Why we can’t clone a Neanderthal—or any ancient organism

I’m not a huge fan of sci-fi, but one sci-fi movie I have seen is “Jurassic Park.” You’ll remember that the dinosaurs in that park were cloned from dinosaur blood (which contains DNA because reptiles, unlike mammals, have red blood cells with nuclei), and that blood was from the stomachs of mosquitoes that had bitten dinosaurs and then gotten preserved in amber.  Well, that reconstruction feat is impossible for scientists at our present stage of knowledge and technical abiliity—for the very same reasons it’s impossible to re-create any ancient organism from “fossil DNA.” This is relevant because of recent speculations, fueled by Harvard geneticist George Church and picked up and disseminated widely by the press, that we might be able to clone a human Neanderthal, since we now have a sequence of the Neanderthal genome.  (I’ve written before about George Church’s accommodationism; see here and here.)

First a bit about how animals are cloned. It’s usually done by taking a nucleus out of one cell (the nucleus contains most but not all of an organism’s DNA) and then transferring it to the egg of another individual from which the nucleus has been removed.  For example, you could clone your cat before it dies by removing a bit of tissue, taking out the nucleus from one cell, and putting that nucleus into the egg of a female cat from which the nucleus has been removed. The egg would then be implanted into a “surrogate cat,” which would carry the “fertilized” egg having the genetic constitution of your own cat.  If all goes well—and it often doesn’t!— the cat will produce a kitten largely genetically identical to your cat, enabling you, in principle, to have the same pet forever. (This isn’t guaranteed, though, as the mitochondrial DNA of your pet would not be transferred in this procedure, and somatic cells in the body undergo mutations during the life of an organism, so the skin cell of your cat won’t be genetically identical to the fertilized egg that produced it. See my discussion of this at the end of the piece.)

At any rate, this whole kerfuffle arose when Church floated the issue of producing a modern, living Neanderthal in this way. As Huffpo reports:

In a controversial interview that has ignited commentary across the world, a respected Harvard professor of genetics has suggested an “extremely adventurous female human” might someday serve as surrogate mother for a cloned Neanderthal baby.

Besides saying that the cloning of a live Neanderthal baby would be possible in our lifetime, George Church told Der Spiegel magazine that using stem cells to create a Neanderthal could have significant benefits to society. “The first thing you have to do is to sequence the Neanderthal genome, and that has actually been done,” Church said.

“The next step would be to chop this genome up into, say, 10,000 chunks and then … assemble all the chunks in a human stem cell, which would enable you to finally create a Neanderthal clone,” Church told Der Spiegel.

Scientists completed the first sequence of the Neanderthal genome in 2010, finding genetic evidence suggesting ancestors of modern humans successfully interbred with Neanderthals, at least occasionally. More recent research has suggested Neanderthal DNA makes up 1 percent to 4 percent of the genomes of modern Eurasians. [The 10 Biggest Mysteries of the First Humans]

The benefits, according to Church, include an increase in genetic diversity. “The one thing that is bad for society is low diversity,” Church said. “If you become a monoculture, you are at great risk of perishing. Therefore the recreation of Neanderthals would be mainly a question of societal risk avoidance.”

In his book “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves” (Basic Books, 2012), Church writes, “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.”

The HuffPo piece reports that Church’s statements have been overblown by the press, and he’s clarified his stand (see video at the link), saying that he wasn’t actually looking for a woman to bear a Neanderthal baby:

Church’s statements in the Der Spiegel interview have been wildly distorted, according to some observers. “There’s always a danger in taking one little comment and blowing it out of proportion,” John Hawks, associate professor of biological anthropology at the University of Wisconsin–Madison, told LiveScience.

“He’s really talking about science fiction,” Hawks said of Church’s comments, adding that with current technology, the cloning of any long-extinct species is “completely impossible.”

“We are a long way from taking DNA information and making a living cell from it,” Hawks said. And while the cloning and rebirth of extinct animals and humans sounds fascinating, it’s really not a scientific priority. “It seems to capture people’s imagination, but it’s not on anyone’s agenda,” Hawks said.

. . . Church himself has distanced himself from the media frenzy surrounding his Neanderthal commentary. “The real story here is how these stories have percolated and changed in different ways,” Church told the Boston Herald. “I’m sure we’ll get it sorted out eventually.”

Yet I still see claims all the time that we can use “fossil DNA” to re-create dinosaurs, mammoths, or other extinct life forms—so long as we have their DNA.  But, as Hawks noted above, this is impossible with modern technology. And while there are several reasons why it’s impossible, there’s one big problem that will take decades to overcome:

Genes occur on chromosomes.

