Genetically Modified Babies: An Insider’s View

“We hope you have mercy for them,” He said.

“Gene surgery is and should remain a technology for healing. Enhancing IQ or selecting hair or eye color is not what a loving parent does. That should be banned. I understand my work will be controversial, but I believe families need this technology.”

While He kept his work secret, he did seek input concerning the ethics of germ-line editing. One trusted source was William Hurlbut, who served on the US President’s Council on Bioethics from 2002 to 2009. Hurlbut discussed the ethics of human embryonic stem cell research with Vision in a 2006 interview. As adjunct professor in neurobiology at the Stanford University School of Medicine, he now speaks again with Vision’s Dan Cloer, this time regarding his contact with He Jiankui, or JK.

DC You were quoted, “I knew where he [He Jiankui] was heading and tried to give him a sense of the practical and ethical implications. But he kept returning to the good that could be done.” That sounds like you were telling him that germ-line editing is not a good thing, but he was saying it is a good thing to do as soon as possible.

WH I can see how that’s a little confusing. What I meant was I never agreed with him on what he was doing in the first place. But beyond my personal opinion of it, I suggested that he just go very, very slowly in approaching it. This is exactly what the National Academies has called for. While I don’t agree with them on everything—such as the problem of creating and destroying embryos, for example—I do think that it is wise at the very least to follow their advice regarding scientific consensus and public engagement. So I was saying to JK that, quite apart from what I think personally of your project, you need to slow down and stay in step with the National Academies’ approach. Those are your scientific colleagues, and those people have more collective wisdom than any single individual would.

DCWas JK speaking with you specifically about editing embryos for HIV?

WHYes, he did talk about that, but I didn’t know he was getting close to implanting. I knew that was his long-term goal.

DCOne would figure that someone would eventually give germ-line editing a try.

WHWell, yes. This would happen eventually, and probably pretty soon.

DCDo you think something like this is coming along with any other investigator?

WHI would hope that everyone has sobered up a little. Wouldn’t you think?

[After this interview took place, Russian biologist Denis Rebrikov announced his intention to repeat He’s CCR5 gene editing, with modified protocols, and also to use CRISPR embryo editing for preventing hereditary deafness in the children of deaf parents.]

DCYes, but we could be somewhere in the gestation of another baby that won’t be announced until it’s born.

WHThat’s true. Right now, in this critical environment, they might not say anything about it even if it was born. But there is another baby. You knew that, right?

DCYes, I have heard that JK has another baby still to be born. But I’m still waiting for real evidence that this has actually happened. Who has seen Nana and Lulu? It’s hard to trust the news; things are reported, then disappear—a news mirage. Maybe this was just a trial balloon to see how people would react?

WHI wasn’t in the room, but it happened. The twins happened. It’s as sure as knowing through the news about any celebrity having a baby. I have seen pictures and know quite a bit about this. You can be confident it happened; but whether the editing was effective or not, we don’t know that.

But you’re right in some ways to be skeptical. Woo Suk Hwang’s fraudulent claim of cloning human embryos [in 2004] comes to mind. But this is real. Hwang thought people would not be able to figure it out before he could actually do it. I met him, and JK is a very different guy.

“JK is a very nice person to talk with and is sincere in wanting to do good. He pushes the edges, and maybe goes over the edges, but he’s not a liar.”

JK was certainly ambitious and wanted to do an important “first” in the world; he wanted fame and fortune at some level. It’s just human nature to want to prosper and have prestige and financial gain, and many people are doing so. But I think the real point is that JK had a considerable amount of idealism and hope that he would help people. He kept saying to me, “We have to get this moving along, because the science is safe.” He was convinced the science was safe.

I can’t say if that is correct, but from talking with people in the field, I get the sense that the off-target effects [random edits to the genome] are probably manageable. JK felt that if we waited too long, the discussion would slow down the progress toward helping the patients that needed germ-line therapy and parents that wanted it for their children.

DCWas He worried that this work might have the opposite effect and slow the progress toward acceptance and clinical use?

WHI talked to him about all that. Without my knowing that he had already done this, I kept telling him, “You are too eager; you will end up humiliating yourself. And, yes, you might even slow the science down.” After the fact (I have talked to him since the initial announcement), JK thought he would face criticism in Europe and America and that it would take some time for them to come around. But he didn’t think he would be so criticized in his own country. I think he was probably right—that if the births had not been leaked at the summit [in Hong Kong in November 2018] and roundly condemned by the scientists convened there, the outcome might have been different. If the results had been released the way he had wanted, rather than leaked, I think JK would not have been in so much trouble. And in China, maybe not any.

DCHow did he intend the results to be released?

WHHe was submitting papers to leading journals and he wanted to get the journals’ approval and publication. He had arranged for the Associated Press to come film him, which they had done. But the story was still confidential at that point. He wanted the press, not just for the fame, but because he knew it was going to be dramatic. He didn’t feel capable with his English and lack of experience to explain the situation clearly enough.

DCSo you’re saying the prerecorded media was for the sake of clarity?

WHYes. I told him, “JK, if you do this it’s going to make every headline on every newspaper around the world. You realize that, don’t you?” I sort of got him clued up to that, but he didn’t think it would be criticized as it was (as a publicity grab). It’s a sad story, really. Here you have a guy from a small village, and he just didn’t have that much life experience to put it in perspective.

DCWhat about his science? When I saw the news, I initially questioned his credentials for doing this kind of work.

