I'm feeling bewitched by this entire story of rejection of He Jiankui. Could someone here please describe in layman's terms what's wrong with the _ethics_ of germline editing?
Edit: yes it's gonna be crazy expensive and 10+ years will pass before the tech is ready for mass use, I realize that.
People don't like that it's permanent, and transmitted.
If you have money, you can make your kids AIDS (and Cholera, and Smallpox) resistant.
They see that as "unfair", and conveniently forget money buy high education and network.
Some other people disagree for religious reason - they say it's "playing god", but I do not understand their arguments. Humanity has done selective breeding for centuries, and nobody ever complained.
It's just doing the same with better methods, as the CCR5 mutation discussed in the article was not created by humans, but naturally selected.
> Humanity has done selective breeding for centuries, and nobody ever complained.
Nobody has ever complained about eugenics? About master races vs. inferior breeds of human, or about hereditary caste systems? I think you need to brush up on your history before making such claims.
I imagine OP is talking about how we get to select our partners, not eugenics. And how, generally speaking, the wealthier and better looking a person is the wealthier and better looking their partner and then children will be.
Edit, to add: the same is likely true for realized intelligence as well.
I got downvoted for expressing this opinion before but the only real issues are implementation related.
#1: The technology isn't mature enough and has some "mistargetting" that adds or deletes where it shouldn't.
#2: It is a reckless disregard for human life to not do generational animal trials before humans. If we cannot say make mice redfurred or immune to a mouse disease without major side effects like vastly increased cancer risk doing so in humans is unconscionable.*
*Medical ethics has a bit of weirdness in that if someone is certainly doomed otherwise it is more permissible to try something crazy.
If we could accessibly edit DNA mistakes with no more risk or difficulty than say preventing blood type mismatch related miscarriage then it having a few people with "bad traits carried onto offspring" wouldn't be a big deal.
It is often en vogue to complain about it cementing a class divide but under that logic education is unethical because it priveledges those who can afford it over those who cannot.
It is not at all equivalent. In developed countries, education is accessible to most or all. (The USA is not a developed country by this measure)
If you aren't worried about humanity splitting into multiple species along economic lines, I don't know what to tell you. I guess the film Gattaca was just a fun romp for you? I guess you must assume you will be one of the "haves" and to hell with everyone else, if you get yours?
No, they make a good point. If you restrict your focus to countries where higher education is expensive, it definitely is one of many ways in which parental wealth translates into an advantage for offspring. To say it's free or cheap in some countries is just missing their point.
There are also ways in which parental wealth is a disadvantage. It can weaken that grit, ambition, and drive to accomplish things.
While I worry about the implications as much as you do (Gattaca was a great, thought provoking movie) I think the grandparent comment is completely correct that there may be no way to prevent it. If we outlaw it our country, other countries may not. It only takes one group from now until the end of the human race to pursue this for that bifurcation of the human race to be possible.
Maybe it's not such a bad thing. If we don't make ourselves better, whatever the cost, we may find ourselves replaced by artificial life one day.
It boils down to the fact that there are large potential (if improbable) downsides to messing with DNA, and people have a strong cognitive bias against actively inflicting harm vis a vis just allowing harm to happen on its own.
I personally don't think it's possible to prevent this kind of thing in the long term, so everything ranging from edited children born with horrible disabilities to deleting some potentially beneficial mutation paths in the human genome from existence is going to happen anyway.
Against He specifically, the biggest factor that causes consternation is that He seems to have been more motivated by winning the accolades of being first than by actually doing good work. The work came out of nowhere, wasn't exactly successful (in that neither of resulting gene edits actually reflected the intended result), and it's unclear if the parents actually understood what they were consenting to.
To the broader topic, one of the major issues is that genes are nowhere near so cut-and-dried as they are portrayed in science fiction. Rather famously, the mutation that confers sickle-cell anemia also confers resistance to malaria. But for most genes, we don't know what the side-effects of their mutations will be. How can you properly ask for consent to a procedure whose consequences are often unknown and perhaps unknowable? All the more harder when the person on whom the greatest burden is borne is not yet in existence, let alone capable of giving consent.
Human experiments without consent is about more than just the parents. A huge factor is early experiments will result in a lifetime of suffering for the infants due to any mistakes or unknown consequences etc. The ethics might be more debatable if we knew what was going to happen, but there are huge unknowns here.
