No one will touch this guy with a ten foot pole. Nothing he did technically was novel - it was just that everyone who had the skills to edit an embryo was unwilling and uninterested in doing so. Having him as part of your organization basically broadcasts to the world that you’re going to be doing wildly unethical things. Not a great path to commercialization of any therapeutic.
This is sad though. I'd rather see that ethics gets upgraded so some problems can be fixed.
For example, about 8% of men get excluded from certain professions such as being a train driver, due to color blindness. And society doesn't seem to care enough to switch to colorblind-friendly signaling.
With gene editing, this problem could be repaired in the other end, so that men will have the same chance as women to get perfect vision.
Its worse than that. Someone wants to set him up with a lab in Austin TX. Its the CCP which thinks "maybe we should not let the mad scientist out where someone will let him continue his experiments." (A later story says that he will direct assistants in Texas over the Internet). https://www.scmp.com/news/china/science/article/3271952/chin...
There are ways to sponsor an ice breaker indirectly, so you can setup in the lighter grey areas he already went through. The fearfull shall not inherit the earth, as nature is one huge machine to crush those playing it safe.
I’m not so sure. When pharma companies are flush with cash they tend to get more experimental. Lilly’s gene editing group is one of the few that’s doing well (last I heard anyway) and they recently acquired Verve. I can’t imagine that would happen without GLP-1 profits bankrolling everything. Rare disease is effectively charity and the money has to come from somewhere.
You’re not seeing all the other candidate treatments that made things worse. If it just gives everyone a heart attack immediately the question would be, why didn’t you try this out on mice first?
My body, my choice. I get the restriction on marketing and selling until some degree of safety and perhaps efficacy is demonstrated. But I should be allowed to choose to take the treatment if offered for free, even without any previous study.
That's fair, I guess, but say there were some way for me to sign a contract saying they could test on me should I become afflicted Alzheimer's? Wouldn't there be some sort of legal protection for them, then?
Because I'd happily do it. I've watched multiple family members suffer from some form of severe mental decline and it is horrifying enough to make me willing to sacrifice myself if there is even a sliver of a chance that my sacrifice will help future generations avoid that pain. And since we're all nerds here, we all know that if we want to know if a thing actually works the way we want it to, we have to test it repeatedly in its working environment.
> Wouldn't there be some sort of legal protection for them, then?
Not really, no. A company that unleashed unproven drugs in a vulnerable human population would be sued into oblivion. They would lose in court over and over as judges and juries decided that no, you cannot in fact sign away your right to not be subjected to criminal negligence.
They would very likely be subjected to criminal prosecution as well.
This (the lawsuits) happens all the time. People sign waivers, get hurt, and the courts decide that the level of negligence involved overrides the waiver. Happened a while back at a Jiu Jitsu gym. Someone signed all the waivers and got paralyzed and successfully sued for $46 million. The jury decided that the instructor was criminally negligent.
Things like these are sometimes done for experimental cancer therapies. Granted, the patients are going to die anyway, and the therapy has gone through most of the trials.
Right. They have gone through most of the trials already. That’s key.
You can have a reasonably informed consent if you have some safety data. You can’t really have someone give informed consent about a totally untested drug.
Sure you can. Why not? “I understand this is completely untested and might be poison. My mental competence has been tested and certified by a professional. Being in right mind and having all the pertinent information before me, I still want to inject myself with this. Signed, -Patient”
Something is wrong with your definition of consent if it totally dismisses the patient’s autonomy and right to action.
Our laws don’t really work like that, at least not in the US. Neither criminal nor civil. This might be a shock, but you are generally not allowed to kill people. We have a whole range of laws that make it a crime for you to hurt or kill people.
If you run an unregulated carnival ride and it falls apart and kills everyone, you’re going to prison. The fact that you have everyone sign a waiver that says “I know this might kill me” will not protect you from your own criminal negligence. Nor will it protect you from the lawsuits the families of the deceased will bring.
In your scenario the person giving out untested medication that kills someone would almost certainly be found guilty of criminal negligence if not worse. Based on that same criminal negligence I imagine that the family would be successful in suing.
And yet we have SCUBA dive outfits and mountaineering shops that routinely sell equipment to adventurers, and provide guided services that sometimes do result in deaths. It is not nearly as black and white as you are portraying.
