Stay Ahead, Stay ONMINE

The dire wolf has returned from the dead. A Dallas company ‘de-extincted’ them

Colossal Biosciences has announced that it has brought the dire wolf back from extinction. The Dallas-based “de-extinction” company announced the rebirth the once extinct dire wolf. The dire wolf, largely assumed to be a legendary creature made famous from the HBO hit series Game of Thrones, was an American canid that had previously been extinct for over 12,500 years. I’ve done an interview with the company leaders, who were really planning to make the announcement tomorrow until The Atlantic decided to break the news embargo. I’ll run that interview later. The successful birth of three dire wolves is a revolutionary milestone of scientific progress that illustrates another leap forward in Colossal’s de-extinction technologies and is a critical step on the pathway to the de-extinction of other target species, the company said. Yep, it’s like the plot of Jurassic Park. 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 birth of red wolves provides further evidence of the link between de-extinction efforts and the company’s growing capacity to support conservation efforts globally through de-extinction technology innovation. This news comes on the heels of the recent announcement of the Colossal woolly mouse, which previously held the record for unique germline edits in an animal with eight precision edits. With the dire wolves, Colossal has made 20 unique precision germline edits including 15 edits from the ancient gene variants that have not existed in over 12,000 years, setting a new bar for precision germline editing in any animal. Beth Shapiro, George R.R. Martin and Ben Lamm. “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,” said CEO of Colossal Ben Lamm, in a statement. “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. ” Lamm told me he showed the dire wolves in their safe enclave to George R.R. Martin, author of A Song of Ice and Fire, and Martin broke down in tears. Just last month, Colossal Biosciences said it had created mice with the wooly hair of the wooly mammoth. The company is trying to bring back the wooly mammoth, the dodo and the thylacine. The two litters of Colossal’s dire wolves include two adolescent males (Romulus and Remus) and one female puppy (Khaleesi, named after a Game of Thrones character). 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). “Preserving, expanding, and testing genetic diversity should be done well before important endangered animal species like the red wolf are lost. 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,” said Harvard geneticist and cofounder of Colossal, George Church, in a statement. The wolves are thriving on a 2,000-plus-acre secure expansive ecological preserve that is certified by the American Humane Society and registered with USDA. Colossal employs ten full time animal care staff to support the wolves’ physical and mental well-being. The entire preserve, which includes specialized engagement zones and habit types, is enclosed by 10-foot-tall, zoo-grade fencing with redundant perimeter security. Within the 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. “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,” said Robin Ganzert, CEO of American Humane Society, in a statement. “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. Ultimately Colossal plans to restore the species in secure and expansive ecological preserves on indigenous land. Dire wolf pups. “The de-extinction of the dire wolf is more than a biological revival. Its birth symbolizes a reawakening – a return of an ancient spirit to the world. The dire wolf carries the echoes of our ancestors, their wisdom, and their connection to the wild,” shared MHA Nation Tribal Chairman Mark Fox, in a statement. “Its presence would remind us of our responsibility as stewards of the Earth – to protect not just the wolf, but the delicate balance of life itself. The work of the team at Colossal Biosciences is not only significant to our lands and people, but for conservation efforts across the globe. The ability for technological innovation to bring forth something so culturally and spiritually significant to indigenous people is paralleled by the far reaching impacts that this technology provides for the future of stewardship on our planet in species diversity and conservation.” An overview of dire wolves Dire wolves (Aenocyon dirus) were distributed across the American midcontinent during the Pleistocene ice ages. The oldest confirmed dire wolf fossil, from Black Hills, SD, is around 250,000 years old. Colossal’s genomic data indicate, however, that the lineage first appeared during the Late Pliocene, between 3.5 and 2.5 million years ago, as a consequence of admixture between two more ancient (and now extinct) canid lineages. Dire wolves were as much as 25% larger than gray wolves and had a slightly wider head, light thick fur and stronger jaw. As hyper-carnivores, their diet comprised at least 70% meat from mostly horses and bison. Dire wolves went extinct at the end of the most recent ice age, around 13,000 years ago. “I have spent nearly 10,000 days in the field studying the behavior of the wolves in Yellowstone National Park. Prior to Yellowstone, I worked in Denali National Park in Alaska where I studied wildlife species that live on the tundra: wolves, grizzlies, caribou, and Dall sheep,” said Rick Mcintyre, author and internationally recognized as one of the world’s foremost experts on wild wolf behavior, and Colossal Conservation Advisory Board Member. “Later, I spent some time on the northern and western coasts of Alaska. I was born far too late to see now extinct Ice Age species such as dire wolves and mammoths. “ He added, “Long ago, my Celtic ancestors probably lived among those animals in northern Europe and may have had some role in contributing to their extinction. I never thought I might live in a time when we have the science to bring back those species and restore them to selected sections of their former homeland. I have a dream that some time in the near future I can go back to Alaska, or a similar place in Northern Europe or Asia, and see those extinct species that have been brought back thanks to science. When that happens, I will begin to study the behavior of dire wolves.” For many people, introduction to the dire wolf occurred through the lens of entertainment, rather than the natural world. Mentions of this legendary prehistoric canid in role-playing games like Dungeons & Dragons; video games like World of Warcraft; music like the Grateful Dead’s aptly-named song, “Dire Wolf”; and most notably, George R.R. Martin’s best-selling fantasy novel series, A Song of Ice and Fire and its TV adaptation, Game of Thrones. “Many people view dire wolves as mythical creatures that only exist in a fantasy world, but in reality, they have a rich history of contributing to the American ecosystem,” said Game of Thrones creator, esteemed author, and Colossal Investor and Cultural Advisor George R.R. Martin. “I get the luxury to write about magic, but Ben and Colossal have created magic by bringing these majestic beasts back to our world.” The science behind the return of the dire wolf A baby dire wolf. The birth of dire wolf pups proves the efficacy of Colossal’s de-extinction protocols and the feasibility of creating a standardized toolkit for de-extinction. The dire wolf pups set the record for number of precise genetic edits in any living species. The company performed a record 20 precise edits to the genome, all modifications derived from analysis of the dire wolf genome with 15 of those edits being the exact extinct variants. Together these edits contribute to a larger, stronger body and a longer, fuller coat with light pigmentation. To de-extinct the dire wolf, Colossal:● Extracted and sequenced ancient DNA from two dire wolf fossils;● Assembled ancient genomes from both, and compared those to genomes from living canids including wolves, jackals, foxes, and dholes;● Identified gene variants specific to dire wolves;● Determined that dire wolves had a white coat color, and long thick fur – aspects of the dire wolf phenotype that were unknowable from fossils and consistent with animals that lived during cold periods of the Pleistocene ice ages;● Performed multiplex gene editing to a donor genome from their closest living relative, the gray wolf, resulting in edits 20 sites in 14 genes with 15 of those edits being extinct variants;● Screen edited cell lines via whole genome sequencing and karyotyping;● Cloned high quality cell lines using somatic cell nuclear transfer into donor egg cells;● Performed embryo transfer and managed interspecies surrogacy; and,● Successfully birthed an extinct species. 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 500 times more coverage of the dire wolf genome than was available previously. Interspecies gestation Colossal’s computational 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 gray wolf is the closest living relative of dire wolves – with dire wolves and gray wolves sharing 99.5% of their DNA code. Interestingly, the analysis also revealed that dire wolves have a hybrid ancestry, which helps to explain the previous uncertainty. Colossal’s analyses indicated that the dire wolf lineage emerged between 3.5 and 2.5 million years ago as a consequence of hybridization between two ancient canid lineages: an ancient and early member of the tribe Canini, which may be represented in the fossil record as Eucyon or Xenocyon, and a lineage that was part of the early diversification of wolf-like lineages including wolves, dholes, jackals, and African wild dogs. “Our novel approach to iteratively improve our ancient genome in the absence of a perfect reference sets a new standard for paleogenome reconstruction ,” said Beth Shapiro, Colossal’s chief science officer and a leading expert in the field of ancient DNA, in a statement. ”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.” Analyses of the dire wolf genome allowed Colossal to identify the key variants in dire wolves that are not found in other canids that tell the story of dire wolf evolution. For example, Colossal identified multiple genes undergoing positive selection that are linked to dire wolf skeletal, muscular, circulatory, and sensory adaptation. The team discovered dire wolf specific variants in essential pigmentation genes revealing that dire wolves had a white coat color – a fact that is impossible to glean from fossil remains alone. The team also identified dire wolf specific variants in regulatory regions that alter the expression of genes. From this list, Colossal used its proprietary computational pipeline and software to select 20 gene edits across 14 distinct loci as targets for dire wolf de-extinction, focusing on the core traits that made dire wolves unique including size, musculature, hair color, hair texture, hair length, and coat patterning. Based on Colossal’s genomic analysis, the team used gray wolves – the closest living relative of dire wolves – as the donor species for establishing cell lines. Using Colossal’s novel approach to establish cell lines from a standard blood draw, the team collected blood during a normal veterinary procedure and established cell lines from blood epithelial progenitor cells (EPCs). The team 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,” said Christopher Mason, a scientific advisor and member of the board of observers for Colossal, in a statement. “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.” Colossal edited 15 extinct dire wolf variants into the donor gray wolf genome, creating dire wolves that express genes that have not been expressed for more than 10,000 years. These target genes were selected because each is linked to one or more key traits that made dire wolves unique among canids. For example, Colossal targeted CORIN, a serine protease that is expressed in hair follicles and suppresses the agouti pathway, impacting coat color and patterning. The dire wolf CORIN variants impact pigmentation in a way that leads to a light coat color. Colossal also edited dire wolf specific variants in a multi-gene regulatory module that has been linked to variation in body size as well as ear, skull, and facial morphology. The region encodes eight genes that establish species-specific constraints in skeletal size and structure, and has been linked to features including differences in human height and the diverse beak shapes among finch species. One gene encoded by this module – HMGA2 – is directly associated with body size in dogs and wolves. Another gene in this module – MSRB3 – has been linked to variation in ear and skull shape among canines and other mammals. Given the role of these genes in establishing species-specific size and morphology, the dire wolf team edited dire wolf-specific variants into gene enhancers (DNA sequences make it more likely that the gene will be transcribed into RNA) in this genomic region. For each high impact variant identified as linked to a target phenotype, Colossal’s dire wolf team created a detailed profile of all potential impacts on a donor gray wolf genome. To ensure healthy outcomes, the team discarded variants that would incur some risk outside of the predicted phenotype or prioritized variants already evolved in gray wolves with the predicted phenotype. For example, Colossal edited the protein coding region of LCORL, a transcription factor that regulates gene expression by influencing whether a gene is transcribed. Variations in LCORL have been linked to variation in body size in many species, including humans, horses, and canids. The dire wolf has three changes to the LCORL protein sequence that are predicted via 3D modeling to alter the way the protein folds precisely at the location where LCORL should bind to a major gene silencing complex known