Hi, your friendly, local pathologist here. I'm the kind of doctor that diagnoses liver diseases, cancer, lots of infections, inflammatory processes, benign tumors, and runs the lab that a lot of other doctors use the results from to inform a lot of their other decisions.
If you really want to learn about this stuff, Robert Weinberg's The Biology of Cancer is where to start. It introduces concepts starting where a high school student could understand and carefully walks through the history of our development of knowledge until, by the end, the pithy chapters are helping novel concepts for real science flower in your brain all on their own. It's the best book of biological science I have ever read. 10/10, will read again.
Pathology... reminds me of all those studies with accident victims all over the world (and often as early as the 70s - today's numbers are likely much worse) that show 30% or half the population being liver-toxic in vitamin A (in all age groups). Lots of health problems are simply downstream from that.
Most of the body doesn't regenerate because there was not enough evolutionary pressure. Even with regeneration you could still easily die from some severe injury, blood loss or disease. While salamander regeneration is impressive, it has its limitations. For example, no known adult salamander can regenerate an entirely removed eye. Also if you chop a salamander, it will not regenerate like a Planarian worm, it will just die. And a fun fact, Axolotls can regrow a limb yet cannot regenerate an adult eye lens.
Also, although the article is mostly true, there are some inaccuracies:
>> Neurons and cardiac muscle cells don't reproduce after childhood
There is some evidence showing a slow cell turnover in cardiac muscle, estimated around ~1% per year in young adults, falling toward ~0.5% in older people. Most neurons don't regenerate, but there an evidence that some parts of the adult brain (such as hippocampus) still produce new neurons, although the number is very low.
I have an axolotl. They're really incredible creatures, with way more personality and interests than you would expect. They are really soft, and almost have the same density as water, so they can be neutrally buoyant and even swim rapidly like a fish. They're also very sensitive to sharp things; mine recently got a cut from an aquarium decoration, which healed fully over the course of a week. Her previous owner had neglected her and induced tail curl, which took longer to heal (a few months) but did fully heal. I have since adjusted her tank to give it all flat or smooth surfaces, with some variety.
evolution doesn't act on the species or even individuals, it acts on the genes which is why it looks like evolution acts on the individual and its close family unit.
people have a hard time grasping this concept for some reason.
my favorite example to illustrate this is the trait of being poisonous. if evolution cared about species and then every single one would be poisonous and all predators would have to hyper specialize in prey (arms race between a particular poison and its resistance). it's precisely because it's so difficult to elicit a benefit from this strategy for the lineage that it's so rare. almost always a mutation in coloration has to happen to set the lineage apart from the others first. and then the lineage has to survive the disadvantage long enough.
basically, the genes do not generally contain blueprints but rather processes utilizing existing cellular machinery. a "mutation" can occur in a machine which will allow a propagating difference.
and there is nothing special about populations. it's merely the only way to observe most changes. gene frequencies in gene pools.
Regeneration is unlikely to warrant eternal life. In the wild, most animals die before even showing serious signs of aging. Even if regeneration increased lifespan, poorly adapted individuals would still die.
The author suggests humans are overturned to repairing skin and blood, but I strongly disagree. People with problems with wound healing can face significant disability and mortality. Wound healing allows us to have surgery and close up with simple sutures. A lot of complications post-surgery in humans and other animals are specifically from impaired wound healing capability. It’s a good trade-off: nearly everyone will eventually get cut open by accident or on purpose. The skins ability to heal is so amazing that many types of wounds require nothing other than some cleaning, the body will fully clot, bridge, build, and scar back to most retained function. Wound healing allows us to heal large burns and even simply leave many wounds open to air.
Complications with healing are pretty brutal. Necrosis, amputation, infection are all common without the built-in cascade we have.
I thought the reason was well known, and the article briefly touches it...
The liver's great ability to regenerate largely boils down to how homogenous and simple the liver actually is. It's structured more like a battery pack, where you have individual cells that are largely functionally identical to each other that perform the bulk of the work, and they happen to be connected together. If an individual cell fails, (for the most part) all you need to do is merely regrow a new one, and it's orientation matters little (relatively speaking as compared to other organs) so long as it's connected to the rest of the battery pack (organ).
Contrast that to something like a kidney, which has complex orientation that is formed via growth, and which has a high degree of different types of cells where replacing a part isn't as simple as merely regrowing the part which failed, but also about that growth happening in precisely the right location. So instead of it being like having to replace a failed cell in a battery pack, it's like replacing a wheel to a car. Attaching it anywhere (like the windshield for example) won't necessarily fix the issue, it needs to be connected to the axle...
Also, the liver metabolizes a lot of toxins, and some cells die in the process, so there was a strong pressure to replace them. That pressure was our ancestors insisting on eating toxic things like mushrooms and spoiled food until it didn't immediately kill them.
Many problems with would healing are due to nutrient deficiencies. For example, people who are sulfur deficient will heal and recover much slower than those who are not.
That's why so many professional athletes take MSM (Methylsulfonylmethane). Their bodies would not be able to recover as quickly without the extra sulfur.
The problem is not wound healing, the problem is over the top inflammatory responses, and yeah with out them injuries could be much worse, but we get a lot of diseases because of accumulated damaged from long term inflammations. Point is doing simple things like eating a bit of sugar spikes your inflammatory reactions, causing all sort of problems down the road.
Ideally we could have a switch, low inflammatory reactions when good, high inflammatory reactions on injuries.
Your liver makes platelets so if your liver function is not optimal, wound healing is harder.
Some people also have rare diseases where they don’t have clotting factors so require a transfusion of clotting factors before surgery for optimal wound healing.
I have first-hand experience! My immune system slowly killed my liver (primary sclerosing cholangitis), and I had a transplant. (btw, for $0, thank you to the Australian health system)
I received a cut-down liver from the donor; I got the bigger lobe, a child recipient got the other lobe.
Within a few months of transplant, the new liver had regrown, but (probably because of the transplant orientation) rather than growing across to the left, it grew down the side of my body.