Human DNA, for example is arrayed on 23 pairs of chromosomes, and those chromosomes are unique bodies, each carrying their own subset of genes arrayed in a particular linear order. Chromosomes are complicated structures (read about them here), for they contain not just DNA, but specific DNA-associated proteins (“histones”), a “centromere,” a special part of the chromosome which helps it move to a daughter cell when cells divide, and “telomeres,” repeated bits of DNA at the end of chromosomes that protect the chromosome from degrading.

To produce an organism, its genome must be sitting on chromosomes, and on the proper number of chromosomes. You can’t just take a whole genome and stick it into a recipient cell, expecting that cell to behave normally.  The genome first has to be assembled in proper order—and that means the perfectly proper order (no room for error here), with all the bits in the right sequence.  Then it has to be packaged into those chromosomes, for without chromosomes cells can’t divide properly and you can’t produce a whole organism from that single cloned cell. To get an organism from one cell, there has to be millions of cell divisions.

Not only do we lack the ability to assemble bits of DNA (what we have from Neanderthals) into a complete genome, but we are nowhere close to putting that DNA onto chromosomes in the proper order. Until we do that, we won’t be able to bring back any species from fossil DNA.  I doubt that we’ll have this ability within the next 50 years, if that.

But the problems go beyond that.  DNA degrades with age, and some types of degradation (like changes of one DNA “base” to another) cannot be detected by sequencing, but would still render the reconstructed clone inviable because those mutations would be lethal in the re-created organism.  The genomes of many species, including ours, contain repeated elements dispersed throughout the genome. Much of this is “junk,” some of it may have unknown but essential functions, but all of it would cause problems trying to reconstruct an ancestral DNA sequence. We don’t know exactly how many of these things there are nor exactly where they all sit on the DNA. If you screw that up, you will likely not get a viable “egg.” Finally, trying to assemble bits of fossil DNA (or DNA “cloned” from those fossil sequences) is likely to cause copying errors, creating even more mutations that will make the “clone” inviable.

And, of course, for the Neanderthals we don’t have a complete DNA sequence in order, and there is controversy about how much is original, how much may be contaminated, and so on.

Now I am not a molecular biologist, and am just speculating about what I know as an evolutionary geneticist. There may eventually be ways to assemble a complete fossil genome with all the bits in the proper places, and even to ensure that the repeated DNA elements are in the right places and that the assembly process doesn’t itself create errors.

But there is no way I know around the problem of having to put that DNA onto the proper number of chromosomes in the proper order. We can’t just assemble chromosomes the way we can synthesize DNA.  And until we can do that, reconstructing dinosaurs, Neanderthals, or any species from fossil DNA is simply out of the question.

So, as Hawks noted above, take this idea as science fiction, as it was in “Jurassic Park.” And the next time somebody tells you that cloning Neanderthals or dinosaurs is within the realm of science, remember the chromosomes.

But, of course, you can still clone your pet, because it’s alive and has its genome properly packaged onto chromosomes. Remember, though, that the clone won’t be genetically identical to Fluffy because of those factors I mentioned above. An article by Dr. Sophia Yin tells you the difference between a cat and her cloned offspring.

The picture below shows you what to expect when you clone your cat: Rainbow, on the left, is the genetic mother, via cloning, of cat CC (“copy cat”) on the right. They don’t even look alike: Rainbow is a calico and CC a tiger tabby with patches.  Why are they different? Coat color genes are inactivated in body cells, and which body cell you use as the donor nucleus can affect the color of its offspring. As Dr. Yin explains, cloning a tuxedo cat may produce another tuxedo cat, but with the white and black patches in different places. And don’t expect your cloned  cat to behave the same way, either. The same processes that make a clone look different from its donor can make the clone behave differently from its donor.

As Yin notes:

Consequently, your chances of ever having your pet cloned are slim. But even if the technology were available, the take home message with CC is that cloning will not resurrect your pet. Instead, you would be more likely to get something that looked similar to your beloved pet but that acted quite differently, or your clone could even end up looking like a complete stranger. Now that would be a dream, turned nightmare!

rainbowandcc

The result of cat cloning: donor (left) and clone (right)

82 Comments

  1. GM
    Posted January 27, 2013 at 7:11 am | Permalink

    It did not become at all clear to me what exactly he meant technically when reading the interview a few days ago. It’s not at all clear to me how he think he’s going to assemble a genome inside hESCs.

    Perhaps he meant that we can edit the genome (PMID: 23287722) of a hESC into that of a neandertal in a series of steps? I can imagine doing that but it would be an extremely laborious procedure. And even then, there are still the following problems:

    1) Nobody has yet successfully cloned a human, let alone from hESCs, which are apparently not quite as pluripotent as mouse ones (PMID: 21074044).

    2) It is far from clear what epigenetic differences there were between neandertals and humans and how this would affect the phenotype. Perhaps there were none, but who knows.

    It is definitely a worthwhile experiment to do, but we’re indeed quite far from being able to actually do it

    • Posted January 28, 2013 at 8:23 am | Permalink

      (1) It is unethical to experiment on humans like that. Cloning a human shouldn’t be any more difficult than cloning any other large mammal, give or take a few species-specific hiccups.

