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While I agree with your first point, I think you're off base on the second. If, as the OP suggests, it would be possible to develop a toolkit such that the concerns about time/resources you raise in your first point are moot, then I think it's worth chasing that down. The result isn't saving 3 people but rather making it possible (profitable?) to do the same for anyone with these sorts genetic transcription errors.

While you're correct that an individual treatment using this approach can never be tested against thousands of patients to determine safety (as it might only be needed by 3 people), it's either try it or watch thousands of people die.

>f, as the OP suggests, it would be possible to develop a toolkit such that the concerns about time/resources you raise in your first point are moot, then I think it's worth chasing that down.

I do agree that this is something worth following. If it's really provable that this platform solution is universally safe, that's amazing. But that doesn't mean the system is broken. Just that until now, this was probably not the proverbial low-hanging fruit of medicine, even with a million people there are diseases affecting billions. It may still be worth more investing in those disease that affect billions.

>it's either try it or watch thousands of people die.

How many of these genetic diseases are deadly? A lot of these mutations may be bad but not deadly. If now the treatment is universally approved and kills some people, think about who's going to take the responsibility for it?

> If now the treatment is universally approved and kills some people, think about who's going to take the responsibility for it?

Same as any other medical intervention. A substantial number of people die as the result of routine surgery for problems that themselves weren't life-threatening. Medicine, like engineering, involves tradeoffs and risk assessment, and there is not likely to be a perfect outcome. All we can do is work on the "best" outcome for the most people.

> The result isn't saving 3 people but rather making it possible (profitable?) to do the same for anyone with these sorts genetic transcription errors.

The amount of work that goes into making sure that any single treatment isn't going to have unknown side effects is non-trivial. Just because there is a common toolkit doesn't make this safety testing go away. It automates the design of the safety tests somewhat, but doesn't make them any less important. This means that for every... single... anti-sense oligo that's designed, there needs to be significant testing done to make sure that it does what is expected and doesn't have any adverse side effects.

In many cases, it's the first part -- the design of the treatment -- that is rate limiting. The benefit of something like these N-of-1 ASO trials is that you're streamlining the first step in the process. But that doesn't mean you can just skip the other steps. And yes, these steps are expensive.

> Yes, there are millions with some mutation. But changing around mutations needs to go through some form of medical process to see if it's safe. The current processes are there because historically there has been a lot of abuse for profit. We can't just platform allow any genetic editing. Some of these edits might be dangerous.

Let me rephrase this less charitably: You are willing to rob millions of suffering people the chance of a cure, by mandating a system that effectively prevents a cure from being developed. This is in order to save some of the very same people from the effects of unsafe treatment. It is patently absurd, but that's exactly the system that we have right now. Nobody wants to take on the legal liability of killing a terminal cancer patient with an experimental treatment unless they have military-grade legal assistance at their disposal.

It's also clearly not working when countless desperate people opt for "alternative medicine" and various quackeries that aren't held to those standards, simply because they're not advertised as "medicine" in the legal sense.

If you've ever asked yourself why health care is so expensive in the US, don't overlook the safety standards and the legal liabilities that medical practitioners incur. Look at the value of settlements in US courts. Practitioners require expensive legal insurance, and they'll charge you for it.

>You are willing to rob millions of suffering people the chance of a cure, by mandating a system that effectively prevents a cure from being developed.

The cure may be worse than the disease, I bet not every one of these one-off mutations is deadly, and how debilitating it is may vary. I'm not trying to rob anyone from the chance of a cure, I'm just saying that to save the most people, resource allocation makes sense.

Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.

> I'm not trying to rob anyone from the chance of a cure, I'm just saying that to save the most people, resource allocation makes sense.

I wasn't arguing with resource allocation, I was arguing with your "safety concerns". My takeaway from the article is that with the current framework, any treatment needs to go through countless trials individually, hence it is literally impossible to do any trials to prove the safety or efficacy any treatment that is bespoke to a handful of people.

In our system, it's the responsibility of private companies to productize findings from research and development. As a result, resources aren't allocated to save the most people, they're allocated to make the most money. If you make it expensive to develop treatments for diseases, or you limit the profit that can be made from these treatments, those treatments will never be developed. No pharma company loses money just because people die. They lose money from dead people they could have treated at a profit.

> Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.

The incentives are aligned towards not taking risks. You will not read a headline "Millions of people died as a result of overly strict safety standards". Even though that may very well be the case, it would just be a conjecture. On the other hand, if a handful of people die from some FDA-approved drug, it's all over the news, people will demand consequences, million-dollar lawsuits will be filed, and so on.

> If you've ever asked yourself why health care is so expensive in the US, don't overlook the safety standards and the legal liabilities that medical practitioners incur. Look at the value of settlements in US courts. Practitioners require expensive legal insurance, and they'll charge you for it.

Texas did some malpractice law changes back in 2003. It would be interesting to see if in impact their health care costs.

it seems like business people need to wrap their mind around creating a process that allows these one off solutions to be made more easily. There are probably over a million people with a one off genetic problem that would be worth at least 100,000 to solve. Making a one off solution once is obviously not the solution, but instead engineering the process to allow the one off solutions to be generated more quickly and easily.

1,000,000 * 100,000 = 100,000,000,000

A possible 100 Trillion dollar industry seems like a very stupid thing to ignore.

The other thing to remember is that making a genetic toolkit to fix genetic errors is a potentially low liability solution, if well tested, documented and proven. The liability would still rest primarily with the practitioner.

$100B, but I think your point still stands.

"A possible 100 [b]illion dollar industry seems like a very stupid thing to ignore."

Even taking your optimistic numbers at face value, that's revenue, not profit. A 100 billion dollar industry with what I would conservatively estimate as having several trillion in costs is not something we can pursue.

I've got my own boutique genetic problems in my house (not quite a one-off in effect, but probably technically novel), so I've got skin in the game, but this is just wishful thinking. Even just funding all the known rare diseases is not something we can really afford, let alone dedicating millions to every one-off mutation. We aren't that rich.

I'm sympathetic to claims we ought to have enough for food and water and basic housing for everybody, but that does not translate into having enough to create custom bespoke medical research programs for everybody, or even a significant fraction of "everybody". If nothing else, food, water, and basic housing are widespread skills; fixing genetic errors would always bottleneck on the number of available people who can do it, which is never going to be as large as the number of people who can build some sort of house.

@carlmr, I understood the position better now. Maybe states should completely fund or control medical researches. This is one thing which should never be done for profit.

>For Lydia’s, there are only two others in the entire world — one in Greece and one in England

Both countries with socialized medicine and yet they still didn't come up with a cure. It happened in one of the most, if not the most, capitalistic tech-hubs in the world. Maybe there's just something about the private sector that gets things done.

> Both countries with socialized medicine and yet they still didn't come up with a cure.

This is misleading. The original post was about medical research, which neither in Greece nor in England is any more "socialized" than elsewhere. They might have national health services, but those buy their medicines from the same private actors as any hospital in the United States.

Also note that the original article is specifically not about profit-driven R&D but about a donation-funded, non-profit venture. The (hopeful!) success of such a venture does not really translate well into an argument for private, for-profit medicine R&D.

You could argue that it's the raw capitalistic drive of SV that is uniquely able to generate the wealth necessary for such non-profit ventures, ok, fine (there are also counter arguments to this), but this was not really the point of the original comment.

As the article argues, there's no profit to be made because of lack of patentability. If this is the case, maybe an adjustment in incentives on the side of the law would fix this and make the private sector interested.

A lot of the big medical innovations still come from the private sector. The question is only whether we can get the interests aligned here.