It's all good and functions fine, it's just that now my right-side of my body isn't as 'saggy' as my left because of the area it grew in to.
It's an amazing organ, and it truly sucks when you don't have a well-functioning one.
Possible? yes. Practical, not really. Living liver donors (at least in Australia) are rare, because (unlike kidney donations) it's an extremely risky procedure for a living donor. My donor was a deceased donor, and I'm forever grateful for their (and their family's) decision.
Actually, after doing a bit of reading, repeat living donations aren't possible because the regenerated liver doesn't have the same structure of blood vessels and bile ducts needed for transplant, as well as having the scarring etc from the first transplant. e.g. https://www.reddit.com/r/askscience/comments/50hcj4/can_i_re...
Wow, I didn't know it was such a small number. I know someone with liver failure due to AATD and amazingly one of his close friends is a match and a healthy non-drinker to boot.
> Brains. After you reach adulthood, neurons don’t divide. If some of your neurons die—which happens every day—then they’re gone. If you get a brain injury, the other neurons will try to “learn around” the injury, but the neurons themselves are never replaced.
This is a very outdated view. Neuroscience has shown that neurogenesis continues throughout the entire life span of humans, albeit at a much slower rate. You might have a hard time recovering from a serious brain injury or stroke but losing a few brain cells won’t change a thing.
> And even after taking [immunosuppressants], there’s a 30% chance the kidney will be rejected within 10 years. This is not helpful.
To the author: thank you, you made my day. It had been a very, very long time since I last read an article on the Internet that felt written by a human being - with humor, some poetry, and science.
Immunosuppressants like tacrolimus given at too high of a level for many years can wear down your kidneys faster requiring a transplant potentially after ten years.
Even if we assume your body has a foolproof is_same_species() test, your neighbors' cells may:
1. Be healthy, but have the wrong priorities or behavior, so that they start doing the wrong tasks or sending the wrong messages in the wrong places. [0]
2. Be healthy, but they're just a creepy flesh-mask a parasite has constructed around itself.
3. Be individually hijacked by viruses, and your body won't have the same baseline information to tell that they've deviated from your neighbor's standard.
4. They may be fully human, but gone feral into a transmissible tumor [1].
____
[0] This is actually a risk from pregnancy, as overambitious fetal cells leak into the mother.
I'm a kidney transplant patient myself. Your cells have HLA markers to distinguish your own cells from foreign cells. That is to prevent your immune cells from attacking your own body. This also makes it harder to find a organ match.
The reason I needed a kidney transplant is because of an auto disease called IgA Nephropathy where the IgA antibody has a small defect that causes the rest of the immune system to attack it and the whole mess clogs up the kidney filters over time.
The way your body detects foreign cells is the same way your body detects foreign cells. It detects anything that doesn't have your, specific, randomly-generated at conception, friend-or-foe markers.
In all these cases cells that are "other than your own" are in your system and need to be eliminated, in the case of cancer it's your own cells but with significant mutations, as far as I can tell there is always an immune response although in some cases it is actually counter productive.
"Some day, your immune system may decide to attack your pancreas."
Immune attack of the pancreas is usually a disease of youth. Type 2 diabetes which is overwhelmingly the diabetes associated with aging is not an autoimmune disease.
I don’t know how adult 22 is considered but yeah. A younger sibling got it when they were ~13.
When we noticed the signs and went into the ER a few of the (younger) doctors thought it was Type 2, while the attending knew it was just late onset Type 1.
MODY is something else entirely (a genetic mutation driven disease with distinct pathophysiology from Type 1). What’s being discussed here is LADA (late autoimmune diabetes in adults).
LADA itself isn’t that rare but it is a small minority of all cases of diabetes in older adults.
Same. At first he was happy as he lost a load of weight, then it kept happening and he nearly died in the office. Just collapsed one day. Insulin is an amazing invention. My dog, a little pug, gets porcine insulin after prednisone saved her life but gave her type 1.
You might want to check out the low vitamin a crowd. Some weirdos in there, but we all do very well. Seems to help with many autoimmune disorders (for me: allergies and nightly urination almost gone).
> but the process is slow and clumsy and can only produce tiny blood vessels.
This isn't entirely true. I have notable damage to one side and in the recovery process there was a significant increase in the visibility of the surface veins on that side. It's still clearly there years later. Existing vessels can grow larger when repair processes kick in.
The punishment for Prometheus stealing fire from the Gods and gifting it to humanity, was to be chained to a rock and having an eagle feed on his liver which would regrow the next day.
For what it's worth, Prometheus was a Titan, and Titan was immortal, so his liver regrowing the next day wasn't really that special. If eagle fed on his heart, or lungs, they would've regrown too.
The Greeks chose liver because it symbolized the defiance Prometheus had against gods.
I don't know about the Greeks but I know a lot of ancient cultures thought the liver was the most important organ (probably because it's full of blood).
For example in Persian poetry the word liver is found pretty much everywhere you would expect to see the word heart.
"You are my liver" is a nice/romantic thing to say to this day.
There's really no knowing why the Greeks chose liver, or some specific Greek chose liver.
It could have been because the liver was regenerative and they were using the titan with the regenerating liver as another reference to humanity, or it could have been as someone pointed out because predators like to eat the liver first, or it could have been that you can take damage to the liver and live for hours afterwards in agony whereas the same amount of damage to the heart or lungs is apt to cause death to come much quicker.
Perhaps there are undiscovered variants out there were the eagle or a serpent or some other animal attacks his genitals, or his eyes.
But at any rate the Eagle ate his liver, it means nothing in particular, and at the same time it means every particular interpretation we can place on it.
Whatever the actual reason for choosing the liver was, we can be certain it wasn't its regenerative property, since such proprerty was unknown to the Greeks at the time.
Probably not, I don't think I ever read Galen mentioning it, but then again people would get injured in the liver and recuperate better than other injuries I suppose, which makes me think it is surprising if he didn't.
