mammoths

editorial:-mammoth-de-extinction-is-bad-conservation

Editorial: Mammoth de-extinction is bad conservation


Anti-extinction vs. de-extinction

Ecosystems are inconveniently complex, and elephants won’t make good surrogates.

Are we ready for mammoths when we can’t handle existing human-pachyderm conflicts? Credit: chuchart duangdaw

The start-up Colossal Biosciences aims to use gene-editing technology to bring back the woolly mammoth and other extinct species. Recently, the company achieved major milestones: last year, they generated stem cells for the Asian elephant, the mammoth’s closest living relative, and this month they published photos of genetically modified mice with long, mammoth-like coats. According to the company’s founders, including Harvard and MIT professor George Church, these advances take Colossal a big step closer to their goal of using mammoths to combat climate change by restoring Arctic grassland ecosystems. Church also claims that Colossal’s woolly mammoth program will help protect endangered species like the Asian elephant, saying “we’re injecting money into conservation efforts.”

In other words, the scientific advances Colossal makes in their lab will result in positive changes from the tropics to the Arctic, from the soil to the atmosphere.

Colossal’s Jurassic Park-like ambitions have captured the imagination of the public and investors, bringing its latest valuation to $10 billion. And the company’s research does seem to be resulting in some technical advances. But I’d argue that the broader effort to de-extinct the mammoth is—as far as conservation efforts go—incredibly misguided. Ultimately, Colossal’s efforts won’t end up being about helping wild elephants or saving the climate. They’ll be about creating creatures for human spectacle, with insufficient attention to the costs and opportunity costs to human and animal life.

Shaky evidence

The Colossal website explains how they believe resurrected mammoths could help fight climate change: “cold-tolerant elephant mammoth hybrids grazing the grasslands… [will] scrape away layers of snow, so that the cold air can reach the soil.” This will reportedly help prevent permafrost from melting, blocking the release of greenhouse gasses currently trapped in the soil. Furthermore, by knocking down trees and maintaining grasslands, Colossal says, mammoths will help slow snowmelt, ensuring Arctic ecosystems absorb less sunlight.

Conservationists often claim that the reason to save charismatic species is that they are necessary for the sound functioning of the ecosystems that support humankind. Perhaps the most well-known of these stories is about the ecological changes wolves drove when they were reintroduced to Yellowstone National Park. Through some 25 peer-reviewed papers, two ecologists claimed to demonstrate that the reappearance of wolves in Yellowstone changed the behavior of elk, causing them to spend less time browsing the saplings of trees near rivers. This led to a chain of cause and effect (a trophic cascade) that affected beavers, birds, and even the flow of the river. A YouTube video on the phenomenon called “How Wolves Change Rivers” has been viewed more than 45 million times.

But other scientists were unable to replicate these findings—they discovered that the original statistics were flawed, and that human hunters likely contributed to elk population declines in Yellowstone.Ultimately, a 2019 review of the evidence by a team of researchers concluded that “the most robust science suggests trophic cascades are not evident in Yellowstone.” Similar ecological claims about tigers and sharks as apex predators also fail to withstand scientific scrutiny.

Elephants—widely described as “keystone species”—are also stars of a host of similar ecological stories. Many are featured on the Colossal website, including one of the most common claims about the role elephants play in seed dispersal. “Across all environments,” reads the website, “elephant dung filled with seeds serve to spread plants […] boosting the overall health of the ecosystem.” But would the disappearance of elephants really result in major changes in plant life? After all, some of the world’s grandest forests (like the Amazon) have survived for millennia after the disappearance of mammoth-sized megafauna.

For my PhD research in northeast India, I tried to systematically measure how important Asian elephants were for seed dispersal compared to other animals in the ecosystem; our team’s work, published in five peer-reviewed ecological journals (reviewed here), does find that elephants are uniquely good at dispersing the seeds of a few large-fruited species. But we also found that domestic cattle and macaques disperse some species’ seeds quite well, and that 80 percent of seeds dispersed in elephant dung end up eaten by ants. After several years of study, I cannot say with confidence that the forests where I worked would be drastically different in the absence of elephants.

The evidence for how living elephants affect carbon sequestration is also quite mixed. On the one hand, one paper finds that African forest elephants knock down softwood trees, making way for hardwood trees that sequester more carbon. But on the other hand, many more researchers looking at African savannas have found that elephants knock down lots of trees, converting forests into savannas and reducing carbon sequestration.

