I made quick promise at the end of my review of Gene: An Intimate History, that I would be reviewing a number of books about a certain individual who wanted to ‘win’ the gene editing arms race. And how very reckless he was.
That man, of course is Hè Jiànkuí. This is the man who tried—and succeeded—in inducing heritable CRISPR-mediated genome modifications in human embryos that then resulted in live births. Hank Greely’s CRISPR People: The Science and Ethics of Editing Humans is a rather comprehensive account of the events that lead up to this pivotal point in the history of genome editing. Pivotal is a word I had to chose rather carefully here; ‘landmark’ sounded too positive. ‘Clusterfuck’ may also be a suitable descriptor. Make no mistake, I am not a fan of what Hè did. And neither is Greely.
Greely is a law professor at Stanford who works on the ethical legal and societal implications of emerging biotechnologies, with a special interest in reproduction. He’s also the director of the Stanford Center for Law and Biosciences. This means that CRISPR People shares some similarities with Jorge Goldstein’s recent book on gene patents in that the author is quite well connected to a number people involved in the events described. For example, Jennifer Doudna contacts Greely personally to attend a workshop on bioethics. He also knows Paul Berg* and is friendly with one of the professors Hè worked under as a postdoc. This is not someone who has been merely watching from the bleachers.
CRISPR People is split into four sections. The first covers the background and provides a reconstruction of the events leading up to Hè Jiànkuí’s experiments. This section also covers the legal and ethical discussions concerning CRISPR editing before the news of the first CRISPR babies came to light. What would we have reasonably expected Hè to know before he started his work?
The second section covers the initial reaction to the news and (the rather messy) aftermath. The condemnation from other Chinese academics was swift and strong, with a joint statement published on WeChat within a day. This outraged response to the news suggests that Hè’s work was not open knowledge in China. Most sources from outside of China are also shocked and appalled—with maybe the exception of George Church.***
Greely also tries to establish how many academics from outside of China had prior knowledge of Hè’s intentions—he identifies at least six. And to resort to a colloquial term here, no one dobbed him in. Some of these people tried to advise him not to proceed, but no one passed their knowledge of the experiments onto any kind of authoritative body. Which then raises the question—who, exactly, should you tell? It’s all well and good to say scientists need to speak up, but who do you snitch to? Personally, if the concern was based about someone in my own country or institution, the President/Vice-Chancellor, etc might be a good bet, or a national governing body, but for someone who’s on a different continent? That’s far less clear. And I do wonder what adverse effects snitching culture might have on the exchange of scientific information. I’m a bit undecided on how best to proceed with this one.
The last two sections provide an assessment of Hè’s experiment and the how we should proceed. I think it’s correct that Hè did want to be seen as a ‘winner’ here: while Hè’ did have a background in genome sequencing, he not have a background in either genome editing or reproductive technologies. His justification’s for editing the gene in question—CCR5, whose functionality is linked to HIV tolerance—are quite specious. I also should point out that the genes, and gene mutations, Hè considered targeting were previously found and characterized in caucasian populations and not Han Chinese ones. So he knows nothing of the effects the genetic background could be having.
This then has a knock-on effect with regards to informed consent; if the lead researcher doesn’t seem to have a good understanding of what he is doing, can we really say that the couples who signed up to these clinical trials know what they are a signing up for?
Yeesh.
The final section of the book is where it is very clear from his writing that Greely is a bioethicist and a lawyer. While technical, the arguments laid out here are straight forward and very to the point, laying out a wide range of arguments and counterarguments for and against germ-line genome editing in different scenarios.
Not all cases are the same: is the trait mono or polygenic? Are there known risks of epistasis (gene interactions)? Are there other interventions available—pre-implantation genetic diagnostics, perhaps? Or PERP and free condoms for HIV, rather than taking chunks out of CCR5? Changing a well-characterized, deleterious mutation involves a very different level of ethical calculus than making changes that are less well characterized in their effects and with a murkier risk:benefit ratio.
One of the more important points he emphasizes is the importance of social acceptance before proceeding. As messy as that is, science (with a capital S) cannot proceed without the support of the societies that it exists in. In my own opinion, while strong, clear communication is often a good start, it’s often not enough.**** While seeking pubic approval is important, I think we do have to be the ones that lead the horse to water.
As a small aside here, as reckless as Hè was, I am actually rather glad he didn’t try to do something like engineer taller or smarter children with his attempts to be ‘first.’ I think that would have made things worse: could you imagine how much stronger, or reactive, public option would have been if he had done that? And how much harder it would have been to have a measured discussion of risks and benefits?
Another point that Greely writes at length about—and I am glad that he does—is that there is no one human germline and no one human genome. This is something that really needs to be hammered home to anyone legislating what can and cannot be edited in the future. I know it’s probably well-meaning, but the quote from UNESCO made me cringe:
“The human genome underlies the fundamental unity of all members of the human family, as well as the recognition of their inherent dignity and diversity. In a symbolic sense, it is the heritage of humanity.”
But this is very much not true. The human population is a population, and contains considerable variation. Every person has their own unique germline genome. Again, I bring up the fact that Hè kept on considering gene-editing targets that had been previously characterized in mostly caucasian populations and then applying them to a completely different population. Making edits in individuals from one population may result in some very different effects than if performed in another. I personally worry that we’ll start seeing attempts to pass legislation regulating this kind of technology made by people who hold simple, somewhat romantic, but very much wrong ideas about the nature of the human genome.
…There is a lot that’s covered here in the last section of the book, and there’s a lot there that I have some opinions on. But this is ostensibly a book review and not an op-ed, so I’ll leave that there. I’ll make it clear though that my opinions are based on the subject at hand, not Greely’s coverage of it, which, as I mentioned above, is thorough.
If you’re interested in reading about the Hè Jiànkuí affair and you want to understand why so many of us came out so strongly against what he did, CRISPR People is an excellent place to start. .
For cbr17bingo, this is Borrow. I had this one on hold at the library for a while.
And Hè? He’s out of prison and might just be moving to Austin, Texas…
I fear he’s going to try and make friends with certain billionaire with skewed ideas about reproduction.