Just went and checked, evidently he never said anything about it.
old American translation of Galen and Hippocrates for anyone interested, as it can be
difficult to find otherwise
But why were those accompaniments chosen for the liver? Because all three foods are high in tyramine, which is toxic if you're on an MAO Inhibitor. Why would Hannibal be on an MAOI? I have no idea, tbqh. They're for depression and Parkinson's, not antipsychotics.
There are a bunch of Japanese words (including a several loanwords from Chinese) that use the liver / gallbladder metaphorically for courage. Both derive from associations between the humours and personality / behavior. I have no idea, however, why both Eastern and Western naive psychology associate gall with, well, gall.
I'm thinking the Greeks chose liver because it is the first thing that many predators will eat from a kill - large, more nutrient-dense than almost any other tissue, and relatively quick to access.
Other animals do get heart cancer, which is fascinating. It's still very uncommon compared to other cancers, but not virtually absent as it is in people.
I am in awe about how wonderfully engineered by evolution the body is. E.g., what we are able to do with it and how it heals itself when we have an injury. Sure, many people would not live long without external intervention, but many others would. I still want to see the robot that can survive 80 active years without maintenance.
Compared to most animals that spend their entire day foraging for food, it's not too bad. Adapting to eating dense and very nutritious animal flesh is a great time-saver, and as we didn't evolve long fangs, we had to learn to use tools instead, and the rest is history. (mixing cause and effect here for dramatic purposes)
I think learning to cook food was likely a greater benefit. It's like we externally expanded our means of digestion.
I watched a Ted talk where the speaker suggested our large brains with their high energy consumption would not have been possible were it not for cooking.
Steak I’d imagine, which is a prerequisite to growing a very energy-intensive organ such as our brain. Couldn’t have supported such a brain if we had been ruminants.
Bone marrow came first. We were scavengers for the longest time. We invented tools to break the bones hyenas would leave. Skulking little scavengers.. until spears were invented then hoo boy - shit went exponential.
The human machine doesn't just survive without external intervention, it actually gets better at being a machine. Speed, endurance, power, coordination... all improve with usage.
When you watch those sci-fi shows and folks have nanobots implanted in them that heal wounds really fast or do other cool things I can't help but think in many ways we already have that technology we just need it to do more, faster as our brains and ability to create things have outpaced the rate of evolutionary change.
Humans have assisted each other medically, supported injured and disabled tribe members, and sought out medicinal herbs since long before history was written. I'm not sure how you'd delineate between modern health care and when humans never had some notion of health care and/or support when bodies enter failure modes. We don't survive well without a lot of assistance and care, and living long lives required plenty of bodily maintenance regardless of how fortunate and healthy we were.
I think, if you add clarity, such as how aspirin alone is a wonder, how iodine to clean wounds is a life saver, how soap is a miracle, and all the parasites we don't have, yet all this we take for granted.
We are certainly much healthier, with the little trinkets we keep in our houses.
Willow bark was used like aspirin.
Soap is a old concept (ash is desinfectant as is vinegar ). Alcohol for cleaning wounds is a very old concept alike. As was jumping into clean water every day (also in winter).
Yes, and all of those solutions are suboptimal compared to the modern variants, were not always available, and making alcohol required technology (just as fire usage was technology).
The real point here, is a lot of people today don't realize how supported they are, with medicine and the trappings of modern life. The simple things I've listed are quite literally a wonder, but to the modern human, often it's not even considered a big deal.
Even in a rural remote areas of Canada or the US, you can just get in your vehicle, drive for half an hour, and then suddenly be surrounded by tens of thousands of products to make you healthier. A city dweller can walk for five minutes, and have the same.
"The real point here, is a lot of people today don't realize how supported they are, with medicine and the trappings of modern life. "
No doubt. But I like to spend time in remote wilderness, so I do know what I have and do not have there. I definitely feel healthier if I am outside more often and can take care of various injuries myself, but if I would really need one, I surely would call for a modern medical helicopter and not go find some plants.
One of the problems with modern life is that we've forgotten how many things will try to kill you given half a chance. So we grow up complacent with normalcy bias and end up inventing imaginary personal threats - like being scared of vaccines - instead of dealing with real collective threats like climate catastrophe.
There was no "average" lifespan back then. It is a bimodal curve, one peak young, one peak old. "Life expectancy" is far more about the size of the two peaks than an average. In modern society the old peak very much dominates, but even then "life expectancy at birth" is still substantially influenced by the size of the two peaks. Much of the difference across the developed world actually comes down to what doctors classify as a live birth. (Big negative correlation between infant mortality and stillbirth.)
Gurven, Michael & Hillard Kaplan (2007). “Longevity Among Hunter-Gatherers: A Cross-Cultural Examination.” Population and Development Review, 33(2), 321–365
If you made it past age 5 as a hunter-gatherer you’d likely live to 50-60 years of age.
It’s also worth noting that, while this is (I think) likely the most cited paper on the topic, all the observed societies are from the 20th century. So we can’t necessarily extrapolate from that that hunter-gatherers 300,000 years ago fared the same.
Many if not most of these oddities about humans come down to either they don’t affect reproduction, or because humans are social animals. Menopause makes sense because a grandmother will have more successful descendants if she stops having babies and helps her daughters with the grandkids. I would guess the few other species that exhibit menopause are also social animals.
This is discussed at the bottom of the article:
"Menopause: Humans, killer whales, pilot whales, beluga whales, false killer whales, narwhals one group of chimps in Uganda.
No menopause: Everything else"
So, monkeys and apes (besides one species of chimps) don't get menopause, elephants don't get menopause, lions don't get menopause.
If your prediction is, social animal => menopause, it's wrong 99% of the time.
It seems it might be more a combination of whether it's a social animal and how much help / how much danger the offspring is actually in. There's not a whole lot that fucks with elephants, and not a lot that successfully fucks with the young ones. And female elephants universally live in groups and collectively all protect each other. Female lions tend to do the same, and also have very few things that fuck with them.
Conversely human offspring is especially weak and incapable and susceptible to harm, and experiences a lot of threat even within the same species.
Not sure where that are of whale and chimps fit into that - flukes can also happen I guess.
