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Scientists Demonstrate Mammalian Tissue Regeneration
telomerewhythere writes "A quest that began over a decade ago with a chance observation has reached a milestone: the identification of a gene that may regulate regeneration in mammals. The absence of this single gene, called p21, confers a healing potential in mice long thought to have been lost through evolution and reserved for creatures like flatworms, sponges, and some species of salamander. 'Unlike typical mammals, which heal wounds by forming a scar, these mice begin by forming a blastema, a structure associated with rapid cell growth and de-differentiation as seen in amphibians. According to the Wistar researchers, the loss of p21 causes the cells of these mice to behave more like embryonic stem cells than adult mammalian cells, and their findings provide solid evidence to link tissue regeneration to the control of cell division. "Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring," said the project's lead scientist.' Here is the academic paper for those with PNAS access."
We can all be Wolverine now? Cool!
Now I can finally start my restaurant (which specializes in mouse-tail delicacies) without PETA breathing down my neck. "Look: it's growing back!" Mouse-tail soup anyone?
...welcome our new, non-scarring, regenerating....
too easy, forget it.
You know this discussion will degenerate into how this can be applied to growing a longer penis.
"No matter where you go, there you are." -- Buckaroo Banzai
What the side effects are. One would(perhaps naively) assume that regeneration is an obvious survival advantage, and that losing regenerative capabilities would be a handicap. That being so, one would tend to suspect that an anti-regeneration gene would be fairly strongly selected against. Since this gene is, in fact, rampant in mammals, one is led to the suspicion that there must be some sort of upside.
Is it something more or less irrelevant to modern humans(at least those wealthy enough to ever be genetically engineered), something like "without any sort of medical care, most serious injuries were fatal before regeneration could occur, so the extra energy costs weren't worth it", or is it some kicker of the "Well, without a whole bunch of other adaptations possessed by certain amphibians and creepy-crawlies, you'll 'regenerate' yourself entirely full of tumors by age 20." flavor?
The next step is to make some p21 specific RNA interference molecules and shut it down in an adult, non-regenerative mouse. Then clip its ear and see what happens.
Since it also increases apoptosis, would this make a good diet pill?
On the one hand you take life too seriously, and on the other, you do not take playful existence seriously enough. Seth
"She turned me into a newt!"... "I regenerated!".
Isn't this the backstory to the Lizard? He tries to regrow his arm using amphibian DNA, and whoops - he turns into a Lizard.
Hm, it sounds really stupid now that I've typed it out.
This is, obviously, the holy grail for many injuries and holds out immense hope for amputees etc. etc. There's one thing about it that has me concerned. Darwinism is cruel. It causes the weak to fall by the wayside of evolution and the strong to perpetuate the best of the species. Nature does things for a reason. The question in the back of my mind is: if we fool with this, what are the underlying natural reasons for the gene to be turned off? We aught to be taking a very close look at the consequences of turning on this gene before we start trying to fool mother nature. In short, I'm not against it, I'm just concerned and cautious - are you?
*** Don't be dull.***
Somewhat not being able to regenerate (or something deeply related with that) gave us an evolutionary advantage. Is pretty tempting to just make pills to turn that off, but what will be the cost? Don't think that you will fall into not being able to get older or make new memories, but still stinks to too good to be true.
...in practice, do we have the technology to knock this gene out in humans? That's the key thing. Either you have to engineer every human to have the gene before birth, or you have to do a live fix. And a live fix has all sorts of complications.
Of course, I'm completely ignoring potential side effects. This is best if you imagine a drug for it being advertised: "Regrowitol may cause side effects including cancer, accessory limbs, mutation into evil lizard creature..."
We're living in the future, sure. But we don't have all the cheat codes for reality yet.
A lot of people are asking why evolution has taken away our regenerative capacities, and are guessing what the downside of this regeneration is.