as the PRC2 domain. Interestingly, large dog breeds (which are domesticated gray wolves) have a variant of LCORL that is missing the PRC2 domain entirely. As the dire wolf version is predicted to have a similar phenotypic impact as the variant found in larger dog breeds, and because of the potential for LCORL to interact with other genes in the gray wolf genetic background that are not edited, Colossal’s dire wolves express the protein that is found in the largest grey wolves. This choice allows for the predicted phenotypic impact and without any additional risk. “Functional de-extinction uses the safest and most effective approach to bring back the lost phenotypes that make an extinct species unique,” said Shapiro. “We turn to ancient DNA to learn as much as we can about each species and, whenever possible, to link specific extinct DNA sequence variants to each key trait. In some cases, we learn that variants already present in the surrogate species can be used to engineer that key trait. In those cases, engineering existing variants into the donor genome is an optimal path, as that path provides strong confidence in the outcome with minimal risk to the animal.” The dire wolf genome has protein-coding substitutions in three essential pigmentation genes: OCA2, SLC45A2, and MITF, which directly impact the function and development of melanocytes. While these variants would have led to a light coat in dire wolves, variation in these genes in gray wolves can lead to deafness and blindness. The team therefore engineered a light colored coat in Colossal’s dire wolves via a path known to be safe in gray wolves: by inducing loss-of-function to MC1R and MFSD12. These genes influence expression of pigments eumelanin (black) and pheomelanin (red) in melanocytes that deposit to the coat, achieving the lighter pigmented coat color phenotype suggested by the dire wolf genome but without any potential health impacts. “When I learned of Colossal’s approach to engineering the light coat color into their dire wolves, I was simultaneously impressed and relieved,” said Elinor Karlsson, associate professor in Bioinformatics and Integrative Biology at the UMass Chan Medical School and Director of Vertebrate Genomics at the Broad Institute of MIT and Harvard, in a statement. “By choosing to engineer in variants that have already passed evolution’s clinical trial, Colossal is demonstrating their dedication to an ethical approach to de-extinction.” The path to the dire wolf and the red wolf also led to innovations reaching beyond de-extinction, including advances in ancient DNA genome reconstruction and genotype-to-phenotype prediction, as well as optimized tools for multiplex gene editing. Another important contribution from the project are Colossal protocols to establish cell lines directly from blood that can be used for somatic cell nuclear transfer. The collection of whole blood is a rapid and noninvasive procedure that is routinely carried out on sedated wolves for veterinary monitoring purposes. These field collections provide a valuable opportunity to isolate expandable endothelial progenitor cells (EPCs), which are cells that are involved in vascular repair and neovascularization and differentiate into the cells that line blood vessels. Isolated EPC cell lines can be frozen for later genomic analyses and, Colossal has now shown, can be used to successfully clone wild canids. Biobanking and cloning EPCs from threatened or endangered populations of wild wolves provides a safety net to preserve the genomic diversity present today from further loss and extinction. “Whether due to natural or human-induced changes in climate, habitat and food source, the extinction of an untold number of species is a loss to our planet’s history and biodiversity. Modern genetics lets us peer into the past, and modern genetic engineering lets us recover what was lost and might yet thrive. Along the way, it invents the tools that let us protect what is still here. As humans we have a unique capacity and moral obligation to steward the earth for the benefit of ourselves and all living things, for now and for the future,” said Alta Charo, Professor of Law and Bioethics and Colossal Bioethics Lead, in a statement. A leap forward for red wolf recovery The technology developed within the Colossal de-extinction pipeline has immediate applications for conservation efforts globally. The research undertaken to birth the dire wolf has been successfully paralleled to the birth of two litters of the red wolf. Colossal’s two litters of red wolves include one female and three males from a total of three different cell lines. Colossal generated the cell lines, collected from the southwest Louisiana population, using its novel method of insolating EPCs following a standard blood draw. The pups were born after somatic cell nuclear transfer into a donor oocyte followed by embryogenesis and embryo transfer into a surrogate mother. Both embryo transfers resulted in the birth of healthy red wolf pups. “In a world where humans are rapidly eroding the environment, species (especially wolves) need allies. One of the most impactful ways to be an ally is to use science to help discover and preserve lost genes, genetic diversity, and phenotypes. We now have the technology that can edit DNA to increase resilience in species that are facing extinction or to revive extinct genetic diversity and species. We get to witness the de-extinction of the dire wolf, which is a marvel of scientific progress, and just the start of numerous species we can bring back to create a better, more habitable, and balanced world. I am beyond thrilled that such technologies are also being leveraged to support programs of preventing extinction in endangered species like the red wolf,” said Bridgett von Holdt, Princeton associate professor of Evolutionary Genomics and Epigenetics. Currently listed as critically endangered, fewer than 20 red wolves remain in North America, which makes them the most endangered wolves on the planet. Thousands of red wolves once roamed across most of eastern North America. But by 1960 they were nearly extinct. The Endangered Species Act and a captive breeding program have been critical to securing the reintroduction of red wolves back into the wild in eastern North Carolina. The Fish and Wildlife Service’s Red Wolf Recovery Program successfully grew the wild population to more than 120 wolves. When the program was halted in 2015, however, the population crashed to as few as seven wolves. In 2021 the program resumed, but red wolves have struggled to regain their numbers. One challenge has been to maintain genetic diversity among the captive and re-wilded population of red wolves, all of which descend from only 12 founder individuals. Adding Colossal’s red wolves to the captive breeding population would increase the number of founding lineages by 25%. “The dire wolf project is surreal and unreal at the same time. It’s recreating reality that stemmed from reality, from millennia ago. To think that in this day dire wolves aren’t just mythical illusions and tales told in movies that we believe may have had origins in reality…Now, we have the science and ingenuity to bring life back to once existing reality. Colossal is drastically changing the prognosis for countless endangered species around the world,” said Aurelia Skipwith, former director of the U.S. Fish and Wildlife, in a statement. “The company’s work to combat extinction of the red wolf creates hope for so many other critically endangered species fighting for survival.” The research program for the dire wolf has also helped efforts to develop technologies for the red ‘ghost’ wolf, unique canids, found only on the gulf coast of Texas and Louisiana who carry lost DNA and biodiversity of the red wolf. Researchers Bridgett vonHoldt of Princeton University and Kristin Brzesk of Michigan Technological University lead the Gulf Coast Canine Project which aims to understand the genetic ancestry of the wild canines persisting along the Gulf Coast of the United States. They study how red wolf ancestry shapes morphology and behavior, and the support of Colossal has helped them accelerate their research through the inclusion of data from the red wolf genome, the assembly of a reference genome for the recovery population’s red wolves, and finally the creation of a pangenome for US native canids.The hope is that this work can set precedent for other species with a complicated genetic history, while also improving the capacity of conservation efforts for the red wolf, today. In addition to the challenges of reintroduction, the red wolf’s biggest threat of extinction comes from limited genetic diversity that resulted from the population’s bottleneck that occurred during its rapid decline. The technology and understanding developed through Colossal’s red ‘ghost’ wolf project has now unlocked additional genetic diversity and red wolf ancestry that can be a resource to create a genetic rescue program for the red wolf population. “The extinction crisis is a massive, mostly unattended, and growing worldwide problem. I applaud Colossal for taking bold and innovative steps to arrest and reverse the crisis by developing cutting edge genetic techniques to undergird reintroduction efforts of imperiled species. By collaborating with Dr. vonHoldt on red wolf recovery, Colossal creates potential to increase the genetic diversity of this species which exists only because of a captive population founded by a paltry 14 individuals. Perfecting genomic tools to integrate “ghost alleles” from Gulf Coast canids would increase red wolf genetic diversity and generate knowledge for recovering other imperiled species, like the bolson tortoise, that are compromised by restricted ranges and reduced genetic diversity.”- Mike Phillips, Director of the Turner Endangered Species Fund and project lead for rewilding gray wolves in the Greater Yellowstone Ecosystem. From conservation to rewilding Colossal’s long term goal is for their red wolves to be re-wilded through current US conservation efforts in collaboration with the US government. “Colossal’s successful de-extinction of the dire wolf represents a massive coup for conservation,” said Matt James, Colossal’s Chief Animal Officer and Colossal Foundation Executive Director. “The technologies developed on the path to the dire wolf are already opening up new opportunities to rescue critically endangered canids. The creation of less-invasive sampling tools such as our EPC blood cloning platform allows for the conservation community to ramp up biobanking efforts of those species on the brink.” Colossal’s de-extinction mission always includes plans to rewild associated species in alignment with global conservation efforts. Research suggests that rewilding wolves can have massive impacts on factors that drive climate change and support biodiversity. Inspired by the US Fish and Wildlife’s bold efforts to rescue the red wolf from the brink of extinction, Colossal has created technological platforms to offer key tools to those in the fight to save the world’s most endangered wolf. “Today’s dire wolf announcement represents an exciting scientific step and demonstrates the power and possibilities of genetic technologies,” said Barney Long, Phd, 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. “As someone who’s fascinated with canids—I’ve written about coyotes and wolves—the idea of being able to have dire wolves again is tremendously, personally exciting, and I think it’s going to be exciting to a lot of people. An organization like Colossal, to me, is one of the things that gives me hope. If I were looking 100 years out, I would say that we’re very likely to have animals once again that we thought were always gone—just as I once thought I was never going to get to hear a wolf howl… That was something I really never thought I’d have a chance to experience, and it became reality. And so, that makes me think that more and more, we’re going to get to experience what Henry David Thoreau lamented back in the 1850s—that he wasn’t getting to experience an entire heaven and an entire Earth. And I think that’s something to look forward to.” – Dan Flores, A. B. Hammond Professor Emeritus of the History of the American West at the University of Montana-Missoula Partnerships The effort to de-extinct the dire wolf, genetic rescue of the red wolf, and innovative gray wolf conservation programs are all made possible through Colossal’s collaborative work with a broad spectrum of Indigenous communities, conservation organizations, and scientific experts. Colossal extended its deepest gratitude to the MHA Nation, the Nez Perce Tribe, the Karankawa Tribe of Texas, Indigenous Led, and the Wind River Tribal Buffalo Initiative, whose ancestral knowledge and insights have guided the company’s efforts. Colossal Biosciences and the Colossal Foundation also thank the many conservation organizations whose expertise and passion fuel these initiatives, including the American Wolf Foundation, Re:wild, Conservation Nation, Gulf Coast Canid Project, International Coexistence Network, Wolf Connection, Grizzly Systems and the Yellowstone Wolf Project. Colossal was founded by emerging technology and software entrepreneur Ben Lamm and world-renowned geneticist and serial biotech entrepreneur George Church, and is the first to apply CRISPR technology for the purposes of species de-extinction. Colossal creates innovative technologies for species restoration, critically endangered species protection and the repopulation of critical ecosystems that support the continuation of life on Earth. Colossal is accepting humanity’s duty to restore Earth to a healthier state, while also solving for the future economies and biological necessities of the human condition through cutting-edge science and technologies. To follow along, please visit: www.colossal.com.

