Top of the front page and no comments? I take it this is being upvoted by lots of folks like myself that are relative laymen but hopeful that this is a meaningful advance. Won't someone explain the practical significance?
If you have a stem cell then in theory you can program it to differentiate into any kind of cell, allowing things like tissue regrowth, repair injuries, make a new lung or liver etc.
Stem cell research has a lot of controversy due to the fact some years ago you could only get stem cells from embryos.
For some people (like the Catholic Church) that was a huge ethical issue.
Now it is not.
Embryonic stem cell research has always been problematic for the Catholic Church, yes, and it will remain so (although there's also a strong argument even from Catholic ethicists that developing things like vaccines from stem cell lines where the contributing embryo died in the 1970s can be licit, because the participation in the death of the embryo is so remote and the benefit potentially so high).
Research on adult stem cells or induced pluripotent stem cells already didn't face the same objections.
It sounds like this is more about an improvement in the technique of inducing pluripotency that could reduce negative complications, rather than a whole new unobjectionable procedure that hadn't existed before.
Bit much to say ESC research was “always” problematic. The notion that life begins at conception was not one that, e.g., St. Thomas Aquinas agreed with. Analyze the ethical issues using his views about life beginning with quickening and you might reach different conclusions than those of the Church today.
I thought that this was such an obvious point that I would not have to make it, but it just goes to show that whatever HN’s comment policies may be about civility and substance, they don’t seem to require a quite basic application of the Principle of Charity. So let me spell it out.
Yes, I am aware that Saint Thomas Aquinas was a medieval theologian and that embryonic stem cell research did not exist at the time.
Maybe you want to argue that there is some necessary connection between ESC research and the period of Church history where the development of Church moral doctrine treats life as beginning with conception. If so, great, argue that. Otherwise, “ESC research has always been problematic” is just a boring claim about the screamingly obvious. Because there are other potential moral or ethical frameworks within which you could evaluate ESC. Or perhaps you would say that those frameworks are not official Church doctrine, thus they’re not Catholic, even if they were taught by saints and Doctors of the Church. If so, you’re also probably the kind of person who says that someone who disagrees with the Church about the morality of contraception isn’t really Catholic, no matter what they say or do on Sundays. But then I congratulate you on erasing the vast majority of Catholics worldwide.
Why on earth would you cite the ethical standards of a 13th century author whose views were based on 13th century scientific understanding when commenting on a living institution's assessment of a 20th century technology? Thomas' views on embryology had long since been superseded in Catholic moral theology once the field of embryology advanced.
Thomas represented the best of Catholic theology for his time, but it would be monumentally ignorant to act like the Catholic Church is somehow still beholden to the the moral conclusions he drew from incomplete scientific understanding.
> Maybe you want to argue that there is some necessary connection between ESC research and the period of Church history where the development of Church moral doctrine treats life as beginning with conception.
Of course I do. The necessary connection is that that's when ESC was created. It couldn't have been created without the very developments in embryology that rendered Thomas' conclusions moot.
Talk about something so obvious it shouldn't need to be said.
Correct me if I'm wrong, but ESCs have been more or less 100% hype and "future promise" with no actual current uses coming to fruition. In contrast, adult stem cells have been used for a lot of treatments and a lot of uses. For me, this casts doubt on the whole push to eliminate restrictions on ESCs.
Layperson here: Stem cells are like clay. They're very useful.
Figuring out all these fine details are likely to lead us to be able to reset our bodies and either drastically extend our lifetimes, or give us a better body in our later years.
This one step might not be part of your medical treatment anytime soon, but we're unlocking fundamental knowledge that we will be wielding, and we don't yet know how powerful that will be.
I believe this (human aging and longevity, biomed) is the most important work.
As usual, the manuscript itself is a bit more discrete than the press release, but this sentence in the conclusion shows the potential benefits - scalable and practical resetting of somatic stem cells, which has been a barrier in translation to actual therapies:
- "Our work shows that TNT reprogramming is a practical and scalable approach to overcome these intrinsic characteristics of hiPS cells, which is important for the clinical delivery of this technology."
stem cells are pluripotent, meaning they have more than one developmental fate.
further on they become putative, meaning the possibilities are narrowed to a particular cell type.
stem cell therapies used to involve extensive selection processes, to harvest cells that develop according to therapeutic goals.
wiping out determined fate, means far less process required, and produces an effectively universal [or near so] stem cell that will be fate determined by surrounding tissue and diffusive signals.
yes helpful. Developmental biology is a very sophisticated discipline, most people require years of post doc study, in order to attain a global understanding of the topic.
thats a simple approach, application of a pseudo tissue similar to skingrafting is another, implantation of 'scaffold' protien construct, implanted with stem cells is another. e.g. 'ghost' organs or tissue, grafting.
a somewhat complex approach is to "wipe" [dedifferentiate] in situ stem cells in vivo, allowing surrounding tissue signaling to program stem cells and induce a developmental path.
keep in mind i am being simple for the sake of understanding.
to keep it simple, this is just scratching the surface of what is there.
teratogenesis is a major hurdle to the tech.
to a large extent it is induction of a process that is autonomously regulated.
consider, the gotchas involved in reusing materials to produce structure.
or the complexity involved in changing the nature of a large multinational conglomerate of corporations.
the difficulty lies in 're-vectoring' an assembly to alter process that is dynamic and has many possible responses to one specific change, dependent on past event, multiplied by each cell in the respondent cohort.
assembly theory, and informatic complexity apply here, overtop the biological phenomenon.
