Ethical Considerations in Human Genome Modification
Human genome modification is essentially what the name entails; a group of technologies that give scientists the ability to change a human’s DNA, either by adding, removing, or altering genetic material. As with any other scientific advancement, human genome modification is having its fair share of uncertainty and investigation for potential risks & benefits.
Medically, gene editing technologies could begin a new era for genetic disease treatment and medical advancements. However, such radical changes and different uses pose serious ethical concerns requiring careful research and smart approaches. The public seems to have a wide variety of opinions, depending on their backgrounds, the scenario in which it’s being used, side effects, etc. According to Pew Research Center, 52% of US adults think gene editing to reduce a baby’s risk of developing disease is crossing the line, versus 46% saying it’s for the baby’s good, with more religious people feeling it’s meddling with a human’s natural state.
By examining the possible risks and wide variety of moral perspectives on this potentially life-changing technology, we can identify unforeseen consequences, enabling us to raise awareness of improved safety and ethical protocols to scientists. This way, we can help foster responsible use of gene editing technologies, ensuring the well-being of individuals and society as a whole.
The CRISPR technique, which stands for Clustered Regularly Interspaced Short Palindromic Repeats [of genetic information] is a genetic editing procedure first used by researchers at the University of Berkeley in 2012. This relatively new piece of technology proved to be more effective than other existing technologies such as ZFN and TALEN, portraying better results in precision, accessibility, and price.
This technique uses the DNA of bacteria that create an immunizing mechanism against certain viruses. These DNA sequences can effectively locate viruses that enter bacteria and launch enzymes that will break them down. This allows the enzymes to recognize future viruses using the resulting fragments, therefore immunizing the bacteria.
Human Germline Modification
There are three types of cells which can be modified by gene editing technology:
Somatic: Only affects the individual and is non-heritable to offspring.
Embryonic: Usually affects the individual but could affect offspring if used for germline modification. Embryonic cells are used for the development of the embryo.
Gametes: Affects both the individual and Is heritable to offspring. Examples of gametes include sperm cells and ova/eggs.
Gene editing that takes place in embryonic cells and gametes is called germline modification. This type of genome modification is not only edited in the individual but is also passed down to every cell of an embryo, which will also affect the offspring and subsequent generations.
This is different from heritable genome modification which is used to modify embryos that are transferred to the uterus to initiate pregnancies. On the other hand, germline modification is used to modify gametes or early-stage embryos in a lab, resulting in a DNA different from the parents and is not used for reproduction. These are most commonly used to edit faulty elements of one’s DNA.
As a result of its ability to modify both the individual & generations of offspring, human germline modification entails numerous ethical and safety considerations. Hence, it is prohibited in most countries around the world, including the US, UK, China, and the entire European Union.
Ethical Concerns in Germline Modification
Regardless of whether treatment works or not, ethical concerns are always present. These include:
Issues related to potential failure:
1. Off-target effects: These are unwanted effects on the genome in addition to the intended genetic change. With germline modification of early-stage embryos, off-target effects have a dangerous potential to spread their impacts to multiple organs of the embryo. As the purpose of germline editing is ultimately to make sure the edits are included in every cell of the embryo, off-target effects can also be included with these edits, thus putting the offspring and generations to come in danger.
2. Mosaicism: This is an issue in which several populations of cells have a different genetic makeup in the edited person’s body. Mosaicism could occur when the edits are being done after the division of an initial cell embryo into two cells. This could be problematic as the disease that the modification intends to prevent could still occur if all the cells do not have the desired edit. As mosaicism is not well-known yet and is unpredictable, it could lead to new diseases or incomplete embryo development.
Figure 1: Later-stage embryo with mosaicism caused by the addition of CRISPR after maternal DNA mutation (a) versus uniform later-stage embryo due to the addition of CRISPR before DNA mutation (b).
Issues related to potential success:
1. Eugenics: This refers to the selection of positive traits and the removal of diseases or traits that are viewed negatively. Eugenics in both forms raises concerns as it seems to reinforce prejudice and create societal expectations of normalcy. This is especially true when this technology is used more for ‘enhancements’ than therapeutic purposes. But perhaps the most uneasiness is felt when realizing this technology’s potential in identifying some individuals and their traits as ‘unfit’. Any form of selection of traits in a person wrongly reflects on the ‘fitness’ of the person and the value of people with those traits in our society.
2. Procreative Beneficence: Allowing parents the control to change aspects of their children’s genetic inheritance defines a sort of expectation to ‘create the best children in society’, which is known as procreative beneficence. This stereotype degrades people with those ‘unwanted’ genetic aspects and makes them feel not welcome or secluded in society.
3. Social Justice and Inequalities: If access to germline modification were to become a reality, it would most probably be expensive, available to a certain geographical location, and might not be covered by all insurance/health systems. That being said, unequal access will create socioeconomic, cultural, and geographic divides, even though genetic diseases exist universally. This could in turn also reduce the number of resources available for those with genetic diseases to treat them.
Given the nature and number of unanswered ethical and scientific questions, germline modification shouldn’t be performed unless the following thresholds are developed.
1. Defining acceptable methodologies and setting minimum standards & maximum thresholds to measure the impact of off-target mutations.
2. Consensus on the admissible genome edits and their potential for unintended consequences
General Uses and Conclusions
Moving away from germline modification, let’s discuss the general uses of gene editing technology and their ethical considerations.
In the United States, a study has been conducted relating to the ethical concerns for the therapeutic use for curing hemophilia. 21 participants from various states took part in the hemophilia study, and the overall consensus was if it didn’t affect the mother or the offspring significantly, then it would be considered acceptable, but normal treatment would be the best option. However, the biggest concern was about the safety of the baby.
Another study in the United States has been conducted using 1,600 adults regarding the use of gene editing technology for therapeutic versus enhancement purposes and whether it’s heritable or non-heritable. Regardless of whether it would be passed down to the offspring, the majority has stated that it should strictly be used for therapeutic purposes only. Theology, philosophy, and research ethics have all outputted the same consensus.
Gene editing technology is acceptable when used for curative purposes, not for enhancement due to potential off-target effects, mosaicism, and the negative impact on families and society. Much more research needs to be conducted and more regulations need to be in place in order to prevent misuse and to ensure safe and practical application.
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