Why is the liver so weirdly regenerative?

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 .

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.

> 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.

"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.

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.

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.

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

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

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.

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

Very nice, well written and interesting! Amazing!

Anybody on HN knows platforms to discuss this ?

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.

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

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.

> 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.

   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.

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

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