============================
rejection rate is ideally not a consequence when these stem cells originate from the recipient.
the tech of topic deals with genetic manipulation, and is simplistic as DNA is not the only component having influence. cytoplasmic factors, as well as the state, and point of process are informatic and determinative.
You would probably want to induce differentiation in vitro before injecting to make sure it turns into the right cell type but stem cell therapy hasn’t worked out particularly well.
One of the easiest problems to understand is that the cellular potential for infinite replication is what causes tumors/cancers too.
Not really. Anyone could but not everyone. You need people to uphold the Ponzi scheme of capitalism to funnel money to the trillionaires.
Edit: I’d really love to know what these damn down voters are thinking. You literally think everyone can just be a trillionaire? Where is the value being produced? Where is the money coming from? Trillionaires passing each other money around???
Capitalism has lifted billions out of poverty. It is not a zero sum game. People will invent new things and new industries. There are infinite possibilities to discover and all of those are new products and services and experiences to build.
All the commodities humans need for huge increases in per capita wealth are plentiful throughout the universe. NASA wants to explore an asteroid that just by itself is worth $10 quintillion because of all the precious metals in it. That isn’t even the biggest one discovered. There are going to be endless asteroids and entire planets like these.
And there will be endless planets that can be settled and colonized and terraformed.
I do wonder about that valuation, though. Unless they only manage to extract the value so slowly it doesn't flood the market, wouldn't the "precious" medals just become less precious? At least the ones where the value largely comes from scarcity?
This example has nothing to do with this specific asteroid, but it makes the general point: If the amount of gold available doubles over 50 years, the market could probably handle it. But if it goes up 2x per year for 50 years? The price craters.
Yes the prices would plummet but that means wealth per capita increases in real terms. Producing the goods and services that depend on those cheaper commodities will become much cheaper. If we get to a world where everything of value today costs $1 to produce tomorrow, that’s a much wealthier (non zero sum) world.
(I say that in jest, but it's awfully typical of how governments do seem to solve problems. "Trillionaires can buy whatever they want, so let's print enough money for everyone to be a trillionaire!" is awfully similar to "People with college degrees have higher lifetime earnings, so let's make college free so everyone can have a college degree!")
I haven't downvoted you, but you are overlooking the forest for the trees.
Compared to the richest person alive in 1923 or 1823, or 1023 for that matter, we have a lot more at our disposal. In this sense, we are much richer than them. You could be the King of England and if you got cancer, it was lights out, no exception for His Majesty. Going still back in history, even Genghis Khan had to defecate in a desert and wipe his behind with his own fingers, though he ruled of majority of Eurasia at some point.
Contemporary people aren't all trillionaires, but they certainly enjoy a much higher standard of living than tycoons of yesterday.
Very cool research! The title is poorly worded, so the quick summary is that we've known how to create stem cells (induced pluripotent stem cells, or iPSCs) from non-stem human cells for a while, but they aren't as "good" at being stem cells as embryonic stem cells (ESCs). So this paper is not presenting a new way of making stem cells, but is very cool nonetheless.
Sidequest - epigenetics. You have your DNA that codes for the proteins and rnas that do lot sof important life things. But all your cells have the same DNA so how is a skin cell and a neuron both able to exist with the same DNA? There's a layer of regulation on top of the genes that determines what genes are expressed, how much, and what forms (you can get different proteins from the same DNA sequence, look up exons and introns if curious). If these forces of gene regulation are inherited across generations of cells (e.g. when a white blood cells divides, it makes another white blood cell with all those relevant regulatory factors set without having to start again from a stem cells), we call that "epigenetics"
This paper looked at the epigenetic factors that result in iPSCs not behaving like ESCs and identified differences/aberrations in how certain epigenetic patterns (some keywords to Google include DNA methylation and histones in epigenetics) develop through the process of becoming stem cells/reprogramming. The technique they developed resets the aberrations in the iPSCs to make them function better.
(Warning - opinion/speculation/I reserve the right to be wrong): This is very cool in terms of making better iPSCs for research purposes. I'm not sure what impact it would have in using iPSCs in medicine. iPSCs are essentially barely controlled cancer cells which is not great for putting inside people, and this paper doesn't provide a new way of creating stem cells. Maybe better reprogramming makes them easier to control and safer/more functiononal? But using them therapeutically is a different conversation and not every paper needs to solve all the things in the universe, even if that would make for a more clickable title.
iPSCs are useful when you want to run experiments in hard to obtain cell types. For example, brain cells. It’s hard to justify drilling into a person’s head to take a sample. Much easier to use some iPSCs derived from skin or fat cells.
Obviously iPSCs are cell models and not the actual cells you want, but they are usually better than immortalized cell lines or cadavers.
I believe the original comment wasn't written to say that he doesn't know how iPSCs can be useful (obviously they are very useful), but he doesn't know how this breakthrough/paper makes much of a difference.
He's getting at the fact that we've known how to induce pleuropotency for quite some time (I did some reach in this in orthopaedics in 2010), which is what the article title is misleading us to believe.
I was adding in a little bit of context to explain why people should care about iPSCs - even if they are not used as therapies. Mainly because the last paragraph in GP comment focused on the dearth of direct clinical applications.
My point is that iPSCs are still quite useful in pharmaceutical research and development - a therapy adjacent area.
Improved cell models are still a pretty big deal. Part of the reason for high costs and failure rates in pharma R&D is that experimental models we use to generate data are imperfect. Better models = better data = better decisions.
