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What's going on with gene therapies?

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Re: What's going on with gene therapies?

#51

Post by anon84873628 »

southernplaces7 wrote: post #45
anon84873628 wrote: post #40

Earlier quoted context omitted.

I find this comment to be downright insulting to the parent. You manage to: 1) Call them entitled for feeling angry 2) Remind them that other people have it worse 3) Imply they're stupid for imaging things could work any other way And then try to defend your obviously immature, unproductive, and unsolicited criticism in the "I'm just being logical!" excuse. The parent didn't go on a screed and rage at the world. They…

I see nothing insulting in my comment, unless you think that just so much as questioning any of the premises of an emotional response in someone suffering is automatically an insult. In that case, you're just wrong and irrationally so. Being sick doesn't make a person free of possibly feeling entitled or coming to unreasonable conclusions, nor does it make it wrong to question their feelings. I did so fairly politely…

Please, you didn't just ask genuine innocent questions. You assumed many things about the OP's mindset then passed judgment on it.

You refer several times to argument and debate but you're tilting at windmills. The OP didn't make an argument. The closest thing is "Such is the state of medicine for profit, I guess." which is more of a resigned, bitter observation than overt indictment of capitalism.

If you want to use that as a prompt to say why no other funding model is better, then ok fine. But there are polite ways to do it which acknowledge the legitimacy of the person's feelings.

What's different about my comments is that they address things actually in the text and are in the spirit of bystander intervention and setting the tone of the commons.

Re: What's going on with gene therapies?

#52

Post by baggy_trough »

outworlder wrote: post #48
baggy_trough wrote: post #4

Earlier quoted context omitted.

Wouldn't the same problem occur with any system that has to prioritize resources (that is, any realistic system)?

Maybe not. Because such as system, by design, would have to create a lot of common, shared infrastructure. Once you have centralized the ability to edit genes, most of that machinery can be repurposed for less 'profitable' endeavors. A very crude comparison would be time sharing a radiotelescope. If you want to build one to run school experiments, it's prohibitive. But once you have one, you can use any spare capacit…

Isn't that happening already, through progression in gene technologies?

Re: What's going on with gene therapies?

#53

Post by JohnMakin »

anon84873628 wrote: post #51
southernplaces7 wrote: post #45

Earlier quoted context omitted.

I see nothing insulting in my comment, unless you think that just so much as questioning any of the premises of an emotional response in someone suffering is automatically an insult. In that case, you're just wrong and irrationally so. Being sick doesn't make a person free of possibly feeling entitled or coming to unreasonable conclusions, nor does it make it wrong to question their feelings. I did so fairly politely…

Please, you didn't just ask genuine innocent questions. You assumed many things about the OP's mindset then passed judgment on it. You refer several times to argument and debate but you're tilting at windmills. The OP didn't make an argument. The closest thing is "Such is the state of medicine for profit, I guess." which is more of a resigned, bitter observation than overt indictment of capitalism. If you want to use…

I genuinely appreciate these responses because you state them much calmer and clearer than I can. To me, and I’m not accusing anyone here of this, these discussions feel really dishonest or at the very least completely unempathetic. I see in another comment this user says they feel sympathy, but clearly not empathy. and that’s fine to me! very few people have experienced what I have and will experience, in the specific way that I have, and my heart personally reaches out to anyone else that deals with some health condition that limits their quality of life or worse. I have, however, spent a ridiculous amount of time in the healthcare system, for a variety of reasons other than this specific topic, and know that this kind of callousness is more of a feature than a bug. To my mind, it’s also extraordinarily inefficient.

I’ll pose an argument to the rationalist crowd that I feel likes to think and feed deeply off these types of discussions:

say I’m destined to create the cure for cancer or bring about the singularity or whatever. I’m not, but let’s say I was. And I fall and hit my head one day and die because some billionaire decided that my condition wasn’t worth investing a miniscule fractional percentage of his wealth.

would that be wasteful?

Re: What's going on with gene therapies?

#54

Post by iamleppert »

I had hemophilia gene therapy. It worked for a period of time but the results were not permanent. The problem with many of the gene therapies is that they do not change the nuclear DNA, they just insert copies of working genes into the cell. If a cell dies, it’s gone. The results aren’t carried through to new cells during division.

The other problem is with viral vector based gene therapy is you can’t have it again. You develop antibodies which prevent it from working again, and it could cause a dangerous immune response.

Then there’s the cost. My single treatment cost $3 million as part of a clinical trial, and lasted about 3 years. Normally, it costs about $1 million a year for my normal factor product, which I had to go back on. So I guess it was a wash and it was nice to be free of the medication for a few years. But it’s definitely not perfect and has its own limitations.

Re: What's going on with gene therapies?

#55

Post by MichaelZuo »

outworlder wrote: post #48
baggy_trough wrote: post #4

Earlier quoted context omitted.

Wouldn't the same problem occur with any system that has to prioritize resources (that is, any realistic system)?

Maybe not. Because such as system, by design, would have to create a lot of common, shared infrastructure. Once you have centralized the ability to edit genes, most of that machinery can be repurposed for less 'profitable' endeavors. A very crude comparison would be time sharing a radiotelescope. If you want to build one to run school experiments, it's prohibitive. But once you have one, you can use any spare capacit…

Yeah humans can setup a radiotelescope time-sharing system.

But chimpanzees can’t, regardless of how much effort they put in.

So a time-sharing system 1 million times more complex cannot be created by people who are probably not even 1000x smarter than an average chimp.

Re: What's going on with gene therapies?

