7 ms·

Editing Babies? We Need to Learn a Lot More First

39 points by yesprabhu 8y ago

hd4 8y ago
The Chinese realize what others refuse to, it's a race and whoever wins sets the rules. And what would they gain by waiting and losing the first-mover advantage? The article talks about risks, they are certainly not that concerned about risks, not as long as they get the upper hand in biotech and genome manipulation.
- Zeebrommer 8y ago
  > Dr. He’s university has disavowed knowledge or support of the research and said an inquiry is underway. Sounds more like an individual rogue action than coordinated effort backed by vision of "the Chinese".
vaultcool 8y ago
How often did Chinese researchers claim to have done something incredible, without proper proof and lack of data, and it turned out to be a total scam? This really feels like another one of these, we'll see what happens, but I wouldn't hold my breath.
- tgb 8y ago
  But the difference here is that, to the best of my knowledge, there's nothing particularly difficult about CRISPR in humans. It's routine in other mammals and had previously been done on human embryos. The thing holding everyone back was ethical concerns and the possibilities of off-target effects, side-effects of the mutation, etc. So I'd err on the side of assuming they did do it.
  - buboard 8y ago
    Also George Church says it's "probably accurate" https://www.statnews.com/2018/11/26/claim-of-crispred-baby-girls-stuns-genome-editing-summit/?utm_content=buffer8fbbd&utm_medium=social&utm_source=twitter&utm_campaign=twitter_organic https://www.statnews.com/2018/11/26/claim-of-crispred-baby-g...
    - gwern 8y ago
      It's worth noting that none of the moderators or questioners at the talk expressed any skepticism that He had done it. They all took for granted He had.
      - buboard 8y ago
        do you know why? my guess is they had previous contact/correspondence throughout the pregnancy Edit: there are slides of his presentation: https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29fN_7qJg7fLA4qlrd https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29...
        gwern 8y ago
        It's really not that implausible a thing to do, you know. People have been editing human embryos with CRISPR since at least 2014. And He has past experience, it seems, and had networked a fair amount and seemed to know what he was doing. George Church also has said that he's seen some of the data and it looks right to him. Combine that with all the data on the slides, and while you can debate the ethics or how useful it would be or how well it actually worked, it seems increasingly plausible that he did something like what he claimed, and he's not simply faking it all.
booleandilemma 8y ago
Meanwhile China is actually doing it and soaking up the investor money, interested researchers, and gaining the lead.
- adventured 8y ago
  That's false. The city of Boston by itself leads China in CRISPR tech and innovation.
  - baybal2 8y ago
    Have you noticed just how many genetic technology in US is actually made in China? Boston companies may have high profile, but all the dirty work is done in China by research outsourcing labs staffed with interns.
    - vedtopkar 8y ago
      Do you have a source for this? This may be true in other fields but most genome editing industry work is almost certainly done stateside.
    - dekhn 8y ago
      I don't think this is true. i work with a people who are CRISPR experts, what's happening in cambridge (not boston) is legit and local.
winchling 8y ago
>We should not proceed down this road until we know far more about the consequences of what we are doing. In the present climate of pessimism it's worth reminding ourselves that we never know all the consequences of what we're doing. The 'Precautionary Principle' kills people too; it merely does so in a less obvious way. Personally I think we should be going hell for leather in identifying and eliminating genetic diseases that arise from known mutations. And we should of course expect new problems to arise down the road from these treatments.
- mannykannot 8y ago
  This is a particularly bad example to make that case over, as it is hard to discern any scientific or medical justification for it, while the known risks are considerable. Frankly, it looks to me like a posterity-grabbing stunt - an attempt by the researcher to write himself into the history books.
  - candiodari 8y ago
