Gene editing human babies
Dec. 9th, 2018 12:53 pm![[personal profile]](https://www.dreamwidth.org/img/silk/identity/user.png){kind=small}
livI'll probably get round to making a post noodling about different social media platforms and gathering links about the Tumblr purge and so on. But lots of people have interesting views about that. For now, something to make my journal interesting to all my potential new readers where I have a specific contribution to make:
Who has been following this real-life horror story where a scientist claims to have gene edited human babies? It's absolutely all over the technical press but I haven't seen much lay discussion. If any of this story is true, it's a massive first with extremely far ranging implications. Let me break this down: He Jiankui is claiming that he has edited the genes of human embryos and that twin girls were born a couple of weeks ago with their genes deliberately altered. That means every cell in their bodies will express the edited sequence. If they go on to have children of their own, their offspring and all future generations of their descendants will have this alteration. (The account is slightly confusing because the romanization of the scientist's name, He, is identical to the male singular pronoun. Sorry about that.)
If it's real. If it's real it's as big as human cloning, and it's also a complete ethical disaster with bad science at every stage.
What He claims to have done is that took some human embryos created by IVF from a father who is HIV+ and a mother who is seronegative. He then used a very recently developed technique called CRISPR/Cas9 to change the sequence of a gene which encodes a protein that the HIV virus would normally bind to. In theory, this change means that the cells can not be infected by HIV. Then. Then he took these edited embryos and implanted them back into the mother and, we are told, she went through a normal healthy pregnancy and gave birth to twins. There is some vague evidence from similar approaches in animals that these babies may be protected against at least some strains of HIV. NB not "immune to" HIV as a lot of popular reports are saying, it's not that they can mount an immune defence against AIDS, it's that their cells can't be infected with the virus in the first place.
This decade has seen a major revolution in molecular biology: until really very recently it was just accepted as fact that you can't directly edit mammalian genes. You could alter genes, but it was always a scattershot approach, you never had precise control over what new sequence you'd get. So it was a bit rubbish even for doing experiments, and certainly not adequate for medical use. Around five years ago, there was a new technology developed, based on modifying some really obscure enzymes from bacteria, so now we can, in principle at least, change any genetic sequence at will. Nowadays, any molecular biologist can buy a kit from mainstream scientific suppliers and edit genes in most types of cells, including human cells.
Up until now, people have been cautiously improving the safety and reliability of this technique and holding off on using it in actual living humans. There are particularly strict prohibitions against editing embryos, because of the multi-generational implications and potential for eugenics. Until this rogue scientist, He, went on unpaid leave from his university, and secretly and with a very sketchy and hardly documented ethical approval process, recruited a bunch of Chinese couples who wanted to have children but the potential father was HIV+. He doesn't seem to have clearly explained to these parent volunteers what he was doing, some vague talk about an HIV vaccine, which this certainly isn't. It's possible that he talked his subjects into avoiding the normal precautions you would take if trying to conceive when the father is HIV+. Even if he didn't deliberately increase the babies' risk of contracting HIV, he at very least ignored the existing and effective ways of preventing transmission from an HIV+ sperm producing parent, which are both safer and more certain to work than this highly experimental gene editing thing.
He then made a big fanfare of a press release. Nothing's published in peer reviewed journals, but based on He's own report, most scientists who work in the field believe that the precautions taken to check that the editing had worked correctly were entirely inadequate. Part of the reason why normal, ethical scientists don't try to gene edit humans is that CRISPR/Cas9 technique isn't completely reliable yet, there's still a high chance of what's called "off-target effects", namely editing unrelated genes by mistake, which is going to have entirely unpredictable consequences. And it seems like He has done some cursory checks to make sure this didn't happen, but not proper, rigorous ones.
Then He went into hiding, occasionally popping up to claim to the media that he's a great maverick who has advanced the medical field by ignoring all the petty rules that Hold Science Back. Every statement I've seen from him makes him come across more like the most clichéd of cartoonish "mad scientists".
Because of this pattern of behaviour, I think there's quite a high chance that the whole thing was a fraud. Remember Woo Suk Hwang, the Korean scientist who in the early 2000s claimed to have made a cloned human, using the techniques applied to breed Dolly the Sheep? Yeah, he made the whole thing up. When something this big is published in a press release and skips the peer review stage, I am very skeptical that any of this human gene editing actually occurred. (Of course, now He has grown a conscience and tells us he can't reveal the real identity of his supposedly engineered babies because he wants to protect their privacy.)