Most species make a baby (or babies), raise them to maturity before having another. Even a low chance of successfully raising another child is advantageous over no chance at all from turning off the baby maker. Humans, however, have children of a range of ages, making more before the first is finished. Having another inherently takes away from the ones that already exist. Having another that probably won't make it can be an evolutionary negative.
And humans have a much longer portion of their life spent on each offspring. This increases the chance of death before completion and thus makes more evolutionary pressure towards not putting effort into futile things.
Note that this works even if she is alone and doesn't help with the grandkids.
But if you want to avoid withdrawls.. you better harvest and store that honey. And that wheat- all that beer, all that mead. Just to stop shivering.. the addiction of civilization.. and all you need is earthen kegs and a cellar.
I’ve been waiting 10 years for articles like this on HN. I used to wonder why nobody here was discussing or building startups around health. Turns out they are, but those topics are discussed on specialized medical forums.
Apparently, physical health isn’t something you’re going to talk about with investors and users, even though it affects everyone. Before AI, this field was too specialized and there were very few founders willing to work in it.
This is a platform and we are discussing this, which means such a platform isn't enough for what you need. Not judging, actually I've felt a degradation in engagement quality as of late, maybe it's personal bias, but the discussions seem more shallow or aggressive.
In any case, what would you expect from such a platform? That would help with recomendations.
I was in the same place you are now but looking for places to discuss philosophy and looking at the state of mainstream sites like Reddit I decided the open web isn't a place for such discussions because of the sheer volume of noise.
I think the best place to discuss most things nowadays is the real world, but it takes time to build connections in the real world. HN is still a place of real productive discussions but not without a lot of moderation and even so it's still barely functional.
The author cops to teleology, apologizes for it, then continues to use it to explain these behaviors.
This is always a problem when one tries to view biology through an engineering lens. The functions we see today emerged well after the genes themselves started on the path that allowed them to support these specific functions in us. Nor are the genes restricted to exactly identical functions even when their sequence is identical. The context of each cell matters.
Rather than beginning from external function and going down to find energy, replication and cancer/escape from multicellularity as factors affecting these organ’s behavior, it’s a lot better to go cell up, where metabolism, DNA replication, waste clearance, and cell to cell communication and cell-microenvironment sensing are all constantly having to be balanced.
The functions we see from ensembles of cells are composed of these cell level behaviors multiplexing.
And when we look at the eukaryotic cell, we don’t just see linear DNA. We also see mitochondria. Our mitochondria reproduce and proliferate in all cells, depending on energy requirements. The process also produces a lot of reactive oxygen species which need to be kept tamped down to prevent damage.
And the mitochondrial endosymbiotic event also potentially explains why we have linear DNA in a separate compartment. From first eukaryotic common ancestor (FECA) to the last eukaryotic common ancestor (LECA), you had two genomes inside one cell, and by the time we got to LECA a bunch of DNA from the alphaproteobacter that became mitochondria migrated to the core genome, leaving the mitochondrial genome to remain circular.
The exact time and reason for linearization of DNA is (as yet) lost to deep time. But we can see a path from two circular genomes to one linear one circular and construct a fairly believable hypothesis to why you got linearization: as cell type increased, you needed more transcript copies, and access to different transcripts at different times at different rates. A linear genome is much better able to accommodate these requirements. And this has resulted in prokaryotes also partially or fully linearizing some of their genomic material when the need arises (Cyanobacteria, the first autotrophs, have some strains with linear ends, and Lyme disease and streptococcus also break from full circularity).
This linearization is also critical for mitosis and meiosis.
As far as the exact causal chain, we are, at the moment, groping in the blind, since the FECA->LECA transition occurred some 2 billion years ago, and we don’t have candidate fossils. They are reconstructed from genomic puzzle pieces, which is why we have these holes.
In that transition timetable, it is possible commitments were made that shape everything we see today.
Beyond doubt, those commitments had to thread everything a single cell has to thread.
And then came multicellularity, which had its own tradeoffs.
Teleology doesn’t help because none of these early commitments were being made with the specifics of our current lifestyle in mind, or even that complex beings like us could exist.
Evolution is a blind watchmaker. Ignore that and you’ll end up with nice sounding ideas that may not quite fit what we see.
I feel like this is obvious. Eventually dying of all the weird body failures doesn’t inhibit your ability to procreate, but if you cannot survive alcohol or other various poisons you’ll never make it to a fertile age.
Picking the wrong berry from a bush isn't so difficult. Ask me how I know. And, for my second encounter, don't think because you see an animal eating it, it's safe!
Did you know birds do not have receptors for capsaicin? They can eat any pepper and it doesn't affect them. So if you see a bird snacking on a pepper that's red or greenish-yellow, wrinkly, and has a pointy end, well ... watch out
And onions are mildly toxic to cats and dogs. There is a lot less shared responses as to what is toxic or edible across species.
Basically every flavor compound in an herb or spice we eat is a poison directed at insects, microbes, or other creatures. (much less every medicinal or psychoactive compound found in nature)
My guess is that this is half the story. It seems like there would be some advantage to some creatures of not aging, or having individuals who have significant longer life spans.
This is common in evolutionary algorithms anyway so it's notable we don't see it in nature, at least not in the form of extended lifespan perhaps measured by average lifetime heart beats. It's easy to imagine a world where nature might want to keep the alpha lion around longer than the others so it can have more offspring, for example.
> There is, if there were no advantage a whole lot more species would die immediately after reproduction like the octopus.
I didn't just meant extending lifespan, I meant extending the time an individual is fertile.
> The utility of genetic diversity puts a lot of pressure against this.
High levels of elitist selection lowers diversity and can have a negative impact on a population's adaptive ability, but there is a sweet spot to diversity. Maximally diverse is just noise after all.
A small amount of elitism is generally what you would expect to be selected for, and we certainly see this other forms in most creatures, but never in the form of extended life span. That makes me suspect there's probably something fundamentally difficult about extending an organism's lifespan given our biological architecture and that's why evolution has favoured other forms of elitist selection.
