Baby is healed with first personalized gene-editing treatment
nytimes.com
nytimes.com
And an Editorial piece (more technical than the NYT): https://www.nejm.org/doi/full/10.1056/NEJMe2505721
That is one of the most incredible things I have ever read.
(core war, anybody?)
The talk of "crawling along the genome" is kinda fundamentally wrong though and is a bit irking - CRISPR kinda just bumps around until it hits a PAM site, in which case it starts checking against sgRNA. Much more random than they make it seem
About CRISP, it's like the ultimate Perl+Regex for the body.
It was only in college, when I read Douglas Hofstadter’s Gödel, Escher, Bach, that I came to understand cells as recursively self-modifying programs. The language alone was evocative. It suggested that the embryo—DNA making RNA, RNA making protein, protein regulating the transcription of DNA into RNA—was like a small Lisp program, with macros begetting macros begetting macros, the source code containing within it all of the instructions required for life on Earth. Could anything more interesting be imagined?
Someone should have said this to me:
> Imagine a flashy spaceship lands in your backyard. The door opens and you are invited to investigate everything to see what you can learn. The technology is clearly millions of years beyond what we can make.
>
> This is biology.
–Bert Hubert, “Our Amazing Immune System”
I misread this as "fleshy" for a moment, and the quote almost works better that way.
True programmatic biology is still very underdeveloped. I have seen logic gates, memory, and state machines all implemented, but I don't think anybody has built somethign with a straightforward instruction set, program counter, addressable RAM, and registers that was useful enough to justify advanced research.
Hilarity subsequently ensues.
Further, your immune system does some clever combinatorial swapping to achieve diversity (https://en.wikipedia.org/wiki/V(D)J_recombination). The generated diversity is then screened by the immune system to find highly effective antibodies that bind to specific foreign invaders.
Doing something actually interesting from an engineering perspective makes for fun science fiction, but as always, the specific details in that story would be a very unlikely outcome.
Which, yeah, that's a miraculous discovery. And it was well worth the 2023 Nobel in Medicine.
Like, the whole system for gene editing in vivo that we've developed is just crazy little discovery after crazy little discovery. It's all sooooo freakin' cool.
That's good if your goals are to detect genetic modification which may be considered cheating in competitive sports.
That's bad if your goals are to detect genetically modified people and discriminate against them.
I see a near future where the kind of people who loathe things like vaccines and genuinely believe that vaccines can spread illness to the non-vaccinated feel the same way about other things like genetic modification and use legal mechanisms to discriminate and persecute people who are genetically modified.
I'm not totally sure. If I understand it correctly, the mRNA contains pseudouridine, and it makes the protein that will edit the DNA. The edited DNA should look like a normal one.
[And no, I am not anti-vax, nor anti-gene-editing.]
I'm not arguing about whether the risks of the attenuated virus outweigh the benefits. I think the data are very clear there. (Heh -- and I'm sure the vast majority of people will agree with that statement, even if they disagree on what the clear answer is....)
It's just that one shouldn't mock a belief without including the necessary qualifiers, as otherwise you're setting up an argument that can be invalidated by being shown to be factually incorrect.
As for genetic modification of humans, IMO there are a lot of very good reasons to be wary, most of them social. Fatal hereditary conditions are obviously an easy call. What about autism (not saying there's a genetic link there to use, just a what if)? Or other neurodivergence? Like being a troublemaker in class? Or voting for the party that doesn't control the medical incentive structure? Heck, let's stick with the fatal hereditary conditions, and say the editing does not affect germ cells. Is it ok if the human race gradually becomes dependent on gene editing to produce viable offspring? Or let's say it does extend to germ cells. The population with resources becomes genetically superior (eg in the sense of natural lifespan and lower medical costs) to those without, creating a solid scientific rationale for eugenics. Think of it as redlining carved into our blood.
I don't think discrimination against the genetically modified is the only potential problem here.
As humans, we'll deal with these problems the way we've dealt with everything else transformational. Namely: very, very badly.
If it turns out some pathogen or chemical made me autistic, regardless of whether or not I could be cured as an adult, I'd have certainly preferred to live the reality where I had been as a child.
I'm not going to claim that I know the perfect place to draw the line.
To me the wildest scenarios take this off the table.
Nothing in medicine is certain. Nearly any medical treatment has a small chance it could kill you. There’s a small, but non-zero chance of a lethal infection even if they injected you with saline, odds that rise dramatically in less than sanitary conditions.
Ironically the use of the attenuated oral vaccine for polio was because of the risk of infection in places where the availability of sterile syringes was hard to guarantee. It’s all about the relative odds.
I also think that gene repair is a net positive. I would just like us to, for once, look ahead and foresee some of the foreseeable consequences and act to mitigate them before the bulk of the damage is done.
I don't think it's necessary to slow the development; gene therapy is too desperately needed, and slowing it down so that we can prepare is not going to cause us to prepare.
Assuming requisite safety of course.
If we could make most children smart, productive, ambitious, courteous, civil, conscientious, honorable, strong... the value to society is probably high enough to justify covering it for almost anyone.
Somehow society (or indeed parts of it) decided to use it as a tool of further segregation rather than overall prosperity. I’m afraid same might apply to this.
I don't really see how this affects e.g. what I do for my children. I will absolutely be turning them into the closest to superhuman the current state of treatments lets me, traveling internationally if I need to. If someone else decides to segregate access to treatment, that is a separate, wrong act that will not hold me back from giving my children every advantage possible.
(Yes, I understand this is a positional arms race, but 1. that doesn't change the individually-optimal outcome, and 2. that doesn't change that society net benefits from it.)
I am, afraid, that this kind of genome modification will further increase divide in a society and turn social lifts off even more. I.e. it's not gonna be your kid to get "improve" brain genes first, and later your kid wouldn't get a chance to get it ever again for their children.
Just to be clear I'm not against of the progress, this thing is fascinating and really shows how awesome humans are. And I get why you'll get it if possible for your kid. I'm just not sure its benefits for the society mean it's gonna be anyhow affordable for regular people.
> use legal mechanisms to discriminate and persecute people who are genetically modified
I believe there is no way this will happen, because legal mechanisms are driven by the whims of the rich, and they will want gene editing to be legal. So there will beno legal mechanisms to discriminate against those who have been edited.
Please tell me there are measures to prevent this going into the wild. Please tell me this won't be used in large-scale industrial farming.
So the real trick here isn't the mRNA, it's the nanobubbles. Basically, you're putting these bits of mRNA into these little fat bubbles and then injecting those into the blood. Making those bubble shelf stable is really hard, hence the issues with temperature and the covid vaccine. To then make those little fat bubbles stable-ish in the blood is also a really hard thing to do. They have to get to the right places (in this baby's case, the liver) and then degrade there, drop off the mRNA, and not mess up other tissues all that much. Like, it's not terrible to make these micelles degrade in vivo, but to have them do that and not degrade in the tubes, ... wow... that is really difficult. There's a reason that Moderna is so highly valued, and it's these bubbles.
To try to then put these in a weapon that could do this though the airways would be, like, nearly impossible. Like, as in I think the second law of thermodynamics, let alone biology, and then simple industrial countermeasure like a N95 respirator, yeah, I think all of that makes it pretty much impossible to weaponize.
(Hedging my bets here: I don't know if they had to do all that with this baby, as you can kinda go from lab to baby really fast, since it's such a special case. But for mRNA based vaccines and cancer treatments, you have to deal with the shelf stable issue)
(Also, other bio people, yes, I am trying to explain to laymen here. Please chime in and tell me how I'm wrong here)
Something that a lot of people are unaware of is that US Military is allowed to do this. I forget the exact EO, but it was signed by Clinton and is in the 12333 chain of EOs. Mostly, this is used for the Anthrax vaccine. But, it does give clearance to do other forms of medical experimentation on warfighters.
No, really, I am serious here. This is true. I may have the details a bit off, so sorry there, but they can and do preform medical experiments on people without their consent. Now, to be fair, France does this too. They do sham surgeries over there. Non-consenting human medical experimentation is quite the rabbit-hole.
So, I can kinda see in the next 10 years, certainly the next 50, a routine shot given to warfighters to help them with things like blood loss, or vitamin C production, or fast twitch muscles, or whatever. The legal framework is already there and has been for a while, it's just an efficacy issue, honestly.
I cannot imagine a more effective weapon than an invisible gas that melts you alive, and there are MANY chemical and bio examples of these types of weapons.
