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.
Vitamin A is in eggs, dairy (butter, milk, cream), in meat fats like pork and grain-fed beef, in salmon, in liver, in cod liver oil. Vitamin-A precursors (carotenes) get converted into Vitamin A in the body, they are in red and orangey fruits and vegetables such as carrot, tomato, chili, chili-powder spice, bell pepper, sweet potato, apricot, mango, butternut squash, grapefruit, watermelon, papaya, passion fruit, cantaloupe, pumpkin, also in dark greens like kale, collard greens, spinach.
Carotenoids are used as a natural food colouring, beta-carotene is E160a, e.g. I've seen it in Red Leicester cheese, yellow custard powder, red jelly, in glace cherries. American law requires vitamin A fortification in reduced-fat dairy. Companies optionally fortify it in things like wheat flour, or breakfast cereal. Retinoids are in beauty and moisturising skin creams and sun tan lotions, and sometimes used as extreme acne medication.
Things that have been promoted for "good health" for decades, such that someone who wants to avoid it needs to deliberately choose an awkward diet of non-colourful foods like potato, rice, onion, parsnip, coconut, apple, pear, cucumber, zucchini, black beans, white beans, lean meats or carefully chosen meat fats, breads made from un-fortified flour, avoiding many restaurant, take-away, or processed foods and "eat the rainbow" variety of fruit and veg.
Grant Genereux has proposed that overflowing the liver's ability to store and process Vitamin A / retinoids leads to them circulating in the blood, that they can enter cells bypassing the normal methods, can cause damage which makes cells denature and burst, which triggers an immune system response to try and find an attacker, which gets misdiagnosed as the immune system causing the damage. And has proposed this as a mechanism which explains some of the 25 - 50 million Americans having unexplained auto-immune diseases.
Proposing that retinoic acid builds up inside body cells over years and decades even whan taken ordinary 'safe' levels, not enough to trigger hypervitaminosis A or acute symptoms but chronically accumulating until the body has so much of it stored that cell damages releases retinoids into the bloodstream which enter nearby cells, denature some of them, releasing their stored retinoids, causing a domino effect which we know as an auto-immune flare-up. And that it's a matter of luck where the concentration is higher whether that makes a skin rash or a kidney or joint or thyroid inflammation, or just generally high "inflammation".
It's an interesting hypothesis with a lot of specific testable claims and specific proposed mechanisms, mixed with quite a lot of conspiracy theorising and less-testable claims.
I'm past the comment edit window, but incidentally these two Harvard pages[1,2] say that:
- the recommended daily vitamin C is 90mcg for men and 75 for women, the upper limit is 2000mcg. That's a safety margin of 22x, and exceeding the upper limit may cause diarrhoea and gastrointestinal distress.
- the recommended vitamin A is 900mcg for men and 700 for women, and the upper limit is 3000mcg. That's a safety margin of 3.3x, and even that upper limit has "some evidence that this much preformed vitamin A might increase the risk of bone loss, hip fracture, or some birth defects".
- "Sometimes people take cod liver oil for vitamin D but may not be aware it is also very high in vitamin A, beyond the RDA at 192%"
That is, even without any alternative views on it, it's much easier to go above the safe levels, easier to do accidentally, and the risks are more serious.
Consuming lots of dairy (including fortified), lots of colorful veggies every single day year round, maybe adding multivitamins, fortified flour. Then there's the liver hype in some circles.
Your Wikipedia page references a paper in footnote 21 which says:
> "In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods"
and
> "Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons"
Google tells me that "Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage".
Carotene conversion cannot both be "a minor contributor" to body levels of Vitamin A and also the main way billions of people get Vitamin A. So my guess is the Wikipedia page has mistakenly taken 'excentric cleavage' to be the only conversion method. Still, ignoring carotenes entirely, the referenced paper also says:
> "observational studies suggest that more than 75% of people may be routinely ingesting more than the recommended dietary allowance (RDA) for vitamin A"
> "Dietary vitamin A is obtained from preformed vitamin A (ie, retinyl esters from animal foods, fortified foods, and pharmaceutical supplements) as well as from provitamin A carotenoids from plant sources. Preformed vitamin A is efficiently absorbed and utilized by humans at absorption rates of 70–90%. Up to 75% of dietary vitamin A in Europe, the United States, and other industrialized nations is preformed vitamin A (1, 2), which is largely derived from multivitamins, fish liver oil, and the fortification of foods such as milk, butter, margarine, breakfast cereals, and some snack foods. In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods. These are absorbed much less efficiently, at rates of 20–50%, depending on each person’s vitamin A status and other dietary and nondietary factors (3, 4). The cleavage of provitamin A carotenoids to retinal is a highly regulated step, and vitamin A toxicity from provitamin A sources is largely impossible. In contrast, absorption and hepatic storage of preformed vitamin A occur very efficiently until a pathologic condition develops."
Indeed, but they neither explain nor cite what they mean for it to be "highly regulated" or how/why that means toxicity is largely impossible.
If you take "the cleavage of provitamin A carotenoids" and Ctrl+F for 'cleavage' or 'carotene' in that paper, the only other mentions are this:
> "An acute elevation of retinoids other than retinyl esters—eg, retinoic acid—occurs after the ingestion of a large amount of vitamin A, possibly because the intestinal absorptive capacity is overwhelmed, which leads to the oxidation of retinol to retinoic acid by the intestinal enterocytes (30) and to the rapid formation of retinoic acid from retinol in certain cells (5). Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons."
That is, they only seem to be talking about excentric cleavage and not central cleavage. My limited understanding is that beta-carotene is roughly two retinoic acid molecules chained together, and cleaving them in half is what makes two retinoic acid molecules, and that non-central-cleaving would be different. See skeletal formula on right for these two pages:
(You can also wonder if beta carotene can produce 90% of circulating vitamin A in developing countries, whether getting lots of beta carotene in developed countries can raise the base level in the body, which then leads to easier overdose from preformed vitamin A)
Possibly if you have many symptoms that sound like isotretinoin or tretinoin side effects (the latter is active vitamin A, the former just a twisted form of it).
As for measuring: there might be spillover of retinyl esters (storage form in the liver) into serum, but that's nothing that's commonly measured. (Serum retinol levels do not correlate with liver levels AT ALL.)
At least for isotretinoin, that would look like: dry skin, chapped lips, dry eyes, dry nostrils, dry mouth, photosensitivity, body aches in the morning.
It can also raise liver enzyme values and change lipid values.
(I recently finished a round of Accutane, basically high dose vitamin A)
In general, we don’t do curative surgeries for metastatic cancers. The thinking is that it is has spread that much away from where it started, there little point going to cut out where it started alone. Are we then to cut out every place it has spread to and every how it got to those places.
We do do palliative surgeries if warranted but the intent there is not to cure, but to relieve some symptoms and transiently improve quality of life.
Please direct any specific questions you have about your sisters case directly to her doctors
The method of printing is not the major cost differential in a book. Hardbound or softbound, the production costs don’t differ all that much. That is why ebooks are not substantially cheaper than a printed book.
Does SV40 cause cancer?
