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.
So long as the research has a conclusion, it's not a failure. We learned something. There may be something to be said for whether or not the research is a worthy topic, but that's a different conversation.
Without some research the current President would probably not be healthy enough to be in office, clearly we have to reduce the risk of that happening again.
The most frustrating thing is they all get away with endless daily lies and just move onto the next subject, NIH might never recover, certainly not this decade.
> Hours after Musk asserted that USAID had restored its Ebola prevention efforts, the agency informed several organizations working with the U.S. government to prevent the spread of the virus overseas that their contracts had been terminated
> organizations — which included UNICEF, which had been working with USAID on Ebola prevention in Uganda and other countries — were among thousands of organizations affected by the Trump administration’s move to cancel foreign-assistance contracts
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?
The alternative being implemented is that insiders could not police themselves, so outsiders are doing it for them with far less precision.
It’s like a hoarders show where everyone is shocked (SHOCKED!) that things had gotten as bad as it is, the hoarder has lost the capability to determine what is valuable or necessary, so a third party with no attachment or sentiment comes in to clean house and throws out the good with the bad.
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.
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...
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.
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.
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.
> 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.
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.
I was referring to the election of Trump and the people he's appointed. Everything was rotting from the inside out and infested, and like with everything that is rotted/rusting, you will have to carve it all out to clean it, and sometimes you unfortunately take out legitimate and healthy things.
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.
That's true, but I have lots of experience with the NIH, and haven't found it stultified nor corrupted. In fact, did you hear they recently funded a project that reversed type 1 diabetes?
Besides what others have said, the government is immune from many of the multi-agent coordination problems that trap other types of entities. It's basically the essential reason we have government at all.
So no, not all things government does can be replaced by the private sector, for reasons of game theory.
Slashing is not permanent. It is important to slash in order to determine a middle ground. If a company fires 100 employees and certain operations stop functioning, they may hire back 10 employees and reassess. If operations are still not functional enough, they will hire 10 more. This process continues until everything is operational again. The result is a company that functions just as effectively as before but with fewer employees. This is an optimization of resources and efficiency.
>It is important to slash in order to determine a middle ground
That's not true.
> If a company fires 100 employees and certain operations stop functioning, they may hire back 10 employees and reassess
How likely is it that 10 employees come back? How likely is it that critical institutional knowledge is lost forever?
> The result is a company that functions just as effectively as before but with fewer employees
Does it? Have you ever been through a reorg or restructuring at work? Do things ever get back to just as effective as before any time soon?
> This is an optimization of resources and efficiency
It's squandering human capitol, knowledge and reduced efficiency both in the short term and long term. It's the most expensive way to reduce your overhead. A far cry from optimization.
> How likely is it that critical institutional knowledge is lost forever?
In the digital age, almost impossible. Documentation, process automation, and knowledge transfer mitigate this risk.
> Does it? Have you ever been through a reorg or restructuring at work? Do things ever get back to just as effective as before any time soon?
Yes, I've been through many re-orgs at AWS. If done right, things get better fairly quickly (3-6 months).
> It's squandering human capital, knowledge, and reduced efficiency both in the short term and long term. It's the most expensive way to reduce your overhead. A far cry from optimization.
Not necessarily. The short-term pain of restructuring can lead to long-term efficiency gains. Organizations that fail to optimize end up bloated and sluggish, which is far more costly in the long run. Smart cuts, when combined with proper reallocation of resources, create a more effective organization.
> In the digital age, almost impossible. Documentation, process automation, and knowledge transfer mitigate this risk.
Nobody is so thorough at documenting that their job is 100% documented and the documentation is fully up to date.
You think Jim, who's been training the new hires on the factory floor for a decade, who knows all the tricks to making this fit together at wiget factory even when the process instructions are vague, has documented everything?
Could document everything?
Just be cause digital records are present doesn't mean they're complete, up to date or accurate.
Institutional knowledge is a thing, and it's very valuable. You can't wave it away and say we're in a digital age.
> You think Jim, who's been training the new hires on the factory floor for a decade, who knows all the tricks to making this fit together at wiget factory even when the process instructions are vague, has documented everything?
No, I don't think so. That's why the lay-offs predominantly target probationary employees.
Your last sentence undermines the point in this case. What Musk and Trump are doing are hardly "smart cuts". They couldn't possibly be, with how quickly executed. They are a sledgehammer.
It hasn't been limited to probationary employees. Here's one example: https://www.science.org/content/article/nih-ban-renewing-sen...
Agencies have also been directed to make plans for "significant reductions". For example, EPA plans to cut 65%. Fish and Wildlife and the Bureau of Indian Affairs are preparing for up to 40%. These latter cuts haven't happened yet, but they're very likely.
