“JK Told Me He Was Planning This”: A CRISPR Baby Q&A with Matt Porteus

Xconomy National — 

Last week, Chinese researcher He Jiankui stunned the world with his claim to have created the world’s first gene-edited humans. He said he had used CRISPR-Cas9 to change the DNA of the embryos of twin girls, to make them immune to HIV infection, then implanted them in their mother’s womb. He announced on video the girls were born healthy.

Three days after the shocking revelation, he defended his work at an international summit in Hong Kong. The organizers said they had no idea what was coming when they scheduled him. After He’s presentation, two leading researchers, Robin Lovell-Badge of the Francis Crick Institute in London and Matthew Porteus of Stanford University, interviewed him onstage. (Pictured, above. Lovell-Badge is not pictured.) Other than a few questions from the summit audience, Lovell-Badge and Porteus remain the only people who have questioned He in public after he made his claims—which are still unverified. (He said at the summit he has submitted his work to a scientific journal but did not say which one.)

During the onstage interview, He, who sometimes goes by “JK,” said he was proud of his work, and repeatedly cited as motivation the stigma that China’s HIV-positive citizens face. When asked why he chose HIV immunity when there are other proven—and less controversial—ways to prevent HIV transmission, He seemed unmoved by the concerns and criticism, insisting the procedure addressed an “unmet medical need, not just for this case but for millions of children, because an HIV vaccine isn’t available.”

While Harvard University geneticist George Church has stood up for He, most other reactions have been negative, from dozens of Chinese scientists to National Institutes of Health director Francis Collins to officials of his own university in Shenzen. He has been on a leave of absence since early 2018.

Xconomy spoke with Porteus about the historic import of He’s claim and the live interview with He (pronounced “Huh”). We also discussed Porteus’s own knowledge of He’s intentions months ago, and what he and others contacted by He could have done differently. Porteus’s Stanford lab works on genome editing in the pursuit of therapies for pediatric blood diseases, and Porteus was on the organizing committee of the Hong Kong summit.

[The conversation has been edited and condensed.]

Xconomy: Before He’s announcement, were you of the mind that a gene-edited human would be inevitable?

Matthew Porteus: Perhaps I was too much of an optimist and believed that when it occurred it would in a more transparent fashion, with more public discussion, in a more rigorous and well-thought-through way. What’s so disappointing is how, well, almost reckless He was to do this, with a lack of transparency and defending his ideas before he began. In science we defend what we do and get our ideas tested, and he didn’t do that.

X: When did you and Lovell-Badge know you’d be the first people in the world to interview He about his work?

MP: Robin and other people met with JK for several hours to discuss what he’d done. At that point, the near-universal negative assessment was starting to come out, including statements from Chinese authorities. At that point He fell back into a shell, and we were concerned. We thought it was important that he explain his work and be questioned, but not in an overtly hostile manner. We tried to create a situation for that to happen. I think we were successful.

I’m glad he did it, but he continued to be nontransparent, vague. When I asked, “Is there another pregnancy out there?” he said there’s one. Now people are wondering if that’s true, is there only one more? He showed no humility. He didn’t answer in a thoughtful or clear way.

X: Do you think there was a language barrier? He seemed to need help with the questions from the audience.

MP: I don’t think so. It was hard to hear on stage. All three of us were straining to understand what people were asking. Through my personal conversations with him and seeing him talk at two conferences, I think his facility with English is not an excuse. He knew what he was being asked.

X: In response to questions about secrecy, He said that in years leading up to this he spoke publicly and privately about his work.

MP: I was at the Cold Spring Harbor and Berkeley meetings he referred to. At both meetings, he discussed his work editing embryos from mice and non-human primates. He did not discuss his intention of initiating a trial—actually, to call it a clinical trial or an experiment gives it an imprimatur that it doesn’t deserve. It was neither of these things. It was his… activity, I guess is the best way to describe it. Anyway, he did not disclose or discuss or defend his plans. And he did not discuss why he picked the target he picked. On every level this is irresponsible.

X: Is there a question whether there was funding from entities beyond his own resources?

MP: I don’t know. Again, he was very vague about where the money came from, “Well, from my startup funds and my own pocket.” That’s not satisfactory.

We need to allow China and the Chinese authorities to perform an investigation. Listening to some senior Chinese bioethicists, stem cell biologists, and others, they’re just as angry and disappointed as everyone else, and there’s likely to be a full investigation.

X: The technology is out there. Couldn’t someone who wants to do it just go to a place where regulations don’t exist?

MP: It still takes some technical skill. You need to be able to do IVF, and you need to be able to do injections, and understand how CRISPR works. That’s accessible to a lot more people that perhaps we realize.

X: David Baltimore, the chair of the summit’s organizing committee and a legendary figure in biology, talked last week about the scientific community falling short. [Baltimore was also co-organizer of the historic 1975 meeting near Monterey, CA, to debate the risks of the then-new field of recombinant DNA. Porteus wrote his undergraduate thesis on that debate, and he later worked as a post-doc in Baltimore’s California Institute of Technology lab.] Does the community’s consensus, which called human germline editing irresponsible but stopped short of calling for a ban, need more teeth?

