Why is the liver so weirdly regenerative?

(dynomight.substack.com)

152 points | by jbotz 6 hours ago ago

108 comments

  • senfiaj 42 minutes ago ago

    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.

    Liver regeneration is not perfect either: https://www.youtube.com/watch?v=rOv7Sr3X-eo .

    • asdfman123 15 minutes ago ago

      Actually I would argue that the evolutionary pressures run against it: if one generation dominates then the species can't evolve.

  • cityofdelusion 2 hours ago ago

    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.

    • seethishat an hour ago ago

      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.

    • WhiteOwlLion an hour ago ago

      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.

      • BigTTYGothGF an hour ago ago

        > Your liver makes platelets

        Megakaryocytes are primarily bone marrow cells.

  • Noe2097 2 hours ago ago

    > 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.

    • WhiteOwlLion an hour ago ago

      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.

      • buildsjets 35 minutes ago ago

        I asked ChatGPT if it is OK to an explain a joke without being asked to do so, and She said no.

    • varispeed 13 minutes ago ago

      Why nature did this? So that 3rd parties don't engage in organ swaps?

      Almost like Apple with component serialisation.

  • epcoa 2 hours ago ago

    "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.

    • joshmarinacci an hour ago ago

      Adult onset Type 1 has become a lot more common in recent decades. Ask me how I know.

      • patagurbon 35 minutes ago ago

        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.

      • mschuster91 an hour ago ago

        Just like a ton of other autoimmune diseases.

        • ramijames 43 minutes ago ago

          Psoriasis sufferer checking in. Brutal.

  • vconnor 3 hours ago ago

    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.

    • bheadmaster 3 hours ago ago

      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.

      • pazimzadeh 2 hours ago ago

        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.

        • The_Blade an hour ago ago

          i mean it's called the liver not the dier

      • bryanrasmussen 3 hours ago ago

        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.

        • bheadmaster 3 hours ago ago

          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.

          • bryanrasmussen 2 hours ago ago

            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

            https://oll.libertyfund.org/titles/coxe-the-writings-of-hipp...

      • mwigdahl 2 hours ago ago

        I thought they chose it because it tastes great with some fava beans and a nice Chianti.

      • seizethecheese 3 hours ago ago

        Why would liver signal defiance?

        • bheadmaster 3 hours ago ago

          I phrased it awkwardly. Simply put, in Ancient Greece, liver was something like heart in modern society. It was the seat of human emotions.

          So by destroying Prometheus' liver, Zeus attempted to destroy his human emotions, including his pride and defiance against gods.

          • seizethecheese 2 hours ago ago

            I don’t think it was phrased awkwardly, I was just curious.

        • Sleaker 3 hours ago ago

          It was the believed area of emotion, passion and 'soul'. I think western/modern religion has morphed from the liver to the heart essentially.

          • pinkmuffinere 2 hours ago ago

            This is still the normal in the middle east (and likely elsewhere)! In Turkey you call somebody dear to you "my liver" as a pet name.

        • jephs 3 hours ago ago

          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.

        • Bluestein 3 hours ago ago

          Humors perhaps. Not my area, so I do not recall the correspondence ...

      • bell-cot 3 hours ago ago

        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.

  • joshmarinacci an hour ago ago

    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.

  • amluto 5 hours ago ago

    The lack of heart cancer might be more complex than the OP imagines:

    https://www.science.org/content/blog-post/no-heart-cancer-th...

    • jaggederest 3 hours ago ago

      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.

  • schnuri 5 hours ago ago

    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.

    • dgunay 4 hours ago ago

      Well, we do at least have to eat enough food and sleep ~1/3rd of our lives. That's kinda maintenance

      • vconnor 2 hours ago ago

        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)

        • nerdralph 2 hours ago ago

          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.

          • NetMageSCW 31 minutes ago ago

            Which came first, steak or intelligence?

      • yhjc2692 3 hours ago ago

        quite the delightful maintenance too

      • micromacrofoot 3 hours ago ago

        that's absolutely maintenance, without it you have a total system failure in a week

    • ericmay 3 hours ago ago

      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.

    • onlypassingthru 2 hours ago ago

      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.

      • fhn an hour ago ago

        until you get old and goes the opposite direction

    • RobotToaster 4 hours ago ago

      Humans don't last long without topping up their fluids and consumables.

    • markyc 4 hours ago ago

      no you don't

    • chistev 4 hours ago ago

      The human body can't survive 80 active years without maintainance. They take drugs, they see the doctor, etc.

      • CookieCrisp 4 hours ago ago

        What did people do 500 years ago?

        • EduardoBautista 4 hours ago ago

          Die as a child at alarming rates

          • lukan 3 hours ago ago

            But those who did not, got quite old without ever seeing a doctor.

