Return From Extinction – Technology Networks

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The prospect of “reviving” an extinct species – or a, genetic hybrid version of it – is moving closer to reality thanks to the sophistication of genome engineering technologies coupled with our ability to extract and sequence archaic DNA samples.

In September, the biotech/genetics company
Colossal – co-founded in 2021 by renowned geneticist Professor George Church and serial entrepreneur Ben Lamm – announced it had raised $15 million in funding for a project that aims to “de-extinct the woolly mammoth”.

The company’s mission is not to engineer a complete replica of the woolly mammoth in a laboratory. Rather, it is to create a genetic hybrid that combines woolly mammoth genes with the DNA of an Asian elephant.

Professor Church joined Technology Networks in an exclusive interview for The Scientific Observer, exploring the backstory of Colossal, his aspirations for the project and why “mammoth-sized” interventions are needed to combat climate change.

Several of these goals are linked to climate change and helping endangered species. Church and his colleagues at Colossal believe that by reviving a hybrid version of the woolly mammoth and introducing it into the Arctic tundra, the habitat can be re-established, restoring the rich biodiversity and ultimately preventing the release of harmful greenhouse gases into the atmosphere from the melting ice.

“Elephants are the only animals which efficiently knock down trees and the resulting increase in grass yields three favorable outcomes: higher photosynthesis – hence new carbon sequestration, higher reflectance (albedo) – hence less solar warming, and more trampled snow – hence higher cold conductance to help freeze the ground and keep methane from escaping,” Church said.

Protecting Asian elephants – which are an endangered species – is also a priority for the biotech company, Church explained. By genetically engineering beneficial traits into the Asian elephant, he hopes that the company can help to promote their survival and reproduction. This brings us to the how of Colossal’s de-extinction agenda.

The concept of de-extinction is not a novel phenomenon, and
several methods for reviving a “proxy” version of an ancient species have been proposed in recent years. Colossal’s strategy revolves around the genome engineering techniques that have been refined in Church’s lab over recent years, utilizing CRISPR-Cas9 technology.

The woolly mammoth genome has been obtained from ancient archaeological samples revealed by the melting permafrost. Next-generation sequencing technologies allow Colossal to read the genome and compare it to the Asian elephant. Using this sequencing data, the scientists can identify which genes are mammoth-specific and encode the traits that Colossal wants the mammoth-hybrid to bear. These features include fat “clumps” on the mammoth’s back that provided insulation, long shaggy hair and its short compact ears.

Skin cells – extracted from the Asian elephant – will be edited using CRISPR-Cas9 methods to insert the mammoth-specific genes into the nucleus. This nucleus will then be inserted into an egg that has been generated from stem cells in a lab. The egg will be encouraged to divide via artificial means before being inserted into an African elephant surrogate mother, which will then carry the calf to term. While Asian elephants are an endangered species, African elephants are classified as a “threatened species”. That is Colossal’s reasoning behind using the latter species as the hybrid’s surrogate parent, to avoid placing any further pressures on the remaining Asian elephant populations.

Colossal is also considering whether an artificial womb could be used to carry the hybrid to term. Scientists at the Children’s Hospital of Philadelphia have worked on several different prototypes of an “extra-uterine support device” that they tested using
lamb fetuses. However, these pre-clinical studies have been several weeks in duration, whereas the gestation period of an elephant is two years. Furthermore, there is a notable size difference between a lamb fetus and an elephant fetus; thus, while the results from pre-clinical studies have been promising, it’s not clear – for now, at least – whether the technology could be translated for use in this project.