Last November, the scientific field was faced with an unexpected announcement by Chinese scientist Jiankui He, who claimed he had genetically edited two human embryos. The announcement was met with global condemnation and frustration that Jiankui He had proceeded with such work in the absence of ethical approval from the authorities, and with the known risks associated with gene-editing: "They’ve jumped the gun by a good 10 or 15 years and in a field like human reproduction that’s actually really risky," biologist and author Nessa Carey said.
There was a subsequent rush amongst authorities to enforce a legal and ethical framework for gene-editing experiments to ensure their safety and justification, and until this was in place any further experiments of the sort were called to be banned. However, it seems such stern warnings have not dissuaded all scientists.
An article published yesterday in Nature outlined the intentions of Denis Rebrikov, a molecular biologist from Russia, to produce gene-edited babies, making him the "second" Jiankui He. Rebikrov is the head of a genome-editing laboratory at Russia’s largest fertility clinic, the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow and is a researcher at the Pirogov Russian National Research Medical University, also in Moscow. Acknowledging that if he opted to do this prior to Russia updating their regulations on gene editing he would be breaking the law, he responds: "I think I'm crazy enough to do it".
Jiankui He used the CRISPR-Cas9 tool to create a specific mutation in the CCR5 gene that encodes a protein used by the human immunodeficiency virus (HIV)-1 to enter cells. This mutation, CCR5 Δ32, is carried naturally by some individuals and can confer innate resistance to HIV-1. Despite recent research suggesting that malfunction in this gene is linked to a higher rate of mortality, Rebikrov intends to target the exact same gene.
Jiankui He opted to modify the CCR5 gene in embryos that were created from fathers with HIV. In contrast, Rebirov plans to disable the CCR5 gene in embryos that will then be implanted into HIV-positive mothers, thus allegedly reducing the risk of them passing the virus on to the baby in utero. According to the article, Rebrikov already has an agreement in place with a HIV centre in the city to recruit HIV-infected women into the experiment.
One of the inventors of CRISPR, Jennifer Doudna, expressed her concerns regarding the biologist's plans to Nature: “The technology is not ready,” she says. “It is not surprising, but it is very disappointing and unsettling.”
Rebrikov anticipates that the health ministry will clarify the rules on the clinical use of gene-editing of embryos in the next nine months. The article states that to avoid punishment for the experiments, he first intends to seek approval from three government agencies, which could take between one month to two years.
A large concern associated with gene-editing technologies, such as CRISPR, is the possibility of off-target effects, resulting in unintentional changes to the genome – the consequences of which cannot be wholly anticipated. Efforts to refine such technologies and improve their specificity are ongoing, but thus far a "gold-standard" technique is not available.
Rebrikov claims that he is developing a technique that can ensure that there are no off-target mutations, and plans to post preliminary findings online within a month, but Doudna declares scepticism here: “The data I have seen say it's not that easy to control the way the DNA repair works.”
The Code of the Wild film documentary took filmmakers and CRISPR scientists to China, where they were the first to stumble across and bring the world's attention to the work of Jiankui He. Read more about the documentary and gene-editing in China here.
Reference: David Cyranoski. 2019. Russian biologist plans more CRISPR-edited babies. Nature. doi: 10.1038/d41586-019-01770-x.