Could Extinct Animals Be Brought Back to Life?
- 演化之聲
- Mar 10
- 3 min read
The American biotechnology startup Colossal Biosciences recently announced what it described as a breakthrough in reviving the dire wolf, an achievement that even appeared on the cover of TIME magazine and attracted considerable public attention. The dire wolf (Aenocyon dirus) was a canid species that lived roughly between 120,000 and 10,000 years ago, from the Late Pleistocene to the Early Holocene. It stood about 100 centimeters tall and measured around 180 centimeters in body length, and it was once widely distributed across both North and South America.
In this project, the research team extracted fragments of DNA sequences from a dire wolf tooth dating to about 11,500 years ago and from a skull approximately 72,000 years old. DNA preserved in fossils often undergoes molecular degradation and fragmentation over time. It is generally estimated that DNA can survive for at most about one million years under favorable conditions, making it extremely difficult to recover complete and high-quality genetic sequences from ancient remains. In this study, the researchers applied high-throughput deep sequencing to the recovered DNA samples, greatly improving sequence accuracy. As a result, they obtained DNA sequence data of higher quality than that reported in previous studies of dire wolves, with coverage exceeding 500-fold. From these data, they identified meaningful gene sequences that could serve as the basis for subsequent gene-editing work.
Because DNA must function within a living cell, the research team selected cells from one of the dire wolf's closest living relatives, the gray wolf (Canis lupus), to act as the genetic host. However, the experiment did not involve inserting the entire dire wolf genome into gray wolf cells. The somatic cell nucleus of a gray wolf contains 39 pairs of chromosomes, carrying roughly 20,000 protein-coding genes and nearly 9,900 non-coding genes. As mentioned earlier, obtaining complete DNA sequences from fossils is extremely difficult, and the total number of genes involved is enormous. Therefore, the researchers adopted a selective strategy: instead of reconstructing the entire genome, they modified only 14 gray wolf genes to match dire wolf versions. Editing a single gene can require weeks or even months of laboratory work, so this approach allowed the team to perform relatively limited genetic engineering while still producing animals with an outward appearance resembling dire wolves.
Among the fourteen edited genes, only one—LCORL—has been publicly identified by Colossal Biosciences so far. The names of the remaining thirteen genes have not yet been disclosed. They may include genes related to traits such as coat color, embryonic development, and muscle development. The LCORL gene itself is primarily involved in regulating skeletal growth.
For the gene-editing procedure, the researchers used blood cells from gray wolves. After collecting blood samples, they isolated white blood cells, which contain nuclei, and applied the widely used CRISPR/Cas9 gene-editing system. Synthetic dire wolf gene sequences were used to replace fourteen homologous genes located at twenty loci on gray wolf chromosome regions. Once editing was complete, the nucleus of the modified blood cell line was transferred into an enucleated gray wolf egg cell, initiating embryonic development.
The experiment ultimately produced three genetically modified pups that outwardly resemble dire wolves. All three animals have entirely white coats. Two of them, born on August 1, 2024, were named Romulus and Remus, after the twin brothers of Roman mythology. The third pup, born on January 31, 2025, was named Khaleesi, inspired by the fantasy series A Song of Ice and Fire.
But are these wolf pups truly dire wolves?
Although Colossal Biosciences describes this research as “de-extinction”, meaning the restoration of an extinct species, the reality is more nuanced. Out of tens of thousands of genes in the genome, only fourteen were modified. This means that more than 99.9% of the pups' genetic material still comes from gray wolves. In other words, these animals are genetically engineered organisms whose outward appearance may resemble dire wolves, rather than genuine representatives of the extinct species.
Even if the claim of reviving dire wolves may be somewhat exaggerated, the technological achievement behind this work undoubtedly represents a major milestone in synthetic biology—one that may be comparable in significance to the birth of Dolly the cloned sheep decades ago.
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Author: Shui Ye-You
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