, all of this builds on the assumption that deafness requires a cure, yet many believe that it does not.

Deafness is often viewed through a cultural lens that emphasises the diversity and identity of the deaf community. Some argue that elaborate, expensive, and unnatural procedures for selecting embryos without serious genetic mutations conveys the message that people with disabilities are less highly valued than those without. It is crucial to recognise that the assumption of deafness as a condition requiring a cure may stem from societal norms rather than an inherent medical necessity.

This issue could be considered a counter-narrative to designer babies. Again, it is not new and has courted controversy as far back as 2002 when a same-sex couple (both of whom are deaf) intentionally selected for a sperm donor with a history of deafness.

These examples demonstrate that this is not an issue for just medical professionals to debate. It is an ethical hot potato and we ought to involve everyone from doctors to ethicists, to people living with disability when deciding what is the ‘right’ thing to do.

Social inequities

The implementation of PGS and genetic editing raises concerns about potential social inequities. Access to these technologies may be limited by factors such as cost, availability, and geographical location, creating disparities in who can benefit from these advancements. This can result in unequal opportunities for individuals and families to access genetic testing, diagnosis, and treatment options.

It would be folly to pretend this is a new phenomenon. Healthcare systems are often structured in such a way that those with more wealth have access to the best care. Some pharmaceutical treatments have a monthly cost amounting to a deposit on a first-home. The factors leading to this inequality are vast and profound and this article cannot do justice to them all.

Existing inequalities, however, should not amount to a justification for further inequalities. For example, the sale of one’s organs is almost universally illegal (Iran comes to mind as an exception) despite the fact that there is an argument that this would save lives. In a world where organ markets are prohibited, the ailing and ageing rich may buy organs from the poor, ‘satisfying’ both parties.

There is a visceral disgust to this idea regardless of seeming benefits to both seller and buyer. This disgust should perhaps be evoked when we decide on the future inequalities that will emerge (some are already here) from these technologies.

It is crucial to address these social inequities to ensure that genetic editing and PGS are accessible, affordable, and ethically applied for the benefit of all individuals, regardless of socioeconomic status or background. The organ market example shows us that we can adopt a moral-based policy even if, to speak crudely, lives are lost in the process.

The Benefits of PGS and Genetic Editing

PGS offers several potential benefits in reproductive medicine. By analysing embryos created through IVF, PGS enables the identification of genetic abnormalities, such as a mutation in the CFTR gene that causes cystic fibrosis (CF), and chromosomal disorders before implantation. This screening process allows for the selection of genetically healthy embryos, increasing the chances of successful pregnancies and reducing the risk of miscarriages. PGS can be particularly beneficial for individuals or couples with a history of genetic disorders, advanced maternal age, or recurrent pregnancy loss. It provides valuable information that helps healthcare professionals and patients make informed decisions about embryo selection, improving the overall success rates of assisted reproductive technologies and potentially enhancing the health outcomes for children born through IVF.

In addition to screening for monogenic diseases such as CF, a gene editing technique called Adenine Base Editing (ABE) has been demonstrated to effectively edit the CFTR mutation in intestinal organoids using cells from CF patients without detectable off-target effects. However, these therapies still remain in the research phase.

Gene editing is a vital component of CAR-T cell therapy, a groundbreaking immunotherapy for certain cancers. This therapy involves techniques like CRISPR-Cas9 to modify a patient's own T cells to express a synthetic receptor that targets cancer cells specifically.

Conclusion

The rapid progression of genetic editing technologies offers immense potential benefits, but it also presents ethical challenges that demand careful consideration. The swift advancements in genetic editing have outpaced the development of comprehensive regulatory and legal frameworks. It is crucial to ensure that as we harness the power of genetic editing, we simultaneously engage in robust ethical discussions and establish appropriate regulatory mechanisms. It is essential to balance the pursuit of scientific knowledge and technological advancement with consideration of the ethical implications and societal impact.