Colossal’s website offers links to peer-reviewed research that support their suppositions on the ecological role of woolly mammoths. A key study offers intriguing evidence that keeping large herbivores—reindeer, Yakutian horses, moose, musk ox, European bison, yaks, and cold-adapted sheep—at artificially high levels in a tussock grassland helped achieve colder ground temperatures, ostensibly protecting permafrost. But the study raises lots of questions: is it possible to boost these herbivores’ populations across the whole northern latitudes? If so, why do we need mammoths at all—why not just use species that already exist, which would surely be cheaper?

Plus, as ecologist Michelle Mack noted, as the winters warm due to climate change, too much trampling or sweeping away of snow could have the opposite effect, helping warm the soils underneath more quickly—if so, mammoths could be worse for the climate, not better.

All this is to say that ecosystems are diverse and messy, and those of us working in functional ecology don’t always discover consistent patterns. Researchers in the field often struggle to find robust evidence for how a living species affects modern-day ecosystems—surely it is far harder to understand how a creature extinct for around 10,000 years shaped its environment? And harder still to predict how it would shape tomorrow’s ecosystems? In effect, Colossal’s ecological narrative relies on that difficulty. But just because claims about the distant past are harder to fact-check doesn’t mean they are more likely to be true.

Ethical blind spots

Colossal’s website spells out 10 steps for mammoth resurrection. Steps nine and 10 are: “implant the early embryo into the healthy Asian or African elephant surrogates,” and “care for the surrogates in a world-class conservation facility for the duration of the gestation and afterward.”

Colossal’s cavalier plans to use captive elephants as surrogates for mammoth calves illustrate an old problem in modern wildlife conservation: indifference towards individual animal suffering. Leading international conservation NGOs lack animal welfare policies that would push conservationists to ask whether the costs of interventions in terms of animal welfare outweigh the biodiversity benefits. Over the years, that absence has resulted in a range of questionable decisions.

Colossal’s efforts take this apathy towards individual animals into hyperdrive. Despite society’s thousands of years of experience with Asian elephants, conservationists struggle to breed them in captivity. Asian elephants in modern zoo facilities suffer from infertility and lose their calves to stillbirth and infanticides almost twice as often as elephants in semi-wild conditions. Such problems will almost certainly be compounded when scientists try to have elephants deliver babies created in the lab, with a hodge podge of features from Asian elephants and mammoths.

Even in the best-case scenario, there would likely be many, many failed efforts to produce a viable organism before Colossal gets to a herd that can survive. This necessarily trial-and-error process could lead to incredible suffering for both elephant mothers and mammoth calves along the way. Elephants in the wild have been observed experiencing heartbreaking grief when their calves die, sometimes carrying their babies’ corpses for days—a grief the mother elephants might very well be subjected to as they are separated from their calves or find themselves unable to keep their chimeric offspring alive.

For the calves that do survive, their edited genomes could lead to chronic conditions, and the ancient mammoth gut microbiome might be impossible to resurrect, leading to digestive dysfunction. Then there will likely be social problems. Research finds that Asian elephants in Western zoos don’t live as long as wild elephants, and elephant researchers often bemoan the limited space, stimulation, and companionship available to elephants in captivity. These problems will surely also plague surviving animals.

Introduction to the wild will probably result in even more suffering: elephant experts recommend against introducing captive animals “that have had no natural foraging experience at all” to the wild as they are likely to experience “significant hardship.” Modern elephants survive not just through instinct, but through culture—matriarch-led herds teach calves what to eat and how to survive, providing a nurturing environment. We have good reason to believe mammoths also needed cultural instruction to survive. How many elephant/mammoth chimeras will suffer false starts and tragic deaths in the punishing Arctic without the social conditions that allowed them to thrive millennia ago?

Opportunity costs

If Colossal (or Colossal’s investors) really wish to foster Asian elephant conservation or combat climate change, they have many better options. The opportunity costs are especially striking for Asian elephant conservation: while over a trillion dollars is spent combatting climate change annually, the funds available to address the myriad of problems facing wild Asian elephants are far smaller. Take the example of India, the country with the largest population of wild Asian elephants in the world (estimated at 27,000) in a sea of 1.4 billion human beings.