Did and does SV40 inadvertendly inside the Polio Vaccine in the late 1950ies and 60ies cause cancer?
Does the Pfizer proces 2 SV40 promotor in the Covid Vaccine cause cancer?
Is SV40 DNA (or its fingerprints) found inside actual cancer tissue these days? What type of research is performed on it?
Does DNA contamination in general cause cancer?
I don't know if you're friendly enough to address these isssues. Probably not.
> I don't know if you're friendly enough to address these isssues. Probably not.
A fantastic closing if the goal is to make people not answer your questions. I don't know if you're friendly enough to explain why you made your comment so hostile. Probably not.
SV40 can 'immortalise' cells, turning off regulatory functions which prevent uncontrolled division, which is an important part of carcinogenesis. This has been shown to contribute to cancer in experimental systems.
> Did and does SV40 inadvertendly inside the Polio Vaccine in the late 1950ies and 60ies cause cancer?
The evidence suggests not significantly, although it's impossible to rule out for some unlucky individuals.
The SV40-exposed cohorts rates of cancers don't differ that greatly from unexposed groups, so we can say with certainty that the rate is much less in humans than seen in laboratory systems. There were suggestions of differences for some cancers, but these are heterogeneous and often confounded, and the general consensus now seems to be the effect was small if not zero. I don't think there's a definitive answer on why - possibly the exposure was sufficiently low or the virus was not effective at infecting humans to significantly affect the carcinogenic processes.
> Does the Pfizer proces 2 SV40 promotor in the Covid Vaccine cause cancer?
Certainly not by the mechanism intact SV40 causes cancer.
That depends on the production of particular SV40 proteins which interfere with cell functions, which aren't present in that promoter.
> Does DNA contamination in general cause cancer?
In general, no.
Cells are constantly exposed to both native and foreign DNA fragments, and have plenty of mechanisms for dealing with them. Even if fragments were somehow incorporated and expressed, most are not inherently carcinogenic.
You are ignorant and disrespectful and i'm higly disappointed from human to human.
"friendly enough to address these issues".
He is not part of some research group who is researching this type of topic. You assume he is a bad faith actor with your "probably not".
Either accept the status quo / research on this topic, or do the research yourself but don't take some potential conspiricy shit to hn by cheap shooting someone else with your 'probably not'.
And if you really struggle with this type of things, get help.
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.
> Most of the body doesn't regenerate because there was not enough evolutionary pressure.
All basal metazoan branches (ctenophora, porifera, placozoa, cnidaria) have species that are capable of whole body regeneration, so this trait was likely lost on the bilaterian branch (which includes chordates like ourselves). If anything, there are evolutionary pressures to loose this trait.
For example, consider how frequently people lose a limb, and further consider the ratio of survival to death for injuries in that general ballpark. Then balance this quality of life improvement, for those who survive, for those injured in the first place, against the fact that all people with such a biological capability will almost certainly experience a significantly higher rate of cancer. Because in a nutshell cancer is uncontrolled proliferation while regeneration is controlled proliferation. (It would be very interesting to know the rate of incidence of various cancers in axolotls if they lived anywhere near as long as a human.)
I have read somewhere that losing a limb naturally (e.g. tearing, biting) stretches and closes up blood vessels in a way that cutting with a scalpel doesn't, and that natural limb loss has less bleeding than surgery/stabbing/Hollywood suggests.
I have no idea of the truth of this, but there are anecdotes of farmers losing limbs and walking back to their tractors, driving back to the farm, then driving themselves to hospital, and the like.
Yes that's kind of (but not entirely) my point. It's actually quite difficult (for a human) to lose a limb in a sudden accident without immediately dying. So it's exceedingly rare (~all historical civilisations) to be injured in such a manner, it's at least somewhat rare to survive such an injury (historically just about impossible), and even if you had flawless regeneration you'd be at a serious physical disadvantage (ie from an evolutionary fitness perspective) in multiple ways for an extended period. Meanwhile carrying said trait is consistently killing people off the entire time.
I think the extended period is a point that needs consideration. I don't know how long it takes a salamander to regrow a limb, but given the sheer size of any given limb in an adult human, it would take quite some time to regrow it to anywhere near its former state.
Yes, that was my point. Amputations are quite uncommon, they usually lead to death (blood loss / infection, starvation, vulnerability to predators, etc) For relatively intelligent species they are even more avoidable. Regeneration would add very little benefit from natural selection point of view. Most body parts are durable enough for survival and reproduction.
Not "pressure to lose this trait" as much as "no pressure to improve it"?
As anatomy gets more complex, the process of getting it from "arbitrary heavily damaged state" to "functioning state" gets more complex too. And mammals are a bit more anatomically complex than placozoa.
If your entire body is a hollow sphere 4 cells thick, "repairing arbitrary damage" is very simple and natural. When you have bones, blood vessels, nerves, muscles and tendons, all wrapped in skin - all of which have to be restored correctly for a lost limb to function well? The gap between "just plug the holes" and "restore the function" grows, and the complexity of implementing usable regeneration goes up massively.
Humans can repair most of simple tissue-level damage well enough. The complexity equivalent of placozoan regeneration is in place. Rebuilding complex anatomy is what's often unimplemented. Seems like that is the part that requires some novel adaptations rather than simply not deactivating the mechanisms that are already there.
I read a book on epidemics where some modern theories on death were essentially its selected for to force potential infecting organisms to keep starting over on mastering a given genetic environment. Ones grandchildren are more likely to survive the successor plague than you are, hence a population with excessively long life would have died out. I think the evidence was from long lived trees? (Pandemic by Sonia Shah).
> Most of the body doesn't regenerate because there was not enough evolutionary pressure.
Maybe, but isnt this basically tautological? "You didnt evolve this way because of how evolution works". The more interesting question is why did certain parts evolve the way they did, and can we harness the knowledge?
Exactly, limbs are quite large portion of the body, that's why many think salamanders would have no problems with regenerating all other smaller body parts. And that's not the case.
Dr Michael Levin at Tufts has a lot of electro based theories about regeneration based on findings with Palnarians he adjusts the voltage states and gets two headed liniages amongst the many many other things his lab covers
Getting "old" is a recent and tiny sliver of human evolution. It's only been the last 100 or so years that we've really started to push the boundaries of what the body is capable of and our biology has never really had a chance to deal with it and "develop" a solution.
This isn’t correct. For example, when Edmond Halley created the world’s first life table in the 1690s, he estimated that approximately 5% of his city’s adult population was >70. Getting old is not new.
Even still, if we were able to continue on current aging trend, including food availability and whatnot, for another hundred thousand or million years; what evolutionary pressures exists that would make our biology able to live even longer than our current status quo?
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.
> our ancestors insisting on eating toxic things like mushrooms and spoiled food
Presumably this didn't happen because are ancestors were dumb, but rather because the ability to process slightly spoiled food is a significant advantage in an environment where fresh food is sometimes scarce?
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.
Blanche spinach, try not to eat them raw. Speaking of oxalates, I did not know yam leaves were inedible. Saw a little tender shoot, bit a little piece off. Tastes like mushroom. I don't think it's toxic but it's like eating glass.