And because the whole story is so ethically horrifying, with the parents not properly consenting to be in such a revolutionary trial, and the babies having an unknown risk of contracting HIV (might be lower than unmodified babies, might not be), and an unknown risk of basically random side effects, I am really hoping it is, in fact, a fraud. I hope the terrible experiments never happened and He is just trying to hog the limelight. I was expecting at some point in the next five to ten years that there would be a big breakthrough in human gene editing, because now we have the tools there are so many huge medical problems we could tackle. But I wasn't expecting it to be like this.
Please feel free to ask any questions. I haven't done CRISPR/Cas9 gene editing myself but I have a 20-year career of doing that sort of experiment but with worse tools, and I'm happy to explain this stuff at whatever level is most helpful.
Who has been following this real-life horror story where a scientist claims to have gene edited human babies? It's absolutely all over the technical press but I haven't seen much lay discussion. If any of this story is true, it's a massive first with extremely far ranging implications. Let me break this down: He Jiankui is claiming that he has edited the genes of human embryos and that twin girls were born a couple of weeks ago with their genes deliberately altered. That means every cell in their bodies will express the edited sequence. If they go on to have children of their own, their offspring and all future generations of their descendants will have this alteration. (The account is slightly confusing because the romanization of the scientist's name, He, is identical to the male singular pronoun. Sorry about that.)
If it's real. If it's real it's as big as human cloning, and it's also a complete ethical disaster with bad science at every stage.
What He claims to have done is that took some human embryos created by IVF from a father who is HIV+ and a mother who is seronegative. He then used a very recently developed technique called CRISPR/Cas9 to change the sequence of a gene which encodes a protein that the HIV virus would normally bind to. In theory, this change means that the cells can not be infected by HIV. Then. Then he took these edited embryos and implanted them back into the mother and, we are told, she went through a normal healthy pregnancy and gave birth to twins. There is some vague evidence from similar approaches in animals that these babies may be protected against at least some strains of HIV. NB not "immune to" HIV as a lot of popular reports are saying, it's not that they can mount an immune defence against AIDS, it's that their cells can't be infected with the virus in the first place.
This decade has seen a major revolution in molecular biology: until really very recently it was just accepted as fact that you can't directly edit mammalian genes. You could alter genes, but it was always a scattershot approach, you never had precise control over what new sequence you'd get. So it was a bit rubbish even for doing experiments, and certainly not adequate for medical use. Around five years ago, there was a new technology developed, based on modifying some really obscure enzymes from bacteria, so now we can, in principle at least, change any genetic sequence at will. Nowadays, any molecular biologist can buy a kit from mainstream scientific suppliers and edit genes in most types of cells, including human cells.
Up until now, people have been cautiously improving the safety and reliability of this technique and holding off on using it in actual living humans. There are particularly strict prohibitions against editing embryos, because of the multi-generational implications and potential for eugenics. Until this rogue scientist, He, went on unpaid leave from his university, and secretly and with a very sketchy and hardly documented ethical approval process, recruited a bunch of Chinese couples who wanted to have children but the potential father was HIV+. He doesn't seem to have clearly explained to these parent volunteers what he was doing, some vague talk about an HIV vaccine, which this certainly isn't. It's possible that he talked his subjects into avoiding the normal precautions you would take if trying to conceive when the father is HIV+. Even if he didn't deliberately increase the babies' risk of contracting HIV, he at very least ignored the existing and effective ways of preventing transmission from an HIV+ sperm producing parent, which are both safer and more certain to work than this highly experimental gene editing thing.
He then made a big fanfare of a press release. Nothing's published in peer reviewed journals, but based on He's own report, most scientists who work in the field believe that the precautions taken to check that the editing had worked correctly were entirely inadequate. Part of the reason why normal, ethical scientists don't try to gene edit humans is that CRISPR/Cas9 technique isn't completely reliable yet, there's still a high chance of what's called "off-target effects", namely editing unrelated genes by mistake, which is going to have entirely unpredictable consequences. And it seems like He has done some cursory checks to make sure this didn't happen, but not proper, rigorous ones.