And even the case of sickle-cell is extremely straight forward compared most genes and what traits they influence. Even hair color is controlled my multiple genes and is not full understood.
It’s why I am personally a bit watery on predictions that CRISPR is going to be a miracle cure anytime soon. CRISPR is like having a modern machine shop complete with high precision CNC machines in the Bronze Age. You know there is big potential but do you really know what to do with it, or how? Can you use it to its full potential?
It's impossible to have a steroids-optional elite sports league because all the non-steroid-users would get outcompeted, effectively turning it into a steroids-mandatory league. Either everyone uses steroids or they're completely banned - there's no middle ground.
In the jargon of game theory, in the absence of a ban, everyone doping is the only strong Nash equilibrium.
The fear is gene edited babies would trigger the same effect: If I'm in my country's richest 3% and I know parents in the richest 2% are gene-editing their children to be healthier/smarter/prettier, can I afford not to do the same?
And we can't rely on national governments to provide bans - if I'm Country A's leader, can I afford to ban gene editing if our rival, Country B, is making full use of it?
Isn't this the exact same situation with nukes? Why are we banning gene editing when nuclear proliferation is all but expected at this point? Is it because MAD does provide some stability, or because we're more used to nukes as a concept?
I'm struggling to see the similarities with nukes to the point I'm not sure what to put forward as a key example of why they are different. Following with your call out though yes, nukes stopped being something you could do to further your position and turned into something that is very negative for everyone's position a long time ago. Even before this point nukes seem like a completely different dynamic though, they only move you "forward" in use by moving the other side back making the average worse and you can't exactly use them against a section of a population rather other geographic groups as a whole.
The only similarity I can draw is that both have been restricted internationally.
I see the problem with steroids in sports. They are unhealthy and sports is a zero-sum game.
But what's the problem with manipulating people to be healthier, smarter and more attractive? Wouldn't that improve the world? Everyone benefits if humankind becomes less dumb.
Well, this is all very hypothetical stuff. There might be no downsides at all! Hell, if I could safely make my future children 6 inches taller and 20 IQ points smarter, I'd do it.
But many people have imagined dystopian consequences - creation of a lifelong underclass; negative side-effects that take decades to manifest; having big corporations and government gatekeeping conception; monoculture and loss of genetic diversity; what would become of us pre-editing humans; impact of state control of genetically-predicated personality traits; and so on.
What about the countries, ethnic groups and religions that can't afford to edit the genes of their children.
Is their destiny to be out-competed by those groups with the best gene editing technology?
What if a particular highly effective gene editing technique is perfected and patented in country A and they refuse a license to country B because they are rivals?
What if in country Z only ethnic group X is allowed to receive the treatment?
What do you mean by out-competed? For humans, reproduction has very little to do with the traits that people might want to select for. Just about every group that could afford such treatment is already has a low fertility rate.
I watched that movie and wished that I could have been the beneficiary of such editing. Once it's possible it seems obvious to want to do it. What's the problem?
I don’t have a problem with it, but certain worldviews would driving motivators in the world would be very upset about gene editing. Like imagine if in 50 years billionaires are biologically immortal. That’d be quite something.
It's not like there's a fair competition between people today. The richest babies already have extraordinary advantages over poor babies.
It really just exposes that people in power don't want to make it obvious that they've got an unfair advantage, and that basing society off of competition is what's bad.
>The fear is gene edited babies would trigger the same effect: If I'm in my country's richest 3% and I know parents in the richest 2% are gene-editing their children to be healthier/smarter/prettier, can I afford not to do the same?
> Hopefully China will keep advancing science, while the West goes into another dark age due to its religions.
.. given this and the uighur thing, they certainly do seem to have a knack for atheist eugenics. Opium of the masses and the inevitable march of dialectical materialism, amirite?
> Opium of the masses and the inevitable march of dialectical materialism, amirite?
You have different values, good for you.
Some of us prefer science and progress. You live in your country with your values, please do not export them on us and we will do the same.
The rest of the world is free to opt in China generosity. I am sure one belt one road will help Africa more than all your charities and religious missions combined.
> You live in your country with your values, please do not export them on us and we will do the same.