MP: It would be irresponsible if the scientific community didn’t look internally and ask: were there things we could have done differently in the past? I consider this to be a failure because it shouldn’t have happened. About nine months ago, in February, JK told me he was planning on doing this. His email said that he was in the Bay Area visiting with a graduate student of his, and they’d love to set up a time to talk.

X: So you met face to face?

MP: Yes. He started out on his non-human primate work, that he had modified embryos and attempted to implant them into animals but gotten no pregnancies. I was like, oh, thanks for the update. Then he said, now we’ll start doing this in humans. That was shocking to me. I was totally blindsided.

I was more than chiding him. I was berating him. I told him he was putting the entire field at risk through his reckless actions. He was in what I thought was stunned silence. But he didn’t try to defend himself. The graduate student was with him but didn’t say anything to my recollection. I hadn’t heard from him since. [He had also told other scientists of his intentions months before his revelation.]

X: If you could go back to February, what would you have done differently?

MP: Two things: One is call other people I knew he might have been speaking to, and as a group we might have come up with a decision. And perhaps I could have reached out for advice to someone more senior who has led study commissions and academies, who understands the sociology of science, and without revealing the confidence, run the situation by them and get their feedback.

David Baltimore’s comment at the summit, that if you hear about something like this, you should tell someone—I’m not sure he’s exactly right. I still believe we need to trust other people on the other side of the table. Trust that one side will behave responsibly, and that the other side will respect confidences. If we lose that, we’ll have lost a lot. On other hand, in medicine we have patient-doctor confidentiality, but it’s also codified that if a patient plans to hurt themselves or others, you have an obligation to disclose. Perhaps this fits that scenario where it’s such an egregious overstepping of bounds that it’s worth violating the unwritten culture. That’s where it would have helped talking with somebody more senior and getting feedback. I needed to do more. In retrospect I wish I had done that.

X: But then what concrete steps could you have taken?

MP: I don’t know. One could be to call reporters and describe to them the situation and let them investigate. Another is to overtly go public and shout it from the mountains. A third option would have been to directly go to people in China: I want you to be aware of a researcher in your country. JK claimed to me he had IRB approval [sign-off from a medical ethics committee]. And he still claims that. It’s not clear if it’s real. To me it was like OK, you have some IRB review, they signed off.

X: Stat is reporting that someone from the He Lab reached out to a University of Pennsylvania researcher about modifying a cholesterol-related gene in embryos. Has anyone else, from He’s lab or otherwise, reached out to you about this kind of work?

MP: No. But I’ve thought a lot about this, and I think if we’re going to deter someone else, a lot of bad press isn’t going to do it. It needs more substantive penalties.

X: Will this lead to more scrutiny of research that uses viable human embryos, even if they are never intended to create a pregnancy?

MP: The Crick Institute’s Kathy Niakan in her session [just before He spoke on Wednesday] highlighted why we need to do this in viable human embryos. [Her presentation showed that editing embryonic DNA, even if the editing hits the right spots, can still cause problems.] The key was, that’s research. It was highly transparent. There was no intention to implant them to create a pregnancy. That’s the line in the sand that got crossed [with He].

X: From what you’ve seen, do you think he actually did it?

MP: My prior probability was that he did it. What I saw on the slides reinforced that these girls’ CCR5 gene has been modified to contain sequences that have never been seen in the human population before. But that doesn’t get in the way for the need of independent assessment.

[Academics in Massachusetts and Australia have posted analysis of He’s data, with concerns that his work, if real, has not matched the natural mutation, known as Delta32, that gives some humans HIV immunity. Instead, they ask whether he has created a new form of the CCR5 protein that has never existed in humans before.]

X: Does verification mean violation of the parents’ and girls’ privacy?

MP: It’s inevitable that one day these girls’ identities will be revealed. There’s too much interest. Nonetheless, a formal investigation doesn’t have to reveal publicly their identity. We have plenty of ways to audit things confidentially.

X: If an audit shows there has indeed been a CCR5 modification, does that necessarily mean that He’s lab did it?

MP: The deletion known to be in the human population is very different than what he created. That’s an easy thing to distinguish.

X: When you were on stage, there were security guards on hand, and Lovell-Badge prefaced He’s presentation by warning the audience to behave. Did it cross your mind that someone could rush the stage, maybe take a swing at this guy? What was the feeling up there?

MP: It was tense, but I didn’t feel there were any physical threats in the auditorium. JK had expressed feeling threatened. We tried to assure him that we weren’t going to tolerate that sort of threat or harassment. The audience behaved quite well.

X: What’s the next step?

MP: One, I hope somatic cell editing [modifying genes that are not passed down to future generations] for research and therapies doesn’t suffer from this. Two, I think we need to give breathing room to the Chinese authorities to investigate in the way they deem most appropriate. I encouraged [He] on stage to be more transparent and to post things so we better understand what happened. And we need a lot more discussion about what happened and how we can prevent it in the future, without preventing the positive aspects of genome editing from reaching patients.