8 ms·

Pardon my ignorance but why is it unethical to use CRISPR on human embryos? Is it a question of the technology being still too immature or the more philosophica

Pardon my ignorance but why is it unethical to use CRISPR on human embryos? Is it a question of the technology being still too immature or the more philosophical question of whether it should be used at all? Something else?

zozbot123 8y ago
> Is it a question of the technology being still too immature or the more philosophical question of whether it should be used at all? Yes, of course.
fromthestart 8y ago
Ethics aside, it might not be safe. https://www.livescience.com/63075-crispr-damage-cell-mutations.html https://www.livescience.com/63075-crispr-damage-cell-mutatio...
sys_64738 8y ago
They could edit the DNA to do something truly horrendous. E.g. The Fly movie via DNA modification.
- deleted 8y ago
  [deleted]
- sannee 8y ago
  Are you being hyperbolic or do you actually think that the current (or at any point in the next few hundred years) genetic modification technology is capable of doing anything close to transforming humans to "fly-hybrid creature"?
shard972 8y ago
Because it completely turns a lot of our societies meta-narratives inside-out. One of them being that humans are born equal, how can we believe that we are created equally by a common creator if now some are being created to be "better" than everyone else? Is there a point where we end up creating someone that isn't human? If they aren't human, what kind of rights are they to have? So many weird questions that we don't exactly have the answers ready at hand.
- hyperdunc 8y ago
  This metanarrative as you decribe it is clearly false. More precisely, the idea is that humans should have equal rights and equal access to opportunities. In practice we don't even have that.
  - alexandercrohde 8y ago
    Maybe clearly false to you, but certainly not to everyone.
  - shard972 8y ago
    A meta-narrative doesn't require its promises to be realised physically for it to be "true" within a population. It's just a case of wether or not people "believe" it to be true.
est31 8y ago
In principle I think that we should consider doing germline edits in humans. In general, if we have the ability to improve ourselves, we should absolutely do it. However, in this specific instance, I think being strict on the scientist is okay. The scientist made a mutation that was supposed to make the babies immune to HIV. But it turns out that the alleged CCR5 mutation that he induced a) didn't make the babies immune to all HIV strains only most of them (there are CXCR4 based HIV strains) [1], and b) made them more susceptible to other diseases like west nile virus infection [2]. He didn't just do that, he also circumented the approval infrastructure of science that is supposed to watch out for unethical experiments. If such behaviour is rewarded, people will start to do ethically questionable experiments. Biology is still in the shadow of past ethical violations like e.g. the HeLa cell samples that were being used throughout science without consent from the donor. Or think of the contergan scandal where the manufacturer company advertised that pregnant women should take contergan. Later it turned out that it had an absolutely harmful effect on fetuses, crippling them for life. The worst thing about this: the company knew about the effects but chose to hide the facts from the public. I don't say that we shouldn't do germline edits at all. We should just be really careful at what we are doing, especially at the start. After all we are forcing (we don't ask the baby) a human being to live with that genetic change for an entire lifetime and their offspring. Instead, we could maybe have started with one of those really ugly hereditary diseases that end in certain early death due to an unpopular mutation of a certain gene... Changing that gene to the popular variant would be objectively helpful and meaningful. [1]: https://www.nature.com/articles/d41586-018-07545-0 https://www.nature.com/articles/d41586-018-07545-0 [2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118086/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118086/
- saagarjha 8y ago
  > In principle I think that we should consider doing germline edits in humans. In general, if we have the ability to improve ourselves, we should absolutely do it. What if not everyone has the ability to improve themselves, say due to cost?
  - pests 8y ago
    Doesn't this already manifest in the form of gyms, advanced medicine, proper exercise and nutrition, and various other "improve ourselves" things that require money?
19f191ty 8y ago
Lots of nuances. This Twitter thread by a prominent biologist provides a detailed response to your question, worth a read. https://mobile.twitter.com/thattai/status/1067958258911064065 https://mobile.twitter.com/thattai/status/106795825891106406...
dyu 8y ago
It's like editing a piece of code without fully understanding what it does, without unit tests, and your text editor may be buggy.
- wjn0 8y ago
  I like that analogy. An even better one: porting the code of `sed' to a new operating system without fully understanding it, using `sed' to automatically correct bugs in fundamental operating system code without checks, recompiling said OS, and hoping it works perfectly.
- dis-sys 8y ago
  > It's like editing a piece of code without fully understanding what it does, without unit tests, and your text editor may be buggy. No, it is far worse than what you described. your described buggy code can cause damages but you have the choice to delete them all to stop any further damages. There is no such option for experiments done on humans.
  - webmaven 8y ago
    > There is no such option for experiments done on humans. There are, unfortunately, options for deleting humans with "buggy code", the real problems surround the fact that it is other - probably "buggy" - humans making the determination of which humans to mark for deletion.
- nsoonhui 8y ago
  And on top of that, the piece of code is fully spaghetti, poorly understood and documented, and contains tight coupling between components. You don't know what breaks and the implication, until it really breaks.
  - heavyset_go 8y ago
