On Nov. 28, He Jiankui — a postdoctoral fellow at Stanford from 2011-2012 — announced to hundreds of scientists, colleagues and journalists that he had created the world’s first genetically edited babies: twin girls with the pseudonyms Lulu and Nana whose DNA he claims to have altered to make them HIV-resistant.

Though not verified, He’s work has been met with international outcry. Many consider such work to be an unethical violation of scientific norms and, amid conflicting reports about his current whereabouts, He has not been heard from since around the time of the announcement.

He conducted postdoctoral research at Stanford in 2011 under bioengineering and applied physics professor Stephen Quake before returning to China in 2012 to open his own lab. He returned to Stanford at least four times afterwards to speak with various researchers and bioethicists including Quake, pediatrics professor and co-founder of CRISPR Therapeutics Matthew Porteus M.D. ’94 Ph.D. ’94 and adjunct professor in Stanford Medical Center William Hurlbut ’68 M.D. ’74.

November summit

He gave a presentation of his work at the second International Genome Editing Summit in Hong Kong, a conference aimed at addressing rapid advances in genome-editing research and the ethical, legal and social implications of new technologies in the field.

He was originally slated to appear in a panel alongside other scientists to discuss human embryo editing, but after news broke that He’s lab had conducted genetic tests on implanted human embryos, organizers rearranged the schedule to allow him to address the situation. He had released a video the previous day claiming that his lab had carried out successful embryonic gene surgery on two girls born “safe and healthy” several weeks prior.  

“He was [initially] supposed to be one of several speakers,” Hurlbut said. “So what they did was put all those speakers in an earlier session and clear a whole hour for [him].”

Robin Lovell-Badge, a member of the Summit’s organizing committee and head of the Stem Cell Biology and Developmental Genetics Laboratory at the Francis Crick Institute, said before He’s presentation that the summit organizers did not know of his experiments when they first invited him to speak or even until the story broke the night before.

“In fact, he had sent me the slides he was going to show in this session, and [they] did not include any of the work that he will talk about about,” Lovell-Badge said prior to He’s presentation at the Summit. “There was some clinical data but nothing involving implanted human embryos.”

Ethical implications

Critics have called attention to the ethical implications of He’s work — namely, that genetic manipulation to eliminate genetic disease at the embryonic stage could eventually lead to a slippery slope of using genetic manipulation to create “designer babies,” or human embryos genetically modified to have certain desirable traits.

Stanford Law professor and bioethicist Hank Greely said that these concerns can be overstated but not without justification.

“People worry that this is unnatural and therefore bad, that it could lead to inequality, that it could lead to too-early unsafe uses of the technology, that it could lead to people being forced to use this method against their will,” Greely wrote in an email to The Daily.

Hurlbut mentioned that while CRISPR-Cas9 — the gene-editing technology used by He in his experiments — is incredibly powerful, it would still be difficult to produce designer babies at present.

“All the things we really care about — things like beauty, longevity, intelligence — are controlled by many genes,” Hurlbut said in an interview with The Daily. “There’s not one gene for intelligence [or beauty or longevity] — it’s the whole constellation of an organism. So none of this is going to be easy, and that’s probably good.”

A more short-term concern Greely raised was the potential for CRISPR to cause biological harm to babies through “off-target” modifications.

“It’s like you shoot the bullet at one part of the genome, and it’s like a shotgun, and it hits all sorts of parts,” Hurlbut said, referring to “off-target” effects. “It could conceivably promote deregulation of genes that cause cancer and a bunch of other problems, so one has to be very careful in its use.”

Hurlbut said that immediately after CRISPR-Cas9 first gained traction in 2015, the idea of intervening in human genetics was considered by some scientists, but many were concerned with off-target effects.

According to He, his lab plans to monitor Lulu and Nana for the next 18 years, and in initial assessments “no off-target editing or large deletions occurred.”

What sets He’s work apart

Scientists and physicians have been using CRISPR-Cas9 as a gene-editing tool ever since its introduction in 2012, as its precision makes repairing mutations practical and efficient. For instance, researchers at Stanford’s Lucile Packard Children’s Hospital utilize CRISPR to treat genetic diseases such as sickle cell.

The thousands of diseases that get caused by a single defective gene, like muscular dystrophy, hemophilia and Tay-Sachs, are examples of where CRISPR can be useful. Most such diseases have no known treatment or cure.

Other advances in CRISPR use have not generated as much controversy as He’s work, as they focus on altering the genome of somatic tissues. He’s research, on the other hand, involves germline gene editing, which changes genes that get passed onto future generations.