Those of us with who get injuries that are life threatening, our genetics have engineered us to be culled from the gene pool. It's to protect the gene pool from other genes.
It's like if car makers made a car with square wheels but every time the car got into an accident it would repair itself so we would keep driving it. Evolution instead blows up the car as soon as it gets into a accident, so then only round wheeled cars remain.
I greatly resent having to be a biological organism and subject to all the poor engineering and design decisions that entails.
The first word of that sentence implies its absurdity quite beautifully. She resents, therefor she is.
And then this:
Brains. After you reach adulthood, neurons don’t divide. If some of your neurons die—which happens every day—then they’re gone. If you get a brain injury, the other neurons will try to “learn around” the injury, but the neurons themselves are never replaced.
We need more neuroscience in schools! This summary is technically correct ofc, but to imply that the brain is missing some obviously-better option is absurd. We're meat that thinks, y'all; it's far from crap.
IIRC the slow loss of neurons is more than balanced by the additional fine-tuning - unless you get dementia, if course.
Loss of neurons isn't disastrous as long as it's not too many. Babies are born with several times more neurons than children have, and spend a few months letting all the useless ones die. Apparently it's better to start with a random tangle and prune it to shape (like cutting a box hedge) than to make a hedge grow in a box shape to begin with.
And IIRC brains can grow more neurons under some circumstances (certain drugs?) - they just normally don't.
"While questions remain regarding the precise extent, rate, and functional relevance of adult neurogenesis in the human brain, as well as important methodological considerations, multiple independent approaches now converge in support of its persistence throughout adulthood."
I get its just a framework to understand what is happening, but I always hate the phrasing of describing a 'decision' to a process like evolution. There are no decisions being made in the process, just a series of outcomes that lead in a direction
Evolution is literally just the observation that there are lots of things that self-replicate.
That's it. That's the entire thing. Plus some nuance about things that self-replicate faster than other things...
It occurs at all levels. Amyloid protein in Alzheimer's patients is self-replicating. So are cells. So are individual parts of cells. Sometimes things replicate by being parts of a larger thing that replicates, sometimes they don't. It's all one big chaotic tangled mess with no particular purpose or design. Human cells evolve, so do humans, so do human societies. So do rocks.
Sure, those are the ingredients for evolution to occur. Replication and variation affecting selection.
But it's also pretty reductive to say it's the entire thing. You'd be hard pressed to describe the history of life on earth using only those three concepts. You could do it, but it would be a bit like describing the workings of a human cell exclusively using quantum field theory.
There are many emergent concepts, the understanding of which brings a lot more explanatory power. Things like selective pressure and evolvability. Our understanding of evolutionary biology and evolution in general indeed continues to evolve nearly 2 centuries after On the Origin of Species.
One of the most interesting things to me is that the process of evolution itself evolves. Variation, replication and selection evolve over time. Evolution seems to accelerate. Evolution can even create entirely new substrates for itself on top of the old ones. If you look at all the traits that distinguish humans from our closest relatives, the brain sizes, the slow maturation of offspring, our vocal chords, complex language, etc, there's a single thread running through all of it, namely an entirely new evolutionary substrate: culture. Once culture appeared, evolution accelerated massively. And cultural evolution itself seems to accelerate. It took several hundreds of thousands of years to get to the agricultural revolution, but then it only took several thousand years to reach the industrial revolution/enlightenment. From there it took centuries to invent the computer, about half a century for the internet and now society changes dramatically within a single decade, some might even argue a single year. In certain specific cases, we can even do evolution in the span of hours or minutes (seconds?) now, with genetic algorithms and the like.
And yes, biological evolution, cultural evolution and genetic algorithms all operate via variation, selection and replication, but it should be pretty clear by now how important all the little details and emergent phenomena are for understanding the differences between them.
No, evolution is not an observation that there are things that replicate. Darwin's view, which has survived mostly intact, is that there is replication with variation and that more fit individuals replicate at a higher rate ("survival of the fittest" isn't a correct description; plenty of less fit individuals do replicate, but they contribute very little to the population genetics in the long run)
And amyloid protein doesn't self-replicate. An instance of the misfolded form causes other folded proteins of the same type to transition to the misfolded form. It's a form of catalysis, not self-replication.
Seems like splitting a hair. In a world abundant with other amyloids, they'd self-replicate. Cells likewise need nutrients and a favorable environment.
In retrospect I conclude you're right (that it's splitting a hair). I went back and some literature does use the term self-replication although at least within my academic circles, we consider autocatalyzed template matching simpler than self-replication.
Possibly a reference to A.G. Cairns-Smith, who speculated about evolving clay crystals. (They can sit in a stream and accumulate minerals, and reproduce that way.)
I mean, that might be the fundamental driver of evolution, but we have observed a lot of other emergent properties that happen because of that process, and those observations form our understanding of what those self-replicating things lead to.
Indeed, I’ve heard so many people misunderstand it because of this type of wording. Like there is still some plan and series of steps we’re following - which really misses the whole point and why it’s worth knowing in the first place
Is there something that causes every substack article to be several times longer than it needs to be? There's just so much color and filler around the information I was interested in
I can't judge if you are correct or not. It would be more convincing if you could name some of the problems. Since the article is "garbage", there should be lots of things wrong to choose from.
He's right, it's garbage and we should know enough (it's high-school level education) to reject it without an explanation. The fact that we don't is actually scary.
Evolution does not care about creating perfect bodies, that's not how it works. Aging and death are superpowers of an unique arrangement of matter, not bugs.
We know diabetes and other issues come from changes humans introduced in our diets, not faults in the evolutionary process.
The text draws from a weird mixture of religious influence (it's not explicit) that lowkey estabilished things should be perfectly designed (in science, mentioning "design" is an issue; fine but aged badly in science communication). It's just not the correct framing to be educational about how our bodies work, and sets up wrong expectations about what we know of nature.
I agree. Very shallow "sources" and no qualifications to be speaking on a medical topic. There is a role for pop science to disseminate knowledge but this is pure speculation.