    Not only that, compilation time takes 9 months and it could take several decades for a fatal bug to pop up in production.
samfriedman 8y ago
It's really all of the above. For a technology as monumental as human germline editing, the scientific consensus is that we are not yet ready to perform these experiments. There is a widely-supported moratorium on the type of research Dr. He has done, from the ethical implications of the work to the not yet fully understood risks of off-target edits when performing CRISPR modfifications. And even so, what Dr. He did can only be described as bad science. He conducted a study with woefully misinformed participants, and it would appear that there are significant technical shortcomings in his procedure as well. For instance, Dr. He proceeded to implant modified embryos even after confirming that the attempted knockout of the CCR5 gene was unsuccessful. In summary, Dr. He's research flew in wanton violation of worldwide standards for ethics and safe scientific practice, while failing to accomplish anything of note.
- thatoneuser 8y ago
  I’m getting mixed information from these comments. You say he failed to accomplish anything of note. Others have said that his work did leave the subjects immune to some HIV. You say the participants were ill informed, other comments (and his own claims) state that there was a high degree of understanding and communication with reasonably intelligent backgrounds. What’s going on here? This seems like a recurring phenomenon with unethical science - people shut it down wholesale while refusing to entertain the positives. I mean don’t get me wrong - this seems unethical on several levels, but if the work shows actual successful avoidance of HIV in the patients then that’s something we have tested and done that we hadn’t before. If the subjects really have that immunity, then saying he’s “failed to accomplish anything of note” is a pretty unethical claim itself.
koenigdavidmj 8y ago
If it’s China, then the answer is simply that it’s embarrassing.
jcranmer 8y ago
There are several issues: * The technology is still new. We don't have a very strong grasp on the potential ways that CRISPR can go horribly, horribly wrong (as in delete-an-entire-chromosome-wrong) and having technology in place to watch for these failures. * Biology in general suffers from the problem that a lot of our parts are co-opted to do several different things, so knocking out something that is making you sick could have a side effect of suddenly making your kidneys stop working or other serious effects. * Germ-line edits are heritable. The potential consequences of things going wrong affect more than just the person in question, and the recourse for fixing them is unclear. * Consent is tricky. The person who is affected is, by definition, not yet alive to offer consent. Given the potential consequences... it's something that is going to want a fairly involved discussion on how to properly seek consent. The thing about this tale is that the researcher in question flubbed just about everything that could be flubbed. The participants were told by the researcher himself (BIG no-no) that this was an experimental HIV vaccine and apparently nothing at all about it being CRISPR. Furthermore, HIV transmission via paternal sperm donation is very easy to guard against with conventional methods; the gene knocked out may not have actually been sufficient to protect against the HIV strains the father had; and the actual results were pretty damn poor (one embryo was mosaic, another had only one chromosome affected). The general mood after He gave his presentation changed from "oh dear" to "hand me the pitchfork." A silver lining is that it does seem that the Chinese community has been clear in emphasizing that it is not condoning this sort of wildcat experimentation, which is one fear that many people have had in the past.
- TomMarius 8y ago
  > * Consent is tricky. The person who is affected is, by definition, not yet alive to offer consent. Given the potential consequences... it's something that is going to want a fairly involved discussion on how to properly seek consent. Noone gives consent for their birth > Furthermore, HIV transmission via paternal sperm donation is very easy to guard against with conventional methods; the gene knocked out may not have actually been sufficient to protect against the HIV strains the father had Irrelevant, that it's not perfect doesn't mean it shouldn't be done. Many treatments are not perfect. Of course if it introduces new diseases then it's a problem, but dismissing it because it doesn't solve world hunger is weird.
fanf2 8y ago
Best explanation of the issues I have seen is https://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/ https://www.theatlantic.com/science/archive/2018/12/15-worry...
linkmotif 8y ago
This is a vast, fundamental question in bioethics. The question is whether manipulating humans like this, even if technically successful, is good and right. The concerns might be religious or secular, or both. What do we want humanity to be? Do we really want a future where people tailor make babies? Like, what does it even mean to be human? For many people who think about these questions—myself included—the answers seem quite complicated.
JohnJamesRambo 8y ago
As a scientist myself, you should always be very wary of things like this because scientists often think they have things totally figured out and then boom, oops, we knew nothing and the gene you altered or change you made has about 100 different effects that we hadn't thought of or known about. You make these sorts of mistakes in a human being and you've just given them problems for the entirety of their lifetime that they never asked for. "First, do no harm" is harder to live up to than you think.
Vinnl 8y ago
As I understand it, though I haven't seen it clearly mentioned by the sibling comments, the primary issue is that applying this technique to human embryos will not only affect those embryos, but all their offspring. If you make a mistake there, the effects of that would be felt on the scale of humanity.
ajross 8y ago
Gene interactions remain poorly understood. Any such editing is potentially inflicting a lifetime of congenital disease on any child produced, from whom it's obviously impossible to get consent ahead of time.

