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“We May Resurrect The Mammoth Sooner Than You Think” by Lila Shapiro from the Huffington Post

December 20, 2015

“We May Resurrect The Mammoth Sooner Than You Think”

12/18/2015

COURTESY OF LONGNOW.ORG

Of all the varied and incredible possibilities presented by the controversial new gene-editing technique known as CRISPR-Cas9, perhaps the most intriguing are efforts to bring animals back from extinction. Candidates for de-extinction, as the process is known, include species like the passenger pigeon (the last one died in captivity in 1914), the dodo (last seen in 1662) and the sea cow (1768, a mere 27 years after it had been discovered by Europeans.)

These projects are not pipe dreams. 

Dr. George Church, a molecular biologist at Harvard University who is working on such projects, estimates that a variation of the first new woolly mammoth (which disappeared some 4,000 years ago) may be born as soon as seven years from now. Like other proponents of de-extinction, he hopes the animals will play a key role in slowing or reversing climate change. 

If you’ve seen “Jurassic Park” (and is there anyone who hasn’t?), you’re already familiar with the basic idea behind how it would work. First, scientists would retrieve DNA from the frozen remains of a woolly mammoth that was preserved for centuries in the frozen tundra. Then they would splice that DNA into an Asian elephant genome — a step that Church’s lab completed earlier this year. The two species are so closely related, Church said, that if mammoths were alive today, they could successfully breed with elephants. If Asian elephants’ DNA were tweaked to more closely resemble that of their ancient relatives, they might be able to give birth to a furrier, fattier hybrid.

A month after Church’s lab announced its gene-splicing success, an international group of scientists published a paper showing they had sequenced the woolly mammoth’s entire genome, drawing a “road map” for changing an Asian elephant’s chromosome to make it more mammoth-like. With CRISPR, making those changes is faster, cheaper and easier than ever before. The method allows researchers to change, delete or replace genes in any plant or animal (picture the precision and ease of the find-and-replace function in a word document).

Church and other scientists in the field say this work is decidedly not about creating Mammoth Park. The hope is that these “cold-adapted Asian elephants” will be capable of repopulating the vast tracts of tundra and boreal forest in Eurasia and North America, a goal they feel will help protect endangered Asian elephants and at the same time revive an ancient grassland in the tundra, which could prevent the melting of Siberia’s permafrost.

Of course, the project is not without its critics. Duke University conservation ecology professor Stuart Pimm called the idea “molecular gimmickry” in an opinion piece for National Geographic. 

“At worst,” he wrote, “it seduces granting agencies and university deans into thinking they are saving the world. It gives unscrupulous developers a veil to hide their rapaciousness, with promises to fix things later. It distracts us from guaranteeing our planet’s biodiversity for future generations.”

The Huffington Post caught up with Church to talk about the potential for de-extinction efforts to help delay climate change, the ethical quandaries inherent in the work and his response to the critics. This interview has been edited for clarity and length.
What’s the latest in the world of de-extinction?

The way we’re framing it these days is we’re bringing DNA back from the past to improve modern survival and diversity. So rather than bringing a whole species back, you can augment current-day species. Because in practical terms, you have to have a modern-day host anyway, so you might as well help that host while you’re at it.

My favorite example is the Asian elephant. It has two big threats to its existence — it’s going extinct, just like the mammoth did, and it’s mainly because humans are exacerbating all of its other problems. 

The whole point of the project is merging modern molecular techniques with environmental conservation projects. So, for example, bringing back alleles from the mammoth, just bits of DNA, that can make the modern species compatible to cold. 

COURTESY OF LONGNOW.ORG
Building a mammoth out of an Asian elephant begins with three major adaptations.

So how does it work? If you do bring the woolly mammoth genes into the elephant, would it just naturally migrate to northern territories?

The precedent is the bison. The bison was essentially extinct worldwide, with just a couple hundred left, so you needed a plan that included land all over Russia, Europe and North America. And now there’s 500,000 of them, so ranchers and conservational land and so forth can accommodate the bison. It will probably be even easier for the mammoth, because it’ll be even further north, where there are even fewer people and fewer demands on the property. It’s not like we’re going to build a city or a factory in Siberia.  

And it would help the environment — it would help restore the rich ecosystems that are based on woolly mammoths and grass, rather than what many ecologists consider a much poorer ecosystem that we currently have, based on trees and moss.

Do you think these projects could be one of the keys to reversing climate change?

That’s going to be a multi-pronged effort. But this could be one of the major prongs, because the Arctic tundra has about two and a half times more carbon trapped in it than all the forests of the world put together. So if it melts, that carbon gets released. And if that gets released, it would be the equivalent of burning down all the forests of the world two times over.

So anything you could do to stabilize that would be good. In the case of the elephants, they’ve done experiments where they’ve set aside plots of land and do a treatment similar to what mammoths could do [to the habitat], using tanks or tractors to knock down trees and punch holes in the snow. This has resulted in a 15 to 20-degree lower soil temperature — and that would stabilize the carbon and buy us a few more decades of time to figure out other solutions.