That's correct. It hasn't been limited to probationary employees only, but many are. Those who are not either aren't needed or will be rehired if operations cannot continue without them.
It's not just about the literal employee contracts. Telling all USAID workers to cease operations and come home within 30 days is still a "cut" even if they are still employed. Not hiring seasonal workers for national parks is a cut. Removing info from the CDC website is a cut. Cancelling the meeting on flu vaccines is a cut.
It's a very hamfisted deliberate disruption of all operations and services. Which, again, can hardly be called "targeted" by any metric.
How the heck do you apply this process to fundamental research? It's pretty much always the case that with basic research you could have cut 95% of studies after the fact and it wouldn't have made much difference in the end.
The problem is you don't know which 95% of studies beforehand.
Neither companies nor governments fire 100% of their personnel unless a division is no longer needed. Governments, especially, have safeguards to ensure essential functions continue, so they don't simply stop functioning all of a sudden. From a bird's-eye view, a government is not much different from a company. They both allocate resources, manage personnel and strive for efficiency.
> 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.
As a T1D: can confirm. Taking insulin is a hassle, but definitely not "I'd rather take immunosuppressants". I'm having a hard time even contextualizing how much worse that is.
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.
I am of the glum opinion that the hideously interwoven nature of our immune system is at least partly a security feature rather than an engineering flaw.
That said, we might still learn from the success of its contemporary attackers, who haven't been slacking over the past millions of years either.
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.
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.
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.
Do you have any evidence that cancer develops resistance to rapamycin? I’d love to read a study. The data I linked shows lower incidence of cancer among transplant patients taking rapamycin than the general population.
Off hand my first thoughts are (a) well it would make sense that the non-rapamycin-sensitive cancer cells would naturally be selected for - but that doesn't mean that your rates of cancer would be higher - and (b) how do you square this with the measured lower cancer rates in transplant patients on rapamycin?
My take, admittedly more research needed on my part, is that the cancer risk of anti rejection drugs is because the immune system would normally nuke some of these from orbit. However rapamycin works differently and doesn’t suppress the immune system so even with resistance developing the cancer risk would still be somewhere between lower and neutral.
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.
I've experienced quasi-remission twice now. Both times when I got so sick from food in a foreign country that I couldn't eat for days (and had no appetite for it either). I lived on water. Afterwards, for 1-2 weeks, I did not require insulin (while eating a lot).
I used to think it was due to the pills they gave me there, or perhaps due to the bacteria (or virus?) causing some strange temporal abating of auto-immune response and regrowth of beta-cells. But seeing this is making me reconsider that (I was doubting the effect of the medicine since I took some home and took it in a healthy state but did not get the good effects).
I've been Type 1 for 20+ years and have measurable remissions based on blood tests. Low level functioning of pancreas again.
The thing that moved the needle for me was fasting + ultra running (which from my understanding implements a fasting-like response by the body in some ways).
Interesting that not eating for a while correlated with what seems like increased pancreatic activity...
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.
> Most research fails
So long as the research has a conclusion, it's not a failure. We learned something. There may be something to be said for whether or not the research is a worthy topic, but that's a different conversation.
Without some research the current President would probably not be healthy enough to be in office, clearly we have to reduce the risk of that happening again.
Negative results are not a failure - this perception is one of the biggest problems with academia
Scientists and their work is not "fungible"
There is going to be AT LEAST a whole generation of loss of progress at this point.
Everything is going to slowly crawl to a stop
and it's not an accident but by design, it's right out of Project2025
https://www.science.org/content/article/nih-ban-renewing-sen...
Don't worry they'll take credit for saving this
Are you referring to the recent Ebola prevention-related cuts?
https://www.npr.org/sections/goats-and-soda/2025/02/27/g-s1-...
The most frustrating thing is they all get away with endless daily lies and just move onto the next subject, NIH might never recover, certainly not this decade.
https://www.washingtonpost.com/politics/2025/02/26/elon-musk...
> Hours after Musk asserted that USAID had restored its Ebola prevention efforts, the agency informed several organizations working with the U.S. government to prevent the spread of the virus overseas that their contracts had been terminated
> organizations — which included UNICEF, which had been working with USAID on Ebola prevention in Uganda and other countries — were among thousands of organizations affected by the Trump administration’s move to cancel foreign-assistance contracts
[flagged]
( 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?
The alternative being implemented is that insiders could not police themselves, so outsiders are doing it for them with far less precision.