This doesn't really work as an argument, though. If someone said "You believe murder is wrong, I don't, don't try to force your morality on me" to justify murder, most people wouldn't buy into that logic. Obviously not all cases are as clear-cut as that, but when it comes to ethical concerns, the attitude of "you do your thing, I'll do mine" doesn't really apply.
Science isn't linear, it's not really forwards or backwards. Cultural values drive scientific research, especially technology and application of research.
One of the more pernicious aspects of this debate is that talking about it without being labelled a luddite is difficult. However, there are several practical concerns about He's work that were raised by geneticists.
The first and most obvious one is simple, we don't actually know if the changes worked. Unless He were to introduce HIV to these children, we don't know what their "immunity" is, and we don't know to what extent it would be conferred,
> The key takeaway is that CCR532 does not guarantee immunity to HIV infection and possible death. It only works for strains of HIV-1 that use only CCR5 as a co-factor along with CD4 to infect T cells. A few reporters seem to have noticed, or at least commented, on the importance of CXCR4, including early news stories from the ATLANTIC, NATURE, and BLOOMBERG.
But those facts then disappeared probably because ‘complete’ protection against HIV infection made for a better story, a better dilemma, and a better thought experiment, even though that it did not match the reality of the situation for the two baby girls.
Once you understand this, Mr. He is less of a heroic Prometheus, and more of a meek, milquetoast Josef Mengele, conducting unethical experiments badly at a much, much smaller scale but with possibly greater fallout (from a very narrow perspective - I do not wish to make light of the loss of life that Mengele's experiments led to nor the suffering he brought onto others. I am talking about the cross-generational effects of what He has done.).
The second fact that no one has talked about is that we don't actually know how the changes will be expressed in their bodies and how they will be spread. More bluntly, CRISPR is an amazing tool that is sharper than anything we've had, but it is still fairly coarse. There are several "off-target effects". A bioethics statement in Nature stated as much,
> Third, reporting of off-target effects and highlighting of the risks of gene-editing embryos was insufficient. Off-target and undesirable ‘on-target’ effects are common- place with the use of CRISPR–Cas9 and represent the most prevalent risks to an organ- ism. He acknowledged such risks in his pub- lic statements but falsely reports that he has determined how to eliminate them or interpret them as irrelevant to the functioning organism.
We have assigned it far greater precision and ability to propagate changes than it actually does. It's also rather easy to mess up. So we don't actually know if these changes were propagated to all of the cells of the blastocyst. We don't know how they will be expressed and we don't know what will happen.
> Any unintended and deeply uncertain improvements in the cognition of the twins cannot be counted as a benefit in an ethical assessment of He’s experiment. Quite the opposite: the possibility of any brain effects should be considered yet another risk of the work.
> What about the benefits to science? The fact that apparently healthy children could be born after embryo editing is, certainly, a novel finding of some value. Given earlier successes with monkeys, as well as other mammals, it is not deeply surprising—but nei- ther was it completely certain. Even closely-related species sometimes differ markedly in reproduction and early development.
Indeed what those studies have taught us is that these tools are still too primitive for such discussons.
What makes this more horrifying is that by doing this, He has altered all future descendants of these gi...
For everyone concerned about the tech being not ready, equality, etc: isn't it better to allow this experimentation in the open with proper oversight rather than attempting to ban it and in doing so drive it underground? This genie is out of the bottle, it cannot be put back. All that bans will do is simply ensure that all of those concerns are even worse: worse tech due to less funding, less accessibility except for the elite due to the whole thing being underground, less scientific review.
It is being allowed with proper oversight. These people are just experimenting underground.
The problem with this tech isn't just the Übermensch (or should I say, ÜberTiāncháo) that we will have to deal with, but more subtle. For instance, a percentage of northern europeans are already partially genetically immune to HIV/AIDS [1]
People with sickle cell anaemia are already somewhat immune to Malaria [2]. Some gibbering genius in a laboratory might decide to cure the human race of Anaemia and inadvertently cause millions of people to start dying of malaria or dengue.