    First, the event reported on is almost certainly a scam (HIV resistance ? Seriously ?). But let's assume it's valid. But I don't agree at all with the sentiment. Most/all current gene editing is about fixing known issues, and in nearly all cases (at the moment) it seems like the edited gene, even if it goes disastrously wrong, would still be superior to the "natural" gene. E.g. MVD, MS, ... Should we also outlaw (and enforce) that people with known genetic defects produce babies the "natural" way ? How about people where we don't know what exactly is wrong, but clearly something is wrong (e.g. very small, bone disease, large family incidence of leukemia, ...). There's some justification for that as making those babies produces a LOT of terrible suffering, but aside from the moral problems it seems very impractical to do this as well. A LOT of "suboptimal" humans are produced, a LOT of humans are born with a body that just ... won't work in certain ways or will die in painful ways in a decade or less. Mostly in cases where the odds of a better outcome than the parents had is zero (meaning the terrible outcome was testable beforehand or even predictable). So I would argue there is plenty of reason to give people access altered babies. Perhaps there are indeed some bridges not to be crossed, but I would argue that we should probably still cross them a few times to see first. That will suck badly for a few babies, but not doing it has sucked for ~0.5% of humanity for all of history (that's about the incidence of genetic defects that kill on average before adulthood, all taken together). That means this year alone half a million babies will be born with genes so defective they will never grow up (but the vast majority of them will gain enough intelligence to make the inevitable suffering really bad before they die) That's not counting serious defects, like Down syndrome, that won't kill but have incredibly bad consequences nevertheless. Nor is it counting people born with disabilities that will survive (e.g. blind, deaf, paralyzed (ouch), deformed, ...) I feel like that makes it reasonable to say that we should do nothing until we have something like 10000 edited babies born. Hopefully at that point we will know what works, actually have some data, and know what doesn't work and perhaps cut that half a million figure in half or better. That won't change the number of people who are screwed by their genes meaningfully. In fact, it ought to make it possible to lower that number by a LOT. This is one of those cases where "doing nothing" is not the morally neutral option. Doing nothing is accepting the status quo as good enough. The status quo is that worldwide, something like 20 million children are on death row due to bad genes. 5 US states worth of children. Most of them are children with no real outward sign of any problem, who will just die, relatively suddenly (meaning from "going to school and playing" to dead takes months, no more).
anvandare 8y ago
First one to get the (nuclear|genetic|quantum decryptor| ...) superweapon wins. That's been always true. Any government who's currently protesting and proclaiming they never will partake in it are either (1) idiots or (2) lying.
- Nasrudith 8y ago
  Really apart from nukes which had a brief preproliferation period when have superweapons been worth it? Most of the time they have been holes to put money in and get ego out from the Paris railway gun to the megatanks of Nazi Germany.
  - maroonblazer 8y ago
    I don't follow this area so my reply may be naive but it seems like developing super-weapons would be worthwhile if only to be able to detect when others are doing the same.
  - bohadi 8y ago
    Likewise, the large benefit being a perceived halo of invincibility. A 'superweapon' further provides political positioning to maneuver before, during, after some confrontation. My point here is to say worth valued in effects viewed as secondary.
- TomMarius 8y ago
  Or (3) too weak and trying to gain sympathy from other governments.
- Symmetry 8y ago
  This was a straightforwards application of well understood and disseminated science, it is entirely unlike a secret superweapon. Even if this technique is banned in the US and not in China I have no doubt that many Americans would still play medical tourist to have enhanced babies. There might be large differences in the willingness of Chinese versus American parents to have their children modified but that isn't a matter of government intervention.
20kleagues 8y ago
Kinda unrelated but I was amazed at the speed with which the webpage loaded. In the age of bloated websites, being able to start reading the content within a second of clicking was refreshing. Kudos to the NYT developers!
paraditedc 8y ago
Since we are in the fallout stage now, it is important to note that this news is poorly received within China, with most organizations against it or denying ties with it. I wrote a summary of reactions in China on my blog if anyone is interested (no paywall, no ads): https://paraditedc.com/2018/11/26/doubts-within-china-on-gene-edited-babies-story/ https://paraditedc.com/2018/11/26/doubts-within-china-on-gen...
baybal2 8y ago
Human genetic engineering is a great thing! All research to advance it and bring it into practical use should be encouraged.
imtemplain 8y ago