That’s the story but it doesn’t hold up. Chemical weapons were used as recently as the Syrian civil war. I also think if they were really effective in modern warfare, Russia would have long ago deployed them in Ukraine.
More here: https://acoup.blog/2020/03/20/collections-why-dont-we-use-ch...
Nowadays we have riot control agents that can be tailored to demographics, react more violently in the presence of sweat, or contain psychoactive ingredients. Nanoparticle dispersion bypasses common gas masks and clothing protection. Even if you’re completely geared up, they can be engineered to last on surfaces for a long time, or react only in the presence of certain triggers. Imagine thinking you’re safe until someone turns on a certain light bulb and you cook inside your protective gear because you were actually exposed 12 hours earlier in an undetectable manner.
Additionally, that “if you can find them” is doing some pretty heavy lifting. The range of explosives and kinetics is hilariously low, and the actual percentage of your military with the level of mobility he seems to be referring to is infinitesimal.
This argument more correctly explains why chemical weapons aren’t a great defense against precision strike groups. It also doesn’t get into detail with concepts like dropping a bomb right in the middle of a firefight knowing it literally cannot harm your own troops, short of the physical metal accidentally falling on one of your own troops.
A terror attack on civilians is a lot different than modern militaries using them on each other.
Yes, it isn't effective outcome in terms of meeting their objective
> It also doesn’t get into detail with concepts like dropping a bomb right in the middle of a firefight knowing it literally cannot harm your own troops
That's a video games logic, it doesn't work like that in practice. Even civil grade riot control tear gas grenade is pretty traumatic because it still explodes to disperse the gas (source : implied first hand knowledge). That and warfare is messy, which means half the time half the protective gear will be destroyed from the usual exploding and shooting happening, gas gets carried away by the wind in a random direction, etc, etc.
No, it’s science. There are about a million ways to protect your own troops if that’s actually what you want to do.
It feels like you’re arguing against the idea of chemical weapons from the 1940s, rather than nearly a century later.
You don’t need protective gear. You can create sprays, lotions, inhalants, and other countermeasures that don’t stop working the second a piece of cloth rips. Shit, You could make a biological agent that avoids a DNA marker created with an mRNA vaccine. Likely not nearly as fast, but perfectly lethal.
Modern chemical weapons and biological weapons are absolutely incomparable to their Vietnam counterparts.
The reason that the body doesn't alarm as much to Pseudouridine, is that it's not a 'natural' RNA base. Meaning that, for the most part, nature really never uses it and so we haven't evolved to look out for it. Nature uses Uridine and so immune systems have evolved to look out for random bits of RNA in the body that use it and then clean that all up.
It's like if you're looking to clean up legos in you house with a romba that only cleans up legos. And all of a sudden it finds a duplo. It's going to take a hot second to figure out what to do with the duplo. And in that time, you can sneak by and build a duplo fort. (Look, I know this analogy is bad, but it's the best I can come up with on the fly, sorry. If anyone else wnats to come up with a better one, please do!).
The Pseudouridine is used up and degraded very quickly inside the cell, minutes at the very very longest, more like microseconds. It's just part of a messenger (the 'm' in 'mRNA') to tell the cell to do things.
You might see mRNA gene editing in factory farms, but it would just be easier to do germline editing instead and skip spraying animals, plants, and fungi. Why waste the equipment, right?
If anyone else does know, please chime in!
https://www.statnews.com/2017/01/10/moderna-trouble-mrna/
By the time COVID vaccines came around a few years later there was no evidence they had fixed the problems with lipid nanoparticle delivery. I looked for such evidence extensively at the time, for example, announcements by Moderna of breakthroughs or trials of new drugs. Today the situation seems not much different. Note that Moderna's wikipedia article has a section on "rare disease therapeutics" but it's literally empty:
https://en.wikipedia.org/wiki/Moderna#Rare_disease_therapeut...
Because of their failure to progress beyond COVID vaccines Moderna's share price got slaughtered, falling from a peak of ~$450 to ~$25 today.
I don't know if other companies were able to find breakthroughs here, after COVID I stopped following the topic. Unfortunately, although mRNA tech has great potential, when normal safety standards were reimposed it appears that Moderna went back to being unable to make anything safe enough to launch.
But we didn't take these vaccines once. We took many of them. Am I to understand a known side effect is liver toxicity for multiple doses?
It's easy to find papers discussing the problem, just search Google Scholar. Example:
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1002/prp...
Integration was proven in 2024, unfortunately :(
https://www.medrxiv.org/content/10.1101/2024.03.24.24304286v...
"Of the S1 positive post-vaccination patients, we demonstrated by liquid chromatography/ mass spectrometry that these CD16+ cells from post-vaccination patients from all 4 vaccine manufacturers contained S1, S1 mutant and S2 peptide sequences"
They can tell the difference between vaccine spike and virus spike as the vaccine spike was modified for stability. The exact pathway is speculated to have been DNA contamination due to manufacturing process defects. Sequencing of vaccine vials has shown far higher levels of DNA contamination than is considered safe, and the lipids would bring DNA into the cells just as well as they do mRNA making the safe levels much lower still.
https://www.medrxiv.org/content/10.1101/2024.03.24.24304286v...
But yes further study has to be made.
Given the merry movement to call the COVID vaccines gene editing, it rankles.
Do you know of any good resources that I can use to get up to speed on the exact methods they used for the baby?
My understanding, outdated as it is, is that we're using the mRNA to go in and create CRISPR-CAS9 slicers/dicers and additionally to that, the correct genes (not mRNA) to get stitched in. I would love to know more about how I am wrong here, as I am sure I'm not even close to really understanding it.
Thanks!
EDIT: well, I suppose the question is whether cells of living beings could produce the U required for the viruses. But if not, then a wild virus using U instead of T to bypass our immunity also would not be a threat for that very reason.
Basically, the real deal technology here is the lipid bubbles that deliver the payloads to the right cells, not the base modification. You can go look at them, and a lot of other comments in this thread for more info on that tech.
TLDR: No way that anyone can bypass anything. These lipid bubbles are a miracle that they work at all; they're so unstable, it boggles the mind we can even use them to begin with. Doing any large scale DNA editing on an unsuspecting population would be so insanely expensive and difficult, I certain moving to the Moon would be cheaper.
One of the treatments for sickle-cell involves switching off the gene that makes the malfunctioning red blood cells, but of course that's not sufficient; you'd stop making red blood cells completely and you'd die. So it's combined with a modification that switches on a gene that all humans express pre-birth that causes your body to make "super-blood": red blood cells with significantly more binding points for oxygen. This is necessary because a fetus gets oxygen from its mother's blood, so the increased binding affinity is useful for pulling the oxygen towards the fetus at the placental interface. After birth, expression of that gene is disabled and regular RBC genes switch on.
So the therapy doesn't "fix" sickle RBCs; it disables the body's ability to make them and re-enables fetal RBCs! I have seen no literature on whether having fetal RBCs in adulthood has any benefits or drawbacks (besides changing the affinity ratio for their fetus if the patient gets pregnant, I imagine increased-affinity RBC could help for athletics... But I also imagine it requires more iron to generate them so has dietary impact).
From shadowgovt:
> I have seen no literature on whether having fetal RBCs in adulthood has any benefits or drawbacks (besides changing the affinity ratio for their fetus if the patient gets pregnant
This was exactly the question that popped into my mind when I read about switching from normal adult RBCs to fetal RBCs: does this therapy reduce the likelihood of carrying a baby to term?
No problems really..never knew I had it until I was told I had thalassemia trait as part of genetic testing. My hemoglobin panel shows fetal hemoglobin.
This is even more great reading behind the above:
After edits were disabled, I thought perhaps there's a page for Charpentier too, which there was, but later than i could edit.
They're both amazing scientists.
https://www.sciencehistory.org/stories/magazine/the-death-of...
This isnt entirely unlike the method mRNA vaccines use. Through some clever biochemistry, mRNA vaccines get bits of code into cells where the cell's built in code compilers manufacture proteins that induce immunity.
We have developed software patches for our biology.
> until it finds the exact DNA letter that needs to be changed.
This pine is disingenuous (at best). There is no way of guaranteeing where the DNA is inserted. It is designed to only slot into a very specific portion of the DNA but they don't have a way to control that precisely, the accuracy is high but "exact DNA letter" is skipping over a few pretty important details.
To be clear I'm not saying it is ineffective or unsafe, only that the claim made is marketing speak and not actually true.
I do still question their claim of 100% precise results though. At least based on that high level description I can definitely see it being safer, but I question any scientific claim that is an absolute.