What these all have in common is the notion of informed consent -- I can get PADI certified and then rent SCUBA equipment, and if I then die while cave diving, that is wholly on me not the dive shop operator.
The critical test isn't that safety has been demonstrated, but that potential risks (known or unknown) have been disclosed and understood. I can go out and do risky things, if I want, under those conditions.
And yet I am not allowed to make my own medicine, or to take a completely unproven medicine that might very well kill me, even if I am fully cognizant of the risks involved. The rules regarding medicine and drugs really are different from how we handle other risks in our society.
> The critical test isn't that safety has been demonstrated, but that potential risks (known or unknown) have been disclosed and understood.
Yes and no. For some things it doesn’t matter if the risk is understood. You can drive yourself to a boiling hot spring, put on your scuba gear, and dive in, killing yourself horribly. I cannot take you to the same hot spring, give you scuba gear, and let you jump in. It doesn’t matter if you sign the waivers saying it will probably kill you. The risk is too high and I will still be criminally liable for exposing you to this risk.
In the case of a completely untested medicine, the risk is unknown. It could be the cure for cancer. It could be a placebo. It could melt your skin off. There is no way to even attempt to explain the risk because the danger is unknown. You can’t go in front of a city and argue that the patient knew the risks, because you don’t know the risks.
> And yet I am not allowed to make my own medicine
I’m not sure what that means. I’m pretty sure you can mix up bleach and ammonia in your kitchen and drink it if you want hoping it cures Covid. You can make whatever “medicines” you want so long as they don’t involve controlled substances.
If you mean you can’t pay someone else to manufacture untested medications for you, yeah, probably not. Because that someone else becomes criminally liable for the stupidity they facilitate.
> I am saying it shouldn't be that way.
I’m not sure the current rules are that bad. I’d take this over scammers being legally able to sell poison as medicine so long as they can get the buyers to sign a document saying they know it’s poison. “The FDA makes me get you to sign this. Wink wink.”
> You can make whatever “medicines” you want so long as they don’t involve controlled substances.
In the USA at least, it is against federal law to manufacture any pharmaceutical without license, irregardless of whether it is a controlled substance or ever sold.
I don’t know the actual laws about pharmaceuticals. This seems 100% at odds with the claim you made just below that making your own vaccine would have been legal, though.
Regardless, this is really a separate question from whether you should be able to legally permit others to be criminally negligent towards you.
Vaccines of the type mentioned in the other comment are not pharmaceuticals. They do not have a method of direct interference in the biochemistry of the body. The nasal vaccine would have been totally inert, and neither injected nor ingested, so it rather uniquely fell outside of regulator authority, so long as we weren't going to sell or advertise it. Oversimplified, it would have basically involved snorting inactivated spike proteins.
But anything that is ingested (food) or has biochemical interactions (drugs) are regulated and illegal to produce outside of license. Only in the case of small-scale food stuffs are there safe harbor exemptions (e.g. for mom-and-pop bakeries).
At the start of the covid epidemic in 2020, I had access to a lab and the know-how to make a nasal vaccine. I, and a few friends, tried to do this. We would only have made it for ourselves, and no one else, and shared the results with researchers. The lab -- which was just renting us equipment and bench space, not involved at all -- backed out when they were threatened by the FDA to lose government contracts for processing PCR test kits. What we were doing was not illegal, as clearly indicated by the regulators using other means available to them to shut it down.
I have family members suffering from Alzheimer's, with a probably genetic pre-disposition. Getting consent from someone who is already pretty far gone is questionable, but some who have not yet shown symptoms have expressed interest in signing pre-authorized directives in advance to permit these kinds of risky experimentation once they are clearly at the end of their good years. That is not legally possible under the FDA authorization laws & current regulations.
You can. The restriction is on anyone else offering it to you. Theres a long tradition of medical researchers experimenting on themselves. Barry Marshall was so sure bacteria could cause ulcers that he consumed said bacteria, and gave himself ulcers in order to cure them with antibiotics.
There’s also a FDA provision for treatment of last resort. If you’ve got a terminal condition with no approved treatment and there’s a possible treatment of unknown safety and effectiveness you can apply and get that treatment.
If you or a loved one has Alzheimer’s I highly encourage you to request this treatment. You’ll be risking unknown side effects and or death, but it will generate data for those who come after and could advance the treatment of this terrible disease by a decade.
