Colossal is a company that got its start with a splashy announcement about plans to do something that many scientists consider impossible with current technology, all in the service of creating a product with no clear market potential: the woolly mammoth. Since that time, the company has settled into a potentially viable business model and set its sights on a species where the biology is far more favorable: the thylacine, a marsupial predator that went extinct in the early 1900s.
Today, the company is announcing a third de-extinction target and its return to the realm of awkward reproductive biology that will force the project to clear many technical hurdles: It hopes to bring back the dodo.
A shifting symbol
The dodo was a large (up to 1 meter tall), flightless bird that evolved on the island of Mauritius in the Indian Ocean. As European sailors reached the islands, it quickly became a source of food for them and the invasive species that accompanied them. It went extinct within a century of the first descriptions reaching Europe.
Its lack of fear for humans initially turned it into a metaphor for foolishness. But as concerns for human-caused extinctions and ecosystem disruptions have risen, the metaphor has shifted to one where the dodo represents a preventable tragedy caused by human thoughtlessness. It's that latter metaphor that made its de-extinction appealing to Colossal. "I think a lot of it is the name recognition," said Beth Shapiro, a biologist at the University of California, Santa Cruz, who's collaborating with Colossal. "You know, I think people don't really care about extinctions, in as much as it doesn't impact them personally. But the dodo somehow has this real draw to people.
"By targeting something that is so famous—really the icon of human-caused extinction—I think we're going to draw more people into thinking about it," Shapiro told Ars. (She's also collaborating on a separate project that's looking into de-extincting a second of these icons, the passenger pigeon.)
In the case of the thylacine and mammoth, Colossal made the case that returning these keystone species to the habitats they once inhabited will alter the habitat significantly, changing which species can survive and thrive there. The company's argument for restoring the dodo is, in many ways, the converse: We will have to restore the ecosystem before a revived dodo can survive there.
"If [dodos] are to be able to reestablish thriving populations on Mauritius, it's going to require removing many of the invasive species that were introduced there. And in that way, this project will help to reinvigorate and revive these ecosystems," Shapiro said. "By making sure that dodos can survive there, we'll have to create a habitat that is also beneficial to other endemic Mauritian flora and fauna that maybe are struggling to survive because of the invasive species rather than because of the absence of dodos."
Technical hurdles
The dodo is also a new direction in a biological sense, in that it's a bird. In mammals, things like cloning, gene editing, and other manipulations are done all the time and have been used successfully in various species. Birds, partly because of their use of eggs, require different techniques—techniques that haven't been as thoroughly developed or widely deployed. In fact, they've only been used in a single species, the domestic chicken.
The techniques developed there are dramatically different from what's available in mammals. In chickens, we don't have stem cells that can reconstitute an entire embryo, and it's not clear that we could use them anyway, given that the initial development of the embryo is so closely tied to egg production. But we do have what are called primordial germ cells (PGCs) that act a bit like stem cells—they can divide indefinitely in culture dishes—but are committed to only forming germ cells, which go on to produce eggs and sperm.
During normal chicken development, the primordial germ cells migrate through the circulatory system and reside in the developing gonad. PGCs can be manipulated in culture and then moved from the culture dish to the circulatory system at this stage, allowing them to form genetically engineered germ cells and give rise to offspring that carry the same engineering. This works partly because of the egg; a small hole can be opened, the PGCs transferred, then the hole can be taped over and the chicken embryo can continue to develop.
(There's a good review of these technologies available.)
However, we don't know whether these techniques work well or at all in species beyond chickens. Or whether PGCs from one species can successfully enable reproduction when transplanted into a different one. Or how size mismatches between eggs and developing embryos work out. Or any of a large number of additional questions. So, it's possible that the technology development needed to enable the dodo de-extinction could hit a brick wall well before trying to engineer any dodo-like DNA sequences into its closest living relatives, the Nicobar pigeon.
Worth the effort?
For several reasons, Colossal sees the risks as being worth the effort. One of these reasons is simply its business model, which involves recognizing when the technologies needed for de-extinction can be useful in medicine, biotechnology, or agriculture. Many species of birds are raised commercially, and it's possible that streamlining PGC manipulations and enabling them in other commercial species could generate revenue for Colossal.
Developing these technologies for birds is also in keeping with Colossal's interest in ecosystem restoration. "We're losing a lot of birds, which are really, really critical to ecosystems, and there's just not enough money going into it," Colossal's Ben Lamm told Ars. "We could start working on the dodo while further developing some of these underdeveloped and underfunded technologies around bird conservation."