Evolutionary biologist Beth Shapiro studies ancient DNA. She’s published on the genetic makeup of woolly mammoths, passenger pigeons, and camels that once roamed North America. And in her new book, How To Clone a Mammoth, Shapiro, the associate director of the Paleogenomics Institute at the University of California at Santa Cruz, delves into the many technical hurdles and ethical concerns of attempting to revive extinct species.

In an interview with Yale Environment 360, Shapiro emphasizes that, despite the title of her book, if mammoths are ever brought back, it be won’t be through cloning, which requires a living cell. Rather, mammoth traits might be engineered into their closest living relative, the Asian elephant. And that technology, she says, might be best used to benefit the endangered elephant. What if these techniques can be used to engineer Asian elephants capable of living in colder climates, she wonders? “If we could do that,” she says, “then we could expand the range of potential habitat for Asian elephants.” And possibly, she says, save that species from going the way of the mammoth.

Beth Shapiro

Shapiro, a MacArthur Fellow, also points to gene editing technology as a way to insert lost genetic diversity (and therefore increased disease resistance) into small populations of struggling species such as the black-footed ferret. She admits there are inherent ecosystem risks to these approaches, but maintains they are worth it. “We are in the midst of an extinction crisis,” she says. “Why would we not use whatever technologies are available to us, assuming we can go about doing it in a reasonable and ethical way?”



Yale Environment 360: In your book you write that ecological resurrection, not species resurrection, should be the real goal of de-extinction. Tell me more about that.



Beth Shapiro: It’s not possible to bring a species back once it is gone. It’s not possible to bring a species back that’s 100 percent identical to one that used to be alive. We and every organism are much more than the sequence of our our genomes. We are a product of both our DNA sequences and the environment in which we live. Even if we could come up with a way to swap out all of the places in the genome of an elephant with the version of each gene that actually once existed in mammoths, we would not end up with something that was a mammoth. Being exposed to the hormones of an elephant mom if we’re a developing mammoth embryo, or being fed an elephant diet, or being raised by elephants is going to effect the expression of our DNA. For this reason and for ethical reasons, technical reasons, and ecological reasons, probably the best use of this type of technology is not to attempt to resurrect something that’s gone, but to try to revive and revitalize ecosystems that exist today.



e360: When you talk about ecological resurrection or restoration, let’s take the mammoth for instance, what does the mammoth do for us from an ecological perspective?



Shapiro: I don’t know, and I’m actually not sure that we really want to bring mammoths back. I think mammoths are a particularly problematic species because of the ethical challenges involved. If we were going to bring mammoths back we’re going to have to involve elephants in some way, at least the way the technology exists today. And we have very little idea of how to meet the physical and psychological needs of elephants when they’re living in captivity. Until we’ve figured out how to do that, we shouldn’t be having elephants in captivity at all, much less using them in hair-brained scientific creative experiments to bring back mammoths. Especially if we don’t really know what a compelling ecological reason to bring back mammoths might be.

What we are never going to have for a species that is extinct for a long time is a living cell.

So might we want to use de-extinction technologies to edit the genomes of elephants? Asian elephants are the closest living relatives of mammoths and these animals are endangered. What if we could use this same technology, in an ethical way, to engineer Asian elephants that were capable of living in colder climates? If we could do that then we could expand the range of potential habitat for Asian elephants, potentially biding our time so we could clean up the habitat where they belong to the extent we could figure out how to protect them there, and they could potentially be saved from extinction. These are the kinds of applications of this technology that I can see might be much more compelling than bringing back something like the passenger pigeon.



When we think about the passenger pigeon, one thing that one would need to do would be to show what role these animals played in the habitat when they were alive and that sufficient habitat exists, so that if we were to place them back in that habitat they would be able to survive. We would also need to be able to predict what interactions they’re going to have with other species that are also now fighting for a much smaller amount of habitat than when we had passenger pigeons around. This is the same kind of question we’ll need to ask for any candidate species for de-extinction.



e360: You emphasize that we will not be cloning mammoths in the way, for instance, Dolly the sheep was cloned.