The moment we allow this we are done as humans. Even if it can be labeled as "safe" someday, we will eventually be replaced by machines if we combine gene editing with AI. It may even take a thousand years but it will happen for sure. It just takes an evolutionary pressure or even just a preference among humans that favors designer babies. At some point it will be disadvantageous to reproduce the natural way or even to not sterilize your designer babies from the get go and the designed humans will most likely be advancing this technology further with every generation. At that point a machine would be our true replicator and we'd be lost.
kanzure 8y ago
Here's a transcript of Jiankui He's talk in Hong Kong on his human embryo editing project: http://diyhpl.us/wiki/transcripts/human-genome-editing-summit/2018-hong-kong/jiankui-he-human-genome-editing/ http://diyhpl.us/wiki/transcripts/human-genome-editing-summi...
Symmetry 8y ago
I wonder to what extent the existence and use of CRISPR to edit a baby will serve to normalize the relatively less radical practice of IVF embryo selection[1] on a wider range of criteria than we currently accept. That would also open the door to some enhancements. Many traits that parents might care about are deeply polygenetic and not amenable to the sort of editing we can currently perform but could still be selected for in this manner. [1]https://en.wikipedia.org/wiki/Preimplantation_genetic_diagnosis https://en.wikipedia.org/wiki/Preimplantation_genetic_diagno...
- bluGill 8y ago
  There are ethical concerns in some areas. However I have no ethical concern about knocking out the Downs Syndrome gene (though how you would do this is a different question). Likewise blind or deaf genes can go. As can high cholesterol genes.
  - Symmetry 8y ago
    Downs Syndrome is caused by an extra copy of a chromosome, not a specific gene variant or mutation. It's something you could avoid by embryo selection but not by conventional gene editing techniques.
    - bluGill 8y ago
      Right, thus the comment that I don't know how you would edit out Downs.
LeicaLatte 8y ago
China and India have much different problems compared to most other countries. There in lies the opportunity too.
frgtpsswrdlame 8y ago
It's interesting. We actually can't edit for complex traits like intelligence or schizophrenia at present because they seem to be deeply polygenic and Chabris has basically led us to stop identifying specific genes and their mechanisms. This means that we know genes play some role in schizophrenia but have no idea what it is the genes are doing. Consider for example a gene that makes mothers less affectionate with their children. GWASs and the like pick this up as genetic causation of schizophrenia, and maybe editing that gene is even a good thing, however it's not really what we think of when we think of 'genetic causation of schizophrenia.' Even something like height, a gene that makes your joints marginally larger will have a small effect on your height and get picked up. However, would it actually be beneficial to give your kid bigger joints so that they're a bit taller? So then we're basically restricted to curing simple diseases where specific genetic causes are already identified. Or are we? It seems to me the real risk is not from rich people engineering smarter babies, it's a company who says they can genetically engineer a smarter baby but mostly just tinker around with inconsequential traits. Then we get an 'uber race' of people who believe that they are elite in essence, immutably so, when actually they're not that different. Like the racism of old.
deleted 8y ago
[deleted]
refurb 8y ago
Derek Lowe has a nice summary of the situation and why it's sloppy science.[1] Multiple microinjections were needed to try to ensure that the majority of cells in the embryo were indeed affected, He said, and even so neither of the twin girls appears to be a clean job of it. One of them is mosaic for the desired 32-amino acid CCR5 deletion, and the other, if I’m reading this right, is heterozygous for a five amino acid deletion. Wonderful, a complete hack job. [1]http://blogs.sciencemag.org/pipeline/archives/2018/11/28/after-such-knowledge http://blogs.sciencemag.org/pipeline/archives/2018/11/28/aft...
- buboard 8y ago
  Curious why this wasn't asked during his talk. Aren't +/- knockouts valid knockouts ?
- buboard 8y ago
  from reddit's biologists i got this: > he actually doesn't report a mosaic at the CCR5delta32 locus - just a mosaic off-target effect in a non-coding region that disappears when sequencing tissues from the baby and heterozygous knockouts are still knockouts so i m not sure why they are so quick to discredit the work
buboard 8y ago
For anyone interested , the slides from his presentation are online https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29fN_7qJg7fLA4qlrd https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29... And livestream: https://livestream.com/NASEM/events/8464254/videos/184103056 https://livestream.com/NASEM/events/8464254/videos/184103056 1:17:00
nootropicat 8y ago
I don't understand the inconsistent morality. I bet the author wants abortions to be legal. If the edited baby turns out to be damaged just abort it, then try again, no big deal.

