Most animals have the ability to regenerate lost parts, but not most of the tetrapods (the descendants of the four-legged creatures that invaded land; tetrapods include amphibians, reptiles, birds, and mammals).
Salamanders are the tetrapods best at regenerating lost parts: some can replace lost limbs, eyes, hearts (!) and tails at any stage of their life. Other salamanders can regenerate parts only when young, before metamorphosis into adults. Frogs can replace lost limbs, but only the limbs they have when tadpoles. As adults they lose this ability. Fish can replace some fin rays, but not lost fins. Lungfish (freshwater fish in the subclass Dipnoi) can apparently replace lost entire front or rear fins. Another primitive freshwater fish, Polypterus, can apparently regenerate its pectoral fins, though it’s not known whether this ability is limited to juveniles. Here’s a Polypterus:
Finally, and I bet you didn’t know this (neither did I), we humans can regenerate our fingertips, though this happens more readily in children than adults. I’ve added this photograph of fingertip regeneration suggested by reader Mark Sturtevant in a comment, which comes from a nice page summarizing animals’ ability to regenerate. It’s a bit grisly, but hell, we should be able to stand looking at this for the sake of education:
Other than that, though, humans can’t regenerate anything other major parts. The study of regeneration in salamanders has thus become a sort of cottage industry in biology, for if we could figure out how they do it—and they’re making some progress here—maybe we could help amputees regrow their limbs, something that God has proven incapable of doing—though He’s said to be able to cure many other ailments.
The information on regeneration across groups that I just gave came from a new paper in the Proceedings of the Royal Society (Series B) by Nadia Fröbisch et al. (link and free download below). But the main point of the paper was a striking new finding: fossil amphibians from 300 million years ago apparently had the ability to regenerate limbs, too. This, I think, is the first time that any fossil has been shown to have the ability to regrow lost body parts.
The authors studied many specimens of the primitive amphibian Micromelerpton credneri, from 300-million-year-old deposits in Europe. This is what one looks like; the preservation is remarkable (the scale bar is 1 cm., and there are about 2.5 cm per inch). The authors note that in this specimen you can see the shadow of the skin, the pigments in the retinas, the external gills, and the pattern of scales. This is not really a salamander, but a primitive amphibian whose placement in the tree of tetrapods will be shown shortly:
Looking at many specimens, the authors found that in some of the limbs there were signs of regeneration that resemble those seen in modern salamanders when they lose their limbs. They claim (and I can’t judge this, but take their word for it) that these anomalies are not simple deformities in the limbs of salamanders that have not lost their limbs.
Here is one sign of regeneration, two fused “phalanges” (fingers, if you will); normal specimens have four fingers on their front “hand,” this one has a bifurcated finger so there are five digits:
Another putatively regenerated limb, a foot this time. Feet normally have five digits, this one has six, with both central digits being thinner than normal. This, the authors say, is also a sign of regeneration and not just a deformity.
One potential problem with the results, which the authors discuss, is that while these are likely signs of regeneration, they don’t show that the regeneration happened in adults. The digits could have been lost and regrown as juveniles, and the signs of regeneration simply persisted in the adult, which may not themselves have lost the ability to regenerate limbs. In other words, these primitive amphibians may be like frogs or some salamanders, having regenerative abilities only when young.
So what does this mean for the evolutionary history of regeneration? The authors included a nice phylogenetic diagram of fish, amphibians, and other tetrapods, both primitive and modern, showing their regenerative capabilities. The placoderms (extinct armored fish) and chondrichthyes (fishes with cartilage: rays, skates, and sharks) can’t regenerate. Polyptera and Dipnoi can (the asterisks supposedly indicate regeneration only in juveniles, but we don’t know that for these two groups). We don’t know about the fishapod Tiktaalik, Acanthostega (one of the first tetrapods with limbs), or Eryops, an early and extinct amphibian. In fact, we don’t know the regenerative capabilities of anything without a gray box (indicating some regneration) or yellow box (those species whose phylogenetic placement is unsure; frogs and salamanders thus appear in two places).
Amniotes (birds, reptiles, and mammals) can’t regenerate anything.
What the authors suggest from this is because the “outgroup” of tetrapods—the lungfish and Polypterus, which are fish—have regenerative abilities, as well as some of their descendants (frogs and salamanders), it is possible that the ancestor of all tetrapods, an early fish, also had the ability to regenerate body parts. In the descendants that can no longer do it, like us, we might have lost that trait. In the language of cladistics, regneration is “symplesiomorphic”: an ancestral trait.
