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Gene therapy restores hearing to children with inherited deafness (cosmosmagazine.com)
508 points by keploy 6 months ago | hide | past | favorite | 217 comments



This 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)


I 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.


Let'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.


Has there been any cases of this happening for other technologies?

That's like saying "now that we invented canals let's try to fix the world's irrigation problems before making fountains and water parks"


We're 8000 million people.

We can, and always will, work on many different things at once.


The amount of people who can actually work on anything meaningful in this field is double-digit at best. Sure, if you add up "many different things" you have plenty of people who can work on plumbing, programming, and gene editing. What are you going to do for geneCAD? Right, absolutely nothing. It doesn't matter how many of you there are; you could be 8000 million or 8000 trillion people and still accomplish nothing.


This assumes things are static. There are millions of programmers now, but certainly weren't 100 years ago.

The tools to investigate this will get cheaper and easier, driving more people into the field hoping for the next big win, a big payout, or just to make an impact.

Anyone can make a small circuit design have have a fab print it for you. The same could happen here, all you need to do is provide the sequence


I wish it were possible to achieve an entirely non-human body, but I don't think that's going to happen within any of our lifetimes.


Make sure to read Daniel Dennett before you change too much, you might forget who you are and become someone else entirely.

https://en.wikipedia.org/wiki/What_Is_It_Like_to_Be_a_Bat


I have Dissociative Identity Disorder, so I already become someone else all the time...

In all seriousness, at times I do genuinely wish species transition were possible. Imagine gender dysphoria but for species, so species dysphoria. It may sound insane, but honestly so can the entire concept of dissociative identities.

I don't know if I'd want to change my brain, but the physical properties of the body definitely. I want the body to be a fluffy quadruped...

Thank you for the link though, that is very interesting. It is intuitive, but not something that normally comes to mind~


I hope you're joking about wanting to become a "fluffy quadruped". Or, if not, I see why we had asylums.


I didn't feel like fully explaining. Still, foxes and wolves and cats and so on are all fluffy quadrupeds and something like that is what I feel I would rather the body be.


It is the very definition of insane. That doesn't mean we shouldn't have sympathy for it, but it's important to recognise when certain aspects of our psyche isn't sane or good and accept that.


I never meant to claim it's good or sane that I want an animal body, but it's something I can't really help. I don't have the delusion that it's ever actually going to happen, I just can't help but wish that it would.


I remember the Therian and Were community, back in the day. Some overlap with the furry community, but not a perfect subset.


Yes, those are very similar. I occasionally use the term otherkin for myself, as a non-specific term for "one who identifies differently from the body", but I do tend to get along well with therians. (And queer people in general, I suppose.)


you are what you are, there's no escape from that


Unfortunately.


You can do both things at the same time.


That'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.


In all likelihood if we were to get to the point of it being safe and cheap enough for genetic engineering cosmetic "upgrades" then that would through economies of scale drive enough money that medical research funding would be a solved problem. Also anyone wanting the chrome pipes and spoilers package is going to want their engine tuned. Whats the point of having functional wings if you heart blows out trying to use them.


Cosmetic 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.


Hell, 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-cani...


And cigarettes have benefited the lung cancer research centers. Just because it works doesn’t make it the best course.


Economies of scale. Shiny hubcap manufacturers will very generously subsidise the R&D for other, more worthy users of a technology. They aren't competitive or independent, they're synergistic. The billions of dollars we "wasted" on making video games look more realistic gave us a revolution in high-performance computing that nobody could have created intentionally.


Each gene therapy is a unique "medicine". There is little economy of scale, at least for the hardest part.


That's due to a lack of theory and useful abstractions in the tools used to modify genes. We're so early on in the development of that field that if this were computers, we'd still be assembling devices by arranging logic gates by hand. Custom cosmetic gene therapy is a great way to incentivize the better tools.


No, not really.

Genes are far more complex than inserting a sequence into a delivery mechanism.


"they aren't independent"

That interdependence may be beneficial, though.

Experience and revenues from cosmetic treatments will help health-restoring treatments.


> breathless proposals for ways to design shinier hubcaps whenever some promising new technology appears

I wouldn't underestimate the emotional toil of dealing with illness and death [1].

