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Biotech Science

Cloning Mammoths 66

Posted by michael from the elephantine-problems dept.
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."
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Cloning Mammoths More

Cloning Mammoths

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  • Code rot probably not the best analogy (Score:4, Informative)

    by Quixotic Raindrop ( 443129 ) on Thursday July 17, 2003 @03:01PM (#6463922) Journal
    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.
    • 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.

      They had a pretty hard time with the neanderthal femur they found a while back. I think with something this old, you'd need many, many decent DNA samples, and do serious statistical analysis to figure out which copies were most right.

      Then again, I could just read the article...

      • Re:Code rot probably not the best analogy (Score:5, Informative)

        by bcrowell ( 177657 ) on Thursday July 17, 2003 @08:38PM (#6466997) Homepage
        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 (Score:4, Informative)

      by Sgt York ( 591446 ) <`ten.knilhtrae' `ta' `mlovj'> on Friday July 18, 2003 @12:38PM (#6471709)
      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.

      • Code doesn't rot like living cells. I said nothing about DNA not rotting (just for the record).
      • That's true... the only way to go about it would be to build a complete sequence from many cells (several thousand to get a complete enough picture, I would think), encode it, then resynthesize the entire genome from scratch. The first half of that would require the same kind of effort that went in to the Human Genome Project; the second half a much more advanced development of currently-existing chromosome synthesis techniques. I'd guess we're 10 years away from (a) being cheap enough to do on a bunch of

  • Would you want to? (Score:3, Funny)

    by Creepy Crawler ( 680178 ) on Thursday July 17, 2003 @03:03PM (#6463940)
    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
    • > But ask yourself: Why did they die out?

      I heard it was because humans killed them off. But then maybe the story's changed since I heard it :-/

      My "t" key doesn't work. Dumb "t" key.

    • Because... Re:Would you want to? (Score:5, Funny)

      by WolfWithoutAClause ( 162946 ) on Thursday July 17, 2003 @03:21PM (#6464155) Homepage
      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.)

    • Re:Would you want to? (Score:4, Insightful)

      by mess31173 ( 462954 ) on Thursday July 17, 2003 @04:30PM (#6464979) Homepage
      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 [sciam.com]. Although some claim it could be weather. The article [sciam.com] addresses both possiabilities.

      • 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.
        • 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 bon

  • That mammoth ain't the only thing being cloned around here! [slashdot.org]

    Well, actually I guess this new article is a follow-up to last year's work by this Japanese team so it doesn't technically count as a dupe.

    GMD

    • Re:Clone (Score:3, Funny)

      by oever ( 233119 )
      Slashdot rule #2 and 3: all articles about clones and Duplo should be posted a factor of two times.
  • 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.

  • Huh? (Score:2, Insightful)

    by FroMan ( 111520 )
    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? (Score:2, Informative)

      by TCQuad ( 537187 )
      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 bas
    • Also, when cells die the DNA is nicked into little itty-bitty pieces, even when the rest of the organism is still alive. (This happens in apoptosis and necrosis). If you're extra bored look up TUNEL and ISEL+ staining with google to see how that can be used to find dead cells. I've never tried to clone a mammoth, but I assume this would make it a lot harder.

      • Re:Huh? (Score:2, Interesting)

        by ravenousbugblatter ( 682061 )
        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
    • There are a lot of really hairy problems to cloning. And these are only the ones that we know about.
      1. The cell differentiation process swaps around bits of DNA code as the cells decide what they are to become (bone, liver, heart, eyeball, etc...) Sure, each cell, theoretically, has all the same DNA, it's just the sequences are scrambled. We'd have to identify each individual gene and it's reliable sequence from these multiple sources to get things off the ground.
      2. From the "Dolly" and other cloning exp
      • Like you, I do it in the armchair too. As I understand it they introduced a different set of chromosomes from another cell and inserted them in an adult cell, then gave it an electric shock to induce mitosis.

        As the cell they introduced the new chromosomes to would have had old mDNA, I wondered if that might have been the reason for Dolly's premature ageing.

