--- title: The Science Behind the Return of the Dire Wolf description: Here's how Colossal Biosciences brought the dire wolf back after more than 10,000 years. canonical: https://time.com/7275439/science-behind-dire-wolf-return/ author: Jeffrey Kluger article:opinion: false article:content_tier: free article:published_time: 2025-04-07T13:14:28.000Z article:modified_time: 2026-10-19T07:51:23.088Z article:section: Science og:title: The Science Behind the Return of the Dire Wolf og:description: Here's how Colossal Biosciences brought the dire wolf back after more than 10,000 years. og:url: https://time.com/7275439/science-behind-dire-wolf-return/ og:site_name: TIME og:image: https://static.time.com/v3/assets/bltea6093859af6183b/bltdb2fd720a3f9ba55/6998c58693610c82ecc2f837/colossal-biosciences-lab-dire-wolf.jpeg?branch=production&width=1200&quality=75&auto=webp&crop=16:9 og:image:width: 1440 og:image:height: 810 og:image:alt: colossal-biosciences-lab-dire-wolf og:type: article twitter:card: summary_large_image twitter:title: The Science Behind the Return of the Dire Wolf twitter:description: Here's how Colossal Biosciences brought the dire wolf back after more than 10,000 years. twitter:image: https://static.time.com/v3/assets/bltea6093859af6183b/bltdb2fd720a3f9ba55/6998c58693610c82ecc2f837/colossal-biosciences-lab-dire-wolf.jpeg?branch=production&width=1200&quality=75&auto=webp&crop=16:9 ---  # The Science Behind the Return of the Dire Wolf > Sponsored content. 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Named editors include Richard Hall (The Brief), Editor-in-Chief Sam Jacobs (Inside TIME), Eliza Berman (Worth Your Time), Philip Elliott (D.C. Brief), Justin Worland (Future Proof) and Harry Booth (In the Loop). Health Matters is written by TIME's health desk. #### How do I sign up for a TIME newsletter? Go to time.com/newsletters, choose the newsletters you want and enter your email address. There is no cost and no subscription requirement. ### Sources * TIME Newsletters: [time.com/newsletters](/c/time-nl-network-2026q3/newsletters?i=8560f526-2e08-41d7-9a75-a5385e85d9a6&cr=time-nl-network-2026q3-v1) ## Video: Return of the Dire Wolf [Watch (HLS stream): Return of the Dire Wolf](https://cdn.jwplayer.com/manifests/bs34qQnK.m3u8) (7:46)  _Published 2025-04-07. Colossal's project to revive the once-extinct dire wolf could also prevent existing but endangered animals from slipping into extinction themselves._  by [Jeffrey Kluger](https://time.com/author/jeffrey-kluger/)  ## Jeffrey Kluger Editor at Large Apr 7, 2025 1:14 PM UTC Colossal's project to revive the once-extinct dire wolf could also prevent existing but endangered animals from slipping into extinction themselves.  by [Jeffrey Kluger](https://time.com/author/jeffrey-kluger/)  ## Jeffrey Kluger Editor at Large Apr 7, 2025 1:14 PM UTC Nature gave the world the dire wolf [2.6 million years ago](https://www.britannica.com/animal/dire-wolf), and then, through the hard hand of extinction, took it away—some 10,000 to 13,000 years ago when the last of the species died out. Now, the dire wolf is back, brought bounding into the 21st century by [Colossal Biosciences](https://colossal.com/), a Dallas-based biotech company. On April 8, [Colossal announced it](https://time.com/7274542/colossal-dire-wolf/) had used both cloning and gene-editing based on two ancient samples of dire wolf DNA to birth three pups, the six-month-old males Romulus and Remus and the two-month-old female Khaleesi. “Our team took DNA from a 13,000 year old tooth and a 72,000 year old skull and made healthy dire wolf puppies,” said Colossal CEO Ben Lamm in a statement that accompanied the announcement of the births. “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.” **Read more:** [**The Return of the Dire Wolf**](https://time.com/7274542/colossal-dire-wolf/) So what, exactly, does that work involve? Traditional cloning—the kind that famously resulted in [Dolly the sheep](https://time.com/4384947/dolly-sheep-cloning-history/) in 1996, and has since been used to create clones of pigs, cats, deer, horses, mice, goats, gray wolves, dogs and more—is a relatively straightforward, if invasive, process. First, a single cell is taken from a tissue sample of the animal to be cloned. That cell’s nucleus—which contains the individual’s entire genetic code—is then extracted and inserted into a donor ovum from the same species whose own nucleus has been