That's cool, but the article doesn't seem to say anything about where this ability came from, only that the mice already had it. So they were genetic anamolies? I guess the question for me was whether or not we understand what's different in these mice. The article hints that we do, but is frustratingly incomplete.

Good to see your name, orthogonality. Thanks for the post.

The phantom limb effect would drive you crazy:

"Now you don't see it. Now you do!"

Would it feel like a new limb? Would it itch/throb while it was growing?

Can you imagine what this might mean for action movie special effects?

If it were as easy and troublefree as they present it to be in that article, then mice with those genes activated would have a tremendous evolutionary advantage over those which don't. We're not talking about foreign genes, here, we're talking about native genes which are dormant. These were switched off. In other words, there's almost certainly an advantage to having them off rather than on. Now, mind you, this would have to be evaluated in the correct evolutionary context, one which most people are unfamiliar. For example, suppose having those genes activated interferes with an important reproductive function. Then it would obviously be selected against but, given certain constraints, we could still put this to use in humans.

I'm inclined to think the price paid in more complex animals is a greatly increased likliehood of tumors. But that may only be if the genes were switched on universally--they're showing therapies where they don't need to do anything at all like that. But the point remains that there's necessarily some evolutionary disadvantage for more complex animals to have the ability to regenerate because less complex animals do it regularly and the benefits of it are obvious. There has to be a reason that ability is switched off. You can't say that making a complex organ is, well, too complex because obviously the body manages to do it in the first place.

Holy shit, that's incredible!

...and hey ortho!

They've amputated their heart and it's grown back. Huh? I must be missing something here because I don't understand how that'd work without killing the animal. I mean how quickly is this happening?

And you know what? Jewellers won't be happy about this - no more earrings!

Miracle Mice would be a great name for a band. Or a cartoon. I'm just saying.

Very cool. kmellis, I think the key to this would be to be able to manipulate the switching on and off of genes. We can do that (in part) for certain genes in mice already ("conditional knockouts" whereby you can switch off a certain gene or transgene at the time you decide). Thus, any side effects of having normally suppressed gene activity turned on would hopefully be minimal.

I think they just damaged the heart, dodgy.

omiewise: thanks!

dodgygeezer: they flash-froze small portions of the heart.

kmellis: good analysis and likely right, but see, for example, today's NY Times, on how genes for sperm competition in chimps win out, even if they bring along with them other, deleterious, genes. Mammals may have switched off the genes for regeneration as a side0efect of some other gene's more immediate effect.

Great, now somebody is going to have to invent a better mousetrap. Again.

I want one of these for my cat - she'd love it!

Mammals may have switched off the genes for regeneration as a side0efect of some other gene's more immediate effect.

Yeah, that's what I meant by "correct evolutionary context". (Or did I erase that part?)

Point is, in the environment of adaptation where more complex animals--including us--evolved, there's a negative selective pressure of some sort against those genes being switched on. However, as humans no longer live in that environment of adaptation, you can't strictly say that changing something like this is "bad for us". It may have been "bad" in a way that was profound then but is trivial now. Or it still may be very profound. The point is that until we have a good idea of what the consequences of switching those genes on are, we can't tell one case from the other. And we don't have a good reason to assume the former case and disregard the latter.

Honestly, there's such strong and obvious evolutionary advantages of regeneration of organs that it's very hard for me to believe that there isn't some very profound price to be paid in more complex animals. And because the distinction, just as a matter of observation, seems to be the cut-off between less complexity and more complexity (although, Williams reminds us to think carefully about what we think we mean when we say "complexity" in this context), I'm thinking that it's the interaction between cancerous cells and the immune system's ability to recognize them.

Great post! That's not all that this researcher is into.

These were switched off. In other words, there's almost certainly an advantage to having them off rather than on.

Is it always advantage -vs- disadvantage though? Couldn't it (actually it's about 12 or so genes I understand, maybe only 1 of which may have been turned off) just as likely have been switched off in evolution between amphibians and mammals somewhere simply by chance. Maybe some other more advantageous mutation occurred coincidentally at the same time.

Chance and not conferrence of advantage is the key element in evolution is it not. So I don't know that I agree that switching these genes on is necessarily going to turn out to be disadvantageous or rife with potential side affects (I mean, it might be, but it's as speculative as thinking that there was a logical reason for their having been turned off in the first place no?).

In any event, this is pretty amazing news and combined with the increase in in vitro stem cell research, may help in developing organ regeneration t'would think.

These were switched off. In other words, there's almost certainly an advantage to having them off rather than on.

Not necessarily. That statement is getting dangerously close to an ID way of thinking. peacay pretty much sums it up: it's not necessarily advantage vs. disadvantage.

Consider this scenario: (with the caveat that very few phenotypes result from single genes, but we'll go with it for now)

Gene R ("regeneration gene") regulation is linked to that of Gene C ("optimal night vision") in that when Gene C is expressed, gene R is not. Now obviously gene R is an advantageous gene, but only at the level of the individual. As long as the animal lives long enough to reproduce, there is no selection pressure for gene R. Evolution occurs at the species level. Gene C on the other hand is subject to more selection pressure, because optimal night vision probably helps against predation and hunting, or whatever. Thus, gene C will be selected for, over gene R. It's not the end of the world that you lose gene R, because, although you might be more likely to die younger without it than with it, you probably still will be able to reproduce.

I'm writing this on the fly, but I hope it's kinda coherent.

I for one welcome our cheese loving organ-regenerating laboratory-livin' whiskered amphibian mutant overlords!

Not necessarily. That statement is getting dangerously close to an ID way of thinking. peacay pretty much sums it up: it's not necessarily advantage vs. disadvantage.

