You may have heard about recent attempts to resurrect the woolly mammoth, a hairy, beloved ice age creature.
But there’s a mammoth-sized catch: Even if the eccentric venture succeeds, the biotech company behind the effort — Colossal Biosciences — can’t churn out Jurassic Park-style clones of the woollies of yore. Due to technical limitations, the company is engineering an elephant-mammoth hybrid, also known as a “mammophant.”
The main sticking point is that a genetically identical clone would require plenty of well-preserved woolly mammoth DNA from over 4,000 years ago, when the animal disappeared. But so far, researchers have only uncovered fragments of DNA in frozen remains.
So the company will use CRISPR technology to tinker with the genome of the Asian elephant, the closest living woolly relative, to reflect that of the mammoth. More specifically, Colossal’s team will swap out certain elephant genes for woolly mammoth ones.
Colossal is pursuing a similar approach with the Tasmanian tiger, a long-gone meat-eating marsupial that resembled a wolf with zebra stripes. Now, the company says it plans to add the dodo to its hyped-up de-extinction portfolio, according to a recent announcement. To support its expanding mission, Colossal recently raked in $150 million in investments (including cash from a CIA-funded venture capital firm).
These hybrid creations could protect their former habitats from the impacts of climate change, Colossal claims on its website. The new mammoth could, for example, maintain grasslands that guard the Arctic’s thawing permafrost.
And if the company can overcome some of the barriers that prevent CRISPR from being used ubiquitously — such as the limited amount of DNA that can be edited at once — then the team claims it could share these possible breakthroughs with other fields like medicine or the conservation of still-living birds.
“Colossal will remind people not only of the tremendous consequences that our actions can have on other species and ecosystems, but also that it is in our control to do something about it,” Beth Shapiro, a biologist at the University of California, Santa Cruz, and a member of Colossal’s scientific advisory board, tells Inverse.
Why de-extinct the dodo?
While the long-gone pigeon relative is widely regarded as a clumsy and ignorant creature, it was actually pretty smart and resilient. The flightless bird lived on the island of Mauritius and went extinct in the latter half of the 17th century due to human activities like hunting and deforestation.
Last March, Shapiro announced that she and her colleagues had become the first to sequence the entire dodo genome. This work was two decades in the making, beginning when Shapiro was a Ph.D. student at Oxford University, where she pinpointed the Nicobar pigeon as the dodo’s closest living relative.
“The dodo is the icon of human-caused extinction.”
Now, a revived dodo-like animal could help fight off invasive species on Mauritius and benefit the ecosystem as a whole, according to Shapiro.
“The dodo is the icon of human-caused extinction,” she says. “Everybody has heard of the dodo, and everybody understands that the dodo is gone because people changed its habitat in such a way that it could not survive.”
How it works
There are three ways to “de-extinct” a species. First off, there’s old-fashioned selective breeding. This doesn’t require any genetic modification — a close relative of the extinct species is bred for various ancestral traits, including certain behaviors or physical characteristics. Cattle breeders have opted for this method to revive the auroch, a massive species that poachers killed off in the early 17th century.
Then, there’s cloning. Unfortunately, Jurassic Park lied: You can’t just create a clone from ancient genetic material. The animal needs to have disappeared relatively recently and had its cells properly preserved.
For example, in the 1980s, scientists froze cells from the dwindling black-footed ferret in liquid nitrogen. Then in 2020, a company called ViaGen placed a cloned embryo into a ferret surrogate, and a black-footed ferret named Elizabeth Ann entered the world. Now, biologists are coaxing Elizabeth Ann to birth kits and help bring genetic diversity to her sparse, inbred species.
Colossal Biosciences has chosen the third route: genetic engineering. Once the team edits an Asian elephant’s skin cell to give it certain mammoth characteristics, the cloning process kicks off: They’ll place the mammoth-like elephant nucleus into an Asian elephant egg and zap it with an electrical current. The egg will then be implanted into the womb of an African elephant (a relative with a relatively stable population compared to the Asian elephant). Colossal may also work with an artificial uterus.
Creating an avian embryo will prove difficult.
Similar to how the company is customizing the Asian elephant genome to revive the mammoth, Colossal will slice up the Nicobar pigeon’s DNA and add in certain dodo fragments.