> create stem cells (induced pluripotent stem cells, or iPSCs) from non-stem human cells for a while,
Have some liposuction, chemically and mechanically alter some of the fat cells into iPSC's in the test tube, that's more like a factory process, that conjures up images of 90's garage based Ecstasy labs, before reinjecting back into the body.
Its not something the body can do itself, and its one of the things used in cancer treatments to boost the number of immune cells to compliment the chemical cocktail that you'll never find in Wetherspoons.
It should be noted that melatonin increases the release of stem cells from bone marrow, so getting plenty of sleep seems to be important, throughout life.
I think you're referring to a different type of stem cells, multipotent stem cells like mesenchymal cells or hematopoietic cells. iPSCs aren't used in a process like that at this time
Mscs are just a type of multipotent stem cell, and iPSCs can be differentiated into them. For any of the msc therapies today though you won't use iPSCs, you'll just get mscs directly from adipose tissue
It seems like we are so close to some huge breakthroughs in longevity. With stem cells we can do things like this.
"The extent of change caused by a heart attack is too great for the heart to repair itself or to prevent further damage from occurring. Notably, however, cardiopoietic stem cell therapy reversed, either fully or partially, two-thirds of these disease-induced changes, such that 85% of all cellular functional categories affected by disease responded favorably to treatment," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine.
We have been “close” to some breakthrough with stem cells for at least 15 years now except every time it either doesn’t work or ends up causing cancer (e.g. tumorigenicity and immunogenicity).
We are already there. The FDA has approved hematopoietic stem cell transplantation. And there are over 3000 clinical trials under way. We know already that we can effectively treat some blindness.
The reason I mentioned heart disease is because of how widespread it is and how dramatically it might increase average lifespan. For heart disease specifically it is indeed hard to tell how far away we might be from stem cell treatment being a success.
But stem cell treatment as a whole has already delivered.
Perhaps this is a naive question, but wouldn’t a preventative measure for heart disease (stopping obesity via, say, ozempic) do more for longevity than repairing the heart after dysfunction has taken root?
Not to mention the quality of life improvements from never being sick in the first place.
in such a case isolated treatment of pathos may help but would not be a complete treatment, and would result in chasing subsequent sequelae, over a protracted therepeutic effort.
>>Perhaps this is a naive question, but wouldn’t a preventative measure for heart disease<<
preventive and corrective measures, in response to health issues should be instituted in the context of the whole organism[patient]
cardiac cirrhosis, is an example of secondary pathology related to a common set of disease conditions [heart disease].
correction of pathologic state of one organ via stem cell therapy, is a start but is not complete, heart disease is not always preventable by way of lifestyle choices, as genetic, and traumatic causes will effect occurence.
protracted illness often leads to secondary, or even, systemic issues concurrently presenting, at time of first examination.
any therapy must take this context into account.
The old adage of “an ounce of prevention is better than a pound of cure” is only true, when prevention is possible.
Cardiac cirrhosis is just a bad example, it’s difficult to estimate prevalence but it’s very rare and even then most cases don’t matter as it reflects a state of severe systemic dysfunction (i.e. patient is on deaths door for several other reasons). Fixing the heart at that point won’t accomplish anything with respects to cirrhosis. Right sided heart failure is also rare outside of advanced LHF or preventable causes of pHTN.
Congestive heart failure as a whole was attributable to preventable causes in something like 95% of cases in the NHANES cohort. The 5% of other cases is variable but sure, some are not preventable.
Point being that prevention is possible and remains the preferred approach for the overwhelming majority of people, as the parent comment was inquiring about:
> Perhaps this is a naive question, but wouldn’t a preventative measure for heart disease (stopping obesity via, say, ozempic) do more for longevity than repairing the heart after dysfunction has taken root?
Probably. Obesity also increases the risk of many types of cancers. This appears to be due to the chronic inflammation and immune system effects. In 20 years it will be interesting to see what cancer rates are in patients that have been taking GLP-1 drugs.
Fully agree that we still need to develop treatments but from a prevention perspective if you maintain a healthy weight and diet (i.e. avoid metabolic syndrome) don’t smoke, and don’t use cocaine you should be doing really well from a coronary artery disease perspective barring some hereditary lipid disorder.
Throw on a statin at 35-40 for good measure (expert opinion, not strong evidence but many of my physician colleagues do it too).
Not all heart disease happens due to lifestyle choices. There aren't a lot of preventative treatment options for people who have a family history of heart disease.
Stopping obesity with ozempic might extend lifespan but it won’t fully correct loss of health span due to poor nutrition and lack of exercise. I don’t know if any drugs can correct for a poor lifestyle. They can correct for some major issues caused by poor lifestyle, but cardiovascular disease is only one slice of that miserable pie.
> But stem cell treatment as a whole has already delivered.
Clinical trials underway does not equal delivered. In the 3 years since your review article talking about future applications none of these hypothetical applications have been delivered yet.
I imagine that in the future what will happen is that when a child is born, their stem cells (possibly from the umbilical cord) will be cryogenetically preserved and will form a reservoir from which medical interventions can be prepared as much as 50 years later.
Of course, this assumes we will put a new premium on human life not just limited to the children of the privileged few, which in turn presumes some kind of limitation on human reproduction (steady state population in which births == deaths). Implies a high degree of rationality - who gets to reproduce, and who doesn't? It would take a lot of energy to preserve all those stem cells, after all, and energy supplies really are limited.
That future was the same one advertised 13 years ago when I started medical school. We were already storing cord blood back then.