There are plenty of "problem" genes that we carry in our genome that scientists will want to "fix", and then we will discover the hard way why those genes are there in the first place. This absolutely needs to be controlled. The coming man will not be an Übermensch, but a CRISPR-castrato
Research with human participants is being over-sighted to the point that real research is virtually impossible. I say this, having seen the IRB approval process for human subject research. Research institutes just don't want to take on the risk
> Early last March, the state of Washington was the site of the first major coronavirus outbreak in the U.S. As COVID rates and the need for tests were spiking, BGI Group, the world's largest biotech firm - a global giant based in China - approached the state of Washington with an enticing offer… BGI proposed to build and help run state-of-the-art COVID testing labs... the company made similar proposals to more than five other states, including New York and California…. And, after federal officials warned against partnering with BGI, each state said no to BGI's labs… It's not just China that's recognized what a valuable commodity your DNA can be. As you'll hear: some of the fastest-growing U.S. tech companies are in this space, as well. In fact, you may have already surrendered your DNA…"
I think the elephant in the room is not He's work, but the fact that embryonic selection is already commercially available from Steve Hsu's Genomic Prediction[1] and other companies.
It doesn't impart new genes, so it can't give HIV immunity if the parents don't have it, but it can screen large numbers of embryos and allow the parents to select the one(s) they want based on their genetic makeup
It is done using well established technology and can select the factors that people really care about: intelligence, and freedom from disease, gender, and mental health.
Genomic Predictions is already working with 200 IVF clinics and screening millions of embryos a year. Many countries have laws against using the technology to screen for anything but disease (e.g. higher intelligence), but some do not.
Creating multiple embryos in the lab then screening them for diseases etc. can of course help with some situations, but if both chromosomes from one parent carry some variant of a gene, you can't get rid of it. Similarly, you can't introduce desired variants if none of the two parents want them. So arbitrary edits are way more powerful.
I think powerful is a loaded word, but the rest of what you said is correct. They are different technologies for different things. Crispr is "good" for single genes. Screening is "good" for polygenic traits. For example, intelligence is thought to be linked to over 500 genes. This would not be good target for embryonic editing, even if the error rate was extremely low.
48 comments
[ 4.0 ms ] story [ 106 ms ] threadEdit: yes it's gonna be crazy expensive and 10+ years will pass before the tech is ready for mass use, I realize that.
If you have money, you can make your kids AIDS (and Cholera, and Smallpox) resistant.
They see that as "unfair", and conveniently forget money buy high education and network.
Some other people disagree for religious reason - they say it's "playing god", but I do not understand their arguments. Humanity has done selective breeding for centuries, and nobody ever complained.
It's just doing the same with better methods, as the CCR5 mutation discussed in the article was not created by humans, but naturally selected.
Nobody has ever complained about eugenics? About master races vs. inferior breeds of human, or about hereditary caste systems? I think you need to brush up on your history before making such claims.
Edit, to add: the same is likely true for realized intelligence as well.
#1: The technology isn't mature enough and has some "mistargetting" that adds or deletes where it shouldn't.
#2: It is a reckless disregard for human life to not do generational animal trials before humans. If we cannot say make mice redfurred or immune to a mouse disease without major side effects like vastly increased cancer risk doing so in humans is unconscionable.*
*Medical ethics has a bit of weirdness in that if someone is certainly doomed otherwise it is more permissible to try something crazy.
If we could accessibly edit DNA mistakes with no more risk or difficulty than say preventing blood type mismatch related miscarriage then it having a few people with "bad traits carried onto offspring" wouldn't be a big deal.
It is often en vogue to complain about it cementing a class divide but under that logic education is unethical because it priveledges those who can afford it over those who cannot.
It is not at all equivalent. In developed countries, education is accessible to most or all. (The USA is not a developed country by this measure)
If you aren't worried about humanity splitting into multiple species along economic lines, I don't know what to tell you. I guess the film Gattaca was just a fun romp for you? I guess you must assume you will be one of the "haves" and to hell with everyone else, if you get yours?
There are also ways in which parental wealth is a disadvantage. It can weaken that grit, ambition, and drive to accomplish things.
While I worry about the implications as much as you do (Gattaca was a great, thought provoking movie) I think the grandparent comment is completely correct that there may be no way to prevent it. If we outlaw it our country, other countries may not. It only takes one group from now until the end of the human race to pursue this for that bifurcation of the human race to be possible.
Maybe it's not such a bad thing. If we don't make ourselves better, whatever the cost, we may find ourselves replaced by artificial life one day.
