More groundbreaking research funded by the NIH. It's sad to think about how much the US is going to lose with the arbitrary slashing and burning and purging.
Most research that is pointed towards important things does get funding from NIH. Most research fails. NIH has a bucket of money for every major issue facing the population. Just takes a few PhD's and a hypothesis to write a proposal.
The important thing is that these things get funded. It doesn't matter what institute funds them. If an institute becomes stultified and corrupt, there's no reason to champion it over creating another.
It's all well and good to suggest that each program receiving funding gets a thorough review. Of course, that review needs to be by experts, to ensure it gets a fair shake. Who are the experts in the field? The odds that you can be an expert in the field (by publication count, let's say) without having already been funded by the NIH is pretty slim. So now your experts are also insiders.
That's going to be a big problem as very few insiders are going to be willing to rock the boat. Even if it's necessary.
Maybe you've got a good idea of how to solve this "good review requires experts, experts are very likely insiders, insiders are unlikely to rock the boat" problem. It would be wonderful if there was some solution, even if it was hard.
> Maybe you've got a good idea of how to solve this "good review requires experts, experts are very likely insiders, insiders are unlikely to rock the boat" problem.
You're the one who has identified this as a problem, shouldn't you be the one to suggest an alternative?
Couldn't at least part of the reviewing be done by foreign experts?
Having said that, this smells witch-hunty to me. The US can boast decades of excellence in medical and biological sciences, which in turn generates a massive windfall. Completely upending the architecture behind this dominance on the suspicion that a few hundred million bucks are less-than-optimally spent is a hell of a gambit, and even ignores all the higher-order effects that even that "spare change" bring about.
You've made at least 2-3 personal attacks against me while seemingly not even trying to address the problem that I highlighted. If that's your goal, OK. It definitely goes against the spirit of the rules here if not the letter.
Delaying the flu vaccine? Ok that's bad, sure.
It's also a real goalpost move and also doesn't address the technical problem "insiders going to inside" I raised in answer to the parent's paraphrased "I can't understand this, why is this necessary?"
I don't know that doing things this way is strictly necessary. But I also don't think it's reasonable to just hand-wave away or worse completely fail to even acknowledge much less actually address the insiders problem.
We spend a large portion of the federal budget on human death prevention. It sounds like hyperbole, but anyone dying from administrative changes is literally “world ending” for them.
If a plan to cut bureaucracy was somehow analyzed to find that we could save 5% of the US budget in exchange for 10,000 lives, reasonable people might consider otherwise. To take these changes against life-saving organizations without first analysis of consequences is pretty reckless.
Q> Can you explain why the sledge hammer approach, removing funding for things wholesale and causing large amounts of destruction (both economic and health) is reasonable?
And your answer was
A> It looks like there is a problem with the current system, and changing something would be beneficial.
And, while I agree that the sentiment ("changing something would be beneficial") is fair... as an answer it falls squarely into "We should do something, this is something, so we should do this", which is categorically ridiculous. The way to approach these types of issues, where changing things can (and does) have real, significant impact on lots of people, is to come up with a plan and discuss what the impacts/tradeoffs are. It is _not_ to just do the first thing that comes to mind and then ignore the people who's lives your destroying.
> But I also don't think it's reasonable to just hand-wave away or worse completely fail to even acknowledge much less actually address the insiders problem.
ok but burning down a house with a family in it because of a hypothetical burglar usually isn't a good solution.
It's simple, really. Make it so the experts have 0 leverage. Maybe have "the workers" make all the decisions! ??? Profit? :-) They tried this in Soviet Union...
I'm sure you have direct economic interests. Odds are good someone in your circle is type 1 diabetic, and helping that person will indirectly help you.
Yes, immunity is the big problem. You probably need to replenish the islets either way. Also, I don't think doctors would be content giving someone that isn't suppressed this without loads of research.
> To prevent islet rejection, immune-suppressing drugs are given over the long term.
This makes it a non starter. Immunosuppressants are generally considered a worse quality of life than insulin treatment. That's why pancreas transplants are generally only done for type 1 diabetics if they are already on immunosuppressants.
I'm hopeful that someday we'll have a good system for "caging" cells to prevent an immune response (in either direction) while also permitting the visitors to sustain themselves with blood nutrients and regulate hormones or clean waste.
Sort of like the role of the blood-brain barrier, or maybe a placenta.
Yes! I think there was some work being done with a islet transplant like that. I'm not sure of the details though - it's probably a long way off, if it works.