Tackling these problems head on requires (a) exposing researchers to that toil and (b) removing from the pool anyone who doesn't want to do that. Given how much of Silicon Valley culture is built on borderline-ludicrous optimism (once it's over the border it no longer qualifies as building), it makes sense that the indirect approach finds resonance here in a way the direct one does not.

Where your argument finds ample purchase is in the asymmetry of idiot luxury spending in our society to basic and applied research of any kinds, wings or Wilm's tumour.

[1] https://www.statnews.com/2016/09/19/mental-health-doctor-res...


Moreover, they are at this stage the exact same problem- requiring not competing but identical research: we need to understand generally how biology works enough to predictably engineer it.


> they are at this stage the exact same problem- requiring not competing but identical research

I'd go one step further in arguing they're complementary. The personalities that will work on e.g. wings or longevity are not the types drawn to curing diseases, much less the boring ones.

Broadening the field from solving mundane problems to solving daring ones is net positive. You gain personalities that would have otherwise stayed away. (You see something similar in space programmes.)


And a huge part of what steered talented people into programming over biomedicine was the relative freedom. The more you can do without the drag of convincing a vast bureaucratic/political machine to let you try your idea, the more people will contribute to progress.


Actually you can't because there is a limit to resources in both time and money.


Na, this isn’t it, you one of them that talks let’s solve poverty before spending money on xyz


Just ensure that there’s good a insurance system to finance the rare health issues, and the market will take care of the hubcaps and spoilers.

Solving e.g. male pattern baldness or bone loss from peridontitis means guaranteed billionaire from out-of-pocket treatments alone.


What do you get from admonishing someone for saying the kinds of things that they just said?


Why do you consider an attempt to focus a public discussion on the most important uses of a new technology to be an admonishment?


it certainly reads as one, and calling them "most important" reveals your bias that those uses are more important too.

Like it or not, the way society is currently arranged, making stuff for rich people is more profitable than making things for poor people, and greed can kick in, so people do things out of love of money rather than necessity. were the deck stacked more equal, maybe things would be different, but human psychology is devilishly complex.


Most of those problems in the US are caused by lifestyle, and can't really be changed without behavioral modification. And a lot of our health issues are a matter of poor access to healthcare.


This assumes that the fundamental nature of human beings can't be changed, which is the presupposition that genetic engineering denies.

The entire point of genetic engineering is to try to engineer people at the cellular level. A fanciful example would be modifying human metabolism to be more similar to those of birds that consume most of their calories in the form of simple sugars. Humans can't eat a diet of 100% sugar and remain healthy, but other animals can. It may be possible to change that fact, if we know how to edit our genes.


Are you saying you could see sugar being somehow folded into the many different proteins that make up the vast number of tissues in our bodies. Or are you saying our tissues could be constructed out of sugar crystals instead?


Proteins can be synthesized from sugar as a carbon source. We know this because there are bacteria that can survive and reproduce with no nutrients in their environment other than glucose.

In fact you don’t even need sugar. Carbon dioxide and water alone are sufficient. Plants produce their entire biomass using nothing but carbon dioxide, water, sunlight and trace elements from soil.

Amino acids and proteins don’t occur without life. Living creatures have the ability to synthesize all amino acids and proteins from simpler compounds.


Sex changes/gender transitions is an actual boring health problem. The inability to assume the correct gender for a trans person often leads to social rejection, violence, poverty, prostitution, murder, and suicide.


If through gene editing you could also erase someone's disphoria what option would you choose?


Isn’t it obviously good to get rid of someone’s problem? Otherwise it wouldn’t be a problem.


If your perception doesn't match your body, would you prefer to change the perception or change the body?


It seems pretty clear to me that changing one’s body is preferable to changing who you are. The former is something you’re born with, but the latter is something you can decide for yourself.


Suppose, as you do, that your body is not who you are. Then your identity lies solely in your brain. But if that's the case why would disphoria even exist?

If you feel like a man but you don't look like a man, why could that cause any identity problems? It must mean your body is actually part of your identity, so changing it changes who you are


The problem with this argument is that it leads to the conclusion that all change is pointless. If your body is who you are, and you can’t control it, then it’s best just to accept whatever you’re given.

