Monday, October 14, 2024

De-Extinction and the Resurrection of the Woolly Mammoth



To start with, using the elephant genome, we begin with a full 99% of the DNA.  Obviously huge.  We then identify snips of DNA from remains and use CRISPR to insert.  It will still be long and time consuming, but also doable.

In fact, it should be possible to restore the entire Pleistocene Menagerie and maintain them in refugia.

I do think we need the mastodon and the mammoth in particular as they can assist us in forest management using proper husbandry.


De-Extinction and the Resurrection of the Woolly Mammoth

Woolly mammoths may be coming back by 2028. The dodo could plausibly follow. But how does "de-extinction" work? And is it wise for humanity to try to bring species back that have been lost to history?


Brian Klaas

Oct 07, 2024

https://www.forkingpaths.co/p/de-extinction-and-the-resurrection?

In 2028, if all goes according to plan, a six foot five narcoleptic scientist with a bushy white beard will resurrect the first living woolly mammoth in 4,000 years. And that mammoth—if the science works—may soon be lumbering, in all its hairy glory, across the frozen plains of North Dakota.


This is the story of the science, the ethics, and the risks and rewards of the emerging field of de-extinction—the revival of species that no longer exist.


Humans may soon be able to bring species back from the dead. But should we?


I: Unlocking the Ancient Secrets of the Permafrost

About fifteen years ago, a brilliant scientist named Beth Shapiro was in the Canadian Yukon, nearly 2,000 miles northwest of Vancouver, extracting bones from the permafrost.


Gold miners, hoping to access metal-rich gravels underneath the long-frozen soil, were deliberately melting the permafrost, producing runoff and exposing that which had long been hidden from human eyes. But Shapiro didn’t care about the gold. She cared about something much more valuable to her: prehistoric DNA, locked away in bones impeccably preserved in the frozen earth.


Perched next to a big pile of frozen dirt, holding an enormous shovel, Shapiro looks into the camera and records the moment.


“What we’ve just found—you can see—is one, two, three, four pieces of mammoth bone here. This is part of a vertebra,” she says, while holding a bone the size of her head. “And the neat thing about this is that these are the small pieces.” Smiling, she claps her hand on the real prize, hidden within the mound of earth behind her. “These pieces are still frozen in the permafrost. We can’t get them out at all, which means they’re going to be really well preserved.”1


That pristine quality mattered because Shapiro was not just hunting for mammoth bones. Instead, as one of the world’s leading experts on ancient DNA, Shapiro was searching for specimens of those little snippets of A’s, T’s, G’s, and C’s that can let scientists like her glimpse biological history that had previously been beyond the realm of what we could know about the distant past.


A few years later, in 2015, Shapiro wrote How to Clone a Mammoth, a tantalizing examination of how modern scientific breakthroughs are taking the fiction out of science fiction. She chronicled how researchers were bringing human ingenuity to the cusp of a task previously imagined only for gods: resurrection.


But even though Shapiro could see that de-extinction was on a trajectory to become technically feasible, she warned of the potential pitfalls, the ethical minefields, and the ecological unknowns. Woolly mammoth de-extinction, she said, “is something that we should not do”; calling it a “terrible idea”; and suggesting that the notion of using living elephants as surrogates to usher woolly mammoths back to Earth was a “crazy, hare-brained scenario.”2


Now, a decade later, Shapiro has clearly changed her mind. She’s the chief scientist for a well-funded, cutting-edge startup called Colossal Biosciences, the brainchild of Harvard’s genomics wizard, George Church—the six foot five narcoleptic—and Ben Lamm, a serial entrepreneur working on the most ambitious project of his life. And Lamm, who has raised hundreds of millions of dollars on a flagship idea, that “crazy, hare-brained scenario” of using elephants to give birth to a mammoth, believes that we are only a few years away from once again seeing those majestic creatures walk the Earth.


II: Filling in the Gaps: A Reverse Jurassic Park

In the 1993 film Jurassic Park, scientists extract dinosaur DNA from blood trapped within mosquitoes encased in amber (all of which is scientifically impossible).3 But, according to the film, because the “Dino DNA” is imperfect and incomplete, they successfully fill in the gaps with frog DNA (never mind that birds, not frogs, would be the obvious choice). Though that Hollywood “science” was fanciful mumbo-jumbo, it turns out that inverting the central idea of Jurassic Park is becoming increasingly feasible.