It’s like a hoarders show where everyone is shocked (SHOCKED!) that things had gotten as bad as it is, the hoarder has lost the capability to determine what is valuable or necessary, so a third party with no attachment or sentiment comes in to clean house and throws out the good with the bad.
Out of curiosity, how much direct experience do you have with the NIH? Or are you just assuming that what you say is true?
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.
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.
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".
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.
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.
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.
> 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.
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.
I was referring to the election of Trump and the people he's appointed. Everything was rotting from the inside out and infested, and like with everything that is rotted/rusting, you will have to carve it all out to clean it, and sometimes you unfortunately take out legitimate and healthy things.
That is an assertion without evidence. Just because lots of people say it doesn't make it true.
And even if it is true, you could carefully and surgically remove the rot, instead of chopping off whole limbs.
And even then, you can do it following the laws set by Congress, rather than by executive decree.
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.
That's true, but I have lots of experience with the NIH, and haven't found it stultified nor corrupted. In fact, did you hear they recently funded a project that reversed type 1 diabetes?
> If an institute becomes stultified and corrupt
Are you implying the NIH is "stultified and corrupt"?
If so, care to back that claim up?
Besides what others have said, the government is immune from many of the multi-agent coordination problems that trap other types of entities. It's basically the essential reason we have government at all.
So no, not all things government does can be replaced by the private sector, for reasons of game theory.
There is no certainty the new order will be better than the previous one.
Trying to fix the world with a sledgehammer.
Then fund it yourself! Don't try to force me to pay for it.
I hope that you do not consume a single dime of government resources that I'd prefer not to pay for. But I'm going to be that's not true.
What does this comment mean? What institute are you referring to in this cryptic comment?
Slashing is not permanent. It is important to slash in order to determine a middle ground. If a company fires 100 employees and certain operations stop functioning, they may hire back 10 employees and reassess. If operations are still not functional enough, they will hire 10 more. This process continues until everything is operational again. The result is a company that functions just as effectively as before but with fewer employees. This is an optimization of resources and efficiency.
>It is important to slash in order to determine a middle ground
That's not true.
> If a company fires 100 employees and certain operations stop functioning, they may hire back 10 employees and reassess
How likely is it that 10 employees come back? How likely is it that critical institutional knowledge is lost forever?
> The result is a company that functions just as effectively as before but with fewer employees
Does it? Have you ever been through a reorg or restructuring at work? Do things ever get back to just as effective as before any time soon?
> This is an optimization of resources and efficiency
It's squandering human capitol, knowledge and reduced efficiency both in the short term and long term. It's the most expensive way to reduce your overhead. A far cry from optimization.
> That's not true.
No, that's ^ not true ¯\_(ツ)_/¯
> How likely is it that 10 employees come back?
Pretty much nobody is irreplaceable.
> How likely is it that critical institutional knowledge is lost forever?
In the digital age, almost impossible. Documentation, process automation, and knowledge transfer mitigate this risk.
> Does it? Have you ever been through a reorg or restructuring at work? Do things ever get back to just as effective as before any time soon?
Yes, I've been through many re-orgs at AWS. If done right, things get better fairly quickly (3-6 months).
> It's squandering human capital, knowledge, and reduced efficiency both in the short term and long term. It's the most expensive way to reduce your overhead. A far cry from optimization.
Not necessarily. The short-term pain of restructuring can lead to long-term efficiency gains. Organizations that fail to optimize end up bloated and sluggish, which is far more costly in the long run. Smart cuts, when combined with proper reallocation of resources, create a more effective organization.
> In the digital age, almost impossible. Documentation, process automation, and knowledge transfer mitigate this risk.
Nobody is so thorough at documenting that their job is 100% documented and the documentation is fully up to date.
You think Jim, who's been training the new hires on the factory floor for a decade, who knows all the tricks to making this fit together at wiget factory even when the process instructions are vague, has documented everything?
Could document everything?
Just be cause digital records are present doesn't mean they're complete, up to date or accurate.
Institutional knowledge is a thing, and it's very valuable. You can't wave it away and say we're in a digital age.
> You think Jim, who's been training the new hires on the factory floor for a decade, who knows all the tricks to making this fit together at wiget factory even when the process instructions are vague, has documented everything?
No, I don't think so. That's why the lay-offs predominantly target probationary employees.
What do you believe "probationary employees" means?
What is their average tenure at the department?
They are in the first year of employment.
No. They are in the first year of their current level/role. That may mean the first year of employment. It could also mean they were promoted.
Is this actually the case? what about people who were promoted or moved positions?
Is this the case for all federal jobs or can it be longer for some roles?