And that "eating glass" comment is related to how I know. I boiled a wild "edible" (skunkweed leaves) in 3 changes of water; what I should have done is either dry it completely or (better) treat it with lye. Bad memory mistake. Yeah: eating glass shards.
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.
Cells are specialized to their function, as well as to their diseases. The trade offs mentioned in the article seem simplistic, trying to capture the billions of years of evolution. Repair, regeneration, regrowth and cancer have distinct mechanisms that vary from cell type to type.
Liver regeneration has been known since the ancient times: in Greek mythology an eagle was eating the liver of Prometheus every day for thousands of years after Zeus punished him for donating the fire to humans but he survived to be saved by Hercules.
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.
The article complains about a lot of questionable design aspects of the human body, including menopause. Only us and a couple of whales (and apparently one specific chimp population I wasn't aware of?) go through menopause, making us infertile long before we die. Why is that? Wasn't more kids supposed to be better?
I recently learned about this (not sure if it was a YouTube video or an article): apparently, it's not that we become infertile long before we die, it's that we live long past our fertility ends. And the reason for that is really simple: old people have accumulated a lot of knowledge that is valuable to teach to younger generations. The alternative is not to be fertile longer, but to die younger.
Presumably, menopause only occurs in species that learn and teach, and are able to accumulate so much knowledge that it becomes useful to keep experienced individuals alive longer so they can continue to teach.
> 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.
Kidney failure and jokes... OK, I feel obliged to share a true story. A relative of mine donated their kidney to one of their siblings. A couple of years ago we were all playing "naughty Santa" AKA "white elephant". It was the donee's turn and they chose to steal the donor's present. The donor replied "oh man, that's just like when you stole my kidney!" I've never laughed and cried so much in my life.
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.
In this case nature was just indifferent to transplants as they weren't a thing even 100 years ago.
As others have explained, foreign cells usually meant trouble, so fighting them by default was a good choice. And there was no pressure to allow transplants specifically, because they didn't exist.
Also, (I think) you usually need a transplant later in life, after reproduction, so too late for evolution to affect it. So even if we had transplants for millions of years, it might not have made much difference either.
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.
There is zero inherent way to tell a malicious group of proteins and RNA or cells or biological process from a non-malicious once. They are both the same exact activity. Your body is killing cells all the time, so even cell death isn't a certain indicator (though is an indicator in the innate immune system and cells dying the "wrong" way will activate a response)
The only useful signal is "This wasn't here yesterday". Your body generates B cells with a little sensor that has it's own special systems to have especially randomized sensor activity. Your body is generating random binding sites because there's no rules for what a hostile protein would look like.
Then it prunes these B cells by showing them a bunch of proteins your body is capable of producing, and killing any cell that signals for proteins your body normally has. This leaves you with a bunch of B cells that have random sensors tuned to only trigger for things that weren't in your body yesterday.
This is great, because it's a proactive measure against evolution. It's the core innovation of the adaptive immune system, and a massive advancement in biological self defense.
Cells from someone else will have some different markers and proteins than found in your body. Human genetics are 99% the same yes, but there is massive diversity in the remainder.
Note that this constraint is not biological in nature! Any general purpose "programming" environment cannot differentiate between "Hostile" and "Benign" by function or structure alone! The body, like many smart cybersecurity groups, made an allowlist. Though the way that allowlist is made is fascinating
> 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.
"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.
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).
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.
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.
You left out the important part, that Greek influence made it all the way to Japan, in some cases identifiably intact: "[The Greek wind god] Boreas became the Japanese wind god Fujin through the Greco-Buddhist Wardo/Oado and Chinese Feng Bo/Feng Po ("Uncle Wind"; among various other names). The mother deity Hariti [Kishimojin in Japan] was inspired by Tyche."
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.
> 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.
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.
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.
Uhh thanks for sharing I guess? The third paragraph just nukes the idea of divulging anything, it's obviously written entirely for specialists in the field (chromatin remodeling? the Nesprin-2 protein? mechanotransduction?). What I'm trying to say is no layperson would walk away from this article with a slight idea of why there's no cancer in the heart.
The small intestine section was the most interesting part to me. It turns the whole thing from "regeneration causes cancer" into a much more annoying engineering problem: regeneration, cancer suppression, energy use, and the actual mechanical job of the organ are all coupled.
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.
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.
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.
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.
The entire species is designed to deal with 'far off' threats and ignore them. Think of any animal, let's take a squirrel. It has to be afraid of cats, canines, bird of prey, and at the same time leave the burrow every day, and all day long look for food.
If the predator is not breathing down your neck? You are watchful but ignore it.
Similarly, our ancestors and ourselves? We are social animals. We live in a pack. We share defense with our tribe. You and your neighbour will stand back to back, to fight off barbarians. Meanwhile, in parallel, we need to defend ourselves from members of our tribe. The very person who fights back to back with you, to save your community, may be your tribal competitor. Whether for dominance or breeding, we fight amongst ourselves. We know there is risk of our neighbour, our fellow community member attacking and killing us, meanwhile? We lay our head down and sleep.
We're designed to take low probability threats, and cast them off, and nothing is more low-probability than 'it will happen in the mysterious future'.
Global warming is as 'far off' thing. You may say "But this and this is happening!", and I agree! But I still live in my house, I still have grass and trees, I still have food, and so for most people "far off in the mysterious future" is a valid response.
If you can't see the enemy before you, it is easy to shrug away. If you cannot see the threat as impending, it is easy to ignore.
It's in our very nature. It's a requirement to sleep soundly at night.
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.
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.
Nature's solution for all these problems so far has been to die, as harsh as it sounds. You try to get the important stuff (whatever that is to you) done before that happens, and then you are supposed to pass on the torch to whoever comes after.
This site was painful to read on mobile. Each time I switched to another app and then back it automatically scrolled to the top and I had to painfully rediscover where I left.
In case someone uses it: I want to be mentioned! theGeatZhopa is my name and I want to say thank you to my parents and my girlfriend supporting me.
With the mRNA based vaccines during the COVID pandemics, there has been some reports of resistance and loss of efficiency of the vaccines after vaccinating >3-4 times. It was said the body don't see the actual mRNA pieces but starts to attack the carrier-molecules. Later on, I've seen some paper I don't remember, but it stated the antibodies stopped reacting to that mRNA at all (got used to). There was also a story of a man who vaccined more than 400x with the mRNA vaccines (stupid honk!).
So, may be this is a way for Transplantation? Take the surface molecules of donor, put them on xxx and admister them next months and years while constantly reducing the suppression.
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.
Me and you both. This could be a theme for a social network, massive just like the rest but in any particular instance anyone won't be able to reach more than a fixed number of people, shuffling periodically.
to avoid concentrating users relationships into bubbles ? i'd be worried there would be no way to build meanful long term conversation (unless I didn't understand your idea)
Maybe you could have permanent access to the threads you stated, but for new interactions you'd be limited to very small group of people for a period of time.
But I thought more in terms of less is more. Introducing artificial temporary scarcity to foster creativity instead of relying on sheer volume of information to increase the chances for high quality interactions, which also increases the absolute volume of low quality noise.