removed. The ovum carrying the new genetic material is allowed to develop into an embryo and then transferred into the womb of a surrogate, which ultimately gives birth to an exact duplicate of the animal from which the donor cell was taken. Colossal says its dire wolf work had key differences. Scientists first analyzed the genome of the dire wolves contained in the ancient tooth and skull. Comparing those genomes to that of the gray wolf—the dire wolf’s closest living relative—they identified 20 differences in 14 genes that account for the dire wolf’s distinguishing characteristics, including its greater size, white coat, wider head, larger teeth, more powerful shoulders, more-muscular legs, and characteristic vocalizations, especially howling and whining. Next, they harvested endothelial progenitor cells (EPCs), which form the lining of bloodvessels, from the bloodstreams of living gray wolves—a less invasive procedure than taking a tissue sample—and edited the 14 genes in their nuclei to express those 20 dire wolf traits. This is trickier than it seems, since genes often have multiple effects, not all of them good. For example, as the company explains in its press release, the dire wolf has three genes that code for its light coat, but in gray wolves they can lead to deafness and blindness. The Colossal team thus engineered two other genes that shut down black and red pigmentation, leading to the dire wolf’s characteristic light color without causing any harm in the edited gray wolf genome. Once this was finished, the edited nuclei were next extracted from the cells and inserted into denucleated gray wolf ova. The ova were left to grow into embryos and 45 were transferred into the wombs of two domestic hound mixes. One embryo in each surrogate mother took hold, and after 65 days of gestation, Rolulus and Remus were born. A few months later, the procedure was repeated with a third surrogate who ultimately gave birth to Khaleesi. All three births were conducted by scheduled cesarean section to minimize the chances of injury during delivery. No surrogate dogs had a miscarriage or stillbirth during the process. Colossal plans to use similar techniques to bring back the Ice Age woolly mammoth in 2028, editing living cell nuclei from Asian elephants—the mammoth’s closest living kin—to express mammoth traits preserved in nearly 60 sets of Ice Age remains. In early March, [the company announced](https://time.com/7264043/colossal-biosciences-woolly-mouse-bring-back-mammoth/) that it had successfully tested its methods in laboratory mice, producing 38 woolly mouse pups which bear the mammoth’s signature shaggy coat. Now it says it’s on track to have a surrogate elephant pregnancy in 2026 (elephants take nearly two years to gestate). Other work in Colossal’s labs involves not bringing back extinct animals but attempting to save endangered ones. Endangered species can suffer from several issues, including a lack of genetic diversity—known as a “genetic bottleneck.” The relatively few animals left repeatedly mate with one another, and the inbreeding results in birth defects, sterility, and health problems proliferating through the species. Colossal has targeted some species with these problems, and is working to genetically edit more diversity into their populations. One such project involves the all-but vanished pink pigeon. The pink pigeon species is indigenous to the island nation of Mauritius and once thrived there, until it lost its habitat as more and more of the island was given over to sugar plantations. Humanity’s introduction of rats and cats—which attack pigeon nests—drove the bird’s numbers down to just ten individuals. With the help of captive breeding programs, more than 650 pigeons were hatched and raised and released back on Mauritius. But with so few birds from which the captive population was bred, the species is experiencing high levels of infertility because of the genetic bottleneck. To get around that, the scientists first tap into the fertilized egg of a pink pigeon and extract what are known as primordial germ cells (PGCs)—the cells that eventually become sperm and egg. In the lab, scientists then genetically edit the PGC genome to introduce greater genetic diversity—though at the moment Colossal is still studying the pink pigeon alleles and doesn’t yet know what traits that more-diverse coding will produce. Then, using the fertilized egg of a common chicken—which