      I personally think cloning a neanderthal would be unethical for the same reasons as a human.

  2. marksolock
    Posted January 27, 2013 at 7:15 am | Permalink

    Reblogged this on Mark Solock Blog.

  3. Alice Wonder
    Posted January 27, 2013 at 7:15 am | Permalink

    Thank you for this very well written article. I was just reading about the Dodo and speculations that it could be cloned.

    The problems they spoke of were that Dodo birds were likely a species where the young had to learn from their parents and possibly even the population, and there are no Dodo birds to teach cloned young.

    Funny that e-mail notification for this blog, which seems to indicate an even bigger problem, came in while I was reading that.

    • GM
      Posted January 27, 2013 at 7:17 am | Permalink

      How do you clone birds?

      • Alice Wonder
        Posted January 27, 2013 at 7:22 am | Permalink

        Given that they are reptiles, probably the same way you clone a Velociraptor.

  4. starskeptic
    Posted January 27, 2013 at 7:23 am | Permalink

    But mammals have white cells that have DNA in them…

    • Posted January 27, 2013 at 8:00 am | Permalink

      Do you mean white blood cells.

      • starskeptic
        Posted January 27, 2013 at 12:46 pm | Permalink

        Yeah – Med Tech short hand, sorry.

    • whyevolutionistrue
      Posted January 27, 2013 at 8:05 am | Permalink

      Yes, indeed (I’ve corrected the above to show that I’m talking about red blood cells). I suppose in principle you could get white-cell DNA from an amber-preserved mosquito that bit a mammal, but it would be a lot harder (there are many fewer white than red cells) and at any rate all the other objections remain.

  5. Joe Pickrell
    Posted January 27, 2013 at 8:17 am | Permalink

    Church’s lab is working on technology for engineering massively parallel substitutions in a genome. In principle, one could make a list of all the spots in the human genome that are different between humans and Neandertals, then take a human genome and put in all the relevant substitutions. This gets around your chromosome problem (people have talked about bringing back mammoths in a similar way using elephants).

  6. DiscoveredJoys
    Posted January 27, 2013 at 8:26 am | Permalink

    Implanting a manufactured ‘fertilised’ egg into a human volunteer, an egg that might grow into a sentient but possibly defective baby?

    Even if you could surmount the technical details you would still have to get the experiment through an ethics committee. You might even need primary legislation changes.

    • Posted November 12, 2013 at 5:36 pm | Permalink

      Well they did that to a mammoth and it did have a defect.

  7. Simon Hayward
    Posted January 27, 2013 at 8:30 am | Permalink

    It’s not clear to me why Church would cite increased genetic diversity as a reason for doing this experiment. This would seem to be a case of manufacturing a problem to justify an end (although I’m basing this on a report of his comments, not the original). We have a robust, and still growing, human population. One can well argue that the excessive number of humans population is a problem per se. However, it’s hard to see that we face any sort of crisis due to inbreeding. All the data with which I am familiar suggest an increasing rate of human evolution associated with this large and recently urbanized population. We would appear to be spitting out genetic variants very nicely all on our own, without the need for further additions from extinct humans, whose adaptations to city life would seem questionable, indeed we may already have incorporated the once useful components of their genome.

    • Diane G.
      Posted January 27, 2013 at 12:14 pm | Permalink

      I was wondering the same thing, but you said it better.

    • Posted January 28, 2013 at 8:31 am | Permalink

      Actually, the data suggest we’re accumulating deleterious mutations a slightly scary rate.

      Finally, a consideration of the long-term consequences of current human behavior for deleterious-mutation accumulation leads to the conclusion that a substantial reduction in human fitness can be expected over the next few centuries in industrialized societies unless novel means of genetic intervention are developed.

      http://www.pnas.org/content/107/3/961.long

      Also, the population geneticist in me insists I warn you not to confuse population size with effective population size. Humans have been through a substantial bottleneck only 20-40,000 years ago; our current genetic diversity reflects that, whatever our current numbers.

  8. Frank Troy
    Posted January 27, 2013 at 8:36 am | Permalink

    Jerry, thank you for this clear and helpful discussion. I don’t often read responses or write them at this site, but as someone whose career was spent trying to teach university students how to write well, I very much appreciate the excellent writing skills you exhibit routinely in your posts. I value your efforts to make the sciences accessible to non-scientists. Thank you again for your efforts.

  9. Posted January 27, 2013 at 9:03 am | Permalink

    I think Dr Yin is overly pessimistic a about the results of cloning: “Instead, you would be more likely to get something that looked similar to your beloved pet but that acted quite differently…” It is surely an overstatement to say that the more likely outcome is an offspring that behaves “quite differently” from the parent.

