[gota]

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)

[dyauspitr]

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.

[akoboldfrying]

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.

[Almondsetat]

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"

[BurningFrog]

We're 8000 million people.

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

[vsuperpower2020]

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.

[gibolt]

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

[LoganDark]

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.

[telesilla]

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

[LoganDark]

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~

[vsuperpower2020]

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

[simianparrot]

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.

[ben_w]

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

[abdulhaq]

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

[dyauspitr]

You can do both things at the same time.

[akoboldfrying]

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.

[smegger001]

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.

[evilduck]

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.

[JumpCrisscross]

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...

[_factor]

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

[jdietrich]

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.

[refurb]

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

[inglor_cz]

"they aren't independent"

That interdependence may be beneficial, though.

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

[JumpCrisscross]

> 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...

[_yb2s]

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.

[JumpCrisscross]

> 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.)

[abecedarius]

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.

[refurb]

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

[m3kw9]

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

[marvin]

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.

[Teever]

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

[akoboldfrying]

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

[fragmede]

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.

[jmcgough]

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.

[landryraccoon]

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.

[xedrac]

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?

[landryraccoon]

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.

[gurumeditations]

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.

[Almondsetat]

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

[sillysaurusx]

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

[Almondsetat]

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

[wouldbecouldbe]

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

[Almondsetat]

What?

[groovy2shoes]

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.

[Almondsetat]

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.

[narrator]

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.

[nkrisc]

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.

[slfnflctd]

"...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.

[dyauspitr]

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.

[awwaiid]

(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????!!!!

[JumpCrisscross]

> 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.

[nkrisc]

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

[galangalalgol]

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.

[nkrisc]

I meant as a human.

[hinkley]

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.

[BurningFrog]

I thought the same thing.

The lack of Moon atmosphere is a real problem though.

[hinkley]

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

[abecedarius]

Heinlein, "The Menace from Earth"

[diego_sandoval]

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

[dyauspitr]

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.

[nkrisc]

> 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?

[dyauspitr]

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.

[nkrisc]

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.

[nonameiguess]

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.

[kevin_thibedeau]

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.

[dyauspitr]

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.

[Auracle]

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.

[ben_w]

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?

[Auracle]

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.

[_yb2s]

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.

[Nesco]

Could you provide some resources/links please?

[_yb2s]

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.

[taf2]

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

[mylons]

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

[inglor_cz]

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...

[hinkley]

Dan Simmons, Hyperion Cantos. “Biosculpting”

[TyrianPurple]

Excuse me, are you The Qu?

[antegamisou]

We need to keep away biotech OpenAI-wannabes apparently.

[tim333]

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...

[m3kw9]

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

[toufka]

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

[bglazer]

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/

[toufka]

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.

[bglazer]

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

[rekttrader]

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

[rguiscard]

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.