HN Reader

Detailed New England Journal of Medicine article about this case: https://www.nejm.org/doi/full/10.1056/NEJMoa2504747

And an Editorial piece (more technical than the NYT): https://www.nejm.org/doi/full/10.1056/NEJMe2505721

> To accomplish that feat, the treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.

That is one of the most incredible things I have ever read.

If someone in the year 2050 was to pick out the most important news article from 2025, I won't be surprised if they choose this one.

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...

As a father, the idea of being told my 1 week old baby is going to die would be my worst nightmare. The fact these doctors and scientists saved this childs life is a monument to modern medical science. This is absolutely insane. Hopefully the child doesnt need a liver transplant, but this is a great leap forward.

> But KJ’s treatment — which built on decades of federally funded research — offers a new path for companies to develop personalized treatments without going through years of expensive development and testing.

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.

When my second son was born and was just so very tiny some genetic test came out questionable. We were very strongly encouraged to go to Childrens hospital ASAP to get more tests. He handled it well, being just a few weeks old. The tests came with "he's a carrier of something obscure but nothing to worry about", so it's all forgotten.

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.

NYT isn’t super specific here, but they made it sound like the disease treated is liver related. My understanding is that the liver is a good place to start with CRISPR-type gene treatments, in that the liver normally deals with anomalous shit in your bloodstream, say, like CRISPR type edits. So anywhere outside the liver is going to be significantly harder to get really broad uptake of gene edits.

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.

My daughter has a genetic condition (PKU) that is also caused by a single letter change in her DNA and also causes brain damage if she consumes too much protein. Luckily it can be controlled with a strict low-protein diet (<10 grams a day).

This is SO exciting! The fact that there is a chance of a cure has absolutely made my day!

Does this mean when they grow up, their own offspring will also have this defect and require a correction? And, if so, does this mean it is now introducing this defective gene into our gene pool?

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.

The work outlined in the actual paper is quite remarkable. Within this 6 month period they generated transgenic mice with the precise mutations (paternal and maternal) this baby had in order to test treatment for functionality and toxicity as well as a doing a toxicity study in monkeys.

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.)

This is incredible work. Its jaw dropping to learn that something like this is possible at all. Sometimes I wish I could work for a company whose products make a meaningful positive contribution to the work.

Do companies like this have a need for SWEs? Are there opportunities for a backend SWE without any background in hardware or biology?

Hmm, I thought clinical gene editing (gene therapy) was frowned upon because it's inherently risky and fraught with ethical hazards. What technically and ethically has changed since 2005 beyond CRISPR?

Damn what a strange time to be alive. Juxtaposing this against the constant nonsense coming from RFK is as jarring as it gets.

>KJ has made medical history. The baby, now 9 ½ months old, became the first patient of any age to have a custom gene-editing treatment, according to his doctors.

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.

Can you imagine the emotional rollercoaster of this for the parents

I think it was here a few years ago that I read a comment saying that sick children will be the Trojan horse for normalizing gene editing of humans, because who could say no to sick children, right? Well, guess it's here now, so how long utill the eugenics wars start?

I thought the first gene edited babies were from He Jiankui

Honestly the biggest barriers to a lot of advancement right now in biology from medicine to our food supply depend squarely on getting uneducated people over their aversions to modern science. It is crazy. We are really at the “I don’t trust that locomotive/airplane/car” stage where what the public understands about the field is so far away from the state of the art and the risk considerations that have been put in place by the actual domain experts who have thought of all your concerns already. It isn’t just lay people either but government officials in charge or permitting and approvals that need the most convincing. They might be out of the field themselves for a decade or more.

Are the edited genes inherited, or the original ones? Does the previous question have an answer that depends on the babies sex?

From an evolutionary perspective it‘s interesting how the further medicine gets, the more we inherit genes unfit for life without medical support.

Here's the actual paper

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.

Could this be used to actually change the DNA of transgender people?

Not quite. The child still has the disease and will need lifelong treatment for not only the disease itself, but also the gene editing procedure.

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.

I prefer the Perplexity summary over the nytimes' style of weaving facts with narrative:

https://www.perplexity.ai/page/baby-born-with-life-threateni...

I wonder if this also affects germline cells so he won't pass the same disease on to his children. If it does, that would be a complete departure from almost all medical treatments we use because most of them are just compensating for the effects of bad genes and leaving them in the gene pool to degrade the health of future generations.

Gattaca here we come!

Let's be specific, they don't know if he is fully cured. They need more time to conclude efficacy.

Pandora’s box just opened

Again

Did you mean to post the same link for both?

A Gattaca moment ?

Did AI help at any step in the process?

We done to Musunuru an amazing cardiologist.

we progress closer and closer to a "red rising" type future -- exciting and scary. exciting for the family and child <3

Research funded by the NIH which our government is actively gutting

I love how the last lines of the article read,

> “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

Could this be used to heal adults with the same genetic disorder?

My girlfriend and a couple friends work at one of the companies that developed this and they're quite excited and proud of it and I of them.

I know nothing of this area, but it seems to me this could make cloning easier, right?

Incredible to see science and love come together to rewrite a baby’s future.

I can’t read the full article, but I’m wondering how they got FDA approval for a one-off personalized treatment here outside a trial?

Aren’t people dying because they were waiting for FDA approval for other experimental treatments?

That is great news and my congratulations to the parents. Hopefully it's something that we can repeat many times in the future.

I am sure this article would have been mentioned in Homo Deus

What does this mean for longevity research? Could the same treatment potentially be adapted to make edits that could lengthen lifespan of healthy people?

Do you think someday soon we will have the equivalent of an LLM coding assistant, but for gene editing?

Thank you scientists! Next, pretty please figure out how to grow ironmouse a new immune system! <3

This is incredible. Probably the most exciting piece of news I’ve read in years.

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Good thing RFK pushed out the official overseeing this financing and the current administration is actively defunding the organizations that produced this.

Better to have more disabled or dead babies instead of science.

/s

the road to hell is paved with good intentions. In our lifetimes we will see a brave new world controlled through eugenics.

Not to downplay what a huge achievement this is and how far the field of medicine has come, but ...

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?