Specific to the editing vs insertion mechanism, I question how it doesn't run into similar constraints where the mechanics of targeting exact portions of the DNA can occasionally miss or impact the wrong segment of DNA entirely.
I haven't dug as deeply down the base pair conversion though, so I could absolutely be wrong!
I had heard about CRISPR a while back but most reporting on it kind of hand waved over the mechanisms of how it actually accomplishes its work. What these researchers have figured out to make this work absolutely blows my mind.
They specifically tested for off target edits in the mouse study and found no harmful edits (and very rare off target ones). That plus the specific targeting of the liver cells (no germ line effect expected), makes this a low risk approach and certainly better than doing nothing.
An interesting part of the study was determining what a clinical dose _should_ be. You need enough to edit enough liver cells. But don’t really want to completely overdo it to limit potentially negative side effects. Seems like they got it right enough here, with the first dose having some effect and the subsequent dose having more.
The counterintuitive part is how fast thermal motion is relative to the size of dna.
In body temperature water, the thermal velocity of water molecules jostling around everything is ~600m/s. The nucleus of a human cell is ~6µm in diameter. That is, your average water molecule bounces around at a speed that makes it move from one end of the nucleus to another roughly 100 million times per second.
Larger molecules move more slowly, but they still zip around fast enough that nothing needs to "seek" to a specific position in a cell to get there, everything will touch everything just from thermal random walk in a very short time. So how biology works is that inside the cell there might be just one messenger, which will have to hit a specific piece of dna just right in order to do anything, but that's still nearly instantaneous from our perspective.
Essentially you can design an rna molecular that contains a 20 nucleotide long sequence that can target your region of interest, with the caveat that there is a standard recognition sequence proximal to your sequence of interest (PAM sequence)
You'll end up with mosaicism (cells with different DNA) but presumably you have enough of the new cells to fix the problem the original ones had.
You don't need to fix all the body, you just need to fix some of the, say, liver, and you're good.
> The implications of the treatment go far beyond treating KJ, said Dr. Peter Marks, who was the Food and Drug Administration official overseeing gene-therapy regulation until he recently resigned over disagreements with Robert F. Kennedy Jr., the secretary of health and human services.
For example it's no coincidence this is a liver disease as basically almost everything you inject in the bloodstream ends up concentrating in the liver by default - if you needed to target another organ with your LNP it would be much harder. Most of the time people are trying to stop stuff accumulating in the liver!
The liver has other special properties that are helpful as well.
Having said all that - it is still a massive achievement.
> That is one of the most incredible things I have ever read.
Biology is incredible - and you can do incredible things if you leverage it.
solvable
- able to dissolve in solvent
- able to be solved.
Here is a use in the title of a quite famous popular science book from the 1960's.
https://www.routledge.com/The-Art-of-the-Soluble/Medawar/p/b...
For those who don't understand this stuff - we are now capable of editing some of a body's DNA in ways that predictably change their attributes. The baby's liver now has different (and better) DNA than the rest of its body.
We still are struggling in most cases with how to deliver the DNA update instructions into the body. But given the pace of change in this space, I expect massive improvements with this update process over time.
Combined with AI to better understand the genome, this is going to be a crazy century.
Further reading on related topics:
https://www.lesswrong.com/posts/JEhW3HDMKzekDShva/significan...
https://www.lesswrong.com/posts/DfrSZaf3JC8vJdbZL/how-to-mak...
https://www.lesswrong.com/posts/yT22RcWrxZcXyGjsA/how-to-hav...
They think that the key to scientific thinking is to forego the moral limitations, not to study and learn. As soon as you're free from the shackles of tradition you become 100% rational and therefore 100% correct.
Like, I'm sure there are people who approximately match the description you're giving here. But I've spent a lot of time around flesh-and-blood rationalists and EAs, and they violently diverge from the account you give here.
The key to scientific thinking is empiricism and rationalism. Some people in EA and lesswrong extend this to moral reasoning, but utilitarianism is not a pillar of these communities.
On the other hand, maybe that is some kind of fallacy itself. I almost want to say that "scientific thinking" should be called something else. The main issue being the lack of experiment. Using the word "science" without experiment leads to all sorts of nonsense.
A word that means "scientific thinking is much as possible without experiment" would at least embedded a dose of skepticism in the process.
The Achilles heel of rationalism is the descent into modeling complete nonsense. I should give lesswrong another chance I suppose because that would sum up my experience so far, empirically.
EA to me seems like obvious self serving nonsense. Hiding something in the obvious to avoid detection.
A good name might be rational Altruism because in practice these people are from the rationalist movement and doing Altruism, or what they feel is Altruism. But the "rationalist" title suffers from similar problems.
They might have lost the plot somewhere along the line, but the effective altruism movement had some good ideas.
Color me unconvinced. This will work for some situations. At this point, it's well known enough that it's a target that has ceased to be a good measure (Goodhart's Law).
The usual way to look at this is to look at the percentage of donations spent on administrative costs. This makes two large assumptions: (1) administrative costs have zero benefit, and (2) non-administrative costs have 100% benefit. Both are wildly wrong.
A simple counterexample: you're going to solve hunger. So you take donations, skim 0.0000001% off the top for your time because "I'm maximizing benefit, baby!", and use the rest to purchase bananas. You dump those bananas in a pile in the middle of a homeless encampment.
There are so many problems with this, but I'll stick with the simplest: in 2 weeks, you have a pile of rotten bananas and everyone is starving again. It would have been better to store some of the bananas and give them out over time, which requires space and maybe even cooling to hold inventory, which cost money, and that's money that is not directly fixing the problem.
There are so many examples of feel-good world saving that end up destroying communities and cultures, fostering dependence, promoting corruption, propping up the institutions that causing the problem, etc.
Another analogy: you make a billion dollars and put it in a trust for your grandchild to inherit the full sum when they turn 16. Your efficiency measure is at 100%! What could possibly go wrong? Could someone improve the outcome by, you know, administering the trust for you?
Smart administration can (but does not have to) increase effectiveness. Using this magical "how much of each dollar... ends up being used to fix some problem" metric is going to encourage ineffective charities and deceptive accounting.
As someone who has occasionally given money to charities for homelessness and the like I don't really expect it to fix much. More the thought that counts.
In reality, they're simply lay people who synthesize a lot of garbage they find on the Internet into overly verbose pseudo-intellectual blog posts filled with both the factual inaccuracies of their source material and new factual inaccuracies that they invent from whole cloth.
I posted a question where I referred to something by the wrong name.
Someone said I was confused / wrong, so I corrected myself and restated my question.
For some 10 minutes they just kept dogpiling on the use of the wrong term.
Never a bunch a stupider people have I met than LessWrong people.
50 replies arguing about how you can simplify your for() loop syntax and not one reply with an actual answer.
I still think there's a lot to learn from those articles for most folks uninvolved in this area, even if some of their immediate optimism has additional complications.
I think what I mostly took away is a combination of technologies is likely to dramatically change how we have babies in the future.
1. We'll make sperm/egg from skin cells. This has already been done in mice[1], so it is not science fiction to do it in people.
2. When we're able to do this inexpensively, we could create virtually unlimited embryos. We can then select the embryos that have the most optimal traits. Initially, this may be simple things like not choosing embryos with certain genes that give higher risk of certain diseases.
This may involve selecting traits like intelligence and height (there are already companies that offer this embryo selection capability [2]).
3. Instead of creating a lot of embryos and selecting the best ones, we could instead create just one embryo and edit the DNA of that embryo, which has already been done in humans [3]. Alternatively, we could edit the DNA of the sperm/egg prior to creating the embryo.
The fact that none of this is science fiction is just wild. All of these steps have already been done in animals or people. Buckle up, the future is going to be wild.
[1] https://www.npr.org/sections/health-shots/2023/05/27/1177191...
[2] https://www.theguardian.com/science/2024/oct/18/us-startup-c...
[3] https://www.science.org/content/article/chinese-scientist-wh...
- how further can we push this to make the best, most optimized human?
- what are moral implication of this?
- what are the side effects / downsides?
What gets harder are polygenic traits that even today we don’t have great data on what are the causal alleles. But that is also not a technological limitation either but a statistical one from insufficient sampling of these polygenic phenotypes.
There are lots of hereditary illnesses and conditions that could probably be tweaked with DNA editing, if we can identify the responsible genes. If someone can cure male pattern baldness they’ll be rich.
Eventually this will be the outcome of our species to edit the gametes themselves. The issue to overcome for this again won’t be technological as that is pretty much solved but getting people over their own “ick” factor.