    Even in ordinary reproduction with all its gene reshuffling, many behavioral traits are inherited. Many pet breeds are well known for their characteristic personality traits. Cloning would only increase the resemblance between mother and offspring, relative to ordinary reproduction.

  10. Yiam Cross
    Posted January 27, 2013 at 9:35 am | Permalink

    So Jurassic Park is fiction? I’m gutted. Explains why I was having so much trouble booking tickets, though.

    I’m glad we have at last found something that’s impossible for humans to do, I was getting bored with all the things that experts of the time said would be impossible but are matter of course everyday occurrences now.

    • Posted November 12, 2013 at 5:41 pm | Permalink

      its not impossible they have created a mammoth in korea.

  11. Michael Fisher
    Posted January 27, 2013 at 9:39 am | Permalink

    Hi Jerry ~ Your post is a little above my head, but I think I detect something missing…

    Even if everything else is perfect do you not also require a Neanderthal womb for the Neanderthal egg? Surely any womb other than a Neanderthal womb would result in faulty development? I’ve never understood [for example] how we would develop a “recovered” mammoth from an elephant womb ~ surely there’s some “switches” that have changed their function in an Elephant womb?

    With regard to the above it’s obvious that “blueprint” is a poor analogy for what DNA does, but I think “recipe” is also weak. What’s a good one?

    • Michael Fisher
      Posted January 27, 2013 at 9:46 am | Permalink

      Is the womb regarded as part of the “extended phenotype”?

    • Filipe
      Posted January 27, 2013 at 10:54 am | Permalink

      Humans and neandertals bred a few tens of thousands years ago so they should be compatible.

      Domestic cats have served as surrogate mothers for wild cat species that are way more distant than humans and neandertals. Mammoths are also closer to indian elephants than those are to african elephants, there shouldn’t be much of a problem.

      • Michael Fisher
        Posted January 27, 2013 at 11:15 am | Permalink

        Thanks for that

        But let us suppose a “Neanderthal” was successfully brought forth from a modern human womb & let us suppose it had a phenomenal musical ability…

        And let us further suppose that we generated a whole tribe of “Neanderthals” & [on average] they also were far superior to modern humans at the art of music…

        Does it follow that the Neanderthals of 30,000 years ago were [on average] extraordinary musicians or is possible that it’s an artifact of a modern human womb + Neanderthal DNA?

        • Alice Wonder
          Posted January 27, 2013 at 11:18 am | Permalink

          They may make outstanding music, but I’m not sure they’d be able to handle buying car insurance.

          • Michael Fisher
            Posted January 27, 2013 at 11:35 am | Permalink

            Alice. What do you mean? Are you taking “the micky” out of me & my question?

          • starskeptic
            Posted January 27, 2013 at 1:00 pm | Permalink

            Expensive way to test a commercial…

    • Mark Joseph
      Posted January 27, 2013 at 7:18 pm | Permalink

      I remember reading something by Stephen Jay Gould stating that to pull off a Jurassic Park, we would need not only the genome for the animal but a mother, too, so that the animal could develop normally.

    • Posted November 12, 2013 at 5:44 pm | Permalink

      Well when the baby mammoth was born from the elephant it took help to push it out but there is no more help from humans.

  12. Posted January 27, 2013 at 9:49 am | Permalink

    Reblogged this on Sarvodaya and commented:
    Sorry to burst anyone’s bubble, but you never know what future technology may hold.

  13. Posted January 27, 2013 at 9:53 am | Permalink

    All advances in science, and all revutionary breakthroughs, start with someone speculating about something not currently possible. If you can’t conceive the possibilities, you can’t begin anything. What you show, in this article, is not skepticism, but a lack of imagination. Half the scientists, mathematicians, and engineers at NASA were Star Trek geeks, and today we have theories from NASA how folding space-time might be possible to simulate faster than light warp drives. We have printers that I can purchase for a couple of thousand dollars that will create 3 dimensional objects with moving parts, and the inventor calls it a “replicator”. 20 years ago someone would have told him the idea was ridiculous.

    Cloning in any form was science fiction not so long ago too, and I’m sure the first person to speculate about it had his or her critics scoffing at the notion.

    • Grania Spingies
      Posted January 27, 2013 at 10:08 am | Permalink

      There’s a zero quantity of scoffing or lack of imagination going on here.

      This is in fact an excellent post that clarifies the difference between what science and technology can do – at present – and what the semi-literate media report in sensationalist and misleading ways.

      Nowhere does it state that no how is this ever going to be done in the future of humankind. It simply educates on where the pitfalls are.

    • Michael Fisher
      Posted January 27, 2013 at 10:28 am | Permalink

      Scott

      You’ve added nothing to the conversation except “snide”

      Let’s look at what JAC wrote below the sensational title:-

      …Well, that reconstruction feat is impossible for scientists at our present stage of knowledge and technical ability for the very same reasons it’s impossible to re-create any ancient organism from “fossil DNA”…

      Speculation is wonderful fun, but “snide” is poor currency on a beautiful Sunday. Get a life son.