That’s contrary to most of human history, where we specifically try not to take what we’re dealt.

It’s useful to ask yourself: why should vaccines be "allowed" (or "accepted" or "they’re good") but body change shouldn’t be? They’re both as artificial as a Twinkie.


That’s like trying to cure depression by getting rich. It hardly ever works


What?


Cutting off body parts to treat body dysphoria is something that should be done with great care and rarely leads to solving the underlying mental problems.

Trans is a much discussed variant that is hard to have a normal talk about, but there are many more variants, for instance women hating their breast & wanting to remove them, I think most people here would agree that intensive psychological treatment are preferable to actually removing healthy body parts. But in the end an adult can do what they want.


Erasing someone's dysphoria would also fundamentally change their identity and personality. If I were to suffer a head injury today that so altered my personality, the result would be very unpredictable. I could become a better person, or a worse one. I could lose my wife, my career, everything. But even if the outcome were positive, I wouldn't be me anymore. This me would cease to exist, replaced by a new one.

On the other hand, a bodily alteration is much more predictable, and, importantly, I'd still be me. I wouldn't become some other person.

This me has an instinct for self-preservation. Thus, if both options were available, I would absolutely choose transition over erasure.


You seem to come from the point of view that body and mind are quite separate, and that changing your body through surgery and hormones and other chemicals has less effects on the "real you" than a change in brain wiring would cause.


No 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.


Taking 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.


"...are you suggesting coconuts migrate?"

Seriously, lesser-schooled folks don't realize the extent to which evolution took tiny variations over an extremely long time to achieve physical flight. The way it arose differently in pterosaurs, birds and bats is fascinating.

I think younger children are capable of understanding more about genetics than we often suppose. More of these concepts should be taught at younger ages.


I have a bachelors in bioengineering, I’m not a “lesser schooled individual”. Just because evolution took a long time doesn’t mean we have to, you can run millions of simulations virtually, something that nature has to do over millions of years. Are the simulations going to be perfect? Probably not but there’s a lot that can be gleaned through simulations combined with observations in the real world.


(a) I like your analysis (b) maybe the wings are just for show so that you flap them out at clubs every now and then right when the music hits the drop or something and everyone is like WHHAAA????!!!!


> it would have to completely transform you into a completely different creature, simply due to the physics of flight

In OP's defence, they never mentioned flight. Maybe they just want a peacock train.


Ok, fair enough. I hadn’t considered that. In my mind, wings you can’t fly with are worse than no wings.


Tell that to am emu or ostrich, or don't, their claws aren't vestigial.

I would opt for smaller tweaks like an extra rhodopsin folding with longer features so I could see near (like tv remotes) ir. re-enable hibernation. Things some mammals already have would be good starts.


I meant as a human.


A futurist I knew of long ago pointed out that the Moon’s gravity is light enough that the human skeleton could achieve sufficient lift without sustaining damage in the process.

True, you might have to be a junior Olympian to do it, but it’s possible.

On earth your pectorals would tear off of your sternum long before you achieved takeoff.


I thought the same thing.

The lack of Moon atmosphere is a real problem though.


Don’t bump into the top of the dome. You’ll get charged for disinfecting the equipment.


Heinlein, "The Menace from Earth"


All that energy will be better spent designing jetpacks powered by portable nuclear reactors.


Your 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.


> 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?


If it’s pure caloric intake there are plenty of dense fats that will let you do that without having to eat all day. Or your body could create all the proteins you need like silverbacks. Either ways, I’m saying in a sufficiently advanced society there should be enough ways to thread that needle to maintain what you want while modifying the rest. None of this is physically impossible.


No, not physically impossible to have large flying creatures. What I’m suggesting is that by the time you modify a human so they can fly, they’re not really human anymore.

But that may be more of a philosophical debate so I’ll leave it at that.