is far more plentiful than a pink pigeon egg—they inject the PGCs into the embryo. Once there, the cells travel to the gonads and create an embryo that, after it hatches, grows, and reaches sexual maturity, will produce not chicken chicks, but pigeon chicks. Eventually, those pigeons would be released into the wild population, producing genetically diverse young and helping to fortify the species. None of this is easy and none of it comes cheap—though with a valuation of $10.2 billion, Colossal has the resources to pursue the science without too much concern about the price. And the company is not going it alone. It is partnering with conservation organizations such the [American Wolf Foundation](https://www.americanwolf.org/), The [Mauritian Wildlife Foundation](https://www.mauritian-wildlife.org/), [Save the Elephants](https://savetheelephants.org/), and [Conservation Nation](https://conservationnation.org/). The company worked with [the indigenous MHA Nation](https://www.mhanation.com/) tribes (Mandan, Hidatsa, and Arikara) on the dire wolf project, and the tribes have expressed a desire to have dire wolves live on their lands in North Dakota. Colossal also says it's in advanced negotiations with the government of North Carolina to use its conservation strategies to help strengthen the endangered red wolf population there. The company also believes that the new EPC cloning technique will allow them to save blood samples of existing species in a biobank as a hedge against their ever becoming endangered in the future. Romulus, Remus, and Khaleesi, the most conspicuous of the animals to emerge from Colossal’s labs, will surely not be the last. ## Transcript [00:01] The howl of a dire wolf hasn't been heard on planet Earth for more than 10,000 years. [00:08] That's because the species is extinct. [00:11] Or was colossal. [00:14] Biosciences is a Dallas based company that's using [00:17] genetic engineering to de-extinct long gone species, [00:22] and this is the first time colossal's dire wolf pups, [00:26] who are now six months old, [00:28] have been seen by the public. [00:32] Hey, Ben. It's Jeff Kluger from time magazine. [00:36] Um, a pleasure to meet you. [00:38] Yeah. Tell me a little bit about what the goal [00:42] is for de-extinction and rewilding, ultimately. [00:47] Why are you doing this work? [00:49] It became abundantly clear that we need new tools and technologies for conservation. [00:54] And so we thought this was a really cool way that we could [00:56] create value, create impact, Uh, [00:59] inspire people and then also hopefully thoughtfully rewild some of these species, [01:04] which apparently will also have ecological benefits [01:07] to these different potential ecosystems. [01:10] To try and do that, [01:11] colossal needed to understand dire wolves at a genetic level. [01:15] The company has documented the process from the beginning [01:18] and shared this footage with time for a cover story. [01:23] So can you tell me a little bit about what went into engineering the dire wolf? [01:30] We extracted DNA from two fossils that we knew from [01:34] previous work had some amount of preserved ancient DNA. [01:38] One was a 13 000 year old bone, [01:41] and the other was a 72,000 year old bone, [01:44] an inner ear bone. [01:45] We were able to generate two genomes, [01:48] two dire wolf genome sequences from that which we then compared [01:52] to all the other wolves for which there's already been data generated. [01:56] And when we do that, [01:58] we want to figure out where it is that these two dire wolves are similar to each other, [02:03] but different from the other wolves that are out there. [02:06] And so we come up with this list of genes where they're distinct. [02:10] Now, our goal in the Dire Wolf project, [02:12] just like with all de-extinction projects, [02:14] is to re-engineer the core traits, [02:18] the core characteristics that made these extinct species unique [02:23] and able to fill whatever role that they [02:25] filled in their ecosystems when they were still alive. [02:29] Using this knowledge, colossal then made 20 modifications to [02:34] 14 genes in the DNA of common gray wolf cells. [02:39] These relatively few tweaks to the genetic code produced some big differences. [02:45] The dire wolves white coat, large size, [02:48] characteristic vocalizations like that howling [02:51] you heard at the beginning of the story, and