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Gene therapy restores hearing to children with inherited deafness
- gota 2y agoThis stuff seems miraculous. > "Through minimally invasive surgery, Shu injected adeno-associated virus (AAV) engineered to carry and deliver functioning copies of the human OTOF transgene, into the children’s inner ears. " Can't read that and not get curious, excited, for the future. Congratulations to all those involved in the research and thanks to all who contributed to it - including all taxpayers if public funding was given, even indirectly (i.e. in the schooling and education, grants, for said researchers)
- dyauspitr 2y agoI can’t wait for a geneCAD where we for example, design wings for a human body and then it works out the rest and generates a CRISPR based AAV that you can inject yourself with. True race and sex changes too. Hopefully in the next 50 years but that’s wishful thinking.
- narrator 2y agoNo doubt you'll see an Android/Apple split and the Apple people won't be able to date the Android people because of incompatible augmented pheromones that smell funny if you're not on the same platform.
- hinkley 2y agoDan Simmons, Hyperion Cantos. “Biosculpting”
- kevin_thibedeau 2y agoThere are potential serious downsides if these inserted genes end up on a different chromosome than normal and become carried by gametes to offspring who may suffer from overexpression.
- dyauspitr 2y agoI presume at the point we can generate CAD like designer gene modifications, overexpression would just be another problem that can be fixed by more modification.
- Auracle 2y agoEh, maybe you’ll run into the problem the Asgard had in Stargate. Too much editing over time = couldn’t procreate anymore. Little bugs add up.
- ben_w 2y agoThat was a plot device that didn't make sense to me: they could upload and download a functional copy of their brains (and also human brains), but they didn't keep a backup copy of their old DNA?
- Auracle 2y agoI agree, plus they at one point had a whole damn older preserved Asgard. That and how rushed they made their end of that particular story in the last episode made me hate it.
- samstave 2y ago[dead]
- antegamisou 2y agoWe need to keep away biotech OpenAI-wannabes apparently.
- mylons 2y agoit’s happening! i just finished something that assists in “CRISPR Design” and helps gene editors.
- nkrisc 2y agoTaking it seriously for a moment, that still seems outlandish even in a sci-fi scenario. The amount of changes that would be necessary to the body for a human to achieve autonomous powered flight would be substantial. Given our overall density, we would need enormous wings and musculature. Consider that the heaviest flying birds alive today weigh maybe 40lbs and have a wingspan of 8ft or so. If we naively extrapolate that linearly then an adult weighing 160lbs would need a 32ft wingspan. There were flying pterosaurs that weighed much more than the heaviest flying birds today, but they were also the size of small planes and it’s a bit of a debate how well they even flew. They may have struggled to even take flight. So injecting yourself with some designer DNA isn’t just going to make you grow wings, it would have to completely transform you into a completely different creature, simply due to the physics of flight. Additionally, you need not only to be able to fly, but your body needs to function well enough to stay in this new state. You would also likely need an enormous caloric intake to support the massive new growth, or it would take a very, very long time. It wouldn’t be designing wings for a human, it would be designing a be creature based on a human but not human at all, really. Call me shortsighted but I don’t really see how that will ever be possible.
- dyauspitr 2y agoYour point seems to be that massive changes are required to achieve wings. I’m saying that’s not impossible and an acceptable modification to whoever wants to do this to themselves. As long as you can maintain the brain as is, I don’t see there being a problem with radically modifying the rest of the body. Argentavis magnificens had a wingspan of around 24ft and weighed around 72 kgs or a 160lbs which is close to what an average human weighs. If you compare growth rates to other mammals like elephants, I doubt a change like that would take much more than 5-10 years.
- nkrisc 2y ago> As long as you can maintain the brain as is, That’s the question, can a human sized body that can fly additionally support a human sized brain? I suspect you would have to spend nearly every waking minute eating to support both. Or at least a substantial portion of your day. No time for hacking, gotta eat. You’ll probably have to pay full up front for this, as no one will finance you since you’ll be too busy foraging for sugary fruit or carrying livestock off to your eyrie to work a job to pay it back. Finally, this raises another question I won’t even attempt to answer: is it even possible for you to still be “you” in another body? How responsible is your body, beyond just your brain, responsible for making you who you are?