Yep. The hard, if not kear impossible part will be just resetting the one part of the immune system attacking the islets without turning off or resetting the immune system.
The promising part here is that someday it will be possible to take stem cells from a patient and specialize them to islet cells. Similar to what they’re doing here with vascular cells. It’s far too expensive at the moment, but ultimately the process will be improved and refined, and the costs will come down. At least that’s my hope for a cure.
Easiest method may be to nuke the immune system and put a new one in place. As the immune system consists of several parts it may be sufficient to just replace one of them.
not really? this is basically already deployed as a cure for AIDS (with an N in the single digits iirc). the issue is not technical, it's that it's such an extreme solution that without more safety data it's ethically a hard sell for a condition like diabetes.
So it's a trade-off between increased risk of cancer[0] and the consequences of type 1 diabetes? Doesn't sound like a fun trade-off but I don't know anything.
If you take rapamycin or a rapalog as an anti-rejection drug, your risk of cancer is lower - not higher - because it's not actually an immune suppressant so much as a drug that prevents hyperimmunity. [1] Other immune suppressants work differently but it's not a blanket true statement that taking anti-rejection drugs will increase your risk of cancer. Depends what you take.
You can read the section in [1] titled "Cancer prevention in humans."
> Starting from 2004, numerous studies demonstrated that rapamycin and everolimus reduced the incidence of various cancers in organ transplant patients.
[edit] In fact in addition to its use as an anti-rejection medication, rapamycin is used as chemotherapy to treat certain forms of cancer.
I don't think that's how Type I Diabetes works. People get Type I Diabetes because their immune system attacked their own insulin producing cells in the first place. It's an autoimmune disease. So if you replenish those cells, they'll just get attacked again.
Possibly, it is defo important to keep tabs on how these patients fare after a few years. before we rush to ship this
From above link:
>A 25-year-old woman with type 1 diabetes became the first person to successfully receive a transplant of insulin-producing cells derived from her own reprogrammed stem cells
Type 1 diabetic here: you're right, it's a bad tradeoff. We already can do pancreas transplants for T1D, but the reason it's very uncommon is that immunosuppressants are a very bad tradeoff. Insulin treatment is preferred in the vast majority of cases.
Stuff like this will never be a breakthrough until it doesn't need immunosuppressants. The best advancements in diabetes treatment will most likely continue to be on closed loop artificial pancreas systems.
I wouldn't call closed loop systems much of an advancement... Sure, it doses insulin automatically based off of CGM data, but it's barely any better than just injecting yourself. Cons even outweight the pros for some - being constantly attached to a device is no fun. And the slugishness of exogenous insulin (both: the way it is injected and its time of action) diminishes any attempts to achieve precision using CGM data and algorithms in controlling diabetes. Not to mention CGM data isn't that accurate/rapid enough also. All in all, it's just not efficient, calling these systems 'artificial pancreas' is more of a marketing gimmick than reality, thus why a proper cure is needed.
Insulin-specific immunotherapies are currently under development. We will soon be able to restore tolerance to insulin, and other pancreatic antigens such as GAD-65, without the need for broad immunosupressants. Ideally, this should stop β cell destruction and conversion to T1D from auto-antibody positive status, as well as facilitate islet transplants with minimal side effects for those that are already T1D patients.
The author claimed no competing interests, yet his research is used for the patents. We'll see how it plays out in the real world after all the stardust settles.
Awesome. Hopefully when this is perfected they'll be enough pancreases to cure everyone. My pancreas is ear marked for my sibling should I become an eligible donor.
And not just mice, but mice engineered with “T1D like” conditions. Human testing too early is certainly undesirable but these studies with mice, while necessary and important, are nothing newsworthy for the general public (but good for fundraising for follow up work).
Not if it requires immune suppressants. They can already transplant whole pancreases. They rarely do because the resulting lifetime of immune suppression is worse than the quite effective insulin injections.
Any research could pay big benefits eventually but this is far from "great news". It's a step forward along a path that is actually well behind the others.
I think you and I have a different approach to science.
I see research as not entirely linear and think that multiple paths should be funded. Most paths won't be "the definitive answer" but add capability, or definitively rule out an approach, that can be used in other scenarios. TheFineArticle shows a different path to the others and they made a great step on it - that seems like money well spent to me.
What I get from reading your post is that it's some kind of race and only the one currently winning should be lauded. I'm not sure if that is what you intend to communicate though.
