So now we know more about the CRISPR human baby story. And it’s even worse than it looked. Let me recommend this report from Sharon Begley at Stat, from the International Human Genome Summit in Hong Kong, but it’s not going to make you happy to read it.
It turns out that He Jiankui devoted quite a bit more time to working out the publicity for his gene-editing efforts than he did to assessing their implications. He’s had people filming the process for months and has rolled out YouTube videos explaining his project. A good deal of thought went into that part. But when he presented details of the embryo work itself, the audience found that 31 embryos from eight couples (one set of prospective parents later dropped out) had been injected with CRISPR reagents. 70% of these were found to be DNA-edited. Multiple microinjections were needed to try to ensure that the majority of cells in the embryo were indeed affected, He said, and even so neither of the twin girls appears to be a clean job of it. One of them is mosaic for the desired 32-amino acid CCR5 deletion, and the other, if I’m reading this right, is heterozygous for a five amino acid deletion. Wonderful, a complete hack job. (Update: thanks to Sean Ryder on Twitter, we have a graphic showing the actual situation, at right. None of these are the desired 32-residue deletion, and we know nothing about any of them). No reason not to just plow ahead, naturally. I mean, reasonable outside observers might look at this situation and declare the whole experiment to be fearsomely botched up, but History calls. (See this Twitter thread for more details, and here’s a transcript of the talk).
All this means that, in spite of Dr. He’s hand-waving about protection from HIV, we have absolutely no idea if either of these girls will have any such protection from their CCR5 editing. To the best of my knowledge, neither of these genetic backgrounds has been found in the wild-type human population (and let me tell you, it feels very strange to type that phrase, but that’s where we find ourselves now). The two girls will be monitored until they turn 18 (and one hopes afterwards if they give consent), but the effects? Who knows! That’s for them to find out, thanks to the extraordinary arrogance of He Jiankui. If they turn out OK, that will be due to sheer luck. And what will it mean if something bad happens? Who knows! Both of these poor children are one-offs, and cannot even be compared to each other since they’re so different. He did disclose that another pregnancy is underway, but how this third child’s genome has been messed up, I don’t yet know.
David Liu (of Harvard and Beam Therapeutics) was there to ask pointed questions of He (as did several others), and I absolutely agree with him when he said afterwards that “It’s even more appalling and abhorrent now“. Alta Charo of Wisconsin called the whole effort “misguided, premature, unnecessary and largely useless” and that’s right on target, too. I would add “criminal” to that list myself, because it does appear that the consent forms that the parents signed told them that this was an HIV vaccine research project. It appears that Dr. He was the only person to explain the experiment and the consent form to the patients, and God only knows what he told them or what they understood of the work itself. By American legal standards, he has (I’d say) exhibited depraved indifference to human life, and in a better world he’d stand trial for it.
It’s hard to see how this could have been done much worse. It’s obvious that human embryonic gene editing is not ready for use yet, and this is not the work of some brave pioneer because we already knew that. Going ahead with this experiment was reckless, dangerous, counterproductive, and arrogant beyond belief. The title of this post is from Eliot’s “Gerontion”: After such knowledge, what forgiveness? And I do not have it in me to forgive He Jiankui.