- taf2 2y agoThat would be cool - maybe a simple 20/20 vision would be a great next step after hearing
- akoboldfrying 2y agoLet's try to fix the world's vast number of actual, boring health problems before trying to add the equivalent of spoilers and chrome-plated hubcaps to perfectly healthy human bodies.
- dyauspitr 2y agoYou can do both things at the same time.
- akoboldfrying 2y agoThat's true if we assume unlimited resources and equal awareness/perceived social value of the two applications. But I think the former doesn't hold, and the latter is greatly influenced by sites like HN, where I'm disappointed to consistently (if not exclusively) see breathless proposals for ways to design shinier hubcaps whenever some promising new technology appears. Yes, they can and likely will both happen to some extent, but I think they aren't independent, so I feel justified in trying to nudge the public conversation back towards the issues that I think matter more.
- evilduck 2y agoCosmetic surgery for vanity has helped improve the techniques and procedures and even the number of skilled practitioners that can then help those with disfigurements and deformities.
- JumpCrisscross 2y agoHell, cancer treatment for pets has advanced human oncology [1]. Scientific discovery is rarely zero sum. [1] https://www.upstate.edu/whatsup/2019/0220-treatment-for-canine-cancer-serves-as-model-for-humans.php https://www.upstate.edu/whatsup/2019/0220-treatment-for-cani...
- _factor 2y agoAnd cigarettes have benefited the lung cancer research centers. Just because it works doesn’t make it the best course.
- _yb2s 2y agoSynthetic biology CAD software does exist, and works better than most people would expect, but of course are not at the level you are imagining yet.
- Nesco 2y agoCould you provide some resources/links please?
- _yb2s 2y agoIt's hard to summarize because there are about a dozen different categories of things that could reasonably considered "biological CAD" and often would all be used together in a single synthetic biology project. For example: Retrobiosynthesis simulates biochemistry backwards, to find the steps necessary for a biological system to build something, usually a small molecule. Galaxy-SynBioCAD / Retropath would be one example: https://jfaulon.com/galaxy-synbiocad-portal/ https://jfaulon.com/galaxy-synbiocad-portal/ Constraint based metabolic modeling models cellular metabolism, and lets you simulate adding and removing chemical reactions to a cell, and predict the outcomes. COBRApy would be one example software tool: https://opencobra.github.io/cobrapy/ https://opencobra.github.io/cobrapy/ Design editors for DNA plasmids, like the Teselagen design editor let you construct DNA sequences representing new biological capabilities to be added to an engineered cell, which can then be synthesized or constructed. Teselagen design module: https://teselagen.com/design-module/ https://teselagen.com/design-module/ Generative AI systems can 'hallucinate' functional proteins and DNA sequences that meet a design specification for function and/or shape. For example, GenerateBio's Chroma model can literally take a 3D file designed in a standard CAD program, and then automatically come up with an amino acid sequence that will fold into a protein with that exact 3D shape- and it actually works. https://github.com/generatebio/chroma https://github.com/generatebio/chroma An emerging field is coupling all of these types of tools with predictive models to enable 'inverse design' where you create a spec of what you want, such as a material with some desired properties, and it will automatically suggest biological routes to it.
- inglor_cz 2y agoOur bodies are very much not suitable for flight. Birds look differently from the inside. It might prove easier to grow biological pylons for external jet engines...
- TyrianPurple 2y agoExcuse me, are you The Qu?
- m3kw9 2y agoI thought you can’t just inject genes and then the body will start replicate it. Does it need periodic injections?
- rguiscard 2y agoThat is why the gene is put into a harmless virus which will injects the gene into cells. It takes advantage of what virus usually does.