She was on immunosuppressants, so how long the new beta cells would last without those is still an open question. Other similar, ongoing trials are showing promising results.
More groundbreaking research funded by the NIH. It's sad to think about how much the US is going to lose with the arbitrary slashing and burning and purging.
Most research that is pointed towards important things does get funding from NIH. Most research fails. NIH has a bucket of money for every major issue facing the population. Just takes a few PhD's and a hypothesis to write a proposal.
Don't worry they'll take credit for saving this
The important thing is that these things get funded. It doesn't matter what institute funds them. If an institute becomes stultified and corrupt, there's no reason to champion it over creating another.
> If an institute becomes stultified and corrupt
Are you implying the NIH is "stultified and corrupt"?
If so, care to back that claim up?
What does this comment mean? What institute are you referring to in this cryptic comment?
There is no certainty the new order will be better than the previous one.
Trying to fix the world with a sledgehammer.
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( I am neither a voter in the U.S. elections nor do I have direct economic interests there)
Could you point me to an articulation that explains why arbitrarily purging (mentioned by your parent post) has been necessary ( mentioned by you)?
It's all well and good to suggest that each program receiving funding gets a thorough review. Of course, that review needs to be by experts, to ensure it gets a fair shake. Who are the experts in the field? The odds that you can be an expert in the field (by publication count, let's say) without having already been funded by the NIH is pretty slim. So now your experts are also insiders.
That's going to be a big problem as very few insiders are going to be willing to rock the boat. Even if it's necessary.
Maybe you've got a good idea of how to solve this "good review requires experts, experts are very likely insiders, insiders are unlikely to rock the boat" problem. It would be wonderful if there was some solution, even if it was hard.
> Maybe you've got a good idea of how to solve this "good review requires experts, experts are very likely insiders, insiders are unlikely to rock the boat" problem.
You're the one who has identified this as a problem, shouldn't you be the one to suggest an alternative?
I contributed heavily to a paper once. One of my reviewers lit it on fire with ample, good criticism.
There may be problems with the system (show me one without), but it does work.
Out of curiosity, how much direct experience do you have with the NIH? Or are you just assuming that what you say is true?
Couldn't at least part of the reviewing be done by foreign experts?
Having said that, this smells witch-hunty to me. The US can boast decades of excellence in medical and biological sciences, which in turn generates a massive windfall. Completely upending the architecture behind this dominance on the suspicion that a few hundred million bucks are less-than-optimally spent is a hell of a gambit, and even ignores all the higher-order effects that even that "spare change" bring about.
You're insane. Jaw dropping ignorance justifying world ending cruelty.
You understand that they're delaying the flu vaccine in a way that will kill 10,000 elderly people next year?
You've made at least 2-3 personal attacks against me while seemingly not even trying to address the problem that I highlighted. If that's your goal, OK. It definitely goes against the spirit of the rules here if not the letter.
Delaying the flu vaccine? Ok that's bad, sure.
It's also a real goalpost move and also doesn't address the technical problem "insiders going to inside" I raised in answer to the parent's paraphrased "I can't understand this, why is this necessary?"
I don't know that doing things this way is strictly necessary. But I also don't think it's reasonable to just hand-wave away or worse completely fail to even acknowledge much less actually address the insiders problem.
We spend a large portion of the federal budget on human death prevention. It sounds like hyperbole, but anyone dying from administrative changes is literally “world ending” for them.
If a plan to cut bureaucracy was somehow analyzed to find that we could save 5% of the US budget in exchange for 10,000 lives, reasonable people might consider otherwise. To take these changes against life-saving organizations without first analysis of consequences is pretty reckless.
It _seems_ like the question was
Q> Can you explain why the sledge hammer approach, removing funding for things wholesale and causing large amounts of destruction (both economic and health) is reasonable?
And your answer was
A> It looks like there is a problem with the current system, and changing something would be beneficial.
And, while I agree that the sentiment ("changing something would be beneficial") is fair... as an answer it falls squarely into "We should do something, this is something, so we should do this", which is categorically ridiculous. The way to approach these types of issues, where changing things can (and does) have real, significant impact on lots of people, is to come up with a plan and discuss what the impacts/tradeoffs are. It is _not_ to just do the first thing that comes to mind and then ignore the people who's lives your destroying.
> But I also don't think it's reasonable to just hand-wave away or worse completely fail to even acknowledge much less actually address the insiders problem.
ok but burning down a house with a family in it because of a hypothetical burglar usually isn't a good solution.