>>>Eventually this will be the outcome of our species to edit the gametes themselves. The issue to overcome for this again won’t be technological as that is pretty much solved but getting people over their own “ick” factor. This is a new fear unlocked, as this will be like another cosmetic surgery procedure, which from my minimal understanding does not affect DNA that is delivered to offsprings - that could be changed but require a lot more work, but like you mentioned - it is easier to do before fertilization :). It is catch22 situation rn.
Probably requires getting investors over their profit incentive first, why treat a heritable disease for the offspring if you can charge them on a per person basis?
How to avoid having only parts of the liver with the new DNA, and some other parts with the old DNA? Like a chimeric liver - isn't this something bad?
Really incredible story and I'd love to know the process for receiving this, for example FDA approval etc. It's nice to see such in-your-face results from Federal funding programs. Without being political, it's sometimes hard for regular people to appreciate just how much good actually comes out of Federal Funding. There was another thread where someone even said something along the lines of : "Well during war things get done faster" . This simply isn't true. It might be done louder but Federal Funding never stopped pushing things forward.
"The implications of the treatment go far beyond treating KJ, said Dr. Peter Marks, who was the Food and Drug Administration official overseeing gene-therapy regulation until he recently resigned over disagreements with Robert F. Kennedy Jr., the secretary of health and human services."
"But KJ’s treatment — which built on decades of federally funded research"
"The result “is a triumph for the American peoples’ investment in biomedical research,” Dr. Urnov said."
"The researchers emphasized the role government funding played in the development."
"The work, they said, began decades ago with federal funding for basic research on bacterial immune systems. That led eventually, with more federal support, to the discovery of CRISPR. Federal investment in sequencing the human genome made it possible to identify KJ’s mutation. U.S. funding supported Dr. Liu’s lab and its editing discovery. A federal program to study gene editing supported Dr. Musunuru’s research. Going along in parallel was federally funded work that led to an understanding of KJ’s disease."
"“I don’t think this could have happened in any country other than the U.S.,” Dr. Urnov said."
This is an article about federal funding of medical research with a cute baby as the human interest bit.
https://innovativegenomics.org/news/first-patient-treated-wi...
It’s crazy encouraging that this worked out for this kid, and I’m somewhat shocked this treatment was approved in the US - I don’t think of us as very aggressive in areas like this. But to me, really hopeful and interesting.
Right off the bat, the liver receives roughly a quarter of all cardiac output, either directly or second hand from the digestive organs. Additionally, the liver has a fenestrated endothelium which, while not completely unique in the body, uniquely allows molecules like lipid nanoparticles (LNPs) to access liver cells. Finally, the liver is the site of most lipoprotein processing, and LNPs can be designed to take advantage of the existing pathways to get the gene editing mRNA into the hepatocytes. All this is to say that if you have a genetic condition that primarily effects the liver, there's a lot more hope for treatment in the near term than for others.
Good lecture on the difficulties of finding appropriate platforms for delivering gene therapies to cells for anyone interested [1]
mRNA vaccines are highly localized: you get a sore arm because most of it only gets taken up by muscle cells around the injection site, which spend some time producing the antigen and triggering a primary immune response (the inflammation aka the sore arm).
As for being localized it's true however after vaccine dose S proteins have been detected also in remote locations in the body because you can't make something 100% localized.
If you had an infusion that doesn't trigger immune system you could just increase the dose significantly, put it in the blood and most likely it would have reached all cells that blood reaches.
But I'm speculating a bit here.
I can remember getting a sniffle at night and waking up fine the next morning a few times.
I think I had two doses of covid mRNA vaccine.
I have actually forgot what it is like to be sick. It almost feels like the covid vaccine gave me some kind of super immunity. I never get the flu shot either. I have not had the flu in 5 years for sure.
People born with this lack the enzyme CPS1, which screws up the urea cycle and causes a build up of ammonia. Ammonia build up is bad for your nervous system.
As to the FDA stance, it tends to be more willing to go ahead with compassionate uses like this when it's clearly life or death.[1]
[1] https://www.statnews.com/2025/05/15/crispr-gene-editing-land... This discuss a little of the FDA stuff but not much more detail, it sounds like they did let them skip some testing.
Three interesting thing come out of it from me. First, I was on Microsoft insurance which was quite gold plated at a time, a blessing only obvious in rear-view mirror, because Childrens was quite excited to continue any number of tests. Second, the technology of all this is absolutely amazing and I am so happy that it was available to me, and it has likely gotten better. Three, I want that tech to continue to expand and current destruction up there is going to hand this torch to someone else, which makes me sad.
One of the biggest perks of working for Microsoft for a long time was their health coverage. I can't tell you the number of times I'd be doing initial paperwork for a doctor's appointment and the receptionist would be like, "Oh you have THAT insurance, we're going to do all of the tests." I've heard they since cut back on it a little, but it truly was gold plated.
What America really needs is an NHS not tied to employment or exploited by fraudsters delivering worse care for profit. Human rights shouldn't be perks of employment.
Pretty much every lab test is available in Australia if you are willing to pay for it; if they don’t have a local lab capable of running the test, they’ll send the sample overseas
The real question is whether it is covered by insurance or not, and a lot of the time the answer is “no” - I recently forked out over US$500 for genetic tests on one of our kids (which the paediatrician recommended), although the results weren’t particularly helpful (“rare variant of uncertain clinical significance”)
I know this is an issue with caesarean section. It is becoming more prevalent because those who require it are surviving, making it more likely to happen in their offspring.
Hopefully not, but even then no one can say what progress will make science in the next 25 years.
Back in the 50's people thought we would be driving in flying car in 2000.
You can't compare that to gene-editing treatments, that's two completely different level.
Self driving car were always almost feasible, 20 years ago top gear made cars you could drive with controller like kids do with toy cars. We already had camera and computer, it was just a matter of raw CPU performance and software development..
Just because you can hit some germ-line cells in the liver, for example, doesn’t imply you’ll have good penetration into the reproductive organs.
We can’t zap people and change all their DNA at once, unless we can intervene at the point it’s just a few cells.
>>>There are also medical procedures (PGD) to bring that chance to virtually 0%. For that one gene only. DNA is a math of sum of genes and from what I have read humans are not better than nature(which is not perfect, but very basic) at selecting best specimens of eggs and sperm, but yes - whatever they have picked - PGD might be able to root out that one single mutation, and introduce variety of other mutations or miss good genes from other combinations. So, it all depends...
You state this as a fact and I've heard it as a strong hypothesis, but I wasn't aware of much evidence to confirm it?
https://www.ncbi.nlm.nih.gov/books/NBK546707/
"If this trend continues, by 2030 the highest rates are likely to be in Eastern Asia (63%), Latin America and the Caribbean (54%), Western Asia (50%), Northern Africa (48%) Southern Europe (47%) and Australia and New Zealand (45%), the research suggests."
https://www.who.int/news/item/16-06-2021-caesarean-section-r...
Note: Coincidentally, WHO's article I've linked is lamenting that Sub-saharan Africa only had 5% cesarean due to less availability of the procedure. It is their perspective that the increase in percentages is a good thing and indicates progress, instead of being concerning. And, they find Sub-saharan Africa's low numbers concerning, instead.
Side Note: I also found lots of interesting articles which I haven't posted here, about epigenetic side effects caused by caesarean deliveries like leukemia, illnesses and other genetic issues. But, that seems out of scope for your question. You can make a quick search and find these, though.
"A female-to-female familial predisposition to caesarean section was observed. It could be caused by biologic inheritance, primarily working through maternal alleles and/or environmental factors. The results imply that both mechanisms could be important."
https://pubmed.ncbi.nlm.nih.gov/18540028/
"Large-scale epidemiological studies indeed evidence that women born by C-section are more likely to deliver by Caesarean than women born vaginally, owing primarily to genetic rather than social factors."
Pretty sure their perspective is that "saving the lives of mothers and babies" indicates progress.
> While a caesarean section can be an essential and lifesaving surgery, it can put women and babies at unnecessary risk of short- and long-term health problems if performed when there is not medical need.
> Rather than recommending specific target rates, WHO underscores the importance of focusing on each woman’s unique needs in pregnancy and childbirth.
> WHO recommends some non-clinical actions that can reduce medically unnecessary use of caesarean sections, within the overall context of high quality and respectful care:
That's the potential conundrum, if it turns out to be vastly increasing the need to save those lives than in the past due to a evolutionary pressure on the gene pool. If the WHO is right and we're going to start seeing 50 - 63% increases by 2030, what's in store for the human race if this rate of expansion keeps up?
