Few slightly technical things not addressed in the linked article but worth pointing out:
- The most prevalent types of HIV prevalent in Asia are the T-tropic X4 strain which does not depend on CCR5 for infection. The proper genetic target CXCR4 is not a viable target for germline gene editing because it's essential for embryo development[0]. In other words, the children would not be immune to HIV in any case.
- The editing was done using a single sgRNA template and a 20bp+ deletion cannot be produced with this setup. Therefore it's likely that the experimenters never attempted to replicate the naturally occurring Δ32 variant in the first place.
- Δ32 is well studied and known to abolish CCR5 function at both RNA and protein levels. However, both of Nana's CCR5 alleles are novel and it's possible that some function may still be retained because the DNA changes are not extensive enough[1]. These edits really serve no purpose and should never have been implanted.
"The most prevalent types of HIV prevalent in Asia are the T-tropic X4 strain "
Great comments.
There is (at least there was when I followed this more than a decade ago) some data to support that x4 tropic HIV is more aggressive/pathogenic, so forcing the infection towards x4 tropism by removing CCR5 may increase the virulence of the infection.(with some caveats on this).
Independent of that. This is mind-blowingly unethical. At very least, He should be ostracized and provided no opportunity to do science, let alone medicine.
This is inevitable. Folks with a will to do this (edit embryos) can clearly do so. In fact this 'researcher' (or con man) did it 'in secret' which means without any institutional support. If this guy can do it in his basement, then what hope is there of putting the genie back in the bottle?
Folks go to all sorts of crazy medical clinics already, for all sorts of crazy reasons. I predict within the year, the rise of a 'custom baby' clinic in some country with lazy medical ethic enforcement. And folks will flock there and pay through the nose.
All the argument in the OP is irrelevant. The technical reasons this instance went wrong are irrelevant. The ethics argument is irrelevant.
We have to suit up, to prepare to deal with designer babies among us in their thousands, and soon.
I agree. We should embrace and get the most out of this technology, not shun it. Same with genetic engineering for plants and animals in the food chain.
This is the point everyone needs to recognize. I predict we will also reach a point where viruses can be engineered, and engineering defenses will be a public health concern.
This is the world to come, and ethics aren’t a viable defense. The gene pool is going to be stirred up in ways we’ve never seen before, and it’s going to be a good reason for us to stop focusing on our differences and start thinking and acting as one species.
CRISPR and the coming/heralded genetic revolution are BIG deals. Right up there with the Internet, the Bomb, and Fire. Our world is going to be very different due to this revolution. Events like these immediately prompt even the most uninterested person to have deep philosophical conversations; it's that simple and yet grand. This stuff is important, yo.
That said, this revolution is a bit different, as it's not just the economics, the social structure, the food, or the power source that is being changed, it's your kids. Placental mammals are, generally, very protective of their young and we spend a LOT of time and food in raising them. Things like the genetic revolution are going to vastly disrupt that relationship, one that is ~65 million years old. Yes, today we have seen the first step in that timeline and it's not here yet. But all of us know that this power, for the perceived benefit of our progeny, is like an apple is to Adam; we have to eat it.
But there's the rub. We're doing this because we'll want our kids to be better off [0]. But then they will not be your kids. At first, they will mostly be your kids, minus some small percents here and there. But as the generations pass (10, likely less?) the relationship between mother and child will become looser and less obvious. The child won't resemble you, won't behave like you, and sooner than you'd think, won't think of you as a parent.
Here's the other thing, they will be Übermensch too. Not at first, yes, and there will be a lot of 'issues' along the way, ones that very much may derail the whole train. But we all know that they will be here eventually (500 years? 200 years?). The kids will be smarter, faster, stronger, gritter, handsome, charming, witty, etc. You won't hate them or fear them, you will want to be them and be around them and have your kids be like them too. Why? It'll be proven to 95% +/- 0.27% probability (give or take) that the gene editing works, just like you'd think, endlessly reviewed and studied over and over.