I’m not saying it will never happen, but this is a really challenging treatment paradigm to get right and I don’t believe it’s “around the corner”. I don’t doubt we’ll have something in 50 years, it’s like battery tech.
I lost my mother a couple weeks back, to two type 2 myocardial infarction about a week apart. Getting cancer and dying a couple months later certainly beats dying a week later.
Don't think it'd have helped much in her case (a massive aortic stenosis, hard to fix at 87), but there are others who would love to have the chance to choose the lesser of two evils.
That's very easy to say until it's your partner, mother/father, or child on the other side of that assertion.
If you're curious and have time, I'd suggest the following excellent exploration of the idea of extinguishing natural death by CGP Grey. He uses an interesting analogy to help challenge the ingrained belief that natural death is just
https://youtu.be/cZYNADOHhVY?si=oCqVGD5RX9Q0Cnrk
We only need to look at nature to see that everything dies. It is natural, and necessary.
I am not in any way saying that people should be euthanized or disease not treated or that people not live out their natural lives. But artificial extension of life will only result in those who can afford it staying in power forever.
We only need to look to nature to find the immortal jellyfish.
Much of medical science is "artificial" extension of life. Natural would be you dying of Smallpox at a young age. Instead you've artificially extended your life with a vaccine.
That's a logical fallacy. The argument you are responding to is not logical, but rhetorical (argument by analogy, based on the premise that analogous systems behave in similar ways). Logical fallacies don't apply to rhetorical arguments in a logical way.
We can all do better than pedantically pointing out logical fallacies, as no argument outside of mathematics is completely logical.
Living forever and living longer shouldn't be grouped together; living forever means unbounded existence and unbounded consumption over time. That's a fundamental paradigm shift for our entire system of being human.
Saving extending the lives of more children is unfortunately, a statistics change for our current world. Unlimited life means all models of economics, morality generally, class, etc will be affected.
> Unlimited life means all models of economics, morality generally, class, etc will be affected.
That's also going to happen with automation — and I don't just mean AI, as it has been happening continuously since the power loom led to Karl Marx inventing Communism, or possibly even earlier with the social and technological changes of Adam Smith's era and the end of feudalism.
> That's very easy to say until it's your partner, mother/father, or child on the other side of that assertion.
The idea isn't that poor people will get life extension, it's that families of billionaires will get it. And no it won't "trickle down" life expectancy is actually decreasing in USA despite tech gains.
Didn't most of the additional deaths come from COVID, drug overdoses and suicides? While those are terrible and need to be addressed, those don't seem to be related to availability of medical treatment.
>Deaths of despair are linked to economic system configuration,[..]
Sure there is a correlation between deaths of despair and poverty. However, the argument here was that healthcare advances won't tickle down with the evidence being declining life expectancy. That's a totally different claim. As of 2021 over 90% of Americans had health insurance coverage and AFAIK the vast majority of proven, legitimate treatments are available to those insured people. (sauce: https://www.census.gov/library/publications/2022/demo/p60-27...).
>pushed by the wealthy to remain static
What class war, conspiracy nonsense is this? Do you think "the rich" get together once a year, smoke cigars and discuss what policies to convince everyone of in order to keep the poors down because they are idiots who believe the world is a zero-sum-game?
If each person would be better off if there were fewer people, then you're looking at a zero sum game.
If some groups have outsized resources to play that game, it wouldn't be surprising if they found themselves playing it. There doesn't have to be any conspiracy. Unless they take steps to interrupt the process, people's behavior naturally aligns with whatever is best for the group they feel they're part of.
It's how we got racism and lots of other toxic garbage. To pretend it doesn't exist is to give it a place to hide.
> Do you think "the rich" get together once a year, smoke cigars and discuss what policies to convince everyone of in order to keep the poors down because they are idiots who believe the world is a zero-sum-game?
Sort of. No cigars though, just "how can we solve the poors without giving up what we have?" Notice no public policy or tax increases to actually solve the problems.
The rich and powerful need everyone to use any such tech, even if only to find the edge cases where it doesn't work right.
That the USA has a seriously messed up healthcare system and declining life expectancy is a problem for the USA, and part of the reason I didn't move there.
If there is a working longevity treatment, do you think that other nations will tolerate it being used for US billionaires and no one else?
Literally everyone ages. 8 billion potential patients on the planet, with the population still growing. If you sell the cure for USD 100 to half of them, you make a lot more money (real money, not just market value) than Elon Musk.
CGP Grey doesn't explore what happens after death is defeated. I can't imagine how it can lead to anything but a stagnated society, with prejudices and inequalities enshrined forever.
Wouldn’t it be the other way around? Now, since the effects of our prejudice, inequality etc, are usually borne way after we die, we don’t get to see the effects of our decisions. If we get to live a lot longer, we’ll be wiser in making better, more balanced decisions.
As for stagnation, sure earth itself is quite overpopulated, but there is nothing technologically stopping humanity from colonizing the solar system.
If humanity gets it shit together and becomes slightly more organized, those experiments in society will just happen in geographically different places.
The “red mars, blue mars, green mars” trilogy explores this quite well, even if the science is a bit dated, the politics aspects of the books are quite interesting, tackling future colonization and longevity’s political pressures and opportunities.
That's a very rosy view of humans. The average person gets older, not wiser; they see the consequences of their actions and find someone else to blame. Real social and cultural change comes from new generations.
