A&M scientists address validity of de-extinction project, applications for biodiversity – The Battalion

The cover of Time Magazine’s May edition features a striking image of a large, white wolf. Above it, the word “extinct” in all caps is crossed out with a bold, red line. 

Texas biotech startup Colossal Biosciences claims to have “de-extincted” ancient dire wolves, producing three pups named Romulus, Remus and Khaleesi, who carry genetically modified genomes.

Colossal deciphered segments of 80,000-year-old dire wolf DNA, reconstructing the genome using American gray wolf and domestic dog genes to fill in the gaps. Texas A&M scientists say the pups are not resurrected dire wolves, but rather genetically modified gray wolves with targeted traits. And while the pups may not be dire wolves, these traits may make them look, act or grow like their ancient counterparts.

Beth Shapiro, Ph.D., chief scientist at Colossal, confirmed this in a YouTube video.

“Discovering which parts of a genome makes an animal look and act like another is one of the hardest problems in biology,” Shapiro said in the video posted to Colossal’s YouTube account. “It is something that we had to solve to know which parts of the genome we wanted to edit to make a grey wolf more like a dire wolf.”

Colossal achieved this by using a multi-editing gene system called CRISPR Cas-9, making 20 total edits over 14 genes. Fifteen of those edits were reconstructed to mimic ancient dire wolf DNA.

The extent of which genes were deleted or changed is unknown; many scientists are waiting for the startup to publish their findings. Colossal has not disclosed the percentage of dire wolf traits their pups contain.

“The only way to ‘de-extinct’ something would be to transfer a fully intact cell nucleus, such as one that has been frozen, into an egg that’s had its nucleus removed,” Brian Davis, Ph.D. and A&M professor of biomedical genetics, said. 

That egg would be placed inside a surrogate, which would then grow to become an embryo, a fetus and eventually a baby wolf.

Professor of rice genomics and genetics Michael Thomson, Ph.D, said CRISPR Cas-9 modifies native genes, or genes that are already in a species. 

“You’re not adding anything from another species, like ancient dire wolf DNA into gray wolves — you’re simply modifying what was already there,” Thomson said. 

Colossal claims grey wolves are the closest living relatives to dire wolves, but a 2021 study published in Nature confirmed that “although they were similar morphologically to the extant grey wolf, dire wolves were a highly divergent lineage that split from living canids around 5.7 million years ago. There is no evidence for gene flow between dire wolves and either North American grey wolves or coyotes.”

Sam Stropue, Ph.D., a postdoctoral researcher in Davis’s Evolutionary Medicine Lab, said the question of what to call these wolves is similar to labeling a striped horse a zebra.

“Let’s say you take a horse and change it to have stripes: would you consider it a zebra or a genetically modified horse that looks like a zebra?” Stropue said. “The answer is up for debate.”

Colossal has said the motivation behind the dire wolf project is to fill empty ecological niches as a solution for the biodiversity crisis. Many species like the wooly mammoth, the Tasmanian tiger and the dodo bird are extinct largely due to human causes. Colossal said they want to make up for those mistakes.

“As we lose species within an ecosystem, a hole is created,” Matt James, chief animal officer at Colossal Biosciences, said in a YouTube video. “If you think of a Jenga puzzle, you’re sort of pulling blocks out of the tower when an animal goes extinct, creating instability. If we can find ways to restore animals that provide specific functions, we can create more stability within an ecosystem.”

Davis said dire wolves have been extinct for over 10,000 years. The food that they ate — megafauna like large camels, native north American horses and mammoths — doesn’t exist anymore. Little is known of how dire wolves interacted with their native environments, except for inferences made from fragmented bone structures.

“As someone who is conservation minded, I would rather see animals that are struggling today get this attention,” Stropue said. “There are many issues of habitat shrinkage, where animals have been completely wiped out of their native ranges. Look at the recent extinction of the white rhino; scientists are hoping to clone frozen cells from that animal and reintroduce it to its current, existing habitat.”

Colossal does have a separate conservation program called The Ghost Wolf Genetic Rescue Initiative. It aims to restore critically endangered American red wolves by using genetics from Galveston’s ‘ghost wolves,’ or coyotes that possess a significant amount of red wolf DNA.

“It hasn’t gotten as much media coverage,” said Davis. “I think that the red wolf project is heads above, as far as importance, than anything else Colossal is doing. Red wolves are a species that’s alive today and really struggling. And if you can use technology to help them, that’s conservation: the application of cloning technology to save species.”

While genetic modification isn’t a common occurrence in everyday life, scientists have been using CRISPR to advance research since 2013 and have been able to improve medicines, increase nutritional values of crops and produce organisms with disease resistance.

“I ultimately think we should be careful about what we’re doing so the results impact conservation in a positive way,” Stropue said. “There are many different genome sequencing technologies out there. Sometimes, just having a sequence of DNA is not informative, it tells us very little and is missing key information. For example, ancient DNA is very fragmented, you must have context of where that sequence is, what it’s doing and where it came from to properly use it. Not everything is black and white, much like the information surrounding the dire wolf project.”

Davis said that as soon as Colossal publishes their findings, he plans to independently evaluate their data with his undergraduate students. 

“I am eager to read the peer reviewed publication and look at their genetic data ourselves,” Davis said.

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