I’ve been under a rock for the last week or so, first at a conference in San Diego, and then fighting off a nasty combination of strep throat, laryngitis, and double ear infections. (So when I say “under a rock,” I mean hiding under the blankets in my bed, spending most of my time sleeping.) So while bits and pieces of the “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes” paper published in Protein & Cell by researchers from Sun Yat-sen University in Guangzhou, China, made its way to me, it wasn’t until today I felt well enough to say anything about it–mostly because I don’t expect what I have to say will be very popular. So without further adieu, a few unpopular thoughts on Zhou, Huang, et al’s paper.
The paper was rejected by Nature, Science, other top journals, for being unethical.
Hah. Ahem. Look, if Nature, Science, et al, want to make that sort of “it’s unethical we can’t publish it” claim, they might want to do so when the ethics-inclined folks who’ve been around a while are, I don’t know, busy, off tilting at other windmills, at a conference in Bermuda, or something. Because history here isn’t really kind to the so-called “top journals” when it comes to publishing unethical material; see, for just a really short course on it, the Fouchier and Kawaoka H5N1 gain-of-function debacle. “Top journals” were burned by the response to the H5N1 enhancement debacle, and were flat-out caught unaware that such a thing as “bioethics” had enough of a voice to be heard. They don’t want to be caught again, so they’re walking away from anything possibly controversial right now, and the debate over CRISPR/Cas9 has already been going up in the flames of controversy.
In short, any time any “Top Journal” says “we’re concerned about the ethics” you should actually read “we don’t want to be involved in any mainstream media controversy.”1 They learned this with H5N1 GOF issue to the point that these days, any debate over GOF/dual-use research of concern/potential pandemic pathogen research is met with a chorus of “la la la can’t hear you publish what?”
OH MY GOD THE CHINESE ARE MAKING GENETICALLY MODIFIED HUMAN BEINGS!
Really? Is it time for the great Bondsian bad guy freak-out? Do you suppose the folks who are making this claim picture Zhou, Huang, et al, twirling Fu-Manchu moustaches while wearing Zhongshan suit-inspired lab coats as they look upon an army of genetically modified super humans being incubated in chained women who were discarded as babies for being female? How many tropes do you suppose are shoved into this image of evil?
Again, take it from an old-timer: “we have to do it before the Chinese” has been a rallying cry for an awful lot of the science that falls at the intersection of bioethics and transhumanism. Why? Because “the Chinese” stands for “people who don’t have our values and belief systems-they’re DIFFERENT.” We’ve heard it with cloning humans, dual-use research of concern, with just about everything, and now we’re hearing it with CRISPR/Cas9: “we” have to do it before the big scary Not Western people do it!
Except some researchers from China do it and what–it’s suddenly “not ethical” because they’re Chinese? Pundits, scientists and otherwise, are freaking out not because “omg someone edited embryos with CRIPSR!” but because “the Chinese” have. (And do you note how most folks are just saying “the Chinese” as if the paper has no authors? See: creating a big bad menace in your mind.) And unfortunately, this excuse isn’t limited to Top Journals rejecting the paper for claims of it being unethical. The concern shows up in Paul Knoepfler’s blog, as well:
It is worth noting that the current study had institutional ethical approval according to a statement in the paper:
This study conformed to ethical standards of Helsinki Declaration and national legislation and was approved by the Medical Ethical Committee of the First Affiliated Hospital, Sun Yat-sen University. The patients donated their tripronuclear (3PN) zygotes for research and signed informed consent forms.
Would an institutional review board in another country such as the US have given the green light to making GM human embryos? I don’t know.
The emphasis there is mine, and it’s one I dislike making,2 since I do consider Paul a friend. But what this shows is just how pervasive the idea that “the Chinese aren’t moral like us” is: Zhou, Huang, et al, swore to the study conforming by ethical standards required by the Helsinki Declaration as well as their own national legislation, noted it was approved by a MEC–and people are still questioning whether it was ethical enough, because they’re Not Western.
Which ties into the third issue people seem to be having,…
OMG the Chinese did CRISPR/Cas9 editing this is so worrying aren’t you bothered YOU SHOULD BE BOTHERED!
Well, no, I’m not bothered by the paper. I am bothered that Protein & Cell did such a rapid turn-around on peer review for the paper, but I have that concern whenever any journal does such “rapid turn-around” (and you’re kidding yourself if you think this is an isolated event-it’s very much not). Nor am I bothered that “the Chinese” did this particular CRISPR/Cas9 experiment, just like I’m not bothered by human embryonic stem cell research. The researchers (and again, let’s think for a minute about the alienating and Othering going on by insisting on referring to the folks behind this research as “The Chinese”) answered some pretty important questions about the immediate applicable functionality of CRISPR/Cas9 editing–which is especially important given the recent moral panic going on about the technology as a whole.3 In short, they learned two major pieces of information that have direct implications for any conversation about future use in humans–and bans on the technology.
- CRISPR isn’t 100% accurate, and sometimes “missed,” inserting DNA in the wrong place. This is problematic, because instead of offering a cure for $Whatever, it can actually create a new problem. So, not a benign “oops.”