- toufka 2y agoIf the DNA is in the cell's nucleus, the DNA will be utilized to produce whatever gene is encoded in the DNA. But if the DNA is just floating around on its own it will not survive a cell division event and the material would need to be periodically reinjected to keep working. However, if the injected DNA is part of a full chromosome, it will be replicated when the cell divides - and will be permanent as long as the cell or its progeny survive. Some viruses will just inject the DNA into cells, but will not become part of the cell's genome ("transient" transduction). Other viruses (like lentiviruses and these adeno-associated viruses [AAVs]) inject their DNA not just into the cells, but also have machinery that splices their payload DNA directly into the cell's chromosomes ("integrated"). The location in the genome of the splicing event is relatively random. Random is not necessarily great as it could interrupt other genes already in the chromosome. CRISPR is a now-famous tool that helps "integrate" DNA into a specific spot in the genome by being guided to a specific location with a small piece of a specific sequence. Once the DNA is integrated, any cell, and any of the cell's progeny, will produce or "express" the gene on the delivered DNA. In this case, they delivered the 5991 characters of DNA associated with the OROF gene [1]. [1] https://en.wikipedia.org/wiki/Otoferlin https://en.wikipedia.org/wiki/Otoferlin
- rekttrader 2y agoThank you for this description of how it works. It seems like truly beautiful and terrifying magic.
- bglazer 2y agoThis is actually not totally correct. AAV’s form episomes, which are circular DNA structures that are basically extra chromosomes. The fact that AAV’s don’t randomly insert themselves into DNA makes them safer for clinical uses like this. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519600/
- tim333 2y agoI'm sure there will be other treatments based on AAV and CRISPR. I'm interested in ALS as a relative has it and that stuff is one of the only approaches that might work. The had a go on mice with so so results - lived longer but no cure https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30011-3 https://www.cell.com/molecular-therapy-family/molecular-ther...
- Something1234 2y agoWait until they have kids. The deafness gene will be passed along. Soon enough we'll be like the cars with the hardware without the software or the locked features.
- david38 2y agoWe have this already. As a species we are susceptible to many diseases which we have to take vaccines for, every generation.
- pfannkuchen 2y agoI don't think susceptibility to viral diseases like measles is typically regarded as a genetic defect, is it? Any more than being flammable is a genetic defect, anyway.
- roywiggins 2y agoThere are a few people who are genetically immune to HIV, but it's quite rare. Whether everyone else is therefore genetically deficient is sort of a matter of perspective, I suppose. https://en.m.wikipedia.org/wiki/Innate_resistance_to_HIV https://en.m.wikipedia.org/wiki/Innate_resistance_to_HIV
- bitcurious 2y agoFortunately won't be a big issue, as: >OTOF-related deafness is inherited in an autosomal recessive manner. If both parents are known to be carriers, each sib of an individual with OTOF-related deafness has at conception a 25% chance of being deaf, a 50% chance of having normal hearing and being a carrier, and a 25% chance of having normal hearing and not being a carrier. source: https://www.ncbi.nlm.nih.gov/books/NBK1251/ https://www.ncbi.nlm.nih.gov/books/NBK1251/
- patmorgan23 2y agoHow is this any different from people who suffer from other genetic disorders that we have treatments for? Or people who just suffer from a chronic disease that requires regular treatments/medication for them to stay alive/health? (HIV, Diabetes, etc)
- roygbiv2 2y agoGene therapy is coming on well. Hopefully it'll help my kid when he's older. From what I'm being told, the gene that effects him is very large and difficult to fit into the viruses they use for gene therapy. My understanding is very limited so I could be very wrong here.
- speedylight 2y agoHow hard is it to introduce permanent mutations to DNA in adults, across every cell in the body? That seems like the holy grail of gene editing to me!
- zac256 2y agoThis is an area of active research, and there are many issues to solve. A technology that distributes a gene editor throughout the body is called a delivery vector, and it is typically a modified virus. After the patient is two years old, many large molecules do not pass through the blood brain barrier. Typically most of the treatment ends up in the liver. Viruses and the gene editor can be toxic. Combining the two previous points the correct dose for most of the body can be highly toxic to the liver. The delivery vector may support genes up to a specific size (in kilobases) which may be smaller than the gene you are trying to fit. Sometimes you don't want to target organs that the delivery vector hits. Sometimes you want to target organs that the delivery vector misses. And more. There is rapid progress being made here and all kinds of caveats and nuance to the above.
