Cloning Mammoths

Anonym Feigling writes "For your consideration... An article over at the New Zealand Herald discusses some of the challenges a japanes team faces as it attemps to develop a system to create a clone from 20,000 year-old mammoth tissue samples discovered in Siberia. It seems to me that shortly after death, any animal's/plant's "cellular repair mechanisms" (for the lack of a better...) will fail, and thus the probability of finding a single cell with perfectly intact DNA from which to create a clone is pretty well zero. Interesting stuff, but it seems that practical considerations (think code rot) would make it difficult."

Comments

Code rot probably not the best analogy

[Quixotic Raindrop]

I get what you're saying, but code doesn't really "rot" in the same way that living cells do. I believe that if there are any intact cells they'd be lucky, but you don't need an intact cell to extract a DNA sample.

Re:Code rot probably not the best analogy

[bcrowell]

They had a pretty hard time with the neanderthal femur they found a while back.
AFAIK, they only analyzed the mitochondrial DNA (mtDNA) from the neanderthal sample, not the nuclear DNA that codes for proteins. They also did Oetzi, the 5000-year-old man they found in an alpine glacier.

mtDNA is only inherited from your mother, and is useful as a clock because it's not strongly selected for. There's also a lot more mtDNA in a cell than nuclear DNA, which makes it easier to recover mtDNA from an old sample than it is to recover nuclear DNA. Even though mtDNA is easier than nuclear DNA, they didn't even try to recover the complete mtDNA genome on these samples -- they just used them statistically, as clocks.

The neanderthal DNA showed that our last common ancestor with the neanderthals was 500,000 years ago, which implies that we're separate species, i.e., it supports the total replacement model (we lived alongside neanderthals and Homo erectuses for a long time, and then they went extinct) rather than the multiregional model (where H sapiens arose through worldwide interbreeding with other archaic hominids).

Oetzi's mtDNA was virtually indistinguishable from the mtDNA of the people who currently inhabit the region.

Re:Code rot probably not the best analogy

[Sgt York]

Getting intact full DNA from a living cell, prepared freshly is a challenge. And it does "rot", just like living cells. It's a molecule, and anything that will decay a cell will take the DNA in that cell along with it.

There is also molecular decay, independent of decomposition from microorganisms. DNA is subject to autocatalytic acidic hydrolysis; that is, in any solution with a pH lower that about 6 or 7, it will break itself up into little chunks. Most tissues become quite acidic after death. The DNA is still there, kinda, but it's broken up into little bits.

You don't need intact cells to get DNA, that is true. But to clone, you need a full genome, intact. Each chromosome needs to be a full sequence. For other applications, busted up DNA is fine. You can sequence, look for similarities, etc. But to clone, you need the whole thing, all in it's correct pieces.

Would you want to?

[Creepy Crawler]

Knowing how much just plain elephants eat and destroy, would we want double-sized hairy elephant?

Scitentifically, that's cool. But ask yourself: Why did they die out?

fp

Re:Would you want to?

[mess31173]

But ask yourself: Why did they die out?

Odds are, the reason that they died out, along with around 70 other species of giant mammals around that time is us. Although some claim it could be weather. The article addresses both possiabilities.

Re:Would you want to?

[alleycat0]

The disappearance of Pleistocene megafauna coincided with the extinction of numerous other species, many of which likely would have been considered as sources of neither food nor other resources, thus casting doubt on the theory that humans hunted mammoths into extinction.

ObCredentials: IANAP (P=paleontologist) but i spent most of my life as a professional archaeologist.

Re:Would you want to?

[willtsmith]

I believe the concept that ice humans hunting mammoths AT ALL is pretty silly.

The things are just too damn big to bring down with spears. It's also fairly questionable that "cliff hunting" took place. Today's elephants are VERY SMART and can find food over hundreds of square miles of territiory at EXACTLY the right time of year. If Mammoth are similar in their intellect it's doubtful Mammoth groups would return to the same scene over and over to be slaughtered.

I have produced large piles of animal bones and tossed them in the trash. That doesn't mean I killed the animals. Large amounts of bones at the bottoms of cliffs could just as plausibly be thrown over as trash after cutting off carcass pieces of dismembered Mammoth pieces (from natural deaths).

Finally, anyone who thinks ice age men killed mammoths should try hunting a modern elephant with a spear. Have you ever seen the size of an elephant gun? Even those don't bring them down ever time. Even if you DID get close enough, you would likely be gored or trampled do death after the first poke (if you managed to get through their hide).