There's nothing wrong with speculation on HN. Speculation is intimate with curiosity, and curiosity, not correctness, is the guiding value of this site.
It may seem odd to demote correctness in that way, but it doesn't mean we value incorrectness. Correctness is good, just not at the top of the hierarchy. Curiosity (specifically, intellectual curiosity) is what we're optimizing for: https://hn.algolia.com/?dateRange=all&page=0&prefix=true&sor....
We value the freedom to meander curiously. Some paths turn out to be wrong [1], but that is how new things are learned, and it's a good way to spend time. People are allowed to be wrong on HN as part of figuring out what's true [2]. Truth is crucial, but one ought not to squeeze the throat of speculation so tightly that wrong things aren't allowed to be spoken, or fun to be had.
[1] not saying the OP is right or wrong - I have no idea - but the article looks like the fun kind of meandering that has a place here.
Edit: https://www.etymonline.com/search?q=meander - "from Greek Maiandros, name of a river in Caria noted for its winding course". Is there a better website than etymonline?
If you really want to learn about this stuff, Robert Weinberg's The Biology of Cancer is where to start. It introduces concepts starting where a high school student could understand and carefully walks through the history of our development of knowledge until, by the end, the pithy chapters are helping novel concepts for real science flower in your brain all on their own. It's the best book of biological science I have ever read. 10/10, will read again.
https://wwnorton.com/books/9780393887655
Also, although the article is mostly true, there are some inaccuracies:
>> Neurons and cardiac muscle cells don't reproduce after childhood
There is some evidence showing a slow cell turnover in cardiac muscle, estimated around ~1% per year in young adults, falling toward ~0.5% in older people. Most neurons don't regenerate, but there an evidence that some parts of the adult brain (such as hippocampus) still produce new neurons, although the number is very low.
Liver regeneration is not perfect either: https://www.youtube.com/watch?v=rOv7Sr3X-eo .
people have a hard time grasping this concept for some reason.
my favorite example to illustrate this is the trait of being poisonous. if evolution cared about species and then every single one would be poisonous and all predators would have to hyper specialize in prey (arms race between a particular poison and its resistance). it's precisely because it's so difficult to elicit a benefit from this strategy for the lineage that it's so rare. almost always a mutation in coloration has to happen to set the lineage apart from the others first. and then the lineage has to survive the disadvantage long enough.
https://en.wikipedia.org/wiki/Structural_inheritance
basically, the genes do not generally contain blueprints but rather processes utilizing existing cellular machinery. a "mutation" can occur in a machine which will allow a propagating difference.
and there is nothing special about populations. it's merely the only way to observe most changes. gene frequencies in gene pools.
Complications with healing are pretty brutal. Necrosis, amputation, infection are all common without the built-in cascade we have.
The liver's great ability to regenerate largely boils down to how homogenous and simple the liver actually is. It's structured more like a battery pack, where you have individual cells that are largely functionally identical to each other that perform the bulk of the work, and they happen to be connected together. If an individual cell fails, (for the most part) all you need to do is merely regrow a new one, and it's orientation matters little (relatively speaking as compared to other organs) so long as it's connected to the rest of the battery pack (organ).
Contrast that to something like a kidney, which has complex orientation that is formed via growth, and which has a high degree of different types of cells where replacing a part isn't as simple as merely regrowing the part which failed, but also about that growth happening in precisely the right location. So instead of it being like having to replace a failed cell in a battery pack, it's like replacing a wheel to a car. Attaching it anywhere (like the windshield for example) won't necessarily fix the issue, it needs to be connected to the axle...
That's why so many professional athletes take MSM (Methylsulfonylmethane). Their bodies would not be able to recover as quickly without the extra sulfur.
Ideally we could have a switch, low inflammatory reactions when good, high inflammatory reactions on injuries.
Some people also have rare diseases where they don’t have clotting factors so require a transfusion of clotting factors before surgery for optimal wound healing.
Megakaryocytes are primarily bone marrow cells.
I received a cut-down liver from the donor; I got the bigger lobe, a child recipient got the other lobe.
Within a few months of transplant, the new liver had regrown, but (probably because of the transplant orientation) rather than growing across to the left, it grew down the side of my body.
It's all good and functions fine, it's just that now my right-side of my body isn't as 'saggy' as my left because of the area it grew in to.
It's an amazing organ, and it truly sucks when you don't have a well-functioning one.
2024: 11,458 total (604 from living donors)
This is a very outdated view. Neuroscience has shown that neurogenesis continues throughout the entire life span of humans, albeit at a much slower rate. You might have a hard time recovering from a serious brain injury or stroke but losing a few brain cells won’t change a thing.
To the author: thank you, you made my day. It had been a very, very long time since I last read an article on the Internet that felt written by a human being - with humor, some poetry, and science.
Almost like Apple with component serialisation.
Even if we assume your body has a foolproof is_same_species() test, your neighbors' cells may:
1. Be healthy, but have the wrong priorities or behavior, so that they start doing the wrong tasks or sending the wrong messages in the wrong places. [0]
2. Be healthy, but they're just a creepy flesh-mask a parasite has constructed around itself.
3. Be individually hijacked by viruses, and your body won't have the same baseline information to tell that they've deviated from your neighbor's standard.
4. They may be fully human, but gone feral into a transmissible tumor [1].
____
[0] This is actually a risk from pregnancy, as overambitious fetal cells leak into the mother.
[1] https://en.wikipedia.org/wiki/Clonally_transmissible_cancer
The reason I needed a kidney transplant is because of an auto disease called IgA Nephropathy where the IgA antibody has a small defect that causes the rest of the immune system to attack it and the whole mess clogs up the kidney filters over time.
1. Bacteria
2. Parasites
3. Cancer
In all these cases cells that are "other than your own" are in your system and need to be eliminated, in the case of cancer it's your own cells but with significant mutations, as far as I can tell there is always an immune response although in some cases it is actually counter productive.
Immune attack of the pancreas is usually a disease of youth. Type 2 diabetes which is overwhelmingly the diabetes associated with aging is not an autoimmune disease.