Shapiro: Cloning is a specific scientific technology that involves taking a living cell from an animal and tricking that cell into reverting to the type of cell that’s capable of becoming every type of cell that makes up an organism’s body: lung cells, heart cells, brain cells, skin cells, whatever. This technology exists, it’s pretty powerful but it’s not particularly efficient. There are a lot of cells that are tempted to revert like this and very few that actually succeed. What it requires is a living cell. What we are never ever going to have for a species that is extinct and has been for a long time is a living cell. And so as long as we don’t have a living cell, we will not be cloning a mammoth.



e360: In your book, you discuss alternative methods using editing technology. Walk me through them.



Shapiro: The most likely way that one might consider bringing a mammoth back, or creating a mammoth that contains some mammoth-like traits, would be to use genome engineering technologies, the most powerful of which have been developed in the last couple of years is called CRISPR-cas9. What this would do would be to take a living cell, which in the case of a mammoth, would be an Asian elephant cell growing in a dish. And then if you could create a little robot that you could program to go to a very specific place in the genome, like a specific gene that you knew you wanted to change, and insert that robot into that cell living along with a piece of DNA, that would be the mammoth version of the gene that you want to change. The robot would go into the nucleus of the cell and find exactly that place in the cell that you programmed it to go to, cut the DNA there, and then replace that DNA that it cut with the mammoth version. So you could swap out elephant versions of genes for mammoth versions of genes. This robot exists, but it’s not anything that’s been synthetically created. Bacteria and archaea use it as a means of protecting themselves from getting sick from invading pathogens. They chop up pathogen DNA. We can use that technology to swap out pieces of the Asian elephant genome for the mammoth version of different parts of DNA.



‘Why would we not use whatever technologies are available to us, assuming we can go about it in an ethical way?’

e360: You point out in the book that de-extinction carries some risks. You talk about unintended consequences to ecosystems, unanticipated interactions between species. But it seems that in your calculus you’ve determined that not at least pursuing de-extinction is riskier. How so?



Shapiro: We are in the midst of an extinction crisis. We have tools at our fingertips that we could use to try to stop the mass extinction event that’s underway right now, but what we’re doing right now is not enough. My argument is that we need new approaches, we need new weapons in this arsenal we have. We are playing conservation triage, why would we not use whatever technologies are available to us, assuming that we can go about doing it in a reasonable and ethical way. We’re never going to be able to predict every single consequence of introducing something into a habitat, just like we can’t predict every consequence of what’s going to happen when an invasive species gets into a habitat. And then we can’t predict every consequence of what might happen if we remove that invasive species from the habitat. But if we don’t do anything, then the risk of losing everything that is there today is great. And I think that is a risk that we can’t deal with.



e360: David Ehrenfeld, the conservation biologist, worries that efforts to achieve de-extinction will take away from much needed traditional conservation efforts. He’s certainly not alone in that concern. How do you respond to that?



Shapiro: I completely disagree. I think that that statement assumes both something wonderful and something terrible about people. The wonderful thing that it assumes is that people generally care about extinction. I don’t think that’s true. I think for the most part your average everyday person doesn’t care about extinction inasmuch as it doesn’t affect them personally. And that’s horrible. Maybe this new technology, or a potential technical solution to this, could get a very small percentage more of people to care about it. And that would be a good thing. But the terrible thing that it assumes is that the people out there like me and like the people who are making these comments who do care about extinction are all of a sudden going to stop doing so if some far-fetched idea that doesn’t work becomes promoted enough by the popular press.



The other complaint that I also get is that it’s going to take money away from long-standing conservation efforts, and I also think that’s not true.

‘This might be a way of drawing new money into conservation from people who are technology-oriented.’

You can’t get people who care about saving the polar bear to give money to save frogs, and you can’t get money from people who want to save frogs to give money to people who care about the panda. It’s not like these people who have specific opinions about what the most important thing are all of a sudden are going to stop caring about those things if this crazy technology comes out. I think this might be a way of drawing new money into conservation, potentially from people who are very technology-oriented who haven’t really thought about the fact that there might be a technological solution to some of the problems that we’re facing.



e360: Ehrenfeld has also said that gene-editing technologies employed in the de-extinction science may be valuable to conservation by helping reintroduce genetic variation into small existing populations.