- inciampati 2y agoHow perfect can your reaction be? Can you get to 99.999999999999%?
- sircastor 2y agoI’m curious about the effect on the deaf community. I understand there’s resistance to “fixing” deafness as some consider it a component of their culture and community, not unlike queer people and the attempts to “fix” them. https://en.wikipedia.org/wiki/Cochlear_implant#Criticism_and_controversy https://en.wikipedia.org/wiki/Cochlear_implant#Criticism_and...
- devilbunny 2y agoThere is a fascinating documentary about this, but I cannot recall its name. One segment talks about a form of sign that represents sound, so that the child learns their family’s language (rather than sign language, which is another language entirely). It is very unpopular in the deaf community despite its advantages for daily life.
- lazyasciiart 2y agoSounds like Signed Exact English, which is disliked both for the context around it and for being more awkward than a natural sign language (e.g I think it doesn’t take advantage of using positions in space for grammar, it only uses the hand shapes and movements?) I don’t know of any language agnostic phonetic sign used as a first language for children: that sounds about as hard as making them learn through writing instead of talking.
- gugagore 2y agoThey are likely talking about "cued speech".
- akoboldfrying 2y ago>It is important to consider the sociocultural context, particularly in regards to the deaf community, which has its own unique language and culture Frankly, I disagree. I think a deaf person should be entitled to decline a low-risk treatment that would cure or mitigate their own deafness -- but to make that decision for a child is altogether different. Deliberately restricting a human being's sense experience throughout their lives should be considered child abuse, in the same basket as female genital mutilation. It's also about the most selfish thing I can imagine -- especially given that there's no reason I can see why a hearing child of deaf parents can't grow up "bilingual", learning both spoken and sign languages.
- 911e 2y agoHow likely to cure tinnitus ?
- tux3 2y agoZero chance, unfortunately. The cause of tinnitus is not with the OTOF gene. The best case scenario is that this wouldn't do anything.
- ck_one 2y agoThere is also active development for tinnitus/noise induced hearing loss. Dr Chen from Harvard is working on it. He was also involved in the research linked in the article. They are getting closer to a cure. Here is an interview with him: https://www.youtube.com/watch?v=lJr86MUYJ8M https://www.youtube.com/watch?v=lJr86MUYJ8M
- carterschonwald 2y agoThis is the sort of stuff I conceptualize as a true tech(nical/nology)startup. I realize that’s in some ways at odds with the meaning in practice. But this is amazing technology.
- GOD_Over_Djinn 2y agoDiscoveries like this should be shared with the world - not gatekept by rent-seeking venture capitalists. Wouldn’t you rather be Jonas Salk than Scrooge McDuck? https://en.wikipedia.org/wiki/Jonas_Salk https://en.wikipedia.org/wiki/Jonas_Salk > Salk was immediately hailed as a "miracle worker" when the vaccine's success was first made public in April 1955, and chose to not patent the vaccine or seek any profit from it in order to maximize its global distribution
- chris_t 2y agoRent-seeking has a technical definition; earning money from things you invented does not meet it. While Salk is obviously an inspiring example, a wise society should happily incentivize the development of useful technology.