When we noticed the signs and went into the ER a few of the (younger) doctors thought it was Type 2, while the attending knew it was just late onset Type 1.
e.g. microberto on X, nutrition detective on YT
This isn't entirely true. I have notable damage to one side and in the recovery process there was a significant increase in the visibility of the surface veins on that side. It's still clearly there years later. Existing vessels can grow larger when repair processes kick in.
The Greeks chose liver because it symbolized the defiance Prometheus had against gods.
For example in Persian poetry the word liver is found pretty much everywhere you would expect to see the word heart.
"You are my liver" is a nice/romantic thing to say to this day.
It could have been because the liver was regenerative and they were using the titan with the regenerating liver as another reference to humanity, or it could have been as someone pointed out because predators like to eat the liver first, or it could have been that you can take damage to the liver and live for hours afterwards in agony whereas the same amount of damage to the heart or lungs is apt to cause death to come much quicker.
Perhaps there are undiscovered variants out there were the eagle or a serpent or some other animal attacks his genitals, or his eyes.
But at any rate the Eagle ate his liver, it means nothing in particular, and at the same time it means every particular interpretation we can place on it.
Just went and checked, evidently he never said anything about it.
old American translation of Galen and Hippocrates for anyone interested, as it can be difficult to find otherwise
https://oll.libertyfund.org/titles/coxe-the-writings-of-hipp...
So by destroying Prometheus' liver, Zeus attempted to destroy his human emotions, including his pride and defiance against gods.
Possibly because it's filled with strong acid.
https://www.science.org/content/blog-post/no-heart-cancer-th...
I watched a Ted talk where the speaker suggested our large brains with their high energy consumption would not have been possible were it not for cooking.
(If we are talking about hunter gatherers, not poor exploited peasants)
We are certainly much healthier, with the little trinkets we keep in our houses.
The real point here, is a lot of people today don't realize how supported they are, with medicine and the trappings of modern life. The simple things I've listed are quite literally a wonder, but to the modern human, often it's not even considered a big deal.
Even in a rural remote areas of Canada or the US, you can just get in your vehicle, drive for half an hour, and then suddenly be surrounded by tens of thousands of products to make you healthier. A city dweller can walk for five minutes, and have the same.
No doubt. But I like to spend time in remote wilderness, so I do know what I have and do not have there. I definitely feel healthier if I am outside more often and can take care of various injuries myself, but if I would really need one, I surely would call for a modern medical helicopter and not go find some plants.
If you made it past age 5 as a hunter-gatherer you’d likely live to 50-60 years of age.
So, monkeys and apes (besides one species of chimps) don't get menopause, elephants don't get menopause, lions don't get menopause. If your prediction is, social animal => menopause, it's wrong 99% of the time.
Conversely human offspring is especially weak and incapable and susceptible to harm, and experiences a lot of threat even within the same species.
Not sure where that are of whale and chimps fit into that - flukes can also happen I guess.
Most species make a baby (or babies), raise them to maturity before having another. Even a low chance of successfully raising another child is advantageous over no chance at all from turning off the baby maker. Humans, however, have children of a range of ages, making more before the first is finished. Having another inherently takes away from the ones that already exist. Having another that probably won't make it can be an evolutionary negative.
And humans have a much longer portion of their life spent on each offspring. This increases the chance of death before completion and thus makes more evolutionary pressure towards not putting effort into futile things.
Note that this works even if she is alone and doesn't help with the grandkids.
Apparently, physical health isn’t something you’re going to talk about with investors and users, even though it affects everyone. Before AI, this field was too specialized and there were very few founders willing to work in it.
In any case, what would you expect from such a platform? That would help with recomendations.
I think the best place to discuss most things nowadays is the real world, but it takes time to build connections in the real world. HN is still a place of real productive discussions but not without a lot of moderation and even so it's still barely functional.
This is always a problem when one tries to view biology through an engineering lens. The functions we see today emerged well after the genes themselves started on the path that allowed them to support these specific functions in us. Nor are the genes restricted to exactly identical functions even when their sequence is identical. The context of each cell matters.
Rather than beginning from external function and going down to find energy, replication and cancer/escape from multicellularity as factors affecting these organ’s behavior, it’s a lot better to go cell up, where metabolism, DNA replication, waste clearance, and cell to cell communication and cell-microenvironment sensing are all constantly having to be balanced.
The functions we see from ensembles of cells are composed of these cell level behaviors multiplexing.
And when we look at the eukaryotic cell, we don’t just see linear DNA. We also see mitochondria. Our mitochondria reproduce and proliferate in all cells, depending on energy requirements. The process also produces a lot of reactive oxygen species which need to be kept tamped down to prevent damage.
And the mitochondrial endosymbiotic event also potentially explains why we have linear DNA in a separate compartment. From first eukaryotic common ancestor (FECA) to the last eukaryotic common ancestor (LECA), you had two genomes inside one cell, and by the time we got to LECA a bunch of DNA from the alphaproteobacter that became mitochondria migrated to the core genome, leaving the mitochondrial genome to remain circular.
The exact time and reason for linearization of DNA is (as yet) lost to deep time. But we can see a path from two circular genomes to one linear one circular and construct a fairly believable hypothesis to why you got linearization: as cell type increased, you needed more transcript copies, and access to different transcripts at different times at different rates. A linear genome is much better able to accommodate these requirements. And this has resulted in prokaryotes also partially or fully linearizing some of their genomic material when the need arises (Cyanobacteria, the first autotrophs, have some strains with linear ends, and Lyme disease and streptococcus also break from full circularity).
This linearization is also critical for mitosis and meiosis.
As far as the exact causal chain, we are, at the moment, groping in the blind, since the FECA->LECA transition occurred some 2 billion years ago, and we don’t have candidate fossils. They are reconstructed from genomic puzzle pieces, which is why we have these holes.
In that transition timetable, it is possible commitments were made that shape everything we see today.
Beyond doubt, those commitments had to thread everything a single cell has to thread.
And then came multicellularity, which had its own tradeoffs.