Shapiro: That’s exactly what I meant by the first question that you asked me, which was something about what do I see as environmental restoration. That’s it.



e360: What species that might first play out in?



Shapiro: The species that I always talk about is black-footed ferrets. This is a population that is very much in danger of going extinct. There’s a disease that’s killing them right now. They went through a very tight population bottleneck; they have almost no genetic diversity. It would be awesome if we could use this technology to look at black-footed ferrets that lived prior to the population bottleneck and isolate parts of their genome that provide resistance to disease and increase the diversity in that part of the genome in these populations. The biggest problem with the idea of genetic rescue is that we have very little idea about what genes do what in any species”¦.



We don’t know very much about this stuff, but fortunately we live in a time period where there’s a hugely growing resource of available genomes from different species for comparative analysis. We will get to the point where we know what genes provide what functions, or code for proteins that provide different functions. That is where the real wins in terms of genetic rescue will come.



e360: The science of de-extinction isn’t being done in a vacuum. For instance, there’s Revive and Restore, the organization backed by Stewart Brand and Ryan Phelan that supports de-extinction efforts. On the other hand after you gave a TED talk on your work you say you got hate mail. So what is the effect of such an emotionally-charged atmosphere on the work?



Shapiro: I think there’s a huge misconception about how much science is actually going on. In the back corner of George Church’s lab[at Harvard] they have a few people who are using a tiny amount of resources that are available to them to attempt to swap out genes in elephant cells which are growing in culture in a dish in a lab. I have a student who’s trying to convince me that it’s a good idea to bring passenger pigeons back to life. There’s a group in Australia who are thinking about the gastric-brooding frog but have stuck because they can’t cause the cells to actually grow up. There’s a group in New Zealand that is thinking about bringing a Moa [an extinct bird] back to life and are working on sequence the moa genome, which is not de-extinction, in itself. There’s a Spanish group that’s thinking about the bucardo [a subspecies of Spanish ibex that went extinct in 2000], and there’s the back-breeding group for the auroch [an extinct species of wild cattle] in Holland. That’s it. That’s everything that’s going on in the world right now.

‘There’s a huge misconception about how much science [on de-extinction] is actually going on.’

The reason that people hate me, the reason I get angry emails every time somebody hears a talk that I’ve given, is that people say if I would give just a small amount of the money that I’m getting for de-extinction to conservation then I could make a much bigger difference. I’m not getting any money, and I’m not actually doing any active de-extinction science in my lab. So they can have 100 percent of the money I’m getting and it still won’t make a dent in what they’re doing.



I don’t care that people get angry because I think that what we need in conservation is creativity. When people get worked up about something, whether it’s worked up in excitement like Stewart or Ryan or worked up in anger like some of the people who send me hate mail, these people are being more creative. The Revive and Restore group has brought together a whole bunch of scientists and conservation biologists who are interested in coming up with new plans to try to stop the ongoing extinction crisis. We might not be doing any hands-on science in the lab right now that’s directed at this, but this coming together of people who have new ideas and new ways of thinking, there’s no way they’re not going to contribute something great to conservation.



e360: A decade from now, where do you think de-extinction technology will have taken us?



Shapiro: I have absolutely no idea. It depends on what species you’re talking about, it depends on what regulations people decide to impose. Every species that’s a candidate for de-extinction has different technical, ethical, and ecological hurdles associated with bringing them back. With zero money invested in it, we’ll probably be about where we are right now.



I’m negative about de-extinction. If you want to interpret it as the resurrection of 100 percent identical copies of something that’s extinct, that is not possible. It’s kind of an imaginary construct, but it’s one that people can grasp. It’s much harder to sell people on the excitement of genetic rescue, even though that is definitely the more important implementation of the same technology. Even the listserv that Revive and Restore runs just changed its name from De-Extinction to Genetic Rescue. There’s clearly a turn in what this community views as the most important outcome from this work. The priority of this technology isn’t in anybody’s mind to bring an extinct species back to life. It’s to save species and ecosystems that are alive today from becoming extinct.