        BTW, my user name has nothing at all to do with Dolly the sheep, a dollyknot is a special kind of English truck drivers knot, its called a dollyknot, b
    • Yes, do this by developing nanotech dis-assemblers to take apart tons of these broken cells and put together a good cell copy...then they can clone it by using nanotech to make another copy (who needs the old biotech way of cloning...it's too error prone...better to develop and use nanotech methods where you have precise computer software/hardware control over all the processes)

  • Don't always need an intact DNA (Score:5, Interesting)

    by WolfWithoutAClause ( 162946 ) on Thursday July 17, 2003 @03:35PM (#6464344) Homepage
    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.

    • Well, I dunno, I don't think DNA likes to work in cells unless at least chromasome-wise it is fairly intact. There's tons of machinery designed to make protiens from DNA and to help it split that expects DNA to be coiled up in a certain way - namely in a chromasome. --
      If grocery store strawberries are so big because they are quadraploid, then imagine how big my balls would be if I was quadraploid...

    • Re:Don't always need an intact DNA (Score:5, Informative)

      by TCQuad ( 537187 ) on Thursday July 17, 2003 @05:19PM (#6465514)
      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.
      • I think the idea is that you pcr all the fragments at once....so you aren't starting with one and going to the end, you are starting at thousands of places and filling in inbetween. obviously it is very complex to avoid errors and accidental matching this way, but it could be done.
      • Well, probably a few more than that, but here goes. DNA in a cell isn't just sitting there all unwound, There are many huge sections of it all bundled/wrapped up around little protein cores which reduces the volume of DNA and more importantly only exposes the sections of it that are needed by the cell at that moment. This is controlled by other proteins within the cell. #2 would be that we don't have any idea of what all the upregulator proteins are like in mamoths. If we just stick the DNA into, say, a
    • no offence but all you wrote is total bs - you have no idea how far from reality you are...
    • What's wrong with splicing DNA code in from frogs?? It worked fine here!
    • Good idea, but PCR doesn't work on things that big. I heard a guy that PCR'd a 10kb fragment once, but I didn't believe him until I saw it. Chromosomes are on the order of megabases.

      Also, you won't know what part goes where. It would be like piecing together a shredded picture of a page of random dots. You don't know what a certain peice "says" until you have it in the context of the sequence around it. Even then, it takes a lot of work to figure it out.

      • Also, you won't know what part goes where. It would be like piecing together a shredded picture of a page of random dots. You don't know what a certain peice "says" until you have it in the context of the sequence around it. Even then, it takes a lot of work to figure it out.

        Yes, but that's what the human genome project did- they took the genome, deliberately chopped it up into fragments, and then sequenced each fragment. You then solve the giant jigsaw on a computer.

        • That's why I said "It takes a lot of work to figure it out" instead of saying "It's impossible to do".

          HGP took thousands of people dedicating years of their lives.

        • Yes, but that's what the human genome project did- they took the genome, deliberately chopped it up into fragments, and then sequenced each fragment. You then solve the giant jigsaw on a computer.

          At a cost of about a dollar a base pair (2.7 billion dollars for 3 billion base pairs)... I don't know about you, but I'm not really a big proponent of spending billions of dollars so I can look at a wooly mammoth.
  • That's like installing Windows to prove your computer can boot.

  • Not can do, but should do? (Score:4, Funny)

    by jpsst34 ( 582349 ) on Thursday July 17, 2003 @03:51PM (#6464525) Journal
    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 [homestarrunner.com] just to clean up after the fucker!


    • > Except that their prohibitive size would mean you'd probably have to hire a poopsmith just to clean up after the fucker!

      Smith? Do you dispose of it by turning it into 44mm3r3d 5417 or something?

    • 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.

    • What I'd really like to see is someone try to clone one of those massively large deep-sea squids from their washed up remains.

      Now that would be a great pet!

      Not only would it be good for scientific research into deep sea life, but you could also sic it on powerboaters and those bungholes with jetskis!
  • A japanese team, eh? And here I thought HeretiCorp would be USA based.

    Does "Kusari" have some meaning in japanese per chance? That one is still a mystery.

  • Caspian Tigers ( driven extinct by the romans ) or Tasmaninan Tigers driven extinct recently might be an easier thing to clone, or Barbary Lions. Something with a bit fresher meat.

