Woolly Mammoth DNA Inserted into Elephant Cells

News Article Science Topics
Mar 27, 2015

Photo by Jonathan S. Blair/National Geographic

By Tanya Lewis

The idea of bringing extinct animals back to life continues to reside in the realm of science fiction. But scientists have taken a small step closer to that goal, by inserting the DNA of a woolly mammoth into lab-grown elephant cells.

Harvard geneticist George Church and his colleagues used a gene-editing technique known as CRISPR to insert mammoth genes for small ears, subcutaneous fat, and hair length and color into the DNA of elephant skin cells. The work has not yet been published in a scientific journal, and has yet to be reviewed by peers in the field.

Woolly mammoths (Mammuthus primigenius) have been extinct for millennia, with the last of the species dying out about 3,600 years ago. But scientists say it may be possible to bring these and other species back from the grave, through a process known as de-extinction.

But we won’t be seeing woolly mammoths prancing around anytime soon, “because there is more work to do,” Church told U.K.’s The Times, according to Popular Science. “But we plan to do so,” Church added.

Splicing mammoth DNA into elephant cells is only the first step in a lengthy process, Church said. Next, they need to find a way to turn the hybrid cells into specialized tissues, to see if they produce the right traits. For instance, the researchers need to make sure the mammoth genes produce hair of the right color and texture.

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13 comments on “Woolly Mammoth DNA Inserted into Elephant Cells”

  • 1
    Reckless Monkey says:

    I would like them to genetically engineer a dwarf elephant about the size of a large dog, that can keep the grass down and wake up the neighbours with it’s relatively high pitched but adorable trumpeting every morning. But a dawf mammoth would be even better!

  • 2
    Roedy says:

    How do they know the function of various mammoth genes?. Are these functions common to a many living species?

    How do you find out the function of a gene. Does it require you to sequence a large number of individuals, encode their traits and have a computer look for correlations? Or do you damage a gene, then look at the offspring and see the result?

  • 3
    LaurieB says:

    Last fall George Church spoke at Harvard and I attended because I thought I’d hear an update of where we are at with cloning, but instead he spoke about the CRISPR technique mentioned in the article above. At that time I left wondering why we need CRISPR at all. Why not just clone the mammoth? Or for that matter, why not clone the six extinct animals that are being considered as good candidates for that de-extinction procedure?

    Since a one hour lecture wasn’t enough to answer my questions (although it did inspire questions) I bought Church’s book Regenesis: How Sythetic Biology Will Reinvent Nature and Ourselves coauthored by Ed Regis, 2012. I’m not far enough into the book yet to discuss it but on page 11 of my hardcover version there is a basic description of how this elephant to mammoth regeneration would take place:

    You could start, for example, with an elephant’s genome and change it into a mammoth’s. First you would break up the elephant genome into about 30,000 chunks, each about 100,000 DNA units in length. Then, by using the mammoth’s reconstructed genome sequence as a template, you would selectively introduce the molecular changes necessary to make the elephant genome look like that of the mammoth. All of the revised chunks would then be reassembled to constitute a newly engineered mammoth genome, and the animal itself would then be cloned into existence by conventional interspecies nuclear transfer cloning (or perhaps by another method, the blastocyst injection of whole cells.)

    The same technique would work for the Neanderthal, except that you’d start with a stem cell genome from a human adult and gradually reverse engineer it into the Neanderthal genome or a reasonably close equivalent. These stem cells can produce tissues and organs. If society becomes comfortable with cloning and sees value in true human diversity, then the whole Neanderthal creature itself could be cloned by a surrogate mother chimp-or by an extremely adventurous female human.

    That last line of his resulted in some serious media attention and makes me smile every time I read it. But here is an explanation, again, from his book, page 9, of interspecies nuclear transfer cloning mentioned above:

    Genomic technologies can actually allow us to raise the dead. Back in 1996, when the sheep Dolly was the first mammal cloned into existence, she was not cloned from the cells of a live animal. Instead, she was produced from the frozen udder cell of a six-year-old ewe that had died some three years prior to Dolly’s birth. Dolly was a product of nuclear transfer cloning, a process in which a cell nucleus of the animal to be cloned is physically transferred into an egg cell whose nucleus had previously been removed. The new egg cell is then implanted into the uterus of an animal of the same species, where it gestates and develops into the fully formed, live clone.

    Here is a video of Stephen Colbert interviewing George Church:

    http://thecolbertreport.cc.com/videos/fkt99i/george-church

    Roedy

    I will skim through Regenesis to see if I can find the answer to your question and if so, I will post it.

  • 4
    LaurieB says:

    Reckless Monkey,

    Hmmm, how to accomplish this…Oh! I know! Problem solved. 🙂

    Insular dwarfism
    From Wikipedia, the free encyclopedia

    The skeleton of a dwarf elephant from the island of Crete.
    Insular dwarfism, a form of phyletic dwarfism,[1] is the process and condition of the reduction in size of large animals over a number of generations[a] when their population’s range is limited to a small environment, primarily islands. This natural process is distinct from the intentional creation of dwarf breeds, called dwarfing. This process has occurred many times throughout evolutionary history, with examples including dinosaurs, like Europasaurus, and modern animals such as elephants and their relatives. This process, and other “island genetics” artifacts, can occur not only on traditional islands, but also in other situations where an ecosystem is isolated from external resources and breeding. This can include caves, desert oases, isolated valleys and isolated mountains (“sky islands”). Insular dwarfism is one aspect of the more general “island rule”, which posits that when mainland animals colonize islands, small species tend to evolve larger bodies, and large species tend to evolve smaller bodies.

