Nana K's Miscarriage

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Lore & Background

He Jiankui, working at the Southern University of Science and Technology (SUSTech) in Shenzhen, China, started a project to help people with HIV-related fertility problems, specifically involving HIV-positive fathers and HIV-negative mothers. The subjects were offered standard in vitro fertilisation services and, in addition, use of CRISPR gene editing (CRISPR/Cas9), a technology for modifying DNA. The embryos' genomes were edited to inactivate the CCR5 gene in an attempt to confer genetic resistance to HIV. The clinical project was conducted secretly until 25 November 2018, when MIT Technology Review broke the story of the human experiment based on information from the Chinese clinical trials registry. Compelled by the situation, he immediately announced the birth of genome-edited babies in a series of five YouTube videos the same day. The first babies, known by their pseudonyms Lulu (露露) and Nana (娜娜), are twin girls born in October 2018, and the second birth and third baby born was in 2019, named Amy. He reported that the babies were born healthy.

In Their Own Story

On 10 June 2017, a Chinese couple, an HIV-positive father and HIV-negative mother, pseudonymously called Mark and Grace, attended a conference held by He at SUSTech. They were offered in vitro fertilisation (IVF) along with gene-editing of their embryos so as to develop innate resistance to HIV infection in their offspring. They agreed to volunteer through informed consent and the experiment was carried out in secrecy. Six other couples having similar fertility problems were subsequently recruited. The couples were recruited through a Beijing-based AIDS advocacy group called Baihualin China League. When later examined, the consent forms were noted as incomplete and inadequate. The couple were reported to have agreed to this experiment because, by Chinese rules, normally HIV positive fathers were not allowed to have children using IVF.

Reader's Guide

He Jiankui took sperm and eggs from the couples, performed in vitro fertilisation with the eggs and sperm, and then edited the genomes of the embryos using CRISPR/Cas9. The editing targeted a gene, CCR5, that codes for a protein that HIV uses to enter cells. He was trying to reproduce the phenotype of a specific mutation in the gene, CCR5-Δ32, that few people naturally have and that possibly confers innate resistance to HIV, as seen in the case of the Berlin Patient. However, rather than introducing the known CCR5-Δ32 mutation, he introduced a frameshift mutation intended to make the CCR5 protein entirely nonfunctional. According to He, Lulu and Nana carried both functional and mutant copies of CCR5 given mosaicism inherent in the present state of the art in germ-line editing. There are forms of HIV that use a different receptor instead of CCR5; therefore, the work of He did not theoretically protect Lulu and Nana from those forms of HIV. He used a preimplantation genetic diagnosis process on the embryos that were edited, where three to five single cells were removed, and fully sequenced them to identify chimerism and off-target errors. He says that during the pregnancy, cell-free fetal DNA was fully sequenced to check for off-target errors, and an amniocentesis was offered to check for problems with the pregnancy, but the mother declined. Lulu and Nana were born in secrecy in October 2018. They were reported by He to be normal and healthy.

Did You Know?

• He Jiankui was listed in Time magazine's 100 most influential people of 2019.
• The first genetically edited babies, Lulu and Nana, are twin girls born in October 2018.
• He Jiankui was sentenced to three years in prison with a fine of 3 million yuan on 30 December 2019.
• The World Health Organization has issued three reports on the guidelines of human genome editing since 2019.
• In 2020, the National People's Congress of China passed a Civil Code and an amendment to Criminal Law that prohibit human gene editing and cloning with no exceptions.