    • GM
      Posted January 27, 2013 at 10:38 am | Permalink

      I would not use Star Trek and, in general, the space age fantasies from the 60s and 70s, as an example of dreams becoming a reality.

      Because we are very very far from where so many thought we would be at this time in history and not only that, but it is quite clear we will never be there. In case you haven’t noticed, the US does not even have a manned spaced program anymore…

      Cloning is a somewhat different case though – there is nothing that complicated about cloning itself, it has been routinely done for quite a long time. It’s just that the sci-fi vision of cloning is one of the more unrealistic sci-fi concepts. And, as I said above, nobody has been able to clone a human yet and there are issues with the pluripotency state of hESCs. We can write these off as a social problem (we have not been allowed to freely do these experiments and as a result we have not solved the technical problems yet) and the technical feat may become possible in the future. But clones in the form of what the public imagine when they hear the word are never going to appear.

  14. MNb
    Posted January 27, 2013 at 9:54 am | Permalink

    “The genome first has to be assembled in proper order—and that means the perfectly proper order (no room for error here), with all the bits in the right sequence.”
    Somehow I picture an IDiot in my mind licking his/her lips when reading this …

  15. schwa95
    Posted January 27, 2013 at 10:19 am | Permalink

    Actually, immature mammalian erythrocytes DO have nuclei.

    • starskeptic
      Posted January 27, 2013 at 1:19 pm | Permalink

      But normally circulating in numbers even smaller than the number of white cells.

      • starskeptic
        Posted January 27, 2013 at 5:39 pm | Permalink

        technically, not even normally circulating at all…

  16. Posted January 27, 2013 at 10:35 am | Permalink

    What I find interesting when talk of cloning is brought up is the apparently pretty widespread idea that the cloned animal is actually the same exact being as the animal that was cloned. As described in episode 291 of This American Life, where a beloved bull was cloned after he died…the owners persistently think it is the same animal, even after it acts far more aggressively than the original bull and almost kills one of them.

  17. bric
    Posted January 27, 2013 at 10:44 am | Permalink

    This was discussed on this week’s ‘Skeptics’ Guide to the Universe’ podcast; it seems the original interview was with Der Spiegel and Church’s points suffered rather in translation both to and from German: what he said was that given present progress it might be possible at some time in the future, and at that point there would of course need to be a discussion of the ethical implications.
    This eventually came out as – http://www.dailymail.co.uk/news/article-2265402/Adventurous-human-woman-wanted-birth-Neanderthal-man-Harvard-professor.html?ito=feeds-newsxml

    see http://www.imediaethics.org/News/3719/Woman_not_wanted_to_make_neanderthal_clone_baby__misquoted_harvard_prof_george_church_.php

  18. Barney
    Posted January 27, 2013 at 10:44 am | Permalink

    Where would this leave the idea of cloning mammoths? Are the chromosomes in the nuclei of mammoth meat fresh enough for dogs to eat when thawed (or is that a legend?) intact enough for cloning?

    • GM
      Posted January 27, 2013 at 10:51 am | Permalink

      It seems to be a legend at least as far as I am aware

      The approach Church is suggesting would be a lot more difficult to apply to the mammoth though. The differences between humans and neanderthals are not that many, so genome editing, while still a huge challenge, is much more feasible than it would be for mammoths and elephants, the divergence between which is greater.

      Also, I am not aware of any elephant embryonic stem cell lines as of now, and it is not clear to me how one would establish them – elephants are not exactly easy to work with animals.

      • Filipe
        Posted January 27, 2013 at 11:04 am | Permalink

        An Indian elephant female successfully gestated one hybrid produced with an african elephants (though it didn’t survive long), so I wouldn’t expect much of a problem regarding a mammoth, a much closer relative.

        • GM
          Posted January 27, 2013 at 11:51 am | Permalink

          I am not talking about the actual reproductive process, I am talking about the genome editing that has to be done

        • GM
          Posted January 27, 2013 at 11:51 am | Permalink

          Also, the elephant genome is not completely sequenced, so that has to be taken care of first before any of this is attempted

          • John Scanlon, FCD
            Posted January 28, 2013 at 5:30 am | Permalink

            That sort of thing only takes one lab a few week these days, no?

            • GM
              Posted January 28, 2013 at 5:35 am | Permalink

              Next-gen sequencing has not exactly excelled in the area of producing finished genome sequences.

              It definitely does not take a few weeks for a lab

      • gillt
        Posted January 27, 2013 at 7:17 pm | Permalink

        I am not aware of any elephant embryonic stem cell lines as of now

        Lol, maybe because there isn’t a clinical use for pachyderm ESCs and not because it’s a significant technological hurdle. We’ve induced skin cells into stem cells before, and even done interspecies nuclear transfer, even in non-model organisms. Are you familiar with the story of the Pyrenean ibex, the first extinct species to be “regenerated” (briefly)? Exciting times!