- carterschonwald 2y agoWell said
- sooheon 2y agoIntellectual monopolies disincentivize development and incentivize rent seeking. Here, rent seeking is legal action and lobbying intended to protect and extend monopolies, instead of advancing science. Other than economic logic, we have natural experiments to back this up: i.e. the steam engine patent granted to Watt and Boulton in 1772 and its chilling effect on engine duty improvement (and the explosion of progress after patent expiry), and the modern pharmaceutical industry developing most strongly precisely where chemical patents were not granted, in 19th C. continental Europe, and slowing down wherever patent protections were eventually introduced, at the request of rent seeking lobbyists. https://fee.org/articles/do-patents-encourage-or-hinder-innovation-the-case-of-the-steam-engine/ https://fee.org/articles/do-patents-encourage-or-hinder-inno... http://www.dklevine.com/papers/anew09.pdf http://www.dklevine.com/papers/anew09.pdf
- nick7376182 2y ago[dead]
- arjie 2y agoThrough a mutual acquaintance, I met someone who did a little work for on the OTOF gene therapy and it really is remarkable stuff. My wife and I had our embryos screened by Orchid Health since we have a related genetic condition: a pathogenic mutation in GJB-2. Amazingly, Decibel Therapeutics has has one of these in R&D and the OTOF success gives us hope. We have a few embryos that are affected and the more that can grow up healthy the more chances we'll have at children. The technology itself is unbelievably futuristic: involving using a virus to deliver a repaired gene into existing cells. This form of non-syndromic hearing loss may well be repaired two generations from now. An interesting thing is if you follow along with the literature, some Chinese labs report success with these gene therapies in kids on the cusp of teen age. That's remarkable. It will give a lot of people today the chance to have healthy kids in the future even if they were unfortunate enough to carry the genes today. Personally, the fact that I can practically hold a whole genome sequence of our embryos on my computer means the future is here. Last time, I posted a few links for everyone interested in the subject https://news.ycombinator.com/item?id=40312242 https://news.ycombinator.com/item?id=40312242
- SJC_Hacker 2y agoScreening can also "repair" inherited deafness through selection - you simply don't produce offspring to those that have the defect.
- nehagup 2y agoWhen I try and imagine what that must be like from the inside—I can’t think of anything more exciting or scary than to gain a new sense.
- herbst 2y agoThere are magnet Implantats you can put into your finger which lets you feel magnetic fields.
- meindnoch 2y agoThat's not a new sense, just using the existing tactile system with a magnet.
- iandanforth 2y agoSenses are defined by what they sense, not how they are sensed. A person can have their sight partially restored through implants that bypass rod/cone activation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934168/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934168/
- meindnoch 2y agoThat's still signaling through the optic nerve. If they would restore vision by using e.g. the cochlear nerve, that would be something.
- knodi123 2y agoyou'd be surprised. I've heard about people experimenting by wearing a belt with dozens of haptic motors and a compass, so that it always indicates the direction of north. After a while wearing it, they stop consciously feeling the sensation of the vibration, and just feel "northness". And then when they take off the belt, they feel weirdly disoriented for a while, even in familiar places.
- LadyCailin 2y agoThere is a belt you can wear that has vibrators around it, and it always vibrates the north facing side. I read that people who wore that for a few weeks started gaining the ability to create much more accurate maps in their head, which makes sense, this is how pigeons do it too, they basically can just always sense where north is.
- nehagup 2y agoIf I'm interpreting the article correctly, it seems like the amount of hearing recovered is pretty good. I was wondering how much hearing was actually restored.
- 29athrowaway 2y agoThe genetic corrections are not inherited, right?
- zac256 2y agoIt's considered taboo/forbidden for genetic corrections to target the germline. I think that's an unfortunate misapplication of ethics, presumably due to fears about eugenics.
- BurningFrog 2y agoIt's taboo in Western medicine. I doubt the whole world will respect that.
- djur 2y agoMy understanding is that it's more about mitigating risk than avoiding an association with eugenics. If the gene therapy has unforeseen consequences the harm is multiplied with every generation and is harder to address once found.
- myrloc 2y agoHow can I get involved in this work as a software engineer?
- rjh29 2y agoIf you can't find out yourself then you're probably not motivated enough.
- MrDresden 2y agoHaving worked at a large world renowned genetics laboratory as an SWE I believe I can say that it is unlikely you will have the option of having any direct input into this kind of work, in that role. That being said, there is a lot of things an SWE can do in a support role. Some of the things I did were data processing pipelines (both automatic and human centric UI for phenotype gathering) and interconnected networks of scientific instruments, as well as some deployments of R and Python code. Sure, your name wont show up along with hundreds of others in the Nature publications, but you will know that you contributed to the overall success. And it does feel good.
- jdthedisciple 2y ago> Two of the children even gained an ability to appreciate music. Interesting: Does this mean that the other 3 children are still kind of indifferent to Music and presumably other kinds of sounds?
- meindnoch 2y agoThere's a certain age beyond which you cannot learn proper speech. There's a certain age beyond which you cannot learn absolute pitch. It wouldn't be surprising if there was a certain age beyond which you cannot learn to understand music.