P21 is involved with anti-cancer. It arrests the cell cycle when DNA damage occurs, allowing the damage to be repaired (so mistakes are not carried forward into new generations). Or if the damage is too severe, the cell is made senescent (they lose the ability to reproduce and instead lead out a gentle retirement, performing their normal job until they just die of old age)
P21 knockout mice show a lot of carcinomas and P21 is also up-regulated by and works to remedy excessive oxidative stress. It's very unlikely this research is going to lead to a pill that knocks out P21 and lets us grow limbs back. It will only lead to a greater understanding of how our pathways work.
Minor note to above for the pedantic: when I say "have the gene before birth" I mean "have the modification".
Of course the caveat to using mice to judge how a gene affects long-term development of cancer is that there really is no "long-term" on a human scale in mouse studies, since they only live about 3 years at most.
I'm also not entirely familiar with the effect of p21-deficiency in cases where major tumor suppressors are deregulated or otherwise deficient. It is feasible that in the absence of further regulation, the absence of a major cell cycle checkpoint will lead to a more severe phenotype, whether in terms of being more tumor prone, or development of more aggressive tumors.
My guess is that while not having this gene results in wonderous regenerative abilities, it'll also increase your chances of developing cancer before the age of 20 by a bajillionfold. Not a problem for mice, but certainly a problem for men.
... when science does? Cheap shots aside, here's hoping that this actually get a practical application that will help people in the future.
...to prevent uncontrolled tissue growth, AKA cancer?
45 5F E1 04 22 CA 29 C4 93 3F 95 05 2B 79 2A B2
This might be true, the bad mutation might even be non fatal but that is not really the point. The thing to consider is the evolutionary advantage (or disadvantage) it gives. I would think that bad mutations give an evolutionary disadvantage and thus be selected against. So the question really is... "What sort of evolutionary advantage does it impart?" I really don't know the answer and I suspect that the researchers are just beginning to answer that question.
But this still makes me giddy for the future of Medicine.
Nothing lasts forever but the certainty of change.
It is unlikely that a process so complex as mammalian tissue regeneration be controlled by a single gene. Moreover, p21 mutations have been associated with cancers. Which brings forth another question: why is it that only "lower" organisms (and mammalian fetuses) are capable of scar-less tissue regeneration? The answer is yet to be discovered but it is very likely that evolution had to stroke a balance between cancer control and tissue regeneration. It won't be easy to figure out "the way back" to regeneration, or even to avoid the risks of such a path.
People Eating Tasty Animals But then as the Nugent says "You have to Kill it, before you Grill it."
there are 10 types of people in this world, those who read binary and those who don't. which are you!
The only reason that mammals with an active p21 gene and the inability to regenerate tissue continued on and p21 suppressed mammals did not is because chicks dig scars. No perfectly healthy scarless male is going to attract a hot chick who is only interested in the dummy injury prone type.
Honesty may be the best policy, but apparently by elimination, dishonesty is the second best policy.
What is the reason that life forms without that ability won the evolutionary war in the first place?
What bad could come from that ability? Side-effects?
Because I really can’t see any downsides.
Anyone here who is a bit more of an expert than the random coward? ;)
Any sufficiently advanced intelligence is indistinguishable from stupidity.
Here is the academic paper for those with PNAS access.
I have access to a PNAS. Sometimes I let my wife have access to it, too.
Presumably in the past there must have been some evolutionary advantage to developing scars rather than regrowing a new limb. It is possible that this might not be a factor that helps us now. For example perhaps it allowed more rapid recovery from a serious wound whereas now, with hospitals and modern medicine, a more complete recovery would be an advantage over speed. However until we have some idea what the advantage was/is it would be wise to proceed with some caution.