Also maybe after quarantine is over your thread could be accessible to everyone else so others could join later, as long as the group agrees to open up the discussion.
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!
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)
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
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.
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.
Interesting. It seems to have a blind spot of "what evolution want", though it does exposes that point "because evolution’s goal isn’t to make you happy, it’s to maximize reproductive fitness."
And so, from the very same premise, evolution don’t necessarily need individuals that are long standing, even less in environment which are themselves very unstable. As long as species continues to exists, evolution made its job. In more stable environments, long life span is causing less pressure on chance for the species to remain viable. A large motile animal in ocean don’t have to face that much significant changes in environment compared to their out-of-water counterparts. Of course the environment alone don’t explain everything in term of most efficient strategy, size matter, mobility mode matters, how much of such an environment exist and how large the population can grows before facing a demographic cap, just to cite the first that comes to mind.
I’m not a biologist, at all, and even a random layman as myself can comes with these obvious ideas.
That said, I also have all kind of blind spots, no doubt about it, and I didn’t even write a very nice to read issue on the topic unlike the author of TFA.
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 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
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."
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?
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.
https://wwnorton.com/books/9780393887655
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.
Why would that many people have so much vitamin A ?
Vitamin A is in eggs, dairy (butter, milk, cream), in meat fats like pork and grain-fed beef, in salmon, in liver, in cod liver oil. Vitamin-A precursors (carotenes) get converted into Vitamin A in the body, they are in red and orangey fruits and vegetables such as carrot, tomato, chili, chili-powder spice, bell pepper, sweet potato, apricot, mango, butternut squash, grapefruit, watermelon, papaya, passion fruit, cantaloupe, pumpkin, also in dark greens like kale, collard greens, spinach.
Carotenoids are used as a natural food colouring, beta-carotene is E160a, e.g. I've seen it in Red Leicester cheese, yellow custard powder, red jelly, in glace cherries. American law requires vitamin A fortification in reduced-fat dairy. Companies optionally fortify it in things like wheat flour, or breakfast cereal. Retinoids are in beauty and moisturising skin creams and sun tan lotions, and sometimes used as extreme acne medication.
Things that have been promoted for "good health" for decades, such that someone who wants to avoid it needs to deliberately choose an awkward diet of non-colourful foods like potato, rice, onion, parsnip, coconut, apple, pear, cucumber, zucchini, black beans, white beans, lean meats or carefully chosen meat fats, breads made from un-fortified flour, avoiding many restaurant, take-away, or processed foods and "eat the rainbow" variety of fruit and veg.
Grant Genereux has proposed that overflowing the liver's ability to store and process Vitamin A / retinoids leads to them circulating in the blood, that they can enter cells bypassing the normal methods, can cause damage which makes cells denature and burst, which triggers an immune system response to try and find an attacker, which gets misdiagnosed as the immune system causing the damage. And has proposed this as a mechanism which explains some of the 25 - 50 million Americans having unexplained auto-immune diseases.
Proposing that retinoic acid builds up inside body cells over years and decades even whan taken ordinary 'safe' levels, not enough to trigger hypervitaminosis A or acute symptoms but chronically accumulating until the body has so much of it stored that cell damages releases retinoids into the bloodstream which enter nearby cells, denature some of them, releasing their stored retinoids, causing a domino effect which we know as an auto-immune flare-up. And that it's a matter of luck where the concentration is higher whether that makes a skin rash or a kidney or joint or thyroid inflammation, or just generally high "inflammation".
It's an interesting hypothesis with a lot of specific testable claims and specific proposed mechanisms, mixed with quite a lot of conspiracy theorising and less-testable claims.
I'm past the comment edit window, but incidentally these two Harvard pages[1,2] say that:
- the recommended daily vitamin C is 90mcg for men and 75 for women, the upper limit is 2000mcg. That's a safety margin of 22x, and exceeding the upper limit may cause diarrhoea and gastrointestinal distress.
- the recommended vitamin A is 900mcg for men and 700 for women, and the upper limit is 3000mcg. That's a safety margin of 3.3x, and even that upper limit has "some evidence that this much preformed vitamin A might increase the risk of bone loss, hip fracture, or some birth defects".
- "Sometimes people take cod liver oil for vitamin D but may not be aware it is also very high in vitamin A, beyond the RDA at 192%"
That is, even without any alternative views on it, it's much easier to go above the safe levels, easier to do accidentally, and the risks are more serious.
[1] https://nutritionsource.hsph.harvard.edu/vitamin-a/
[2] https://nutritionsource.hsph.harvard.edu/vitamin-c/
Consuming lots of dairy (including fortified), lots of colorful veggies every single day year round, maybe adding multivitamins, fortified flour. Then there's the liver hype in some circles.
“High intake of provitamin carotenoids (such as beta-carotene) from vegetables and fruits does not cause hypervitaminosis A.”
From Wikipedia
https://en.wikipedia.org/wiki/Hypervitaminosis_A
Your Wikipedia page references a paper in footnote 21 which says:
> "In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods"
and
> "Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons"
Google tells me that "Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage".
Carotene conversion cannot both be "a minor contributor" to body levels of Vitamin A and also the main way billions of people get Vitamin A. So my guess is the Wikipedia page has mistakenly taken 'excentric cleavage' to be the only conversion method. Still, ignoring carotenes entirely, the referenced paper also says:
> "observational studies suggest that more than 75% of people may be routinely ingesting more than the recommended dietary allowance (RDA) for vitamin A"
The entire paragraph containing your first quote:
> "Dietary vitamin A is obtained from preformed vitamin A (ie, retinyl esters from animal foods, fortified foods, and pharmaceutical supplements) as well as from provitamin A carotenoids from plant sources. Preformed vitamin A is efficiently absorbed and utilized by humans at absorption rates of 70–90%. Up to 75% of dietary vitamin A in Europe, the United States, and other industrialized nations is preformed vitamin A (1, 2), which is largely derived from multivitamins, fish liver oil, and the fortification of foods such as milk, butter, margarine, breakfast cereals, and some snack foods. In developing nations, however, 70–90% of vitamin A is obtained from provitamin A carotenoids in plant foods. These are absorbed much less efficiently, at rates of 20–50%, depending on each person’s vitamin A status and other dietary and nondietary factors (3, 4). The cleavage of provitamin A carotenoids to retinal is a highly regulated step, and vitamin A toxicity from provitamin A sources is largely impossible. In contrast, absorption and hepatic storage of preformed vitamin A occur very efficiently until a pathologic condition develops."
Indeed, but they neither explain nor cite what they mean for it to be "highly regulated" or how/why that means toxicity is largely impossible.
If you take "the cleavage of provitamin A carotenoids" and Ctrl+F for 'cleavage' or 'carotene' in that paper, the only other mentions are this:
> "An acute elevation of retinoids other than retinyl esters—eg, retinoic acid—occurs after the ingestion of a large amount of vitamin A, possibly because the intestinal absorptive capacity is overwhelmed, which leads to the oxidation of retinol to retinoic acid by the intestinal enterocytes (30) and to the rapid formation of retinoic acid from retinol in certain cells (5). Whereas retinoic acid can be produced from excentric cleavage of β-carotene in humans (31), it is generally considered a minor contributor to circulating concentrations, at least in normal, healthy persons."