Will we reach a time when no one can be naturally born and almost our entire race has to be conceived in external gestation devices or cease to exist? And, when we reach that point will we look with concern towards Africa and wonder at how sad it is they're still conceived naturally.
Edit: I don't have the answers. I'm not sure what we should do to course correct or if we need to. But, it is definitely something that should be looked into before it is too late, if it isn't already. And, that is why I brought it up in the context of this breakthrough, to ask if we've considered similar consequences. And, if we have a way to mitigate them if that turns out to be the case.
"A female-to-female familial predisposition to caesarean section was observed. It could be caused by biologic inheritance, primarily working through maternal alleles and/or environmental factors. The results imply that both mechanisms could be important."
https://pubmed.ncbi.nlm.nih.gov/18540028/
"Large-scale epidemiological studies indeed evidence that women born by C-section are more likely to deliver by Caesarean than women born vaginally, owing primarily to genetic rather than social factors."
Interesting. That makes sense. I wonder if the type of research being pursued in TFA might be helpful.
In any case, I also have to wonder whether it's necessarily a bad thing. I quoted 'natural' births earlier because... what is natural? The amount of medical knowledge and technology that go into births doesn't seem very "natural" to me, and this has advanced through the ages to where we are now - where we, rightfully so, look sadly on areas where lack of such technology and knowledge result in more preventable deaths of babies, even if their methods are more "natural"
Of course, to be honest, I'm not very familiar with the pros and cons of c-sections vs natural births - particularly when the question is whether to have a child. I suppose that, given the choice between a c-section and the alternatives, most women will opt for a c-section, and as you point out, that means their daughters likely will have to as well
So what might the solution even look like, apart from exploring the aforementioned gene-editing technology - or other technology - to prevent the genetic factor of c-sections? I would hope that "don't offer c-sections" is not a serious option. "Stop having kids" is one I'd personally suggest, but that's obviously not a sane global solution either.
It's an interesting problem I'd be curious to hear more about - as I said, I'm not very familiar with this.
To reply after a certain number of child comments, you have to open the comment by clicking the timestamp thing
I'm also afraid I don't understand your response. Can you elaborate?
We met again.
We know that infants are generally larger than 50 years ago and one of the factors which trigger birth is the inability of the mother's metabolism to support further growth of the fetus.
That, combined with the fact that all over the world availability of nutrition is much better than half a century ago points to this being the culprit.
Do companies like this have a need for SWEs? Are there opportunities for a backend SWE without any background in hardware or biology?
Of course they do. Biology and medical research can't get enough software people. But they're not as well funded as advertising or spying companies, for example, so you might have to take a significant pay cut.
I wouldn't pigeon hole yourself as a "backend engineer". Why do people do that? Software is software. The bit that matters is the core model and algorithms etc. Whether it's exposed as a web server, a CLI or just a library is a peripheral detail.
It's totally possible for a decent software engineer to learn just enough biology to get by. The limiting factor might be your interest, though. But if you have that then go for it. Get a book on genomics right now.
https://jobs.danaher.com/global/en/search-results?keywords=S...
There are two categories of software we need help with:
1. Salesforce for science. We don't have big data in terms of volume; we have big data in terms of heterogeneity. Tons of small data sets that need context to be interpreted, including measuring uncertainty. This software, often called an eLN or LIMS, is offered by expensive vendors who each have their custom, locked-in implementations. Every organization needs customization on top of this that can be developed and change with the changing direction of the bench scientists.
2. Informatics tools. Much of the heavier computational tools (bioinformatics, molecular dynamics, stats) were developed by academic labs, who don't have the training or incentives to create sustainable software. Alternatively, they are made by vendors who write software on short-term contracts, so they don't have expertise in house. Our mass spec vendor told us to put their analysis servers on our Citrix so employees could access it. Citrix! If you can convince those vendor to hire you and rewrite their software, please do.
Despite cool tools like alphafold making headlines, the software needs in drug development are more mundane. We need people who are excited to sit down with bench scientists and help them figure out how very normal tools can be applied to their work.
This is SO exciting! The fact that there is a chance of a cure has absolutely made my day!
To those thinking about commercialization opportunities, these two steps seem the most labor intensive and time consuming, but also the most necessary in order to actually have confidence to inject completely customized gene editing therapy in a kid.
(Also worth highlighting for folks opposed to animal research.)
Somatic editing is becoming more common (see Casgevy) but there are technical hurdles that prevent its application to many cases.
Genuine question- how do we know that? Is it just that the edits are very improbable to accumulate in the gonads in sufficient quantities to persist? We can’t actually prevent some fraction of them from reaching other parts of the body, right?
This is _not_ the first human to be treated with a treatment under the wide umbrella of gene therapy based on their own edited genes. There probably is a more narrow first here but the technical details get lost in journalism which is a shame.
What's intriguing is not the 'custom' part, but the speed part (which permits it to be custom). Part of what makes CRISPR so powerful is that it can easily be 'adjusted' to work on different sequences based on a quick (DNA) string change - a day or two. Prior custom protein engineering would take minimum of months at full speed to 'adjust'.
That ease of manipulating DNA strings to enable rapid turnaround is similar to the difference between old-school protein based vaccines and the mRNA based vaccines. When you're manipulating 'source code' nucleic acid sequences you can move very quickly compared to manipulating the 'compiled' protein.
https://www.npr.org/2023/06/08/1178695152/china-scientist-he...
This research is instead a therapy used to treat an already born baby, and it doesn't modify all the cells in the body. Many cells in the body that are transformed by this technique will eventually die and be replaced by clones of stem cells which weren't transformed. I haven't read in detail about whether this therapy targets stem cells, and how long term effective the treatment will be- hepatocytes (liver cells) turn over constantly, so I would expect if the treatment did not affect the hepatocyte stem cells, it would only last ~months and the treatment would have to be repeated.
A quick search suggests that liver regen involves dividing mature liver cells to replace turnover. If so, I'd suspect that they'd continue to carry the.crispr edit forward.
There could be other babies that can also grow up to be future Hitlers. So let's say 4 such babies exist. By killing one I eliminated 1/4 for futures with Grown up Hitlers that exist.
This whole thread is getting flagged. Likely by an irrational parent who can't even compute natural selection, babe, and Hitler all in a single paragraph.
It’s perfectly reasonable to say that while a technology has the propensity to be used for evil, it also has positive applications and that the real benefit now outweighs the potential downside in a hypothetical future.
Otherwise you will go down a rabbit hole at the bottom of which lies a future where we all just kinda dig in the dirt with our hands until we die because every technological innovation can be used in a variety of ways.
Like, it’s silly to me that I can’t bring a 1.5” blade keychain utility knife on a flight, and then they hand me a metal butter knife in first class. I could do way more damage with that. But they allow the butter knife because the utility has shown to far outweigh the potential downside that hasn’t manifested.
> I will slaughter a baby if I know for a fact that baby will grow up to be the next Hitler
This is one of those things that is easy to say precisely due to the impossibility of it ever actually becoming a real decision you have to make.
It's true. But things like this should be easy to say right? Like we may not be able to act logically. But we should be able to think logically, communicate logically and show that we are aware of what is logical.
My post got flagged meaning a lot of people can't separate the two things. So for example I may not be able to kill the baby in reality, but I can at least see how irrational I am.
The person who flagged me likely not only can't kill the baby. He has to construct an artificial reality to justify why he can't kill the baby and why his decision must be rational.
It would maybe be easier for a 15-25 y.o. to kill a baby they don't know and whose parents/family they don't know, and maybe even easier if they don't speak their language or look like them. Of course, the baby wouldn't be the only one you'd have to kill, most likely.
I submit that it would be very very different if you found out that your 4 year old child was going to go on to be the next Hitler. For a "normal" person, I think they would go to the ends of the earth to try to shape them into the kind of person that wouldn't do it. I think very few people would coldly calculate "welp, guess I gotta execute this adorable little child I've grown so attached to" as it looks up at them saying "I love you so much forever, mommy/daddy" with their little doe eyes.
(ETA: it also brings up side questions about nature vs nurture and free will)
And then consider the lifelong repercussions of the emotional fallout. You can use all the logic in the world to justify the action, but your human brain will still torment you over it. And likely, most of the other human brains that learn about it would torment you as well.
