Potential Future Risks Arising from Advancements in Gene Therapy

 by Christine Zhou

Gene therapy holds great promise for treating various diseases, but like any medical intervention, it also carries potential risks and ethical considerations. 

There are risks which are generated by the media of delivering genes into cells. A vector is usually required to deliver the modified gene into the cells since a gene cannot easily be edited in the cells. The most common vectors are viruses due to the ability of recognising certain cells and injecting the gene material into them. Scientists replace the virus’ original genes with ones needed for gene therapy. This can lead to unwanted immune system reactions. The immune system may attack the newly introduced viruses mistakenly. Thus, inflammation can be caused and even organ failure can be triggered in severe cases. The second risk is the potential of introducing errors or off-target gene effects. Errors can occur when the altered viruses infect additional cells such as healthy cells, while Off-target effects occur when gene editing mistakenly targets a DNA sequence that was not intended. If these happen, both targeted and healthy cells could be damaged, causing other illnesses such as cancer. What can be even more serious is that these altered genes could be passed to offsprings, modifying descendants’ traits. In addition, it is possible for the viruses to recover their original ability to infect the cells and cause disease once they are injected into the body.

There are also concerns about the “designer” mutations involving modifying specific genetic traits according to one’s preferences, such as “designer babies”. The children’s skin colour, eye colour, hair colour or even their IQ, athletic ability or talent, can be altered by modifying their genes in embryos according to their parents’ preferences, which can cause both ethical and social issues. For those children, they may lose their right to choose and develop into who they want to be, and they are likely to be over-controlled by their parents to do many things they might not like according to their acquired abilities after gene modification. There are also worries that genome editing may only be accessible to affluent people due to its huge expense, which may exacerbate existing disparities in healthcare access and interventions. Most people may not have the accessibility to suitable genetic treatments, which is not fair to everyone. Moreover, some people fear that, taken to extremes, gene editing could create different classes of individuals defined by the quality of their engineered genomes.

When using genetic technologies, the necessity also needs to be well considered. In 2018, He Jiankui, a Chinese scientist of Southern University of Science and Technology in Shenzhen, China, was sentenced into prison after announcing his claim to have created genetically modified human twins to make them HIV negative using gene-editing technology called CRISPR. Their father, Mark, who was HIV positive, did not want to pass his infection to his offsprings, so he and his wife Grace took part in He’s trial. [1] He’s team altered the twin’s CCR5 genes when they were newly fertilised embryos floating in a petri dish. CCR5 acts as a coreceptor for HIV when the virus enters a host cell. [2] If this gene is edited, the possibility for HIV to infect the cells can be reduced. One of the twins had both copies of CCR5 altered, while the other had only one copy altered. It is still possible for people with only one copy of CCR5 to get HIV, while they may stay healthier for longer if they do get it. The scientists then transferred them to their mom’s uterus to begin the pregnancy. Although he claimed that the babies had their genome sequenced after birth, confirming that the gene editing had worked safely, He was still punished. The birth of gene-edited babies was a landmark, which means it was a deeply controversial step for science and society. Firstly, from a technical level, the CRISPR-Cas9 technology is not perfect due to the unknown potential health risks to the two gene-edited babies. At the same time, this gene modification can be passed on to the offspring of twin sisters, which can cause potential health risks in more people. Secondly, there are many mature technologies that can be used to make parents with HIV have healthy babies. For example, if a father is infected with HIV, pregnancy can be prepared by reducing the virus level in the father’s blood to an undetectable level through highly effective antiviral drugs, or by in vitro fertilisation through sperm washing. If a mother is infected with HIV, the chance of transmission can be reduced to almost none through effective antiviral drug treatment, birth assistance and scientific breeding. From these it seems like that the high-risk attempt of gene editing is completely unnecessary. It can be concluded that scientific research should give priority to the meaning of human existence before scientific exploration. [3]

Despite the rapid progress and undeniable power of gene-editing technologies, we are still in the early stages of understanding their impact on the genetic makeup of embryos and the future health and development of individuals. The social and ethical issues surrounding gene therapy in humans remain severe [4. In order to monitor the use of gene therapy, the World Health Organisation (WHO) issued new recommendations on human genome editing for the advancement of public health. WHO will foster international collaboration in the governance of such applications, to encourage appropriate ethical review of clinical trials involving human genome editing and to promote equitable access to medicines that are developed using the technology. [5] 

References:

[1] Robbins, R. (2018) Chinese scientist claims first gene-edited babies born, Scientific American. Available at: https://www.scientificamerican.com/article/chinese-scientist-claims-first-gene-edited-babies-born/ (Accessed: 10 Sep 2023).

[2] CCR5: NIH (no date) CCR5 | NIH. Available at: https://clinicalinfo.hiv.gov/en/glossary/ccr5 (Accessed: 10 Sep 2023).

[3] Liu, Y. and Yingzhe, X. (2019) Development and challenges of gene editing technology.  Available at: https://cjb.ijournals.cn/html/cjbcn/2019/8/gc19081401.htm (Accessed: 10 Sep 2023).

[4] What are the ethical concerns of genome editing? (no date) Genome.gov. Available at: https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns (Accessed: 10 Sep 2023).

[5] Ledford, H. (2021) Who should lead on genome-editing policy, advisers say, Nature News. Available at: https://www.nature.com/articles/d41586-021-01922-y#:~:text=Among%20its%20recommendations%20are%20to%20foster%20international%20collaboration,to%20medicines%20that%20are%20developed%20using%20the%20technology. (Accessed: 10 Sep 2023).