more. [02:54] That DNA was transferred to dinucleotide egg cells, [02:58] meaning cells without their own genetic material, [03:01] and then developed into embryos and were then implanted in [03:05] the wombs of surrogate mothers who were hound mix dogs. [03:10] We didn't know how big these embryos would grow, [03:12] and we wanted to make sure that the surrogate was healthy, [03:14] so we picked large dogs. [03:17] Romulus and Remus, named after [03:19] the Roman mythological twin brothers who were raised by a wolf, [03:23] were born on October 1st, [03:25] 2024, and in January they were joined [03:29] by a younger sister that the colossal team named Khaleesi. [03:34] Each wolf is on track to grow to as large as six feet long and £150. [03:40] Colossal isn't planning to reintroduce them to the wild. [03:45] Instead, the three Direwolves will live out their lives on a fenced 2000 acre preserve. [03:51] Colossal does not want to disclose this location in order to protect the animals. [03:56] I think these are the luckiest animals ever. [04:00] They will live their entire life on this protected ecological reserve, [04:04] where they have all sorts of space and they have natural denning environment, [04:09] and they have a inclement weather hut that they can go and hide out in if they need to. [04:13] They have 24 hour veterinary care. [04:17] Direwolves aren't the only species on Colossal's de-extinction agenda. [04:23] An American company says it has genetically engineered [04:26] mice so that they have developed some traits, like mammoths. [04:31] A small but potentially important step in [04:33] a quest to eventually bring back the prehistoric woolly mammoth. [04:36] They hope to de-extinct the woolly mammoth as early as 2028. [04:41] The company is also hoping to bring back the dodo and the Tasmanian tiger. [04:47] If some of this genetic tinkering feels familiar, [04:51] It's because Hollywood has been here first. [04:54] And spoiler alert we all know that didn't end well. [04:59] So naturally, bioethicists have some concerns here. [05:04] When you're playing with nature, [05:06] uh, nature usually wins. [05:08] Uh, nature is much more complicated than the ability of our brains to understand it. [05:13] Genes do many things. [05:14] There may be a lot of unintended consequences. [05:16] Let's say we alter a gene to make extra hair or to make it burn metabolism more, [05:22] to burn fat more. [05:24] Uh, those genes may do other things in ways that we just don't even understand. [05:27] So we may create animals that have lots of medical problems. [05:30] If we start tinkering with genes, [05:32] we may create a super mouse, [05:34] a super rat that kills all the other animals around. [05:38] But the team at colossal says their mission to restore [05:42] extinct species is also about stopping the disappearance of endangered ones today, [05:48] as experts predict Earth will lose 30% of its genetic diversity by 2050. [05:55] Colossal has used techniques learned from the Dire Wolf project to clone four red wolves, [06:02] a small but important step in fortifying that endangered species. [06:07] The four new wolves could help inject fresh DNA into the red wolf gene pool, [06:12] which currently suffers from a so-called genetic bottleneck, [06:16] the result of too few individuals carrying [06:19] too little genetic variety to keep the species healthy. [06:23] Yes, it would be really amazing to see a mammoth. [06:27] It would be great for the habitats of Tasmania to [06:30] have a keystone predator reintroduced into that ecosystem. [06:33] But the tools that we're developing on the path to [06:37] these species have immediate application to species that are not yet extinct. [06:42] A future that is both biodiverse and filled [06:45] with people we should be giving ourselves the opportunity to [06:49] see what our big brains can do to reverse some [06:52] of the bad things that we've done to the world already. [06:55] There's a huge need to help prevent animals from becoming endangered and going extinct. [07:02] We need to spend more money on conservation, particularly now. [07:06] There's a lot of threats that lands that we have as national parks, [07:10] and there's preserves are going to be used for drilling oil, for instance. [07:13] So there's a lot of habitats where species now live that are going to be under threat. 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