That is, they only seem to be talking about excentric cleavage and not central cleavage. My limited understanding is that beta-carotene is roughly two retinoic acid molecules chained together, and cleaving them in half is what makes two retinoic acid molecules, and that non-central-cleaving would be different. See skeletal formula on right for these two pages:
https://en.wikipedia.org/wiki/%CE%92-Carotene
https://en.wikipedia.org/wiki/Retinoic_acid
(You can also wonder if beta carotene can produce 90% of circulating vitamin A in developing countries, whether getting lots of beta carotene in developed countries can raise the base level in the body, which then leads to easier overdose from preformed vitamin A)
How could I determine if I’m in/out of this group
Possibly if you have many symptoms that sound like isotretinoin or tretinoin side effects (the latter is active vitamin A, the former just a twisted form of it).
As for measuring: there might be spillover of retinyl esters (storage form in the liver) into serum, but that's nothing that's commonly measured. (Serum retinol levels do not correlate with liver levels AT ALL.)
At least for isotretinoin, that would look like: dry skin, chapped lips, dry eyes, dry nostrils, dry mouth, photosensitivity, body aches in the morning.
It can also raise liver enzyme values and change lipid values.
(I recently finished a round of Accutane, basically high dose vitamin A)
What are accident victims?
People who died in an accident, think car accident or fell off a roof. Otherwise healthy people who didn’t die of a disease.
I'm about halfway through this book and I can second the recommendation.
Any other similar books ?
Hi Doctor. My sibling recently was diagnosed with liver Mets. Is it really incurable? Docs here refused surgery in 36F
In general, we don’t do curative surgeries for metastatic cancers. The thinking is that it is has spread that much away from where it started, there little point going to cut out where it started alone. Are we then to cut out every place it has spread to and every how it got to those places.
We do do palliative surgeries if warranted but the intent there is not to cure, but to relieve some symptoms and transiently improve quality of life.
Please direct any specific questions you have about your sisters case directly to her doctors
Surely. Since the conversation was already going i asked. Thank you very much for your opinion.
Retired anesthesiologist here. I'm buying Weinberg's book based on your review as soon as I finish this comment. Thanks!
My grandpa and his dad were both pathologists, so I always appreciate seeing one in the wild.
Thanks for the rec, I'm buying it just so I can explore their world a little bit.
Thank you
>flower in your brain all on their own
almost like... cancer itself
A paperback is $235.62.
What is it printed on??
The internet archive has a copy of the epub, but I have no idea if it’s a legal copy or piracy:
https://archive.org/details/the-biology-of-cancer-3rd-editio...
The method of printing is not the major cost differential in a book. Hardbound or softbound, the production costs don’t differ all that much. That is why ebooks are not substantially cheaper than a printed book.
When kids have to buy a textbook for school the price goes way up
paperback $127.30 here: https://www.amazon.com/Biology-Cancer-Robert-Weinberg-dp-039...
ebook $100.64 here: https://www.vitalsource.com/products/the-biology-of-cancer-r...
Cheaper material than this
https://www.amazon.ca/Hyperart-Thomasson-Akasegawa-Genpei/dp...
Stretched dodo hide, tanned and prepared by blind monks.
Same as Necronomicon, surely.
Well, this one should have left copyright long ago and you can reprint it everywhere? :)
Isn’t copyright duration like 70 years? How could it have left copyright (one of the editions were published in 2013)?
https://en.wikipedia.org/wiki/Necronomicon
I meant this Sci Fi book
I always thought invoking demons was more occult fantasy genre and not science fiction, but it is a matter of perspective I suppose.
You are right, but since Im a Philistine, I would put bock genres in the same bucket - excuse me :-D
the hopes and dreams of the publisher, author probably sees a very small %
Liver cells
Does SV40 cause cancer? Did and does SV40 inadvertendly inside the Polio Vaccine in the late 1950ies and 60ies cause cancer? Does the Pfizer proces 2 SV40 promotor in the Covid Vaccine cause cancer? Is SV40 DNA (or its fingerprints) found inside actual cancer tissue these days? What type of research is performed on it? Does DNA contamination in general cause cancer? I don't know if you're friendly enough to address these isssues. Probably not.
> I don't know if you're friendly enough to address these isssues. Probably not.
A fantastic closing if the goal is to make people not answer your questions. I don't know if you're friendly enough to explain why you made your comment so hostile. Probably not.
Not the GP poster, but some answers:
> Does SV40 cause cancer?
Yes, in a range of animal models at least.
SV40 can 'immortalise' cells, turning off regulatory functions which prevent uncontrolled division, which is an important part of carcinogenesis. This has been shown to contribute to cancer in experimental systems.
> Did and does SV40 inadvertendly inside the Polio Vaccine in the late 1950ies and 60ies cause cancer?
The evidence suggests not significantly, although it's impossible to rule out for some unlucky individuals.
The SV40-exposed cohorts rates of cancers don't differ that greatly from unexposed groups, so we can say with certainty that the rate is much less in humans than seen in laboratory systems. There were suggestions of differences for some cancers, but these are heterogeneous and often confounded, and the general consensus now seems to be the effect was small if not zero. I don't think there's a definitive answer on why - possibly the exposure was sufficiently low or the virus was not effective at infecting humans to significantly affect the carcinogenic processes.
> Does the Pfizer proces 2 SV40 promotor in the Covid Vaccine cause cancer?
Certainly not by the mechanism intact SV40 causes cancer.
That depends on the production of particular SV40 proteins which interfere with cell functions, which aren't present in that promoter.
> Does DNA contamination in general cause cancer?
In general, no.
Cells are constantly exposed to both native and foreign DNA fragments, and have plenty of mechanisms for dealing with them. Even if fragments were somehow incorporated and expressed, most are not inherently carcinogenic.
You are ignorant and disrespectful and i'm higly disappointed from human to human.
"friendly enough to address these issues".
He is not part of some research group who is researching this type of topic. You assume he is a bad faith actor with your "probably not".
Either accept the status quo / research on this topic, or do the research yourself but don't take some potential conspiricy shit to hn by cheap shooting someone else with your 'probably not'.
And if you really struggle with this type of things, get help.
PURCHASE OPTIONS: Ebook Courseware $94.95, Paperback with Courseware Access $235.62 (FREE SHIPPING!)... Take your adverts someplace else.
What's your objection exactly? Those are standard prices for even semi-modern technical books.
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 .
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.
https://ambystoma.uky.edu/teachers_materials/axolitbook/Axol...
Oh no! I read that one as a teenager. Hunting!
> Most of the body doesn't regenerate because there was not enough evolutionary pressure.
All basal metazoan branches (ctenophora, porifera, placozoa, cnidaria) have species that are capable of whole body regeneration, so this trait was likely lost on the bilaterian branch (which includes chordates like ourselves). If anything, there are evolutionary pressures to loose this trait.
