Why don't humans regrow lost limbs?

[Rob060870]

Dear readers,

I have been thinking about this for a while and would appreciate it if anyone could kindly give me their input.

It is a tragedy when people lose their limbs or are born without them. I have read that some other animals can regrow limbs if they are lost such as the newt or Salamander.would it be possible to use a biological marker such as bioluminescence to identify the processes involved and then use gene therapy or another treatment to engineer a Human to perform the same neat trick?

thanks for your input.

 

[Borek]

Research is being done on the subject.

http://www.scientificamerican.com/article.cfm?id=regrowing-human-limbs

 

[Rob060870]

Thankyou for the link Borek, its is an interesting subject I think.

 

[Ken Natton]

I’m not sure whether to take this notion seriously. The only reason why I am taking this on myself is because none of the serious biologists who contribute to this forum have.

So. Limb development in human beings is something that happens during the embryonic stage. The human embryonic developmental stage lasts about eight weeks, after conception. Once it’s over, your opportunity for any seriously different or new morphology is gone. To the largest extent all that happens after that is that you get bigger. Okay, yes that’s not entirely true. There is some measure of further development that occurs all the way through birth and onward until adulthood. Also the human body has this extraordinary ability to repair itself. And yes, to some extent, that repair process is a tiny little echo of what occurred on a much larger scale during embryonic development. But it’s a long way from being the same thing. And even if technology did find a way to re-trigger the embryonic developmental sequence, if you were an adult who had lost a limb, what you would develop would be an infant limb. To regrow an adult limb would be a completely different prospect than what happens during embryonic development. You’ll gather, to me, the suggestion is ridiculous. And because a particular species of lizard can do it, is no indication whatever that human beings will ever be able to do it.

 

[madcat8000]

Well ken the issue with your POV is that all lower animals can do this easily, so the challenge isn't that hard. Id barter that the internal muscluature of a crab arm or leg is far more complicated than ours...rip it off though and he gets a new one. On this one we got the short end of the evolutionary stick.

 

[Borek]

if you were an adult who had lost a limb, what you would develop would be an infant limb.

I guess infant hand is much better than no hand at all.

And because a particular species of lizard can do it, is no indication whatever that human beings will ever be able to do it.

So you suggest that we should not try, because the idea seems ridiculous? Look around - we are surrounded by things that were once just a ridiculous ideas.

I agree that it is far fetching and may prove impossible at some stage. But to not try would be a mistake.

 

[Ken Natton]

Yes, okay, I was not for one moment disparaging the efforts of biology laboratories. I have seen, on television quite recently, a programme that showed a laboratory somewhere in the USA – I’m sorry I forget where – where they have successfully grown a rat heart – and it was beating! Believe me, no-one needs to convince me of the extent of the achievement this represents. The programme that showed this was all about people with serious injuries, including lost limbs and including serious spinal injuries, and their prospects for a ‘cure’. The four individuals it focussed on were mentally very strong people who were handling their circumstances very well. But it also showed how strong was the need that each of them had to believe in the prospect that their condition might one day be curable – even if not in their own lifetime – and it also reflected the cruelty of giving such people false hope, which some unscrupulous types are not above doing for personal gain.

But my point was about the embryonic developmental process itself. It is a fantastically complicated sequence of gene expression leading to the making of one protein, which then triggers adjacent cells to express a different gene to make another protein, which in turn triggers other adjacent cells to express another gene… and so on. The developmental process is not even a simple linear growing of the final morphology. The development goes through several stages that are not obvious progressions in the direction of the final form. The point is that in embryonic development, context is everything, and the context of the growing of an embryonic limb is vastly different than the context of growing a new limb for an adult.

 

[hamster143]

As far as I remember (I'm not a biologist), limbs don't regrow because some crucial proteins that are responsible for cell regeneration shut down very early on. And the reason they shut down is because letting them remain active exposes you to a higher risk that some cell in your body will go awry and start dividing uncontrollably, a.k.a. cancer.

 

[jjoensuu]

Two companies have come out with some kind of "regenerative matrix" which, when applied to the cut limb, can trigger a regeneration of the limb. However the regeneration process is not like from a sci-fi movie but a slower process.

The two companies that I know of are:

ACell Inc:
http://www.acell.com/

LifeCell:
http://www.lifecell.com/alloderm-regenerative-tissue-matrix/95/

At least in the case of the ACell product I remember reading that it was based on some found in the stomach of pigs. These substances (proteins, if I do not remember wrong) are what trigger the regeneration process.

