Baby is healed with first personalized gene-editing treatment

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.

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.

https://en.m.wikipedia.org/wiki/Emmanuelle_Charpentier

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)

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.

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.

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.

    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 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

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.

Indiana Jones and Hellboy are pretty explicit about this.

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]

[1] https://youtu.be/6URTjoK58Yc

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).

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.

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.

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.

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.

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...

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 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.

BUT the long term view of creating a technology that can treat any genetic illness (or maybe even any illness?) must outweigh that _eventually_

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.

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.

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