I don't see that at all (either assertion).

Your example is exactly what I was saying. There is greater advantage to having R off than on because having R off is necessary to having C on. Put another way: an individual can have either R or C on, never both. Yes, now that I think about it, I can see how we might think purely in terms of the advantage to having something versus specifically the advantage of not having it. I wasn't thinking along those terms because, in this case anyway, I can't imagine how they would apply.

I don't know what you're saying with the other part, because all selection (with only a few hotly contested exceptions) occurs on the individual level.

"Chance and not conferrence of advantage is the key element in evolution is it not."

I don't know what you're saying here. If anything, the reverse of what you're saying is true because the only really good theory we have for how evolution happens depends upon selection. Without chance, yes, there'd be no evolution. But obviously the greater factor in evolution is inheritance and not chance because otherwise...almost none of us would live through gestation.

Your point about chance would be valid if everything in this scenario were reversed. That is, that there was some heretofore unseen metabolic ability of regeneration in animals that can only be triggered by a very complex and unlikely combination of mutations in the existing genome. In that case, yes, it's completely correct to refute the argument that "if it's not there, there's a 'reason'". But in reality, what we're seeing is something that

a) is common in less complex animals;
b) these less complex and more complex animals share the genetics for the expression of this trait; but
c) in more complex animals this trait has been turned off.

Why "c"? As said above, given that we can assume common ancestry between the less complex and the more complex, and that we can assume a historical progression from less complex to more complex, then we can safely assume that either the trait was explicitly turned off because it was directly selected against, or it was implicitly turned off when a more adapative trait which requires the deactivation of regeneration appeared. The former seems unlikely. That leaves the latter and something like the scenarios I (immune system against cancer) or gaspode (night vision) describe. Either case can accurately, and ultimately, described as being "advantage vs. disadvantage" because, in the end, it all sums to successful reproduction. Lrg is "more advantageous" to Lnv because more Lnv survive to reproduce by evading predators in the dark than Lrg survive by regenerating organs after they've been attacked by predators in the dark.

However, that specific example I think unlikely because where two different adapations known to exist/have existed both have clear advantages over their lack, then if the two gene complexes are only incidentally involved with each other (as one would expect of regeneration and night vision), then because of redundancy it's likely there'd quickly be adaptation that provides both. Only when the two adaptations are essentially at cross purposes and where an entirely alternate evolutionary path would need to be traced in the case of one of them, is it highly unlikely that both traits would likely be found to coexist. This is why I'm thinking in terms of immune system and how it controls cancer cells vis a vis how it is able to recognize differentiating stem cells in a complex organ as being normal and mistakenly identified as cancerous.

OK. I see what you're driving at. But I fundamentally disagree with the concept of "it's been turned off, therefore there must be a reason for it to be turned off".

It could have been turned off "by accident" (ie. thru co-regulation with another gene) and given that the organism can still reproduce without it (albeit maybe have a shorter lifespan) there is no compelling reason for it to be re-selected for (turned back on), further down the evolutionary timescale.

Hence, chance could play a role in turning it off, not any possible deleterious effects.

It could have been turned off "by accident" (ie. thru co-regulation with another gene) and given that the organism can still reproduce without it (albeit maybe have a shorter lifespan) there is no compelling reason for it to be re-selected for (turned back on), further down the evolutionary timescale.

Well, yeah, but you could only think I was disagreeing with that if you thought I didn't know that it really is all about reproduction. But I do know that and that's why I've also repeatedly qualified my argument with "because of the very obvious advantages of regeneration". In what sort of environment can you imagine where being able to regenerate limbs/organs wouldn't be an advantage for both the newly born and those at reproductive age? It's a hell of an advantage.

Also, I just don't get your use of the phrase "by accident". All mutations are "by accident" and so are all evolutionary pressures. If it sounds like I'm making any sort of teleological argument it's only because I find it as difficult to use language without teleology as anyone else.

As I said, the fundamental way of looking at this is that the offspring of Lrg outreproduced the offspring of Lnv (or whatever mutation involved the deactivation of Lrg). From that viewpoint, both adaptations existed in the gene pool and one had the advantage over the other in the environment in which they were adapted.

Looking at this in terms of rabbits is a mistake, of course. The deactivation of the regen gene surely happened around the branch in the mammalian evolutionary tree where they for the most part stopped being able to regenerate large structures. At that point, the gene complex that controls regen was almost certain simpler, and the mutation that allowed a superior advantage was also simpler. Down that branch the regen gene complex was deactivated while more things began to rely on the other, new, adaptation and that gene complex become larger. The inactive regen complex could have become more complex, too, by indirect effects. Eventually you have something as complicated as rabbits where, if you turn that gene back on, you get regen. The question is, how does turning it on affect everything that relies upon the genes involved being off?

In what sort of environment can you imagine where being able to regenerate limbs/organs wouldn't be an advantage for both the newly born and those at reproductive age? It's a hell of an advantage.

Yes it is. But the question of degrees of advantage is irrelevant when you are still able to reproduce. I'm talking in the absence of competition, here.

And I mean, obviously turning the gene back on could fuck things up. I just don't think it *follows* that it will. And if you can induce a temporary upregulation of gene expression (as I was trying to imply in my first post) then you may be able to get around any problems. Maybe not, who knows.

But the question of degrees of advantage is irrelevant when you are still able to reproduce. I'm talking in the absence of competition, here.

I can only understand evolutionary adaptation in the context of selective pressures regarding reproductive fitness, loosely defined (so as to include sexual selection, for example). So, in a way, I can't really parse your point that relies upon a context where "advantage" can exist independently of reproductive fitness.