It's about as close to impossible as you can get. If you tried to do it in the womb, too much deviation from a regular human fetus won't be carried to term. If you try to do it after growth plates have closed, you'd have to destroy every bone in the body first, which would kill you. That gives you some kind of post-birth, pre-puberty window over which some sufficient level of body remodeling can at least happen in principle, but you seem to be underestimating the level of remodeling to do this. You'd need to drastically reduce bone density, which would leave you extremely susceptible to injury. You'd have to undo human adaptations in the spine and pelvis for upright posture, which would be extremely painful. You'd need to effectively swap out the glutes with pecs and undo the adaptations for brachiating arms. Things like your eyes and ears and basic breathing apparatus are not well-adapted for flight. Things like where blood and lymph and other bodily fluids tend to pool in the human body versus where they do in the bodies of flying animals. Just as laying down for too much time will cause it to pool in places your body can't easily clear right now, being horizontal for flight would have the same effect.

It's not just a matter of growing wings. And yeah, the energy demands of making all these changes, as others have pointed out. The only kinds of animals that go through this level of non-fetal metamorphosis are insects with weights measured in the tens of grams, energy needs that kind be sustained by something like a cocoon. How would you meet the energy demands of an adult human going through metamorphosis? You couldn't do it by eating, not only because your gut can't actually digest the amount of food you'd need (you don't have an elephant gut) but also simply because being conscious through the process, unlike insects in a cocoon, would be so absurdly painful that I doubt you'd be able to function and do anything at all, let alone spend all of your time finding and eating food. You'd need to be put into a medical coma and injected with intravenous nutrients to have any shot at all.

Why on earth would we ever try this? In reality, giving yourself genes to grow wings would just kill you.

Look at this picture from Wikipedia showing Argentavis side by side with a human: https://en.wikipedia.org/wiki/Argentavis#/media/File:62628-A...

What sorts of processes do you imagine are necessary to stretch the human body to the size of the Argentavis body without adding any weight? It'd be like getting flattened by a steam roller, then drawn and quartered. Bodily tissue isn't balloons.


There 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.


I 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.


Eh, 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.


That 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?


I 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.


Synthetic 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.


Could you provide some resources/links please?


It'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/

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/

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/

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

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.


That would be cool - maybe a simple 20/20 vision would be a great next step after hearing


it’s happening! i just finished something that assists in “CRISPR Design” and helps gene editors.


Our 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...


Dan Simmons, Hyperion Cantos. “Biosculpting”


Excuse me, are you The Qu?


We need to keep away biotech OpenAI-wannabes apparently.


I'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-ther...


I thought you can’t just inject genes and then the body will start replicate it. Does it need periodic injections?


If 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


This 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/


And that’s why replies are helpful in these kind of explanations. My over-edits became wrong, and then an hour later, unfixable. bglazer is correct.

AAVs, unlike Lentiviruses, do NOT integrate.


The reason I know this is I made the same mistake in a comment on a similar story a few weeks ago!


Thank you for this description of how it works. It seems like truly beautiful and terrifying magic.


That 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.


"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.


Poignant 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.


Through 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


Screening can also "repair" inherited deafness through selection - you simply don't produce offspring to those that have the defect.


Gene 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.


When 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.


There 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.


There are magnet Implantats you can put into your finger which lets you feel magnetic fields.


That's not a new sense, just using the existing tactile system with a magnet.


Senses 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/


That's still signaling through the optic nerve.

If they would restore vision by using e.g. the cochlear nerve, that would be something.


you'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.


This 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.


Discoveries 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

> 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


Rent-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.


Intellectual 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-inno...

http://www.dklevine.com/papers/anew09.pdf


I agree with all of this. The example of the patent on steam engines is fascinating, thank you! It's certainly true government granted monopolies are far from the ideal incentive structure, with many downsides. (And lobbying for EG patent extensions likely IS rent-seeking). Advance market commitments and other systems likely have better characteristics.

I was rather objecting to the misuse of a technical term, and the idea that we should expect all innovation to happen without reasonable incentives.


Ah gotcha, agreed.


There are incentives to developing medical technology beyond the opportunity to become obscenely wealthy. If you do so, you are necessarily depriving some subset of patients that need the treatment. Honestly, I find it pretty unimaginative (and a bit disturbing) that the only “incentive” you can think of for treating sick children is the ability to monetize the treatment - it’s a virtuous endeavor in and of itself. I must say, though, it’s hardly surprising to meet someone with such a worldview on a VC-focused forum.