Instead of taking a degraded, incomplete extinct genome and filling in the gaps with a living species, the reverse is more plausible: take a living species and splice in the most crucial bits from the extinct genome instead. In other words, it’s much harder to try to create a woolly mammoth from scratch, only filling in the gaps with elephant DNA. It’s much easier to take an elephant genome and—using a powerful technology called CRISPR—insert bits of mammoth DNA.


If you were to do that systematically, replacing the key parts of the genome that separate living elephants from extinct mammoths, it’s suddenly not so far-fetched. Rather helpfully, it turns out that because Asian elephants shared a common ancestor with woolly mammoths several million years ago, there’s a 99 percent overlap in their genome, demanding fewer CRISPR snips. We can now easily imagine that a mammoth-like elephant could soon be forged in the lab, then birthed into the real world.


III: The Vision

Imagine this: herds of mammoths grace the frozen steppe, trampling trees while reviving lost grasslands, helping to keep massive stores of carbon safely locked away in the permafrost. Their return regenerates a lost ecosystem, turning wastelands into wildlife havens. And, thousands of miles away from those hairy herds, the science used to create these enormous beasts is being used to protect vulnerable species from extinction and to save human lives.


There is undeniably a certain magic to the notion of humans bringing species back from the dead, a romance to recreating a glimpse of our ancestors’ forgotten world. But the emotional fantasy is not a strong enough justification for de-extinction. Many scientific manipulations of the natural world would be cool. Few are good ideas.


But let’s start with the positives: de-extinction does, by my count, have four strong arguments in its favor.


First, any successful de-extinction would require breakthroughs that, if carefully applied, could significantly boost conservation efforts of existing but endangered species. These wouldn’t replace existing conservation efforts—which are urgently needed—but could enhance them.


For example, it wouldn’t be far-fetched to greatly expand the potential habitat of elephants by tweaking a gene to allow them to comfortably inhabit colder climates, expanding their geographic range. Or, with climate change, similar interventions could help make species more resilient that are dying out because the planet is heating up. Conservation ecology faces a potential cataclysm, and a targeted new tool to save species by making them more resilient to a changing planet could be essential to staving off ecological collapse.


Second, unexpected and transformative scientific innovation often emerges from directed problem-solving. For example, the urgency of vaccine research during the covid-19 pandemic continues to pay dividends in the broader field, as researchers announced last week that they were closer to developing a vaccine to prevent ovarian cancer. One of the researchers acknowledged that their breakthroughs were made possible by the surge of funding, interest, and intense problem-solving needed to tackle the emergency challenges of the 2020 pandemic.


Similarly, it is probable that a well-funded, collaborative effort to bring back mammoths would revolutionize scientific research in ways that have significant spillover benefits within the fields of genomics. Those innovations are likely to be applicable to human health, meaning that it is not just plausible but likely that de-extinction of woolly mammoths could save future human lives.


Third, the reintroduction of key species—like woolly mammoths—can create ecological cascades that regenerate ecosystems with surprising speed. In the vast Arctic expanse of northeastern Siberia, 2,200 miles northeast of Mongolia, there is an experimental nature reserve known as Pleistocene Park. No mammoths, yet, but there are plenty of Ice Age-era animals, or their close proxies: moose, reindeer, bison, musk oxen, yaks, Bactrian camels, Yakutian horses, and the Orenburg fur goat.


The regenerative aspects of the park have been astonishing, though it is widely believed that mammoths would be particularly transformative to the ecosystem. (Currently, the park tries its best to mimic mammoth trampling by driving a large construction vehicle around, nicknamed “the baby mammoth”).



An artistic rendering of a typical Pleistocene ecosystem, with mammoths, cave lions, wild horses, reindeer and woolly rhinos.

In other contexts, it has become clear that the reintroduction of a single key species can have cascading effects, unleashing the natural potential of an area through a series of positive feedback loops. As I explained in Fluke:


In 1995, gray wolves were reintroduced to Yellowstone National Park. It triggered an unexpected trophic cascade, in which the entire ecosystem adjusted abruptly due to this comparatively small change.


