Scientists Demonstrate Mammalian Tissue Regeneration 260
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."
Re:So (Score:0, Interesting)
I have a feeling this causes cancer, eventually...
Re:I for one... (Score:3, Interesting)
All very nice stuff, but... (Score:2, Interesting)
...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.
Re:I for one... (Score:3, Interesting)
Re:It will be interesting to see... (Score:3, Interesting)
Re:Now I can finally start my restaurant... (Score:3, Interesting)
Of course PETA believes any sort of servitude by animals is the same as slavery. They'll never be happy. After all, if they ever got everything they wanted they'd have to find something useful to do with their lives.
Re:I for one... (Score:5, Interesting)
Not necessarily. A lot of small animals are pretty much disposable: they're sufficiently fragile that there's only a very narrow boundary between a trivial injury and a fatal one. (And anyone who's kept small birds and animals will know that if they're hurt beyond a certain point they'll simply go into shock and die.)
So it's entirely plausible that the gene might have been caused by a spot mutation very early on while all mammals were basically mice, and it then had a sufficiently small effect on actual survivability that the trait didn't get bred out. Later, once the small, disposable animals turned into large, expensive ones, it was too late.
It is interesting that both birds and animals appear to lack this trait, though. We both descend from much the same sort of lizards but in different directions. Finding out exactly where this gene sequence appeared might be productive.
(Of course, I want to know when we'll be able to get gene therapy to suppress the gene. Assuming it works in humans, and that the gene doesn't do anything else critical, it might even be fairly straightforward! But probably won't happen soon and I'm certainly not volunteering to be the guinea pig...)
Re:I for one... (Score:2, Interesting)
When you are driving in your car and run over a nail, it's often cheaper to just patch the tire rather than to replace it. You're generally back on the road faster as well.
Re:I for one... (Score:2, Interesting)
In case of large animals it may take very long to replace the lost body part. Maybe adaptation is simply faster, and more energy efficient. Same probably for grievous wounds. Or maybe it's just not worth it at all, and the time it took to replace or get over such injury resulted in death of both. But the suppressed gene code was easier to write? Damn lazy programmers...
Re:Be careful when fooling Mother Nature (Score:3, Interesting)
Any form of health care is dangerous this way.
Consider this: we can (and do) save many children with birth defects, often we are succesfull enough so that they can leard normal life (and even be oblivious to any issues). Problem is that some of theese defects are hereditary. Guess what? Next generation is worse off as far as ratio of defects is concerned.
We obviously will never do "sparta" thing and kill of children society finds undesirable. Nor will anyone with genetic defect be prevented from having children. Neither is civilized resolution or would be even remotelly popular (would you want to risk your child falling victim to it? noone would.)
Anyway, I would not worry about this particular medical advance. This regeneration propably caused cancer if it got out of controll (cancer with nondiversified cells as medium is quite scarry).
Re:What's the downside? (Score:1, Interesting)
Well, it's also useful for medical reasons. If we develop a molecule/protein that counteracts the protein fabricated by p21, we could temporarily get the healing power (for example, to heal damage to internal organs), without giving up the anti-cancer protection. This would be localized, and not too dangerous as the effects are temporary.
Not all mutations are bad? (Score:2, Interesting)
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.
Re:Be careful when fooling Mother Nature (Score:3, Interesting)
I think you have an interesting point here on the resource requirements of regeneration. Part of the obesity problem is that our bodies evolved to store whatever they couldn't use right now for later, so it stands to reason that such things were "turned off" for efficiency's sake. We didn't necessarily evolve in a land of plenty
As for infection rates, I would like to see that study done, too...
Re:So (Score:3, Interesting)
I'm assuming there is some evolutionary reason for curtailing a vigorous healing response. It maybe to reduce the cancer rate, but it could just as simply be something else very important - regulation of immune response for example.
One potentially useful experiment would be to challenge these mice with carcinogen (like ENU) and see what their cancer rate is compared to controls. Alternatively, you could use genetic means (insertion of oncogenes or mating to mice with knocked out tumor suppressor genes) to see if the cancers they develop are more aggressive or more likely to metastasize. In any case, this is a very cool finding.
Re:Now I can finally start my restaurant... (Score:4, Interesting)
Re:caveat (Score:3, Interesting)
The article also says this:
In fact, the researchers saw an increase in apoptosis in MRL mice -- also known as programmed cell death -- the cell's self-destruct mechanism that is often switched on when DNA has been damaged. According to Heber-Katz, this is exactly the sort of behavior seen in naturally regenerative creatures.
Does that mean shorter lifespan for the lifeform overall, or does it simply mean that individual cells will die regularly and then quickly be regenerated?
Re:Now I can finally start my restaurant... (Score:4, Interesting)
The worst part of it is, science believes that cats 'self domesticated' [wikipedia.org]. If anything, denying humans the right to keep cats as pets is animal abuse, since it is denying them an adaptation they developed themselves.
Who ever said these people used logic though?
Re:It will be interesting to see... (Score:2, Interesting)
Shortened lifespan resulting from telomere depletion?
As cells divide, a structure on each chromosome called a telomere assists with the DNA strand re-zipping after it gets copied. Each time this happens, the telomere gets slightly damaged.