Edit:

> Rent-seeking is the act of growing one's existing wealth by manipulating the social or political environment without creating new wealth.

https://en.wikipedia.org/wiki/Rent-seeking

This aligns neatly with my comment - gatekeeping a medical treatment behind artificially high costs to enrich yourself is the very definition of rent-seeking. I think you’re digging yourself in to a pretty deep philosophical hole here, solely out of some need to nerdsnipe people to reassure yourself of your own intellect.


Patents are held by assignees, not the inventors. Inventors do not earn money from patents.


Well said


How 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!


This 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.


How perfect can your reaction be? Can you get to 99.999999999999%?


> 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?


There'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.


> 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.


Interestingly enough, I once read that no one over the age of 60 has ever _retained_ perfect pitch


It 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.


"Aissam, the boy who escaped from a world of silence thanks to gene therapy": https://english.elpais.com/science-tech/2024-06-05/aissam-th...


If 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.


The genetic corrections are not inherited, right?


It'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.


It's taboo in Western medicine.

I doubt the whole world will respect that.


My 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.


All of us have to get real and demand immediate speed-up of LLMs, Gene Therapy, etc. Absolutely nothing else matters.


Millions of people already die of curable diseases. Technology isn't enough, many problems are political


People 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.


Fully 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.


Politics could do with an injection of LLM action. Climate change is arguably the most urgent issue.


Tangent, but this reminds me of http://news.bbc.co.uk/2/hi/health/1916462.stm


Language nit:

You can't "restore" hearing to those who never had it.


That'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.


> 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?


How likely to cure tinnitus ?


Zero chance, unfortunately. The cause of tinnitus is not with the OTOF gene.

The best case scenario is that this wouldn't do anything.


There 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


How can I get involved in this work as a software engineer?


Having 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.


If you can't find out yourself then you're probably not motivated enough.


Does asking the HN community not fall into the category of “finding out”?


What an uncharitable thing to say


I’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...


That would be a terrible reason to give up, or slow down, on research in any area of health science.


There 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.


Sounds 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.


They are likely talking about "cued speech".


>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.


This presupposes an awful lot. If it were truly a risk free magic wand you could wave, then I could see your point.

But none of the current options are risk free, and I doubt this one will be. They all have risks, side effects, and probably the chance of failure. And then the question is how low of a risk is acceptable to restore a child's hearing. These are people who would live an otherwise healthy and normal life, and they'd grow up in an accepting deaf family which is likely already plugged into a community. I can't imagine how it would feel to have a serious side effect (or worse) impact your child when you know they could have gone without that procedure and lived a happy, fulfilling life. But I also understand the desire to give your child every possible opportunity.

All of that is to say, I think it is reductive to compare this to child abuse or FGM. There's no right decision, and parents absolutely will need to make a difficult choice, hopefully prioritizing their child's safety and future above all else.


It's often not about the risk, though. It's sadly common for uppercase-D "Deaf culture" people to decline these kinds of treatments for their kids because they want their kids to be deaf too. That's absolutely child abuse.


> Deliberately restricting a human being's sense experience throughout their lives should be considered child abuse

I've got relatives that teach deaf children. most deaf kids who grow up in societies with mostly hearing kids, want to be normal more than anything. At the same time, for many who are eligible for cochlear implants, getting that early before speech development begins in earnest is very important, ideally when they're just a toddler or younger. Early enough and you'll barely notice any difference in their speech, understanding, etc. However, their parents often decline it and say they want to let their child be the one to choose when they're old enough to- which is far, far outside the best window for developing that area of the brain, as well as speech. They might be behind in those ways for the rest of their lives if they're not given therapy to help catch up.

I understand both sides I guess, but if consent is the issue, why not give them the implant and let them choose to disconnect the receiver then when they're older? Obviously, because they won't want to, and rarely ever do.


>not unlike queer people and the attempts to “fix” them.

To be fair, LGBTQ community isn't 'broken.' Some people are inherently gay, lesbian, etc.

Deafness _is_ an actual defect. The weird thing that we should not strive to fix human defects when they are truly defects is astounding.


Some people are inherently deaf, what's the difference?


Being LGBTQ is not a disability or handicap; it’s simply different, like being red-haired or left-handed.


