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The untold story of ‘circle of trust’ behind world’s first gene-edited babies

sciencemag.org

11–20 of 49 posts

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#11

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.

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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#12
post #4

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 c…

> 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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#13
post #6
post #5

Earlier quoted context omitted.

> 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…

> Some of us prefer science and progress.

This is a simplistic argument that can be used to justify practically anything so long as growth continues.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#14

Earlier quoted context omitted.

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 incr…

Your attempt at whataboutism failed. 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…

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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#16
post #6
post #5

Earlier quoted context omitted.

> 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…

> 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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#17

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.

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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#18

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.

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 broa…

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.

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#19

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.

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 broa…

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?

Re: The untold story of ‘circle of trust’ behind world’s first gene-edited babies

#20
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 CCR5􏰀32 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 girls towards unknown ends without informed consent. In effect, this experiment is not just upon the current generation, but all future generations as the germlines have been edited in, frankly, not-well understood ways.

People outside the field who discuss the topic by talking about the stratification of the rich and the poor etc. are discussing a valid concern. But the real concern is that we aren't there yet. This is a blunt instrument that has been used to change all the future descendants of these children, without any regard or understanding for what will happen or what has already happened.

What do we do now? Prevent these kids from having children a few decades from now? Is that fair to the children?

He and all parties involved have left a mess for the world to clean up.

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