It's simple, really. Make it so the experts have 0 leverage. Maybe have "the workers" make all the decisions! ??? Profit? :-) They tried this in Soviet Union...
I wouldn't call the nomenklatura mere "workers".
I'm sure you have direct economic interests. Odds are good someone in your circle is type 1 diabetic, and helping that person will indirectly help you.
A comment I saved recently offers an explanation: https://news.ycombinator.com/item?id=43147910
I don't agree with it but I understand it.
That’s Fascism baby. Action for actions sake, otherwise the people will notice things aren’t as bad the shouting implies.
If you pair this with genetically engineered hypoimmune islet cells to avoid needing to suppress immune system you could have a viable cure. https://ir.sana.com/news-releases/news-release-details/sana-...
Yes! You can also induce islet cells from the patient's own stem cells:
https://stemcellres.biomedcentral.com/articles/10.1186/s1328...
Except, a diabetic's immune system already wants to kill those too...
True, Sana above are attempting to extend their gene engineering ("HIP") to stem cells as well
>apply the HIP technology to develop therapeutic candidates at scale, including both pluripotent stem cells and donor-derived allogeneic CAR T cells.
Yes, immunity is the big problem. You probably need to replenish the islets either way. Also, I don't think doctors would be content giving someone that isn't suppressed this without loads of research.
> To prevent islet rejection, immune-suppressing drugs are given over the long term.
This makes it a non starter. Immunosuppressants are generally considered a worse quality of life than insulin treatment. That's why pancreas transplants are generally only done for type 1 diabetics if they are already on immunosuppressants.
Lots of biotech companies are working on immunosuppressant-free islet-equivalent transplantation.
Two examples off the top of my head: Sana recently announced islet cell transplantation without immunosuppression (press release: https://ir.sana.com/news-releases/news-release-details/sana-... ) and Vertex (ongoing trial: https://www.breakthrought1d.org/news-and-updates/vertex-laun... ).
I'm hopeful that someday we'll have a good system for "caging" cells to prevent an immune response (in either direction) while also permitting the visitors to sustain themselves with blood nutrients and regulate hormones or clean waste.
Sort of like the role of the blood-brain barrier, or maybe a placenta.
What'd be interesting would being able to shut down specific auto-immune responses. Currently most of what we have are hammers of one sort or another.
Yes! I think there was some work being done with a islet transplant like that. I'm not sure of the details though - it's probably a long way off, if it works.
Yep. The hard, if not kear impossible part will be just resetting the one part of the immune system attacking the islets without turning off or resetting the immune system.
The promising part here is that someday it will be possible to take stem cells from a patient and specialize them to islet cells. Similar to what they’re doing here with vascular cells. It’s far too expensive at the moment, but ultimately the process will be improved and refined, and the costs will come down. At least that’s my hope for a cure.
Easiest method may be to nuke the immune system and put a new one in place. As the immune system consists of several parts it may be sufficient to just replace one of them.
Sounds like 22nd century tech at least. Good to dream of, not practical even for very young here to think it would help them
not really? this is basically already deployed as a cure for AIDS (with an N in the single digits iirc). the issue is not technical, it's that it's such an extreme solution that without more safety data it's ethically a hard sell for a condition like diabetes.
Note this is for the current common approach, not the new approach.
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So it's a trade-off between increased risk of cancer[0] and the consequences of type 1 diabetes? Doesn't sound like a fun trade-off but I don't know anything.
[0] https://www.cancer.gov/about-cancer/causes-prevention/risk/i...
If you take rapamycin or a rapalog as an anti-rejection drug, your risk of cancer is lower - not higher - because it's not actually an immune suppressant so much as a drug that prevents hyperimmunity. [1] Other immune suppressants work differently but it's not a blanket true statement that taking anti-rejection drugs will increase your risk of cancer. Depends what you take.
You can read the section in [1] titled "Cancer prevention in humans."
> Starting from 2004, numerous studies demonstrated that rapamycin and everolimus reduced the incidence of various cancers in organ transplant patients.
[edit] In fact in addition to its use as an anti-rejection medication, rapamycin is used as chemotherapy to treat certain forms of cancer.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC10103596/
Cancer develops resistance to rapamycin. Cancer always finds a way
My point is cancer is worse than DI. At least you can manage DI
There was a recent "breakthrough" involving the same, except with patient's own stem cells, & not just in mice.
https://stemcellres.biomedcentral.com/articles/10.1186/s1328...