---
So, while I think you can say things like that, ie the ability and allowance, I think you should question whether you should. I think saying those kinds of things really doesn't add much to the discussion because I believe it's really just an uninformed platitude that only someone with a lack of life experience would believe.
For me this all highlights the fact that meaty ethical questions don't have a simple reductive answer. Which ties back in to the original problem that OP outright states that this is simply and clearly the wrong path to go down.
(PS the downvoting/flagging could be due to breaking the guidelines around discussing downvotes and flags, and not actually due to the topical content of the posts, and/or assuming bad faith on the part of other users as such: https://news.ycombinator.com/newsguidelines.html)
You should because many choice in life are not strictly black and white. Saving a babies life versus introducing gene editing to humanity. If there was a baby where we knew he would grow up to slaughter millions it's absolutely worth talking about. In the age of AI and gene editing where things are influencing what it even means to be human, it is wise to stop and pause for a minute to ask the right question rather then charge forward with change that can't be taken back all because we wanted to save a baby.
Answering the real question- it's unlikely these techniques will see widespread "recreational" usage any time soon, as they come with a wide range of risks. Further, the scientific community has learned a lot from previous eugenics programs; anything that happens in the future will happen with both social and political regulation.
It's ultimately hard to predict- many science fiction writers have speculated about this for some time, and social opinion can change quickly when people see new developments.
It will be that people just don't have children at all.
If you want make your baby smarter, taller, or more handsome, it's not so easy because these traits involve 1000s of genes.
For this reason I do not think that curying diseases will lead to designer babies.
I'll steelman "fixing defects" by sticking to serious hereditary diseases (and yes, only those that correspond to one or a few known genes). As more and more conditions become treatable, the population with access to resources will have lower healthcare costs by being less susceptible to problems. (Which is a good thing, note!) Insurance companies will have more and more proxies for differentiating that don't involve direct genetic information. Societally, "those people" [the poor and therefore untreated] cost more to support medically and are an increasing burden on the system. Eugenics gains a scientific basis. Do you want your daughter marrying someone genetically substandard, if you don't have the resources to correct any issues that might show up? Probably not, you're more likely to want to build a wall between you and them. Then throw over anyone who falls behind the bleeding edge of corrections.
It'll be the latest form of redlining, but this time "red" refers literally to blood.
But, I think that it's misguided to apply the human problem of othering to a given technology. Regardless of technology X, humans are gonna human. So, if X helps some people, we should consider it on that basis. Because without X, we will still have an endless stream of other reasons to draw red lines, as you allude to. Except in addition we'll also still have the problem that X could've helped solve.
If gene editing to cure diseases leads to a future where people want to shunt off the poor that are now the outsized burden of the healthcare system, the answer from where I sit is to find ways to make the gene therapies available to them, not to cart them off to concentration camps while they await extermination. This will require all the trappings of human coordination we've always had.
Preventing X from ever coming to fruition doesn't at all prevent all possible futures where concentration death camps are a possibility. To me they are orthogonal concerns.
Even if you can convince one culture/society not to do it, how do you stop others? Force? Now you have a different manifestation of the same problem to solve. Society needs to learn how to "yes, and..." more when it comes to this stuff. Otherwise, it's just war all the way down.
> This will require all the trappings of human coordination we've always had.
It is also true to say that we've never had it as quickly as it has been needed, and neither is it done as well as it needs to be. We will blunder into things that are easy to predict in advance if we are willing to look and accept what we see, but we won't.
I absolutely agree that this advance is a great thing and should be pursued further. But I also think that simply categorizing it as good or bad is a way to willfully ignore the unintended consequences. We should at least try to do better.
> Society needs to learn how to "yes, and..." more when it comes to this stuff.
Absolutely. I just think that requires nuance, wide open eyes, and acceptance of uncomfortable truths. Part of the nuance is not boiling it down to a yes/no question of "should this proceed?" (For example, how about: "How can we utilize these new capabilities to maximize benefit and minimize harm, when the only real lever we seem to have to work with is the profit motive? Everything else is getting undermined in its service.")
Well, you're wrong. Where is the line drawn for what constitutes a disease? Retardation? Autism? Eventually every child below, say, 130 IQ will be considered disabled and unable to find work.
Apply this to every other trait: cardiovascular health, strength, height, vision, etc. All forms of weakness can be considered a disease. The end product of eugenics is that mankind will be made into a docile and fragile monoculture.
>If you want make your baby smarter, taller, or more handsome, it's not so easy because these traits involve 1000s of genes.
And? it's obvious that the technology will eventually be capable of this, just not all at once. It starts with single-gene mutations, then it will be 10's of genes, and then hundreds and thousands.
That is the slippery slope: there is absolutely nothing about your reasoning that prevents one step from leading to another.
It's helpful to evaluate claims on this thread in the context of the story. It's possible (though still a very open question) that complex behavioral traits will generally become predictable or maybe even controllable in the future. But those would require breakthroughs (including basic science discoveries breaking in the direction baby-designers want them to) more significant than the announcement on this story.
There's no inherent metaphysical worth in being on any particular level of strength, height etc., so we can spread whatever is the most convenient. I think arguments against (that I see being made) ultimately devolve into some magical thinking and a priori thing bad. (I am glad to be shown otherwise.) In fact we are already messing with human fertility in possibly unsustainable ways, so maybe more tools are needed as a part of the way out.
Of course there is political execution, corruption etc., but I don't see it any different from other technological challenges that civilization has dealt with. I.e. we need better politics but the tech is not at fault. Gene editing is isolated interventions, so it's in that detail more manageable than for example mass surveillance which is hidden and continuous.
One more esoteric argument is that we cannot socially agree on what traits are desirable. The ‘The Twenty-first Voyage of Ijon Tichy’ scenario. So opposite to "monoculture" in a way. But I don't see people expanding on that.
From an evolutionary perspective it‘s interesting how the further medicine gets, the more we inherit genes unfit for life without medical support.
No, it would not depend on the sex of the baby, as the chromosomes that you're editing aren't X or Y.
Evolutionarily, the inheritance of genes is a far slower process than the medical advancements we make, so what I think we're seeing here is a chasing down of the low probability events. In that, most of the evolutionary pressure is coming from things like dirty water and bad food, but as we're solving those low hanging fruit, we have to go to lower probability events to make progress that feels equally important.
Also, if I am wrong here on the answers to the questions, please correct me!
Organs in your body usually keep some very old cells (formed in the embryo) around which act as parents for all the new cells in an organ. Any cell can only divide a limited number of times, so they typically maintain a "tree structure" where the old cells create children and grandchildren (etc) that then differentiate into the organ-specific cells that do the actual organ work.
If you modify only the differentiated cells, eventually they die, and are replaced by descendents of stem cells; if those stem cells didn't get modified, their descendents will not have the fix, and the treatment efficacy reduces over time.
Stem cells from other organs has absolutelly nothing to do with this. Unless you are refering to procedures of planting stem cells from one organ to another to help failing organ, as stem cells are universal cells, that are able to produce cells for any organ.
Anyway, this baby proves we can fix hereditary diseases now.
That comes in many forms:
Black/dark one, nazi style, where you outright sterilise or even kill those with unhealthy/bad genes.
And white/peaceful one, where you‘d appeal to those with unhealthy/bad genes not to procreate and encourage those with healthy/good ones to do.
You can‘t seriously tell me it‘s not extremely unethical for people with huntington‘s disease or cystic fibrosis to have children.
>>>You can‘t seriously tell me it‘s not extremely unethical for people with huntington‘s disease or cystic fibrosis to have children. Don't flatter yourself - your genes are basic and ridddled with bad genes. You do not know what time bomb you are carying in your DNA.
The solution that you are offering is quite simple - procreate early as possible and die not in old age and voila - there are no issues in more than 99.99% cases. But something tells me that you are already older than healthy monkey and do not plan to live in a tree - your bones are too old for that and thanks to evolution are not meant for that.
Evolution of humans in future includes even longer lifespan which naturally comes with children produced at much later age than we do now and that comes with diseases to be dealt with, as that is part of evolution. We do not know much about mutations in DNA - they are never good or bad - they are combinations of something. For example - diabetes type 2 seems to be from genes, that allowed humans to survive hunger for long period of time - are those genes bad, because people are obese nowadays? As for mentioned diseases - we value other humans not by DNA, but what they are to us. You would sing a different song, when their offspring would have any of such disease and you are in luck and not planning to have any.
Second, according to a quick search, 10% of cases of Huntington's Disease are due to new mutations; I suspect (but I'm a HN commenter, no geneticist) this is the case for many other genetic conditions.