 

[arildno]

The point is that in embryonic development, context is everything, and the context of the growing of an embryonic limb is vastly different than the context of growing a new limb for an adult.

Context is always everything, also beyond the embryonic stage.

So, change the local context around the adult limb, or stump of an adult limb, and odd things might begin to happen.

The scale of the undertaking would be mind-boggling and totally unprecedented by anything as yet produced, but that in itself doesn't prove impossibility.

However, I do not think this will ever be done, because the knowledge needed to do it would also open up other technological pathways that will prove a lot more cost-effective:

The minute understanding required, for example, of the neural system would be knowledge that probably quite easily could be coupled with machinery that can translate and transfer neural signals between the extremity and the central neural system.

Thus, getting a computerized arm, rather than a new biological one, is a much more likely prospect We might even prefer it to staid, old biology..

For example, we need not regrow muscular tissue or blood vessels, yet still have a fully functional arm with equal degree of sensitivity as the real thing (or hand), but a lot more durable. Nor do we need to wait a long time for the cells to grow, either, in order to have an arm or hand that does what it is supposed to be doing.


In the future, we can become cyborgs, rather than lizards.

That's my speculation, anyways.


The perfection of prosthetic technology will also open up ethical dilemmas that today are unthinkable:
Why cauterize a flesh wound (or fix a broken bone) and have the patient on lots of antibiotics and a long reconvalescence period when it becomes easier, and a lot cheaper to chop off the limb and replace it with a new one?

Sentimentalists will whimper about their rights for bodily integrity, whereas doctors will fume over irrational patients who wont't take their medicine..

Same old story, but in a new wrapping.

 

[nismaratwork]

Context is always everything, also beyond the embryonic stage.

So, change the local context around the adult limb, or stump of an adult limb, and odd things might begin to happen.

The scale of the undertaking would be mind-boggling and totally unprecedented by anything as yet produced, but that in itself doesn't prove impossibility.

However, I do not think this will ever be done, because the knowledge needed to do it would also open up other technological pathways that will prove a lot more cost-effective:

The minute understanding required, for example, of the neural system would be knowledge that probably quite easily could be coupled with machinery that can translate and transfer neural signals between the extremity and the central neural system.

Thus, getting a computerized arm, rather than a new biological one, is a much more likely prospect We might even prefer it to staid, old biology..

For example, we need not regrow muscular tissue or blood vessels, yet still have a fully functional arm with equal degree of sensitivity as the real thing (or hand), but a lot more durable. Nor do we need to wait a long time for the cells to grow, either, in order to have an arm or hand that does what it is supposed to be doing.


In the future, we can become cyborgs, rather than lizards.

That's my speculation, anyways.


The perfection of prosthetic technology will also open up ethical dilemmas that today are unthinkable:
Why cauterize a flesh wound (or fix a broken bone) and have the patient on lots of antibiotics and a long reconvalescence period when it becomes easier, and a lot cheaper to chop off the limb and replace it with a new one?

Sentimentalists will whimper about their rights for bodily integrity, whereas doctors will fume over irrational patients who wont't take their medicine..

Same old story, but in a new wrapping.

I have to agree here... I'd expect a pretty high-end prosthetic before regrowing a limb, but you know what, there will always be a demand for that. Some people are going to want to be "au natural", and that might be enough to drive research. Personaly, I'd like the full cybernetic package, thanks.

 

[Borek]

However, I do not think this will ever be done, because the knowledge needed to do it would also open up other technological pathways that will prove a lot more cost-effective:

The minute understanding required, for example, of the neural system

This is all pure speculation, but I don't see why we should know how the neural system in the limb works. We have to know how to start regeneration process, but beauty of the solution lies in the fact that if the growing process is started it goes on its own - and it doesn't need detailed instructions from us, as the detailed recipe is already in our DNA.

 

[bobze]

Dear readers,

I have been thinking about this for a while and would appreciate it if anyone could kindly give me their input.

It is a tragedy when people lose their limbs or are born without them. I have read that some other animals can regrow limbs if they are lost such as the newt or Salamander.would it be possible to use a biological marker such as bioluminescence to identify the processes involved and then use gene therapy or another treatment to engineer a Human to perform the same neat trick?

thanks for your input.