I’ve read a bit on the topic too and I think I agree? One of the other obvious occurrences we’re living through is some form of population collapse. Although it’s termed “collapse” I think it’s better conveyed as “global population shrink”. As far as sustainability, I think we can all wait for generational turn over and see what shakes out. But that brings with it other problems like not having enough younger people to care for the elderly or meaningfully contribute to a tax revenue. Anyway, glad you pointed that out. In a cacophony of doom from main stream media (news, social, political, celebrities) maybe this isn’t one of the very big problems that needs global attention right now.
Not just tax and elder care. If you have fewer young people than old then when those young people take the place of their older colleagues in their various professions you wind up losing a lot of tacit knowledge. If there are 1.5 olds for every young then that young one needs to learn 150% of the skills and knowledge that they did before. In such cases the extra information often gets lost. This is how population collapse leads to civilizational collapse.
> The earth is not overpopulated nor in danger of being so.
Depends how you look at it; from a "how much food can we grow" perspective, it's possible to put up hydroponics etc. everywhere (with enough effort) and feed a trillion.
Conversely, if you want to "solve" climate change with a reduced population (rather than rolling out new tech) the maximum sustainable number of humans is about 8 million at today's per-capita average emissions level.
"Maximum" is all about the tech and what it can let us do.
The more a society develops the lower its birth rate. Most of the developed world is well below replacement rate, and the rest of the world will be there soon too.
To be fair I personally believe this is not a case of “rich/educated people have fewer children”, more the case that the way society is structured in those rich/educated places, having children is a bad deal.
It used to be if you had some kids, it was a huuge investment, but you got a lot out of the deal after about 13 years.
But right now, children are still a huge investment, but the parents hardly get any economic incentive for it, the country has “captured” that for its own end.
If governments took this into account and “repaid” this back to the parents, I’m sure people will have way more children.
If societies were structured in such a way that children made economic sense to their parents, I’m sure shrinking population would not be a thing.
Now if something like this has moral problems in and off itself is a different question. I just want to point out that “developed countries are have fewer children” shouldn’t be taken as an absolute truth. It just developed countries as currently structured do not incentivize parents enough. Just look at Israel for example.
It is indeed literally a case of rich/educated people have fewer children. It’s called the demographic-economic paradox. [1]
There’s been a lot of research on this because the effect is so pronounced.
> In decreasing order of strength, fertility (TFR) correlates
negatively with education, [contraceptive prevalence], and GDP per capita, and positively with religiosity. [2]
If you’re educated, rich, non-religious and can bone with impunity you have somewhere between 1 and 2 kids on average, well below the replacement rate of 2.1
It is absolutely a fantastic deal to have kids in Finland where you get months and months of mat and pat leave, etc, and their birth rate is 1.37
Israel is only high because they’re a religious ethnostate and religiosity as the studies show is positively correlated with fertility.
Respectfully I do think the data shows we should take this for granted.
Just a smaller comment to a part of yours. Getting maternity/paternity leave of months is peanuts compared to 2 decades of rearing, and I don't think we can use that as "proof". Parenting is hard and we absolutely should be incentivizing it way more, not with leave, but with more financial subsidies and rewards.
Luckily they're also working on reversing aging. It could turn out that periodically repairing the damage is easier than stopping it from happening at all.
> For derivation of TNT-hiPS cells, the day 7 reprogramming intermediates were transitioned to naive medium (t2iLGoY) instead. When dome-shaped colonies were evident 5 days later, intermediate cells were collected using Accutase (Stem Cell Technologies) and reseeded onto a layer of iMEFs in naive conditions.
It's quite a leap to imagine that developmental processes in cells are entirely reversible, but maybe it's possible. The main thing to look at in this study is this:
> "Professor Polo said the precise molecular mechanisms underlying the iPS epigenome aberrations and their correction were not fully known, and further research was needed to understand them."
Think about the truly ridiculous level of programmatic fidelity involved in human (or any mammalian) reproduction. Two cells, one from the XY male and one from the XX female, merge to form a viable zygote. One cell. Somehow, that cell contains all the information necessary to develop into to a kangaroo, or a whale, or a human, or a naked mole rat. Hundreds of different cell types, expressing thousands of celluar receptor proteins, to keep it all coordinated.
A lot of the developmental processes involve selective deactivation of large regions of the genome (nerve cells don't need much of what heart cells need, and so on), but somehow it's all coordinated. What they're claiming is that this selective deactivation can somehow be reversed, but they don't quite understand how, at a molecular-structural level.
It all points to the 3D structure of the genome being important at many levels, but there's no good way to experimentally analyze that yet, not really.
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[ 2.9 ms ] story [ 205 ms ] threadResearch on adult stem cells or induced pluripotent stem cells already didn't face the same objections.
It sounds like this is more about an improvement in the technique of inducing pluripotency that could reduce negative complications, rather than a whole new unobjectionable procedure that hadn't existed before.
Thomas predates ESC research by centuries--quite a few of them, actually.
ESC research has always been problematic.
Yes, I am aware that Saint Thomas Aquinas was a medieval theologian and that embryonic stem cell research did not exist at the time.
Maybe you want to argue that there is some necessary connection between ESC research and the period of Church history where the development of Church moral doctrine treats life as beginning with conception. If so, great, argue that. Otherwise, “ESC research has always been problematic” is just a boring claim about the screamingly obvious. Because there are other potential moral or ethical frameworks within which you could evaluate ESC. Or perhaps you would say that those frameworks are not official Church doctrine, thus they’re not Catholic, even if they were taught by saints and Doctors of the Church. If so, you’re also probably the kind of person who says that someone who disagrees with the Church about the morality of contraception isn’t really Catholic, no matter what they say or do on Sundays. But then I congratulate you on erasing the vast majority of Catholics worldwide.