39 points by yesprabhu 8y ago

hd4 8y ago

The Chinese realize what others refuse to, it's a race and whoever wins sets the rules. And what would they gain by waiting and losing the first-mover advantage? The article talks about risks, they are certainly not that concerned about risks, not as long as they get the upper hand in biotech and genome manipulation.

Zeebrommer 8y ago
> Dr. He’s university has disavowed knowledge or support of the research and said an inquiry is underway. Sounds more like an individual rogue action than coordinated effort backed by vision of "the Chinese".

vaultcool 8y ago

How often did Chinese researchers claim to have done something incredible, without proper proof and lack of data, and it turned out to be a total scam? This really feels like another one of these, we'll see what happens, but I wouldn't hold my breath.

tgb 8y ago
But the difference here is that, to the best of my knowledge, there's nothing particularly difficult about CRISPR in humans. It's routine in other mammals and had previously been done on human embryos. The thing holding everyone back was ethical concerns and the possibilities of off-target effects, side-effects of the mutation, etc. So I'd err on the side of assuming they did do it.
- buboard 8y ago
  Also George Church says it's "probably accurate" https://www.statnews.com/2018/11/26/claim-of-crispred-baby-girls-stuns-genome-editing-summit/?utm_content=buffer8fbbd&utm_medium=social&utm_source=twitter&utm_campaign=twitter_organic https://www.statnews.com/2018/11/26/claim-of-crispred-baby-g...
  - gwern 8y ago
    It's worth noting that none of the moderators or questioners at the talk expressed any skepticism that He had done it. They all took for granted He had.
    - buboard 8y ago
      do you know why? my guess is they had previous contact/correspondence throughout the pregnancy Edit: there are slides of his presentation: https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29fN_7qJg7fLA4qlrd https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29...
      - gwern 8y ago
        It's really not that implausible a thing to do, you know. People have been editing human embryos with CRISPR since at least 2014. And He has past experience, it seems, and had networked a fair amount and seemed to know what he was doing. George Church also has said that he's seen some of the data and it looks right to him. Combine that with all the data on the slides, and while you can debate the ethics or how useful it would be or how well it actually worked, it seems increasingly plausible that he did something like what he claimed, and he's not simply faking it all.

booleandilemma 8y ago

Meanwhile China is actually doing it and soaking up the investor money, interested researchers, and gaining the lead.

adventured 8y ago
That's false. The city of Boston by itself leads China in CRISPR tech and innovation.
- baybal2 8y ago
  Have you noticed just how many genetic technology in US is actually made in China? Boston companies may have high profile, but all the dirty work is done in China by research outsourcing labs staffed with interns.
  - vedtopkar 8y ago
    Do you have a source for this? This may be true in other fields but most genome editing industry work is almost certainly done stateside.
  - dekhn 8y ago
    I don't think this is true. i work with a people who are CRISPR experts, what's happening in cambridge (not boston) is legit and local.

winchling 8y ago

>We should not proceed down this road until we know far more about the consequences of what we are doing. In the present climate of pessimism it's worth reminding ourselves that we never know all the consequences of what we're doing. The 'Precautionary Principle' kills people too; it merely does so in a less obvious way. Personally I think we should be going hell for leather in identifying and eliminating genetic diseases that arise from known mutations. And we should of course expect new problems to arise down the road from these treatments.