Surprising, the genomes of animals are more similar than once thought. The differences come not in different coding regions of genes per say, rather in the timing of expression.

As someone else touched on, during embryonic development the timing of expression along with another important factor: gradients, is crucial to correct development.

Many of these developmental genes are only expressed in embryonic tissues, not present in adults. Nor are the biochemical gradients present in fetuses, present in adults. These "morphogenetic fields" are what drive cell growth and differentiation toward body structure.

Also of note is the type of stem cells found in adults and the fetus. The fetus has more "general stem cells" which can differentiate into many different cell lineages (in deed, at one point a fetus was composed of cells that could become any type of cell). We call this pluripotency (totipotency for the part in parenthesis). Adult stem cells are more limited into what they can become, We have some multipotent cell lines (like hematopoietic cells, which can become any type of blood cell) and many more oligopotent cells, which can only become a few cell lines.

There are a couple of reasons why those pathways are turned off in humans (and most mammals), that has to do with tissue complexity and differentiation.

As someone pointed out, cancer is the "haywire division of cells" and certain genes (when broken) are more prone to cause a cell line to quit it's day job and live life selfishly. We call those genes, oncogenes --Or genes which help turn a cell cancerous.

The life of the fetus or embryo is one big race of division, which means many of those checks and balances on potential oncogenes are "off". Of course, this is fine for a fetus or embryo, from who's standpoint rapid division is a necessity of survival. However, in an adult it would make little sense (evolutionary speaking) to leave these genes on and run the risk of a cancer killing off the organism before successful reproduction (ever wonder why cancer is mostly a disease of age?).

The upside then is a lower risk of cancerous growths claiming you before reproduction; at the cost however, of regenerative ability.

You'll note that animals with "regenerative prowess" have some common features: Small, simple (from a histological stand point), mostly short lived, mostly lacking in (mammalian level) nervous system development, etc

As to whether we'll be able to do it one day? With the advances in gene therapy and our understanding of genetics-I'd venture yes. I think its more likely we'd see grafts grown in a lab then transplanted to our body, before we see some kind of magic tape you wrap around a stump. As someone else mentioned though, this kind of therapy may only be a novel approach to fixing limbs, as our technological abilities (particularly in the field of brain-computer interfaces and cybernetics) may simply beat biology there (and maybe an improvement on evolution's design to boot).

 

[arildno]

We have to know how to start regeneration process, but beauty of the solution lies in the fact that if the growing process is started it goes on its own - and it doesn't need detailed instructions from us, as the detailed recipe is already in our DNA.

Totally WRONG!

Embryonal development is NOT simply a local unfolding of what is contained in the genes; rather, as the embryo grows, it receives, in all its parts, signals from the rest of the body on how, and at what pace that particular part should develop further.

However, as our bodies are already fully developed, we would need to constantly mimic the signal flow that the regrowing limb will need, we can't go out having a cigarette while waiting.
(as a matter of fact, I'll do that just now).

 

[madcat8000]

Sorry arildno but you CANT know that. Scientificly we know next to nothing about how it would work. And even if you are right about the interbody signaling, its just as possible that the new growing limb will put out signals that will cause the adult body to respond with the right signals. Might be totaly self sustaining.

On the other hand I honestly think we'll have replacement bodys and brain transplant technologies first so we might never get to the end of this research chain.

 

[arildno]

Sorry arildno but you CANT know that. Scientificly we know next to nothing about how it would work. .

Incorrect.
There is such a thing called rational expectation..

 

[granpa]

do any animals with a size limit regrow lost limbs? (i.e. any mammals or birds?)

 

[nismaratwork]

Sorry arildno but you CANT know that. Scientificly we know next to nothing about how it would work. And even if you are right about the interbody signaling, its just as possible that the new growing limb will put out signals that will cause the adult body to respond with the right signals. Might be totaly self sustaining.

On the other hand I honestly think we'll have replacement bodys and brain transplant technologies first so we might never get to the end of this research chain.

Yeah, people assumed that about stem cells, and the result is that unless you pre-program them, you end up with a body full of potential neoplastic cells! That bit of research didn't end well at all, and people still seem to think that you can just shove stem cells into a given region with no scaffolding or programming and all will be well.

Remember, a gecko has the genetic instructions to regrow a tail, and a starfish a leg. Humans don't have those instructions for an adult to regrow an adult limb, so you might end with a baby hand and a body full of potentially cancerous cells. Arildno is going with the body of research as it's been shown so far.

granpa: AFAIK, birds do not have the capacity to regrow limbs, nor do ANY mammals, large or small.

