It’s been a year since He Jiankui announced that he’d made the world’s first gene-edited human babies, twin girls with the pseudonyms Lulu and Nana. Widespread condemnation of his actions followed the announcement. But the facts of the case remain unclear, because he has not been transparent about his work.
In his single public appearance following his announcement, at the Second International Summit on Human Genome Editing in Hong Kong in November 2018, He presented his work by racing through about 60 slides in just 20 minutes. Although he showed data about what he had done to the twins’ genes, it was blink-and-you’ll-miss-it, and not enough to convince anyone of his claim that he’d safely edited the genomes of the human IVF embryos that became Lulu and Nana.
At the summit, He did say he’d just submitted a manuscript describing this work to a scientific journal. Twelve months later, however, the manuscript has remained unpublished and its contents mysterious.
He was asked at the summit why he hadn’t posted his manuscript to a preprint server such as bioRxiv or on a public website—something scientists frequently do to invite feedback on early drafts. He claimed that he’d intended to do so, but colleagues had advised him to allow the manuscript to go through peer review by other scientists before posting it. (Normally, formal peer review takes place only when an academic journal is considering publishing a paper.)
By deciding not to release his manuscript right away, He has made it difficult for other scientists to figure out exactly what he did and how he did it. We already know that there were profound ethical problems with He’s work in germline gene editing, which refers to genetic alterations to embryos—or to egg or sperm cells—that can be passed down through the generations. But its scientific merit, and especially its safety, have remained in question.
When I first had the opportunity to look through a complete manuscript from He last November, I immediately realized there were problems.
The most serious was rampant “mosaicism.” This means that the gene edits He made to the embryos didn’t take effect uniformly: different cells showed different changes. Evidence of mosaicism is present in both Lulu’s and Nana’s embryos, as well as in Lulu’s placenta, making it likely the twins themselves are mosaic. Some parts of their bodies may contain the specific edits He said he made, other parts may contain other edits he didn’t highlight, and yet other parts may contain no edits at all. This would mean that the purported benefit of He’s editing— HIV resistance—may not extend to the twins’ entire bodies, and they could still be fully vulnerable to HIV.