            (If we are talking about hunter gatherers, not poor exploited peasants)

            • steve_adams_86 3 hours ago ago

              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.

              • b112 an hour ago ago

                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.

                • lukan 16 minutes ago ago

                  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).

            • fhn an hour ago ago

              quite old as in 50 because the avg lifespan back then is certainly lower than it is now.

            • 1attice 3 hours ago ago

              Citation required

              • Fezzik 3 hours ago ago

                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.

                • 1attice 3 hours ago ago

                  Interesting. Yet as someone approaching the first of those two last numbers, I would say that that isn't very old at all

                  • Fezzik 3 hours ago ago

                    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.

                  • exe34 2 hours ago ago

                    Old people are at least 20-30 years older than I am.

  • warumdarum 3 hours ago ago

    Because alcoholism forces hunter gatherer cultures into settlements, which are the next stage of civilization and reward those doing that choice?

    • asdfman123 10 minutes ago ago

      Actually it may be the opposite. Alcohol is needed for people within settlements to bond.

    • danecek099 an hour ago ago

      I love this theory

    • The_Blade an hour ago ago

      wouldn't it be our ancestors just liked booze too much and the liver said alright genes, hold my beer

      • warumdarum 43 minutes ago ago

        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.

  • daitangio an hour ago ago

    Very nice, well written and interesting! Amazing!

  • agumonkey 3 hours ago ago

    Anybody on HN knows platforms to discuss this ?

    • gchamonlive 3 hours ago ago

      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.

      • agumonkey 2 hours ago ago

        Hacker news is dedicated to 'tech' and I'm looking for advances in biology.

        • gchamonlive an hour ago ago

          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.

          • agumonkey 36 minutes ago ago

            I kinda agree about reddit, either too much noise or gatekeeped (iirc some medical subreddits are mostly students or professionals only).

  • thisisauserid 2 hours ago ago

    Shouldn't the question be, "Why isn't everything else?"

  • randomImmigrant 42 minutes ago ago

    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.

  • Aeolun 3 hours ago ago

    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.

    • nofunsir an hour ago ago

      It's more than possible to make it to adulthood without ingesting a drop of alcohol, even if you're talking about fermented fruit. It's easy, in fact.

    • nomel 3 hours ago ago

      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!

      • colechristensen 2 hours ago ago

        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)

      • cratermoon 2 hours ago ago

        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

    • kypro 2 hours ago ago

      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.

      • colechristensen 2 hours ago ago

        >It seems like there would be some advantage to some creatures of not aging, or having individuals who have significant longer life spans.

        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.

  • card_zero 4 hours ago ago

    > Evolution decided the good outweighed the bad, and I expect that evolution was right.

    We can expect evolution to do the right thing for the genes. Not for us.

    • cortesoft 4 hours ago ago

      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

      • someonebaggy 3 hours ago ago

        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.

        • cwillu 3 hours ago ago

          Rocko can't have kids, because Rocko is just a stupid rock.

          • card_zero 3 hours ago ago

            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.)

        • dekhn 3 hours ago ago

          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.

          • card_zero 2 hours ago ago

            Seems like splitting a hair. In a world abundant with other amyloids, they'd self-replicate. Cells likewise need nutrients and a favorable environment.

            • dekhn 2 hours ago ago

              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.

      • CookieCrisp 3 hours ago ago

        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

      • card_zero 3 hours ago ago

        Oh, fair point, I did the pathetic fallacy (too). Beneficial thing, then.

  • bbor 4 hours ago ago

       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.
    • someonebaggy 3 hours ago ago

      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.

      • rzzzt 3 hours ago ago

        "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."

        https://www.sciencedirect.com/science/article/pii/S193459092...

      • NetMageSCW 28 minutes ago ago

        I’m pretty sure that’s been debunked and they normally do.

    • dekhn 3 hours ago ago

      the claim isn't complete, either. Recent research has demonstrated adult neurogenesis (growth of new cells that originate from neural stem cells).

    • done_lurking 3 hours ago ago

      Why is it absurd to say that the human brain could be better? That seems obviously true to me.

  • monster_truck an hour ago ago

    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

  • dekhn 5 hours ago ago

    [flagged]

    • dang 4 hours ago ago

      "Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something."

      https://news.ycombinator.com/newsguidelines.html

      • dekhn 3 hours ago ago

        [flagged]

    • rwmj 5 hours ago ago

      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.

    • haskellandchill 5 hours ago ago

      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.

      • dang 3 hours ago ago

        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?

        [2] https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...

        https://news.ycombinator.com/item?id=11655206

        • clove 2 hours ago ago

          Based.

        • warumdarum 3 hours ago ago

          What is a new hypothesis other than a conspiracy of circumstances making better sense..