zozbot123 8y ago

> Is it a question of the technology being still too immature or the more philosophical question of whether it should be used at all? Yes, of course.

fromthestart 8y ago

Ethics aside, it might not be safe. https://www.livescience.com/63075-crispr-damage-cell-mutations.html https://www.livescience.com/63075-crispr-damage-cell-mutatio...

sys_64738 8y ago

They could edit the DNA to do something truly horrendous. E.g. The Fly movie via DNA modification.

deleted 8y ago
[deleted]
sannee 8y ago
Are you being hyperbolic or do you actually think that the current (or at any point in the next few hundred years) genetic modification technology is capable of doing anything close to transforming humans to "fly-hybrid creature"?

shard972 8y ago

Because it completely turns a lot of our societies meta-narratives inside-out. One of them being that humans are born equal, how can we believe that we are created equally by a common creator if now some are being created to be "better" than everyone else? Is there a point where we end up creating someone that isn't human? If they aren't human, what kind of rights are they to have? So many weird questions that we don't exactly have the answers ready at hand.

hyperdunc 8y ago
This metanarrative as you decribe it is clearly false. More precisely, the idea is that humans should have equal rights and equal access to opportunities. In practice we don't even have that.
- alexandercrohde 8y ago
  Maybe clearly false to you, but certainly not to everyone.
- shard972 8y ago
  A meta-narrative doesn't require its promises to be realised physically for it to be "true" within a population. It's just a case of wether or not people "believe" it to be true.