  • 5
    David R Allen says:

    @LaurieB. Why can’t they use the Dolly method on the Mammoth. Frozen Mammoths in the tundra. Is the DNA too degraded for the dolly method. When I read the OP above, I wondered why they just didn’t transfer a mammoth genome into an elephant’s egg and put it back in a female elephant.

  • 6
    Alan4discussion says:

    David R Allen Mar 28, 2015 at 5:36 pm

    Why can’t they use the Dolly method on the Mammoth. Frozen Mammoths in the tundra. Is the DNA too degraded for the dolly method.

    I think degradation was the problem. They would have to find good DNA strands from various bodies, or various cells, unless some exceptional specimen is found.

    http://www.livescience.com/37049-cloned-mammoth-still-unlikely.html
    Because flash freezing could preserve the cells, and possibly their genetic information, everyone in the field is searching for the Holy Grail: a mammoth that fell into a frozen lake, which then immediately froze overnight and stayed perennially frozen for 10,000 years, said Hendrik Poinar, an evolutionary geneticist at McMaster University in Canada.

    The chances of finding such a perfect specimen are incredibly slim, Poinar said.

  • 7
    LaurieB says:

    David,

    Yes, that’s what I thought I would hear at the lecture that night. I’ll have more reading time tomorrow and will search that book for the answer.

  • 8
    LaurieB says:

    From Church’s book Regenesis page 143-144

    All of that said, how do we bring back animals that have long since vanished from the scene? That depends on the species and what there is left of it. For species whose intact cells, tissues or other genetic materials have been preserved–as in the case of the bucardo, for example, or species well represented in frozen zoos, labs, or other storage facilities–revival will be possible through straightforward interspecies nuclear transfer cloning.

    A second category consists of species whose genetic material might or might not be too corrupt for cloning. This is true of the wooly mammoth, for example. Although mammoth specimens buried in permafrost may look remarkably lifelike, their DNA is not in the same condition. The wooly mammoth, however, really falls into a class by itself.

    Unlike the Neanderthals, whose remains consist exclusively of teeth, skulls, and other bones, Siberian mammoth carcasses have turned up with hair and even soft tissue on them.

  • 9
    Roedy says:

    Why all that fuss converting elephant to mammoth. Why not just directly synthesis a chunk of mammoth DNA based on what you have cleaned from many samples of mammoth DNA filling in with elephant if necessary.

  • 10
    LaurieB says:

    Roedy,

    See if this section from Regenesis page 146 answers this question:

    A third class of extinct species is represented by DNA samples that are so fragmented and corrupt that their genomes must be laboriously reconstructed from innumerable isolated pieces. This is true of Neanderthal man, whose draft genome Svante Paabo reconstructed in that manner. Unfortunately, the draft genome doesn’t exist physically as actual chromosomes or genes, but only as strings of DNA sequences stored in computers.

    Theoretically, it is possible to convert those sequences into a physical real-life genome by synthesizing short sequences (oligos) in DNA synthesis machines and then stitching them together into chromosomes. In 2010 Craig Venter created his so-called synthetic Mycoplasma bacterium by chemically synthesizing its entire genome, oligo by oligo. However, there is a huge difference between synthesizing a bacterial genome and synthesizing the genome of an animal as large and complex as Neanderthal man. While Venter’s Mycoplasma genome was 1.08 million base pairs in length, the Neanderthal’s genome consists of 3 billion base pairs, as long as that of a modern human. Synthesizing such an object oligo by oligo would take forever–or at least a very long time.

    Fortunately, there’s another way to accomplish the same objective: start with a physical genome that closely resembles the Neanderthal’s and then change it, piecemeal, into the genome of a Neanderthal. Reverse-engineer it into existence.

  • 11
    corey.mcdonald.7798 says:

    It’s called homology. I used to work for a biotech company that specialized in this. Essentially, over time they figure out that a certain gene in any mammal produces body hair for example. How they find this out is a long process that can even involve removing it to see if the creature just doesn’t grow hair anymore. Then they take this gene and search for close matches among a different organisms entire genome. What we found is that genes tend to stay preserved over species for the most part. For example, the gene in spiders that produces silk is very similar to the gene in goats that produces milk. It’s just different enough to actually function completely different, but if you were to line up the base pairs, you would see a lot of similarities. So, they use various software algorithms to look for close matches, and then they usually target the top match. So, if they know a gene in a mouse produces hair, then they find that gene in elephants, then they find that gene in mammoths, then they are in business. The genes could be 10s of thousands of nucleotides long, and they may be a 95% match.

  • 12
    Jude says:

    Why? What possible good outcome if followed to its logical conclusion (the in vitro manufacture of a mammoth embryo) – the world is losing it’s elephants at the rate of 100 +/- a day to the trade in their tusks, human wildlife conflict and trophy hunting. The world is waking up to the cruetlty of having elephants in captivity. A mammoth calf will never be a mammoth – it will be a facismilie of a mammoth, raised by a different species in captivity. This is a terrible decision.

  • 13
    Alan4discussion says:

    I see there is progress in work on the mammoth:

    http://www.bbc.co.uk/news/science-environment-32432693
    .An international team of scientists has sequenced the complete genome of the woolly mammoth.

    A US team is already attempting to study the animals’ characteristics by inserting mammoth genes into elephant stem cells.

    They want to find out what made the mammoths different from their modern relatives and how their adaptations helped them survive the ice ages.

    The new genome study has been published in the journal Current Biology.

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