Ignoring the US for education is silly because it's the place where gene editing is likeliest to be restricted to the richest.
No, unequal access to education is unethical.
While it might be impractical to guarantee absolutely equal education, most people agree access to a basic education is a human right.
Not to mention the splitting of humanity into separate species, based on wealth.
It is a whole mess of ethical concerns. I am astonished that you can't see that.
I personally don't think it's possible to prevent this kind of thing in the long term, so everything ranging from edited children born with horrible disabilities to deleting some potentially beneficial mutation paths in the human genome from existence is going to happen anyway.
To the broader topic, one of the major issues is that genes are nowhere near so cut-and-dried as they are portrayed in science fiction. Rather famously, the mutation that confers sickle-cell anemia also confers resistance to malaria. But for most genes, we don't know what the side-effects of their mutations will be. How can you properly ask for consent to a procedure whose consequences are often unknown and perhaps unknowable? All the more harder when the person on whom the greatest burden is borne is not yet in existence, let alone capable of giving consent.
It’s why I am personally a bit watery on predictions that CRISPR is going to be a miracle cure anytime soon. CRISPR is like having a modern machine shop complete with high precision CNC machines in the Bronze Age. You know there is big potential but do you really know what to do with it, or how? Can you use it to its full potential?
In the jargon of game theory, in the absence of a ban, everyone doping is the only strong Nash equilibrium.
The fear is gene edited babies would trigger the same effect: If I'm in my country's richest 3% and I know parents in the richest 2% are gene-editing their children to be healthier/smarter/prettier, can I afford not to do the same?
And we can't rely on national governments to provide bans - if I'm Country A's leader, can I afford to ban gene editing if our rival, Country B, is making full use of it?
The only similarity I can draw is that both have been restricted internationally.
The (pretty effective) nuclear non-proliferation treaty does beg the question here...
But what's the problem with manipulating people to be healthier, smarter and more attractive? Wouldn't that improve the world? Everyone benefits if humankind becomes less dumb.
But many people have imagined dystopian consequences - creation of a lifelong underclass; negative side-effects that take decades to manifest; having big corporations and government gatekeeping conception; monoculture and loss of genetic diversity; what would become of us pre-editing humans; impact of state control of genetically-predicated personality traits; and so on.
Is their destiny to be out-competed by those groups with the best gene editing technology?
What if a particular highly effective gene editing technique is perfected and patented in country A and they refuse a license to country B because they are rivals?
What if in country Z only ethnic group X is allowed to receive the treatment?
It really just exposes that people in power don't want to make it obvious that they've got an unfair advantage, and that basing society off of competition is what's bad.
Can't you say the same about private school?
Sad to see how the West keep pushing it's agenda and values down the throat of other countries.
Hopefully China will keep advancing science, while the West goes into another dark age due to its religions.
.. given this and the uighur thing, they certainly do seem to have a knack for atheist eugenics. Opium of the masses and the inevitable march of dialectical materialism, amirite?
You have different values, good for you.
Some of us prefer science and progress. You live in your country with your values, please do not export them on us and we will do the same.
The rest of the world is free to opt in China generosity. I am sure one belt one road will help Africa more than all your charities and religious missions combined.
This is a simplistic argument that can be used to justify practically anything so long as growth continues.
This doesn't really work as an argument, though. If someone said "You believe murder is wrong, I don't, don't try to force your morality on me" to justify murder, most people wouldn't buy into that logic. Obviously not all cases are as clear-cut as that, but when it comes to ethical concerns, the attitude of "you do your thing, I'll do mine" doesn't really apply.
Except they seem to be fully kowtowing to the West.
Like this case. Or even the reported - "China bans skyscrapers taller than 500 meters"
Every student they send overseas to study is one more indoctrinated scientist.
The first and most obvious one is simple, we don't actually know if the changes worked. Unless He were to introduce HIV to these children, we don't know what their "immunity" is, and we don't know to what extent it would be conferred,
> The key takeaway is that CCR532 does not guarantee immunity to HIV infection and possible death. It only works for strains of HIV-1 that use only CCR5 as a co-factor along with CD4 to infect T cells. A few reporters seem to have noticed, or at least commented, on the importance of CXCR4, including early news stories from the ATLANTIC, NATURE, and BLOOMBERG. But those facts then disappeared probably because ‘complete’ protection against HIV infection made for a better story, a better dilemma, and a better thought experiment, even though that it did not match the reality of the situation for the two baby girls.
https://academic.oup.com/jlb/article/6/1/111/5549624?login=t...