For example, consider how frequently people lose a limb, and further consider the ratio of survival to death for injuries in that general ballpark. Then balance this quality of life improvement, for those who survive, for those injured in the first place, against the fact that all people with such a biological capability will almost certainly experience a significantly higher rate of cancer. Because in a nutshell cancer is uncontrolled proliferation while regeneration is controlled proliferation. (It would be very interesting to know the rate of incidence of various cancers in axolotls if they lived anywhere near as long as a human.)
When you lose a limb you'd die of blood loss though, right, not the mere lack of a limb.
I have read somewhere that losing a limb naturally (e.g. tearing, biting) stretches and closes up blood vessels in a way that cutting with a scalpel doesn't, and that natural limb loss has less bleeding than surgery/stabbing/Hollywood suggests.
I have no idea of the truth of this, but there are anecdotes of farmers losing limbs and walking back to their tractors, driving back to the farm, then driving themselves to hospital, and the like.
Yes that's kind of (but not entirely) my point. It's actually quite difficult (for a human) to lose a limb in a sudden accident without immediately dying. So it's exceedingly rare (~all historical civilisations) to be injured in such a manner, it's at least somewhat rare to survive such an injury (historically just about impossible), and even if you had flawless regeneration you'd be at a serious physical disadvantage (ie from an evolutionary fitness perspective) in multiple ways for an extended period. Meanwhile carrying said trait is consistently killing people off the entire time.
I think the extended period is a point that needs consideration. I don't know how long it takes a salamander to regrow a limb, but given the sheer size of any given limb in an adult human, it would take quite some time to regrow it to anywhere near its former state.
I mean... think of Deadpool's baby hands. Jesus.
Yes, that was my point. Amputations are quite uncommon, they usually lead to death (blood loss / infection, starvation, vulnerability to predators, etc) For relatively intelligent species they are even more avoidable. Regeneration would add very little benefit from natural selection point of view. Most body parts are durable enough for survival and reproduction.
Not "pressure to lose this trait" as much as "no pressure to improve it"?
As anatomy gets more complex, the process of getting it from "arbitrary heavily damaged state" to "functioning state" gets more complex too. And mammals are a bit more anatomically complex than placozoa.
If your entire body is a hollow sphere 4 cells thick, "repairing arbitrary damage" is very simple and natural. When you have bones, blood vessels, nerves, muscles and tendons, all wrapped in skin - all of which have to be restored correctly for a lost limb to function well? The gap between "just plug the holes" and "restore the function" grows, and the complexity of implementing usable regeneration goes up massively.
Humans can repair most of simple tissue-level damage well enough. The complexity equivalent of placozoan regeneration is in place. Rebuilding complex anatomy is what's often unimplemented. Seems like that is the part that requires some novel adaptations rather than simply not deactivating the mechanisms that are already there.
I read a book on epidemics where some modern theories on death were essentially its selected for to force potential infecting organisms to keep starting over on mastering a given genetic environment. Ones grandchildren are more likely to survive the successor plague than you are, hence a population with excessively long life would have died out. I think the evidence was from long lived trees? (Pandemic by Sonia Shah).
> Most of the body doesn't regenerate because there was not enough evolutionary pressure.
Maybe, but isnt this basically tautological? "You didnt evolve this way because of how evolution works". The more interesting question is why did certain parts evolve the way they did, and can we harness the knowledge?
So even the animals we think of as regeneration champions have a very specific menu of things they can rebuild
Exactly, limbs are quite large portion of the body, that's why many think salamanders would have no problems with regenerating all other smaller body parts. And that's not the case.
Still, regenerating a limb sounds very useful. I'd sign up for that.
Dr Michael Levin at Tufts has a lot of electro based theories about regeneration based on findings with Palnarians he adjusts the voltage states and gets two headed liniages amongst the many many other things his lab covers
Getting "old" is a recent and tiny sliver of human evolution. It's only been the last 100 or so years that we've really started to push the boundaries of what the body is capable of and our biology has never really had a chance to deal with it and "develop" a solution.
This isn’t correct. For example, when Edmond Halley created the world’s first life table in the 1690s, he estimated that approximately 5% of his city’s adult population was >70. Getting old is not new.
Even still, if we were able to continue on current aging trend, including food availability and whatnot, for another hundred thousand or million years; what evolutionary pressures exists that would make our biology able to live even longer than our current status quo?
Actually I would argue that the evolutionary pressures run against it: if one generation dominates then the species can't evolve.
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.
The current model is that evolution acts on the molecular, cellular, and genetic level, and most importantly, at the population level.
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.
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.
We have on evolutionary scales lots of predation damage by the lizards. Thus a turtle with 300 can still give birth, while we can not.
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.
> our ancestors insisting on eating toxic things like mushrooms and spoiled food
Presumably this didn't happen because are ancestors were dumb, but rather because the ability to process slightly spoiled food is a significant advantage in an environment where fresh food is sometimes scarce?
Yes, the same reason that my dogs will puke something up, and then try to re-eat it.
Survival in the wild is harsh, yo. Try for every scrap of food.
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.
Huh, another reason to eat more spinach I suppose.
If you like all those carotenoids and oxalates... If rather just have some onions for sulphur instead.
Blanche spinach, try not to eat them raw. Speaking of oxalates, I did not know yam leaves were inedible. Saw a little tender shoot, bit a little piece off. Tastes like mushroom. I don't think it's toxic but it's like eating glass.
Blanching does nothing to oxalic acid.
And that "eating glass" comment is related to how I know. I boiled a wild "edible" (skunkweed leaves) in 3 changes of water; what I should have done is either dry it completely or (better) treat it with lye. Bad memory mistake. Yeah: eating glass shards.
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.
> Your liver makes platelets
Megakaryocytes are primarily bone marrow cells.
Indeed, but your liver does make clotting factors and also thrombopoietin, which stimulates platelet production.
Cells are specialized to their function, as well as to their diseases. The trade offs mentioned in the article seem simplistic, trying to capture the billions of years of evolution. Repair, regeneration, regrowth and cancer have distinct mechanisms that vary from cell type to type.
Liver regeneration has been known since the ancient times: in Greek mythology an eagle was eating the liver of Prometheus every day for thousands of years after Zeus punished him for donating the fire to humans but he survived to be saved by Hercules.
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.
Hello fellow PSCer! Amazing to hear even partial liver transplants work.
Hello! I hope you're going ok :)
Does this mean a healthy donor could donate a sizable chunk of their liver every year?
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...
There were 709 living donor liver transplants in the United States last year.
2025: 12,344 total (709 from living donors)
2024: 11,458 total (604 from living donors)
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.
The article complains about a lot of questionable design aspects of the human body, including menopause. Only us and a couple of whales (and apparently one specific chimp population I wasn't aware of?) go through menopause, making us infertile long before we die. Why is that? Wasn't more kids supposed to be better?
I recently learned about this (not sure if it was a YouTube video or an article): apparently, it's not that we become infertile long before we die, it's that we live long past our fertility ends. And the reason for that is really simple: old people have accumulated a lot of knowledge that is valuable to teach to younger generations. The alternative is not to be fertile longer, but to die younger.