        FYI: Google multiplex automated genetic engineering or MAGE technology.

        • GM
          Posted January 28, 2013 at 3:17 am | Permalink

          Yes,I completely forgot about MAGE, thanks for pointing it out.

  19. Filipe
    Posted January 27, 2013 at 10:45 am | Permalink

    One thing about neandertals is that european and asian populations bred with them in the last 30,000 years so we carry a lot of their stuff in our DNA. The first step would be a reasonably straightforward one: pick all genes in modern human population from neandertal origin and cut and past them in a modern human genome. I wonder what fraction of the genome would we recover.

    They were essentially the same species and so even the chromosome thing wouldn’t be much of an issue, we could use our genome as a template with only a few minor tweaking.

    The question is more why would we do it? They’d be stuck in our world and culture, their language and culture is gone forever.

    • GM
      Posted January 27, 2013 at 10:53 am | Permalink

      The more important thing is not that we interbred with neanderthals recently, but that we were not that different to begin with.

  20. Posted January 27, 2013 at 10:59 am | Permalink

    Years ago I saw a program about a planned attempt to resurrect the extinct thylacine (Tasmanian tiger). What really bugged me about the work was that he used some of the only fetal thylacine sample (that was preserved in a way that didn’t destroy DNA) just to see how much DNA he could get out of it (not a lot). Although I support the goals of the research, I would have thought that the first step would be to see how difficult it was to ‘resurrect’ a living species using similarly preserved samples, rather than waste some of the few samples you do have just to see if there is DNA.

    As for the Neanderthals, I think the article was suggesting that by inserting the fragments of Neanderthal DNA into a human stem cell, that they would hybridize and be integrated into the existing genome, attaching/replacing the human genes in the proper locations themselves. This assumes that they had the same number of chromosomes as ourselves (which, considering the age of the last common ancestor is probable), and were closer to us genetically than bonobos.

    I wouldn’t be surprised if we get close to achieving the technological ability to do this in a few decades. Consider how much we have advanced in genetic engineering since the 1960′s. David Suzuki loves giving the anecdote about how he was once asked about DNA and expressed his doubts about ever being able to decode it, when a couple of years later the entire triplet code was determined.

    • John Scanlon, FCD
      Posted January 28, 2013 at 6:02 am | Permalink

      Jerry posted about thylacines back in Sept 2011 (it seemed more recent!) and I looked up some of the DNA results (see my comment).
      The famous pouch-young in alcohol at the Australian Museum turned out to be no good for DNA. That goes for most Australian museum vertebrate specimens in alcohol (i.e. even after excluding the large majority that were fixed in formalin), because of the relatively high temperature they’ve been stored at (compared to most European and North American collections).
      There was a sequencing project based at Pennsylvania State (see thylacine.psu.edu/); they estimated that up to 30% of DNA fragments from hair were nuclear, but they may not be still trying to get the complete nuclear sequence.
      Another team partially sequenced mitochondria from 12 specimens and published last year (link).
      I hope to see thylacines back in the wild in my lifetime; it’s something worth working for.

  21. will
    Posted January 27, 2013 at 11:02 am | Permalink

    It’s astounding with all this “synthetic biology” (cloning) and the synthetic evolution we’ve been doing for millenia now (selective breeding amongst farm animals, cats & dogs, etc) that so many average people STILL do not believe evolution is possible or even a valid explanation. WE do it ourselves in real time!

    I understand now why Darwin started off his 1959 book with man-made domestic evolution (selective breeding for a desired outcome). One little mythical story (Genesis, and GOD created every living thing) and people just turn a blind eye to evidence.

  22. Jim Jones
    Posted January 27, 2013 at 12:24 pm | Permalink

    I doubt we will ever build a “time machine” or a FTL starship drive.

    A gene spinner, however, seems far more possible.

  23. MadScientist
    Posted January 27, 2013 at 1:24 pm | Permalink

    Dang – already pointed out that clones won’t even look like the original – and there’s even a cat picture! If a human were cloned I would expect the clone to resemble the original but I’d be very surprised if they so much as looked like fraternal twins. As for assembling DNA – what a joke – good luck getting the folding right and all that. You’d think a geneticist from Harvard of all places would have some idea of the tools he has at hand and how they work. If the reporting of his description is accurate, what he describes doesn’t bear any resemblance to what people have been doing with gene manipulation in the labs for the past 40 years or so.

    • Gregory Kusnick
      Posted January 27, 2013 at 2:03 pm | Permalink

      If a human were cloned I would expect the clone to resemble the original but I’d be very surprised if they so much as looked like fraternal twins.

      I’d expect them to look like identical twins, which are in fact human clones.