Colossal Biosciences has announced that it has brought the dire wolf back from extinction. The Dallas-based “de-extinction” company announced the rebirth the once extinct dire wolf.

The dire wolf, largely assumed to be a legendary creature made famous from the HBO hit series Game of Thrones, was an American canid that had previously been extinct for over 12,500 years. I’ve done an interview with the company leaders, who were really planning to make the announcement tomorrow until The Atlantic decided to break the news embargo. I’ll run that interview later.

The successful birth of three dire wolves is a revolutionary milestone of scientific progress that illustrates another leap forward in Colossal’s de-extinction technologies and is a critical step on the pathway to the de-extinction of other target species, the company said. Yep, it’s like the plot of Jurassic Park.

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 birth of red wolves provides further evidence of the link between de-extinction efforts and the company’s growing capacity to support conservation efforts globally through de-extinction technology innovation.

This news comes on the heels of the recent announcement of the Colossal woolly mouse, which previously held the record for unique germline edits in an animal with eight precision edits.

With the dire wolves, Colossal has made 20 unique precision germline edits including 15 edits from the ancient gene variants that have not existed in over 12,000 years, setting a new bar for precision germline editing in any animal.

Beth Shapiro, George R.R. Martin and Ben Lamm.

“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,” said CEO of Colossal Ben Lamm, in a statement. “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. ”

Lamm told me he showed the dire wolves in their safe enclave to George R.R. Martin, author of A Song of Ice and Fire, and Martin broke down in tears. Just last month, Colossal Biosciences said it had created mice with the wooly hair of the wooly mammoth. The company is trying to bring back the wooly mammoth, the dodo and the thylacine.

The two litters of Colossal’s dire wolves include two adolescent males (Romulus and Remus) and one female puppy (Khaleesi, named after a Game of Thrones character). 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).

“Preserving, expanding, and testing genetic diversity should be done well before important endangered animal species like the red wolf are lost. 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,” said Harvard geneticist and cofounder of Colossal, George Church, in a statement.

The wolves are thriving on a 2,000-plus-acre secure expansive ecological preserve that is certified by the American Humane Society and registered with USDA. Colossal employs ten full time animal care staff to support the wolves’ physical and mental well-being. The entire preserve, which includes specialized engagement zones and habit types, is enclosed by 10-foot-tall, zoo-grade fencing with redundant perimeter security.

