Biotech firm announces ‘pivotal step’ in effort to bring back the dodo

A plan to genetically engineer a version of the dodo, a giant flightless bird that disappeared 400 years ago and became the poster child for extinction, has made some headway, according to Texas-based biotechnology firm Colossal Biosciences.

The company’s scientists said they have succeeded in culturing specialized cells from the rock dove — better known as the humble pigeon. They plan to use the same or similar techniques to culture cells from the dodo’s closest living relative, the Nicobar pigeon, which is from the same family of birds.

Colossal is years away from its long-term goal of creating a living, walking approximation of the dodo that would be indistinguishable from its extinct forerunner, but it described the advance as a “pivotal step.”

“This is the really important step for the dodo project, but also for bird conservation, more broadly,” said Beth Shapiro, Colossal’s chief science officer. “This was a negating step for the dodo project. We needed this in order to move on, and now that we have it, really, we’re off and running.”

The company sparked excitement, as well as controversy, when it announced the birth of three dire wolf pups in April. Colossal scientists said they had resurrected the canine predator last seen 10,000 years ago by using ancient DNA, cloning and gene-editing technology to alter the genetic makeup of the gray wolf, in a process the company calls de-extinction. Similar efforts to bring back the woolly mammoth, the thylacine — better known as the Tasmanian tiger — and another flightless bird, the moa, are also underway.

Colossal also announced Wednesday that it had raised $120 million in additional funding for its work for a total of $555 million since launching in September 2021.

However, the techniques necessary to bring back a bird such as the dodo are different from those the company used to create dire wolves because birds develop in an egg and can’t be cloned in the same way as mammals, making the process more challenging.

“So with birds, the slowest part of this process is that we have to make two generations. We can’t clone the cells, so we have to make moms and the dads separately and then breed them in order to get both copies of the gene to be modified,” Shapiro said. “That is pretty slow.”

Culturing a germ of hope

Colossal’s Wednesday announcement revealed its scientists have figured out a way to grow a vital type of cell, known as a primordial germ cell, which acts as a precursor of egg and sperm cells, from the rock dove (Columba livia), better known as the common pigeon that lives in cities around the world.

The company said it focused on the rock pigeon because the bird is widely bred and distantly related to the dodo. Scientists have previously been able to culture primordial germ cells, or PGCs, of chickens and geese, a technique that has been used to create a chicken fathered by a duck.

“The first cell culture recipe was for chicken PGCs, and was published nearly 20 years ago,” Anna Keyte, Colossal’s avian species director, said in a news release.

“Unfortunately, that recipe has not worked on any other bird species tested, even closely related species like quail. Colossal’s discovery of a recipe for pigeons dramatically expands avian reproductive technologies and is the foundation for our dodo work.”

The team tested more than 300 recipes before happening on the right combination of growth factors, molecules and metabolites that allowed the pigeon germ cells to grow for 60 days. Details of the research, which hasn’t yet been peer-reviewed, were published Wednesday.

Shapiro said the next steps would be to attempt to use the cells to create live rock pigeons birthed by a surrogate chicken, as a proof of concept.

At the same time, Colossal is using a similar culture to grow the primordial germ cells of the Nicobar pigeon, which is more closely related to the dodo. The company noted that it has established a breeding colony of the birds in Texas and begun to collect primordial germ cells.

Beyond that, Colossal would need to be able to edit the germ cells of the Nicobar pigeon with dodo traits, based on genomic information about the extinct bird preserved in museum specimens. Then scientists would inject the edited Nicobar pigeon PGCs into the embryos of regular chickens — roosters and hens — that have been genetically modified not to make their own germ cells. Chickens are preferable to pigeons as surrogates because as flightless birds they are easier to keep and because scientists already know how to genetically engineer them to be sterile, the company said, making them more suitable to the task.

The ultimate goal is that the edited Nicobar pigeon PGCs will continue to develop into functional eggs and sperm, and when the offspring of those modified roosters and hens hatch, the resulting chicks’ eggs and sperms cells will contain the Dodo-like genetic traits.

“Together, these advances — pigeon PGC culture and gene-edited chickens that do not make their own PGCs — set the stage for using surrogate chickens to help bring back dodo relatives, and eventually the dodo itself,” the company said in a statement.

That whole process will take at least five to seven years, said Ben Lamm, the company’s CEO.

Questioning ‘de-extinction’ claims

Critics say that while Colossal’s researchers are advancing the field of genetic engineering, it’s not truly possible to resurrect an extinct animal — any attempt could only create a genetically modified, hybrid species. Suggesting otherwise risks undermining the urgency of protecting existing species and ecosystems, according to conservationists.

The company has said its aim is not to bring back something that’s 100% genetically identical to an extinct species but to create functional copies with key traits.

“Dodos belonged to the pigeon and dove family. So, to the extent that dodos shared many genes in common with the Nicobar pigeon, in theory it would mean the scientists only have to insert the dodo-unique genes into the germ cell, or edit the pigeon genes to make them dodo-like. This could produce a dodo-like bird,” said Scott MacDougall-Shackleton, cofounder and director of the Advanced Facility for Avian Research at Western University in London, Ontario.

However, he said it is impossible to bring back extinct species, as these animals were far more than a set of genes. “During development our genome interacts with parental genomes, hormones and the environment such that genes are turned on or off in complex ways that we cannot know and cannot repeat for an extinct species,” he noted.

“Although it is impressive genetic engineering to insert genes from extinct species into a current species, it is hyperbole to call it de-extinction.”

Wider applications for Colossal’s work

The new technology developed by Colossal has valuable potential applications in avian conservation, particularly in areas where existing bird populations have little genetic variation, according to Cock van Oosterhout, a professor of evolutionary genetics at the University of East Anglia’s School of Environmental Sciences in the United Kingdom. For van Oosterhout, however, the real utility is not in resurrecting the dodo, but in applying the company’s findings to help species recover.

Modifying the genes of endangered species could help them adapt better to declining habitats or diseases that pose a threat, said van Oosterhout, who has received a donation from Colossal for his work on the endangered pink pigeon.

“Can we now find the resistant variant, maybe in an historic sample, or maybe in a very closely related species that we know is resistant to a particular pathogen, and can we edit this back into the general population?” van Oosterhout asked.

Colossal’s “Jurassic Park-style flamboyant science” attracts funders with deep pockets who wouldn’t ordinarily be interested in biodiversity conservation, allowing the company to solve problems that have long eluded many academic researchers, van Oosterhout added.

However, genome editing is just one small piece of a much larger puzzle that is complex to solve, he said. “What we need to do as a society is really prevent extinction, prevent habitat loss. Technology can’t solve the biodiversity crisis. It might save a few species, but it’s not a magic bullet.”

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