    • gillt
      Posted January 27, 2013 at 6:49 pm | Permalink

      As for assembling DNA – what a joke – good luck getting the folding right and all that. You’d think a geneticist from Harvard of all places would have some idea of the tools he has at hand and how they work.

      Good god, why don’t you go to the pioneer of synthetic biology’s website and educate yourself.

  24. gravelinspector
    Posted January 27, 2013 at 1:30 pm | Permalink

    To get an organism from one cell, there has to be millions of cell divisions.

    Umm, well either millions, or 40 or 50. Or somewhere in between. Each division produces two descendant cells from one original, so to a first approximation, after N divisions of your original cell, there are 2^N daughter cells.
    I’d make an educated guess that each cell in a young adult human is, on average, 50 to 60 divisions from the original gamete.

  25. Jim Thomerson
    Posted January 27, 2013 at 1:49 pm | Permalink

    One would not expect a clone of a calico cat to look the same, pattern wise, as the original. Calico patterns are pretty much randomly generated. Calico cats are females heterozygous for color alleles on their X chromosomes. It is happenstance which X is turned off in a cell with will determine color in a particular part of the coat.

    • whyevolutionistrue
      Posted January 27, 2013 at 2:30 pm | Permalink

      Any gene that is heterozygous on the X would face the same problem in females, and of course there is the problem of somatic mutations as well.

  26. Gregory Kusnick
    Posted January 27, 2013 at 2:25 pm | Permalink

    Chromosomes are complicated structures (read about them here), for they contain not just DNA, but specific DNA-associated proteins (“histones”), a “centromere,” a special part of the chromosome which helps it move to a daughter cell when cells divide, and “telomeres,” repeated bits of DNA at the end of chromosomes that protect the chromosome from degrading.

    But presumably all that stuff is coded for in the DNA sequence, right? Or else it would qualify as stably heritable epigenetic information, which you have assured us does not exist.

    So in principle a complete Neanderthal genome (should we be able to piece one together) would contain its own instructions for packaging it into chromosomes, would it not? (I grant that carrying out those instructions might be a serious technical challenge well beyond the current state of the art.)

    • whyevolutionistrue
      Posted January 27, 2013 at 2:30 pm | Permalink

      No, I don’t think so. If you put the entire genome in one big string into a cell, it wouldn’t know to put itself into, say 23 chromosome if it were a human. It would just stay there, inert. Ultimately things like histones are coded for by the DNA, but I don’t think that something like chromosome number and configuration is. The DNA would, for one thing, have to know where to cut itself in the right places for form the proper number of chromosomes.

      • Gregory Kusnick
        Posted January 27, 2013 at 2:58 pm | Permalink

        Sorry, I guess I wasn’t clear. By “a complete genome” I mean the entire DNA sequence of each Neanderthal chromosome, including telomeres. After all, we have this sort of information for the human genome, don’t we? We know which genes are on which chromosomes, and in what order. Why shouldn’t the same info be available for the Neanderthal genome, assuming of course we can find enough fragments of DNA to cover the whole thing.

        I certainly didn’t mean to suggest we should splice all those fragments together into one long string and see what happens.

  27. Thanny
    Posted January 27, 2013 at 2:59 pm | Permalink

    The chromosome problem certainly rings true, but much of the rest would seem to be belied by the work Craig Venter’s company has done.

    They synthesized a bacterial genome in chunks, joined the pieces together in order, then stuck the lot into another bacterium which had its own genome removed.

    Then there’s a bit of question begging. Just how important is the chromosomal structure? Sure, a mismatch often causes partial or complete infertility with sexual reproduction. But is the exact chromosomal structure really important for somatic development?

    I think we can be sure, however, that no one could simply decide to do this, whatever the cost, and have results in only a couple years. There’s a lot of basic bioengineering that needs to be mastered first, which is really the main point Jerry is making (as I see it, quite correctly).

    • whyevolutionistrue
      Posted January 27, 2013 at 3:03 pm | Permalink

      Not at all: most bacteria have a single long strand of DNA: in effect, just one “chromosome”. It’s a lot easier in bacteria because you just join the bits in order, and a lot easier to determine the complete DNA sequence.

      • gillt
        Posted January 27, 2013 at 8:41 pm | Permalink

        I would be interested to know your impression on this method then Jerry, since it’s how George Church said he would attempt cloning a Neanderthal and you didn’t address it.

        MAGE Tech
        http://www.biosciencebridge.com/?q=node/47

  28. Posted January 27, 2013 at 4:00 pm | Permalink

    There are two things that people treat like magic pixie dust these days: computers and genetics. The first will give us the nerd rapture and brain uploading, the second immortality and designer organisms.