Without wolves, elk in the park didn’t need to move much to avoid predators, so they stayed put and munched on willow plants. When the wolves returned, the elk began to move more, eating a more diverse diet, allowing the willow plants to recover. That presented new opportunities for beavers, who had dwindled down to a single colony. Soon, with renewed willow, nine beaver colonies thrived. The rise in beavers changed the streams in the park, boosting the ecosystem for fish populations. The cascade went on and on, and nearly three decades later it’s still only partly understood. And it all began with thirty-one wolves being released into the park in 1995.


Some scientists believe that mammoths could serve a similar role in their ecosystem. However, another possible impact of mammoth resurrection is their most surprising: they could play a role in the urgent fight against climate change.


The reason is somewhat counterintuitive. Mammoths knock down trees. Trees, generally speaking, help mitigate climate change. But in this one context, trees living in Arctic areas covered with permafrost are accelerating climate change. That’s because a tree takes in a lot more energy from the sun than grasses do. In the process, trees make the soil comparatively warmer, which speeds up the melting of the permafrosts underneath. That’s devastating news, because the permafrost contains 1.5 trillion metric tons of carbon—which is “twice as much as Earth’s atmosphere currently holds.” These permafrosts have been likened to the “sleeping giant” of the climate system; we’d be in big trouble if they wake up.


As Paul Mann writes, resurrected mammoths could keep them dozing safely:


This is where our shaggy friends may come in. Mammoths and other large herbivores of the Pleistocene continually trampled mosses and shrubs, uprooting trees and disturbing the landscape. In this way, they inadvertently acted as natural geoengineers, maintaining highly productive steppe landscapes full of grasses, herbs and no trees.


However, innovative ideas always come with risks. De-extinction is no exception. And aside from this scientific hype possibly being too good to be true, there are serious critiques of Colossal Biosciences and the wider de-extinction movement that can’t be easily brushed aside.


IV: The Skeptics

Previously, I’ve explained why, as a general rule, it has served me well to be suspicious of billionaires. Similarly, as a general rule, it has served me well to be suspicious of glitzy start-ups that make ambitious promises about changing the world. Doubly so if the co-founder’s previous experience was largely forged in mobile software and digital gaming, producing such humanity-improving gems as “Shark Punch”—and if the high-profile financial backers include cartoon villain billionaire Peter Thiel, alongside Paris Hilton, self-help guru Tony Robbins, and rich scions who believe that the blockchain will solve everything.


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But targeted investment can spur progress. Speaking in 2015, Beth Shapiro described how de-extinction research was a land of creeping innovation, doing the best they could “on the budgets that they have, which is zero.” At the time, she noted, “all of this work is being done in the back corner of somebody’s lab.” Now, Shapiro, an eminent professor at UC-Santa Cruz—complete with a tattoo of the extinct Dodo—is overseeing scientific research within a commercial venture that has already raised a quarter of a billion dollars in funding.4


Money helps, of course, but it doesn’t solve every problem. And there are serious problems.


Some critics dismiss Colossal’s slick website and confident ambition as hype. It’s not going to be a real mammoth, they say, just a hairy cold weather elephant. Others suggest that the claimed climate benefits are outlandish fantasy. After all, you’d need thousands of mammoths to achieve the desired effect, and given that Asian elephants usually produce one baby during a gestation period that lasts 22 months, even the most ambitious targets for producing herds are a long way off. Meanwhile, climate change demands urgent action, not speculative longshots. Fair enough. But far from disqualifying.


Then, there are those who doubt that it’s possible to produce a viable mammoth from an Asian elephant. In March, Colossal’s scientists overcame a significant technical hurdle, but many more lie ahead.


Others fear that the funding for initiatives like de-extinction will harm rather than help the ecosystem. Perhaps the glamor of a start-up that’s promising a big ticket resurrection could siphon money away from less glamorous conservation efforts that use proven methods. (This strikes me as plausible, but not overly convincing. Because Colossal has attracted funding from non-traditional sources, including obscenely wealthy celebrities, it’s unlikely that they’re taking money that would have otherwise flowed to, say, habitat preservation efforts).