Note in this bit of wikipedia, the factors that go into the regrowth of limbs, such as pre-existing bundles of stem cells, and special "programming". http://en.wikipedia.org/wiki/Regeneration_(biology )

 

[Borek]

Embryonal development is NOT simply a local unfolding of what is contained in the genes; rather, as the embryo grows, it receives, in all its parts, signals from the rest of the body on how, and at what pace that particular part should develop further.

I stand corrected. Partially. What I stated looked like if I think the process goes on its own once started - that's not the case, it needs correct conditions/signals all the way up. My mistake of not being clear.

Still, you need to know conditions needed for the limb to develop, not details about how the regenerated tissues work - they will self organize during growth. That's what I meant.

 

[nismaratwork]

I stand corrected. Partially. What I stated looked like if I think the process goes on its own once started - that's not the case, it needs correct conditions/signals all the way up. My mistake of not being clear.

Still, you need to know conditions needed for the limb to develop, not details about how the regenerated tissues work - they will self organize during growth. That's what I meant.

Ok, now THAT makes sense, and I can easily believe the earlier statement was a miscommunication.

 

[arildno]

I stand corrected. Partially. What I stated looked like if I think the process goes on its own once started - that's not the case, it needs correct conditions/signals all the way up. My mistake of not being clear.

Still, you need to know conditions needed for the limb to develop, not details about how the regenerated tissues work - they will self organize during growth. That's what I meant.

And in order to know about the conditions under which limbs may develop, it is extremely unlikely that we won't harvest a lot of knowledge of how those tissues actually work in the process.
And THAT knowledge might perfectly well be put to more fruitful&economical uses than going for a program of laborious organic regrowth.

 

[bobze]

I stand corrected. Partially. What I stated looked like if I think the process goes on its own once started - that's not the case, it needs correct conditions/signals all the way up. My mistake of not being clear.

Still, you need to know conditions needed for the limb to develop, not details about how the regenerated tissues work - they will self organize during growth. That's what I meant.

Well that's not entirely true either. The body during development goes to great lengths to help the tissues or 3 germ layers organize in a specific fashion.

Lots of disease arise from things where neuroblast cells or a bit of mesenchyme, or some somitomere cells didn't move in the correct way. Then you start seeing really interesting defects like caudal regressions and sirenomelia, etc

The point is, we say that embryonic tissues are "self-organizing"-but their really directed by the interactions of all the different cell types.

There's not really any reason to suspect that that process could be easily (if possible at all) duplicated outside of embryonic development.

 

[nismaratwork]

Well that's not entirely true either. The body during development goes to great lengths to help the tissues or 3 germ layers organize in a specific fashion.

Lots of disease arise from things where neuroblast cells or a bit of mesenchyme, or some somitomere cells didn't move in the correct way. Then you start seeing really interesting defects like caudal regressions and sirenomelia, etc

The point is, we say that embryonic tissues are "self-organizing"-but their really directed by the interactions of all the different cell types.

There's not really any reason to suspect that that process could be easily (if possible at all) duplicated outside of embryonic development.

I disagree; given the proper scaffolding and direction I can see this being very fruitful. As Arildno implied as well, it may be that growing your hand in a "vat", then transplanting it, THEN inducing additional growth of nerves and blood vessels would be ideal.

 

[bobze]

I disagree; given the proper scaffolding and direction I can see this being very fruitful. As Arildno implied as well, it may be that growing your hand in a "vat", then transplanting it, THEN inducing additional growth of nerves and blood vessels would be ideal.

You're not disagreeing

In the embryo that scaffolding has to be setup by gradients and growth factors, etc While the cells contain the DNA to setup those gradients, I'm not sure you could say that tissue's truly self-organize (at least not in the way, you might think of a virus self organizing).

Its wonderfully demonstrated by growing tissue types outside the body. You can harvest a bunch of kidney cells and grow them in a dish, yet they don't self-assemble into a kidney. They require the interactions of friends of neighbors to do so (not to mention a host of other cells types, mostly connective in nature, to add any kind of tissue assembly).I agree with the second part of your post, which is why I said in my first post on this topic;

I think its more likely we'd see grafts grown in a lab then transplanted to our body, before we see some kind of magic tape you wrap around a stump.