But then you get these Übermensch kids making their kids even more Übermenschy. And the problem from before comes screaming in. You're doing all this for your kids, that was the whole point, so that they'd be better off, more genetically blessed. But there is no end to that idea and this kid of revolution can really go exponential (provided there is no 'carrying capacity' to genetics that we've not yet discovered). Eventually, the kids get so far away from the parents that they aren't your kids anymore. The whole reason evaporates into this kinda genetic arms race thingy. Yeah, things will go on for another generation or two past that, but not much more.
We really need to examine WHY we all just know we are all going to get into this genetic arms race. We really need to know how these kids of things end; where are the exit ramps and the what do they look like?
We all want the best for our kids, but now we are facing the question of: how do you define your child?
[0] CRISPR may be able to edit genes in situ, yes, but I am focusing on germline editing and assuming that once fertilized, you're pretty much locked into a set of genes and developmental constraints.
It's exposed by prospective subject parents that when asked what if the experiment went wrong, He's assistant simply said "Don't worry, we would help dispose of the baby."
The small private hospital that approved and held the experiment is one of the "Pu-tian clique", notorious in China for their customarily misleading, predatory and fraudulent medical pratices.
The hospital boss also invested in He's two bio startups, one of which is hawking a failed American 3rd-gen gene sequencing machine "Helicos" that he bought from his American professor, now goes by the name "GenoCare", billed as "the world's most accurate", monopoly-breaking, "fully originally and domestically invented" by him.
From the outside it seems like they're notorious in China for having power and not being han chinese. Lets not let their ethnic stereotypes go unquestioned.
Designer babies are inevitable. From a sheer evolutionary perspective, the group willing to use a successful design mechanism is going to beat out the one that is not over the course of a few generations.
However, the problem here is that we do not currently have the ability to create designer babies. We have a few clumsy tools that resemble the tools we'd actually need to do it, but in much the same way that a butcher's knife resembles a scalpel. It's an improvement over the era where what we had was a jackhammer, but it's still not suitable for the task. Any attempt to get serious about human germ-line editing with the current toolset isn't going to work. That means, there is very little likelihood of successful, happy outcomes, and a lot of room for unhappy, dangerous, or deadly outcomes.
Before people seriously start trying this, we need to tip that balance to a point where it's at least interesting to discuss. An ethical discussion would have to revolve around costs and benefits, and it's a really easy discussion when it's basically all costs and no benefits. We don't need to invoke any particular philosophy or argue about utilitarianism or the virtues of deontology or what we should be deontological about in that scenario.
So while I don't have a complete answer, one step to the "risk reduction" you ask for is that we still need better tooling so we're not trying to do the equivalent of performing brain surgery with a butcher's knife, before there's even anything all that interesting to discuss. We should have those discussions sooner rather than later, but as the article alludes to, "we" collectively actually have. (The fact we have no ability to enforce that discussion is a problem of some sort, though.)
At least human germ-line experimentation isn't infectious, though.
People making a big stink out of ethical concerns virtually ensure that this stuff is going to happen first in a place with the least concern for ethics. China seems to be where the action is on this front.
People worry about designer babies or baby hitlers (to name a few of the cliches). In reality people are trying to fix serious genetic defects and the science to do that in a responsible way is kind of near impossible to conduct in most reputable universities because of ethics. So, it's happening in a much less responsible way elsewhere by people who want to cash in on the obvious demand for any kind of snake oil or real solutions in this space.
Something I've thought about throughout the day is karyomapping, which has been repeatedly successfully used to screen out heritable diseases, but absent from this conversation...
The discussion in the news could really benefit from reminding people what techniques we are currently using, to make it clear how this technique increased risk without advancing outcomes, and to make it clear that the objections aren't simply against all genetic tech.
Don't believe it. For the monkey data, they claim at least one cell was "edited" in 80+% of the embryos and that the "edited" embryos survived to blastocyst stage more often than the controls (ie, there was less than zero toxicity):
https://drive.google.com/file/d/1IXy47dWNQApcNLW-bTSfYD2vxBZ...