If you feel compelled to remove parts of your body and take opposite sex hormones for life, that’s clearly a disability.

If genes could fix your brain to not feel compelled to swap sexes, that would be a huge win in the quality of life for most individuals.

You can pretend that pretty much anything “isn’t a disability, it’s just different.” But that isn’t true.


You're focusing pretty hard on a single letter of that acronym that makes up a small percentage of the overall community.


What makes you think that deafness is not the same as being left-handed?

I mean objectively, not based on the current cultural norms which will be very different 50 years from now.


“Objectively,” left-handed versus right-handed changes nothing about a person’s capabilities in the world, whereas being deaf does.

Cultural norms is an interesting comparison. Despite there being no actual difference in capacity, cultural views forced many left-handed people to be right-handed, making those people miserable in the process for no good reason.


You can't procreate, that sounds like a pretty big difference in capacity?


Gay people can obviously procreate, nothing about your body stops functioning when you are gay.

What you mean is that they don't have sexual attraction towards people of an opposite gender, where if they had a relationship with them, that relationship would encourage procreation.

To me that just doesn't seem like a "difference in capacity".

I personally don't want children, and will probably seek out a partner who likewise does not want children. If I encounter somebody who wants lots of children, I will see that we have different life goals, and I probably won't be very keen on being in a relationship with them. Do you consider me "damaged" or of "diminished capacity" because of it?


Interestingly enough it was still common to train left handed kids in right handed writing up until maybe 40 years ago as it was seen as some kind of defect obviously.


> “Objectively,” left-handed versus right-handed changes nothing about a person’s capabilities in the world,

As a leftie, this is only true in the current world — I live in a culture with a left-to-right writing system, and yet technology means I don't ever need to use a fountain or quill pen.

I did have one teacher who insisted on "no biro" when I was a kid, but they were also my first introduction to "not everyone is actually nice".


Being deaf is surely different from not being deaf but you can't objectively say it's a disadvantage. It's only a disadvantage in a world built for not deaf people, like being left-handed is a disadvantage in a world built for right-handed people.


I can and did say that. The world is easier for non-deaf people. I can’t imagine even many deaf people would argue against that statement.

The correct way to argue against this isn’t to say that “objectively” the world is the same for deaf and non-deaf people; it’s that there’s a culture and language bound up in deafness that don’t deserve to die thanks to medical advances. That is true, and makes treatments like these and what they mean to the deaf community much more complicated and difficult.


If dolphins could communicate with us they would surely tell how much easier it is when you have ultrasonic hearing. All humans are therefore disabled and in need of fixing.

Or maybe not, if dolphins turn to be wiser than an average human.


If all humans could echo-locate except a subset who couldn't, I would say that group is at a small disadvantage, yes, because the set of things the main group can do is 'objectively' greater. I don't know how relevant it would be for us especially in the daytime, but hey.


I agree. However, whether all kids should receive gene therapy to develop the echo-location once the science allows for that is a more nuanced question.


If most buildings lacked light because the vast majority just echolocated, then the those unable would be disabled.

It is okay for there to be a normal human experience, and define inability to participate as a disability.


> It is okay for there to be a normal human experience, and define inability to participate as a disability.

That's what most people normally do, yes. Then many people out there define an "ability to enjoy hetero sex" as a "normal human experience" and therefore see gayness as a disability that needs a cure.

I'm not arguing about the conclusion here, but about the method and the basis for deriving this conclusion.

The initial comment in this thread declared deafness to be an "actual defect" while gayness "is just people being inherently gay". Such division is completely arbitrary and doesn't follow from any law of nature. Only from current societal views which change a lot with time.


> doesn't follow from any law of nature

Natural selection gave us hearing.


Right, and it also gave us a strong desire for the opposite sex. So if you draw the line based on this principle then gayness and deafness will fall on the same side of this line, whichever side it is.

Hence I write that the initial comment making the distinction between gayness being obviously OK and deafness being obviously not OK, look arbitrary to me. This division is cultural.


It’s a disadvantage in the “built” world, but it’s also a disadvantage in the natural world. If you drop a deaf person in the middle of the forest with no one around, they will not be able hear rivers for water, they will not be able to hear animals approaching, etc.