mannykannot 8y ago
This is a particularly bad example to make that case over, as it is hard to discern any scientific or medical justification for it, while the known risks are considerable. Frankly, it looks to me like a posterity-grabbing stunt - an attempt by the researcher to write himself into the history books.
- candiodari 8y ago
  First, the event reported on is almost certainly a scam (HIV resistance ? Seriously ?). But let's assume it's valid. But I don't agree at all with the sentiment. Most/all current gene editing is about fixing known issues, and in nearly all cases (at the moment) it seems like the edited gene, even if it goes disastrously wrong, would still be superior to the "natural" gene. E.g. MVD, MS, ... Should we also outlaw (and enforce) that people with known genetic defects produce babies the "natural" way ? How about people where we don't know what exactly is wrong, but clearly something is wrong (e.g. very small, bone disease, large family incidence of leukemia, ...). There's some justification for that as making those babies produces a LOT of terrible suffering, but aside from the moral problems it seems very impractical to do this as well. A LOT of "suboptimal" humans are produced, a LOT of humans are born with a body that just ... won't work in certain ways or will die in painful ways in a decade or less. Mostly in cases where the odds of a better outcome than the parents had is zero (meaning the terrible outcome was testable beforehand or even predictable). So I would argue there is plenty of reason to give people access altered babies. Perhaps there are indeed some bridges not to be crossed, but I would argue that we should probably still cross them a few times to see first. That will suck badly for a few babies, but not doing it has sucked for ~0.5% of humanity for all of history (that's about the incidence of genetic defects that kill on average before adulthood, all taken together). That means this year alone half a million babies will be born with genes so defective they will never grow up (but the vast majority of them will gain enough intelligence to make the inevitable suffering really bad before they die) That's not counting serious defects, like Down syndrome, that won't kill but have incredibly bad consequences nevertheless. Nor is it counting people born with disabilities that will survive (e.g. blind, deaf, paralyzed (ouch), deformed, ...) I feel like that makes it reasonable to say that we should do nothing until we have something like 10000 edited babies born. Hopefully at that point we will know what works, actually have some data, and know what doesn't work and perhaps cut that half a million figure in half or better. That won't change the number of people who are screwed by their genes meaningfully. In fact, it ought to make it possible to lower that number by a LOT. This is one of those cases where "doing nothing" is not the morally neutral option. Doing nothing is accepting the status quo as good enough. The status quo is that worldwide, something like 20 million children are on death row due to bad genes. 5 US states worth of children. Most of them are children with no real outward sign of any problem, who will just die, relatively suddenly (meaning from "going to school and playing" to dead takes months, no more).

anvandare 8y ago

First one to get the (nuclear|genetic|quantum decryptor| ...) superweapon wins. That's been always true. Any government who's currently protesting and proclaiming they never will partake in it are either (1) idiots or (2) lying.

Nasrudith 8y ago
Really apart from nukes which had a brief preproliferation period when have superweapons been worth it? Most of the time they have been holes to put money in and get ego out from the Paris railway gun to the megatanks of Nazi Germany.
- maroonblazer 8y ago
  I don't follow this area so my reply may be naive but it seems like developing super-weapons would be worthwhile if only to be able to detect when others are doing the same.
- bohadi 8y ago
  Likewise, the large benefit being a perceived halo of invincibility. A 'superweapon' further provides political positioning to maneuver before, during, after some confrontation. My point here is to say worth valued in effects viewed as secondary.
TomMarius 8y ago
Or (3) too weak and trying to gain sympathy from other governments.
Symmetry 8y ago
This was a straightforwards application of well understood and disseminated science, it is entirely unlike a secret superweapon. Even if this technique is banned in the US and not in China I have no doubt that many Americans would still play medical tourist to have enhanced babies. There might be large differences in the willingness of Chinese versus American parents to have their children modified but that isn't a matter of government intervention.

20kleagues 8y ago

Kinda unrelated but I was amazed at the speed with which the webpage loaded. In the age of bloated websites, being able to start reading the content within a second of clicking was refreshing. Kudos to the NYT developers!

paraditedc 8y ago

Since we are in the fallout stage now, it is important to note that this news is poorly received within China, with most organizations against it or denying ties with it. I wrote a summary of reactions in China on my blog if anyone is interested (no paywall, no ads): https://paraditedc.com/2018/11/26/doubts-within-china-on-gene-edited-babies-story/ https://paraditedc.com/2018/11/26/doubts-within-china-on-gen...

baybal2 8y ago

Human genetic engineering is a great thing! All research to advance it and bring it into practical use should be encouraged.

imtemplain 8y ago

The moment we allow this we are done as humans. Even if it can be labeled as "safe" someday, we will eventually be replaced by machines if we combine gene editing with AI. It may even take a thousand years but it will happen for sure. It just takes an evolutionary pressure or even just a preference among humans that favors designer babies. At some point it will be disadvantageous to reproduce the natural way or even to not sterilize your designer babies from the get go and the designed humans will most likely be advancing this technology further with every generation. At that point a machine would be our true replicator and we'd be lost.

kanzure 8y ago

Here's a transcript of Jiankui He's talk in Hong Kong on his human embryo editing project: http://diyhpl.us/wiki/transcripts/human-genome-editing-summit/2018-hong-kong/jiankui-he-human-genome-editing/ http://diyhpl.us/wiki/transcripts/human-genome-editing-summi...