Indians generally revere elephants and tolerate a great deal of hardship to enable coexistence—about 500 humans are killed due to human-elephant conflict annually there. But as a middle-income country continuing to struggle with widespread poverty, the federal government typically budgets less than $4M for Project Elephant, its flagship elephant conservation program. That’s less than $200 per wild elephant and 1/2000th as much as Colossal has raised so far. India’s conservation NGOs generally have even smaller budgets for their elephant work. The result is that conservationists are a decade behindwhere they expected to be in mapping where elephants range.

With Colossal’s budget, Asian elephant conservation NGOs could tackle the real threats to the survival of elephants: human-elephant conflict, loss of habitat and connectivity, poaching, and the spread of invasive plants unpalatable to elephants. Some conservationists are exploring creative schemes to help keep people and elephants safe from each other. There are also community-based efforts toremove invasive species like Lantana camara and restore native vegetation. Funds could enable development of an AI-powered system that allows the automated identification and monitoring of individual elephants. There is also a need for improved compensation schemes to ensure those who lose crops or property to wild elephants are made whole again.

As a US-based synthetic biology company, Colossal could also use its employees’ skills much more effectively to fight climate change. Perhaps they could genetically engineer trees and shrubs to sequester more carbon. Or Colossal could help us learn to produce meat from modified microbes or cultivated lines of cow, pig, and chicken cells, developing alternative proteins that could more efficiently feed the planet, protecting wildlife habitat and reducing greenhouse gas emissions.

The question is whether Colossal’s leaders and supporters are willing to pivot from a project that grabs news headlines to ones that would likely make positive differences. By tempting us with the resurrection of a long-dead creature, Colossal forces us to ask: do we want conservation to be primarily about feeding an unreflective imagination? Or do we want evidence, logic, and ethics to be central to our relationships with other species? For anyone who really cares about the climate, elephants, or animals in general, de-extincting the mammoth represents a huge waste and a colossal mistake.

Nitin Sekar served as the national lead for elephant conservation at WWF India for five years and is now a member of the Asian Elephant Specialist Group of the International Union for the Conservation of Nature’s Species Survival Commission The views presented here are his own.

Editorial: Mammoth de-extinction is bad conservation Read More »

“wooly-mice”-a-test-run-for-mammoth-gene-editing

“Wooly mice” a test run for mammoth gene editing

On Tuesday, the team behind the plan to bring mammoth-like animals back to the tundra announced the creation of what it is calling wooly mice, which have long fur reminiscent of the woolly mammoth. The long fur was created through the simultaneous editing of as many as seven genes, all with a known connection to hair growth, color, and/or texture.

But don’t think that this is a sort of mouse-mammoth hybrid. Most of the genetic changes were first identified in mice, not mammoths. So, the focus is on the fact that the team could do simultaneous editing of multiple genes—something that they’ll need to be able to do to get a considerable number of mammoth-like changes into the elephant genome.

Of mice and mammoths

The team at Colossal Biosciences has started a number of de-extinction projects, including the dodo and thylacine, but its flagship project is the mammoth. In all of these cases, the plan is to take stem cells from a closely related species that has not gone extinct, and edit a series of changes based on the corresponding genomes of the deceased species. In the case of the mammoth, that means the elephant.

But the elephant poses a large number of challenges, as the draft paper that describes the new mice acknowledges. “The 22-month gestation period of elephants and their extended reproductive timeline make rapid experimental assessment impractical,” the researchers acknowledge. “Further, ethical considerations regarding the experimental manipulation of elephants, an endangered species with complex social structures and high cognitive capabilities, necessitate alternative approaches for functional testing.”

So, they turned to a species that has been used for genetic experiments for over a century: the mouse. We can do all sorts of genetic manipulations in mice, and have ways of using embryonic stem cells to get those manipulations passed on to a new generation of mice.

For testing purposes, the mouse also has a very significant advantage: mutations that change its fur are easy to spot. Over the century-plus that we’ve been using mice for research, people have noticed and observed a huge variety of mutations that affect their fur, altering color, texture, and length. In many of these cases, the changes in the DNA that cause these changes have been identified.

“Wooly mice” a test run for mammoth gene editing Read More »

frozen-mammoth-skin-retained-its-chromosome-structure

Frozen mammoth skin retained its chromosome structure

Artist's depiction of a large mammoth with brown fur and huge, curving tusks in an icy, tundra environment.

One of the challenges of working with ancient DNA samples is that damage accumulates over time, breaking up the structure of the double helix into ever smaller fragments. In the samples we’ve worked with, these fragments scatter and mix with contaminants, making reconstructing a genome a large technical challenge.