So the other ethics question to ask: should people be able to get DNA tests for genetic conditions (voluntary)? I'd say yes. Should people be mandated to get DNA tests and be forbidden to procreate if there's something in there? No, that's eugenics. Should people who know they have a genetic condition and there's a chance their child has it too have children? That'd be their choice. I don't think it's fair for people to intentionally place a burden on health care systems like that, but thing is, there's very, very few people that have children with that as the intent.
https://www.nejm.org/doi/full/10.1056/NEJMoa2504747
This site has a much better write up than the NYT:
https://innovativegenomics.org/news/first-patient-treated-wi...
Under normal circumstances, developing and testing a new CRISPR therapy takes years, but this patient — and others born every day with severe genetic disorders — do not have years to wait. Getting all of the pieces together for this emergency need took rapid coordination amongst teams at multiple academic and for-profit organizations, only possible because of both years of preparation and some lucky connections.
...
Prior to receiving the CRISPR therapy, KJ’s prognosis was poor, but there were several factors that made KJ’s case a good candidate for a rapid CRISPR intervention. An ongoing research study at the IGI called INGENUITI enabled the team to immediately enroll KJ and his parents for genome sequencing and analysis. The mutation in KJ’s genome was a single base — just a one-letter change in his genetic code — and one that could be corrected using base editing, a gene-editing technique that only makes a single-letter edit. Additionally, the researchers needed to edit cells in the liver, where the faulty protein is made. The liver is currently one of the organs in the body that can be targeted for in vivo gene-editing therapies using lipid nanoparticles.
...
One of the first steps involved characterizing the mutation in KJ’s genome and designing the guide RNAs that allow the base editor to precisely target a specific letter in the patient’s genome for repair. Kiran Musunuru’s team at Penn accomplished that in record time. Next, the team at the IGI jumped in to do the necessary safety assessment work so that the FDA could assess the risks.
No.
This procedure costing upwards of $800,000 simply trades one disease process for another.
It would be interesting to find out if this child does indeed end up getting the liver transplant that was sidelined for this new one off procedure.
https://www.perplexity.ai/page/baby-born-with-life-threateni...
Heck, if parents could provide a trust fund for their kids in a way that their kids couldn't piss it away, they'd be all over it. (I'm sure this exists to varying degrees.)
Look at what wealthy parents already do to get their kids into colleges or out of jail. I think it's ridiculously naive to think that we parents wouldn't jump at the chance to write generational wealth into our kids' genes.
(This is not an argument that developing this capability is a bad thing and should be stopped.)
Gattaca was a film years ahead of its time, and raises the question of what happens when people try to "fix" human beings beyond disease prevention. A subtle, but important ethical difference. =3
The more we things we cure the higher we will reach and the higher we reach the higher we will raise the bar. I don't think that's a bad thing, but its worth bearing in mind.
I think it is more likely people will create synthetic diseases by experimenting on human beings with unique unpredictable gene expression.
He Jiankui already crossed the ethical boundary in 2018... only to discover his best intentions were still nonsense. The GMO kids he helped edit will have a lifetime to figure out if that alteration negatively affected them, and as adults consider how their own children may change.
People may cross the "Primum non nocere" line, but it can never ethically be justified =3
Aren’t people dying because they were waiting for FDA approval for other experimental treatments?
I mean the precursor to gene editing is selective breeding, which on humans quickly leads to eugenics.
> “I don’t think this could have happened in any country other than the U.S.,” Dr. Urnov said. > “We all said to each other, ‘This is the most significant thing we have ever done.’”
And then in the Discover More section is this article:
> Lab Animals Face Being Euthanized as Trump Cuts Research
Again
Unless those other countries step up and fund it themselves.
They might. They might not.
The technology used on this same article was funded by Max Planck (Germany), Sweden and the NIH to a french and a USA scientist. Should those collaborations stop?
That is changing. Children in my country are moving from learning English to French and German in order to study in European universities. This started after Brexit and will accelerate now.
By pooling our funding / effort we can create a larger body of collaborators to solve problems faster and better.
It could be that the organizations are funding wild stuff that isn’t salient. I’ll concede that.
However, in basic sciences there are so few specialists it is important to share resources. The funding is worse than ever (hello 2006!), and that trend is unlikely to reverse for a while.
Source: I worked in bioenergetics for 10y, my collaborators were from Hungary, Chile, Canada, Israel, Italy, and more! At a major conference on mito energetics they all fit in one big lecture hall (100ish?)
I guess it's still too early in this story's news cycle for the people with anti-views to be making noise yet. No GMOs, but human gene modification is okay. No cloning either. The boogeyman is gonna get us no matter what we do
It is breathtaking to consider how the members of the Administration and their children, parents, and grandparents have benefited from NIH-funded research in innumerable ways that they are shamefully unaware of, every time they visit the doctor or the ER.
They have created a huge rift in this country and I am still trying to figure out if I will forgive my family members and what they'd have to do to set us on a path towards reconciliation.
When there's a contract in place to conduct pediatric cancer research, and the government decides one day to break that contract, and it takes courts to rectify the situation, and then the government defies the courts, and the voters are cheering on the illegal actions of the politicians, well, rage is a mild word for what I feel.
See also: the paradox of intolerance.
Consider that everyone sees themselves as the hero… but that doesn’t mean you actually are, maybe, just maybe you are just as culpable as the person you’re accusing.
Republicans are currently the ones undermining the foundations or our republic, stripping rights from minorites (Texas just passed a bill that made it illegal to be trans), deporting people with no due process, arresting dissenting politicians and academics.
They're the ones plunging this country into economical ruin, destroying medicare and medicaid to transfer the savings to the 1% through massive tax cuts while letting everyone that depended on these programs die.
Everyone in support of these ideas is intolerant in my book, and I don't see why I should show empathy to a people that would rather see me in a camp.
Just based on the stuff you say here it’s pretty clear you very closely align yourself with “progressive values”. Many studies show that those who hold progressive beliefs, struggle to even accurately articulate the values and beliefs of those they believe they appose. Much less actually understand them.
You very clearly exhibit this behavior as well.
If you can’t understand the person who’s talking opposite you there is no way to come to an understanding, if you refuse to attempt to understand them, you can’t blame them for the state of animosity.
But apparently the partisanship is reversed! You think that I am demanding "perfect empathy" (I am not) and you think I have now shown empathy for my family members (which, you don't know the history). You are describing narcissistic behavior, which is quite endemic in my family members, and having dealt with it for decades I also recognize the attempt to blame others for one's own failing.
Yes, it is all breathtaking, but not in the way you think.
Edit: Still reading the article, but so far researchers working in the US have come from India, Russia, born to Taiwanese immigrants, and more.
Better to have more disabled or dead babies instead of science.
/s
He was jailed for illegal medical practices but it seemed like he established a proper lab after serving the sentence and hopefully he is focused on less objectionable practices. https://www.npr.org/2023/06/08/1178695152/china-scientist-he...
That's not to say the research itself is not impressive nor important, but think critically about the fact that this money doesn't exist in a vacuum.
How confident are you the answer isn't very close to zero? We've already curtailed smoking quite a bit in the past 30 years. At the level of an individual, it isn't any particular mystery how to stop obesity or to simply not drink, but population-level interventions attempting to get people to voluntarily behave differently for their own health historically haven't worked well in these specific domains. Throwing more money at the problem doesn't seem like it would obviously change that.
Also keep in mind that overeating and alcohol addiction have significant genetic components. Research into gene editing has the eventual potential to cure damn near any disease, including whatever pet causes you personally think are worth defeating.
Said like that it paints things like there are not far more resources spent on propagating the bad habits (as some ROI is expected from this by some actors), and any attempt to put a social health program in history always ended in major catastrophes.
Maybe even the dirt cheap one, because even 100 dollars could go longer way somewhere in the Sahel.
It is good that the humanity does not have a one-track mind.
I could say I believe the government should fund research into fixing people who think cilantro tastes like soap because for most of us it is delicious and promotes healthy diets. Should I be able to compel (tax) you to pay for that research?
Where that line is drawn will always be wrong to someone. How research is prioritized will always be wrong to someone. Is there an ethical way to determine the best use of collective resources and what portion of one’s property must be taken from them to fund that research.
The cilantro taste stuff does not sound absurd to me at all. In biology, there is no hard wall between banal stuff and critical stuff; they interact and fundamentally operate in the same environment under the same genetic and epigenetic rules. Sure, the research necessary for correcting cilantro-as-soap may be marginal, but there is a chance of discovering something significant along the way.