What’s the history of the idea of reviving extinct species? 

First there was “Jurassic Park.” Then there were breakthroughs in DNA sequencing that allowed us to inexpensively decode ancient DNA as far back at 7,000 years. And now we have the exact DNA for these ancient species and, in some cases, we have appropriate hosts that are pretty close.

There were three steps. One was the basic idea, then the second step was new sequencing methods — some of these are things my lab helped develop — and the third step is new synthesis methods like CRISPR that allow us to test ideas that come out of the sequencing.

What was your reaction when you saw “Jurassic Park” back in the ’90s? Did you think it all looked possible?

I read Crichton’s book in 1990 and saw the movie in 1993. I was pleasantly surprised that the “dinosaur DNA” in the book was actually from a bit of bacterial DNA (not dinosaur DNA) that I worked on in 1978 as part of my Ph.D. thesis. By 1990, my lab was 3 years old and the idea of sequencing ancient DNA was 6 years old. The idea of genome engineering by homologous recombination in animal germ line was 1 year old.

It looked possible to me, especially since my lab was focusing on new technology for genome sequencing and genome engineering.  

How did CRISPR change the game?
CRISPR is about 1,000 times cheaper than previous methods, and that can change everything. It sounds like its just a quantitative difference, but it can result in whole new capabilities. We’ve made 15 different genetic changes already in the elephant genome using CRISPR. This would have been very hard to do prior to this.

And CRISPR is not the bottleneck anymore — it’s growing up the embryos and making sure that they’re developing normally. That’s the bottleneck.

Sergey Brimov, the Russian ecologist and a major proponent of de-extinction of woolly mammoths once wrote “All [that] is needed is to cross mental barriers.”

That’s almost always what’s needed.

Do you think we have a mental barrier when it comes to reviving extinct species?

I think there are some people whose job it is to cross barriers. I’m one of those people. We have to think out of the box in order to make new sequencing and synthesis methods, if nothing else. And in fact I’m a little less extreme in feeling that everyone has to think differently. Usually it’s sufficient that a few people think differently and then they work out the details so it’s a very compelling case.

I think the reason it’s hard to change people’s hearts and minds is that, until you have a few de-extinct mammoth DNA put into Asian elephants, and you can see that they are now woolier and better adapted to the cold and so forth, then you can say, “okay, now let’s scale it up.” And that’s the point you have to start convincing more people.

It doesn’t hurt to start talking about it now because it could be here much faster than it seems. Some of these technologies happen ahead of schedule rather than behind schedule.

What’s your estimate for when we’ll actually see the first woolly elephant?

CRISPR turned out to be easier than expected. The growing of embryos is harder to predict. I would say it will probably take us five years to work out the embryo development part, and then it takes at least two years to go through full gestation. So we might be seeing the first new baby elephants in seven years. Maybe a decade. That’s pretty soon.

What will we call them?

I call them cold-resistant Asian elephants. What are unambiguously woolly mammoths are the DNA we’re drawing inspiration from and literally moving from the computer back into Asian elephants. What the hybrid will be called will be up to popular decision making that’s outside of my realm. I’m not going to call them mammoths unless somebody insists. They’re elephants with mammoth DNA.

What do you think the biggest ethical issues are?

For me, it almost always it boils down to safety and efficacy, whether it’s a human medicine or some ecosystem intervention. For people first, and then other species a close second.

In this case some of the things that come up are, “Won’t they be lonely?” Well, the answer is, you make a whole herd of them, the way that was done with the bison — there are 500,000 bison. We could easily make tens of thousands of these elephants. Another question would be, hasn’t their environment disappeared? Isn’t the reason they died off still here? And I think the answer is, probably the northern part of Siberia is adequately cold. The fact is, it’s not too warm for the Asian elephants [in their current climate], it’s too cold for them. Are you harming the current endangered species? And I think our intention is to only help them.

What is your response to those who call this work “molecular gimmickry”? Or those who say this is a distraction from the work that needs to be done to protect the biodiversity that exists today?

Well, that’s a very vague critique. Here’s a very specific way of protecting the biodiversity in Asian elephants. If they have a better way of protecting Asian elephants, I’m all for it. We’re trying to reduce the loss of the babies to the herpes virus and we’re trying to give them cold resistance to expand their range. I don’t think that’s a distraction or a gimmick; that’s a goal.

The variation on that that I’ve heard is that this takes funding away, or it makes people think that they don’t have to protect current species because we can always bring them back. But the fact is we’re not bringing back species — [we’re] strengthening existing species. That may turn into full de-extinction in the future but only because it’s inexpensive and it has value. 

We’re not just saving the Asian elephants here. If the ecological experiments are correct, these are keystone species that are missing that would stabilize a whole variety of species, plants, microbes and animals, that are all dependent on the keystone species, which is, in this case, the mammoth. You can call them gimmicks if you want, but they’re goal-oriented environmental conservation strategies.