Your last sentence undermines the point in this case. What Musk and Trump are doing are hardly "smart cuts". They couldn't possibly be, with how quickly executed. They are a sledgehammer.
probationary employees
It hasn't been limited to probationary employees. Here's one example: https://www.science.org/content/article/nih-ban-renewing-sen... Agencies have also been directed to make plans for "significant reductions". For example, EPA plans to cut 65%. Fish and Wildlife and the Bureau of Indian Affairs are preparing for up to 40%. These latter cuts haven't happened yet, but they're very likely.
That's correct. It hasn't been limited to probationary employees only, but many are. Those who are not either aren't needed or will be rehired if operations cannot continue without them.
It's not just about the literal employee contracts. Telling all USAID workers to cease operations and come home within 30 days is still a "cut" even if they are still employed. Not hiring seasonal workers for national parks is a cut. Removing info from the CDC website is a cut. Cancelling the meeting on flu vaccines is a cut.
It's a very hamfisted deliberate disruption of all operations and services. Which, again, can hardly be called "targeted" by any metric.
recent promotees are probationary
How the heck do you apply this process to fundamental research? It's pretty much always the case that with basic research you could have cut 95% of studies after the fact and it wouldn't have made much difference in the end.
The problem is you don't know which 95% of studies beforehand.
If a government stops functioning, the result isn't the same as a company.
The argument that 'slashing' is the only way to reduce headcount is also extremely dumb.
Neither companies nor governments fire 100% of their personnel unless a division is no longer needed. Governments, especially, have safeguards to ensure essential functions continue, so they don't simply stop functioning all of a sudden. From a bird's-eye view, a government is not much different from a company. They both allocate resources, manage personnel and strive for efficiency.
Not many safeguards for that under unitary executive theory which is likely to become case law soon. Aside from impeachment.
You realize the whole debate is about what different people consider "essential", right?
It’s historically difficult to advocate for increased budgets & spending. Usually what is cut stays cut.
> 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.
As a T1D: can confirm. Taking insulin is a hassle, but definitely not "I'd rather take immunosuppressants". I'm having a hard time even contextualizing how much worse that is.
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.
I am of the glum opinion that the hideously interwoven nature of our immune system is at least partly a security feature rather than an engineering flaw.
That said, we might still learn from the success of its contemporary attackers, who haven't been slacking over the past millions of years either.
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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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.
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
Do you have any evidence that cancer develops resistance to rapamycin? I’d love to read a study. The data I linked shows lower incidence of cancer among transplant patients taking rapamycin than the general population.
I apologize for not posting any reference. The topic is well known in oncology
https://pubmed.ncbi.nlm.nih.gov/21389767/
Disclaimer: The newer the article, the less reliable it is. There were well disguised garbage articles in the 2000's, but there are too many now.
Thanks I'm going to give it a read!
Off hand my first thoughts are (a) well it would make sense that the non-rapamycin-sensitive cancer cells would naturally be selected for - but that doesn't mean that your rates of cancer would be higher - and (b) how do you square this with the measured lower cancer rates in transplant patients on rapamycin?
My take, admittedly more research needed on my part, is that the cancer risk of anti rejection drugs is because the immune system would normally nuke some of these from orbit. However rapamycin works differently and doesn’t suppress the immune system so even with resistance developing the cancer risk would still be somewhere between lower and neutral.
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.
5 years away?
in mice
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.
Cool! Now fix Type 2, which is managed by reducing sugar intake.
No, wait, just take a pill!
...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.
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Finally with this and Ozempic, I can get diabetes and be fat, and then restart the process again.
Also impact of diet should not be underestimated https://pmc.ncbi.nlm.nih.gov/articles/PMC5357144/
edit: at least on mices for now
I've experienced quasi-remission twice now. Both times when I got so sick from food in a foreign country that I couldn't eat for days (and had no appetite for it either). I lived on water. Afterwards, for 1-2 weeks, I did not require insulin (while eating a lot).
I used to think it was due to the pills they gave me there, or perhaps due to the bacteria (or virus?) causing some strange temporal abating of auto-immune response and regrowth of beta-cells. But seeing this is making me reconsider that (I was doubting the effect of the medicine since I took some home and took it in a healthy state but did not get the good effects).
I've been Type 1 for 20+ years and have measurable remissions based on blood tests. Low level functioning of pancreas again.
The thing that moved the needle for me was fasting + ultra running (which from my understanding implements a fasting-like response by the body in some ways).
Interesting that not eating for a while correlated with what seems like increased pancreatic activity...
If you are interested, Valter Longo in a fairly recent and interesting podcast https://youtu.be/ZwdhdevxlRg?si=sDknOzmwx7Nk_wQR