#56

Post by spwa4 »

l0new0lf-G wrote: post #27

Could it be just that gene therapies should be publicly funded? Taxpayer money has paid for a substantial percentage of research around the world, and it doesn't seem necessary that we rely on profit-driven private companies for the actual therapies when they could be done at publicly funded hospitals too.

It's less the research and more getting a treatment to people. Governments around the world refuse to pay for this, and in fact demand that various risks and expenses be paid by pharma companies, with mostly negative results.

It is so bad that for a lot of treatments, getting them to people costs upwards of hundreds of millions of dollars. And almost all of these efforts fail.

This would mean the government would need to breed (and pay for) lab animals, small and large (from mice to primates). Would need to pay more for medical care, would need to collect (and pay) people to try out experimental drugs and treatments on. If these treatments or drugs have adverse effects, the government would need to shoulder sometimes lifelong payments and care to these people. It would need to cover all this knowing that in 90% or so of cases the whole effort was for nothing.

This is, to put it mildly, not happening.

Re: What's going on with gene therapies?

#57

Post by JPLeRouzic »

iamleppert wrote: post #54

I had hemophilia gene therapy. It worked for a period of time but the results were not permanent. The problem with many of the gene therapies is that they do not change the nuclear DNA, they just insert copies of working genes into the cell. If a cell dies, it’s gone. The results aren’t carried through to new cells during division. The other problem is with viral vector based gene therapy is you can’t have it again.…

I am sorry you experience this disease. I have a question: You said "they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division."

Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene?

I can imagine other cases, for example, progenitor cells were not infected, cells that do not divide, etc...

Thanks for any answer

Re: What's going on with gene therapies?

#58

Post by mandevil »

colechristensen wrote: post #50
mandevil wrote: post #26

Earlier quoted context omitted.

The experience of patients who received Luxterna was that the single most important difference in how large the improvement was and how many complications they had was the quality of the surgeon who delivered the actual therapy. The best surgeons saw much better results and far fewer complications, and these surgeons are way beyond the capability of some grad student in a lab. The best surgeons were way better than o…

There is a point there but those are also a couple of the most extreme examples. The eyes are delicate complicated organs very isolated from the rest of the body and changing blood characteristics requires sterilizing and replacing your bone marrow which is crazy complex and dangerous. There are many more mundane targets for gene therapy. Also one of the benefits of cheap to produce unique gene therapies is once you…

That second point is what the LUMEOS trial demonstrates is not true: LUMEOS tested a AAV2 vector delivered inside the retina by a surgeon (just like Luxterna) yet instead of 80% of patients showing improvements only 40% did(1). What went wrong? What is the difference? That's going to take more research, which makes the whole thing expensive and time consuming and risky.

We are not yet at the point where we can effectively just substitute genes and everything works in vivo, and until we get to that point every fix requires its own Phase III trial, and that (both the costs and the chance of complete failure) is what drives the R&D expense through the roof, even if a single infusion could fix the problem, unlike the other examples I cited.

1: Existing gene editing platforms don't work well for large genes: there is an effective base pair limit for all existing techniques in vivo. Most Stargardt's genes, to pick another similar to Luxterna as an example, are above that limit, and will require new techniques not yet approved in vivo.

Re: What's going on with gene therapies?

#59

Post by iamleppert »

JPLeRouzic wrote: post #57
iamleppert wrote: post #54

I had hemophilia gene therapy. It worked for a period of time but the results were not permanent. The problem with many of the gene therapies is that they do not change the nuclear DNA, they just insert copies of working genes into the cell. If a cell dies, it’s gone. The results aren’t carried through to new cells during division. The other problem is with viral vector based gene therapy is you can’t have it again.…

I am sorry you experience this disease. I have a question: You said " they do not change the nuclear DNA, they just insert copies of working genes into the cell ... The results aren’t carried through to new cells during division. " Isn't this a bit contradictory? I mean, if they insert copies of working genes into the cell, it is in nuclear DNA, so when the cells divide, the daughter cells carry the new gene? I can i…

The working genes they insert are just into the cell envelope itself, not into the cell nucleus. There are actually a lot of DNA that is free floating around in the cell, and are used during protein synthesis, called episome or non-integrated DNA. This is distinct from the DNA inside the nucleus, which gets copied from generation to generation.

There are techniques that work on modifying nuclear DNA but from my understanding it's much harder (like using CRISPR) and has a lot more risks for things like causing cancer due to off-site editing.

The scales that this technology works is mind-boggling. 10^12 to 10^14 per kg of body weight of individual viral particles that all must do the same thing, and work correctly at scale. Even a few errors could cause serious problems.

Re: What's going on with gene therapies?

#60

Post by mrlatinos »

JohnMakin wrote: post #42
southernplaces7 wrote: post #6

Earlier quoted context omitted.

But in all seriousness, who would you direct your anger at in this case? For one thing, being angry in a general sense implies that a fortuitous blend of circumstances is owed to you by the world in a broad sense so that your specific, completely accidental (of nature) misfortune can be remedied. Secondly, many people suffer from much more common conditions that also have no remedy so far (i'm an example of such), an…

Besides how insulting this comment is, which I'm going to ignore, I'd just point out a common theme in this thread is "limited resources" yet those limited resources are currently being incinerated on things like AI sex bots. Seems like a bit of a fallacy or cope to me. Research for some of these things costs essentially a rounding error. The limited resource you're mentioning here is "profit," not actual resources.…

Profit is driven by demand. It incentivizes meeting demand. Profit is not what is scarce. It's our ability to meet everyone's demand. In a reality where profit does not exist, rare disorders are still at the bottom of the list, because demand and net impact is still low.
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