Gene-Editing Baby: A Blessing or a Curse?

By Helen Luojia Zhang

Genome editing technologies enable modifications of DNA sequences in many organisms, leading to changes in the phenotypes. They have been largely applied in areas such as agriculture, medicine, and research. The discovery of CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR associated protein 9) genome editing tool is a technical revolution, allowing cheaper, faster and more accurate DNA editing. This technology is adapted from the naturally evolved bacterial CRISPR-Cas9 defence mechanism which functions to recognise and cleave DNA of invading viruses (Jiang & Doudna, 2017). The altered CRISPR-Cas9 system consists of two key molecules: a guide RNA (gRNA) with complementary sequence to target DNA and the Cas9 endonuclease which acts as molecular scissors. gRNA recognizes and binds to target DNA sequence through complementary base pairing, guiding Cas9 endonuclease to the target location and introduces double-strand DNA breaks. The cell would then repair the damage using either non-homologous end joining (NHEJ), where part of the genome would be lost, or homologous recombination where new information from exogenous repair template would be incorporated (Hsu, Lander & Zhang, 2014). CRISPR-Cas9 has many potential applications including disease treatment. Most of the applications involve genome editing in somatic cells, which cannot be passed on to the next generation. The use of gene editing in human germline cells is, however, controversial in terms of bioethics due to its heritability. 

The entire scientific community was shocked by the birth of gene-edited twins in 2018. Chinese researcher He Jiankui had used CRISPR-Cas9 technology to edit human embryos intended for HIV treatment (Cyranoski, 2019). Embryos with HIV-positive parents were injected with CRISPR construct, which would delete 32bp of CCR5 gene in the embryonic genome, resulting in the CCR5Δ32 gene found naturally in some humans resistant to HIV (Greely, 2019). CCR5 encodes for proteins on the surface of T cells that allow HIV to enter the cells. Dr. He expected this deletion to result in the production of non-functional CCR5 protein, and thus protect T cells from HIV infection. The result, however, did not match his prediction exactly. Instead, one of the twins showed heterozygous CCR5 gene, meaning the T cell would still produce CCR5 protein, though might be in a reduced amount. Both twins also showed differential gene editing outcomes in different cells, resulting in mosaic expression patterns. This indicates the presence of potential defects in CRISPR-Cas9 technology in terms of germline editing. The function of the CCR5 protein is not fully understood, therefore, mutating the gene could possibly lead to medical conditions. The severe consequences of unintentional off-target editing of other genes should not be neglected either.

Dr. He’s experiments had aroused much controversy in the scientific community.  Many scientists who opposed this study criticised Dr. He’s experiments as irresponsible misconduct that violates the world ethical consensus. This experiment was done before adequate animal studies which may have identified potential safety issues. It has been argued that, as the technology progresses, germline modifications could potentially lead to liberal eugenics, where parents can select genes that give healthier, more intelligent children (Christiansen & College, 2017). This might also gradually alter the human gene pool because the engineered traits would be spread over generations. Despite loud protests from some scientists, others hold the view that human embryo editing provides brand-new insights into the function of the genome that cannot be possible through animal studies. This may also enable treatment for life-threatening diseases, not just for the patients, but also for their offspring. Germline genetic engineering also provides a potential approach to solve human aging problems. 

In many countries, embryo gene editing intended for reproduction is banned due to bioethical dilemmas. The application of CRISPR-Cas9 tools to human embryos would lead to an unpredictable future. We might be able to master human embryo editing in a safe way as the technology advances, but the question is, should we? More transparency is required for tight control of this research area to avoid misconduct.

References:

Christiansen, P. K. & College, V. U. (2017) Genome editing: Are we opening a back door to eugenics? Available from: https://sciencenordic.com/a/1451075 [Accessed Nov 29, 2020].

Cyranoski, D. (2019) The CRISPR-baby scandal: what’s next for human gene-editing. Nature. 566 (7745), 440-442. Available from: doi: 10.1038/d41586-019-00673-1. [Accessed Nov 28, 2020].

Greely, H. T. (2019) CRISPR’d babies: human germline genome editing in the ‘He Jiankui affair. Journal of Law and the Biosciences. 6 (1), 111-183. Available from: doi: 10.1093/jlb/lsz010.

Hsu, P. D., Lander, E. S. & Zhang, F. (2014) Development and Applications of CRISPR-Cas9 for Genome Engineering. Cell. 157 (6), 1262-1278. Available from: doi: 10.1016/j.cell.2014.05.010. [Accessed Nov 28, 2020].

Jiang, F. & Doudna, J. A. (2017) CRISPR–Cas9 Structures and Mechanisms. Annual Review of Biophysics. 46 (1), 505-529. Available from: doi: 10.1146/annurev-biophys-062215-010822. [Accessed Nov 28, 2020].