Within the 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.

“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,” said Robin Ganzert, CEO of American Humane Society, in a statement. “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. Ultimately Colossal plans to restore the species in secure and expansive ecological preserves on indigenous land.

Dire wolf pups.

“The de-extinction of the dire wolf is more than a biological revival. Its birth symbolizes a reawakening – a return of an ancient spirit to the world. The dire wolf carries the echoes of our ancestors, their wisdom, and their connection to the wild,” shared MHA Nation Tribal Chairman Mark Fox, in a statement. “Its presence would remind us of our responsibility as stewards of the Earth – to protect not just the wolf, but the delicate balance of life itself. The work of the team at Colossal Biosciences is not only significant to our lands and people, but for conservation efforts across the globe. The ability for technological innovation to bring forth something so culturally and spiritually significant to indigenous people is paralleled by the far reaching impacts that this technology provides for the future of stewardship on our planet in species diversity and conservation.”

An overview of dire wolves

Dire wolves (Aenocyon dirus) were distributed across the American midcontinent during the Pleistocene ice ages. The oldest confirmed dire wolf fossil, from Black Hills, SD, is around 250,000 years old. Colossal’s genomic data indicate, however, that the lineage first appeared during the Late Pliocene, between 3.5 and 2.5 million years ago, as a consequence of admixture between two more ancient (and now extinct) canid lineages.

Dire wolves were as much as 25% larger than gray wolves and had a slightly wider head, light thick fur and stronger jaw. As hyper-carnivores, their diet comprised at least 70% meat from mostly horses and bison. Dire wolves went extinct at the end of the most recent ice age, around 13,000 years ago.

“I have spent nearly 10,000 days in the field studying the behavior of the wolves in Yellowstone National Park. Prior to Yellowstone, I worked in Denali National Park in Alaska where I studied wildlife species that live on the tundra: wolves, grizzlies, caribou, and Dall sheep,” said Rick Mcintyre, author and internationally recognized as one of the world’s foremost experts on wild wolf behavior, and Colossal Conservation Advisory Board Member. “Later, I spent some time on the northern and western coasts of Alaska. I was born far too late to see now extinct Ice Age species such as dire wolves and mammoths. “

He added, “Long ago, my Celtic ancestors probably lived among those animals in northern Europe and may have had some role in contributing to their extinction. I never thought I might live in a time when we have the science to bring back those species and restore them to selected sections of their former homeland. I have a dream that some time in the near future I can go back to Alaska, or a similar place in Northern Europe or Asia, and see those extinct species that have been brought back thanks to science. When that happens, I will begin to study the behavior of dire wolves.”

For many people, introduction to the dire wolf occurred through the lens of entertainment, rather than the natural world. Mentions of this legendary prehistoric canid in role-playing games like Dungeons & Dragons; video games like World of Warcraft; music like the Grateful Dead’s aptly-named song, “Dire Wolf”; and most notably, George R.R. Martin’s best-selling fantasy novel series, A Song of Ice and Fire and its TV adaptation, Game of Thrones.

“Many people view dire wolves as mythical creatures that only exist in a fantasy world, but in reality, they have a rich history of contributing to the American ecosystem,” said Game of Thrones creator, esteemed author, and Colossal Investor and Cultural Advisor George R.R. Martin. “I get the luxury to write about magic, but Ben and Colossal have created magic by bringing these majestic beasts back to our world.”

The science behind the return of the dire wolf

A baby dire wolf.

The birth of dire wolf pups proves the efficacy of Colossal’s de-extinction protocols and the feasibility of creating a standardized toolkit for de-extinction. The dire wolf pups set the record for number of precise genetic edits in any living species. The company performed a record 20 precise edits to the genome, all modifications derived from analysis of the dire wolf genome with 15 of those edits being the exact extinct variants. Together these edits contribute to a larger, stronger body and a longer, fuller coat with light pigmentation.

To de-extinct the dire wolf, Colossal:
● Extracted and sequenced ancient DNA from two dire wolf fossils;
● Assembled ancient genomes from both, and compared those to genomes from living canids including wolves, jackals, foxes, and dholes;
● Identified gene variants specific to dire wolves;
● Determined that dire wolves had a white coat color, and long thick fur – aspects of the dire wolf phenotype that were unknowable from fossils and consistent with animals that lived during cold periods of the Pleistocene ice ages;
● Performed multiplex gene editing to a donor genome from their closest living relative, the gray wolf, resulting in edits 20 sites in 14 genes with 15 of those edits being extinct variants;
● Screen edited cell lines via whole genome sequencing and karyotyping;
● Cloned high quality cell lines using somatic cell nuclear transfer into donor egg cells;
● Performed embryo transfer and managed interspecies surrogacy; and,
● Successfully birthed an extinct species.

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 500 times more coverage of the dire wolf genome than was available previously.

Interspecies gestation

Colossal’s computational 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 gray wolf is the closest living relative of dire wolves – with dire wolves and gray wolves sharing 99.5% of their DNA code.

Interestingly, the analysis also revealed that dire wolves have a hybrid ancestry, which helps to explain the previous uncertainty. Colossal’s analyses indicated that the dire wolf lineage emerged between 3.5 and 2.5 million years ago as a consequence of hybridization between two ancient canid lineages: an ancient and early member of the tribe Canini, which may be represented in the fossil record as Eucyon or Xenocyon, and a lineage that was part of the early diversification of wolf-like lineages including wolves, dholes, jackals, and African wild dogs.

“Our novel approach to iteratively improve our ancient genome in the absence of a perfect reference sets a new standard for paleogenome reconstruction ,” said Beth Shapiro, Colossal’s chief science officer and a leading expert in the field of ancient DNA, in a statement. ”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.”

Analyses of the dire wolf genome allowed Colossal to identify the key variants in dire wolves that are not found in other canids that tell the story of dire wolf evolution. For example, Colossal identified multiple genes undergoing positive selection that are linked to dire wolf skeletal, muscular, circulatory, and sensory adaptation. The team discovered dire wolf specific variants in essential pigmentation genes revealing that dire wolves had a white coat color – a fact that is impossible to glean from fossil remains alone. The team also identified dire wolf specific variants in regulatory regions that alter the expression of genes. From this list, Colossal used its proprietary computational pipeline and software to select 20 gene edits across 14 distinct loci as targets for dire wolf de-extinction, focusing on the core traits that made dire wolves unique including size, musculature, hair color, hair texture, hair length, and coat patterning.

Based on Colossal’s genomic analysis, the team used gray wolves – the closest living relative of dire wolves – as the donor species for establishing cell lines. Using Colossal’s novel approach to establish cell lines from a standard blood draw, the team collected blood during a normal veterinary procedure and established cell lines from blood epithelial progenitor cells (EPCs). The team 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,” said Christopher Mason, a scientific advisor and member of the board of observers for Colossal, in a statement. “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.”

Colossal edited 15 extinct dire wolf variants into the donor gray wolf genome, creating dire wolves that express genes that have not been expressed for more than 10,000 years. These target genes were selected because each is linked to one or more key traits that made dire wolves unique among canids. For example, Colossal targeted CORIN, a serine protease that is expressed in hair follicles and suppresses the agouti pathway, impacting coat color and patterning. The dire wolf CORIN variants impact pigmentation in a way that leads to a light coat color.

Colossal also edited dire wolf specific variants in a multi-gene regulatory module that has been linked to variation in body size as well as ear, skull, and facial morphology. The region encodes eight genes that establish species-specific constraints in skeletal size and structure, and has been linked to features including differences in human height and the diverse beak shapes among finch species.

One gene encoded by this module – HMGA2 – is directly associated with body size in dogs and wolves. Another gene in this module – MSRB3 – has been linked to variation in ear and skull shape among canines and other mammals. Given the role of these genes in establishing species-specific size and morphology, the dire wolf team edited dire wolf-specific variants into gene enhancers (DNA sequences make it more likely that the gene will be transcribed into RNA) in this genomic region.