est31 8y ago

In principle I think that we should consider doing germline edits in humans. In general, if we have the ability to improve ourselves, we should absolutely do it. However, in this specific instance, I think being strict on the scientist is okay. The scientist made a mutation that was supposed to make the babies immune to HIV. But it turns out that the alleged CCR5 mutation that he induced a) didn't make the babies immune to all HIV strains only most of them (there are CXCR4 based HIV strains) [1], and b) made them more susceptible to other diseases like west nile virus infection [2]. He didn't just do that, he also circumented the approval infrastructure of science that is supposed to watch out for unethical experiments. If such behaviour is rewarded, people will start to do ethically questionable experiments. Biology is still in the shadow of past ethical violations like e.g. the HeLa cell samples that were being used throughout science without consent from the donor. Or think of the contergan scandal where the manufacturer company advertised that pregnant women should take contergan. Later it turned out that it had an absolutely harmful effect on fetuses, crippling them for life. The worst thing about this: the company knew about the effects but chose to hide the facts from the public. I don't say that we shouldn't do germline edits at all. We should just be really careful at what we are doing, especially at the start. After all we are forcing (we don't ask the baby) a human being to live with that genetic change for an entire lifetime and their offspring. Instead, we could maybe have started with one of those really ugly hereditary diseases that end in certain early death due to an unpopular mutation of a certain gene... Changing that gene to the popular variant would be objectively helpful and meaningful. [1]: https://www.nature.com/articles/d41586-018-07545-0 https://www.nature.com/articles/d41586-018-07545-0 [2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118086/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118086/

saagarjha 8y ago
> In principle I think that we should consider doing germline edits in humans. In general, if we have the ability to improve ourselves, we should absolutely do it. What if not everyone has the ability to improve themselves, say due to cost?
- pests 8y ago
  Doesn't this already manifest in the form of gyms, advanced medicine, proper exercise and nutrition, and various other "improve ourselves" things that require money?

19f191ty 8y ago

Lots of nuances. This Twitter thread by a prominent biologist provides a detailed response to your question, worth a read. https://mobile.twitter.com/thattai/status/1067958258911064065 https://mobile.twitter.com/thattai/status/106795825891106406...

dyu 8y ago

It's like editing a piece of code without fully understanding what it does, without unit tests, and your text editor may be buggy.

wjn0 8y ago
I like that analogy. An even better one: porting the code of `sed' to a new operating system without fully understanding it, using `sed' to automatically correct bugs in fundamental operating system code without checks, recompiling said OS, and hoping it works perfectly.
dis-sys 8y ago
> It's like editing a piece of code without fully understanding what it does, without unit tests, and your text editor may be buggy. No, it is far worse than what you described. your described buggy code can cause damages but you have the choice to delete them all to stop any further damages. There is no such option for experiments done on humans.
- webmaven 8y ago
  > There is no such option for experiments done on humans. There are, unfortunately, options for deleting humans with "buggy code", the real problems surround the fact that it is other - probably "buggy" - humans making the determination of which humans to mark for deletion.
nsoonhui 8y ago
And on top of that, the piece of code is fully spaghetti, poorly understood and documented, and contains tight coupling between components. You don't know what breaks and the implication, until it really breaks.
- heavyset_go 8y ago
  Not only that, compilation time takes 9 months and it could take several decades for a fatal bug to pop up in production.

samfriedman 8y ago

It's really all of the above. For a technology as monumental as human germline editing, the scientific consensus is that we are not yet ready to perform these experiments. There is a widely-supported moratorium on the type of research Dr. He has done, from the ethical implications of the work to the not yet fully understood risks of off-target edits when performing CRISPR modfifications. And even so, what Dr. He did can only be described as bad science. He conducted a study with woefully misinformed participants, and it would appear that there are significant technical shortcomings in his procedure as well. For instance, Dr. He proceeded to implant modified embryos even after confirming that the attempted knockout of the CCR5 gene was unsuccessful. In summary, Dr. He's research flew in wanton violation of worldwide standards for ethics and safe scientific practice, while failing to accomplish anything of note.