Thomas represented the best of Catholic theology for his time, but it would be monumentally ignorant to act like the Catholic Church is somehow still beholden to the the moral conclusions he drew from incomplete scientific understanding.
> Maybe you want to argue that there is some necessary connection between ESC research and the period of Church history where the development of Church moral doctrine treats life as beginning with conception.
Of course I do. The necessary connection is that that's when ESC was created. It couldn't have been created without the very developments in embryology that rendered Thomas' conclusions moot.
Talk about something so obvious it shouldn't need to be said.
I guess it’s a good thing I didn’t do that, then.
Figuring out all these fine details are likely to lead us to be able to reset our bodies and either drastically extend our lifetimes, or give us a better body in our later years.
This one step might not be part of your medical treatment anytime soon, but we're unlocking fundamental knowledge that we will be wielding, and we don't yet know how powerful that will be.
I believe this (human aging and longevity, biomed) is the most important work.
- "Our work shows that TNT reprogramming is a practical and scalable approach to overcome these intrinsic characteristics of hiPS cells, which is important for the clinical delivery of this technology."
stem cell therapies used to involve extensive selection processes, to harvest cells that develop according to therapeutic goals.
wiping out determined fate, means far less process required, and produces an effectively universal [or near so] stem cell that will be fate determined by surrounding tissue and diffusive signals.
a somewhat complex approach is to "wipe" [dedifferentiate] in situ stem cells in vivo, allowing surrounding tissue signaling to program stem cells and induce a developmental path.
keep in mind i am being simple for the sake of understanding.
teratogenesis is a major hurdle to the tech.
to a large extent it is induction of a process that is autonomously regulated.
consider, the gotchas involved in reusing materials to produce structure.
or the complexity involved in changing the nature of a large multinational conglomerate of corporations.
the difficulty lies in 're-vectoring' an assembly to alter process that is dynamic and has many possible responses to one specific change, dependent on past event, multiplied by each cell in the respondent cohort.
assembly theory, and informatic complexity apply here, overtop the biological phenomenon.
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rejection rate is ideally not a consequence when these stem cells originate from the recipient.
the tech of topic deals with genetic manipulation, and is simplistic as DNA is not the only component having influence. cytoplasmic factors, as well as the state, and point of process are informatic and determinative.
One of the easiest problems to understand is that the cellular potential for infinite replication is what causes tumors/cancers too.
Of course, it will be Stem Cells as a Service. Or SCaaS.
With that said, that's not too different from existing cancer treatment drugs.
Edit: I’d really love to know what these damn down voters are thinking. You literally think everyone can just be a trillionaire? Where is the value being produced? Where is the money coming from? Trillionaires passing each other money around???
All the commodities humans need for huge increases in per capita wealth are plentiful throughout the universe. NASA wants to explore an asteroid that just by itself is worth $10 quintillion because of all the precious metals in it. That isn’t even the biggest one discovered. There are going to be endless asteroids and entire planets like these.
And there will be endless planets that can be settled and colonized and terraformed.
This example has nothing to do with this specific asteroid, but it makes the general point: If the amount of gold available doubles over 50 years, the market could probably handle it. But if it goes up 2x per year for 50 years? The price craters.
(I say that in jest, but it's awfully typical of how governments do seem to solve problems. "Trillionaires can buy whatever they want, so let's print enough money for everyone to be a trillionaire!" is awfully similar to "People with college degrees have higher lifetime earnings, so let's make college free so everyone can have a college degree!")
Compared to the richest person alive in 1923 or 1823, or 1023 for that matter, we have a lot more at our disposal. In this sense, we are much richer than them. You could be the King of England and if you got cancer, it was lights out, no exception for His Majesty. Going still back in history, even Genghis Khan had to defecate in a desert and wipe his behind with his own fingers, though he ruled of majority of Eurasia at some point.
Contemporary people aren't all trillionaires, but they certainly enjoy a much higher standard of living than tycoons of yesterday.
Sidequest - epigenetics. You have your DNA that codes for the proteins and rnas that do lot sof important life things. But all your cells have the same DNA so how is a skin cell and a neuron both able to exist with the same DNA? There's a layer of regulation on top of the genes that determines what genes are expressed, how much, and what forms (you can get different proteins from the same DNA sequence, look up exons and introns if curious). If these forces of gene regulation are inherited across generations of cells (e.g. when a white blood cells divides, it makes another white blood cell with all those relevant regulatory factors set without having to start again from a stem cells), we call that "epigenetics"
This paper looked at the epigenetic factors that result in iPSCs not behaving like ESCs and identified differences/aberrations in how certain epigenetic patterns (some keywords to Google include DNA methylation and histones in epigenetics) develop through the process of becoming stem cells/reprogramming. The technique they developed resets the aberrations in the iPSCs to make them function better.
(Warning - opinion/speculation/I reserve the right to be wrong): This is very cool in terms of making better iPSCs for research purposes. I'm not sure what impact it would have in using iPSCs in medicine. iPSCs are essentially barely controlled cancer cells which is not great for putting inside people, and this paper doesn't provide a new way of creating stem cells. Maybe better reprogramming makes them easier to control and safer/more functiononal? But using them therapeutically is a different conversation and not every paper needs to solve all the things in the universe, even if that would make for a more clickable title.
Obviously iPSCs are cell models and not the actual cells you want, but they are usually better than immortalized cell lines or cadavers.
He's getting at the fact that we've known how to induce pleuropotency for quite some time (I did some reach in this in orthopaedics in 2010), which is what the article title is misleading us to believe.