For each high impact variant identified as linked to a target phenotype, Colossal’s dire wolf team created a detailed profile of all potential impacts on a donor gray wolf genome. To ensure healthy outcomes, the team discarded variants that would incur some risk outside of the predicted phenotype or prioritized variants already evolved in gray wolves with the predicted phenotype.

For example, Colossal edited the protein coding region of LCORL, a transcription factor that regulates gene expression by influencing whether a gene is transcribed. Variations in LCORL have been linked to variation in body size in many species, including humans, horses, and canids. The dire wolf has three changes to the LCORL protein sequence that are predicted via 3D modeling to alter the way the protein folds precisely at the location where LCORL should bind to a major gene silencing complex known as the PRC2 domain. Interestingly, large dog breeds (which are domesticated gray wolves) have a variant of LCORL that is missing the PRC2 domain entirely.

As the dire wolf version is predicted to have a similar phenotypic impact as the variant found in larger dog breeds, and because of the potential for LCORL to interact with other genes in the gray wolf genetic background that are not edited, Colossal’s dire wolves express the protein that is found in the largest grey wolves. This choice allows for the predicted phenotypic impact and without any additional risk.

“Functional de-extinction uses the safest and most effective approach to bring back the lost phenotypes that make an extinct species unique,” said Shapiro. “We turn to ancient DNA to learn as much as we can about each species and, whenever possible, to link specific extinct DNA sequence variants to each key trait. In some cases, we learn that variants already present in the surrogate species can be used to engineer that key trait. In those cases, engineering existing variants into the donor genome is an optimal path, as that path provides strong confidence in the outcome with minimal risk to the animal.”

The dire wolf genome has protein-coding substitutions in three essential pigmentation genes: OCA2, SLC45A2, and MITF, which directly impact the function and development of melanocytes. While these variants would have led to a light coat in dire wolves, variation in these genes in gray wolves can lead to deafness and blindness. The team therefore engineered a light colored coat in Colossal’s dire wolves via a path known to be safe in gray wolves: by inducing loss-of-function to MC1R and MFSD12. These genes influence expression of pigments eumelanin (black) and pheomelanin (red) in melanocytes that deposit to the coat, achieving the lighter pigmented coat color phenotype suggested by the dire wolf genome but without any potential health impacts.

“When I learned of Colossal’s approach to engineering the light coat color into their dire wolves, I was simultaneously impressed and relieved,” said Elinor Karlsson, associate professor in Bioinformatics and Integrative Biology at the UMass Chan Medical School and Director of Vertebrate Genomics at the Broad Institute of MIT and Harvard, in a statement. “By choosing to engineer in variants that have already passed evolution’s clinical trial, Colossal is demonstrating their dedication to an ethical approach to de-extinction.”

The path to the dire wolf and the red wolf also led to innovations reaching beyond de-extinction, including advances in ancient DNA genome reconstruction and genotype-to-phenotype prediction, as well as optimized tools for multiplex gene editing. Another important contribution from the project are Colossal protocols to establish cell lines directly from blood that can be used for somatic cell nuclear transfer.

The collection of whole blood is a rapid and noninvasive procedure that is routinely carried out on sedated wolves for veterinary monitoring purposes. These field collections provide a valuable opportunity to isolate expandable endothelial progenitor cells (EPCs), which are cells that are involved in vascular repair and neovascularization and differentiate into the cells that line blood vessels. Isolated EPC cell lines can be frozen for later genomic analyses and, Colossal has now shown, can be used to successfully clone wild canids. Biobanking and cloning EPCs from threatened or endangered populations of wild wolves provides a safety net to preserve the genomic diversity present today from further loss and extinction.

“Whether due to natural or human-induced changes in climate, habitat and food source, the extinction of an untold number of species is a loss to our planet’s history and biodiversity. Modern genetics lets us peer into the past, and modern genetic engineering lets us recover what was lost and might yet thrive. Along the way, it invents the tools that let us protect what is still here. As humans we have a unique capacity and moral obligation to steward the earth for the benefit of ourselves and all living things, for now and for the future,” said Alta Charo, Professor of Law and Bioethics and Colossal Bioethics Lead, in a statement.

A leap forward for red wolf recovery

The technology developed within the Colossal de-extinction pipeline has immediate applications for conservation efforts globally. The research undertaken to birth the dire wolf has been successfully paralleled to the birth of two litters of the red wolf.

Colossal’s two litters of red wolves include one female and three males from a total of three different cell lines. Colossal generated the cell lines, collected from the southwest Louisiana population, using its novel method of insolating EPCs following a standard blood draw. The pups were born after somatic cell nuclear transfer into a donor oocyte followed by embryogenesis and embryo transfer into a surrogate mother. Both embryo transfers resulted in the birth of healthy red wolf pups.

“In a world where humans are rapidly eroding the environment, species (especially wolves) need allies. One of the most impactful ways to be an ally is to use science to help discover and preserve lost genes, genetic diversity, and phenotypes. We now have the technology that can edit DNA to increase resilience in species that are facing extinction or to revive extinct genetic diversity and species. We get to witness the de-extinction of the dire wolf, which is a marvel of scientific progress, and just the start of numerous species we can bring back to create a better, more habitable, and balanced world. I am beyond thrilled that such technologies are also being leveraged to support programs of preventing extinction in endangered species like the red wolf,” said Bridgett von Holdt, Princeton associate professor of Evolutionary Genomics and Epigenetics.

Currently listed as critically endangered, fewer than 20 red wolves remain in North America, which makes them the most endangered wolves on the planet. Thousands of red wolves once roamed across most of eastern North America. But by 1960 they were nearly extinct. The Endangered Species Act and a captive breeding program have been critical to securing the reintroduction of red wolves back into the wild in eastern North Carolina.

The Fish and Wildlife Service’s Red Wolf Recovery Program successfully grew the wild population to more than 120 wolves. When the program was halted in 2015, however, the population crashed to as few as seven wolves. In 2021 the program resumed, but red wolves have struggled to regain their numbers. One challenge has been to maintain genetic diversity among the captive and re-wilded population of red wolves, all of which descend from only 12 founder individuals. Adding Colossal’s red wolves to the captive breeding population would increase the number of founding lineages by 25%.

“The dire wolf project is surreal and unreal at the same time. It’s recreating reality that stemmed from reality, from millennia ago. To think that in this day dire wolves aren’t just mythical illusions and tales told in movies that we believe may have had origins in reality…Now, we have the science and ingenuity to bring life back to once existing reality. Colossal is drastically changing the prognosis for countless endangered species around the world,” said Aurelia Skipwith, former director of the U.S. Fish and Wildlife, in a statement. “The company’s work to combat extinction of the red wolf creates hope for so many other critically endangered species fighting for survival.”

The research program for the dire wolf has also helped efforts to develop technologies for the red ‘ghost’ wolf, unique canids, found only on the gulf coast of Texas and Louisiana who carry lost DNA and biodiversity of the red wolf. Researchers Bridgett vonHoldt of Princeton University and Kristin Brzesk of Michigan Technological University lead the Gulf Coast Canine Project which aims to understand the genetic ancestry of the wild canines persisting along the Gulf Coast of the United States. They study how red wolf ancestry shapes morphology and behavior, and the support of Colossal has helped them accelerate their research through the inclusion of data from the red wolf genome, the assembly of a reference genome for the recovery population’s red wolves, and finally the creation of a pangenome for US native canids.The hope is that this work can set precedent for other species with a complicated genetic history, while also improving the capacity of conservation efforts for the red wolf, today.

In addition to the challenges of reintroduction, the red wolf’s biggest threat of extinction comes from limited genetic diversity that resulted from the population’s bottleneck that occurred during its rapid decline. The technology and understanding developed through Colossal’s red ‘ghost’ wolf project has now unlocked additional genetic diversity and red wolf ancestry that can be a resource to create a genetic rescue program for the red wolf population.

