Why is the human body so crap except for the liver?

dynomight.net/liver[Epistemic Status: Speculative unifying theory of biology.]I don’t know about you, but I greatly resent having to be a biological organism and subject to all the poor engineering and design decisions that entails. This has many manifestations. A recent one is often wondering, why is the entire body such garbage except for the liver?Take the kidneys. Once you reach adulthood, they start to slowly decay. You can damage them through not-obviously-dangerous stuff like taking too much vitamin D or taking ibuprofen while dehydrated. Significant damage typically leads to scarring and a permanent reduction in function. Or take the gums. If you brush too hard or don’t floss enough, they may retreat down your teeth, never to return. Most of the body is like that.But the liver. My friends, the liver! If it’s injured, it will usually heal without scars. As you age, it typically maintains near full strength. You can give half of your liver to someone else and it will regrow to full size and function in a few months. I’d like to find whoever designed the liver and have them make me a full body.Except here’s a theory: It’s good that most of the body is fragile crap. It would be better if some parts of the body were more fragile.Menopause. We’re still struggling to reconcile modernity with the short human reproductive interval. But did you know that menopause is almost unknown outside of humans? Even the other great apes remain fertile for almost their entire lives. The only known exceptions are (1) killer whales, (2) pilot whales, (3) beluga whales, (4) false killer whales, (5) narwhals, and (6) one specific population of chimpanzees in Uganda.Inuries. If your leg gets chopped off, that’s it, no more leg. Your body will try to grow scar tissue over the wound and then you’re on your own. But if you chop off the leg of a salamander it… grows a new leg. Isn’t that the obvious to do? Why don’t we do that?Telomeres. The ends of your chromosomes have a little repetitive sequence called a telomere. When cells divide, the body tries to copy the DNA, but good-old DNA polymerase can’t quite copy all the way to the end, meaning the telomeres slowly get shorter. After dividing 50-70 times, the telomeres are gone, and the cells stop dividing and then slowly stop working. This is one of the many ticking clocks of aging.Transplants. If you need a new kidney, and someone is nice enough to give you one of theirs, your body will respond by trying to kill it, meaning you have to take horrible immunosuppressants for the rest of your life. And even after taking them, there’s a 30% chance the kidney will be rejected within 10 years. This is not helpful.Diabetes. Some day, your immune system may decide to attack your pancreas. After a while, your pancreas will stop making insulin, meaning that unless you reorient your entire life around keeping your blood sugar in check, your eyes, kidneys, nerves, and heart will constantly accumulate damage. Your immune system should not attack your pancreas.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.Junk. All cells build up various “junk” over time. As they divide, the junk is diluted. But some cells (neurons, various cells in the eyes) never divide, so the amount of junk (e.g. lipofuscin) just goes up and up. This is another ticking clock.Blood. Your flesh needs blood, which your body delivers through blood vessels. Over time, these can get clogged with plaque. The thing to do in this situation is to sprout new blood vessels. Your body knows how to do that. But by default it maintains high levels of various inhibitors (angiostatin, endostatin, THBS1) that tell your cells not to do so. If your heart or brain get starved of blood, your body will try to reverse all this inhibition, but the process is slow and clumsy and can only produce tiny blood vessels.As always in biology, the correct answer is: A lot, it’s complicated. But I think there’s a common thread.The clearest case is probably telomeres wearing down as you get older. At first glance, you might ask, why does this problem exist at all? Bacteria—because they aren’t idiots—have circular DNA, which doesn’t have ends or telomeres. Eukaryotes like us evolved from bacteria. Who decided to replace circular DNA with linear DNA?Or, you might ask, why doesn’t the body re-lengthen the telomeres? Well, actually it does! We have an enzyme designed specifically for that purpose, called telomerase. But, after embryonic development, the body doesn’t bother to use it, except in stem cells, reproductive cells, and certain parts of the immune system. Huh?The reason we have linear DNA instead of circular DNA is contested.1 But whatever. If the body wanted to re-lengthen the telomeres, it could easily do that. Your cells already have DNA to make telomerase. They just don’t use it. Instead, they let the telomeres get shorter until they stop dividing and stop working. Why?Because……Cancer.