    Not surprised about the Spiegel here; that magazine is seriously overrated in my country of origin…

  29. Roo
    Posted January 27, 2013 at 4:56 pm | Permalink

    1. You are rilly, rilly smart Jerry.

    2. I am crushed that I cannot clone Miss Pretty Paws as planned.

    3. My fast-cash plan to sell myself as a neanderthal surrogate mother and retire early is shot to heck.

    That is all.

  30. wildhog
    Posted January 27, 2013 at 6:32 pm | Permalink

    So what does this mean for my plan to pump the stomach of someone who just took the Eucharist, extract Jesus’ DNA, and make a clone of him?

    • Mark Fuller Dillon
      Posted January 27, 2013 at 9:44 pm | Permalink

      It could work.

      No, really, it could work.

      By golly gumdrops, it could work!

      • pjie2
        Posted February 12, 2013 at 4:56 pm | Permalink

        I had a story outline along those lines. Started from the premise that the Transubstantiation isn’t literal, but that the Host only “becomes” Jesus when it’s digested and gets incorporated into DNA.

        So, radiolabel the Host, track it and see where it ends up. If the person consuming the Host is heterozygous for a given variant, then the radiolabelled carbon will get preferentially incorporated into the holiest allele.

        Punchline was when the scientists unveil a bunch of water-walking rodents. Got to try it in an animal model first, you see.

  31. Jim Thomerson
    Posted January 27, 2013 at 7:25 pm | Permalink

    Years ago, I read an SF story. It starts with this heavyset fairly ugly guy being sworn in as World President, swearing to uphold the Consitution which he wrote. He has several Nobel Prizes, Won all the Superbowls he played in, and holds the world records for discus, shotput, javalin and various weight lifting categories, and is the richest man in the world.

    He is a Neanderthal. Time travelers took him as an infant and raised him. The explaination of his success is that he came from a time when humans were under really intese natural selection.

  32. Dominic
    Posted January 28, 2013 at 3:16 am | Permalink

    This article from last week explains the problem of creating identical clones – may be of interest…
    http://sciencenordic.com/does-perfect-clone-exist

  33. Anders
    Posted January 28, 2013 at 5:23 am | Permalink

    Thats what I thought, I tried contacting PZ a while back when Michio Kaku babbled about biology and cloning (a subject he seems to know nothing about) on Big Think: http://bigthink.com/ideas/47438

  34. @eightyc
    Posted January 28, 2013 at 7:45 am | Permalink

    wait.

    so we can’t clone jesus?

  35. Jim Mauch
    Posted January 28, 2013 at 8:05 am | Permalink

    I vaguely remember a biologist asking the question that if we actually could pull off the sci-fi feat of cloning a Neanderthal would’ve send the specie to a zoo or to Harvard.

    • Diane G.
      Posted January 28, 2013 at 6:42 pm | Permalink

      ” . . . to a zoo or to Harvard.”

      Tough choice…

  36. Posted January 28, 2013 at 8:44 am | Permalink

    I gotta disagree. If they can make a bacterial chromosome, they can make eukaryote chromosomes sooner or later. Reconstructing extant critters from DNA sequence will be a first step.

    With extinct ones – sure, we have more issues. Quality of the reference genome is a biggie, and more so with the neanderthal than some others (that’s a big genome, for starters! And it’s hard to pick out human contamination, as you say). But we can figure out where the chromosomes and telomeres go from characteristic repeats (and we can guess about how many repeats there should be from extant related organisms).

    Yes, we need to improve our understanding of chromatin modification and methylation. I would say that was the single biggest obstacle right now. But I would give it till the end of the decade at most. My feeling is that most of it will turn out to be predictable by raw sequence, and probably mostly from coding sequence. The bits that are environmentally modifiable – well, presumably you still get a viable organism either way.

    Of course, if you really want to clone an extinct organism, just tell Craig Venter that it can’t be done…

    • pjie2
      Posted February 4, 2013 at 5:22 pm | Permalink

      Fundamentally we don’t have, and will never have, the correct Neanderthal genome (or even *a* correct Neanderthal genome).

      What we have is a lot of very short reads of Neanderthal DNA which then get assembled using the reference modern human sequence as a template. Even if the reference sequence were perfect, which it’s not, you still have a Neanderthal peg that’s been hammered into a modern human hole. Structural differences won’t and can’t be picked up by this kind of sequencing technology.

    • Posted January 28, 2013 at 11:29 am | Permalink

      Duh! I shoulda thought of that…

      To make a viable organism that way would still run into the problems with DNA modification though. I also foresee problems with things like transposon silencing, if we’re not sure we have all the non-coding DNA and repeats sequenced correctly (as with the neanderthal genome). Not insurmountable, but there.


2 Trackbacks/Pingbacks

  1. [...] But as far as cloning dead things, well there are some problems (as Jerry Coyne points out): [...]

  2. […] are able to successfully clone a Neanderthal from reassembled DNA. There are quite a few technical hurdles to this, but if it happens, and the Neanderthal baby is born and grows successfully to adulthood in […]

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