There is, alas, a more potent version of that critique: concern that creating the impression that extinction is reversible could undermine the urgency to save existing species. After all, if we can bring mammoths back, perhaps some will worry less about the finality of losing the Javan Rhino or the Amur Leopard.


But the most serious problems aren’t technical, nor are they about our attitudes toward living species. Instead, the worries that give me pause, the ones that make me tempted to side with 2015 Shapiro over 2024 Shapiro, aren’t about the science. They’re about the ethics—and the vast, impossible thickets of unknowns that emerge when humanity begins to tamper with unimaginably complex natural systems that we only partly understand.


V: The Gasping Bucardo and The Non-Identity Problem

Twenty-four years ago, the world’s last bucardo—or Pyrenean ibex—was moving across a mountainous landscape in a Spanish national park. Researchers had realized she was the last of her kind, the final living remnant of her species. Alberto Fernández-Arias, a wildlife veterinarian, put a tracking device on her and named her Celia.


Shortly after the dawn of the new millennium, on January 6th, 2000, Celia was found crushed to death by a tree that had toppled onto her. Her species was gone.


Researchers were able to preserve Celia’s cells. And unlike mammoths, the recency of the bucardo—and the close proximity of other similar species—meant that the technical challenges of resurrecting Celia seemed much less daunting.5 She could be cloned. Three years later, after 57 failed attempts, a goat carried a baby bucardo to term, the world’s first successful case of de-extinction.


But it was not a happy ending. Celia’s clone, the baby bucardo, died seven minutes after entering the world. As Carl Zimmer explained:


“As Fernández-Arias held the newborn bucardo in his arms, he could see that she was struggling to take in air, her tongue jutting grotesquely out of her mouth…A necropsy later revealed that one of her lungs had grown a gigantic extra lobe as solid as a piece of liver. There was nothing anyone could have done.”


With this suffering, Heather Browning of Australian National University argues that de-extinction presents significant risks to animal welfare, both in terms of the individual animal conjured back into existence, and with the surrogate mother giving birth to a mutant baby of a different species. (Just imagine how you’d feel after a long, difficult pregnancy if your baby turned out to be a chimpanzee).


We are not yet masters of this fledgling technology, and it’s likely that the early incarnations of mammothified elephants would go badly. Even though Colossal employs some of the world’s best bioethicists and takes these concerns extremely seriously, they’re probably unavoidable and must be weighed up against the potential benefits that would come from potentially more disturbing stories than the botched birth of Celia’s bucardo clone.


These ethical minefields are reminiscent of the late philosopher Derek Parfit’s non-identity problem, or the paradox of future individuals, in which he grapples with how we should consider the rights of living organisms that do not yet exist. Should we repeatedly bring life into the world even if it’s only going to experience it for seven excruciating minutes? How many botched attempts are “worth it,” if we can later give rise to successful de-extinction—and potentially transformative breakthroughs in human health along the process? Is it justifiable to put an elephant through childbirth only to experience the potential trauma and anguish of rejecting its own young as an unnatural alien species? (Of course, humans deliberately kill about 900,000 cows per day, which puts Celia’s tragic clone or an elephant’s mental anguish into some perspective).


However, humanity is also prone to a cognitive trap known as status quo bias, in which the way the world is can feel like the way the world should be. We live in a little snapshot of the natural world which is unlike most other periods in history. What makes our era uniquely “correct,” worthy of being frozen in place as it is? This skepticism gives rise to the reversal test, in which we imagine the opposite of a proposition to be true, allowing us to test our intuitions more clearly. For example, imagine if woolly mammoths already existed and there were only five living specimens left. What would we be willing to do in order to save them? And should we therefore apply the same ethical threshold to bring them back?


But the most fundamental peril—the one that calls into question the mission of de-extinction—isn’t about ethics. It’s about catastrophic risk.


VI: Unknown Unknowns and the Illusion of Control

Throughout my writing, but particularly in Fluke, I have warned against what I call the illusion of control, in which humans discount catastrophic risk because we wrongly believe we can fully understand and tame an unruly universe.