Mammoth tissue samples?

[L. VeGas]

Talk about imprecise. Exactly how big is that? As opposed to what... teeny, weeny tissue samples?

What? Wooly mammoth? What do you mean by that? You mean, like with hair?

The only place to get a wooly mammoth tissue sample from me is my butt. Why would you want to clone that?

Bunch of pervs.

Because... Re:Would you want to?

[WolfWithoutAClause]

Because, they reproduce slowly, and they're finger-lickin good ;-)

(Mammoths died out only 5000-10000 years ago- they definitely would have had run ins with our ancestors.)

Huh?

[FroMan]

IANAMolecularBiologist

I wonder why it is so hard to find a full set of DNA.

I'd have thought that we had the tech to get gobs of DNA from all the different cells that we can salvage then take peices, even if from different cells, and then recombine them to get one full peice?

In theory the DNA should be the same in each cell, so if you take just find where the overlaps are between broken peices... Ah, what do I know, I'm just a code monkey...

Re:Huh?

[TCQuad]

It's significantly more difficult than that. You know those nice, clean chromosome pictures that you see in textbooks? Those are actually from actively dividing cells, the only time that the chromosomes are actually large enough to see in a microscope. Most of the time they're not compacted to that extent and therefore aren't very visible. So picking pieces by any sort of visual inspection at that level is out.

You could run these out on low percent agarose gels, and you'd be able to separate on the basis of size, but you wouldn't be able to tell the difference between a fragment of the X chromosome and the Y chromosome, so it'd be almost impossible to isolate based on size.

And the determination of good v. bad is much more difficult. How long should a mammoth chromosome be? Was this small one cut or that large one ligated? And when you don't know the genome, you're flying blind.

You also can't tell about base-pair damage, etc. without knowing what the sequence was originally. And to get the accurate original sequence, we need living tissue. Therefore, by definition, this is going to be our best guess as to what a wooly mammoth should be. There may be gene differences, etc. compounding the dietary differences that the mammoth will encounter.

The best scenario is to isolate one intact nucleus. Why? Well, if over the course of time the nucleus managed to remain intact, then the cell was probably fairly protected. If the cell was protected to a significant extent, then you're good with most major chromosomal damage and any ones with significant minor base pair damage will be nixed (i.e., the pregancy won't take).

Re:Huh?

[ravenousbugblatter]

It is conceivable that there are cells that would have DNA significantly intact in order to use for cloning. Cells will not begin to undergo cell suicide or necrosis immediately upon death -- they will continue to function for while, waiting for the release of chemicals from the liver and other funs places that will begin to autodigest the body. Cells could also potentially hang otu for a while until they simply run out of glucose (energy source). SO, it's conceivable that a cell very near the surface (for example an epithelial cell, which have been used for cloning before) of the animal could be humming along just fine after the mammoth croaked, and because it was cold there the cell could move into a state of inactivity (there's a reason scientists always carry those buckets of ice around). This cell could then possibly be frozen with it's DNA still relatively intact (keep in mind, even in normal, healthy cells there are estimated to be thousands of single-strand, and even some double-strand, nicks at any given time) and DNA does very well when frozen. So it is possible...but I doubt it will happen any time soon though.

Don't always need an intact DNA

[WolfWithoutAClause]

You can probably take two different, damaged copies of the DNA and PCR amplify them up, and generate a protein to stick them back together in the right way. It would be fiddly as hell, but in principle you can do it perfectly.

Once you have an intact copy of the DNA you can clone with it.

Alternatively, take the fragments of mammoth DNA and sequence them, then run the sequenced DNA through a DNA 'printer'. These machines exist- you feed in the DNA sequence on CD rom and out pops the actual DNA you want. It might take years or even decades(!) but it would certainly be possible in principle.

Re:Don't always need an intact DNA

[TCQuad]

Three considerations:

1) In order to PCR amplify something, you need primers which bind to the target areas and begin the replication. The primers need to have a known sequence, and we don't really know the mammoth genome, so we don't know what we're looking to amplify.

2) Mammoths have multiple chromosomes, so this isn't a one-step process. You'd need to repeatedly amplify section after section on each chromosome. Not impossible (per se), but not really feasible with todays technology due to:

3) Good day, high wind, Herculase (a PCR enzyme for long targets) can get 48,000 base pairs in one cycle with reasonable accuracy. The E. coli genome is 5.4 million base pairs. To PCR the entire E. coli genome you'd need to repeat the process 113 times to get the entire genome; if you're lucky enough to get the max every time, it'd take a lot of complex stitching to get it done. Of course, a mammoth is a lot bigger and more complex than a bacterium. The Fugu (pufferfish) genome is ~100 times bigger than E. coli (300 million), humans ~1000 times (3-4 billion). You can see the difficulty in using PCR for this type of application.