I bet this will come out as made up or fatally misinterpreted somehow.
> ... “it’s a fairly outrageous assumption that any change to this region would lead to some benefit,” Ryder says. “He made new mutations, and there’s no reason to think that they’d be protective—or even that they’d be safe.”
True.
> What’s shocking about this “is the blatant disregard of all the rules and conventions we have in place for how one should approach any proposed intervention,” said Leonid Kruglyak, a geneticist at the University of California at Los Angeles, on Twitter.
That's like saying no one can stab you because it is illegal.
It would seem that the systematic error lies squarely on academia and business ignoring each other for far too long.
ED:
Clearly I have failed the communicate what I mean...
There are two different cultures both using the same tools. One believes it controls the tools and gets to set rules for how they are used. The other does not.
Juxtapose, the censorship board for TV in my country, which decided that calling Yugo surplus "genocide canteens" is bad, but reprehensible filth like Fear Factor and Big Brother is OK for prime time. Clearly, opinions do differ and are allowed to differ. - I call into question: Is the case of bioethics vs. business similar?
>> What’s shocking about this “is the blatant disregard of all the rules and conventions we have in place for how one should approach any proposed intervention,” said Leonid Kruglyak, a geneticist at the University of California at Los Angeles, on Twitter.
>That's like saying no one can stab you because it is illegal.
It's like saying no one should stab you because it is illegal.
The way this article is written makes me appreciate when articles address the parties involved by Title and Name instead of He or She or just his first name.
Mr. Jiankui would have been less confusing. Editors should be able to identify issues like this and adjust the writing to avoid confusion IMHO.
It's at least a little bit promising that the reaction to the CRISPR baby has been resoundingly negative. From the technical errors pointed out by scientists in this case, to the visceral reaction to the idea of "designer babies" to most regular citizens.
Of course, we have some short-sighted scientists who only care about their own work and not the long-term implications, like He himself and Church, but the actions and words of these two were roundly condemned.
Hopefully this buys us enough time to see the real long-term implications of starting a Phenotypic Revolution[1], and we can get some world-wide consensus to stop gene-editing in humans.
To me, the reaction has been thoroughly disappointing. Genetic editing of humans could be the most beneficial medical intervention ever discovered, but almost everyone respectable is calling for a total ban on the technique, ostensibly on the grounds that we lack the precision to do it right. But the real reason, if you read between the lines, is an unfounded and tragic fear of enhancing human capabilities. I reject this mindset. We can and should make better people.
"...He spoke at length with bioethicists William Hurlbut at Stanford University, as well as his son Benjamin Hurlbut at Arizona State University, neither of whom was aware of He’s plans. The elder Hurlbut spent time telling He about opposition to the instrumental use of human embryos in the United States, and the grounds for believing that human life begins at conception."
I know this is probably an unpopular opinion, but CRISPR babies were going to happen eventually. Just like the atomic bomb. Not a matter of if, but when.
If we don't villainize the creators of the atomic bomb (Fermi, Oppenheimer) I see no reason why we should villainize this man.
The reasons for doing so are more practicality and having more to lose. If the baby would have risked some sort of horrifying genetic disease like say the one which causes your flesh to grow back as bone the risks would be totally justifiable.
It is an irony of medicine that dire circumstances make what would otherwise be recklessness permissible since they have nothing to lose.
That said once the technology is ready it would be outright immoral and stupid not to use it. Like not vaccinating against smallpox because it is unfair to those who aren't or not providing education because it would make the educated better off than the uneducated.
My thoughts exactly. The cat is now out of the bag, and the rest of the developed world will now be forced to keep up, even if it’s against their ethics.
Think how simple it would be to 'launder' genetically modified babies (at least in the US). Just leave them on the front step of a hospital and you're good to go.
I can't imagine it would be that difficult for a reasonably sophisticated organization to keep track of the child as it grew up, and with popularity of genetic testing you could probably find them again anyway.
this guy writes 'he's' instead of his and after a few of those i got totally put off this article. the whole second point is just moot. That being said, playing with genes is about as good of an idea as running with scissors with our current understanding of them...