 

Lila Shapiro is a staff reporter at The Huffington Post. She is the 2013 and 2014 recipient of the National Lesbian & Gay Journalists Association’s Sarah Pettit Memorial Award for the LGBT Journalist of the Year. She previously worked at Talking Points Memo, editing TPMCafe. She lives in New York City and can be reached at lila@huffingtonpost.com. Follow her on Twitter @lilapearl.

Entries by Lila Shapiro

As any number of magazine articles and news stories from recent months have noted, we are in the midst of a major genetic revolution. Thanks to a gene-editing technique called Crispr-Cas9, it is now not only possible, but easy, cheap and fast, to change, delete or replace genes in any plant or animal, including people.

Scientists around the world have already used Crispr on a wide range of projects, from developing a kind of wheat that is invulnerable to mildew to stopping cancer cells from multiplying. This week, Scientific American shone a spotlight on China’s “bold push” into the world of genetically customized animals — and the mounting ethical quandaries that follow.

Using Crispr, scientists in China have created beagles with double the amount of muscle mass — the world’s first gene-edited dogs — as well as a new kind of goat, with bigger muscles and longer hair, among other Crispr-altered mammals. The work seems likely to rapidly expand. Minhua Hu, a geneticist at the Guangzhou General Pharmaceutical Research Institute and one of the beagle researchers, told Scientific American that genetically modifying animals is a priority area for the Chinese Academy of Sciences. Another geneticist noted that the Chinese government has allocated “a lot of financial support” for such efforts.

Humans have manipulated the genetic makeup of plants and animals for thousands of years. The beagle is already a product of human genetic manipulation. So are golden retrievers, cats, cows, the salad that you ate for lunch, and every other domesticated animal and plant. But Crispr is far more precise and efficient than any previous technique. As Arthur Caplan, a professor of bioethics at New York University School of Medicine, put it, “We used to have a butter knife, now we’ve got a scalpel.”

The ease and precision of Crispr is partly what fuels the ethical questions that accompany the technology. “Now it’s something that someone with a BS and a couple thousand dollars’ worth of equipment can do. What was impractical is now almost everyday. That’s a big deal,” Hank Greely, a bioethicist at Stanford University, told Wired.

Unlike earlier attempts at gene therapy, changes made with Crispr trickle down to future generations, potentially altering an entire species’ fate. This can have a cascading effect. For example, some researchers are trying to develop a mosquito that is both resistant to malaria and produces fewer eggs, a change that could cause the insects to become extinct. But if there are no more mosquitoes, what will happen to the bats that feed on them?

When Caplan first read a paper on Crispr two years ago, he was blown away by the possibilities. “As soon as I finished reading it, I thought, ‘Holy crap we’re going to have full employment for bioethicists.’”

Of the many ethical questions raised by the technology, one in particular stands out: When will we start using Crispr to make better babies?

China has made headlines in this arena as well. Last April, a group at Sun Yat-sen University published a paper announcing that they had used Crispr to edit human embryos to delete a gene linked to a blood disorder. The embryos were obtained from a fertility clinic, and couldn’t be carried to term. The experiment did not succeed, and, in part, showed how far away we are from using Crispr to create a so-called designer baby.

But Caplan predicts that once the science is firmly established, it will happen. “Everyone’s out talking about fixing diseases or making lab animals to fix diseases, but if you look at how interested people are in getting their kid into the right nursery school so they can get them into Harvard Business School — they’re going to be interested in how they can engineer their kid to be more successful,” he said. “Not next year, but boy that’s going to come quickly.”

Tailor-made pets will come first. Although China’s Crispr work on mammals has so far had mostly practical aims — for example, boosting goatherd incomes by increasing how much meat and wool each animal produces — one Chinese institute is planning to sell gene-edited tiny pigs as pets.

More examples are likely to follow, both in China and around the world. Want a unicorn? How about a chicken that is “de-evolved” to look more like a dinosaur? Scientists say it could happen. It’s easy to envision the dystopian possibilities. What’s to stop someone from creating the world’s most dangerous attack dog?

“I’m going to say, nothing,” Caplan said. As Caplan outlined in a paper recently, published in Embo Reports, there are almost no regulations of any kind in place to shape the way that scientists use Crispr on animals.

Next month, however, that could begin to change. On Dec. 1, the National Academy of Sciences will host a three-day international conference to discuss the scientific, ethical and political issues raised by human gene-editing with Crispr. And on Dec. 7 and 8, the Institute for Laboratory Animal Research will host a conference on the ethics raised by using Crispr on animals. (Caplan is leading sessions on ethical and regulatory issues at the conference.)

But Caplan isn’t betting that the international community will regulate the industry anytime soon. “It’ll take some disaster to do it,” he said. “Otherwise the tendency is to say ‘Oh well, we’ll see where it goes.’”

Lila Shapiro covers the science fiction of science, the imaginative ways scientists are trying to solve the world’s hardest problems. Tips? Email 

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