Presumably, menopause only occurs in species that learn and teach, and are able to accumulate so much knowledge that it becomes useful to keep experienced individuals alive longer so they can continue to teach.
I wonder if it could be related to how long humans remain children and require care to thrive. That may at least be part of the story.
Did you read the whole article? It returns to menopause to discuss the very things you wrote.
> 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.
Kidney failure and jokes... OK, I feel obliged to share a true story. A relative of mine donated their kidney to one of their siblings. A couple of years ago we were all playing "naughty Santa" AKA "white elephant". It was the donee's turn and they chose to steal the donor's present. The donor replied "oh man, that's just like when you stole my kidney!" I've never laughed and cried so much in my life.
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.
I asked ChatGPT if it is OK to an explain a joke without being asked to do so, and She said no.
Does ChatGepete identify as she? I stumble on this when I speak to one shaitan about another shaitan doings
Why nature did this? So that 3rd parties don't engage in organ swaps?
Almost like Apple with component serialisation.
There are extremely good security reasons for it.
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
In this case nature was just indifferent to transplants as they weren't a thing even 100 years ago.
As others have explained, foreign cells usually meant trouble, so fighting them by default was a good choice. And there was no pressure to allow transplants specifically, because they didn't exist.
Also, (I think) you usually need a transplant later in life, after reproduction, so too late for evolution to affect it. So even if we had transplants for millions of years, it might not have made much difference either.
With very few exceptions, if there is something in you that isn't you then you would be better off if it was dead.
Your body gives them a choice: containment or death, which is really just one option unless they can fight back.
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.
Would those markers be usable as a natural UUID?
Not the major HLA markers, no, because there's a ~25% chance it'll match for two siblings [0] and can sometimes match other relatives.
Once you start looking at even more factors, you start reinventing a regular DNA-matching test.
[0] The "Birthday Paradox" makes the odds of confusion even higher with more siblings.
To deal with:
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.
There is zero inherent way to tell a malicious group of proteins and RNA or cells or biological process from a non-malicious once. They are both the same exact activity. Your body is killing cells all the time, so even cell death isn't a certain indicator (though is an indicator in the innate immune system and cells dying the "wrong" way will activate a response)
The only useful signal is "This wasn't here yesterday". Your body generates B cells with a little sensor that has it's own special systems to have especially randomized sensor activity. Your body is generating random binding sites because there's no rules for what a hostile protein would look like.
Then it prunes these B cells by showing them a bunch of proteins your body is capable of producing, and killing any cell that signals for proteins your body normally has. This leaves you with a bunch of B cells that have random sensors tuned to only trigger for things that weren't in your body yesterday.
This is great, because it's a proactive measure against evolution. It's the core innovation of the adaptive immune system, and a massive advancement in biological self defense.
https://en.wikipedia.org/wiki/Germinal_center
Cells from someone else will have some different markers and proteins than found in your body. Human genetics are 99% the same yes, but there is massive diversity in the remainder.
Note that this constraint is not biological in nature! Any general purpose "programming" environment cannot differentiate between "Hostile" and "Benign" by function or structure alone! The body, like many smart cybersecurity groups, made an allowlist. Though the way that allowlist is made is fascinating
> 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.
"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.
Adult onset Type 1 has become a lot more common in recent decades. Ask me how I know.
Isn't that why it got renamed from juvenile diabetes?
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.
Just like a ton of other autoimmune diseases.
Psoriasis sufferer checking in. Brutal.
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).
e.g. microberto on X, nutrition detective on YT
It's so rare in adults it's got the cute name maturity onset diabetes of the young (MODY).
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.
Know someone who developed type 1 diabetes in his 30s.
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.
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.
i mean it's called the liver not the dier
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
https://oll.libertyfund.org/titles/coxe-the-writings-of-hipp...
I thought they chose it because it tastes great with some fava beans and a nice Chianti.
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.
Why would liver signal defiance?
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.
I don’t think it was phrased awkwardly, I was just curious.
Also, liver-toxic people are really angry / choleric, while healthy people are relaxed and composed, so there's something to that.
It was the believed area of emotion, passion and 'soul'. I think western/modern religion has morphed from the liver to the heart essentially.
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.
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 have no idea, however, why both Eastern and Western naive psychology associate gall with, well, gall.
Possibly because it's filled with strong acid.
In Italian, to have 'liver' (fegato) means to be courageous.
The Greeks did get to India. https://en.wikipedia.org/wiki/Greco-Buddhist_art
You left out the important part, that Greek influence made it all the way to Japan, in some cases identifiably intact: "[The Greek wind god] Boreas became the Japanese wind god Fujin through the Greco-Buddhist Wardo/Oado and Chinese Feng Bo/Feng Po ("Uncle Wind"; among various other names). The mother deity Hariti [Kishimojin in Japan] was inspired by Tyche."
Humors perhaps. Not my area, so I do not recall the correspondence ...
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.
> 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.
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.
A couple more points to add to this:
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.
The lack of heart cancer might be more complex than the OP imagines:
https://www.science.org/content/blog-post/no-heart-cancer-th...
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.
Uhh thanks for sharing I guess? The third paragraph just nukes the idea of divulging anything, it's obviously written entirely for specialists in the field (chromatin remodeling? the Nesprin-2 protein? mechanotransduction?). What I'm trying to say is no layperson would walk away from this article with a slight idea of why there's no cancer in the heart.
The small intestine section was the most interesting part to me. It turns the whole thing from "regeneration causes cancer" into a much more annoying engineering problem: regeneration, cancer suppression, energy use, and the actual mechanical job of the organ are all coupled.
Probably evolved because early humans kept finding new ways to poison themselves. Good design for an unforgiving environment.
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.
Well, we do at least have to eat enough food and sleep ~1/3rd of our lives. That's kinda 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.
Indeed, carbs, and cooking to make those carbs available (from grasses, tubers, etc).
Which came first, steak or intelligence?
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.
quite the delightful maintenance too
that's absolutely maintenance, without it you have a total system failure in a week
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.
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.
until you get old and goes the opposite direction
Humans don't last long without topping up their fluids and consumables.
no you don't
Well, so much for that discussion.
The human body can't survive 80 active years without maintainance. They take drugs, they see the doctor, etc.
What did people do 500 years ago?
Die as a child at alarming rates
But those who did not, got quite old without ever seeing a doctor.
(If we are talking about hunter gatherers, not poor exploited peasants)
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.
The entire species is designed to deal with 'far off' threats and ignore them. Think of any animal, let's take a squirrel. It has to be afraid of cats, canines, bird of prey, and at the same time leave the burrow every day, and all day long look for food.
If the predator is not breathing down your neck? You are watchful but ignore it.
Similarly, our ancestors and ourselves? We are social animals. We live in a pack. We share defense with our tribe. You and your neighbour will stand back to back, to fight off barbarians. Meanwhile, in parallel, we need to defend ourselves from members of our tribe. The very person who fights back to back with you, to save your community, may be your tribal competitor. Whether for dominance or breeding, we fight amongst ourselves. We know there is risk of our neighbour, our fellow community member attacking and killing us, meanwhile? We lay our head down and sleep.