Teleology doesn’t help because none of these early commitments were being made with the specifics of our current lifestyle in mind, or even that complex beings like us could exist.
Evolution is a blind watchmaker. Ignore that and you’ll end up with nice sounding ideas that may not quite fit what we see.
Basically every flavor compound in an herb or spice we eat is a poison directed at insects, microbes, or other creatures. (much less every medicinal or psychoactive compound found in nature)
This is common in evolutionary algorithms anyway so it's notable we don't see it in nature, at least not in the form of extended lifespan perhaps measured by average lifetime heart beats. It's easy to imagine a world where nature might want to keep the alpha lion around longer than the others so it can have more offspring, for example.
There is, if there were no advantage a whole lot more species would die immediately after reproduction like the octopus.
Many simpler organisms are vaguely immortal.
>It's easy to imagine a world where nature might want to keep the alpha lion around longer than the others so it can have more offspring, for example.
The utility of genetic diversity puts a lot of pressure against this.
I didn't just meant extending lifespan, I meant extending the time an individual is fertile.
> The utility of genetic diversity puts a lot of pressure against this.
High levels of elitist selection lowers diversity and can have a negative impact on a population's adaptive ability, but there is a sweet spot to diversity. Maximally diverse is just noise after all.
A small amount of elitism is generally what you would expect to be selected for, and we certainly see this other forms in most creatures, but never in the form of extended life span. That makes me suspect there's probably something fundamentally difficult about extending an organism's lifespan given our biological architecture and that's why evolution has favoured other forms of elitist selection.
Those of us with who get injuries that are life threatening, our genetics have engineered us to be culled from the gene pool. It's to protect the gene pool from other genes.
It's like if car makers made a car with square wheels but every time the car got into an accident it would repair itself so we would keep driving it. Evolution instead blows up the car as soon as it gets into a accident, so then only round wheeled cars remain.
And then this:
We need more neuroscience in schools! This summary is technically correct ofc, but to imply that the brain is missing some obviously-better option is absurd. We're meat that thinks, y'all; it's far from crap.Loss of neurons isn't disastrous as long as it's not too many. Babies are born with several times more neurons than children have, and spend a few months letting all the useless ones die. Apparently it's better to start with a random tangle and prune it to shape (like cutting a box hedge) than to make a hedge grow in a box shape to begin with.
And IIRC brains can grow more neurons under some circumstances (certain drugs?) - they just normally don't.
https://www.sciencedirect.com/science/article/pii/S193459092...
We can expect evolution to do the right thing for the genes. Not for us.
That's it. That's the entire thing. Plus some nuance about things that self-replicate faster than other things...
It occurs at all levels. Amyloid protein in Alzheimer's patients is self-replicating. So are cells. So are individual parts of cells. Sometimes things replicate by being parts of a larger thing that replicates, sometimes they don't. It's all one big chaotic tangled mess with no particular purpose or design. Human cells evolve, so do humans, so do human societies. So do rocks.
But it's also pretty reductive to say it's the entire thing. You'd be hard pressed to describe the history of life on earth using only those three concepts. You could do it, but it would be a bit like describing the workings of a human cell exclusively using quantum field theory.
There are many emergent concepts, the understanding of which brings a lot more explanatory power. Things like selective pressure and evolvability. Our understanding of evolutionary biology and evolution in general indeed continues to evolve nearly 2 centuries after On the Origin of Species.
One of the most interesting things to me is that the process of evolution itself evolves. Variation, replication and selection evolve over time. Evolution seems to accelerate. Evolution can even create entirely new substrates for itself on top of the old ones. If you look at all the traits that distinguish humans from our closest relatives, the brain sizes, the slow maturation of offspring, our vocal chords, complex language, etc, there's a single thread running through all of it, namely an entirely new evolutionary substrate: culture. Once culture appeared, evolution accelerated massively. And cultural evolution itself seems to accelerate. It took several hundreds of thousands of years to get to the agricultural revolution, but then it only took several thousand years to reach the industrial revolution/enlightenment. From there it took centuries to invent the computer, about half a century for the internet and now society changes dramatically within a single decade, some might even argue a single year. In certain specific cases, we can even do evolution in the span of hours or minutes (seconds?) now, with genetic algorithms and the like.
And yes, biological evolution, cultural evolution and genetic algorithms all operate via variation, selection and replication, but it should be pretty clear by now how important all the little details and emergent phenomena are for understanding the differences between them.
And amyloid protein doesn't self-replicate. An instance of the misfolded form causes other folded proteins of the same type to transition to the misfolded form. It's a form of catalysis, not self-replication.
https://news.ycombinator.com/newsguidelines.html
Evolution does not care about creating perfect bodies, that's not how it works. Aging and death are superpowers of an unique arrangement of matter, not bugs.
We know diabetes and other issues come from changes humans introduced in our diets, not faults in the evolutionary process.
The text draws from a weird mixture of religious influence (it's not explicit) that lowkey estabilished things should be perfectly designed (in science, mentioning "design" is an issue; fine but aged badly in science communication). It's just not the correct framing to be educational about how our bodies work, and sets up wrong expectations about what we know of nature.
It may seem odd to demote correctness in that way, but it doesn't mean we value incorrectness. Correctness is good, just not at the top of the hierarchy. Curiosity (specifically, intellectual curiosity) is what we're optimizing for: https://hn.algolia.com/?dateRange=all&page=0&prefix=true&sor....
We value the freedom to meander curiously. Some paths turn out to be wrong [1], but that is how new things are learned, and it's a good way to spend time. People are allowed to be wrong on HN as part of figuring out what's true [2]. Truth is crucial, but one ought not to squeeze the throat of speculation so tightly that wrong things aren't allowed to be spoken, or fun to be had.
[1] not saying the OP is right or wrong - I have no idea - but the article looks like the fun kind of meandering that has a place here.
Edit: https://www.etymonline.com/search?q=meander - "from Greek Maiandros, name of a river in Caria noted for its winding course". Is there a better website than etymonline?
[2] https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...
https://news.ycombinator.com/item?id=11655206