My point is that iPSCs are still quite useful in pharmaceutical research and development - a therapy adjacent area.
Improved cell models are still a pretty big deal. Part of the reason for high costs and failure rates in pharma R&D is that experimental models we use to generate data are imperfect. Better models = better data = better decisions.
I am not sure why everyone is convinced that they will not be very useful in therapies...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357081/
https://www.nature.com/articles/s41571-023-00754-1
Have some liposuction, chemically and mechanically alter some of the fat cells into iPSC's in the test tube, that's more like a factory process, that conjures up images of 90's garage based Ecstasy labs, before reinjecting back into the body.
Its not something the body can do itself, and its one of the things used in cancer treatments to boost the number of immune cells to compliment the chemical cocktail that you'll never find in Wetherspoons.
It should be noted that melatonin increases the release of stem cells from bone marrow, so getting plenty of sleep seems to be important, throughout life.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172675/
Mesenchymal stem cells (MSCs) derived from human induced pluripotent stem cells (hiPSCs) provide a novel source for generating adipocytes,
"The extent of change caused by a heart attack is too great for the heart to repair itself or to prevent further damage from occurring. Notably, however, cardiopoietic stem cell therapy reversed, either fully or partially, two-thirds of these disease-induced changes, such that 85% of all cellular functional categories affected by disease responded favorably to treatment," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine.
https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-re...
I’ll believe it when I see it.
The reason I mentioned heart disease is because of how widespread it is and how dramatically it might increase average lifespan. For heart disease specifically it is indeed hard to tell how far away we might be from stem cell treatment being a success.
But stem cell treatment as a whole has already delivered.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367472/
Not to mention the quality of life improvements from never being sick in the first place.
cardiac hepatocirrhosis is one example.
https://emedicine.medscape.com/article/151792-overview
https://www.sciencedirect.com/science/article/pii/S221317791...
in such a case isolated treatment of pathos may help but would not be a complete treatment, and would result in chasing subsequent sequelae, over a protracted therepeutic effort.
You’re talking about an uncommon end stage complication of chronic severe right heart failure.
To the parent comment’s question: yes, prevention is better. If you prevent right heart failure you will not get cardiac cirrhosis.
The old adage of “an ounce of prevention is better than a pound of cure” is still true.
preventive and corrective measures, in response to health issues should be instituted in the context of the whole organism[patient]
cardiac cirrhosis, is an example of secondary pathology related to a common set of disease conditions [heart disease].
correction of pathologic state of one organ via stem cell therapy, is a start but is not complete, heart disease is not always preventable by way of lifestyle choices, as genetic, and traumatic causes will effect occurence.
protracted illness often leads to secondary, or even, systemic issues concurrently presenting, at time of first examination.
any therapy must take this context into account.
The old adage of “an ounce of prevention is better than a pound of cure” is only true, when prevention is possible.
Congestive heart failure as a whole was attributable to preventable causes in something like 95% of cases in the NHANES cohort. The 5% of other cases is variable but sure, some are not preventable.
Point being that prevention is possible and remains the preferred approach for the overwhelming majority of people, as the parent comment was inquiring about:
> Perhaps this is a naive question, but wouldn’t a preventative measure for heart disease (stopping obesity via, say, ozempic) do more for longevity than repairing the heart after dysfunction has taken root?
Throw on a statin at 35-40 for good measure (expert opinion, not strong evidence but many of my physician colleagues do it too).
Given their reputation for making people energetic (not having any interest I've never tried), I wonder if ecstasy and cocaine lead to exercise?
Source? To my knowledge what’s approved is not iPSC.
Hematopoietic progenitors are a different challenge and “low hanging fruit”.
https://www.fda.gov/vaccines-blood-biologics/cellular-gene-t...
> But stem cell treatment as a whole has already delivered.
Clinical trials underway does not equal delivered. In the 3 years since your review article talking about future applications none of these hypothetical applications have been delivered yet.
Of course, this assumes we will put a new premium on human life not just limited to the children of the privileged few, which in turn presumes some kind of limitation on human reproduction (steady state population in which births == deaths). Implies a high degree of rationality - who gets to reproduce, and who doesn't? It would take a lot of energy to preserve all those stem cells, after all, and energy supplies really are limited.
I’m not saying it will never happen, but this is a really challenging treatment paradigm to get right and I don’t believe it’s “around the corner”. I don’t doubt we’ll have something in 50 years, it’s like battery tech.
Don't think it'd have helped much in her case (a massive aortic stenosis, hard to fix at 87), but there are others who would love to have the chance to choose the lesser of two evils.
I know she would.
If you're curious and have time, I'd suggest the following excellent exploration of the idea of extinguishing natural death by CGP Grey. He uses an interesting analogy to help challenge the ingrained belief that natural death is just https://youtu.be/cZYNADOHhVY?si=oCqVGD5RX9Q0Cnrk
I am not in any way saying that people should be euthanized or disease not treated or that people not live out their natural lives. But artificial extension of life will only result in those who can afford it staying in power forever.
Much of medical science is "artificial" extension of life. Natural would be you dying of Smallpox at a young age. Instead you've artificially extended your life with a vaccine.
https://en.m.wikipedia.org/wiki/Turritopsis_dohrnii
We can all do better than pedantically pointing out logical fallacies, as no argument outside of mathematics is completely logical.
There is a difference between living longer/forever and giving a child with terminal cancer a normal full life
Saving extending the lives of more children is unfortunately, a statistics change for our current world. Unlimited life means all models of economics, morality generally, class, etc will be affected.