Then He went into hiding, occasionally popping up to claim to the media that he's a great maverick who has advanced the medical field by ignoring all the petty rules that Hold Science Back. Every statement I've seen from him makes him come across more like the most clichéd of cartoonish "mad scientists".
Because of this pattern of behaviour, I think there's quite a high chance that the whole thing was a fraud. Remember Woo Suk Hwang, the Korean scientist who in the early 2000s claimed to have made a cloned human, using the techniques applied to breed Dolly the Sheep? Yeah, he made the whole thing up. When something this big is published in a press release and skips the peer review stage, I am very skeptical that any of this human gene editing actually occurred. (Of course, now He has grown a conscience and tells us he can't reveal the real identity of his supposedly engineered babies because he wants to protect their privacy.)
And because the whole story is so ethically horrifying, with the parents not properly consenting to be in such a revolutionary trial, and the babies having an unknown risk of contracting HIV (might be lower than unmodified babies, might not be), and an unknown risk of basically random side effects, I am really hoping it is, in fact, a fraud. I hope the terrible experiments never happened and He is just trying to hog the limelight. I was expecting at some point in the next five to ten years that there would be a big breakthrough in human gene editing, because now we have the tools there are so many huge medical problems we could tackle. But I wasn't expecting it to be like this.
Please feel free to ask any questions. I haven't done CRISPR/Cas9 gene editing myself but I have a 20-year career of doing that sort of experiment but with worse tools, and I'm happy to explain this stuff at whatever level is most helpful.
(no subject)
Date: 2018-12-10 04:02 pm (UTC)I'm not sure gene editing is likely to be a useful approach to cancer, because cancer is a multi-gene disease. Changing a single gene, assuming all the practical difficulties could be surmounted, would probably not halt the growth of a tumour, let alone prevent the spread of cancer once metastatic (spread through the body, a feature of what we'd usually define as severe cancer). Cancers are highly mutation prone and are under selection pressure. There have been a number of attempts to block driver genes using traditional methods and what always happens is that a few cells of the cancer find a way to work round the block, and keep growing anyway. If someone had a genetic problem with their liver or bone marrow, and we could fix it in 3/4 of the cells, fine, the problem would be basically fixed. But if we only fixed 3/4 of the cells of a tumour, the remaining 1/4 would just grow even faster.
Diseases caused by a single mutation which mean people can't have genetically related children are a much more likely candidate at least for early applications of the technology. But I really don't know whether I could be ethically comfortable with fixing those mutations by using gene editing. Certainly it would need to be very tightly legally restricted to prevent all kinds of ethically horrible processes.
(no subject)
Date: 2018-12-11 04:52 am (UTC)BRCA1.
(no subject)
Date: 2018-12-11 09:58 pm (UTC)Are you talking about gene editing embryos where there's a family history of BRCA1 mutations, to reduce susceptibility to breast cancer? Or treatment of cancer that is already severe and not treatable with conventional chemotherapy? The first case might have potential, if we collectively decide that gene editing embryos is ethically acceptable. The second is I would say entirely unfeasible.
(no subject)
Date: 2018-12-12 02:29 am (UTC)I don't even know how you got onto the topic of the latter case. Post-natal gene therapies weren't even under discussion, were they? The controversy under discussion is precisely gene editing embryos.
(no subject)
Date: 2018-12-12 11:21 am (UTC)(no subject)
Date: 2018-12-11 10:01 pm (UTC)This isn't simple but what I failed to find when I posted the first response was this story where it already has happened
https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-018-0455-9
Here talens rather than crisprs have been used to treat acute lymphoid leukaemia. These treatments tend to be last resort at the moment but we will get more effective at this
As far as treatment of Mendelian genetic disorders, you are correct there will need to be a lot of oversight and lots of testing before it happens but that doesn't mean it shouldn't be a possible treatment in the rare circumstances where it is the best solution
(no subject)
Date: 2018-12-11 10:19 pm (UTC)I do agree that driver mutations are important, even with heterogeneity. And yes, I can very much see the potential of using gene editing to improve stem cell / immune therapy treatment for haematological cancers. I can't see the Qasim paper cited in that fascinating review, but from the summary of it it looks like a fantastic first step in actually using gene editing clinically.