We should be more careful and also honest when communicating about science to taxpayers.
BUT the long term view of creating a technology that can treat any genetic illness (or maybe even any illness?) must outweigh that _eventually_
In reality, as this process becomes more mature it is going to become inexpensive.
The reduction in cost will almost certainly be similar to reduction in cost needed to sequence an individual's genome, which has fallen from tens of millions to hundreds of dollars.
The only catch is that we have to spend money to get there.
Another catch is that the nations who underwrite this research will turn millions in investments into trillions in dividends and the stingy or poor will be left in the cold.
Seeing that private enterprise is only good at taking publicly-funded work and patenting it, and that in the absence of public funding nothing ever gets invented, we should be all-in on this.
edit: it's apropos that you mentioned obesity because GLP-1 drugs are the direct, irrefutable, product of spending at government labs.
edit2: specifically, a single government scientist playing around with lizard saliva in the 1970s because he thought it was interesting.
There's no evidence to support that gene therapy will ever be inexpensive. We can merely say that the process may become less shockingly expensive.
Sending robber barrons and their girlfriends into space?
When a Utopian dies, of anything, the cause is marked and not forgotten until solved. A fall? They rebuild the site to make it safe. A criminal? They do not rest until he is rendered harmless. An illness? It is researched until cured, regardless of the time, the cost, over generations if need be. A car crash? They create their separate system, slower, less efficient, costing hours, but which has never cost a single life. Even for suicide they track the cause, and so, patiently, blade by blade, disarm Death. Death, of course, has many weapons, and, if they have deprived him of a hundred million, he still has enough at hand to keep them mortal. For now.
My prediction is based on the number of efforts, too numerous to list here, being undertaken to develop lab equipment to automate the extremely labor-intensive workflow and the accumulation of vast libraries of CRISPR-Cas9 screens and dependency maps, the creation of which are also expensive and labor-intensive.
A similar thing has been said about so many cutting edge therapies and technologies in the past that I think you'll end up being quite surprised.
Eventually someone will invent a machine that spits these therapies out like espresso machines.
Getting a new drug or therapy approved for a rare form of a disease and then expanding the indication to the common disease patient population is a well established strategy.
This is something beyond that, and is very valuable as this baby has no actual means of fighting this issue at all.
And who's to say this won't lead to fixing the other things anyway.
Great use of dollars
There are known DNA changes that would probably help all people with chronic diseases, but it's ethically more accepted to go for the more fatal diseases and cleaner cases first, like a rare mutation with a high fix rate.
Instead if no resources is allocated on developing all the technical requirements to do such a thing, humanity ends up with less tools to heal itself, and that's it.
b) the whole point of NIH and other government research funds is to pay for this sort of "not clearly an effective use of dollars" type of research that Pfizer et al won't touch. but you can look at a ton of future applications from this - lipid packaging, CRISPR methods, drug delivery, etc that had to be devised, and could conceivably be commercially viable if the methodology is perfected and the cost comes down.
Of course they do. But untold amounts spent on very few kids could be spent elsewhere on many more. Federal budgets are a zero-sum game.
> Also, I think when they say they want more babies, they want a specific subset of babies to increase.
I've seen quite a few conservative commentators celebrate that the massively disproportionate levels of African-American abortion have been reduced, resulting in more African-American people being born, and zero bemoaning it. So maybe you're right.
> the idea of being told my 1 week old baby is going to die
not
> the idea of my child dying
> my baby is going to die, woe is me
and more of
> have I failed my baby so much as a parent that he won’t even grow to adulthood (much less have a wonderful, happy life)
It’s not exactly a rational feeling; it’s not like this baby was going to die through lack of parental effort or care or anything else that the parents have any real control over, so it’s not like they could have done anything differently.
Nonetheless, it can make you feel like an utter failure of a parent. To some people (I admit, not everybody), that is absolutely crushing.
It only looks irrational if you don't understand what people and feelings are.
I am not a parent but I think if I did have a kid I would try everything I could to keep my child alive and minimize pain in my child's life.
> But your child will die and that's a fact. Is it only ok for it to die after you?
I tried to be the one who didn't do that, but missed the mark. I'd delete it if I could.
Please observe the guidelines, especially these ones:
Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.
Comments should get more thoughtful and substantive, not less, as a topic gets more divisive.
Please don't fulminate. Please don't sneer, including at the rest of the community.
Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith.
Eschew flamebait. Avoid generic tangents. Omit internet tropes.
Please don't use Hacker News for political or ideological battle. It tramples curiosity.
I genuinely can't link any of these to any of my comments, that's why I'm asking. I reread those a couple of times. I really think I've been polite, and I really tried to be, even when called "beteft of humanity", "earnest" and accused of trolling. I did not insult anybody, didn't want to and I certainly didn't want to bring anyone down. I just asked a question that seemed (and still seems) logical to me, only to get shutdown by mass flagging, now by removal of the comment with no real explanation what rules I broke and why I was negative
Please just understand that it can be upsetting to many people in the HN audience, as evidenced by the votes and comments, when the topic of death is addressed in this way: i.e., in a way that seems hyper-rationalist and diminishing of the way premature death – especially of infants and children – is particularly devastating to parents and loved ones.
I might be just shit at expressing my thoughts in English
> when the topic of death is addressed in this way: i.e., in a way that seems hyper-rationalist
This is why I kept pushing and asking - I thought that HN is all about logical thinking and not letting your emotions go through and think for you.
I don't know if you are still insisting that I broke the rules - you don't have to explain in which way I broke them, I understand that I don't understand. A simple yes or no would suffice, if I could ask you.
And thank you for taking the time for discussing this with me. Regardless of the answer for the above question I will refrain from talki
How many people can even afford to get multiple opinions for a weird lump on their back? Or go to the dentist for a strange toothache? How many people can afford to get consistent exercise and eat healthy? How many lives would be saved or at least massively bettered? We already have the means to extend the life expectancy of the average person, and it's not being used. Obviously this is a wonderful medical advance, but it's depressing to wonder who it's for.
I'm as negative about the rich and powerful as anyone but this is such a cynical take - that might have been applied to many medical treatments in the past that have become relatively commonplace and easily accessible to people of all classes, at least in sane countries with sane healthcare systems.
I'm explicitly not saying this work shouldn't be done, it should! But it does not exist in a vacuum, and it would be silly to pretend that it is not colored by vastly unequal access to modern healthcare. The reason I get excited about technology is because of the potential it holds for making us all happier and freer to do the things we like for longer. We are lost if we do not at least speak about the thunderclouds on the horizon for this philosophy of technology.
I think, every once in a while, it's okay to just celebrate without looking for the the clouds :)
Everyone could afford to "eat healthy" and get exercise if governments and social planners put in a modicum of effort. Unfortunately they aren't directly incentives to do so.
Framing either of these things as a wealth issue ignores both how wealthy even the poorest in the world are and the systems responsible for the problem. For everything else there's health insurance, yet another horribly mismanaged system.
Please observe the guidelines, especially these ones:
Be kind. Don't be snarky. Converse curiously; don't cross-examine. Edit out swipes.
Comments should get more thoughtful and substantive, not less, as a topic gets more divisive.
Please don't fulminate. Please don't sneer, including at the rest of the community.
Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith.
Eschew flamebait. Avoid generic tangents. Omit internet tropes.
Please don't use Hacker News for political or ideological battle. It tramples curiosity.
In fact, gene editing completely removes the need for eugenics programs.
this still leaves a slight bitter taste in my mouth: If they edit specific genes one way they can also do the opposite direction. And if I understand correctly, they did with a bunch of lab rats?
Now, this and similar stuff have obviously been discussed before, essentially "12 Monkeys": Somebody releasing some runaway gene-editing mechanism, be it a virus or what not, and using it as means to mass destruction. However, that is not even what I worry about because that is nothing new, viruses have existed longer than most other kinds of life on this planet.
Instead, what just popped into my mind is more like ransomware but on your body cells. Attacker edits victims genes to some condition that is lethal within a week or so and then blackmails them in order to edit it back. Kinda like the "Carrying the Antidote"-trope, only that there is no other cure in time.
Maybe worth a Black Mirror episode ... anyway you heard / read it here first ;)
edit: To the people downvoting, why not engage in the conversation instead? I am not saying we shouldn't be doing this, just that this is a fun crime scenario in a movie. What is wrong with that?
> However, that is not even what I worry about because that is nothing new, viruses have existed longer than most other kinds of life on this planet.