Everyone dies man.
That's also going to happen with automation — and I don't just mean AI, as it has been happening continuously since the power loom led to Karl Marx inventing Communism, or possibly even earlier with the social and technological changes of Adam Smith's era and the end of feudalism.
The idea isn't that poor people will get life extension, it's that families of billionaires will get it. And no it won't "trickle down" life expectancy is actually decreasing in USA despite tech gains.
EDIT: downvote me if you want, you know it's true
https://www.npr.org/sections/health-shots/2023/03/25/1164819...
https://www.hsph.harvard.edu/news/hsph-in-the-news/whats-beh...
Sure there is a correlation between deaths of despair and poverty. However, the argument here was that healthcare advances won't tickle down with the evidence being declining life expectancy. That's a totally different claim. As of 2021 over 90% of Americans had health insurance coverage and AFAIK the vast majority of proven, legitimate treatments are available to those insured people. (sauce: https://www.census.gov/library/publications/2022/demo/p60-27...).
>pushed by the wealthy to remain static
What class war, conspiracy nonsense is this? Do you think "the rich" get together once a year, smoke cigars and discuss what policies to convince everyone of in order to keep the poors down because they are idiots who believe the world is a zero-sum-game?
If some groups have outsized resources to play that game, it wouldn't be surprising if they found themselves playing it. There doesn't have to be any conspiracy. Unless they take steps to interrupt the process, people's behavior naturally aligns with whatever is best for the group they feel they're part of.
It's how we got racism and lots of other toxic garbage. To pretend it doesn't exist is to give it a place to hide.
Sort of. No cigars though, just "how can we solve the poors without giving up what we have?" Notice no public policy or tax increases to actually solve the problems.
https://www.nbcnews.com/id/wbna30851839
https://www.nytimes.com/2022/04/06/us/politics/republican-do...
https://www.independent.co.uk/news/world/bilderberg-group-me...
https://www.vox.com/future-perfect/2019/1/30/18203911/davos-...
That the USA has a seriously messed up healthcare system and declining life expectancy is a problem for the USA, and part of the reason I didn't move there.
Because the rest of the world does not matter?
If there is a working longevity treatment, do you think that other nations will tolerate it being used for US billionaires and no one else?
Literally everyone ages. 8 billion potential patients on the planet, with the population still growing. If you sell the cure for USD 100 to half of them, you make a lot more money (real money, not just market value) than Elon Musk.
As for stagnation, sure earth itself is quite overpopulated, but there is nothing technologically stopping humanity from colonizing the solar system.
If humanity gets it shit together and becomes slightly more organized, those experiments in society will just happen in geographically different places.
The “red mars, blue mars, green mars” trilogy explores this quite well, even if the science is a bit dated, the politics aspects of the books are quite interesting, tackling future colonization and longevity’s political pressures and opportunities.
Depends how you look at it; from a "how much food can we grow" perspective, it's possible to put up hydroponics etc. everywhere (with enough effort) and feed a trillion.
Conversely, if you want to "solve" climate change with a reduced population (rather than rolling out new tech) the maximum sustainable number of humans is about 8 million at today's per-capita average emissions level.
"Maximum" is all about the tech and what it can let us do.
It used to be if you had some kids, it was a huuge investment, but you got a lot out of the deal after about 13 years.
But right now, children are still a huge investment, but the parents hardly get any economic incentive for it, the country has “captured” that for its own end.
If governments took this into account and “repaid” this back to the parents, I’m sure people will have way more children.
If societies were structured in such a way that children made economic sense to their parents, I’m sure shrinking population would not be a thing.
Now if something like this has moral problems in and off itself is a different question. I just want to point out that “developed countries are have fewer children” shouldn’t be taken as an absolute truth. It just developed countries as currently structured do not incentivize parents enough. Just look at Israel for example.
There’s been a lot of research on this because the effect is so pronounced.
> In decreasing order of strength, fertility (TFR) correlates negatively with education, [contraceptive prevalence], and GDP per capita, and positively with religiosity. [2]
If you’re educated, rich, non-religious and can bone with impunity you have somewhere between 1 and 2 kids on average, well below the replacement rate of 2.1
It is absolutely a fantastic deal to have kids in Finland where you get months and months of mat and pat leave, etc, and their birth rate is 1.37
Israel is only high because they’re a religious ethnostate and religiosity as the studies show is positively correlated with fertility.
Respectfully I do think the data shows we should take this for granted.
[1] https://en.m.wikipedia.org/wiki/Income_and_fertility
[2] https://bmcpublichealth.biomedcentral.com/articles/10.1186/s...
> "Professor Polo said the precise molecular mechanisms underlying the iPS epigenome aberrations and their correction were not fully known, and further research was needed to understand them."
Think about the truly ridiculous level of programmatic fidelity involved in human (or any mammalian) reproduction. Two cells, one from the XY male and one from the XX female, merge to form a viable zygote. One cell. Somehow, that cell contains all the information necessary to develop into to a kangaroo, or a whale, or a human, or a naked mole rat. Hundreds of different cell types, expressing thousands of celluar receptor proteins, to keep it all coordinated.
A lot of the developmental processes involve selective deactivation of large regions of the genome (nerve cells don't need much of what heart cells need, and so on), but somehow it's all coordinated. What they're claiming is that this selective deactivation can somehow be reversed, but they don't quite understand how, at a molecular-structural level.
It all points to the 3D structure of the genome being important at many levels, but there's no good way to experimentally analyze that yet, not really.