We're designed to take low probability threats, and cast them off, and nothing is more low-probability than 'it will happen in the mysterious future'.
Global warming is as 'far off' thing. You may say "But this and this is happening!", and I agree! But I still live in my house, I still have grass and trees, I still have food, and so for most people "far off in the mysterious future" is a valid response.
If you can't see the enemy before you, it is easy to shrug away. If you cannot see the threat as impending, it is easy to ignore.
It's in our very nature. It's a requirement to sleep soundly at night.
At least, this is my take on 'far off' threats.
quite old as in 50 because the avg lifespan back then is certainly lower than it is now.
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.)
Citation required
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.
Interesting. Yet as someone approaching the first of those two last numbers, I would say that that isn't very old at all
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.
Old people are at least 20-30 years older than I am.
Because alcoholism forces hunter gatherer cultures into settlements, which are the next stage of civilization and reward those doing that choice?
It's not alcoholism if you are offsetting the baseline deficiency. Drinking every day is basically like taking vitamin D syppliments up north.
Actually it may be the opposite. Alcohol is needed for people within settlements to bond.
I love this theory
wouldn't it be our ancestors just liked booze too much and the liver said alright genes, hold my beer
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.
Nature's solution for all these problems so far has been to die, as harsh as it sounds. You try to get the important stuff (whatever that is to you) done before that happens, and then you are supposed to pass on the torch to whoever comes after.
It's God's sign to drink a pint of Guinness for breakfast, obviously.
This site was painful to read on mobile. Each time I switched to another app and then back it automatically scrolled to the top and I had to painfully rediscover where I left.
Okay but the small intestine villi conveyor belt is the real flex here. Liver gets all the press.
In case someone uses it: I want to be mentioned! theGeatZhopa is my name and I want to say thank you to my parents and my girlfriend supporting me.
With the mRNA based vaccines during the COVID pandemics, there has been some reports of resistance and loss of efficiency of the vaccines after vaccinating >3-4 times. It was said the body don't see the actual mRNA pieces but starts to attack the carrier-molecules. Later on, I've seen some paper I don't remember, but it stated the antibodies stopped reacting to that mRNA at all (got used to). There was also a story of a man who vaccined more than 400x with the mRNA vaccines (stupid honk!).
So, may be this is a way for Transplantation? Take the surface molecules of donor, put them on xxx and admister them next months and years while constantly reducing the suppression.
Anybody on HN knows platforms to discuss this ?
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.
You can't build a moat and make money on good nutrition, you make money with patented drugs and therapies, that's why.
Yeah makes sense. It might also be a different culture, software likes hacking and open source, while serious medicine not so much.
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.
Hacker news is dedicated to 'tech' and I'm looking for advances in biology.
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.
I kinda agree about reddit, either too much noise or gatekeeped (iirc some medical subreddits are mostly students or professionals only).
Just to be clear, I said HN system is barely function but it's by no fault of their own. How can you know for sure I'm not a dog?
I get it. I don't even want something as large and featured as HN. Just a dedicated space.
Me and you both. This could be a theme for a social network, massive just like the rest but in any particular instance anyone won't be able to reach more than a fixed number of people, shuffling periodically.
to avoid concentrating users relationships into bubbles ? i'd be worried there would be no way to build meanful long term conversation (unless I didn't understand your idea)
Maybe you could have permanent access to the threads you stated, but for new interactions you'd be limited to very small group of people for a period of time.
But I thought more in terms of less is more. Introducing artificial temporary scarcity to foster creativity instead of relying on sheer volume of information to increase the chances for high quality interactions, which also increases the absolute volume of low quality noise.
Also maybe after quarantine is over your thread could be accessible to everyone else so others could join later, as long as the group agrees to open up the discussion.
No idea about forums, but for a book with more depth on these issues I liked Uri Alon's Systems medicine.
thanks :)
To solve cancer we just need to engineer extremely redundant genetic controls for cell reproduction.
Checksum the newly built copy and dispose of mistakes at the spot. Will be energy intensive sure.
https://news.ycombinator.com/item?id=33513277
I read this whole thing and literally I am dumber for it.
Must be why our ancestors could eat so much questionable stuff. It's the ultimate biological retry mechanism.
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!
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)
Onion compounds slow down ALDH (aldehyde detox), not sure if for cats it's a different (i.e. yet another) mechanism though.
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
Doesn’t that validate my point? The liver needs to deal with this stuff unless you manage to throw it all up again.
Not all responses are a counterarguments. That one was very clearly supporting, anecdotal, evidence.
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.
This right here is religious propaganda
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.
>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.
> 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.
Shouldn't the question be, "Why isn't everything else?"
Very nice, well written and interesting! Amazing!
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.
Found that opening paragraph really difficult to get beyond ...
Interesting. It seems to have a blind spot of "what evolution want", though it does exposes that point "because evolution’s goal isn’t to make you happy, it’s to maximize reproductive fitness."
And so, from the very same premise, evolution don’t necessarily need individuals that are long standing, even less in environment which are themselves very unstable. As long as species continues to exists, evolution made its job. In more stable environments, long life span is causing less pressure on chance for the species to remain viable. A large motile animal in ocean don’t have to face that much significant changes in environment compared to their out-of-water counterparts. Of course the environment alone don’t explain everything in term of most efficient strategy, size matter, mobility mode matters, how much of such an environment exist and how large the population can grows before facing a demographic cap, just to cite the first that comes to mind.
I’m not a biologist, at all, and even a random layman as myself can comes with these obvious ideas.
That said, I also have all kind of blind spots, no doubt about it, and I didn’t even write a very nice to read issue on the topic unlike the author of TFA.
https://en.wikipedia.org/wiki/List_of_longest-living_organis...
This text makes absolutely no sense from a scientific point of view.
Natural selection is designed into our genes.
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.
> 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 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.
Rocko can't have kids, because Rocko is just a stupid rock.
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.)
Crystals catalyze their own expansion in a suitable solution.
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
Oh, fair point, I did the pathetic fallacy (too). Beneficial thing, then.
Selfish gene theory is discredited as reductionist and mostly wrong. You can't ignore the whole organism.
Says who? Please expand on this discrediting.
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.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."
https://www.sciencedirect.com/science/article/pii/S193459092...
I’m pretty sure that’s been debunked and they normally do.
the claim isn't complete, either. Recent research has demonstrated adult neurogenesis (growth of new cells that originate from neural stem cells).
Why is it absurd to say that the human brain could be better? That seems obviously true to me.
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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"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
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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.
AFAIK scientific "consensus" still says that T1 diabetes (and baby other diseases) is an autoimmune problem not caused by nutrition.
Now sure, others say that retinoids play a role here, but "we know" sounds a bit far fetched.
Sure, the rare diabetes is an exception. ~90% of the cases are T2 which are definitely caused by poor diet and sedentarism.
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?
[2] https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu...
https://news.ycombinator.com/item?id=11655206
Based.
What is a new hypothesis other than a conspiracy of circumstances making better sense..