That would mitigate the cancer risk, since immunosuppression would not be required?
> patient's own stem cells
> immunosuppression would not be required
I don't think that's how Type I Diabetes works. People get Type I Diabetes because their immune system attacked their own insulin producing cells in the first place. It's an autoimmune disease. So if you replenish those cells, they'll just get attacked again.
There were these studies where t1d patients immune system was "restarted" and they became insulin free. https://pubmed.ncbi.nlm.nih.gov/17426276/
Possibly, it is defo important to keep tabs on how these patients fare after a few years. before we rush to ship this
From above link:
>A 25-year-old woman with type 1 diabetes became the first person to successfully receive a transplant of insulin-producing cells derived from her own reprogrammed stem cells
Type 1 diabetic here: you're right, it's a bad tradeoff. We already can do pancreas transplants for T1D, but the reason it's very uncommon is that immunosuppressants are a very bad tradeoff. Insulin treatment is preferred in the vast majority of cases.
Stuff like this will never be a breakthrough until it doesn't need immunosuppressants. The best advancements in diabetes treatment will most likely continue to be on closed loop artificial pancreas systems.
I wouldn't call closed loop systems much of an advancement... Sure, it doses insulin automatically based off of CGM data, but it's barely any better than just injecting yourself. Cons even outweight the pros for some - being constantly attached to a device is no fun. And the slugishness of exogenous insulin (both: the way it is injected and its time of action) diminishes any attempts to achieve precision using CGM data and algorithms in controlling diabetes. Not to mention CGM data isn't that accurate/rapid enough also. All in all, it's just not efficient, calling these systems 'artificial pancreas' is more of a marketing gimmick than reality, thus why a proper cure is needed.
Insulin-specific immunotherapies are currently under development. We will soon be able to restore tolerance to insulin, and other pancreatic antigens such as GAD-65, without the need for broad immunosupressants. Ideally, this should stop β cell destruction and conversion to T1D from auto-antibody positive status, as well as facilitate islet transplants with minimal side effects for those that are already T1D patients.
I'm sorry for your plight and I genuinely hope there will be a much more tenable solution in the near future.
The author claimed no competing interests, yet his research is used for the patents. We'll see how it plays out in the real world after all the stardust settles.
Also impact of diet should not be underestimated https://pmc.ncbi.nlm.nih.gov/articles/PMC5357144/
edit: at least on mices for now
5 years away?
Awesome. Hopefully when this is perfected they'll be enough pancreases to cure everyone. My pancreas is ear marked for my sibling should I become an eligible donor.
in mice
...IN MICE
And not just mice, but mice engineered with “T1D like” conditions. Human testing too early is certainly undesirable but these studies with mice, while necessary and important, are nothing newsworthy for the general public (but good for fundraising for follow up work).
Indeed, I would appreciate if the title were updated to reflect that the subjects were mice, not humans. It’s a bit misleading.
Yeah! How amazing is that! Reversing type 1 diabetes anywhere is amazing.
A way to go until it becomes an option for humans. And then way more to go until it becomes a preferred option.
But this is great news.
Not if it requires immune suppressants. They can already transplant whole pancreases. They rarely do because the resulting lifetime of immune suppression is worse than the quite effective insulin injections.
Any research could pay big benefits eventually but this is far from "great news". It's a step forward along a path that is actually well behind the others.
I think you and I have a different approach to science.
I see research as not entirely linear and think that multiple paths should be funded. Most paths won't be "the definitive answer" but add capability, or definitively rule out an approach, that can be used in other scenarios. TheFineArticle shows a different path to the others and they made a great step on it - that seems like money well spent to me.
What I get from reading your post is that it's some kind of race and only the one currently winning should be lauded. I'm not sure if that is what you intend to communicate though.
Rapamycin increases lifespan of mice more than any other known compound.
Longevity benefits are seen at a much lower dose.
https://en.m.wikipedia.org/wiki/The_dose_makes_the_poison
Late last year a woman's T1D was put into remission using beta cells derived from her own stem cells: https://www.nature.com/articles/s41591-024-03394-9
She was on immunosuppressants, so how long the new beta cells would last without those is still an open question. Other similar, ongoing trials are showing promising results.
great, now let's cure type 2, which gets much less attention
I have great news for you: you can cure it on your own, just get off donuts and move your ass. I'm actually jealous of type 2's.
Finally with this and Ozempic, I can get diabetes and be fat, and then restart the process again.
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