Once you understand this, Mr. He is less of a heroic Prometheus, and more of a meek, milquetoast Josef Mengele, conducting unethical experiments badly at a much, much smaller scale but with possibly greater fallout (from a very narrow perspective - I do not wish to make light of the loss of life that Mengele's experiments led to nor the suffering he brought onto others. I am talking about the cross-generational effects of what He has done.).
The second fact that no one has talked about is that we don't actually know how the changes will be expressed in their bodies and how they will be spread. More bluntly, CRISPR is an amazing tool that is sharper than anything we've had, but it is still fairly coarse. There are several "off-target effects". A bioethics statement in Nature stated as much,
> Third, reporting of off-target effects and highlighting of the risks of gene-editing embryos was insufficient. Off-target and undesirable ‘on-target’ effects are common- place with the use of CRISPR–Cas9 and represent the most prevalent risks to an organ- ism. He acknowledged such risks in his pub- lic statements but falsely reports that he has determined how to eliminate them or interpret them as irrelevant to the functioning organism.
https://sites.tufts.edu/sheldonkrimsky/files/2019/01/pub2019...
We have assigned it far greater precision and ability to propagate changes than it actually does. It's also rather easy to mess up. So we don't actually know if these changes were propagated to all of the cells of the blastocyst. We don't know how they will be expressed and we don't know what will happen.
> Any unintended and deeply uncertain improvements in the cognition of the twins cannot be counted as a benefit in an ethical assessment of He’s experiment. Quite the opposite: the possibility of any brain effects should be considered yet another risk of the work.
> What about the benefits to science? The fact that apparently healthy children could be born after embryo editing is, certainly, a novel finding of some value. Given earlier successes with monkeys, as well as other mammals, it is not deeply surprising—but nei- ther was it completely certain. Even closely-related species sometimes differ markedly in reproduction and early development.
Indeed what those studies have taught us is that these tools are still too primitive for such discussons.
What makes this more horrifying is that by doing this, He has altered all future descendants of these gi...
The problem with this tech isn't just the Übermensch (or should I say, ÜberTiāncháo) that we will have to deal with, but more subtle. For instance, a percentage of northern europeans are already partially genetically immune to HIV/AIDS [1]
People with sickle cell anaemia are already somewhat immune to Malaria [2]. Some gibbering genius in a laboratory might decide to cure the human race of Anaemia and inadvertently cause millions of people to start dying of malaria or dengue.
There are plenty of "problem" genes that we carry in our genome that scientists will want to "fix", and then we will discover the hard way why those genes are there in the first place. This absolutely needs to be controlled. The coming man will not be an Übermensch, but a CRISPR-castrato
[1] https://www.nature.com/scitable/blog/viruses101/hiv_resistan... [2] https://www.cdc.gov/malaria/about/biology/index.html (select 'sickle cell')
> Early last March, the state of Washington was the site of the first major coronavirus outbreak in the U.S. As COVID rates and the need for tests were spiking, BGI Group, the world's largest biotech firm - a global giant based in China - approached the state of Washington with an enticing offer… BGI proposed to build and help run state-of-the-art COVID testing labs... the company made similar proposals to more than five other states, including New York and California…. And, after federal officials warned against partnering with BGI, each state said no to BGI's labs… It's not just China that's recognized what a valuable commodity your DNA can be. As you'll hear: some of the fastest-growing U.S. tech companies are in this space, as well. In fact, you may have already surrendered your DNA…"
It doesn't impart new genes, so it can't give HIV immunity if the parents don't have it, but it can screen large numbers of embryos and allow the parents to select the one(s) they want based on their genetic makeup
It is done using well established technology and can select the factors that people really care about: intelligence, and freedom from disease, gender, and mental health.
Genomic Predictions is already working with 200 IVF clinics and screening millions of embryos a year. Many countries have laws against using the technology to screen for anything but disease (e.g. higher intelligence), but some do not.
https://pitchbook.com/profiles/company/228085-75#overview