“The extinction crisis is a massive, mostly unattended, and growing worldwide problem. I applaud Colossal for taking bold and innovative steps to arrest and reverse the crisis by developing cutting edge genetic techniques to undergird reintroduction efforts of imperiled species. By collaborating with Dr. vonHoldt on red wolf recovery, Colossal creates potential to increase the genetic diversity of this species which exists only because of a captive population founded by a paltry 14 individuals. Perfecting genomic tools to integrate “ghost alleles” from Gulf Coast canids would increase red wolf genetic diversity and generate knowledge for recovering other imperiled species, like the bolson tortoise, that are compromised by restricted ranges and reduced genetic diversity.”- Mike Phillips, Director of the Turner Endangered Species Fund and project lead for rewilding gray wolves in the Greater Yellowstone Ecosystem.

From conservation to rewilding

Colossal’s long term goal is for their red wolves to be re-wilded through current US conservation efforts in collaboration with the US government.

“Colossal’s successful de-extinction of the dire wolf represents a massive coup for conservation,” said Matt James, Colossal’s Chief Animal Officer and Colossal Foundation Executive Director. “The technologies developed on the path to the dire wolf are already opening up new opportunities to rescue critically endangered canids. The creation of less-invasive sampling tools such as our EPC blood cloning platform allows for the conservation community to ramp up biobanking efforts of those species on the brink.”

Colossal’s de-extinction mission always includes plans to rewild associated species in alignment with global conservation efforts. Research suggests that rewilding wolves can have massive impacts on factors that drive climate change and support biodiversity. Inspired by the US Fish and Wildlife’s bold efforts to rescue the red wolf from the brink of extinction, Colossal has created technological platforms to offer key tools to those in the fight to save the world’s most endangered wolf.

“Today’s dire wolf announcement represents an exciting scientific step and demonstrates the power and possibilities of genetic technologies,” said Barney Long, Phd, 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.

“As someone who’s fascinated with canids—I’ve written about coyotes and wolves—the idea of being able to have dire wolves again is tremendously, personally exciting, and I think it’s going to be exciting to a lot of people. An organization like Colossal, to me, is one of the things that gives me hope. If I were looking 100 years out, I would say that we’re very likely to have animals once again that we thought were always gone—just as I once thought I was never going to get to hear a wolf howl… That was something I really never thought I’d have a chance to experience, and it became reality. And so, that makes me think that more and more, we’re going to get to experience what Henry David Thoreau lamented back in the 1850s—that he wasn’t getting to experience an entire heaven and an entire Earth. And I think that’s something to look forward to.” – Dan Flores, A. B. Hammond Professor Emeritus of the History of the American West at the University of Montana-Missoula

Partnerships

The effort to de-extinct the dire wolf, genetic rescue of the red wolf, and innovative gray wolf conservation programs are all made possible through Colossal’s collaborative work with a broad spectrum of Indigenous communities, conservation organizations, and scientific experts.

Colossal extended its deepest gratitude to the MHA Nation, the Nez Perce Tribe, the Karankawa Tribe of Texas, Indigenous Led, and the Wind River Tribal Buffalo Initiative, whose ancestral knowledge and insights have guided the company’s efforts. Colossal Biosciences and the Colossal Foundation also thank the many conservation organizations whose expertise and passion fuel these initiatives, including the American Wolf Foundation, Re:wild, Conservation Nation, Gulf Coast Canid Project, International Coexistence Network, Wolf Connection, Grizzly Systems and the Yellowstone Wolf Project.

Colossal was founded by emerging technology and software entrepreneur Ben Lamm and world-renowned geneticist and serial biotech entrepreneur George Church, and is the first to apply CRISPR technology for the purposes of species de-extinction. Colossal creates innovative technologies for species restoration, critically endangered species protection and the repopulation of critical ecosystems that support the continuation of life on Earth. Colossal is accepting humanity’s duty to restore Earth to a healthier state, while also solving for the future economies and biological necessities of the human condition through cutting-edge science and technologies. To follow along, please visit: www.colossal.com.

Shape
Shape
Stay Ahead

Explore More Insights

Stay ahead with more perspectives on cutting-edge power, infrastructure, energy,  bitcoin and AI solutions. Explore these articles to uncover strategies and insights shaping the future of industries.

Shape

Cato Networks augments CASB with genAI security

CASBs sit between an end user and a cloud service to enforce security policies, protect data, and ensure compliance. CASBs provide enterprise network and security teams with information on how end users are accessing and using cloud resources such as data, applications, and services. They provide visibility into cloud usage,

Read More »

8 unusual Linux commands

3. The column command The column command will display text in columns. Here are two examples of how to use it: $ cat staff | columnJohn Doe Lisa Stone Joanne Zahn Eric Docker Ben MatsonMary Berry Elaine Henry David Bloom Sam Adams Sally Rose$ cat staff | column -tJohn DoeMary

Read More »

AI agents vs. agentic AI: What do enterprises want?

The cloud-provider technical people I know don’t like this approach; they see it as likely to raise barriers to the use of their online generative AI services. Enterprises see their AI agent vision as facilitating cloud AI services instead. If there’s one massive AI entity doing everything, then data sovereignty

Read More »

US Inventory Drop, OPEC Action Lift Oil Prices

Oil rose on the prospect of a de-escalation in the trade war between the world’s two largest economies and a stall in nuclear talks between the US and Iran. West Texas Intermediate futures added 1.9% to settle near $62.50 a barrel, the third gain in the four past sessions, after China signaled openness to trade negotiations with the Trump administration. Pre-conditions for the talks would include a more consistent US position and a willingness to address China’s concerns around American sanctions and Taiwan, according to a person familiar with the Chinese government’s thinking. Elsewhere, Iran said it won’t be drawn into negotiations with the US over its ability to enrich uranium, reducing the potential of looser restrictions on Iranian crude. The US also sanctioned another China-based independent “teapot” refinery for its role in purchasing Tehran’s crude, and Treasury Secretary Scott Bessent said the US would ramp up pressure on Iran. Crude has recovered from a sharp drop to near the lowest in four years brought about by an onslaught of tariffs and counter-levies between the US and its biggest trading partners. Washington on Tuesday started a probe into the need for import taxes on critical minerals, while trade differences with the European Union persist as White House officials said the bulk of the US tariffs imposed on the bloc won’t be removed. Meanwhile, Iraq plans to cut its oil exports this month as it faces growing pressure to adhere to its OPEC+ production target. The country aims to reduce shipments by 70,000 barrels a day, an official with knowledge of the matter said. In another support for prices, US government data released Wednesday showed inventory levels at Cushing, Oklahoma — the delivery point for West Texas Intermediate — fell by roughly 650,000 barrels to the lowest since 2008 for this

Read More »

Keystone Restarts Oil Pipeline After Leak Prompted Shutdown

The operator of the Keystone oil pipeline brought the conduit back into service, putting an end to a week-long outage caused by an estimated 3,500-barrel spill in rural North Dakota.  Most of the oil released has been recovered and remediation efforts have started, South Bow Corp. said in a statement Wednesday. The line will be able to operate at no more of 80% of pressure levels at the time of the April 8 spill. At the time of failure, the line was transporting 17,844 barrels per hour, or the equivalent of 428,000 barrels a day. The restart, delayed by inclement weather, comes roughly two days after it met all conditions imposed by the Pipeline and Hazardous Materials Safety Administration. South Bow will continue to monitor the system as an investigation into the causes of the spill continues, the company said. Keystone can transport as much as 620,000 barrels of Canadian crude daily to US Midwest and Gulf Coast markets. 