Being deaf is objectively a disadvantage because 4 senses is objectively worse than 5 senses.


Most of vertebrates (including human's ancestors) lost the 6th sense of electric fields in process of the evolution. Apparently 6 is not always better than 5 from the nature's point of view. Moles went further to loose sight as well.


I don't think that's quite right, evolution makes trade offs and allocates scarce resources, it's not necessarily because such things would not be beneficial.


It's not clear what "beneficial" means if you consider it separately from the resources required to achieve it.

E.g. it's beneficial to be stronger I guess, and gorillas are always strong whether they use their muscles or not. However for humans nature chose a different path where only the muscles you actively use are strong. This approach seem to work great so far, even though it results in many individual muscles of the body being weak. For each and every of these muscles you can argue that making it stronger would be "beneficial" but as a whole it doesn't seem to work out.


> Most of vertebrates (including human's ancestors) lost the 6th sense of electric fields in process of the evolution.

Human ancestors are not human. Also, the ancestor you are referring to was a fish, and could only sense electric fields under water. Why would the ability to sense electric fields under water be an evolutionary advantage for humans who don't live in water? If it's not an evolutionary advantage, then there is no reason it would propagate.

When I said 5 senses are better than 4, I was clearly referring to senses that are useful in our environment. Answer this question: is a deaf person, all else equal, more likely or less likely to survive and procreate relative to a hearing person?

> Moles went further to loose sight as well.

Moles have eyes and can see. Their vision is just not as detailed as humans. Highly detailed sight isn't an advantage for creatures that live in the dark. However, hearing is a huge advantage for people who live in an environment where sound waves exist.

You're clearly wrong here. Stop reaching so hard and just move on.


No, I'm not wrong, I just don't like relying on "obvious" statements like "5 senses are better than 4". We can't know for sure what was "better" until the human race experiment is finished (and then we won't know either obviously).

Consider this: hereditary autoimmune diseases are usually seen as a disadvantage. However they were a huge advantage during the bubonic plague in Europe, increasing the chances of survival by estimated 40% [1]

If we manage to eradicate these disadvantageous genes we may not survive the next pandemic. I don't have the knowledge to predict whether deafness genes or some other property entangled with them will be advantageous 10000 years from now and neither do you. That's all. Now you can enjoy listening to music all you like, it's just beyond the point.

[1] https://www.nih.gov/news-events/nih-research-matters/how-bla...


Hereditary autoimmune diseases are not a sense, and are irrelevant to this discussion about whether hearing is an objective advantage or not.

I’ll ask again, since you must have missed this question: is a deaf person, all else equal, more likely or less likely to survive and procreate relative to a hearing person?


> I’ll ask again, since you must have missed this question: is a deaf person, all else equal, more likely or less likely to survive and procreate relative to a hearing person?

You know the answer: it can be both ways depending on circumstances.

* In the prehistoric world I think he was less likely to survive. The difference doesn't seem to be dramatic though since these genes were not eradicated from the population.

* In the modern world the difference is close to zero with an unknown sign. Given that in developed countries probability to procreate seem to be limited by a desire to procreate, I can't rule out that e.g. deaf people for some reason have 0.1% more desire to have kids, or any other side-effect. So answer to your question is unknown, requires a study to figure this out.

* In the future hearing can be an advantage or a disadvantage depending on how the circumstances evolve. We see that species gain and loose senses depending on the environment.

EDIT: I would also like to clarify this part:

> Hereditary autoimmune diseases are not a sense, and are irrelevant to this discussion about whether hearing is an objective advantage or not.

It's a human trait which was "obviously good" in the past and is "obviously bad" now. Hence I don't trust statements that other human traits like deafness are obviously good or bad. It's interesting to discuss but it's not granted.


How do you hear predators approaching? It's an objective disadvantage.


This feels a bit tenuous. What world do you envisage where it's a completely level playing field? Do we ban talking, music, sound in movies etc etc??


I think building a completely level playing field is a dangerous utopia. Essentially it's the same idea as fixing people to make them equal, just addressed from the opposite end.


Let me help explain, some left handed people can hear and are not deaf. Objectively that is how deafness is not the same as being left-handed.