Symmetry 8y ago

I wonder to what extent the existence and use of CRISPR to edit a baby will serve to normalize the relatively less radical practice of IVF embryo selection[1] on a wider range of criteria than we currently accept. That would also open the door to some enhancements. Many traits that parents might care about are deeply polygenetic and not amenable to the sort of editing we can currently perform but could still be selected for in this manner. [1]https://en.wikipedia.org/wiki/Preimplantation_genetic_diagnosis https://en.wikipedia.org/wiki/Preimplantation_genetic_diagno...

bluGill 8y ago
There are ethical concerns in some areas. However I have no ethical concern about knocking out the Downs Syndrome gene (though how you would do this is a different question). Likewise blind or deaf genes can go. As can high cholesterol genes.
- Symmetry 8y ago
  Downs Syndrome is caused by an extra copy of a chromosome, not a specific gene variant or mutation. It's something you could avoid by embryo selection but not by conventional gene editing techniques.
  - bluGill 8y ago
    Right, thus the comment that I don't know how you would edit out Downs.

LeicaLatte 8y ago

China and India have much different problems compared to most other countries. There in lies the opportunity too.

frgtpsswrdlame 8y ago

It's interesting. We actually can't edit for complex traits like intelligence or schizophrenia at present because they seem to be deeply polygenic and Chabris has basically led us to stop identifying specific genes and their mechanisms. This means that we know genes play some role in schizophrenia but have no idea what it is the genes are doing. Consider for example a gene that makes mothers less affectionate with their children. GWASs and the like pick this up as genetic causation of schizophrenia, and maybe editing that gene is even a good thing, however it's not really what we think of when we think of 'genetic causation of schizophrenia.' Even something like height, a gene that makes your joints marginally larger will have a small effect on your height and get picked up. However, would it actually be beneficial to give your kid bigger joints so that they're a bit taller? So then we're basically restricted to curing simple diseases where specific genetic causes are already identified. Or are we? It seems to me the real risk is not from rich people engineering smarter babies, it's a company who says they can genetically engineer a smarter baby but mostly just tinker around with inconsequential traits. Then we get an 'uber race' of people who believe that they are elite in essence, immutably so, when actually they're not that different. Like the racism of old.

deleted 8y ago

[deleted]

refurb 8y ago

Derek Lowe has a nice summary of the situation and why it's sloppy science.[1] Multiple microinjections were needed to try to ensure that the majority of cells in the embryo were indeed affected, He said, and even so neither of the twin girls appears to be a clean job of it. One of them is mosaic for the desired 32-amino acid CCR5 deletion, and the other, if I’m reading this right, is heterozygous for a five amino acid deletion. Wonderful, a complete hack job. [1]http://blogs.sciencemag.org/pipeline/archives/2018/11/28/after-such-knowledge http://blogs.sciencemag.org/pipeline/archives/2018/11/28/aft...

buboard 8y ago
Curious why this wasn't asked during his talk. Aren't +/- knockouts valid knockouts ?
buboard 8y ago
from reddit's biologists i got this: > he actually doesn't report a mosaic at the CCR5delta32 locus - just a mosaic off-target effect in a non-coding region that disappears when sequencing tissues from the baby and heterozygous knockouts are still knockouts so i m not sure why they are so quick to discredit the work

buboard 8y ago

For anyone interested , the slides from his presentation are online https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29fN_7qJg7fLA4qlrd https://drive.google.com/drive/u/0/folders/1T1zLTtHS2z_cgl29... And livestream: https://livestream.com/NASEM/events/8464254/videos/184103056 https://livestream.com/NASEM/events/8464254/videos/184103056 1:17:00

nootropicat 8y ago

I don't understand the inconsistent morality. I bet the author wants abortions to be legal. If the edited baby turns out to be damaged just abort it, then try again, no big deal.