With a massive beak, googly eyes, a rotund body, and a disproportionately small feathered tail, the dodo is iconic for all the wrong reasons. The flightless bird vanished in the seventeenth century, and has since been the poster child for human-caused extinction.

But what if we can bring the iconic bird back?

Last week, a biotech company based in Dallas, Texas called Colossal Biosciences announced an audacious plan to “de-extinct” the dodo. Founded by Harvard geneticist George Church and tech entrepreneur Ben Lamm in 2021, the company has ongoing projects to recreate the woolly mammoth and the thylacine, a Tasmanian tiger.

The dodo has now joined this lineup. Similar to previous projects, resurrecting the iconic bird requires huge advances in genetic engineering, stem cell biology, artificial wombs, and animal husbandry. Whether they can fit into a whole new world—300 years later—is hotly debated. Even if the technology works, the resulting “hacked” species would raise a big philosophical question: at what point does resembling a dodo genetically equate to resurrecting the species?

But for Colossal Biosciences, the challenge is worth it.

“A goal here is to create an animal that can be physically and psychologically well in the environment in which it lives,” said Dr. Beth Shapiro, a scientific advisory board member at Colossal Biosciences. A professor of ecology and evolutionary biology at the University of California, Santa Cruz, Shapiro has had a decades-long fascination with the extinct bird.

Other experts in the field are cautiously optimistic, if just for the attention brought to conservation. “It’s incredibly exciting that there’s that kind of money available,” said Dr. Thomas Jensen, a cell and molecular reproductive physiologist at Wells College, to Nature. Whether it’ll work out, he added, remains to be seen.

A Genetic Egghunt

The de-extinction playbook is already laid out.

Step one, decode the extinct animal’s genome. Step two, find its nearest living cousin. Step three, screen for genetic differences, and replace the living animal’s DNA code with that of the extinct species. Finally, produce an embryo that can be brought to life in a surrogate species.

Yeah, it’s not exactly a walk in the park.

Thanks to Shapiro, Colossal has already nailed the first two steps. Back in 2002, her team sequenced a chunk of the bird’s mitochondrial DNA (mtDNA), which live inside the cell’s energy-producing factory, the mitochondria. These genetic codes are passed down solely through the maternal line. Comparing the dodo’s mtDNA with that of their living cousins, the team honed in on the Nicobar pigeon, a peacock-colored bird that roams around the Indian Andamans to the Solomons and New Guinea, as their closest living relative. The two birds shared a common ancestor roughly 30 to 50 million years ago, wrote Shapiro in a 2016 study.

Early last year, she announced that her team has sequenced the entire dodo genome from a museum sample, although the results have yet to be published in a scientific journal. By comparing the dodo’s genome sequences to that of the Nicobar, it’s now possible to hunt down DNA changes that define the dodo—and pinpoint genetic changes needed to transform a Nicobar into its long-extinct cousin.

An Avian Headache

Here’s where the playbook changes.

In mammals, the edited genome—one that resembles the extinct species—is transplanted into an egg cell of its closet cousin and developed into an embryo. The embryo is then brought to life inside the surrogate womb of a living species, a method akin to cloning.

It doesn’t work for birds.

Cloning a species requires access to an egg cell that’s sufficiently developed so it can be fertilized. This stage is hard to capture in avian species. Then there’s the problem of reintroducing a cloned egg back into the body.

“To implant a cloned embryo, one would have to take out the developing embryo from within a developing hard-shelled egg within the female’s body and replace it with the cloned embryo—and hope that the embryo integrates into the yolk of the egg and that all the puncturing doesn’t deform the egg or harm the female,” explained Dr. Ben Novak, lead scientist and program manager for biotechnology for bird conservation at Revive & Restore, company focused on genetically rescuing endangered and extinct species.

Colossal honed in on a different approach for assisted reproduction: utilizing primordial germ cells (PGCs). True to their name, these cells can transform into both sperm and egg-producing cells. The company plans to extract these flexible reproductive “blank slates” from developing Nicobars and edit their DNA sequences to better match those of the dodo using tools such as CRISPR.

It’s a hard task. Most genetic tools are optimized for mammalian species, but those for birds are sorely lacking. So far, scientists have struggled to introduce just a single genetic change into quails. Editing the Nicobar will require thousands of precise DNA changes simultaneously.

Then comes the surrogate challenge. “Dodo eggs are much, much larger than Nicobar pigeon eggs, you couldn’t grow a dodo inside of a Nicobar egg,” said Jensen. He would know: his team inserted PGCs into chicken eggs, creating chimeric chickens that can generate quail sperm (but not eggs). Finding a potential surrogate match for a wild, extinct species is far more challenging.

That said, the rest of the process may be relatively smooth sailing.

In mammals, fetuses are heavily influenced by signals and molecules from the mother’s womb. We can’t yet predict how an extinct species interacts with its surrogate modern mom during pregnancy. In contrast, the bird egg is a relatively insulated environment and the process should be simpler, predicts Shapiro, because “everything happens in an egg.”

What if It Works?

With rapid progress in genome editing and reproductive technologies, Colossal’s moonshot project may just work out. But would the resulting animal actually be a dodo?

To Dr. Mikkel Sinding at the University of Copenhagen, we need to consider both nature and nurture. Genetics is just one aspect that defines a species; societal interactions and the environment further shape a species’ behavior. But for a “resurrected” dodo, “there is nobody around to teach the dodo how to be a dodo,” he said.

Then there are ecological concerns. Even if the dodo retains its natural instincts, it would be brought back into a world that hasn’t existed for 300 years. The bird originally thrived in Mauritius. Today, the island is facing deteriorating forests, oil leaks, and plastics in its surrounding waters. Would an engineered dodo survive in that ecosystem? And if not, is it ethical to raise the creatures solely inside a zoo or otherwise controlled environment purely for our enjoyment?

These questions don’t yet have an answer. However, scientists hope the dodo may highlight environmental issues due to their superstar power. The project could help propel efforts to restore the island’s natural ecosystem, including endemic plants and other animals. In terms of technology, lessons learned along the way could cross over into biotech and medicine—for example, PGC-aided reproduction—ultimately with a far wider reach than de-extinction.

“There’s a new set of potential tools here, a new set of possibilities and opportunities,” said Dr. Ronald Sandler, the director of the Ethics Institute at Northeastern University in Boston.

Image Credit: Rawpixel.com/Henrik Gronvold

Source: https://singularityhub.com/2023/02/14/scientists-say-they-can-bring-back-the-dodo-should-they/