An alternative hypothesis is that the groups in gray independently evolved the ability of regenerate: it would then be a “synapomorphy” (shared derived character).
We can’t decide between these hypotheses at present though the authors favor the former one. The kind of evidence we’d need to decide between these hypotheses would be a bunch of early fossils showing the ability to regenerate, particularly in very primitive tetrapods or their precursors like Tiktaalik. If those had that ability, and it was seen in several early tetrapod species, it would support the notion that the very first tetrapods could all regenerate their limbs, but that the ability has been lost in some groups.
And that would raise the question: if groups like reptiles and mammals lost their ability to regenerate parts, why? It would seem to be a terrific advantage to be able to regrow lost parts. One possible answer is that the developmental system of these groups evolved in such a way that regeneration became physiologically impossible.. But of course we won’t know any of these things until we have better fossil evidence as well as some molecular data on exactly how limbs regenerate. If the molecular and developmental basis of regeneration were similar in all tetrapods, it would suggest that they have inherited that system from an ancestor, as it would be unlikely that such similarity could evolve independently. Biologists are working feverishly on the developmental basis of regeneration.
Maybe God can’t heal amputees, but perhaps science can.
__________
Fröbisch N. B., C. Bickelmann, and F. Witzmann. 2014. Early evolution of limb regeneration in tetrapods: evidence from a 300-million-year-old amphibian. Proc R Soc B 2014 281: 20141550
h/t: Dom
I used to bike a lot without socks and I would lose most of my toe nails from the repetitive force against them. They always grew back.
Now if we could just regenerate tendons and nerves…
Lots of interesting possibilities here, but I can think of two related ones.
1. Not many “wounded survivors.” If the vast majority of a species either escapes predation relatively unscathed or is killed by it, but there are relatively few injured escapees, then regeneration is a mostly useless trait. Mutations in the regenerative capability might not be that deleterious in terms of fitness if only one out of every 100 or one out of every 1,000 members of the species ever gets the ‘chance’ to use it.
2. Slower growth/metabolism. Regeneration is probably most useful as an adaptation when the time to regenerate is fast compared to the incidence of predation – it does a deer no good to take a year to regenerate a leg if that wolf pack is going to consistently attack the herd on a daily basis. So I’d expect it to be preserved more in species that grow fast and that can avoid predation effectively, and for it not to be preserved in species that are going to have to fend off predators on a cycle-speed much faster than their metabolic growth or healing rate.
I was thinking along the same lines:
There might be the possibly of a higher incidence of cancer or something going wrong. Miscarriage rate is 15 to 20 percent for women. Growing a new limb would have some similarities on how and where things could go wrong, except the limb doesn’t actually miscarriage.
How useful is the regenerated limb? Is a partial regenerated or deformed limb more useful then no limb at all? How well is the nerve system regrown on say a complete arm?
It would require more calories intake. The animal is already. Loss of blood on a creature could be horrendous. Growing back a limb might further weaken an already weak animal and make it likely to be dinner for a predator.
I have lots of questions but very few answers.
I particularly like the idea that regeneration is a ‘primitive’ trait, lost in lineages that secondarily evolved an increased metabolism b/c they die before they can regenerate. It is the old ‘use it, or lose it’.
“regeneration is a ‘primitive trait'” seems logical because presumably the earliest animals just grew, with details about growing things like fins, legs, and cilia, coming along later. Then the advantages of various carefully grown complicated body-plans increasingly outweighed the disadvantages of not regenerating so well….and regenerating was not occurring as well because of that complicated body plan. But, in a few species, ways to implement a complicated plan peice-meal was worked out….
If anyone wants to see how we regenerate lost fingertips [and Kevin, it is true for toe-tips as well], then scroll down here.
Not for the squeamish.
Never mind limbs – I wish I could get my rapidly disappearing hair to grow back!
Don’t worry Dave, it’ll come back. Out your ears and nose 🙂
Indeed, TANJ (There Ain’t No Justice), as Louis Wu often said.
That’s what that meant! I just thought it was a made up sci-fi expression.
Felgercarb!!
I grok that!
If it’s male pattern baldness you can fix it with chemical or physical castration…….