 

[madcat8000]

Well there is clearly a mechainsm that allows it to operate in lower animals. The pathways must in someway still be in us, however degraded. Thus with some help amount from the outside it should be replicable in humans. However now that I think about it, it would be too odd to be walking around with a babyarm in a sling while it regrew. Not sure I wouldn't just want a transplant cut off of a clone in the end.

 

[nismaratwork]

You're not disagreeing

In the embryo that scaffolding has to be setup by gradients and growth factors, etc While the cells contain the DNA to setup those gradients, I'm not sure you could say that tissue's truly self-organize (at least not in the way, you might think of a virus self organizing).

Its wonderfully demonstrated by growing tissue types outside the body. You can harvest a bunch of kidney cells and grow them in a dish, yet they don't self-assemble into a kidney. They require the interactions of friends of neighbors to do so (not to mention a host of other cells types, mostly connective in nature, to add any kind of tissue assembly).


I agree with the second part of your post, which is why I said in my first post on this topic;

Hmmm, you're right.

Madcat8000: I don't know that I'd like to depend on a VERY distant relation to amphibians and render that code into an exon... then hope.

 

[Pythagorean]

What about through technology, though? Wouldn't it be possible to use the mechanisms of the salamander's themselves in a technological application of human regrowth?

I remember people have, in recent years, been able to print organs on a Hewlett-Packard printer:

http://www.hpprintercartridges.co.uk/blog/printers-used-to-print-cells-skin-and-organs/

What if we actually designed a technology that printed right onto the human body? The problem with the HP printers (when I heard about them, years ago, in casual conversation) was that the top layers of cells (of say, a heart) were dying before the last layer of cells were printed.

If we could print them directly onto humans somehow... wouldn't the patients host cells keep the tissue alive? And then you could, like, precision laser errors out and reprint? Is this sound in principle? I don't think anyone's "printed" bone either, so that's another complication.

 

[Borek]

The point is, we say that embryonic tissues are "self-organizing"-but their really directed by the interactions of all the different cell types.

So we say they are "self-organizing" because they are self-organizing

There's not really any reason to suspect that that process could be easily (if possible at all) duplicated outside of embryonic development.

I never stated it will be possible for sure, however - as I stated earlier - we are surrounded by things that were considered ridiculous years ago.

 

[Borek]

And in order to know about the conditions under which limbs may develop, it is extremely unlikely that we won't harvest a lot of knowledge of how those tissues actually work in the process.
And THAT knowledge might perfectly well be put to more fruitful&economical uses than going for a program of laborious organic regrowth.

You are mistaking recipe with a cake

 

[Ruslan_Sharipov]

Human lost limbs can grow from stumps. Not by themselves like those of lizards, but when a special surgical technology is applied. It is known that http://en.wikipedia.org/wiki/Ilizarov_apparatus" is used for limb lengthening through lengthening its bone. In a similar way one can lengthen the bone of a stump. Then this bone can be split for to form fingers and other small bones of a palm or of a foot. Soft tissues can be formed by means of plastic surgery.

So, nowadays, lost limbs can be reconstructed without any genomics and stem cells. I would be glad to participate in a group for to implement this idea into practice. Please, let me know contacts of a hospital or a clinic conducting such a research or interested in starting such a research.

 

[Borek]

So, nowadays, lost limbs can be reconstructed without any genomics and stem cells.

Remember, we are not talking about reconstructing something that LOOKS like a limb, we are talking about reconstructing something that SERVES as a limb.

 

[Ruslan_Sharipov]

If you reconstruct bones, and muscles, and blood vessels, and nerves, and joints, and skin,
then your item LOOKING like a limb will SERVE as a limb.

 

[Borek]

If you reconstruct bones, and muscles, and blood vessels, and nerves, and joints, and skin, then your item LOOKING like a limb will SERVE as a limb.

So, nowadays, lost limbs can be reconstructed without any genomics and stem cells.

Do you have any evidence to support a claim that it is currently possible?

 

[Ruslan_Sharipov]

Do you have any evidence to support a claim that it is currently possible?

No, I have not. But I am looking for the opportunity to prove that it is possible in a way I have described in rough details!

 

[Rob060870]

I believe that it is possible and with time will be done as the progress that Mankind is making is exponential and the fact that it already happens in other animals even though they are quite different from us proves that amazing regeneration is possible.