China’s first Gene-Edited Babies May Not Have Been Successful After All
In late 2018, the world was shocked by the news of the birth of the first CRISPR gene edited twin babies. Chinese biophysicist He Jiankui carried out an experiment to create babies with a natural resistance to HIV by editing the CCR5 gene, known to play a role in the immune response. He made claims for a medical breakthrough that could “control the HIV epidemic”, however as he failed to introduce the intended protective mutation it remains unclear if he has been successful. Scientists internationally have called for a moratorium, or an indefinite ban, on gene editing of human embryos amongst widespread outcry that creating the twins Lula and Nana was highly unethical.
The CCR5 Delta 32 gene mutation can be found naturally in some humans and is linked to a natural resistance to HIV. After the original research was received by MIT Technology Review, many say that the task to immunise the twins against HIV may have failed and instead created unintended mutations, as the research team failed to reproduce the exact CCR5 delta 32 variant known to protect from HIV.
MIT Technology Review received a copy of the manuscript “Birth of Twins After Genome Editing for HIV Resistance” earlier this year and have recently released several excerpts. The full manuscript remains unpublished after consideration by at least two prestigious journals, such as Nature and JAMA. Two drafts of the report were made and seem to be edited prior to publication, with one paper stating that the twins were born in November 2018 – despite international uproar in October 2018 when the news of the births first broke.
During screening, pre-implantation genetic diagnosis (PGD) showed two blastocysts were found to be successfully edited. However, not with the CCR5 delta 32 mutation known to confer natural HIV resistance. One contained a frameshift in the CCR5 gene in both copies, and the other had a 15 base pair deletion in one copy of the CCR5 gene. The team only “expected” that these changes may lead to HIV resistance, but they cannot know for sure since the edits are not identical to the known CCR5 delta 32 mutation.
The father was HIV positive, which holds significant social stigma in China and makes it virtually impossible to have access to fertility treatment. A well established technique known as “sperm washing” prevents HIV being passed on to unborn children. This begs the question – if this technique already existed, why did the parents choose to opt for a procedure which could be potentially harmful? Many suggest that the parents may not have known the full extent of what the experiment involved or may not have had another choice.
The paper was shared with a gene-editing specialist, a legal scholar, an embryologist, and an IVF doctor to gather their thoughts. Concluding remarks include that the medical benefits were dubious at best; the experiment went ahead without knowing the effects of the edits they had made; there is no current data to support the claims that He Jiankui and his team propose; and potentially there may have been pressure for the babies’ parents to agree to join the experiment.
Opinions on the use of CRSIPR technology for human germline gene editing remain divided on whether it should be prohibited entirely or given permission to be trialled in patients with lethal congenital diseases.