Well, you missed out on an interesting article. And also I stopped reading your comment when you failed to capitalise "this" at the beginning of a sentence.
If it's ethically defensible to abort a child based on its sex (or for any other non-medical reason), it should be ethically defensible to mess with its genome.
I, for one, welcome our new Chinese designer baby overlords.
[+] [-] Laforet|7 years ago|reply
- The most prevalent types of HIV prevalent in Asia are the T-tropic X4 strain which does not depend on CCR5 for infection. The proper genetic target CXCR4 is not a viable target for germline gene editing because it's essential for embryo development[0]. In other words, the children would not be immune to HIV in any case.
- The editing was done using a single sgRNA template and a 20bp+ deletion cannot be produced with this setup. Therefore it's likely that the experimenters never attempted to replicate the naturally occurring Δ32 variant in the first place.
- Δ32 is well studied and known to abolish CCR5 function at both RNA and protein levels. However, both of Nana's CCR5 alleles are novel and it's possible that some function may still be retained because the DNA changes are not extensive enough[1]. These edits really serve no purpose and should never have been implanted.
[0]:https://www.nature.com/articles/31261 [1]:https://www.ncbi.nlm.nih.gov/pubmed/25043019
[+] [-] vibrio|7 years ago|reply
[+] [-] dhimes|7 years ago|reply
[+] [-] JoeAltmaier|7 years ago|reply
Folks go to all sorts of crazy medical clinics already, for all sorts of crazy reasons. I predict within the year, the rise of a 'custom baby' clinic in some country with lazy medical ethic enforcement. And folks will flock there and pay through the nose.
All the argument in the OP is irrelevant. The technical reasons this instance went wrong are irrelevant. The ethics argument is irrelevant.
We have to suit up, to prepare to deal with designer babies among us in their thousands, and soon.
[+] [-] beerlord|7 years ago|reply
[+] [-] david-cako|7 years ago|reply
This is the world to come, and ethics aren’t a viable defense. The gene pool is going to be stirred up in ways we’ve never seen before, and it’s going to be a good reason for us to stop focusing on our differences and start thinking and acting as one species.
[+] [-] Balgair|7 years ago|reply
That said, this revolution is a bit different, as it's not just the economics, the social structure, the food, or the power source that is being changed, it's your kids. Placental mammals are, generally, very protective of their young and we spend a LOT of time and food in raising them. Things like the genetic revolution are going to vastly disrupt that relationship, one that is ~65 million years old. Yes, today we have seen the first step in that timeline and it's not here yet. But all of us know that this power, for the perceived benefit of our progeny, is like an apple is to Adam; we have to eat it.
But there's the rub. We're doing this because we'll want our kids to be better off [0]. But then they will not be your kids. At first, they will mostly be your kids, minus some small percents here and there. But as the generations pass (10, likely less?) the relationship between mother and child will become looser and less obvious. The child won't resemble you, won't behave like you, and sooner than you'd think, won't think of you as a parent.
Here's the other thing, they will be Übermensch too. Not at first, yes, and there will be a lot of 'issues' along the way, ones that very much may derail the whole train. But we all know that they will be here eventually (500 years? 200 years?). The kids will be smarter, faster, stronger, gritter, handsome, charming, witty, etc. You won't hate them or fear them, you will want to be them and be around them and have your kids be like them too. Why? It'll be proven to 95% +/- 0.27% probability (give or take) that the gene editing works, just like you'd think, endlessly reviewed and studied over and over.
But then you get these Übermensch kids making their kids even more Übermenschy. And the problem from before comes screaming in. You're doing all this for your kids, that was the whole point, so that they'd be better off, more genetically blessed. But there is no end to that idea and this kid of revolution can really go exponential (provided there is no 'carrying capacity' to genetics that we've not yet discovered). Eventually, the kids get so far away from the parents that they aren't your kids anymore. The whole reason evaporates into this kinda genetic arms race thingy. Yeah, things will go on for another generation or two past that, but not much more.
