It’s been almost a decade since Harvard geneticist George Church initially proposed using synthetic biology to resurrect woolly mammoths.
His plan to change history is now moving forward.
Today, Church and software entrepreneur Ben Lamm announced the creation of Colossal, a biotech firm with $15 million in preliminary capital.
The company’s objective is twofold: to employ gene-editing technology to save endangered animals (and, eventually, plants),
and to use those species to transform Arctic ecosystems to combat climate change.
The goal is to utilize CRISPR to insert 60 or more genes from the ancient woolly mammoth into the cells of an Asian elephant embryo,
which is the extinct mammoth’s closest living relative. Colossal asserts that the two species share 99.6% of their genome.
Church’s lab successfully incorporated mammoth genes for small ears, fatty tissue, and shaggy brown hair into elephant skin cells’ DNA in 2015.
Church told Popular Science at the time, “Just making a DNA modification isn’t that substantial.” “We want to read the phenotypes out loud.”
Long-term, Colossal will assist support Church’s mammoth study, while also collaborating with Arctic researchers to pave the way for rewilding.
“We’ve sequenced numerous genomes from frozen woolly mammoth tissues found from Siberia,” Lamm says.
The researchers also analyzed the genomes of several Asian elephants to examine the two species’ differences.
“George Church and his colleagues have really found genes that make up the phenotypic that make an Asian elephant a functional woolly mammoth,” Lamm continues. However, their mission has just begun.
HOW TO MAKE A MAMMOTH OUT OF AN ELEPHANT
CRISPR/Cas9 is an enzyme that can attach to and cut particular locations on a strand of DNA.
It was first found in bacteriophages in 2011. Church’s lab will use the rapidly evolving tool in conjunction with other DNA-editing enzymes such as integrases, recombinases, and deaminases to splice genes from the woolly mammoth into the Asian elephant,
allowing it to adapt to the cold Arctic, where Colossal claims it will help sculpt the landscape to better sequester carbon.
The process is still in its early stages for the team. They’re currently attempting to manifest functioning mammoth genes in live Asian elephant cells.
If they succeed, they’ll have to test the genes in pig and mouse models before moving on to elephants to see if they match the traits they seek.
Church has previously shown that his method can alter the growth of a mammal.
His lab used CRISPR to edit out 62 genes for the porcine endogenous retrovirus—remnants of an ancient zoonotic infection that can transmit to humans,
and produce a live pig carrying those gene edits through somatic cell nuclear transfer, or cloning, in a proof-of-concept study published in Science in 2017.
The procedure entails transferring the nucleus of a genetically modified body cell to an egg cell to generate an embryo.
With the elephants, Church is planning to duplicate the trick. However, grafting in the essence of another species is vastly different than editing a virus out.
“This is something George and his team have been working on over the last five years, not just with pigs and other species, but specifically with elephants,” Lamm explains.
“For Colossal, it’s about leveraging their previous research. We aren’t a brand-new stage in the process.”
If the feat of creating hybrid embryos is successful, they can be implanted in elephant surrogates or grown to a full term in artificial wombs (which are still being developed);
Lamm argues that the latter will probably work better for mass-producing new elephants.
In the next 4 to 6 years, the first cloned calves are projected to arrive.
According to the Asian elephant’s life cycle, the pilot generation would have to wait another 13 years to attain sexual maturity.
“This isn’t going to be a quick process,” Lamm says. “At the firm, our goal isn’t merely to reintroduce a successful little herd of woolly mammoths.
The goal is for the mammoths to successfully rewild in the Arctic. That entails vast populations with interbreedable genetic diversity.”
While the team hopes to start with a small herd of five calves to examine population dynamics,
Lamm predicts that tens of thousands of CRISPR-ed mammoths will be required to have the intended effect on the Arctic ecosystem.
FROM RUGGED TUNDRA TO HAVARD LAB
Though the first elephant hybrids are still years away, Colossal has already made arrangements to release them into the wild.
The business plans to start slowly, with a small herd of these franken-elephants being released into a reserve-like setting in the Arctic tundra where mammoths previously reigned.
To transfer mammoths to Pleistocene Park in northern Siberia, the team will collaborate with Arctic rewilding scientists Sergey and Nikita Zimov.
Pleistocene Park began in 1996 as a father-and-son Ice Age experiment in the Zimov family’s garden.
They’ve let bison, musk oxen, and wild horses roam the 90-square-mile field, but the mammoths have yet to arrive.
Tanks are being used as stand-ins for Church’s herd until Church’s herd is ready.
The reserve has allowed the Zimovs to make key discoveries about the Arctic ecology,
notably its tremendous ability for storing carbon and methane, as Crichton-esque as it all sounds.
Sergey assisted in the publication of research in 2006 that estimated the carbon reserves of the Siberian permafrost to be around 450 gigatons.
However, when the world warms, this frozen pool may thaw and release carbon dioxide into the atmosphere.
Lamm explains, “The Zimovs are conducting a lot of modeling on the implications of rewilding, specifically mammoths and other species.”
“We’re not attempting to reintroduce mammoths into locations where they’ll be fighting for resources with other species in areas where they didn’t originate. We’re returning them to the places and conditions where they formerly flourished.”
Woolly mammoths and other cold-tolerant megafauna were instrumental in the formation of the mammoth steppe ecosystem,
a large glacial grassland that helped to moderate the world’s climate around 13,000 years ago.
The grasses not only absorbed carbon but also created a landscape that reflected light and heat from the sun, thanks to a phenomenon known as the albedo effect.
Mammoths and woolly rhinos were responsible for maintaining the grounds, crushing plants, and uprooting trees.