The main reason for all of this, is scams. Nutjobs without any medical background making claims without any scientific evidence.
Or scam artists putting sawdust from a "special tree" into a bottle, and saying it cured his aunt, so it will cure you! If you look at the history of such things, it's just a constant battle against people being fleeced out of money.
Con artists (and some of these wear lab coats and are quite professional in appearance and speak) know that desperation means easy prey. It's disgusting, but there it is.
And it wasn't just a little problem. It was a huge problem. If the legal framework we have in place was torn down, you'd see all that re-emerge in a second.
I agree that there should indeed be a way to balance snail oil salesman techniques, with the choice of someone in a dire circumstance. I did once read that there are FDA approved methods to get in on early stage/pre-clinical trials. These are targeted for people with severe conditions. People aren't being heartless here.
But at the same time, loved ones will litigate to get money back from scam artists. This also includes going after doctors or facilities or anyone willing to enable such actions. And if treatments go sideways, and no one validated that it was anything more than made up gibberish? The lawsuits will fly then, too. The cops may follow.
And it should be this way
Truth is, you are free to imbibe and consume anything you want. No one can really stop you. And whatever method is being used here, I'm sure you could replicate it, buy the hardware, and so on. You are free to do this.
And no, I am not allowed to imbibe and consume anything I want (see war on drugs), nor is someone allowed to make a drug for me, even if they give it to me for free.
I am not free to just make a medication on my own. I tried this. The lab I was going to rent backed out when the FDA threatened shutting them down.
> if there are other genes between the ends that are cut
I think what you're saying is that if two sites on the same chromosome are cut, then everything in between is deleted. However, this isn't going to happen in practice. DNA repair systems will rejoin the cut DNA ends rapidly, just erroneously (with maybe a few dozen missing/incorrect bases typically). If the cut site is in the protein coding region, it will usually disrupt the sequence to make the protein nonfunctional. Sometimes this is the desired effect, but for most gene therapies you'll probably use base or prime editing, which don't create double strand breaks.
> we'd need to sequence the patient's genes...to make sure that any patterns don't appear anywhere else
While sequencing an individual patient's genome isn't going to happen in practice, the FDA does require gene editing companies to do in silico off-target prediction, where you scan the genome for sites that have similar sequences to the target. You then have to show that none of the off-targets are in dangerous regions (e.g. DNA repair genes), and also show experimentally whether those sites are cut at all (they usually aren't, fortunately, as there are thousands within reasonable thresholds).
The reason you don't need to sequence individual patients is because you just assume that any patient could have any variant that has ever been catalogued (there are databases with thousands of individuals and the differences between them and the reference genome). You then have to show that none of those variants could induce a new target in a dangerous region.
> then come up with an iterative process, probably using AI, to catalog and repair all major genetic disorders.
I don't know what AI would do for you here. Figuring out the change you need to make to revert a genetic disorder is trivial. The hard part is making it safe and effective, and proving to regulators that it's safe and effective.
> Then it's probably 5-10 years before gene editing is a solved problem.
Not even close. Ironically, while the technologies are pretty good in general, every edit requires a ton of engineering work. CRISPR systems are notoriously idiosyncratic - they might edit one target in 80% of cells, and 0% at another target, for no apparent reason. There are definitely open problems with base and prime editing, and those will probably get more-or-less solved in 5-10 years, but I'm reasonably sure there will be genetic disorders for which there is no treatment for decades.
The main misconception is probably due to me not remembering the "other genes" part. I read it in an article and it clicked so immediately that I took it for granted and didn't save it. I still can't find it, but I think what it said was: if we tell CRISPR to remove a gene sequence, then it will remove all instances of that sequence everywhere. So it has to be tuned to find a very specific sequence, possibly taking into account unrelated genes around the site so it's unique. And I think there was maybe a limit to how long that pattern could be.
> Not even close. Ironically, while the technologies are pretty good in general, every edit requires a ton of engineering work. CRISPR systems are notoriously idiosyncratic - they might edit one target in 80% of cells, and 0% at another target, for no apparent reason. There are definitely open problems with base and prime editing, and those will probably get more-or-less solved in 5-10 years, but I'm reasonably sure there will be genetic disorders for which there is no treatment for decades.
