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Comment by PeterisP | Hacker News Reader

Well, a plausible answer is that if we (or random mutations) re-enable those genes then the end result is simply a lot of cancer.

A reasonable default assumption is that each switch in our "genetic configuration" is set to a quite good value.

The only exception is if we see a feature that is beneficial at a high calorie cost - those features have been (reasonably) optimized away during our evolution, but would be useful in modern circumstances where food is not scarce anymore; this is a tradeoff where it would make sense to just turn the dial way to the right from where it had been throughout the last million years.

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> A reasonable default assumption is that each switch in our "genetic configuration" is set to a quite good value.

I'd question that assumption-- each switch in our "genetic configuration" is set to a value, and it's set to one that results in survival often enough for the species to reproduce, but it's not necessarily the optimal value, or even a particularly good one. It's just one that happened to be able to survive under environmental pressures at some particular time.

To put this into a computer science context, genetic algorithms have the same problem-- they can find local maxima easily, but can have difficulty (depending on the nature of the search space) locating global maxima because they can't sacrifice short-term fitness to gain long-term fitness.

>Well, a plausible answer is that if we (or random mutations) re-enable those genes then the end result is simply a lot of cancer.

Interesting idea, but does the risk of cancer have that much selective pressure? It tends to be the "last thing that kills you", after you live long enough to survive everything else. So it seems like any increased risk of cancer would have to be pretty high before it traded off against injury recovery. Then again, "injury recovery" might not have been as beneficial either -- the time to regenerate would still leave you vulnerable, so adaptations favoring avoidance of that injury would have a leg up in selective pressure.

It's typically something that only hits you in old age because your body defends against it quite effectively.

For large animals, I'd believe that it's very rare to have non-fatal injuries that are large enough where regeneration would make a big difference to future life.

According to evolution (which hasn't yet noticed medicine), if something rips off your foot, that's not an injury, you simply bleed to death or die of infection even if you win the fight - unlike, say, various small regenerating lizards. What selective pressure could there be to regenerate feet if there were almost no (alive) people with missing feet until the last few hundred years?

However, risk of cancer is serious selective pressure even with short lives - e.g. https://en.wikipedia.org/wiki/Devil_facial_tumour_disease. Cancer tends to be the "last thing that kills you" exactly because so much of our biology is tuned to resist cancer. Also, all kinds of mechanisms causing our aging problems seem to be simply evolutionary adaptations to resist cancer by limiting cell division.

> if something rips off your foot, that's not an injury, you simply bleed to death or die of infection

That's a false premise.

Plenty of (four-legged) animals can survive just fine without a leg - in fact, it's often said that animals have a spare leg. Some animals might even gnaw their own leg off it's stuck in something and they can't get it out.

It's kind of correlated with size - the smaller the animal is, the easier it is to survive after losing a limb. For a horse, even a broken leg is likely to be fatal.

A missing foot is survivable for a lynx much more so than for a human in the absence of modern medical care.

The same applies for evolutionary pressure in the case of hypothetical regeneration. A lizard can take ~2 months to regenerate a limb, for a human it would take longer simply since the limb is larger and needs to grow more. Prehistoric humans and hominids were calorie limited - if an injured individual is capable and likely to (a) survive for e.g. half a year with the injury and (b) to obtain much more calories than normal to rebuild many pounds of tissue, then apparently there is no strong evolutionary pressure to favor regeneration it as he/she is capable of procreating almost as well even without this feature.

I see what you mean, but it still seems like cancer resistance is a bit "overengineered" relative to what you'd expect from selection pressures. If typical cancer onset were e.g. at age 50 rather than 70, I don't imagine that having much selective relevance in the human ancestral environment, as you'd have raised child-bearing children at that point (and you probably can barely carry your own weight at that point, metaphorically speaking).

OTOH, cancer rate is probably superlinear with respect to error rate, so a small loss of cell instruction robustness corresponds to a disproportionately shorter lifespan.

Cancer is probably selected against to a degree.

At least for most normal healthy males, not dying prematurely of cancer means you've got probably 50 or so years to pass on your genes. If a cancer causing mutation kills you at 30, you may still have the chance to pass on your genes, but you're still being outcompeted in the larger gene pool by those who don't die early and have more children than you. And if not you, then your children who die prematurely may not procreate. Evolution doesn't really have much noticeable effect at the scale of single generations anyways.