We really need to examine WHY we all just know we are all going to get into this genetic arms race. We really need to know how these kids of things end; where are the exit ramps and the what do they look like?
We all want the best for our kids, but now we are facing the question of: how do you define your child?
[0] CRISPR may be able to edit genes in situ, yes, but I am focusing on germline editing and assuming that once fertilized, you're pretty much locked into a set of genes and developmental constraints.
[+] [-] cauldron|7 years ago|reply
The small private hospital that approved and held the experiment is one of the "Pu-tian clique", notorious in China for their customarily misleading, predatory and fraudulent medical pratices.
The hospital boss also invested in He's two bio startups, one of which is hawking a failed American 3rd-gen gene sequencing machine "Helicos" that he bought from his American professor, now goes by the name "GenoCare", billed as "the world's most accurate", monopoly-breaking, "fully originally and domestically invented" by him.
[+] [-] setquk|7 years ago|reply
[+] [-] superkuh|7 years ago|reply
From the outside it seems like they're notorious in China for having power and not being han chinese. Lets not let their ethnic stereotypes go unquestioned.
[+] [-] brownbat|7 years ago|reply
Should gene-edited babies be a scientific goal, and if so how should risks be reduced?
(Or, alternately, are they inevitable and how should risks be reduced?)
[+] [-] jerf|7 years ago|reply
However, the problem here is that we do not currently have the ability to create designer babies. We have a few clumsy tools that resemble the tools we'd actually need to do it, but in much the same way that a butcher's knife resembles a scalpel. It's an improvement over the era where what we had was a jackhammer, but it's still not suitable for the task. Any attempt to get serious about human germ-line editing with the current toolset isn't going to work. That means, there is very little likelihood of successful, happy outcomes, and a lot of room for unhappy, dangerous, or deadly outcomes.
Before people seriously start trying this, we need to tip that balance to a point where it's at least interesting to discuss. An ethical discussion would have to revolve around costs and benefits, and it's a really easy discussion when it's basically all costs and no benefits. We don't need to invoke any particular philosophy or argue about utilitarianism or the virtues of deontology or what we should be deontological about in that scenario.
So while I don't have a complete answer, one step to the "risk reduction" you ask for is that we still need better tooling so we're not trying to do the equivalent of performing brain surgery with a butcher's knife, before there's even anything all that interesting to discuss. We should have those discussions sooner rather than later, but as the article alludes to, "we" collectively actually have. (The fact we have no ability to enforce that discussion is a problem of some sort, though.)
At least human germ-line experimentation isn't infectious, though.
[+] [-] jillesvangurp|7 years ago|reply
People worry about designer babies or baby hitlers (to name a few of the cliches). In reality people are trying to fix serious genetic defects and the science to do that in a responsible way is kind of near impossible to conduct in most reputable universities because of ethics. So, it's happening in a much less responsible way elsewhere by people who want to cash in on the obvious demand for any kind of snake oil or real solutions in this space.
[+] [-] brownbat|7 years ago|reply
The discussion in the news could really benefit from reminding people what techniques we are currently using, to make it clear how this technique increased risk without advancing outcomes, and to make it clear that the objections aren't simply against all genetic tech.
[+] [-] nonbel|7 years ago|reply
I bet this will come out as made up or fatally misinterpreted somehow.
[+] [-] pulse7|7 years ago|reply
[+] [-] bencollier49|7 years ago|reply
[+] [-] IfOnlyYouKnew|7 years ago|reply
"After the talk, He revealed another pregnancy is on the way".
"It is still unclear if He did what he claims to have done."
"But He appears to have leapfrogged over all of those basic checks"
[+] [-] unknown|7 years ago|reply
[deleted]
[+] [-] unknown|7 years ago|reply
[deleted]
[+] [-] ganzuul|7 years ago|reply
True.