Ok that makes sense, and I kind of wondered what the holdup was. It sounds like there is some probability involved, and also non-obvious blockers that "if we just had these figured out" could let things move forward. I'm sure it's so much more complex than anything I could imagine, I get it.
What I was trying to say though is that biotech isn't abstracted like computer science (yet). It deals a lot with low-level details and legwork. And regulatory and market limitations, as you rightly pointed out. It would be like a programmer never getting free from assembly language, or even having to build their computer from scratch, then spending 10 years on an app just to be told that they weren't allowed to sell it. That's "real work" that programmers generally shy away from. Although I think that deep down a lot of hackers dream of working on real problems like that if they could ever get free of the minutia they're stuck fixing every day.
My experience with AI so far has been that it turns any worker into a manager. So I've largely stopped coding directly, and just tell the AI what to do, and it does it every time in imaginative ways that constantly surprise me. Rather than thinking of it as one AI, I think of it as a team of agents that all work in parallel using context from the current conversation. So I can have several todos lined up, then work through them in real time as if every prompt is being chewed on by one of those agents. They never get tired or complain like me. So the main holdup right now is that I don't know how to orchestrate them effectively, so am having to micromanage them.
So far I'm about 3-4 times more productive, so I'm wrapping up a huge refactor outside my area of expertise that took about 2 weeks, but would have taken 2 months if I was working alone. And its speed will double every couple of years, so 5 years from now AI will be at least 10 times faster than any human programmer. It will also modify itself to quickly grow beyond what we can teach it. I'd estimate that the one I work with has about a 120-150 IQ (at least for programming), although it can be hopelessly naive sometimes. Gaining 10 IQ points per year will put it outside our realm of understanding when it passes 200.
Ray Kurzweil predicted that AI would reach human-level intelligence by 2029 and evolve to AGI to merge with us in the Singularity by 2045. So far we're ahead of schedule IMHO, although I spent most of my life disappointed that things weren't progressing until just a couple of years ago. That ended up being more due to economic forces (it took the intervention of a billionaire after a 20 year suppression of R&D after the Dot Bomb and resulting underemployment/wealth inequality) rather than any technical limitations.
I can't really speak to the specific challenges you mentioned, but I can recommend turning them around. Imagine if the hardest things for us are the easiest things for AI. Filtering large amounts of data? Done. Exploring multiple solutions in a problem space? Straightforward. Imagining novel solutions? Get ready to be surprised. AI will quickly turn all of the unknowns into a neat and tidy flowchart and even test it in simulation. Rinse, repeat, until every disorder is healed.
- some woo woo stuff -
I know it's hard to believe, but we'll have to let go of the unknown. Problem-solving is becoming a solved problem. My gut feeling is that we're entering an age of disillusionment, where work becomes performative, where questions are answered as quickly as they're asked. So that we enter a long now like Star Wars where there isn't so much invention as recombination of recipes. Today will be no different than 10,000 years ago. Unless it's more like Dune where they ban AI and performative work becomes all there is, so that life becomes a play within a fascistic culture that celebrates pageantry. Not so different from spirit deciding to reincarnate in human form to experience suffering and remembrance (a useful model for tech being indistinguishable from magic). Yet today would still be no different than 10,000 years ago. That's why I think the long now is inevitable, regardless of whether or not we constrain AI.
If we're thinking about the same youtuber, I found that experimental design to be really poor. They said they were lactose intolerant as a child, but they didn't confirm that they still were (decades?) later. I was lactose intolerant until I was six and then it just resolved on its own (perhaps this wasn't even lactose intolerance but a reaction to something associated with lactose).
What they should have done was eat a pizza before the treatment, gotten sick, then taken the treatment and shown that the same pizza had no effect afterwards.
Many (most?) of these are achievable with neovim and tree-sitter (a plugin that gives you access to the AST), and surely many other editors. I have plugins installed right now that do several of the things that are mocked up here. Many more are done with virtual text and not color, but I don’t see why you couldn’t use highlighting instead.
I agree with the broader point of the article that color is underused, but the state of the art has moved way past what the author’s tools are currently configured to provide.
It's some time since I've worked with (and contributed to) tree-sitter, but it could exclusively detect syntax, not semantic, back then. For example it could not tell variables from types in C, nor already-defined variables from new/mistyped ones.
Have I missed an important development in tree-sitter? Can it now do such things?