> Interesting idea, but does the risk of cancer have that much selective pressure? It tends to be the "last thing that kills you", after you live long enough to survive everything else.

You're assuming that's the default state, rather than the result of millions of years of cancer-preventing trade-offs. If e.g. being able to regenerate lost limbs gives you a 10% chance of dying of out-of-control cancer before reaching breeding age, that trait is going to be selected out fairly rapidly.

Cancer tends to be "the last thing that kills you" in much the same way your keys are always in the last place you look. A significant amount of cellular regulation is devoted to preventing runaway cell division, and sometimes in long-lived and large-bodied organisms those defenses eventually give way.

The ability to regenerate body parts and cancer are not inextricably linked. Take the axolotl. It has the ability to regenerate entire limbs. It's also estimated to be a couple orders of magnitude more resistant to cancer than humans.

Maybe that's the ticket? The cancer resistance is something that allows the axolotl to also keep regrowing limbs around in the genome?

There are also many animals who are long living, and immune to cancer (to varying degrees). Naked mole rats live up to 30 years and almost never get cancer (only one case formally verified so far).

Elephants have many more cells than us, and live to almost the same age, but only have a 5% chance of getting cancer, vs 10%-25% in humans. Lions have a 2% chance of getting cancer.

Out of curiosity, how do we know the cancer rates of various animals?

Someone would have had to examine a lot dead animals of various species to figure this out.

> Take the axolotl. It has the ability to regenerate entire limbs. It's also estimated to be a couple orders of magnitude more resistant to cancer than humans.

The lifespan of of the axolotl is 10-15 years. I'd love to see the cancer rates for 71 year old axolotls.

> A reasonable default assumption is that each switch in our "genetic configuration" is set to a quite good value.

Least awful sounds more correct.

Maybe. The elephants being born without tusks due to ivory hunting pressures changing reproduction dynamics are likely at a disadvantage overall, but in the short term they will survive. Having tusks may be objectively better, but right now it'll get you killed.

Another exception would be if a limb has fallen off or otherwise failed.

Then it would be great to be able to turn regeneration on, for that limb only. Any added risk should be much smaller than the always-on version.

That's a bit much to expect out of evolution. First it needs a way to detect whether a limb has fallen off or otherwise failed. Then it needs to send a biochemical signal to the cells in the area iff the limb in the area failed. Then it needs to activate the regeneration iff the chemical signal is present. And each of these mutations has to be beneficial to the organism (or at least randomly there and costless). You can mush together the detection and signaling by having a local signal (like the biochemistry responsible for scabbing - iirc what happens is blood would do interesting chemistry while bleeding anyways, and so "turn into a scab when that chemistry is happening" is a worthwhile mutation), but still, it's a few too many steps.

I agree. What I was thinking (but didn't say) is that maybe we can make that happen with technology!

And perhaps some people might risk the chance of cancer to grow their body parts back.

Also with regeneration just cut out large chunks containing cancer and hope round 2 of your lungs is better!

Perhaps it could be turned on and off as needed: lose a finger in an accident, and take a drug to turn regeneration on. Grow your finger back in a week, and then take another drug (or stop taking the first drug) to go back to normal.

Your comment was either flagged or downvoted in to oblivion... I have vouched for it as I can't see any reason for either...

That's not how it works. For your finger to be capable of regeneration, the relevant genes would have to be in all your cells beforehand.

Advanced genetic engineering can be used to ensure that particular genes get activated only in the presence of some molecule that isn't naturally present in humans, so it would happen only if you take that particular drug; but it would still be applicable only to "newly built" humans e.g. as part of in vitro fertilization, not as something that can be applied to adults.

Most likely cancer as a disease will be a solved problem before we could enable this body part regeneration thing...if ever.

if you got cancer, just cut that piece off and eat more?

Yeah, just regrow that brain, liver, thyroid gland.

It could be those genes raise chance of cancer everywhere. Not just limbs.

I'd be willing to activate that feature if I was about to die.

Idea was not to activate ability. But to be born with it.

Are there animals that regrow their brain after a partial labotomy? In any case, humans can live with large chunk of brain removed, under the right circumstances.

The liver can regenerate. As little of 25% of the original liver mass can regenerate back to full size after either surgical removal or chemical injury.[1]

[1] https://en.wikipedia.org/wiki/Liver_regeneration

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