The Story of He Jiankui, Now Out of Jail After Editing DNA of Unborn Babies

Chinese biophysicist He Jiankui, who shocked the medical world by claiming he had used gene-editing technology in unborn babies, was released from a prison in China last week after a three-year sentence, according to reports.

He was jailed in late 2019 for violating medical regulations after announcing his work at a conference the previous year.

According to China's Xinhua news agency at the time, a court found that He and colleagues "crossed the bottom line of ethics in scientific research."

There remain many unknowns in the aftermath of He's work, but he claimed that he used a gene-editing procedure known as CRISPR-Cas9 to rewrite the genomes of embryos before the children were born.

The aim of doing this, He said, was to make them immune to HIV by modifying a certain gene called CCR5. Twin sisters, known as Lulu and Nana, as well as a third child known as Amy, were later born to volunteer parents who took part in the research in 2018. He said Lulu and Nana were born healthily, though their status today remains a mystery.

The problem with CRISPR

CRISPR-Cas9 is sometimes described as acting like molecular scissors that can cut strands of DNA at certain locations within a genome. Scientists can then introduce changes to the DNA at the repair stage.

A long-standing issue in gene editing is targeting DNA precisely. Previous editing techniques that used chemicals or radiation allowed no control over where in a genome a mutation might occur.

While CRISPR may have made improvements in this regard, it's far from perfect. Dr. Kiran Musunuru, professor of medicine and director of the Genetic and Epigenetic Origins of Disease Program at the Perelman School of Medicine, thinks the scissors analogy overstates CRISPR's accuracy.

"It's kind of like if you accidentally tear a page, [you can] tape it up, but often the edges of the tear are rough. It doesn't quite match up and you lose some words or you lose some letters; you obscure the meaning of the paragraph.

"So, if you look at it in those terms, it's really crude, and there are potentially bad consequences. So again, using this analogy of making a tear, let's say you accidentally tear through the whole page. Well, that can happen in the genome, too.

"So He Jiankui was trying to turn off a gene called CCR5. We know that people who naturally have this gene turned off are more resistant to HIV infection, and so he was trying to make babies who, as they grew up, would be resistant to HIV infection.

"That was the whole premise, and he was using this crude version 1.0 of CRISPR. It was basically just injecting it into embryos and hoping it would turn off the gene and not cause any problems."

The reveal

He Jiankui's project was not widely known prior to the international genome-editing summit in Hong Kong in late 2018.

Before the summit took place, He reached out to journalists via a publicist, offering them a scientific manuscript outlining his work that he was planning to submit to a scientific journal. Unsure what to make of it, the journalists reached out to experts for their insight.

Musunuru was one of the experts who looked over these early manuscripts. He said he was shocked at what he saw. "My reaction was very visceral, very upset, you know, screaming in my office, 'what on Earth has just happened?'

"I realised that this was for real. He had actually done what he claimed he had done; that these were babies who had been born from embryos that had been edited with CRISPR. And the reason I knew that was because when I looked at the data, I immediately saw evidence that things had gone wrong—that there were off-target edits, as I described before; that the embryos had ended up being a patchwork of edits, so some of the cells were edited, and some were not and different cells had different edits. I could immediately see that looking at the data in the manuscript.

"I still don't totally know whether [He] understood the implications of his own data… it was like he just didn't understand what his own data was telling him."

Musunuru, bound by a confidentiality agreement, could not publicly announce his concerns for several days. But with just days to go before the Hong Kong summit, Antonio Regalado, a reporter for MIT Technology Review, spotted details of He's work on a clinical trials website. The story broke prematurely, and He's work was suddenly thrust into the spotlight.

He released a YouTube video in which he stated the gene experiments had been successful. "The gene surgery worked safely," He said, adding that the babies' genes were sequenced before and after birth to monitor any changes. "No gene was changed except the one to prevent HIV infection," He said.

Despite He's claims, his work met widespread condemnation and the Chinese government began investigating. Xinhua news agency reported that an investigation by the Health Commission of China found He had "deliberately evaded oversight."

By January 2019, He had been fired from the Southern University of Science and Technology (SUSTech) in the city of Shenzhen. By December that year, a court in Shenzhen found He guilty of "illegal medical practices" and of forging ethical review documents.

Fate of the gene-edited children

Joy Zhang, a sociologist and founding director of the Centre for Global Science and Epistemic Justice at the University of Kent, chaired a meeting in March this year to discuss the ethical obligations to protect the three children who were affected by He's work going forward. The meeting became the basis for a subsequent report.

"As far as I am aware, there is little public knowledge concerning the two families and the three children," Zhang told Newsweek. "But we hope the report will help create social conditions for them to lead good and autonomous lives."

Robin Lovell-Badge, head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute, had spoken to He shortly after news of his experiments emerged and criticized the work. He also took part in Zhang's meeting earlier this year.

Lovell-Badge said that the three girls who were affected by He's work should be able to grow up in as normal an environment as possible. "There would have to be very good justification to give any special labels to any of the three girls who are the products of He Jiankui's experiment," he told Newsweek. "We do not do so for children born after any IVF procedure such as preimplantation genetic diagnosis, and we all have unique 'mutations' that occur during the development of the egg, sperm and early embryo that gave rise to us.

"It is far more important that they are allowed to grow up in a normal and caring environment and that they are not subject to anything but a watchful eye—which is something that should happen with all children. If they have any deleterious mutations, then they may need some special care and counseling—but again, this is something that any caring society should provide."

The other question is what He will do next. Musunuru does not think there is much concern of any further tests on the scale of He's previous work. "Given his notoriety and, presumably, close monitoring by his government, I don't think anybody's too worried that He Jiankui will pick up where he left off," he said.

"It's worth noting that he never had a medical license, since he was not a physician and had no medical training whatsoever—which of course was one of the major problems with his 'clinical trial.' I'd also expect that Chinese institutional ethical committees that are charged with approving clinical trials will have a much higher bar than they evidently had in the past."