> 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.
" 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."
Almost certainly? Where do you get this certainty from? There is no obvious reason why we should expect regeneration to be potentially carcinogenic, only because both are proliferations. Claiming it as a fact is way, way beyond what science currently knows.
There is an assumption at your end that controlled proliferation can easily switch over to uncontrolled one, but real natural phenomena don't seem to indicate that.
Axolotls live about as long as dogs and cats do, but unlike them, they rarely suffer from cancer.
We humans are capable of regrowing our fingernails and toenails for our entire life and we indeed regrow them all the time, proliferation taking place 24/7, nonstop. And yet cancer of the nailbed is quite rare, much rarer than other cancers, though not completely unheard of.
Our own children proliferate their cells like hell, growing twentyfold in the process, and yet pediatric cancer is not very common, with only 1 of 300 to 500 kids getting cancer before their 18th birthday. It is much more common in elderly people whose cells don't proliferate that much anymore.
You have no real observations to ground your certainty in, it is purely speculative, and this is not maths, this is biology, with all its glorious mess. Even very smart people usually get their speculations wrong when it comes to biology.
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).
> I think it would be better to describe this as an ‘organelle’ transplant as it would be easier for people to understand and discuss.
Unlike previous attempts, the donor mitochondria are not transferred into the mother egg. Instead the donor cell is denucleated, and the nucleus from a mother's egg is transferred into the denucleated donor cell. Consequently, there is a wide variety of donor specific material, which may influence the early stages of development and only "wash out" after a number of cell divisions.
> But calling it a 3 person baby is unhelpful and misleading as IMO mitochondria DNA is of a different category to chromosomal DNA.
How so? Arguably, mitochondrial genes are much more essential than most nuclear genes.
1. Mutations in any mitochondrial gene often have dire consequences, whereas variants in nuclear genes are much more frequent.
2. Mitochondrial DNA is the most expressed in pretty much any cell by a huge margin. Mitochondria express 13 (IIRC) protein coding genes and two dozen other RNAs. Those 30 odd genes often make up 1-5 % of a cell's whole transcriptome. Only genes coding for ribosomal RNA are more strongly expressed.
You finish your degree, and start your PhD. The first year, you are busy learning techniques and getting caught up with the relevant literature.
You are far too concentrated on learning new things to get any thinking done.
In your second year of your PhD, you are getting better. You can do most things without thinking about them. This frees up your brain to think about other things.
However, your grasp of the wider literature is still lacking, so you use that brainspace to optimise your current experiments (as you should).
In your third year of your PhD, you are starting to write things up: either your thesis, or your first (big) paper. You read a lot more, you know a lot more.
The deep thinking can commence.
Your first postdoc is probably your most productive time: you know what you are doing; you know the state of the literature and which parts are reliable and which aren't; you have a clear idea of what problems need solving.
You are starting to write your first grant applications, but you only need one for yourself and not several to cover the needs of a full lab. You don't have any kids at home.
This is a good time to solve some big problems. It lasts about 2-3 years.
At the start of your second postdoc, you panic. The big problem was harder than you thought and you don't have enough high-impact papers to be competitive in job applications for a principal investigator (PI) role.
You start churning out low-value fillers and collaborating with everyone and their hamster to get your name on as many papers as possible.
The rest of the time is taken up by applying for grants and PI positions. You don't even make it to the interview stage. You start pondering about life outside of academia.
Huge fan of Distill here (and your personal blog).
> In retrospect, I deeply regret trying to run Distill with the expectations of a scientific journal, rather than the freedom of a blog, or wish I'd pushed back more on process. Not only did it occupy enormous amounts of time and energy, but it was just very de-energizing.
Scientific peer review pretty much always is incredibly draining, and (assuming the initial draft is worth publishing) it rarely adds more than a few percent to the quality of the article. However, newcomers are drowning in a sea of low quality SEO spam (if they bother to search & read blogs at all and don't go straight to their LLMs, which tend to regurgitate the same rubbish). The insistence on scientific peer review created a brand, which to this day allows me to blindly recommend Distill articles to people that I am training or teaching. So I, for one, am incredibly grateful that you went the extra-mile(s).
The range notation indicates 95% confidence intervals, not the minima and maxima. If the lower bounds are close enough to zero (and the interval is large enough), then there may some residual probability mass associated with negative values of the variable.
I am a biochemist and neuroscientist and also thought it was fantastic read. It's rare that someone manages to cater to both audiences this well. Kudos!
Some animals get most if not all of their sleep through microsleep [1].
So whatever mechanism "refreshes" the brain, it can work on short time scales.
The switch in brain firing dynamics from wake to sleep (NREM) is very fast -- on the order of one to a few seconds. People in team Nedergaard argue that it is the rhythmic neuronal activity during sleep that promotes fluid flow (though to be fair, some argue its arterial pressure). So their answer to your question would be yes, that should be enough time to enhance fluid flow (fluid is flowing all the time, the question debated by scientists is, whether is it being enhanced during sleep).
I don't think that translates to humans. Sleep disturbances like the micro-arousals triggered by sleep apnea absolutely ruin lives, way before lack od oxygen becomes a problem. Arousals destroy sleep architecture. Humans cannot thrive on microsleep.
I wonder how much of an effect physical brain size has on this. Square-cube law and all that. Bird brains are famously small (though highly efficient).
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.
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