They ate the grass and pooped the nutrients back into the ground, completing the carbon-nitrogen cycle on the steppe.
This terrain was probably better at storing carbon than the Arctic’s tree-covered swaths.
Grasslands, according to a recent study by UC Davis researchers, are a more stable source of carbon sequestration than forests because they are less affected by intense heat and fires, which can release carbon back into the atmosphere.
Furthermore, because coniferous canopies are darker than ice, they absorb more light and heat than they reflect.
The Siberian tundra, according to many experts, has lost its luster since its Ice Age glory days.
Scientists are scrambling to understand out why once-green treetops are browning and the diversity of herbivores in the Arctic is declining.
Colossal has made an educated guess. According to the firm, the woolly mammoth’s disappearance left an ecological hole in the Arctic terrain that has never been filled by another species: “All that’s left are the yak and reindeer herds that support local villages.”
ENDANGERED ELEPHANTS GET A SECOND CHANCE AT LIFE
Outside of the Arctic, Colossal wants to make sure the re-engineered elephants are built to last.
To contribute to population diversity, the business will continue to sequence elephant and mammoth samples to find critical genes in both species’ populations.
They think that by doing so, they will be able to avoid a rogue mutation from wiping off the entire herd.
While Church’s lab works through the frozen mammoth samples retrieved from Siberian permafrost,
the firm is also financing the Vertebrate Genome Project’s study on Asian and African elephants to learn more about the richness of elephant populations in general.
Colossal hopes that by using a genetic time machine, it will be able to give endangered creatures like Asian and African elephants a second chance at life.
It proposes a technique to create a live archive of the huge tusked mammals by producing a franken-species that mashes together DNA from spanning millennia.
“If we can give the Asian and African elephants, and the entire lineage, the ability to survive in a new ecosystem and climate by instilling the genes that existed in their previous ancestors in them,” Lamm says,
“then we have this concept of species extension where we have these entire ecosystems that can not only be rewilded from an Arctic grasslands restoration perspective but also a rewilding perspective.” Hunting and poaching aren’t the only issues. Part of it is due to competition with urbanization and habitat loss.”
Colossal believes it can apply a similar concept to other species, such as the Sumatran rhino if the endeavor succeeds.
It’s a novel approach to environmental protection. Experts like Jesse Reynolds,
who was recently a researcher at the University of California, Los Angeles School of Law’s Emmett Institute on Climate Change and the Environment, are on board.
“If environmentalists are serious about maintaining biodiversity, they must overcome their common hostility to biotechnology,” Reynolds added in an email statement.
It is no longer sufficient to simply protect some land and hope for the best.”
When it comes to experimenting with de-extinction, however, there should be some care.
Reynolds observed in an article published in April in Current Opinion in Environmental Sustainability that some “conservationist synthetic biology” could pose environmental hazards,
and that local and international policies governing how these biotechnologies are employed need to be updated.
According to a UNEP report published in 2019, CRISPR has primarily been used on small groups of organisms in controlled conditions.
Even though the participants were sterilized to prevent interbreeding with wild insects, a modest field trial employing mosquitoes altered for disease control against malaria released in 2019 stirred debate.
Concerns like these are why Lamm believes it’s a good idea to start with the mammoth.
He explains, “We’re not genetically manipulating a mosquito and sending it into the wild where we can’t trace it.”
“With a species like the mammoth, which is huge enough to have radio and different tracking equipment on them, we can easily roll it back if there is an issue.”
ARE ECOSYSTEMS AND DESIGNER SPECIES THE ANSWER?
While the introduction of Colossal offers Church’s experiment new legs, the project’s advantages are still being debated.
Those in favor argue that de-extinction is required to correct human errors; those opposed argue that it is too little, too late, and more showy than useful.
Professor emeritus of integrative biology at The University of Texas at Austin, James Bull, sees no major drawbacks to the mammoth rewilding plan,
but warns that there will be plenty of unknowns to be aware of, as well as fascinating research to be discovered.
In an email, he writes, “Moving genes from one species to replace parts of another’s genome may find multiple incompatibilities—from entire genes to single-base differences.”
“Studies have shown that human genes can substitute for analogous yeast genes, indicating that there may be multiple paths to success. However, it is possible that it will not be simple.”
Even if Church shows that mammoths and Asian elephants can be crossed, it may be difficult to prevent the hybrids from becoming extinct again,
as Bull says, “whether due to dramatic occurrences, sickness, misaligned mating behavior, or faulty genetics.”
Inbreeding, hunting, and warming temperatures are some of the theories for why mammoths went extinct in the first place.
“Wild species imports into new habitats and settings have a poor track record,” Bull says.
Colossal, on the other hand, intends to play the long game and learn from its many failures.
Lamm believes the company will eventually “work on other species to balance that ecosystem,”
which might include introducing a predator to keep the population in control. “However, that’s a long way off,” he continues.
The startup is well aware of the thorny minefield it is entering, and it intends to keep addressing de-extinction skeptics.
Bioethicists, conservationists, animal trafficking researchers, elephant specialists, chemists, and geneticists are among the members of its advisory board.
Lamm says, “We want to make sure we’re doing this most transparently and ethically possible.” “Those are the kinds of dialogues we want to engage with the broader public.”
“It might well be more than a century after the first mammoth is born before there is a strong enough population that there is any ecological impact to measure,” Bull says, assuming that the first generation of the hybrid herd survives, both in the mock womb and in the Arctic.
He says, “I don’t view the possibility of a negative ecological impact as anything to be concerned about right now.” “It’s too far down the road.”