“Altering the genome of somatic tissues — that is, the tissues of the body that are not destined to create sperm and eggs — presents fewer ethical issues since the changes do not get propagated to offspring,” Stanford Cardiovascular Institute professor Mark Mercola told The Daily. “However, clinical trials should [still be] subject to scrutiny akin to other forms of gene therapy.”

Past experiments that altered the genomes of human or animal cells were mostly conducted to create disease models, according to Mercola.

He’s studies differ — and are receiving much more backlash — because he claims to have altered embryos that were taken to term.

Criticisms of transparency

Since last week, He has been denounced by other researchers and health officials for what they perceive as a lack of transparency — both in the secrecy of his experiments and in acquiring adequate consent from subjects — as well as for circumventing the usual process of scientific scrutiny and engaging in peer review.

He left China’s Southern University of Science and Technology (SUSTech) — where he worked as a faculty member in the department of biology — in the dark about his experiments. He elected to go on unpaid leave in February.

“Dr. Jiankui He’s conduct in utilizing CRISPR/Cas9 to edit human embryos has seriously violated academic ethics and codes of conduct,” SUSTech stated on Nov. 28.  According to SUSTech, He’s research was conducted off-campus and went unreported to the biology department and the university.

At the Summit, He claimed to have talked with “not just scientists but also the top ethicists in the United States such as at Stanford and Harvard,” including Quake and Hurlbut. However, despite multiple visits to Stanford, Quake and Hurlbut seemed to have no explicit knowledge of the progress He was making in his clinical trials. But they did have suspicions that he intended to pursue experiments in gene-editing babies.

According to the Chicago Sun-Times, Quake met with He several times over the years but gave only “general advice” and encouraged He to meet scientifically-accepted ethical standards and pursue peer review.

Quake told the Associated Press that he “gave feedback but did not oversee the study.”

Quake did not respond to The Daily’s request for comment.

Hurlbut told The Daily that he had no knowledge of the ultimate direction of He’s research.

“I had no clue that he already had implanted [embryos] — he never indicated to me, but I could see that’s where he could be headed,” Hurlbut said. “I suspected in October, but I never knew.”

While Quake and Hurlbut were kept at least partially in the dark, Porteus said in an interview with Xconomy that he’d been informed by He of his plans to attempt to implant modified embryos in humans. The two met up in February when He was in the Bay Area.

“I was totally blindsided,” Porteus told Xconomy. “I was more than chiding him … I told him he was putting the entire field at risk through his reckless actions.”

Commitment to his research

Over the past two years, He has visited campus every four or five months. He would often meet with Hurlbut on the benches in the back of Tresidder Memorial Union, their meetings lasting hours at a time.

Hurlbut said that he does not support He’s current project and was not advising him in any official capacity.

However, despite disapproving of He’s work, Hurlbut said he likes He personally and enjoyed talking with him. Besides Quake, Hurlbut said he was probably the one at Stanford who knew He the best.

“I realized we both could learn things from each other,” Hurlbut said. “I was learning [details about] the science and his cultural perspective [being educated and trained mostly in China], and I was trying to help him understand what the landscape of ethical considerations looked like. I realized from hearing about his education and research training that he had not been given proper foundations to think through these things.”

Some of the individuals He met with over the years have received criticism for not doing more to stop the experiments. These individuals include Stanford researchers and He’s former adviser at Rice University Michael Deem — who is currently under investigation for allegedly playing a much larger and more active role in a supporting project.

“I think there has been a failure of self-regulation by the scientific community because of the lack of the transparency,” said David Baltimore, Chair of the International Genome Editing Summit and former president of the California Institute of Technology, at the Summit.

However, when asked if he believed any person could have halted He in his work, Hurlbut was skeptical.

“I’m sad to say, but I don’t think [anyone could have changed his mind],” Hurlbut said. “I personally gave him very strong reasons not to do this, and I know that [Matt] Porteus talked to him [at Stanford] … and was very critical of the idea.”

From their conversations, Hurlbut felt that He had decided that it was a step necessary for the advancement of the field.

“He’s an idealist. He’s an inexperienced, perhaps naive, optimist,” Hurlbut said. “I kind of knew [Dr. He] was involved in something of significance. But it’s unfortunate that it had to happen this way. Sad, really, because he seems like a guy with good intentions.”

When asked if better bioethics education could prevent controversial experimentation, Greely acknowledged the importance of bioethics education but said he believes it is not a complete solution.

“Education is good but not a panacea,” Greely said. “He talked with various people about the ethical issues, including two people who have worked in bioethics. They said he shouldn’t do it. He didn’t listen.”

 

Contact Elena Shao at eshao98 ‘at’ stanford.edu.