I’m fairly confident that will never catch on.
I think it works only to prevent baldness later on. Once the follicles degenerate they do not return very well. If I were castrated now I suspect I would still always be bald.
I don’t think that’s true – plenty of prostate cancer patients see a returning head of hair as one of the few positive side effects of ADT
Of course androgens are not the only cause of baldness and won’t affect blood flow
Well, that is good to know! Now where is that pair of rusty scissors?
I’ll be the control to your experimental. 😎
I believe that is only effective as a prophylactic treatment. Applied prior to puberty. Enough examples were recorded from the castrati singers.
One thing that immediately struck me looking at this cladogram. Osteichthyes as a whole have a larval stage, which has been lost in amniotes with the evolution of the amniote egg. As regeneration is more common in larval/juvenile forms, maybe this is something to do with it.
Many lizards regenerate their tails. The externals are quite similar, but the vertebrae inside do not regenerate. I also know of one instance of a (juvenile) crocodilian regenerating its tail (although it was easily detectable as such externally). There is partial limb regeneration in some lizards, but in the cases I can recall at the moment the regenerated limb was more of an extended stalk– covered with scales, but no joints or digits.
Yes. The regenerated tail isn’t as long or tapered as the original. Here’s an article about lizard tail regeneration:
http://www.sciencedaily.com/releases/2014/08/140820164317.htm
The tails of some small lizards detach so easily that the creature seems to “drop” its tail if picked up (that’s one reason that I don’t try to pick them up).
Where I live, the local, ubiquitous wall lizard, Podarcis muralis, does indeed easily lose its tail, usually when chased by a predator. The tail will keep moving for a while, distracting the predator (I have seen cats mesmerized by these twitching tails) and allowing the lizard to escape. The tail then regrows quite quickly, even by a few mm a day if I remember correctly.
I regenerated one of my right thumb and right index finger tips as a result of two different cooking incidents (I’m a lefty so I carve my right hand – these were both done as an adult). It was pretty gruesome but the regeneration is complete, no scaring the nails both regrew properly and the nerves recovered.
In contrast I split the end of the smallest finger on my right hand when I was about 12-14 – no actual tissue loss, just the pieces went in opposite directions and had to be realigned. That injury has left a (not terribly impressive) scar and slightly deformed nail to this day.
It’s interesting that similar injuries can result in such different outcomes.
If you left the split ‘open’ so the wound edges did not heal together I bet you would have regenerated a bifurcated finger tip.
I’ll remember to try that next time…
I guess you’ve ruled out the obvious solution – chop the tip off behind the misalignment and let it grow back.
Can’t imagine why you wouldn’t want to do that.
I don’t think anyone is looking into correcting the mutation that stopped female apes from re-absorbing the uterine lining every unproductive cycle either, like all the other mammals do (except for one species of shrew). Regeneration of limbs will only help a relative few people, but stopping menstruation will help half of the world population.
When I was a tot, about 3, I had the tip of my left thumb cut off (more squished off really) in a car door. It was reattached but healed lopsided, and the nail bed is deformed. I wonder if it would have been better to allow it to regenerate instead of reattaching the removed part.
I sawed off a finger tip, can’t even remember which one anymore, on my left hand in my early twenties and it grew back with no noticable signs of damage. I did pass out from the tetnus shot though. Poor female nurse didn’t quite catch me. My last image was of her sprinting towards me with a very anxious look on her face as I was going down. My take away from the whole experience was that smelling salts work really well.
sub and those fingers are gross.
A couple of comments here. First, I think you have in mind “regeneration of appendages”. Among amniotes, we know that many lizards [several groups, not closely related] and, interestingly, the tuatara have autotomous tails that can regenerate. As far as I can tell, this is usually a complex organ with vertebrae, muscles, nerves, though not exactly matching the original.
Second, “most animals” are arthropods, and the capacity to regenerate appendages is quite variable among arthropods. Crabs, notoriously, easily shed claws and replace them slowly over several molts. Since regeneration of any lost cuticular structure can only occur at a molt, no adult-instar pterygote insects [still “most animals”] can regenerate lost appendages. In “higher” groups of insects — Homoptera, for instance, and endopterygotes [still “most animals”], regeneration tends to be limited or lost. Often what we see the equivalent of a fingertip or nail — partial or full regeneration of a few distal segments of the appendage.