The de-extinction movement is meddling with two realms that we can never claim to understand: the ecology of complex ecosystems and the lingering secrets of the genome’s expression into life. While recent scientific breakthroughs have brought us heady glimpses of the inner workings of both—and much of our food has already been genetically modified—we still don’t fully understand gene expression. With a newly lit candle, we’re feeling our way around an exciting expanse of darkness. But ignorance, when taken seriously, offers a warning.


One of history’s worst calamities was unleashed by a well meaning plan to deliberately alter nature, with the aim of saving human lives. As I wrote in Fluke:


When we try to assert our control over complex systems, much can go wrong. China, under Mao Zedong, found this out the hard way. Mao didn’t understand that nature’s ecology is complex—untamable and sensitive to changes to even a few species. During the Four Pests campaign, China’s dictator ordered citizens to kill rats, flies, mosquitoes, and sparrows. He hoped it would help eradicate human disease. But when the sparrows were wiped out, locusts no longer faced a natural predator. It contributed to unexpected ecological havoc, as the locusts took over. The ensuing famine left as many as 55 million people dead.


What was the slogan of that doomed campaign? “Ren ding sheng tian,” which means “man must conquer nature.”


While it’s unlikely that a single test mammothified elephant will wreak inexplicable havoc, tampering with genes and ecosystems is a dangerous game. There will be unintended consequences. (Already, one rogue Chinese scientist has created two human babies that were gene-edited). Once we go down this road, abuses will inevitably follow.


De-extinction therefore has significant potential benefits, but the long-term trajectory of this research is laced with catastrophic risk from what Donald Rumsfeld called “the unknown unknowns”—the potential disasters we can never successfully avert because we can’t even imagine that they might exist. Colossal Biosciences is entering uncharted territory, and we simply cannot know how it will unfold, for better or worse. It’s a classic case of “radical uncertainty.”


Of course, through ongoing climate change and mass extinctions caused by humanity, we’re already tampering with forces beyond our knowledge or control. In other words, we are conducting a grand and dangerous experiment either way; the difference with Colossal, they might retort, is that it’s being done with at least a serious, thoughtful attempt at mitigating risk.


These intractable dilemmas are why some scientists, such as the paleontologist Tori Herridge, suggest that the limits constraining such seismic changes in our relationship with the natural world should be decided by the public, not by opaque start-ups backed by the rich and powerful. Money, after all, sways minds. Or, as Andy Lamey concluded: “Maybe someday mammoths should once again rule the earth. Mammon, though, is a different story.” 


VII: Resurrection?

Despite these significant ethical concerns and risks, it would be an extraordinary feat of human intelligence and ingenuity to resurrect that which has been lost from the face of the Earth.


If humanity can achieve safe and sensible de-extinction, whether through Colossal or not, there is no time like the present. We are careening toward an era of cataclysmic species loss. Bolstering our toolbox with cutting-edge genomics research to help us conserve what we already have may, paradoxically, be the greatest legacy of de-extinction, using an attempt at bringing back the dead to help keep existing species—maybe even including ourselves—alive.


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1

Shapiro notes that they could collect up to 30 bags of bones every day during that collection process, but that most were from bison. So abundant are bison bones in the permafrost that one of her colleagues took to calling bison the “cockroaches” of the Pleistocene (the period that includes the last ice age and lasted from 2.6 million years ago until about 11,700 years ago). She describes this—and shows the video in the Yukon—in this talk, available on YouTube.


2

In April 1984, a report in the Chicago Tribune noted that “in the Soviet Union, Dr. Sverbighooze Nikhiphorovitch” had successfully created a mammoth-elephant hybrid. It turned out the journalist had read an April Fools gag from the MIT Technology Review, failed to note the date, and reprinted it; it ended up widely circulated across the United States in various well-respected newspapers.


3

The oldest specimen of DNA ever extracted is around two million years old. It was discovered in 2022. Still, that’s a far cry from the minimum 66 million years of preservation that would be needed to sequence dinosaur DNA.


4

The Dodo is one of the several species that Colossal says it hopes to bring back.


5

This used cloning, a scientifically different process than what Colossal is trying. Cloning a mammoth is impossible. See Shapiro’s book for a more detailed explanation.

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