He Jiankui: Creative or Criminal?

         He Jiankui, informally known as J.K., is a Chinese scientist who became well known in 2018 after announcing the birth of twins, Lulu and Nana, whose embryos he had modified using gene-editing technology to make them HIV resistant. CRISPR, a gene editing tool developed in 2012 by Jennifer Doudna and her team, repurposes a protein that bacteria use to protect themselves from viral infection by cutting out their own DNA. Since the creation of this new gene-editing tool, scientists have speculated that it could be used to modify human DNA.
        In Walter Isaacson’s book about Jennifer Doudna and her life up to and beyond the invention of CRISPR, he recalls how she responded to his question about her technology being used for gene-editing in humans. She told him it was “in the realm of science fiction”, but Isaacson seems to disagree, citing J.K.’s experiment. If the creator of the technology couldn’t see this application as possible, why did J.K.?

        Use of CRISPR on human embryos had been theorized before, because there was a clear possibility it could edit human DNA to treat genetic disorders or confer resistance to disease. And, because genes are heritable, these defensive measures would be passed down to an embryo’s future offspring. Editing a gene is risky and can be imprecise, so concerns about potential off-target effects, personal autonomy, and informed consent all turned this application into an important ethical debate among scientists. There were also concerns about a potential “designer baby” industry, where parents could pay to choose certain characteristics for their children. J.K. was motivated, or perhaps blinded, by his roles as both a scientist and father to two daughters, to skirt ethical guidelines and carry out an experiment intended to edit an embryo’s genes to grant resistance to HIV.
        In order to be successful, J.K. had to find a way to edit human genes in a way that would protect the subject from HIV infection. His solution to this was replicating a known genetic mutation artificially using CRISPR. This mutation is called CCR5-Δ32, and it modifies the CCR5 receptor on cells in the immune system in such a way that HIV cannot enter the cell. He chose this mutation because people who have it naturally have been found to have resistance to HIV. It’s also a good choice because it’s a base-deletion mutation (32 nucleotides long, hence the name), which means a section of the DNA is missing. This is the type of edit that the original CRISPR mechanism excels at.
        When announcing the birth of the twins, J.K. said they were “as healthy as any other babies”. He has, however, stated that the long term effects of the modification are not known. There are a few issues that could arise with the twins' health. One problem is that the CCR5 receptor that is not present in people with this mutation is usually important for immune and neurological function. People who naturally have the CCR5-Δ32 mutation are more susceptible to certain diseases, while being more resistant to others. Another issue is that mosaicism was found in the twins, meaning both unedited and edited cells were present. This could mean that parts of their bodies are still susceptible to HIV, but there is no way of knowing what off-target effects will appear once the girls grow up.

        J.K. spent three years in prison for his unauthorized experimentation. Within the scientific community, his actions are widely seen to be irresponsible and dangerous. Support from the public has been mixed, however, with some people believing that the chance of finding a way to better defend against disease is worth the risk this type of genetic intervention carries. He now works as Dean of the Pharmacology Laboratory at Wuchang University of Technology, and has stated his intent to work on human gene-editing experiments again in the future.