thatoneuser 8y ago
I’m getting mixed information from these comments. You say he failed to accomplish anything of note. Others have said that his work did leave the subjects immune to some HIV. You say the participants were ill informed, other comments (and his own claims) state that there was a high degree of understanding and communication with reasonably intelligent backgrounds. What’s going on here? This seems like a recurring phenomenon with unethical science - people shut it down wholesale while refusing to entertain the positives. I mean don’t get me wrong - this seems unethical on several levels, but if the work shows actual successful avoidance of HIV in the patients then that’s something we have tested and done that we hadn’t before. If the subjects really have that immunity, then saying he’s “failed to accomplish anything of note” is a pretty unethical claim itself.

koenigdavidmj 8y ago

If it’s China, then the answer is simply that it’s embarrassing.

jcranmer 8y ago

There are several issues: * The technology is still new. We don't have a very strong grasp on the potential ways that CRISPR can go horribly, horribly wrong (as in delete-an-entire-chromosome-wrong) and having technology in place to watch for these failures. * Biology in general suffers from the problem that a lot of our parts are co-opted to do several different things, so knocking out something that is making you sick could have a side effect of suddenly making your kidneys stop working or other serious effects. * Germ-line edits are heritable. The potential consequences of things going wrong affect more than just the person in question, and the recourse for fixing them is unclear. * Consent is tricky. The person who is affected is, by definition, not yet alive to offer consent. Given the potential consequences... it's something that is going to want a fairly involved discussion on how to properly seek consent. The thing about this tale is that the researcher in question flubbed just about everything that could be flubbed. The participants were told by the researcher himself (BIG no-no) that this was an experimental HIV vaccine and apparently nothing at all about it being CRISPR. Furthermore, HIV transmission via paternal sperm donation is very easy to guard against with conventional methods; the gene knocked out may not have actually been sufficient to protect against the HIV strains the father had; and the actual results were pretty damn poor (one embryo was mosaic, another had only one chromosome affected). The general mood after He gave his presentation changed from "oh dear" to "hand me the pitchfork." A silver lining is that it does seem that the Chinese community has been clear in emphasizing that it is not condoning this sort of wildcat experimentation, which is one fear that many people have had in the past.

TomMarius 8y ago
> * Consent is tricky. The person who is affected is, by definition, not yet alive to offer consent. Given the potential consequences... it's something that is going to want a fairly involved discussion on how to properly seek consent. Noone gives consent for their birth > Furthermore, HIV transmission via paternal sperm donation is very easy to guard against with conventional methods; the gene knocked out may not have actually been sufficient to protect against the HIV strains the father had Irrelevant, that it's not perfect doesn't mean it shouldn't be done. Many treatments are not perfect. Of course if it introduces new diseases then it's a problem, but dismissing it because it doesn't solve world hunger is weird.

fanf2 8y ago

Best explanation of the issues I have seen is https://www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/ https://www.theatlantic.com/science/archive/2018/12/15-worry...

linkmotif 8y ago

This is a vast, fundamental question in bioethics. The question is whether manipulating humans like this, even if technically successful, is good and right. The concerns might be religious or secular, or both. What do we want humanity to be? Do we really want a future where people tailor make babies? Like, what does it even mean to be human? For many people who think about these questions—myself included—the answers seem quite complicated.

JohnJamesRambo 8y ago

As a scientist myself, you should always be very wary of things like this because scientists often think they have things totally figured out and then boom, oops, we knew nothing and the gene you altered or change you made has about 100 different effects that we hadn't thought of or known about. You make these sorts of mistakes in a human being and you've just given them problems for the entirety of their lifetime that they never asked for. "First, do no harm" is harder to live up to than you think.

Vinnl 8y ago

As I understand it, though I haven't seen it clearly mentioned by the sibling comments, the primary issue is that applying this technique to human embryos will not only affect those embryos, but all their offspring. If you make a mistake there, the effects of that would be felt on the scale of humanity.

ajross 8y ago

Gene interactions remain poorly understood. Any such editing is potentially inflicting a lifetime of congenital disease on any child produced, from whom it's obviously impossible to get consent ahead of time.