The wikipedia entry for p21 (http://en.wikipedia.org/wiki/P21) is somewhat misleading about its relationship with cancer. For a good review, see: http://journals.cambridge.org/action/displayFulltext?type=1&fid=1919868&jid=ERM&volumeId=10&issueId=-1&aid=1919860 Excerpt: "However, p21-null mice were found to be more susceptible to chemically induced tumours of the skin (Ref. 94) and colon (Ref. 95), and following irradiation they displayed increased tumourigenesis and metastases (Ref. 96). In addition, using different mouse strains, others have found that p21-null mice exhibit spontaneous tumour formation in the background of other genetic knockouts, such as Muc22/2 (lacking mucin 2) (Ref. 97) and Apc1638/2 (carrying a mutant allele of the adenomatosis polyposis coli gene) (Ref. 98). Furthermore, subsequent to the initial description of p21-null mice, investigators have found that p21-null mice bred on a 129Sv/ C57BL6 50:50 background did in fact develop spontaneous tumours at an average age of 16 months (Ref. 99). Collectively, these mouse studies demonstrated the importance of p21 in mediating the G1 checkpoint, and its ability to function as a tumour suppressor."
Somebody's never watched The Green Mile.
Scarring is much faster, and probably carries a lower risk of infection for creatures that don't have access to medical care.
What medical care do newts have access to?
After all, if you are a purist, and we go the way of the dinosuar, that it is as it should be
Evolutiontologists believe that dinosaurs did not die. They all grew wings and became birds when they saw the meteor coming.
I am the richest astronaut ever to win the superbowl.
It is not that simple in the field of cellular regulation. The mammalian cell has a complex network of signals and signal processing proteins that control the development of the cell - when it divides, when it dies, when it goes into a resting state. Within such a network, there is no simple "one gene - one trait" relationship. Blocking the p21 gene alters the behaviour of this network in a way that makes regeneration possible in mice. The function of the gene - or rather its product - is to block entry of cells into a certain development phase. It acts as a checkpoint mechanism for development. That is not purely a negative trait as in "loss of regeneration", but can be viewed as positive as in "increased control over cellular development". It is quite hard to slap simple evaluations on such functions. The reason why the system evolved that way may be cancer prevention, it may also be a more fine-grained control over tissue development.
Ubi solitudinem faciunt, pacem appellant.
Then with the eventual eradication of death (or continuous delaying of death) our reproductive function will begin to become a liability for our survival on this planet. (Overpopulating the world, depletion of natural resources, etc...)
If we achieve perfect regeneration and become almost immortals, are we going destined to live in a sexless world?... is space colonization the answer to this problem?
Just some food for thought...
As it turned out, p21 knockout mice had already been created, were readily available, and widely used in many studies.
How many studies showing that 'X leaves no lasting damage' are now no longer valid because they were tested on regenerating mice???
Quite off topic, but I don't remember any Jesus-regenerated-a-limb miracles in the Bible, or are there?
As you demonstrate you already know, cancer prevention is partly about restricting the uncontrolled growth of cells; a tumor is cells growing without controls, so many natural defenses against cancer place controls on cell growth, sometimes by inhibiting healthy cell growth as well.
Turning off a gene like p21 is probably going to impact your body's ability to control and respond to cancer:
http://www.google.com/search?q=p21+cancer
In particular, in that search is a powerpoint presentation discussing the body's immunoresponse to cancer, in which p53 initiates and governs several important responses, one of which involves turning on p21 to begin replacing it with healthy cells.
Obviously, that observed response goes away if you knock out p21; it's likely that without the aid of that process, the process is impacted and cancer is more likely to succeed.
There are numerous other examples of p21 aiding cancer prevention, removal, and replacement in that search - have a look.
I'd like to see the comparative cancer rates of normal mice and p21-knockout mice.
In the US, population growth rate is lower than the rest of the world. If the US did not have immigration, our growth rate would be negative. Liberia & Western Sahara are among the highest growth rates.
This could mean that population growth and medical care/human well-being are inversely correlated. If this is true we don't need to worry so much about overpopulation.
Jesus: Mark 3:1
(a "man of god"): 1 Kings 13:4
Jesus also did an ear re-attachment, caused lame to walk & blind to see.
See: John Wayne Bobbit
In our current case, where humans are actually still dying, a negative growth is actually worrisome.
The movie Idiocracy might actually have a very valid point.
Can we grow back entire mouses from tails? :v
So you lose an arm, then it grows back, but it takes 20 years.
And that's 20 years of p21 suppression with enhanced cancer risk.