> What’s shocking about this “is the blatant disregard of all the rules and conventions we have in place for how one should approach any proposed intervention,” said Leonid Kruglyak, a geneticist at the University of California at Los Angeles, on Twitter.
That's like saying no one can stab you because it is illegal.
It would seem that the systematic error lies squarely on academia and business ignoring each other for far too long.
ED:
Clearly I have failed the communicate what I mean...
There are two different cultures both using the same tools. One believes it controls the tools and gets to set rules for how they are used. The other does not.
Juxtapose, the censorship board for TV in my country, which decided that calling Yugo surplus "genocide canteens" is bad, but reprehensible filth like Fear Factor and Big Brother is OK for prime time. Clearly, opinions do differ and are allowed to differ. - I call into question: Is the case of bioethics vs. business similar?
[+] [-] simonh|7 years ago|reply
>That's like saying no one can stab you because it is illegal.
It's like saying no one should stab you because it is illegal.
[+] [-] plgonzalezrx8|7 years ago|reply
Mr. Jiankui would have been less confusing. Editors should be able to identify issues like this and adjust the writing to avoid confusion IMHO.
[+] [-] ericdykstra|7 years ago|reply
Of course, we have some short-sighted scientists who only care about their own work and not the long-term implications, like He himself and Church, but the actions and words of these two were roundly condemned.
Hopefully this buys us enough time to see the real long-term implications of starting a Phenotypic Revolution[1], and we can get some world-wide consensus to stop gene-editing in humans.
[1] https://www.amazon.com/gp/product/1729861563/
[+] [-] quotemstr|7 years ago|reply
[+] [-] entity345|7 years ago|reply
Legal restrictions and ethical concerns will not prevent it.
Then what?
[+] [-] jayrwren|7 years ago|reply
WTF, The Atlantic? Get some copy editing.
[+] [-] _fbpt|7 years ago|reply
Aren't those beliefs themselves harmful?
[+] [-] chasd00|7 years ago|reply
I thought human experimentation like this went out of style after ww2? Isn't this pretty much a crime against humanity now?
[+] [-] conistonwater|7 years ago|reply
[+] [-] yhoneycomb|7 years ago|reply
If we don't villainize the creators of the atomic bomb (Fermi, Oppenheimer) I see no reason why we should villainize this man.
[+] [-] Digit-Al|7 years ago|reply
[+] [-] Nasrudith|7 years ago|reply
It is an irony of medicine that dire circumstances make what would otherwise be recklessness permissible since they have nothing to lose.
That said once the technology is ready it would be outright immoral and stupid not to use it. Like not vaccinating against smallpox because it is unfair to those who aren't or not providing education because it would make the educated better off than the uneducated.
[+] [-] granshaw|7 years ago|reply
[+] [-] aidenolivia|7 years ago|reply
[deleted]
[+] [-] nkg|7 years ago|reply
[+] [-] jcims|7 years ago|reply
I can't imagine it would be that difficult for a reasonably sophisticated organization to keep track of the child as it grew up, and with popularity of genetic testing you could probably find them again anyway.
[+] [-] vectorEQ|7 years ago|reply
[+] [-] jcranmer|7 years ago|reply
Yes, that the name is the same as English's third-plural masculine singular is confusing.
[+] [-] TSiege|7 years ago|reply
[+] [-] unknown|7 years ago|reply
[deleted]
[+] [-] kitotik|7 years ago|reply
[+] [-] IfOnlyYouKnew|7 years ago|reply
[+] [-] unknown|7 years ago|reply
[deleted]
[+] [-] zeroname|7 years ago|reply
I, for one, welcome our new Chinese designer baby overlords.
[+] [-] IfOnlyYouKnew|7 years ago|reply
- it is not actually defensible to abort fetuses based on sex.
- genetic engineering might make populations more susceptible to epidemics
- it would increase pressure on others, or other nations, to follow suit so as not to fall behind in the “race race” of eugenics
- it would seem to devalue non-engineered life, directly threatening the universal dignity of all human beings
- your tired meme is tired
[+] [-] Gokenstein|7 years ago|reply