You are right, in principle, that you should be able to do all of these (eventually) but you also have to remember that each of these processes (not to mention troubleshooting!) takes materials (original DNA) in significant quantities. If we don't have a herd of mammoths, we probably don't have enough for what you suggest.

Not can do, but should do?

[jpsst34]

Here comes the barrage of "proving they can do it without considering if they should do it" posts. Well, here's a good reason why I'd want to clone mammoths: They'd make great pets. Kind of like Porno for Pyros would. Except that their prohibitive size would mean you'd probably have to hire a poopsmith just to clean up after the fucker!

Re:Not can do, but should do?

[dheltzel]

Well, here's a good reason why I'd want to clone mammoths: They'd make great pets.

The government just banned the importation of Giant Rats for pets, do you really think they are going to let you keep a Wooly Mammoth? Even if they don't transmit monkeypox to humans, if they just sneeze on you it could be life threatening. Imagine the death certificate:

Cause of death: suffocated under a blanket of mammoth snot.

Re:Clone

[oever]

Slashdot rule #2 and 3: all articles about clones and Duplo should be posted a factor of two times.

ok, lets get this over with

[mugnyte]

..think of all the Inuit we could feed! (tastes like chicken!)

..something new for the zoo! We need genetically engineered giant peanuts.

..a Wooly Mammoth? like your mom in a sweater?

..Its Woulbie the Wooly! Saturdays at 8! This week: sing along to "I wish you'd thaw my maw"

..That amount of poo will suffice for pre-fab housing! You fool! No smoking!

..Mammoth Rides! Spain's Run Of The Woolies! Jousting! Mammoth Hair coats! Ivory out the wazoo!

..Its whats for dinner. and tomorrow night too. and the next...

..Next stop: Reincarnating Hammurabi! We someone with more heart than the current pres.

.."Nature" Journal Submission Title: F15ST Mammoth B14[H3S!!

Making a hybrid is not really cloning...

[geoswan]

The initial plan was to find mammoth sperm cells, which could be used to inseminate an elephant to create a mammoth-elephant hybrid. But no sperm cells have been found, and other samples retrieved have been rendered unusable by time and climate changes.

Finding mammoth sperm, and impregnating an elephant is not cloning, it is just artificial insemination.

Worth noting is that if it turns out that the mammoth is closely enough related to a modern elephant for a pup to be born that doesn't mean the beginning of mammoth-elephant ranching. Lots of hybrids aren't fertile, like mules.

You ever hear of anyone crossing Indian and African elephants?

Re:Making a hybrid is not really cloning...

[willtsmith]

True.

However, this method (if successful) would be the quickest, easiest way to get a living mammoth (hybrid). Once you had your hybrids you could bank up lots of samples and clone it using the Dolly technique.

Gene therapy could be used to "mammothize" the hybrids. Subsequent clones from "gene-therapized" samples would be even more "mammoth" then previous generations.

Ultimately, even if a fertile mammoth hybrid could be produced, it would take a VERY long time to produce a near-pure mammoth via selective inbreeding. It takes to darn long for the females to reach fertility (which probably contributed to their extinction).

Ultimately, we will have the technology to reproduce a live mammoth given the VERY pristine condition of the frozen mammoth sample. It is a certainty that one could re-constitute a complete DNA through multiple samples.

I think it will teach us a LOT about evolutionary biology (and genetics as a whole) to effectively DEVOLVE elephants (to a common anscestor) and re-evolve them into Mammoths.

Don't forget that modern DNA is littered with discarded/unused sequences. For example, there have been experiments done where researchers generated chickens with TEETH. The information to create teeth and grow them is there (likely from their dinasour anscestors). It just had to be turned back on.

Re:Sorry to be negative and all

[TCQuad]

a single breeding pair does not a healthy, stable population make.

Actually, this may not be true in all cases. Cheetahs, for instance, have had two points in their history at which the population has gone down to a single breeding pair, as determined by population genetics.

Of course, now it would be almost impossible for cheetahs to survive a third catastrophe of that magnitude, due to their low genetic variability, but it is possible for a single mating pair to create a new population.