(That’s our answer to the question in the title of this post: The human body is so crap except for the liver because cancer. As we’ll see, this answer is only semi-correct, and even then only with several caveats. But what do you expect from biology?)Letting the telomeres get shorter is not a mistake. It is a deliberate design decision.2 Often, in your body, the following happens:Some cells get a mutation that causes them to start reproducing too fast.Your immune system decides they’re suspicious and kills them.You’re fine. 👍But sometimes this happens:Some cells get a mutation that causes them to start reproducing too fast.They grow for a while, but then (for complicated reasons3) they stop increasing in number.But they aren’t just sitting there, they’re constantly reproducing and dying, much faster than normal cells.Eventually, they develop another mutation that allows them to overcome whatever was stopping them from growing.This continues for a while, with the cells gradually acquiring more of the mutations they need to grow to a large size.But wait!With all this reproduction, at some point the mutated cells ran out of telomeres and stopped being able to reproduce.Ha! Screw you, mutated cells! 👍To be clear, this also sometimes happen:(Steps 1-6 above)With all this reproduction, at some point the mutated cells figured out how to turn telomerase back on.This re-lengthens their telomeres, so they can reproduce indefinitely.They either stop growing for other reasons (👍) or you use our modern technological civilization to kill/remove them (👍) or they grow so slowly that something else kills you first (🤌) or there is a less desirable outcome (👎).(If you’re a biologist who is outraged at the above description, I’ve written a footnote which I beg you read before yelling at me.4)Having telomeres that wear down is good, because it slows down cancer. It’s also bad, because it means our bodies slowly stop working. Evolution decided the good outweighed the bad, and I expect that evolution was right.Several of the other ways in which the human body is “crap” can be explained in the same way. Why can’t you re-grow your leg if it gets chopped off? Well, that would require that all your cells have a “begin rapid growth mode” button on them, with some external trigger. In a sense, it would require your body to leave your cells sitting around in a state that’s closer to being cancer. Not doing that is good, because it slows down cancer, and bad, because you can’t grow a new leg. Evolution apparently doesn’t like that tradeoff, and again I assume evolution is right.5Fragile kidneys are much the same. We could have kidneys that try harder to repair themselves. That’s probably biologically possible. But it would likely mean more kidney cancer. Arguably, the question isn’t, “Why are the kidneys such fragile crap?” but rather, “Why is the liver so weirdly regenerative?”That question has two standard answers. Answer #1 is that the liver has a hard job. It sits directly downstream of the gut. If you eat toxins or bacterial products or viruses or parasites, the liver sees them at high concentrations before the rest of the body. Not only that, it’s the liver’s job to detoxify stuff, and detoxification chemistry is often self-damaging: The liver breaks toxic stuff down into even-more toxic stuff, and then deals with that stuff recursively. The liver is constantly getting damaged, as part of its job description, so it must be able to regenerate. Evolution designed it to do that, and it just pays the cancer tax.Answer #2 is that the liver isn’t unusual. Your skin can survive wounds. And your intestines can survive exposure to digestive enzymes, bile, and bacteria. The surface layers of both of these are constantly turning over. And, lo and behold, skin cancer and colorectal cancer are both very common.At the other end of the spectrum, neurons and cardiac muscle cells don’t reproduce after childhood. If they die, they’re gone.6 As a result, “heart cancer” is almost unheard of. (The very term “heart cancer” almost sounds ungrammatical.) Brain cancer is a thing, but it’s essentially always in other types of brain cells, not neurons.So maybe we can think of different parts of the body as making different tradeoffs between regeneration and cancer risk:7At first glance, we seem to have a cute little story: Evolution pays the cancer tax for organs that need to interface with the environment, because it’s a harsh world out there. And it pays the fragility tax for organs that can be tucked away so that regeneration isn’t as necessary.Wouldn’t that be nice? Let’s formalize that as a theory.Theory:More regeneration implies more cancer risk.Evolution tunes organs that encounter the environment for more regeneration and more cancer. It turnes organs that don’t for the opposite.Of course, it’s not that