I suppose that most of this trend among insects, at least, can be seen as economic — damaged individuals probably won’t live long enough to make regeneration worthwhile. Among the longer-lived amniotes, regeneration might paper out, but regulation of neoplasms must play some factor..
You’re missing an ‘e’ in the genus name. It’s Micromelerpeton. (It looks like you got this from the Royal Society abstract, which sloppily uses 3 spellings: Micromelerpeton, Micromelerpteon and Micromelerpton.)
I don’t mean to be pedantic but humans can regenerate any number of parts – skin, vasculature, most of a liver, intestinal and stomach linings, etc. This is really just healing, but quite large areas of our body can reform. Most organs if they are sufficiently damaged will cause death anyway. We do seem to have a great deal of difficulty regenerating limbs, however.
I lopped a dime-sized (US 10-cent piece) chunk off the end of my left middle fingertip when I was 18. It all grew back; but there is a scar. And it was very sensitive for years; but not now.
This illustrates something amazing – the persistence of scars. My father has a nitric acid burn scar still slightly visible, 50 years or more after the event.
How does that work? And why doesn’t it happen all the time?
My dad crushed the end of his finger in some sort of grizzly industrial accident when he was in his 20s. I think they cut the end off and now it is odd looking and the nail grows over the tip.
well, it is interesting to see how many of our commenters have been maimed in the past. None of you are allowed around my power tools, btw. 🙂
It;s the ones who are maimed and unable to type who you should be banning.
Q. Who do you look at in a first responder situation? The quiet one, or the screaming one?
A. The quiet one.
Here’s how a physicist can utilize capacitance to save digits:
A safe(r) power tool
And I thought only Time Lords could regenerate!
(Well, somebody had to say it….)
Seriously, thank you for this informative article on a fascinating topic.
Perhaps one way to think about the possibility of whole limb regeneration for humans is to ask, what would regeneration of a whole limb actually look like (the finger regeneration photos give us a rough idea of what’s needed; and the physiology of wound repair gives us an idea of some of the problems). And also: what apparatus would be required to stabilize the organism long enough to allow whole limb regeneration to occur? Interesting puzzle….
FYI, the Human liver is an organ that has regenerative properties. As discussed, the rest of human healing is scar formation.
FYI, the human liver is a gland!
/@
It’s also a solid organ.
Not what my wife, a nurse, was taught!
/@
It’s what I was taught as a trauma surgeon who repaired the organ.
Well, I guess she’s trumped then! Maybe a U.S.-British distinction, though?
/@
Could be. After all we don’t put as many ‘o’s’ in our anatomy terms ;). But the liver is the second most complex organ in the body, with many functions. Some of those functions are most definitely glandular. So everyone can be happy.
I’m happy when my liver continues to function properly in spite of gustatory assaults I inflict upon it.
I’m imagining the following scene in a UK operating theatre:
Transplant surgeon: “OK, let’s harvest the liver next.”
Nurse: “Wait, you can’t! The patient is an organ donor, but the liver is a gland!”
Ah. I’m compelled to post this: https://www.youtube.com/watch?v=buqtdpuZxvk
/@
Love Terry Jones in curlers🐸
Also, if I may play Dr Obvious for a moment, a major factor in limb regeneration is the fact that you aren’t dealing with a single organ, but several, arranged in a very complex manner.
This was going to be my point as well. A primate hand has many more working parts than a lungfish limb, and the developmental program that generates it in the first place is correspondingly more complex. How likely is it that such a complex program can be restarted on a randomly truncated limb and produce anything like the same result?
I have an axolotl named Rose (Axol Rose–get it?). When I bought her, she was missing all but one half of one rear leg–as juveniles, they eat each others’ limbs. Seeing all of the limbs grow back. perfectly formed, was one of the most amazing natural processes I’ve ever been able to witness like that. It is impossible to see something like that and not immediately think, How can humans harness this ability? And if limbs, why not other organs? Why not, in fact, the CNS?
Rose is my funny little friend, but if axolotl blood is the secret to immortality, she better hide in her little log cave.
