He Jiankui's Research on CRISPR Babies Dubbed 'Delusional and Outrageous' as Experts See Manuscripts for First Time

Manuscripts relating to the work of Chinese scientist He Jiankui, who claimed to have performed gene editing on twin girls born in November 2018, have been published by MIT Technology Review. In an analysis piece, the magazine had experts assess the unpublished work—with comments saying the work was "delusional and outrageous," and that its conclusions are an "egregious misrepresentation of the actual data."

He announced the birth of twin girls Lulu and Nana in November 2018 at the International Human Genome Editing Summit in Hong Kong. He claimed to have modified the embryos using the CRISPR gene editing technique to make them more resistant to HIV. Some people carry a mutation in the CCR5 gene that appears to block the pathway for HIV to enter the blood. In his experiment, He said he had not replicated the mutation but had hoped to mimic its effects.

The announcement was met with global condemnation. While gene editing is a promising new technology, researchers do not yet fully understand the consequences. Genes do not perform single tasks, so editing one could lead to a host of unknown consequences. The CCR5 gene, for example, is also involved in memory and cognition.

According to a report in China's state run news agency Xinhua in January, He is being investigated by the government after a review into his work concluded he had carried out gene editing despite this practice being "officially banned in the country."

Another problem with He's work was that he did not make available the research showing what he did during his experiments.

MIT Technology Review said it was sent manuscripts of He's work earlier this year. These papers were sent to experts and the magazine has now published them in parts, showing that He completely misinterprets his data. The team appears to have created new mutations that could lead to HIV resistance, but they did not perform any tests to see if it was successful. The justification for the work in the summary also claims the work could save millions of lives—something the scientists who have now seen the work disagree with.

Fyodor Urnov, genome-editing scientist at the University of California, Berkeley, told MIT: "The claim they have reproduced the prevalent CCR5 variant is a blatant misrepresentation of the actual data and can only be described by one term: a deliberate falsehood. The study shows that the research team instead failed to reproduce the prevalent CCR5 variant. The statement that embryo editing will help millions is equal parts delusional and outrageous."

Hank Greely, professor of law at Stanford University, also highlights the problems relating to the ethics review. According to the magazine, the manuscripts say the research was registered with the China Clinical Trial Registry. However, registration only appears to have been carried out after the twins had been born.

"The article also does not discuss the Chinese ban on assisted reproductive services for HIV-positive parents," Greely told the magazine. "It has been reported that He had other men pretend to be the intended fathers for [the] purpose of the required HIV tests. The article doesn't say this. It seems to me likely to be true—and damning. If true, it means He defrauded the Chinese regulatory process."

The paper also highlights the team's plan to test the girls' blood for HIV resistance and their intentions to monitor their health for 18 years, with potential for this to extend into adulthood. However, as Urnov points out, the team could have performed laboratory tests on embryos to see if the gene editing worked before progressing the research to the stage where babies were born.

"This…proves that the research team placed their interests above those of the couple who donated the embryos and of their prospective children," he told the magazine. "It was essential to have determined that [the new genes would be HIV resistant] before the embryos were implanted. They could have done so using a known assay: introduce the same edits into immune system cells in the laboratory and then infect them with HIV. Only the cells that have HIV-protective variants of CCR5 survive.

"The research team chose not to do that assay. Instead, they made children out of embryos that had forms of CCR5 of entirely uncertain functional impact. Were the researchers in a rush? Did they simply not care? Whatever the explanation, this egregious violation of elementary norms of ethics and of research borders on the criminal."

Since He's announcement, scientists across the globe have called for a consensus on gene editing in humans. In March, Nature published an article by experts including Eric Lander, the president and founding director of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts. In the article, the authors "call for a global moratorium on all clinical uses of human germline editing." They say that while different nations can choose different paths on how to progress this technology, "they would agree to proceed openly and with due respect to the opinions of humankind on an issue that will ultimately affect the entire species."

He has not been seen in public since January. According to AP, he was last seen on a balcony of an apartment in Shenzhen that was owned by the university he was working for at the time. What, if any, punishment he will get is unclear—with Xinhua saying that He and other personnel involved "will be dealt with seriously according to the law."