But creating an avian embryo will prove difficult: The cloning process used for mammals, called somatic cell nuclear transfer, doesn’t work with birds. Mike McGrew, a Colossal scientific advisor, has a potential solution — he has isolated certain immature chicken cells called primordial germ cells and injected them into the eggs of other species to create surrogate mothers.
“Since this process has worked to birth live ducks through the insertion of duck PGCs into chickens, we are confident that this part of the project is just a function of time and focus,” Ben Lamm, co-founder and CEO of Colossal, tells Inverse.
Beth Shapiro’s UCSC colleague, Ben Novak, is also snipping at genomes to revive a lost species. He hopes to usher in the return of the passenger pigeon, which disappeared in 1914, with the help of its living band-tailed pigeon relative.
Proxy problems
Don’t expect a woolly mammoth to roam the Siberian steppe or a dodo to waddle around Mauritius anytime soon. The dodo effort has just begun, and the mammoth team at Colossal remains deep in the editing stages.
They’ve got a lot of work ahead of them: The Asian elephant and woolly mammoth genomes differ by around 1.4 million base pairs, the individual units that compose DNA. With current tech, scientists can only edit up to 33 base pairs at once — so Colossal wants to ramp up CRISPR’s capabilities to edit for hundreds or even thousands of genes simultaneously.
Further, scientists have yet to pin down the specific genes related to certain characteristics, like the mammoth’s resistance to frigid temperatures — over 50 genes may be associated with it.
Ultimately, it’ll be a waiting game to find out if the experiment will work. Once Colossal implants the edited embryo into the womb of an African elephant, the pregnancy lasts a whopping 22 months. Still, Colossal aims to deliver the first hybrid calves by 2027.
Let’s say the project succeeds in creating these mythical hybrids. What will happen when the pigeon-dodos return to their ancestral breeding grounds? After all, these environments will look a lot different from thousands of years ago. And the creatures probably won’t act just like their ancestors.
“[The proxy] would be genetically, physiologically, behaviorally different,” Phil Seddon, a zoologist and conservation biologist at the University of Otago in New Zealand, tells Inverse. “And it would go into an area where something like that hasn’t been for a long time. [There are] lots of unknowns.”
“It will not have real conservation power.”
In a worst-case scenario, a proxy species could introduce pathogens and harm local wildlife — though Seddon says he would be surprised if the mammoth and dodo hybrids do actually wreak major havoc.
But to offer tangible benefits to these ecosystems, the new hybrid species would need to replicate specific details like the dodo’s social hierarchy and parental care behaviors, Piero Genovesi, head of wildlife service at the Italian Institute for Environmental Protection and Research, tells Inverse.
“Whatever organism that will be re-created cannot have this kind of relations, so it will not have real conservation power,” Genovesi says.
Overall, Genovesi doesn’t find the environmental goals realistic. Mimicking the dodo’s role in its former ecosystem “is very far from what we can do in the next decades, and it might be impossible.”
Shapiro says this isn’t the aim — rather, her team wants to create a species that can survive today’s conditions. For that to work, it will be crucial to combat the problems that caused extinction in the first place. For dodos, it could help to identify areas to remove invasive species — work already underway by Mauritian scientists and conservation biologists, she says.
Lamm adds that rewilding projects could take years, and must be done in collaboration with local governments, landowners, Indigenous groups, and the general public.
The conservation catch
You may be wondering: Shouldn’t these millions of dollars in funding go toward preventing all of the living, breathing animals from vanishing in the wake of climate change and human encroachment?
But according to Colossal, de-extinction and conservation could go hand in hand. For example, if the company figures out the bird cloning problem, it could use the technique to boost the population of some living avian species.
“The technologies may, for example, be used to resurrect lost diversity or transfer beneficial traits between populations or species,” Shapiro says. “I believe this investment by Colossal will lead to new approaches to protect and preserve bird species across the world.”
Still, Seddon and Genovesi argue that the investments toward de-extinction endeavors could instead fund efforts to save the 1 million animal and plant species on the brink of extinction around the globe. A significant number of species could be saved at relatively low costs by protecting ecosystems in some of the world’s most vulnerable regions, Genovesi says.
“So instead of letting species disappear and then try to bring them back from extinction, [which] is extremely costly and of little impact in terms of conservation and biodiversity … we should concentrate resources on protecting what is already out there,” he says.
