In current research, genome editing has become an essential and a very powerful tool that holds the capacity to tackle extreme biological problems by purposeful alteration of a specific DNA segment in a cell. In late 2018, Jiankui He (JK), a Chinese researcher revealed his experiments to confer resistance against HIV by conducting germline genome editing on human embryos. JK intended to edit CCR5 gene that encodes for a receptor present on WBCs (White Blood Cells) that is essential for HIV-1 to infect cells. A CCR5Δ32 mutation that slows progression or provides resistance to HIV infection is present naturally in particular European populations, which JK tried to replicate on embryos having a Chinese genetic makeup without considering its ramifications. Previous research has shown that individuals carrying the CCR5Δ32 mutation are still susceptible to certain HIV strains. The naturally occurring CCR5 gene mutant has not been identified in any Chinese population. This indicates the lack of adequate background study regarding the exact functioning of the gene in the Chinese population before conducting the massive scientific experiments. It also puts into question the rationale of the entire experiment when there is an existing technique ‘Assisted Reproductive technology’ (ART) having an extremely high success rate to generate healthy babies without any HIV transmission from the parent to the offspring.
JK’s experimentation had several flaws. For instance, CRISPR-Cas9 method used for genome editing results in a DSB (Double-strand break) at the target site of the genome which is either repaired via NHEJ (Nonhomologous end joining) or HDR (Homology-directed repair) pathway. He employed the NHEJ repair mechanism which often leads to small indels leading to off-target mutations and undesirable on-target mutants as compared to HDR that produces a perfect repair and precise genetic modification at the target site. Additionally, the risks of gain-of-function mutations due to in-frame indels are extremely hard to foresee. Another mistake that was overlooked by JK is mosaicism, that results in mutation being contained in only part of the cells in the embryo. No method has been devised yet to avoid this inefficiency other than careful screening of each individual cell. Evidence shows that JK ignored incorrect on-target alterations, off-target events and mosaicism present in the embryos that were planted in the patients. Furthermore, JK created altogether novel mutations in the CCR5 gene instead of the WT(wild-type) CCR5Δ32 variant resulting in mutants whose effects are unknown. It might not even confer resistance against HIV and could possibly have deleterious effect, damaging the brain & immune system.
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JK’s ways of data handling and inadequate pre-clinical data indicates a troubling lack of basic scientific knowledge and prerequisite understanding of the field. JK clearly bypassed the normal standards of science and clinical research. He directly translated his microinjection protocol conducted on monkey embryos to human embryos without proper standardization. Additionally, only a single line of human embryonic stem cell (hESC) of the edited human embryos was established rather than performing it in triplicates to assess off-target mutations indicating that the quality of research is subpar. There is very less data regarding the number of embryos in total that were genetically manipulated, diagnosed using PGD (Pre-implantation genetic diagnostic) and attempts of implanting them. A major misstep was to not publish any pre-clinical data before performing such a novel clinical procedure which ruled out the crucial component of peer-review.
In conclusion, genome editing is a crucial tool and would provide significant results in the near future in the field of genetic engineering. But, there is a dire need to carefully assess the rationale, clinical procedure, data handling, risks involved and ethics regarding it. The entire episode of ‘CRISPR Babies’ clearly emphasizes the need for precise to perform high quality research while avoiding mistakes that were committed and the need for a more stringent regulatory and ethical framework.
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The Features Of Human Genome Editing.
(2022, February 17). Edubirdie. Retrieved November 15, 2024, from https://edubirdie.com/examples/the-features-of-human-genome-editing/
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