WHHe is sort of a biophysicist, and he is not unsophisticated in this. He was probably one of the best people to do parts of this project—the sequencing, the study of the alterations. So I don’t think that’s the problem. What was lacking was his sense of how to approach a clinical study.

DCWhat went wrong for JK at the summit? He had submitted his data for publication and created some media to explain his work, and then?

WHIt wasn’t the paper; it was the timing. If it had been published, the publishing process itself would have brought a level of credibility because of the normal scrutiny involved; the data analysis would have been vetted. There would have been a close look at the ethical foundations of it as well. But this would have been a long process that probably would have pushed its publication into 2019.

But suddenly at the gene-editing summit, JK was forced into a slide presentation of the data prematurely and under psychological duress. That was the opposite of what he had wanted. He did not want it leaked, embarrassing the summit. But MIT Tech Review scooped it by looking at the regulatory documents in Shenzhen [where He worked in the Southern University of Science and Technology]. They figured out that the germ-line editing had already been done. It was an amazing work of investigative journalism, but the premature revelation really screwed up JK’s plan.

DCIn retrospect it seems to me that at the summit JK’s plan was to lay out the ethical reasoning for safe germ-line editing. That’s the paper I saw before it was taken down. This would set the stage for his later announcement of the birth of Lulu and Nana.

WHThat’s right. JK was going to be given less than 10 minutes on the schedule, and then participate on a panel. Somebody along the way might have asked, “Have you done this?” Or “When are you planning to do it?” But if they hadn’t asked, he would have been okay because he was not going to reveal it there. But everybody lost; it’s a tragedy on every level.

Later, when he was feeling really down and duly rebuked, he sent me an e-mail. He told me that he didn’t feel good about what he had done and that he wished he had waited, wished he had done it more carefully, and that he had chosen the wrong target [the CCR5 gene]. He felt some remorse—considerable remorse, he wrote. It is a bad situation, but you can only be so sympathetic toward him. He endangered a couple of kids’ lives; he overrode the general consensus in the scientific community; and he proceeded too fast.

“It’s hard to know yet whether JK is going to end up famous or infamous. Maybe a little of both.”

DCThe origins of IVF [in vitro fertilization] in the 1970s were also quite controversial, but weren’t Robert Edwards and Patrick Steptoe more open about what they were doing?

WHNot really. It was known that they had been working on IVF and infertility for more than a decade, but the human attempts, and there were many, had all failed. This was not well known. Even so, the Browns knew they were doing something experimental, but they did not expect that their Louise would be the first successful birth. You’re right, though, in that JK knew about Robert Edwards and the more recent so-called three-parent-embryo mitochondrial-transfer work. He realized that these kinds of big firsts in science often take place without considerable general public engagement. But germ-line editing is different in character than anything that’s come before: this affects the gene pool of the human species. Theoretically, a mistake here could echo through the generations. It’s not just the babies he is treating; he is treating all the children that come from those babies’ lives.

DCIt’s surprising to me that this topic is not more widely discussed. The science community is very active, but overall the public response seems very low-key and mostly indifferent.

WHIt’s very troubling that the world is not more concerned. Maybe this is what you get when the news is reduced to trivia. And that is rather sickening, because these are monumental issues. This really is like no other news; it really is about the future of our species. Most things come and go, but this is going to be with us.

That said, I don’t think germ-line genetic engineering, unless it sails off into illegal fertility clinics, will be a major phenomenon, at least not for decades. The real issue to me remains the creation and destruction of human embryos for research. That is the core problem; the use of human embryos as tools—their instrumental use—continues to be overlooked. The trouble is, this is very important science, but it’s not like studying something in a test tube. These embryos are living organisms. The use of human embryos to study developmental biology remains a huge story.

DCIt’s a hinge of history; we’ve swung open the doors to a new world.

WHThe revolution in biology is really gaining momentum. CRISPR was the key piece, because it makes it so fast and easy to alter genes in a controlled way. Of course, advances take place on many fronts as different technologies overlap: gene sequencing, synthetic DNA, microtools for manipulating the materials, and information technology are all roaring in. I believe this will all culminate in neurobiology; that’s what I really study.

DCSo at some point we will CRISPR into the embryo an updated brain? Did JK know that the CCR5 gene was suspected to have a cognitive role besides its HIV-blocking potential?

WHThere are publications that seem to show that CCR5 does have cognitive effects. JK knew that an effect had been reported in mice. As far as I know, he did not know of a human effect; those reports were released more recently.

I kept saying to JK that you can’t assume you’re operating on just one thing here. We only have about 19,000 protein-coding genes. So there is no way that genes do only one thing. It’s pleiotropy: each gene does many things, affects many things. It’s not like a pot of soup where you add ingredients one at a time; it all unfolds together. CCR5 will probably affect many things. How this network of interactions works is a fascinating study, but we have to get our moral grounding correct. We want to investigate these connections, but should we be creating human embryos for research and manipulation in the first place?

DCWe seem to need decision-makers and rules. But where does that come from?

WHMy son Benjamin’s book, Experiments in Democracy, charts out how we might govern these matters. [Benjamin Hurlbut is an associate professor at Arizona State University.] We need to consider what the embryo is and how we should treat it. And there are new iterations on the horizon to consider: synthetic embryos, chimeras [in this case, embryos combining a human and an animal genome], cerebral organoids.

We are at the tip of the iceberg. Many, many things are going to challenge us for decades, even centuries.