But a dramatic paper released on Thursday shows that this isn’t always true. Damage does create progressively smaller fragments of DNA over time. But, if they’re trapped in the right sort of material, they’ll stay right where they are, essentially preserving some key features of ancient chromosomes even as the underlying DNA decays. Researchers have now used that to detail the chromosome structure of mammoths, with some implications for how these mammals regulated some key genes.

DNA meets Hi-C

The backbone of DNA’s double helix consists of alternating sugars and phosphates, chemically linked together (the bases of DNA are chemically linked to these sugars). Damage from things like radiation can break these chemical linkages, with fragmentation increasing over time. When samples reach the age of something like a Neanderthal, very few fragments are longer than 100 base pairs. Since chromosomes are millions of base pairs long, it was thought that this would inevitably destroy their structure, as many of the fragments would simply diffuse away.

But that will only be true if the medium they’re in allows diffusion. And some scientists suspected that permafrost, which preserves the tissue of some now-extinct Arctic animals, might block that diffusion. So, they set out to test this using mammoth tissues, obtained from a sample termed YakInf that’s roughly 50,000 years old.

The challenge is that the molecular techniques we use to probe chromosomes take place in liquid solutions, where fragments would just drift away from each other in any case. So, the team focused on an approach termed Hi-C, which specifically preserves information about which bits of DNA were close to each other. It does this by exposing chromosomes to a chemical that will link any pieces of DNA that are close physical proximity. So, even if those pieces are fragments, they’ll be stuck to each other by the time they end up in a liquid solution.

A few enzymes are then used to convert these linked molecules to a single piece of DNA, which is then sequenced. This data, which will contain sequence information from two different parts of the genome, then tells us that those parts were once close to each other inside a cell.

Interpreting Hi-C

On its own, a single bit of data like this isn’t especially interesting; two bits of genome might end up next to each other at random. But when you have millions of bits of data like this, you can start to construct a map of how the genome is structured.

There are two basic rules governing the pattern of interactions we’d expect to see. The first is that interactions within a chromosome are going to be more common than interactions between two chromosomes. And, within a chromosome, parts that are physically closer to each other on the molecule are more likely to interact than those that are farther apart.

So, if you are looking at a specific segment of, say, chromosome 12, most of the locations Hi-C will find it interacting with will also be on chromosome 12. And the frequency of interactions will go up as you move to sequences that are ever closer to the one you’re interested in.

On its own, you can use Hi-C to help reconstruct a chromosome even if you start with nothing but fragments. But the exceptions to the expected pattern also tell us things about biology. For example, genes that are active tend to be on loops of DNA, with the two ends of the loop held together by proteins; the same is true for inactive genes. Interactions within these loops tend to be more frequent than interactions between them, subtly altering the frequency with which two fragments end up linked together during Hi-C.

Frozen mammoth skin retained its chromosome structure Read More »

dna-from-mammoth-remains-reveals-the-history-of-the-last-surviving-population

DNA from mammoth remains reveals the history of the last surviving population

Sole survivors —

The mammoths of Wrangel Island purged a lot of harmful mutations before dying off.

A dark, snowy vista with a single mammoth walking past the rib cage of another of its kind.

Enlarge / An artist’s conception of one of the last mammoths of Wrangel Island.

Beth Zaiken

A small group of woolly mammoths became trapped on Wrangel Island around 10,000 years ago when rising sea levels separated the island from mainland Siberia. Small, isolated populations of animals lead to inbreeding and genetic defects, and it has long been thought that the Wrangel Island mammoths ultimately succumbed to this problem about 4,000 years ago.

A paper in Cell on Thursday, however, compared 50,000 years of genomes from mainland and isolated Wrangel Island mammoths and found that this was not the case. What the authors of the paper discovered not only challenges our understanding of this isolated group of mammoths and the evolution of small populations, it also has important implications for conservation efforts today.

A severe bottleneck

It’s the culmination of years of genetic sequencing by members of the international team behind this new paper. They studied 21 mammoth genomes—13 of which were newly sequenced by lead author Marianne Dehasque; others had been sequenced years prior by co-authors Patrícia Pečnerová, Foteini Kanellidou, and Héloïse Muller. The genomes were obtained from Siberian woolly mammoths (Mammuthus primigenius), both from the mainland and the island before and after it became isolated. The oldest genome was from a female Siberian mammoth who died about 52,300 years ago. The youngest were from Wrangel Island male mammoths who perished right around the time the last of these mammoths died out (one of them died just 4,333 years ago).