Read More »

Renewable PPA prices shrug off the tariff roller coaster — at least for now

Dive Brief: Solar power purchase agreement prices remain essentially unchanged since the end of 2024, while wind PPA prices declined slightly in spite of uncertain and even adverse policy actions coming out of the Trump administration, according to data from LevelTen Energy’s PPA marketplace. The average North American solar PPA went for $57.04 per MWh in the first quarter of 2025, up 28 cents from the end of 2024 and 9.8% since this time last year. Wind PPA prices dropped more than 5% during the first quarter, but remain 4.4% higher than last year, according to LevelTen Energy. Although an ample supply of solar projects should put downward pressure on solar prices, developers may be reluctant to tighten their margins in the face of policy uncertainty, said Zach Starsia, senior director of the energy marketplace at LevelTen. Data from the next few months could clarify which direction prices are headed, Starsia said. Dive Insight: PPA prices have remained relatively static despite — or perhaps because of — the policy turmoil in recent months, Starsia said. It’s not just the Trump administration’s on-again, off-again tariffs that stand to increase costs for solar developers, he said. Renewable energy developers, who rely heavily on the U.S. Army Corps of Engineers during federal permitting processes, have also been impacted by the Department of Government Efficiency’s cost-cutting. And talk of revamping or repealing the Inflation Reduction Act — while still seen as unlikely — could hit developers hard, Starsia said. With a glut of solar projects set to come online in many U.S. markets, long-term analyses suggest that PPA prices should decline. But uncertainty about the future of trade and energy policy in the U.S. seems to have prompted most developers to hedge their bets by maintaining their asking prices — at least for now.

Read More »

Humber carbon emitter wants government signal on Viking CCS

Power company VPI has called for clarity to progress the Viking carbon capture and storage (CCS) project and help drive the future of heavy industries in the Humber. VPI requested a signal from the UK government in its upcoming comprehensive spending review that it will be selected as an anchor emitter for the CCS project. The group owns the nearly 1.3GW Immingham thermal power plant, which provides power to the Humber’s two large oil refineries. VPI is planning to deploy a £1.5 billion carbon capture proposal, which will utilise Harbour Energy’s Viking CCS pipeline to transport carbon that will be buried in a depleted gas field in the North Sea. VPI chief executive Jorge Pikunic said: “Carbon capture and storage provides a once-in-a-generation opportunity to turn the Humber into a powerhouse of the future. If missed, it may not come again. “For the last five years, public officials have worked tirelessly with industry to set in motion the development of Viking CCS, a unique carbon capture and storage network, here in the Humber. “Proceeding with the next stage of Viking CCS now will demonstrate how a strategic, mission-driven government can successfully transition an industrial hub into a future powerhouse, in a prudent, value-for money driven, just and meaningful way.” Viking CCS The Viking CCS pipeline will transport CO₂ captured from the industrial cluster at Immingham out to the Viking reservoirs via the Theddlethorpe gas terminal and an existing 75-mile (120km) pipeline as part of the Lincolnshire offshore gas gathering system (LOGGS). The project forms part of the UK’s track 2 CCS projects along with Scotland’s Acorn CCS project. While the UK government has backed the track 1 projects with around £22 billion of government funding, the track 2 proposal have not received similar pledges of support. Business leaders have warned

Read More »

APA Corp Makes Leadership Changes, Names Ben Rodgers as CFO

Oil and natural gas exploration and production company APA Corporation has recently made changes to its executive leadership team. The company said in a media release that Ben Rodgers has been named executive vice president (EVP) and chief financial officer (CFO), effective May 12, 2025. Furthermore, Steve Riley will continue in his role as president, while Shad Frazier joined the company as senior vice president, U.S. Onshore Operations. Additionally, Donald Martin will join the company as vice president, Decommissioning, effective May 26, 2025, APA said. In this role as EVP and CFO, Rodgers will oversee all financial activities and departments, including Accounting, Audit, Investor Relations, Planning, Tax, and Treasury. He joined APA in 2018 and previously served as SVP, Finance, and Treasurer. He also served as CFO of Altus Midstream and later as a director on the board of Kinetik Holdings Inc., APA said. He currently serves on the board of Khalda Petroleum Company, a joint venture between APA subsidiary Apache Corporation and Egypt Petroleum Company. In his position, Riney will continue overseeing asset development and operations. Both Frazier and Martin have been added to Riney’s team to help oversee operations. APA highlighted that Frazier has nearly 30 years of industry experience, most recently as vice president, Production Operations at Endeavor Energy Resources, LP. Previously, he held various leadership positions at Legacy Reserves and SandRidge Energy. Martin brings 20 years of operations and decommissioning portfolio experience, most recently as the head of decommissioning and projects at Spirit Energy. He has also managed decommissioning at Canadian Natural Resources, APA said. “I am pleased to welcome Ben to our executive leadership team. He has done a tremendous job and will bring valuable expertise to our financial operations”, John J. Christmann, APA Corporation CEO, said. “I am also excited to welcome both Shad and Donald

Read More »

TotalEnergies Agrees 15-year LNG Supply Deal with Enadom

Global energy major TotalEnergies SE signed a heads of agreement (HoA) with Energia Natural Dominicana Enadom, S.R.L. (Enadom) for the delivery of 400,000 tons of liquefied natural gas (LNG) per year. TotalEnergies said in a media release that the HoA with the joint venture between AES Dominicana and Energas in the Dominican Republic is subject to the finalization of sale and purchase agreements (SPAs). Once the SPAs are signed, the agreement will start in mid-2027, with a 15-year term, and the price will be indexed to Henry Hub. The deal enables Enadom to supply natural gas to the 470 MW combined-cycle power plant, currently under construction, which will increase the country’s electricity generation capacity, TotalEnergies said. This project contributes to the energy transition of the Dominican Republic by reducing its dependence on coal and fuel oil through the use of a less carbon-intensive energy source, natural gas, the company said. “We are pleased to have signed this agreement to answer, alongside AES and its partners, the energy needs of the Dominican Republic. This new contract underscores TotalEnergies’ leadership in the LNG sector and our commitment to supporting the island’s energy transition. It will be a natural outlet for our US LNG supply which will progressively increase”, Gregory Joffroy, Senior Vice President LNG at TotalEnergies, said. TotalEnergies said it is the world’s third largest LNG player with a global portfolio of 40 Mt/y in 2024 thanks to its interests in liquefaction plants in all geographies. “This agreement with TotalEnergies is the result of the confidence placed in the Dominican Republic’s energy sector and, specifically, in Enadom and AES. This partnership, alongside Enadom’s, has demonstrated investment capabilities in providing natural gas to the Dominican electricity market by ensuring a reliable, competitive, and environmentally responsible energy supply. Enadom is proud to play a pivotal

Read More »

Intel sells off majority stake in its FPGA business

Altera will continue offering field-programmable gate array (FPGA) products across a wide range of use cases, including automotive, communications, data centers, embedded systems, industrial, and aerospace.  “People were a bit surprised at Intel’s sale of the majority stake in Altera, but they shouldn’t have been. Lip-Bu indicated that shoring up Intel’s balance sheet was important,” said Jim McGregor, chief analyst with Tirias Research. The Altera has been in the works for a while and is a relic of past mistakes by Intel to try to acquire its way into AI, whether it was through FPGAs or other accelerators like Habana or Nervana, note Anshel Sag, principal analyst with Moor Insight and Research. “Ultimately, the 50% haircut on the valuation of Altera is unfortunate, but again is a demonstration of Intel’s past mistakes. I do believe that finishing the process of spinning it out does give Intel back some capital and narrows the company’s focus,” he said. So where did it go wrong? It wasn’t with FPGAs because AMD is making a good run of it with its Xilinx acquisition. The fault, analysts say, lies with Intel, which has a terrible track record when it comes to acquisitions. “Altera could have been a great asset to Intel, just as Xilinx has become a valuable asset to AMD. However, like most of its acquisitions, Intel did not manage Altera well,” said McGregor.

