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Headline: RAW VIDEO: Game Of Bones! 'Dire Wolves' Recreated By Genetics Firm
Caption: ‘De-extinction’ company Colossal Biosciences have announced the healthy births of their latest effort to bring prehistoric animals back from beyond the grave - ‘dire wolves’. Today, the dire wolf was made famous by the hit HBO series Game of Thrones, as companions of the Stark family, but it was in fact an American canid that had previously been extinct for over 12,500 years. The successful birth of three ‘dire wolves’ is the latest attempt by Colossal to ‘de-extinct’ animals - a project that to date has resulted in mice with wooly mammoth genes. “I could not be more proud of the team. This massive milestone is the first of many coming examples demonstrating that our end-to-end de-extinction technology stack works,” says CEO of Colossal Ben Lamm. “Our team took DNA from a 13,000 year old tooth and a 72,000 year old skull and made healthy dire wolf puppies. It was once said, ‘any sufficiently advanced technology is indistinguishable from magic.’ Today, our team gets to unveil some of the magic they are working on and its broader impact on conservation.” Additionally, Colossal has birthed two litters of cloned red wolves, the most critically endangered wolf in the world, using a new approach to non-invasive blood cloning. The three litters of Colossal’s dire wolves include two adolescent males (Romulus and Remus) and one female puppy (Khaleesi). Colossal also birthed two litters of red wolves from three different genetic founder lines. These litters include one adolescent female red wolf (Hope) and three male red wolf puppies (Blaze, Cinder, and Ash). Sceptics, however, state that the grey wolf's genome is so similar to its dire wolf ancestor that it is difficult to say whether these are genuinely an example of de-extinction - or simply an example of genetically altering modern wolves to look like their legendary ancestor. Colossal extracted ancient DNA from two dire wolf fossils: a tooth from Sheridan Pit, Ohio, that is around 13,000 years old, and an inner ear bone from American Falls, Idaho, around 72,000 years old. The team deeply sequenced the extracted DNA and used Colossal’s novel approach to iteratively assemble high quality ancient genomes, resulting in a 3.4-fold coverage genome from the tooth and 12.8-fold coverage genome from the inner ear bone. Together, this data provided more than 500x more coverage of the dire wolf genome than was available previously. The analysis of the reconstructed dire wolf genome revealed several unknowns of dire wolf evolution. Previous work could not resolve the origin of dire wolves, leading to speculation that jackals may be their closest living relative. Analyses of the high quality dire wolf genome, however, revealed that the grey wolf is the closest living relative of dire wolves – with dire wolves and grey wolves sharing 99.5% of their DNA code. Harvard geneticist and co-founder of Colossal, Dr. George Church sees the project as a vital step forward in preserving the genomes of lost animals. “Preserving, expanding, and testing genetic diversity should be done well before important endangered animal species like the red wolf are lost,” he says. Another source of ecosystem variety stems from our new technologies to de-extinct lost genes, including deep ancient DNA sequencing, polyphyletic trait analyses, multiplex germline editing, and cloning. The dire wolf is an early example of this, including the largest number of precise genomic edits in a healthy vertebrate so far. A capability that is growing exponentially.” Whatever their genetic specificity, the wolves are now thriving on a 2,000+ acre secure expansive ecological preserve that is certified by the American Humane Society and registered with USDA. Within their preserve, the wolves are continuously monitored through on-site live cameras, security personnel, and drone tracking to ensure their safety and welfare. The preserve includes a smaller, six acre secure site where the dire wolves can be further tended to and studied. This smaller area also supports an on-site veterinary clinic, a wolf management facility, an outdoor storm shelter, and natural built dens for the wolves. Robin Ganzert, Ph.D., CEO of American Humane Society, adds: “Colossal has achieved American Humane Society Certification, the prestigious designation ensuring excellence in animal welfare and care. Optimal welfare is evidenced by spacious habitats with ample space and opportunity for animals to socialize, exercise, and exhibit natural behaviors. Staff are passionate, highly engaged and devoted to the animals in their care. We congratulate Colossal as a shining example of excellence in humane care and welfare. The technology they are pursuing may be the key to reversing the sixth mass extinction and making extinction events a thing of the past.” The conservation property will provide lifetime care, feeding, and protection for the wolves. The wolves will be monitored and observed to assess their readiness to move into larger protected and managed care facilities. Long term, Colossal plans to restore the species in secure and expansive ecological preserves potentially on indigenous land. Dr. Beth Shapiro, Colossal’s Chief Science Officer, is delighted with the results. “Our novel approach to iteratively improve our ancient genome in the absence of a perfect reference sets a new standard for paleogenome reconstruction,” she says. ”Together with improved approaches to recover ancient DNA, these computational advances allowed us to resolve the evolutionary history of dire wolves and establish the genomic foundation for de-extinction – specifically for selecting with confidence dire wolf specific genetic variants that establish our targets for gene editing.” Colossal’s team collected blood during a normal veterinary procedure and established cell lines from blood epithelial progenitor cells (EPCs). They then performed multiplex genome editing of these cells followed by whole genome sequencing to confirm editing efficiency and identify any alterations to the genome arising during extended cell culture. The Colossal dire wolf team selected high quality cells with normal karyotypes for cloning by somatic cell nuclear transfer into donor oocytes, followed by short-term culture to confirm cleavage. Healthy developing embryos were then transferred into surrogates for interspecies gestation. Three pregnancies led to births of the first de-extinct species. “The de-extinction of the dire wolf and an end-to-end system for de-extinction is transformative and heralds an entirely new era of human stewardship of life,” says Dr. Christopher Mason, a scientific advisor and member of the board of observers for Colossal. “The same technologies that created the dire wolf can directly help save a variety of other endangered animals as well. This is an extraordinary technological leap in genetic engineering efforts for both science and for conservation as well as preservation of life, and a wonderful example of the power of biotechnology to protect species, both extant and extinct.” In addition to the recreation of the dire wolf, Colossal’s long term goal is for their red wolves to be rewilded through current US conservation efforts in collaboration with the US government. “The dire wolf announcement represents an exciting scientific step and demonstrates the power and possibilities of genetic technologies,” explains Barney Long, Ph.D., Senior Director of Conservation Strategy for Re:Wild. “These technologies will likely transform the conservation of critically endangered species that still exist, and we are excited to apply them to prevent extinctions. From restoring lost genes into small, inbred populations to inserting disease resistance into imperiled species, the genetic technologies being developed by Colossal have immense potential to greatly speed up the recovery of species on the brink of extinction.” Colossal will provide more information about the rescue of the red wolf and restoration of the dire wolf in the coming months following extensive feasibility studies, monitoring, and tracking of the health and well-being of the new species.
Keywords: feature,video,photo,ned stark,dire wolf,puppies,science,technology
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