Wrangel Island, north of Siberia has an extensive tundra.

Enlarge / Wrangel Island, north of Siberia has an extensive tundra.

Love Dalén

It’s a remarkable and revealing time span: The sample included mammoths from a population that started out large and genetically healthy, went through isolation, and eventually went extinct.

Mammoths, the team noted in their paper, experienced a “climatically turbulent period,” particularly during an episode of rapid warming called the Bølling-Allerød interstadial (approximately 14,700 to 12,900 years ago)—a time that others have suggested might have led to local woolly mammoth extinctions. However, the genomes of mammoths studied through this time period don’t indicate that the warming had any adverse effects.

Adverse effects only appeared—and drastically so—once the population was isolated on that island.

The team’s simulations indicate that, at its smallest, the total population of Wrangel Island mammoths was fewer than 10 individuals. This represents a severe population bottleneck. This was seen genetically through increased runs of homozygosity within the genome, caused when both parents contribute nearly identical chromosomes, both derived from a recent ancestor. The runs of homozygosity within isolated Wrangel Island mammoths were four times as great as those before sea levels rose.

Despite that dangerously tiny number of mammoths, they recovered. The population size, as well as inbreeding level and genetic diversity, remained stable for the next 6,000 years until their extinction. Unlike the initial population bottleneck, genomic signatures over time seem to indicate inbreeding eventually shifted to pairings of more distant relatives, suggesting either a larger mammoth population or a change in behavior.

Within 20 generations, their simulations indicate, the population size would have increased to about 200–300 mammoths. This is consistent with the slower decrease in heterozygosity that they found in the genome.

Long-lasting negative effects

The Wrangel Island mammoths may have survived despite the odds, and harmful genetic defects may not have been the reason for their extinction, but the research suggests their story is complicated.

At about 7,608 square kilometers today, a bit larger than the island of Crete, Wrangel Island would have offered a fair amount of space and resources, although these were large animals. For 6,000 years following their isolation, for example, they suffered from inbreeding depression, which refers to increased mortality as a result of inbreeding and its resulting defects.

That inbreeding also boosted the purging of harmful mutations. That may sound like a good thing—and it can be—but it typically occurs because individuals carrying two copies of harmful mutations die or fail to reproduce. So it’s good only if the population survives it.

The team’s results show that purging genetic mutations can be a lengthy evolutionary process. Lead author Marianne Dehasque is a paleogeneticist who completed her PhD at the Centre for Palaeogenetics. She explained to Ars that, “Purging harmful mutations for over 6,000 years basically indicates long-lasting negative effects caused by these extremely harmful mutations. Since purging in the Wrangel Island population went on for such a long time, it indicates that the population was experiencing negative effects from these mutations up until its extinction.”

DNA from mammoth remains reveals the history of the last surviving population Read More »

de-extinction-company-manages-to-generate-first-elephant-stem-cells

De-extinction company manages to generate first elephant stem cells

Large collection of cells with a red outline and white nucleus.

Enlarge / Elephant stem cells turned out to be a hassle to generate. (credit: Colossal.)

A company called Colossal plans on pioneering the de-extinction business, taking species that have died within the past few thousand years and restoring them through the use of DNA editing and stem cells. It’s grabbed headlines recently by announcing some compelling targets: the tylacine, an extinct marsupial predator, and an icon of human carelessness, the dodo. But the company was formed to tackle an even more audacious target: the mammoth, which hasn’t roamed the northern hemisphere for thousands of years.

Obviously, there are a host of ethical and conservation issues that would need to be worked out before Colossal’s plans go forward. But there are some major practical hurdles as well, most of them the product of the distinct and extremely slow reproductive biology of the mammoth’s closest living relatives, the elephants. At least one of those has now been cleared, as the company is announcing the production of the first elephant stem cells. The process turned out to be extremely difficult, suggesting that the company still has a long road ahead of it.

Lots of hurdles

Colossal’s basic road map for de-extinction is pretty straightforward. We have already obtained the genomes of a number of species that have gone extinct recently, as well as those of their closest living relatives. By comparing the two, we can identify key genetic differences that make the extinct species distinct. We can then edit those differences into stem cells obtained from the living species and use that species as a surrogate for embryos produced from these stem cells. This will have to be done using stem cells from a number of individuals to ensure that the resulting population has sufficient genetic diversity to be stable.

Read 17 remaining paragraphs | Comments

De-extinction company manages to generate first elephant stem cells Read More »