Runaway cell division in cancer is usually enabled by the production of a repair enzyme called telomerase, which repairs telomere structures. The cancerous cell is usually already featuring several noteworthy transcription and replication errors, which is what prompts this change in behavior.
In healthy tissue, the production of telomerase would not be initiated, and so after aggressive tissue regeneration, whole cell cultures could start having apoptosis set in, as these telomeres degenerate past their useful life, which would result in huge amounts of necrosis going on.
Being able to do this "Regenerative" trick would be very handy in the operating room, but not so handy in daily life, because of it's increased risk factors, including a potentially much shorter lifespan.
I am interested to see if the p21 knockout effect can be replicated using a synthetic antagonist for the coded protein/enzyme. That would allow for an injectible to be given a few days before surgery, which would eventually wear off, and you would get the best of both worlds.
Re:Be careful when fooling Mother Nature (Score:3, Interesting)
Part of the obesity problem ...
So this gene will be a solution to that problem as well:
You're fat? No problem, just lop off a leg, it'll regrow, and in the process consume the excess belly...
Re:So (Score:5, Interesting)
You are correct. In point of fact, around 90% of the time when you hear that "X gives you cancer" what you should instead read it as is "X causes cancer to happen sooner". Usually this means that exposure to risk factor X reduces your ability to fight off cancer. You've probably got a few carcinogenic cells in you right now that are going to be killed off before they do you any harm. Obviously this doesn't apply in every single case - ionizing radiation falls into that other 10% that really does cause cancer directly - but when you see cancer linked to, say, stress, that falls under the other 90%.
I don't think that tissue regeneration will cause cancer to happen more frequently, for two reasons. The first is that the healing process in humans already accelerates cancer. As do certain immune responses. Essentially, every bit of damage you pick up over your lifetime accelerates the inevitable rise of carcinogenesis by some tiny amount. Regeneration, done correctly, probably won't worsen this.
The second reason is that the reason mammals don't regenerate naturally has to do with speed, not safety. The healing process in mammals essentially slaps a quick patch over the damage in order to get you healthy sooner; we call this patch a scar. Regenerating vertebrates (amphibians, some reptiles) take longer to heal, but heal more completely, which is substantially more viable when you're cold blooded and can go a few days without more food. At some point in our distant evolutionary past, scarring became a more viable approach to damage, as it fixed us up sooner, so selection pressure favored the scarring over the regenerating. Lack of regeneration in humans is a matter of what worked in the wild for our ancestors, not what works today, where the injured have plenty of time to recuperate, and don't run the risk of starvation or predation.
Re:It will be interesting to see... (Score:3, Interesting)
If on the other hand you make the presumption that an ancestor species had it, then you might wonder why we lost that ability. Sure, it might not affect survivability before age of reproduction either way. But then why did only those without the ability survive?
It's a reasonable question when looked at from that angle.
Re:I for one... (Score:1, Interesting)
Evolution doesn't care for, nor has it ever cared for the survival of species on a macro scale.
It can't care.
Ageing doesn't need to stop for their to be evolution, either.
Retroviruses get on fine modifying DNA all the time, some go well, some usually result in cancers and tumors.
It is one hell of a complicated process, but a species could thrive solely on exchanging viruses between each other.
Offspring could still happen, evolution doesn't care for the survival of other species.
It would be up to the species to conserve life for their own sake. (whereas species groups usually end up killing off most of the food supply around them and die)
It would be the ultimate goal of life, the recombining of the old and the new, RNA-world and DNA-world.
And so it shall be, Rand-World!
Re:Which way first? (Score:3, Interesting)
Screw that. 6.5+ billion people on this planet, many with a propensity toward cutting, scarring, beating, or even killing themselves, and we can't find just one who will volunteer to have this done so that we can see what will happen in a human? Christ, I could find a couple of dozen people in the next hour who would be willing to go on a suicide mission to Mars. Doing this kind of thing to an unwilling victim is straight-up evil, but finding volunteers really can't be that hard. Let's just answer the real question that we're trying to solve for rather than relying on these half-assed measures that take years to get to the point.
Re:Degeneration (Score:1, Interesting)
Uh, if this actually DID allow penis modification, the researchers should lead with such knowledge. They'd have all the funding they'd ever need from self-conscious males looking to score an extra inch or five (or perhaps, on a slightly less vain note, to reverse a likely non-consensual circumcision). I'm not trying to be funny; people routinely pony up big time for sex-related investments -- setting aside investments directly involved in the procurement of and enhancement of sex, there's cosmetic surgery, clothes, cars...
I propose that if some scientists would make an effort to double the length of (or regrow) a mouse's schlong instead of fiddling with its tail, they'd be sure to get extra public attention, and the increased funding that would follow would ultimately be beneficial in other, more relevant areas.
Re:Where is the Evolutionary Advantage? (Score:3, Interesting)
Presumably in the past there must have been some evolutionary advantage to developing scars rather than regrowing a new limb.
Speed is one possible reason. Another may be that a lot of scars are caused by things that persist (e.g. splinters, fibers, parasites), and it is potentially useful to encapsulate them in fibrous tissue, rather than regenerating normal tissue.
Likely increases cancer (Score:3, Interesting)
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 [google.com]
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.