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.
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.
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.
If anyone else does know, please chime in!
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.
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.
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?
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.
Assuming requisite safety of course.
[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.
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:
https://www.sciencehistory.org/stories/magazine/the-death-of...
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.
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.
> 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.
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.
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.
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
Hilarity subsequently ensues.
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”
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.
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)
> 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.
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...
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.
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...
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?
- 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.
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.
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.
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.
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).
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.
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.
>>>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."
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.
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.
Do companies like this have a need for SWEs? Are there opportunities for a backend SWE without any background in hardware or biology?
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.
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...
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.
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.
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.
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.
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.
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.
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.
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
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
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.
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
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
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.
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.
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.
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.
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.
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.
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.
BUT the long term view of creating a technology that can treat any genetic illness (or maybe even any illness?) must outweigh that _eventually_
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
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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?