> "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)

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

AAVs, unlike Lentiviruses, do NOT integrate.

Hopefully in the next 50 years but that’s wishful thinking.

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"

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

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

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.

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...

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.)

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~

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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?

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.

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.

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.

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.

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

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.

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

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

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.

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.

Interesting: Does this mean that the other 3 children are still kind of indifferent to Music and presumably other kinds of sounds?

It wouldn't be surprising if there was a certain age beyond which you cannot learn to understand music.

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.

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?

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

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.

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.

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.

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.

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.

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.

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.

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.

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?

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".

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.

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

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.

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.

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

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.

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.

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...

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.

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

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?

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

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.

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.

>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/

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