Under Fire, He Jiankui Says He’s “Proud” to Help Make CRISPR’d Babies

Xconomy National — 

[Updated, 11/28/18, 12:20pm ET. See below.] Is there another CRISPR baby on the way? In his first public appearance since his stunning claim, released on YouTube Sunday, that he helped bring the first genome-edited humans into the world, He Jiankui, a genomics researcher at Southern University of Science and Technology of China in Shenzhen, said there is a second pregnancy in his study. Shrugging off condemnation at home and across the world, He said he was proud of his work.

Like He’s claim of twins recently born who were edited with CRISPR-Cas9 in an attempt to make them immune to HIV infection, there was no supporting evidence for the second pregnancy. Indeed, the main question hanging over this week’s gene-editing summit in Hong Kong, where He spoke Wednesday, remained unanswered: Did he really do it? Are there really twin girls (He calls them Lulu and Nana) somewhere in China whose DNA has been manipulated?

CRISPR-Cas9 has made the possibility of genetically engineered babies loom closer, as scientists in the U.S. and China have disclosed experiments on embryos that would not be implanted into a woman’s womb. But the creation of humans from edited embryos has been considered out of bounds.

Before He appeared, the moderator warned the audience to behave and let him speak. There were also apparently security guards on hand.

He entered the wide stage without a jacket or tie and carrying a briefcase. During his solo presentation, he shuffled through papers on the podium and went quickly through dense slides that first detailed his preclinical work in mice. He then explained the sequencing work that convinced him that the edits worked without missing their targets, first in the edited embryos before they were implanted in the mother’s womb, then again after the children were born. (All his slides are here.)

(The debate over the safety of CRISPR-Cas9, and how much assurance scientists have that mistakes won’t lead to cancer-causing mutations, is far from settled. A new form of CRISPR editing, called base editing, is now gaining momentum because it is potentially more precise.)

He’s aim: Disable the CCR5 gene, which codes for the protein that HIV uses to infect cells. He said today in a Q&A session after his presentation that one of the embryos had both CCR5 gene copies knocked out, making the person immune, but the second embryo had only one copy knocked out, making immunity less certain. The parents were told this and decided to press on with the pregnancy, He said. When asked why he chose HIV immunity as the first, historic test, when there are other ways to prevent HIV transmission, He insisted that it was an “unmet medical need, not just for this case but for millions of children, because an HIV vaccine isn’t available.” HIV is spreading in China even while worldwide cases are decreasing.

The conference chair David Baltimore took the stage briefly during the session to comment. “I personally don’t think it was medically necessary,” Baltimore said. “The choice of the diseases we heard discussions about earlier today are much more pressing than providing some protection against HIV infection.”

Baltimore, who also chaired the first international gene-editing summit three years ago, said He’s work was “irresponsible.” A consensus emerged then, codified in a 2017 report, that human germline editing should only proceed after strong evidence of safety and efficacy, broad societal consensus, and only for urgent medical reasons.

He’s onstage interviewers—making history themselves as the first people ever to ask questions about the shell-shocking claims—were both geneticists: Robin Lovell-Badge of the Francis Crick Institute in London and Matthew Porteus of Stanford University in Palo Alto, CA.

Lovell-Badge noted, as have others since He’s announcement, that disabling CCR5 can increase a person’s susceptibility to other infectious diseases. Other questions about potential consequences arose, such as the girls’ autonomy and privacy as they grow older. If their identities become known, one audience member asked, will the one whose immunity is more certain be pursued as a better mate to pass along those genes? He said he didn’t know how to answer the question.

He at first said that in addition to the pregnant couple, there were seven other couples, but the trial was “on hold because of the current situation.” Only after Porteus pressed again about the other couples did He admit that there was “another one, another potential pregnancy.”

Under questioning, He also revealed details about the consent process for study participants that raised eyebrows. The participants, recruited through an HIV/AIDS group (all the men in the couples were HIV positive, all the women negative), first spoke with He’s lab colleagues. Then He himself spent more than an hour with each couple, he said. No one was trained in providing consent information, and the documents were vetted by four people, He said, but seemed unsure about that figure. The consent forms were posted online during his talk, at least briefly, but hours later were no longer available. (Note: It’s unclear if the demand has overwhelmed the hosting servers, or if the forms have been taken offline. We have kept the links intact for now.)

The top of the form describes the study as an AIDS vaccine development project.

He’s work is unpublished and not peer reviewed, but he said today he has submitted it to a scientific journal. The children’s DNA has not been independently sequenced, either. Harvard University geneticist George Church told Stat this week that he has seen the data and that He’s claims are “probably accurate.”

The admission has caused an international uproar. CRISPR pioneers Feng Zhang and Jennifer Doudna weighed in on Monday. Zhang called for a moratorium on the “implantation of edited embryos.” Doudna said He’s work “reinforces the urgent need to confine the use of gene editing in human embryos to cases where a clear unmet medical need exists, and where no other medical approach is a viable option.”

A long list of Chinese scientists in China and abroad have signed a letter condemning He. (The website Quartz provides a translation here.) And the university that houses He’s lab has distanced itself from his work, saying he has been on unpaid leave for months. Chinese authorities are investigating He’s claims, according to the Guardian, and a Rice University professor who advised He is also under scrutiny for telling the Associated Press that he was present in China during He’s experiments.