  • ok, lets get this over with (Score:3, Funny)

    by mugnyte ( 203225 ) * on Thursday July 17, 2003 @05:11PM (#6465420) Journal
    ..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!!
  • Yeah, that's the ticket. Once a genetically diverse herd of Wooly Mammoths has been developed, we can allow them to roam freely over their former territory. This may cause some slight inconvenience for commuters in Saskatchewan.

    Meanwhile, we can open up the gates of Oklahoma's Tallgrass Prairie Preserve [nature.org] and allow the buffalo to run free across the vast North American prairie. Note that the cities of Bartlesville, Tulsa, and Wichita will be the first scheduled for "redevelopment" as prairie, with their r
    • I don't know about mammoths, but American buffalo are not very aggressive. I've been 20 feet from them at Yellowstone, and they seemed disinterested. Much like cattle.

      I don't think it would be a major problem if they got out.
    • Wayyy off topic but... Jeez, I read that recipe link as

      www.tripleraunch.com [slashdot.org].

      Buffalo Tongue, ewww.

      Regarding the other response to this parent: Seeing a buffalo in a National Park, does not a wild buffalo make. Darwinism will eventually get rid of idiots who try to get close to large animals with herding and stampeding instincts. It's just a step away from trying to feed the bears or pet the lions. I just wish the animals would win more dammit!

      Each sig of mine is a hand crafted, one-of-a-kind.
      • Regarding the other response to this parent: Seeing a buffalo in a National Park, does not a wild buffalo make. Darwinism will eventually get rid of idiots who try to get close to large animals with herding and stampeding instincts. It's just a step away from trying to feed the bears or pet the lions. I just wish the animals would win more dammit!

        Come closer, closer....

        MOO-HA-HA-HA-HA!

        Better yet: How about some frikin' Wooley Mammoths with frikin' lasers attached to their heads!

        (ahem!) HiggsBison

  • Making a hybrid is not really cloning... (Score:3, Informative)

    by geoswan ( 316494 ) on Thursday July 17, 2003 @08:27PM (#6466918) Journal
    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 [slashdot.org].

    You ever hear of anyone crossing Indian and African elephants?

    • 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 selecti
  • But why bother?

    Aside from the fact that this would require a superhuman effort to piece together an intact genome - assuming it's even possible given the state of 20,000 year old DNA - how many Elephant ova would need to be harvested, transformed and then implanted?

    Don't elephants have really long gestation cycles? (the figure 17 months comes to mind - but I'm not sure about this) And you can be sure as anything that elephant multiple births are extremely rare, if not unrecorded.

    How many aborted sheep fo
    • It is about 2 years for an elephant pregnancy.
    • 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.
  • I don't know but do molecular bonds have a life span ? Does the energy of bonds just stay constant and young ? Even the little lugs on the leggo blocks wear down .
  • where mammoth's are breed and raised like cattle. Mmmmmmm Mammoth .....
  • Just a thought - humour me! Human DNA represents about 4Gb of data, including the "junk" DNA. The protein "interpreters" for this source code are pretty complex (we're talking CISC, not RISC!), but the instructions for building the proteins which act as interpreters are also coded into this 4Gb - so I don't think I'm cheating too much when I say that our inherited characteristics fit into this figure.

    Now how much other information contributing to "you" have you received during your lifetime? There's obviou

    • If we breed a mammoth from old DNA, but have no mammoth culture in which to raise it, do we really get a mammoth?

      Not all social animals have culture. Ants for example are social creatures, but are not cultural creatures. even most primates are not cultural. otherwise your point would be a good one. However, you do raise a good point, nonetheless. If mammoths are social creatures, even if they are not cultural, then we may not know if such a mammoth would ever be psychologically healthy or developed. A l

  • So, I'd like to poke my head into this discussion to try to do a little clarification. (famous last words.)

    When we talk about cloning an organism it is different than cloning a gene. Cloning a gene involves finding the DNA sequence for the gene and getting it into a workable format. Like a glorified copy-paste operation.

    Cloning an organism is quite different. To clone an organism you don't need to sequence its genome. For instance, those sheep they keep talking about, I don't think we've finished th

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