The creation of genetically edited babies by Dr. He Jiankui, a Chinese researcher was a breaking news headline in 2018. The discovery of CRISPR/Cas9 has made genome editing easier and less expensive compared to other techniques such as TALENs and ZFNs. It was the first recorded attempt to implant genetically modified embryos in two women who had arrived at the Southern University of Science and Technology (SUSTech) in June 2017 for their fertility problems. The women underwent in vitro fertilisation and were also convinced to participate in an experiment that no one had dared to conduct before.
Dr. He recruited these couples as a part of his experimental endeavours since both of their husbands were infected with HIV and were being managed with ART therapy. Having rationalised that their offspring would be at a risk of HIV, Dr. He conducted genome editing using CRISPR to reduce their risk of HIV infection in the future. The concept of germline edited has remained highly debated and is restricted in most countries since such genetic edits could be easily passed across generations and so would the unintended modifications and their adverse effects if any.
CCR5 gene in humans encodes a protein that facilities the entry of HIV into host cells. Dr. He intended to create human embryos that would be HIV resistant by preventing the entry of HIV into host cells after birth. To eliminate the protein encoded by the CCR5 gene, Dr. He used CRISPR/Cas9 to delete the specific 32 base pair gene segment of CCR5. Since this mutation is found to be prevalent in about 10% of Europeans naturally, it was presumed that such a delta 32 mutation would not have an adverse health effect on the babies after their birth.
Although the babies have not been monitored after their birth, there were several ethical debates right after the experiment was revealed. The basic need to edit the CCR5 gene was questioned since HIV was manageable with ART and promisingly curable with CRISPR/Cas9 based therapeutics. Moreover, although the delta 32 mutation was believed to be benign, it is now known that it plays a definitive role in our immunity against the West Nile virus and Japanese encephalitis, and the presence of the delta 32 mutation in the CCR5 gene increases susceptibility towards these diseases. Furthermore, the possibility of mosaicism meant that all cells within the body would not have the specific delta 32 mutations, implying that the genetically edited babies would still be at a risk of HIV infection. In fact, one of the babies, named Lulu, showed one normal CCR5 gene which meant that the babies were still at a risk of HIV infection. Additionally, the possibility of off-target effects in the genetically edited embryos could not be ruled out which could lead to adverse effects interfering with their normal biological processes in the future.
He Jiankui was later fined and sentenced to imprisonment for 3 years due to conduct of illegal medical practices. The scientific community also confronted the discomforting truth that genome editing regulations and restrictions were violated and CRISPR’s power was unleashed inappropriately. However, this story awakened the world to the concept of genome editing, especially CRISPR/Cas9 technology and its immense prospect of not only treating patients but also protecting future generations.