While the posted examples do look rather like regeneration rather than deformity (there are some patterns of abnormal regeneration in tetrapod embryo limbs experimentally truncated, rearranged, etc, which look very like these examples), you have to be careful arguing from digit counts in general, and in early amphibians in particular. Digit count still remains somewhat variable (examples : allegedly Incitatus ; abundant well-known polydactyl humans ; and there’s a breed of cat which has a high propensity to abnormal digit counts, whose name I forget), but in the early amphibians it was just plain unpredictable : Acanthostega, when it’s feet were discovered, had IIRC 7 pedal digits and 6 manual digits, while another “fish with feet” Ichthyostega had 5 and 6 respectively.
Counting toes isn’t a strong argument.
My hypothesis:
Humans live a long time.
The odds of getting cancer increases incredibly with age.
As an adaptation to combat cancer, most cells specialize and growth is curtailed once mature.
Losing regeneration is a side effect of this.
I actually knew that, by accident [sic!].
A friend cut off a few mm of a finger tip closing a door, and later claimed it had grown back. Never heard of regeneration in humans at the time, but it turned out to be possible.
sub
sub
You should check out extra cellular matrix. Its cool stuff usually derived from pig bladders but can be made form other bits. To make it they wash the bladder in a chemical bath to remove all the cells and leave behind the connective tissue that holds the cells to one another. Then this connective tissue ground up into a powder. ECM has been used for years in veterinary medicine to speed and improve healing from traumatic wounds.
I saw a documentary on ECM where they showed its use in veterinary medicine, on a wounded veteran, and they interviewed a civilian who used it.
The wounded veteran lost the majority of his right thigh muscle to a bomb. In a minor surgery, they opened up his leg and sprinkled ECM all over the damaged tissue. He regained a significant portion of his thigh muscle after a year and several treatments and he is now able to walk without crutches or other aassistance.
The civilian lost his finger tip in a tragic model airplane accident. He regrew his fingertip as an adult of about 60 years old. He was sent a bottle of ECM by his brother who was doing veterinary medical research on it.
Pretty cool stuff! I look forward to when we understand what is going on with this process and know how to use it better. Just imagine what it would mean to someone who was severely wounded in combat, or a car crash to be able to walk again. To have all their limbs intact again and be able to take care of themselves instead of being dependent upon others.
Well that was all very interesting, I try and follow the developments of stem cell research, loads of promise for regeneration there. Unfortuntely this research has a handbreak (that religious lot) in the US, not so Europe and others in the west. I think nano technologies also may have a future role in human regeneration of damaged cells and limbs.
An alternative hypothesis is that the groups in gray independently evolved the ability of regenerate: it would then be a “synapomorphy” (shared derived character).
Sorry, but this is not entirely technically precise: If it evolved several times independently, then it is not a synapomorphy for all those disparate groups together (although it would still be a synapomorphy for each of them individually).
For example, having lost the legs is a synapomorphy for the group ‘snakes’ but it is not a synapomorphy for the group ‘snakes + caecilians’, because in that case it is a convergence in two distantly related lineages.
It’s a bit grisly, but hell, we should be able to stand looking at this for the sake of education:
Right. And it pales in comparison to an image job talk I went to a couple decades ago (for the non-academics, a job talk is a lecture given by someone being interviewed for a faculty position).
This particular individual studied genital warts and the viruses that cause them. Specifically, vaginal ones. No great problems with that, but the first slide she shows is a full screen vagina covered with warts. Still OK, it’s for science etc. But she kept talking and all thru the intro, what was easily 10min, all we had to look at was the same warty, red, clearly irritated (distressed?) vagina. To the relief of many, she finally changed slides. (She didn’t get hired, either.)
Ouch…one hopes it was an anonymous warty vagina:-(
Wow. Even using PPT’s Smart Art wouldn’t help that lecture.
It rarely helps anyway…
/@
Interesting tree. I’ve always understood that caecilians were monophyletic, also frogs and salamanders. How can each group appear in two sister clades?
See the OP!
/@
sub
I had my appendix blow up inside of my abdomen when I was on vacation in Italy and I still have a large dorsoventral surgical scar running down my belly from two years ago. Would you say that is regeneration?
I was foolish to work with a length of wood that was far too short (about 10 cm) on a planing machine. The piece shot out of the planing table like a canonball. The fingers of my left hand were pressing the piece down, so a few millimeters of the fingertips and nails of the index, midddle and ring finger vanished in the blink of an eye. I thought I would never play the violin again.
The fingertips regenerated, fingerprints too!(I was 34). After 21 years, I still feel a slight pain when I press the tip of the index finger.