- CaptainOfCoit 2y ago> There's a certain age beyond which you cannot learn absolute pitch I can understand things like that get harder and harder as you become adult. That it's absolutely not possible beyond a certain age I think is just a commonly held belief that doesn't hold up to scrutiny. What is this age limit where you've never seen anyone be able to gain that skill? I'm sure there are counter-examples.
- rylittle 2y agoInterestingly enough, I once read that no one over the age of 60 has ever _retained_ perfect pitch
- jjk166 2y agoIt is commonly lost in a person's late 50s to early 60s, but there are cases of individuals retaining it into their 70s and 80s. Further, the decline is gradual. Individuals who lose perfect pitch in 440hz tuning typically retain it at 415hz tuning for several more years.
- deepGem 2y ago"The children involved in the study were born with DFNB9, which accounts for between 2 and 8% of hereditary deafness. It is caused by mutations in the OTOF gene which prevent the production of functioning otoferlin protein, which can significantly reduce sound transmission from the inner ear hair cells to hearing nerves." Just shows how much of our body functions we take for granted. Every function has a critical path that is so vulnerable. This is despite the human body having all kinds of redundancies. Our body is so resilient, yet at times, some of the mechanisms are so fragile.
- herodoturtle 2y agoPoignant observation (that we take so much of our bodily function for granted), thank you for adding this to the commentary on this page. And that resilience-with-fragility you speak of instantly reminded me of our giant cloud clusters, with their tiny points of failure that test the limits of redundancy.
- belter 2y ago"Aissam, the boy who escaped from a world of silence thanks to gene therapy": https://english.elpais.com/science-tech/2024-06-05/aissam-the-boy-who-escaped-from-a-world-of-silence-thanks-to-gene-therapy-im-hearing-the-phone.html https://english.elpais.com/science-tech/2024-06-05/aissam-th...
- BurningFrog 2y agoLanguage nit: You can't "restore" hearing to those who never had it.
- ADeerAppeared 2y agoThat's not just a nit. The idea that these are people who are "broken" and need to be "fixed" is something a lot of Deaf people are very opposed to.
- deleted 2y ago[deleted]
- CaptainOfCoit 2y ago> The idea that these are people who are "broken" and need to be "fixed" is something a lot of Deaf people are very opposed to. Are they maybe "opposed" to been seen like that because there was no hope for any solutions besides just being OK with it? In the future when it's more accessible and cheaper, shouldn't being born without hearing be considered a "fault" of sorts, as you can now introduce this sense to them, like most others being born with hearing at birth?
- very_good_man 2y agoAll of us have to get real and demand immediate speed-up of LLMs, Gene Therapy, etc. Absolutely nothing else matters.
- arnaudsm 2y agoMillions of people already die of curable diseases. Technology isn't enough, many problems are political
- jjk166 2y agoPeople die to diseases whose cures are insufficiently practical. It's still a technological problem. Make them cheaper, make them more easily administrated, make them effective after the condition has passed beyond a certain point - these are all things further technological progress can potentially do. Political problems are situations where different elements of society are fundamentally at odds with each other over one option vs another. Freedom vs security, progress vs conservation, reform vs tradition - these are all cases where there are strong arguments on both sides and there fundamentally isn't a right answer. No one is politically in favor of death due to curable disease - eliminate the technological issues that tie curing the disease to something people actually politically oppose, like say higher government spending, and the political opposition goes away.
- arresin 2y agoFully agree. Both have the potential to solve whole groups of problems. Gene therapy especially should be species goal as something to get us to the next stage of evolution.
- bluerooibos 2y agoPolitics could do with an injection of LLM action. Climate change is arguably the most urgent issue.
- throwaway48476 2y agoGenetic issues are more prevalent in communities that practice inbreeding. Eliminating inbreeding seems to be an easier fix than genetic therapy.
- nobodyandproud 2y agoTangent, but this reminds me of http://news.bbc.co.uk/2/hi/health/1916462.stm http://news.bbc.co.uk/2/hi/health/1916462.stm