- Even the embryos that were edited correctly by CRISPR ended up as mosaics-in other words, it wasn’t a universal fix. This, as Carl Zimmer explains, means that it’s a lot harder to take a single cell from an embryo and “verify” that it’s been fixed, and it’s hard to know whether or not the fix will manifest, pass down in the germline, etc.
In other words, as Zhou, Huang, et al say themselves: their “study underscores the challenges facing clinical applications of CRISPR/Cas9.”
But what about the embryos?!
Zhou, Huang, et al used tripronuclear (3PN) zygotes for their research. These zygotes occur in upwards of 5% of IVF attempts, and are discarded because, while they might develop into blastocysts in vitro, they absolutely do not develop further in vivo. In other words, these are non-viable creations4 with a built-in suicide switch: they’re never going to develop into bouncing babies, Chinese or otherwise. In fact, it was because of the very specific concerns over CRISPR/Cas9-mediated gene editing in normal embryos that Zhou, Huang, et al used 3PN zygotes: it says so, right there in the paper. (So what was that about ethical concerns, again? You can’t really say they weren’t thinking about it when they put it right there in the paper. Repeatedly.)
If I were to be moved by the creation of these 3PN CRISPR creations as somehow unethical, then wouldn’t I also be obligated to find human embryonic stem cells unethical? I don’t,5 so in practicing a policy of consistency,…
Look, the panic over the CRISPR paper comes down to this: people somehow believe that there’s “moral control” if Westerners do this research. To which all I can really say is, DURC folks? Maybe y’all missed the boat on how to get traction on this issue, and should have run around all a-panic, OMG THE JAPANESE!6
More seriously, the history of science and medicine should underscore and emphasize the fact that “like us” does not mean “moral and ethical.”
As I was pointing out to Razib Khan and others on Twitter, I was around during the OMG DOLLY NOW WE’RE GOING TO CLONE HUMANS AND THE END IS NEAR panic, which as Khan noted, hasn’t happened–or at least, the Raelians haven’t made us believe. Will the same happen to CRISPR/Cas9-mediated gene editing? It’s hard to say, because the technology is so new, and whether or not we’ll be able to overcome random DNA insertions and mosaic, chimeric embryos is down the line enough that it’s speculative.
But whether we’re on our way to a GATTACA-esque future or not, one thing is certain: the first step to any dialog over CRISPR/Cas9-mediated gene editing isn’t going to be an Asilomar-like conference. It’s going to be to stop demonizing “The Chinese” as being a-moral, immoral scientists.
Edited to add: BTW, this was originally a stream-of-conscious Twitter rant that I was goaded to turning into a full blog post. You can read the original, see comments, etc, starting here.
I respect your perspective on this, but I think you probably overstate your case in terms of there being dissing of the Chinese oversight on this. More on my view of this and the human embryo gene editing story more broadly:
I’m afraid we’ll have to disagree there, Paul. Yes, different countries have different variations in rules – but there are some basics that everyone does agree to when publishing papers, thanks to C0PE, Helsinki, etc. And unfortunately, the way people phrase their objections to researchers does often reflect cultural bias. For example, the vast majority of objections to the 3PN zygote editing references “the Chinese researchers.” Yet, we never heard “the Japanese researcher” or “the Wisconsin researchers” or “the Dutch researchers” when it came to other recent, controversial research (H5N1 GOF studies). Why? Because they’re operating within a framework and culture that most scientists perceive as the normal/right/natural one.
There needs to be a lot more than “well they’re Chinese” to essentially call someone a liar by saying that they’re saying their research adhered to principles all other researchers theoretically adhere to, but they really didn’t. I’ve seen nothing here that indicates that they stepped outside accepted boundaries.
While your point about the “other” and the inherent racism in that is well-founded, surely you can see that this can have parallels with things like the Manhattan project. There’s no particular reason why the Chinese have to be the group responsible for taking this in a bad direction, however their military-industrial complex isn’t structured the same way ours is. The powers that be there do have the ability to say “you will work on this or we will shoot your family.” More likely is that once there’s proof of concept and some information published, other, less-responsible parties might develop more refined techniques more adapted to military use. Much like people were able to independently develop the atomic bomb once they knew it was possible. So yeah, some future Hitler or Stalin or National Front Napoleon worries me. Look at Biopreparat. So yeah, OMG THE FRENCH.
Well no, to be honest, not really—no more so than I worry about our government saying “oh no, we’re not working on bioweapons, that contractor is totally just making weapons-grade airborne anthrax FOR TESTING OUR DEFENSES HONEST.”
When you start saying “ours” and “theirs” and then you rely on racist cultural tropes to defend it, you become part of the problem. And the West, in particular, has a long and ugly history of Yellow Fear to go along with its Yellow Fever.
If you’re going to worry about “less responsible parties” then you should probably direct your concern at things like the gain-of-function work being done, and published, by Fouchier, Kawaoka, et al. When we narrow our suspicions to “country of origin” rather than “specifics of research,” we’re participating in racist behaviour, whether it’s intentional or not.
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