Well thank you, but the question is why one needs "fixing" and the other doesn't. Parent comment made an argument that being gay is like being left-handed so it doesn't need "fixing". That's fine with me, but I don't see how the same logic doesn't apply to deafness.

Many deaf people enjoy their life as it is and don't welcome your attempts to "fix" them.


I didn’t attempt to “fix” anyone. Everyone has to do that themselves.

What about the deaf people that don’t enjoy their life as it is and do welcome the opportunity to hear?


> What about the deaf people that don’t enjoy their life as it is and do welcome the opportunity to hear?

I would be happy if they had such an opportunity.

The question, once again, was different: should the hereditary deafness be eradicated in childhood by gene therapy once advances of medicine allow that?


I think you changed the question and escalated the severity of the proposal so it became easier to knock down as a straw man.

Originally this was about the desirability and capability of enabling deaf people to hear writ large. But now you are framing it as full scale eradication carried out in a way that bypasses consent.


I'm not, please read the whole discussion.

The root of this thread referenced the cochlear implant which produces best results when implanted at a very young age (staring from 9 months) obviously without consent of the patient.

Other author replied that:

> The weird thing that we should not strive to fix human defects when they are truly defects is astounding.

All my comments are essentially stating the disagreement (or rather lack of agreement) with this point of view.

It declares being deaf as a "true defect" that we should "strive to fix". In the context of the gene therapy now available, I understand this means that a deaf-born children should be "fixed" to remove this "defect". This vision is not crazy, but it doesn't strike me as universally true either.


I read it multiple times and the unresponsiveness of this comment serves to further confirm my assessment, that you were unique in introducing the notion of full-scale eradication without qualification into this conversation. The participant you quoted noted a preferability, but you engaged in an original creative act in equating this to eradication.


> The question, once again, was different: should the hereditary deafness be eradicated in childhood by gene therapy once advances of medicine allow that?

Sure, because it's reversible. If they don't like hearing they can always become deaf again.


Wait 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.


Fortunately 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/


How 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)


In vitro fertilization (IVF) combined with preimplantation genetic screening (PGS) is becoming increasingly mainstream. This advanced technique allows us to select embryos with healthy genes, thereby ensuring that babies are born healthy or at least reducing the risk of genetic diseases. Very expensive in US but is getting very affordable in Eastern Europe and Asia.

Another alternative is selective abortions after early genetic testing (though ethic and morale concerns here are huge).


that crazy pro-natalist fascist couple that's been all over the news lately do this. They pick and choose which of their embryos are the most fit overall, and/or which have blond hair I'm sure, and plan to have as many of them as possible. Seems a shame to go through all that, only to beat your kids in front of a newspaper reporter and give them neuroses that'll likely make them rebel against you, but I'm sure if they can invest in crypto stocks they must be very good at predicting the future right?


Deaf people can already have kids


Apart from the other points people have made, it's worth noting that these days parents can avoid having children with inherited genetic disorders through IVF. While there will always be a component of spontaneous mutations resulting in genetic disease, we may approach within a couple of generations a state where most inherited disorders actually disappear or reduce to vastly lower prevalence over time.


Some backward countries (like my own France) forbid that due to concern over eugenics.


I’m sure you have some undesirable genes too, whether you’re aware of it or not.


And we'll cure them too.


We have this already. As a species we are susceptible to many diseases which we have to take vaccines for, every generation.


I 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.


There 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


Any different from people needing glasses?


ah, an eugenicist. and yet, if i stated that eugenicists should be eliminated from the gene pool, you'd be outraged.


Obviously: for a start, since there’s no genetic test for eugenicism, you’d have to wait and eliminate them as adults. They may have already reproduced by then, but there’s also no clear mechanism for inheritance so we don’t even know if that is a problem. If they adopted children do we consider those kids to have inherited it?


The fear of being beholden to a company for your health is not one to dismiss so easily.


get a better healthcare system.


Damn. Might as well just kill ourselves because our children inherit our problems. My parents need glasses, I’ll need glasses. Fuck.

/s


Typical engineers, tipping into eugenics to treat society as an optimization problem...


Genetic issues are more prevalent in communities that practice inbreeding. Eliminating inbreeding seems to be an easier fix than genetic therapy.




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