Read More »

Intelligence at the edge opens up more risks: how unified SASE can solve it

In an increasingly mobile and modern workforce, smart technologies such as AI-driven edge solutions and the Internet of Things (IoT) can help enterprises improve productivity and efficiency—whether to address operational roadblocks or respond faster to market demands. However, new solutions also come with new challenges, mainly in cybersecurity. The decentralized nature of edge computing—where data is processed, transmitted, and secured closer to the source rather than in a data center—has presented new risks for businesses and their everyday operations. This shift to the edge increases the number of exposed endpoints and creates new vulnerabilities as the attack surface expands. Enterprises will need to ensure their security is watertight in today’s threat landscape if they want to reap the full benefits of smart technologies at the edge. Bypassing the limitations of traditional network security  For the longest time, enterprises have relied on traditional network security approaches to protect their edge solutions. However, these methods are becoming increasingly insufficient as they typically rely on static rules and assumptions, making them inflexible and predictable for malicious actors to circumvent.  While effective in centralized infrastructures like data centers, traditional network security models fall short when applied to the distributed nature of edge computing. Instead, organizations need to adopt more adaptive, decentralized, and intelligent security frameworks built with edge deployments in mind.  Traditional network security typically focuses on keeping out external threats. But today’s threat landscape has evolved significantly, with threat actors leveraging AI to launch advanced attacks such as genAI-driven phishing, sophisticated social engineering attacks, and malicious GPTs. Combined with the lack of visibility with traditional network security, a cybersecurity breach could remain undetected until it’s too late, resulting in consequences extending far beyond IT infrastructures.  Next generation of enterprise security with SASE As organizations look into implementing new technologies to spearhead their business, they

Read More »

Keysight tools tackle data center deployment efficiency

Test and performance measurement vendor Keysight Technologies has developed Keysight Artificial Intelligence (KAI) to identify performance inhibitors affecting large GPU deployments. It emulates workload profiles, rather than using actual resources, to pinpoint performance bottlenecks. Scaling AI data centers requires testing throughout the design and build process – every chip, cable, interconnect, switch, server, and GPU needs to be validated, Keysight says. From the physical layer through the application layer, KAI is designed to identify weak links that degrade the performance of AI data centers, and it validates and optimizes system-level performance for optimal scaling and throughput. AI providers, semiconductor fabricators, and network equipment manufacturers can use KAI to accelerate design, development, deployment, and operations by pinpointing performance issues before deploying in production.

Read More »

U.S. Advances AI Data Center Push with RFI for Infrastructure on DOE Lands

ORNL is also the home of the Center for Artificial Intelligence Security Research (CAISER), which Edmon Begoli, CAISER founding director, described as being in place to build the security necessary by defining a new field of AI research targeted at fighting future AI security risks. Also, at the end of 2024, Google partner Kairos Power started construction of their Hermes demonstration SMR in Oak Ridge. Hermes is a high-temperature gas-cooled reactor (HTGR) that uses triso-fueled pebbles and a molten fluoride salt coolant (specifically Flibe, a mix of lithium fluoride and beryllium fluoride). This demonstration reactor is expected to be online by 2027, with a production level system becoming available in the 2030 timeframe. Also located in a remote area of Oak Ridge is the Tennessee Valley Clinch River project, where the TVA announced a signed agreement with GE-Hitachi to plan and license a BWRX-300 small modular reactor (SMR). On Integrating AI and Energy Production The foregoing are just examples of ongoing projects at the sites named by the DOE’s RFI. Presuming that additional industry power, utility, and data center providers get on board with these locations, any of the 16 could be the future home of AI data centers and on-site power generation. The RFI marks a pivotal step in the U.S. government’s strategy to solidify its global dominance in AI development and energy innovation. By leveraging the vast resources and infrastructure of its national labs and research sites, the DOE is positioning the country to meet the enormous power and security demands of next-generation AI technologies. The selected locations, already home to critical energy research and cutting-edge supercomputing, present a compelling opportunity for industry stakeholders to collaborate on building integrated, sustainable AI data centers with dedicated energy production capabilities. With projects like Oak Ridge’s pioneering SMRs and advanced AI security

Read More »

Generac Sharpens Focus on Data Center Power with Scalable Diesel and Natural Gas Generators

In a digital economy defined by constant uptime and explosive compute demand, power reliability is more than a design criterion—it’s a strategic imperative. In response to such demand, Generac Power Systems, a company long associated with residential backup and industrial emergency power, is making an assertive move into the heart of the digital infrastructure sector with a new portfolio of high-capacity generators engineered for the data center market. Unveiled this week, Generac’s new lineup includes five generators ranging from 2.25 MW to 3.25 MW. These units are available in both diesel and natural gas configurations, and form part of a broader suite of multi-asset energy systems tailored to hyperscale, colocation, enterprise, and edge environments. The product introductions expand Generac’s commercial and industrial capabilities, building on decades of experience with mission-critical power in hospitals, telecom, and manufacturing, now optimized for the scale and complexity of modern data centers. “Coupled with our expertise in designing generators specific to a wide variety of industries and uses, this new line of generators is designed to meet the most rigorous standards for performance, packaging, and after-treatment specific to the data center market,” said Ricardo Navarro, SVP & GM, Global Telecom and Data Centers, Generac. Engineering for the Demands of Digital Infrastructure Each of the five new generators is designed for seamless integration into complex energy ecosystems. Generac is emphasizing modularity, emissions compliance, and high-ambient operability as central to the offering, reflecting a deep understanding of the real-world challenges facing data center operators today. The systems are built around the Baudouin M55 engine platform, which is engineered for fast transient response and high operating temperatures—key for data center loads that swing sharply under AI and cloud workloads. The M55’s high-pressure common rail fuel system supports low NOx emissions and Tier 4 readiness, aligning with the most

Read More »

CoolIT and Accelsius Push Data Center Liquid Cooling Limits Amid Soaring Rack Densities

The CHx1500’s construction reflects CoolIT’s 24 years of DLC experience, using stainless-steel piping and high-grade wetted materials to meet the rigors of enterprise and hyperscale data centers. It’s also designed to scale: not just for today’s most power-hungry processors, but for future platforms expected to surpass today’s limits. Now available for global orders, CoolIT is offering full lifecycle support in over 75 countries, including system design, installation, CDU-to-server certification, and maintenance services—critical ingredients as liquid cooling shifts from high-performance niche to a requirement for AI infrastructure at scale. Capex Follows Thermals: Dell’Oro Forecast Signals Surge In Cooling and Rack Power Infrastructure Between Accelsius and CoolIT, the message is clear: direct liquid cooling is stepping into its maturity phase, with products engineered not just for performance, but for mass deployment. Still, technology alone doesn’t determine the pace of adoption. The surge in thermal innovation from Accelsius and CoolIT isn’t happening in a vacuum. As the capital demands of AI infrastructure rise, the industry is turning a sharper eye toward how data center operators account for, prioritize, and report their AI-driven investments. To wit: According to new market data from Dell’Oro Group, the transition toward high-power, high-density AI racks is now translating into long-term investment shifts across the data center physical layer. Dell’Oro has raised its forecast for the Data Center Physical Infrastructure (DCPI) market, predicting a 14% CAGR through 2029, with total revenue reaching $61 billion. That revision stems from stronger-than-expected 2024 results, particularly in the adoption of accelerated computing by both Tier 1 and Tier 2 cloud service providers. The research firm cited three catalysts for the upward adjustment: Accelerated server shipments outpaced expectations. Demand for high-power infrastructure is spreading to smaller hyperscalers and regional clouds. Governments and Tier 1 telecoms are joining the buildout effort, reinforcing AI as a

Read More »

Microsoft will invest $80B in AI data centers in fiscal 2025

And Microsoft isn’t the only one that is ramping up its investments into AI-enabled data centers. Rival cloud service providers are all investing in either upgrading or opening new data centers to capture a larger chunk of business from developers and users of large language models (LLMs).  In a report published in October 2024, Bloomberg Intelligence estimated that demand for generative AI would push Microsoft, AWS, Google, Oracle, Meta, and Apple would between them devote $200 billion to capex in 2025, up from $110 billion in 2023. Microsoft is one of the biggest spenders, followed closely by Google and AWS, Bloomberg Intelligence said. Its estimate of Microsoft’s capital spending on AI, at $62.4 billion for calendar 2025, is lower than Smith’s claim that the company will invest $80 billion in the fiscal year to June 30, 2025. Both figures, though, are way higher than Microsoft’s 2020 capital expenditure of “just” $17.6 billion. The majority of the increased spending is tied to cloud services and the expansion of AI infrastructure needed to provide compute capacity for OpenAI workloads. Separately, last October Amazon CEO Andy Jassy said his company planned total capex spend of $75 billion in 2024 and even more in 2025, with much of it going to AWS, its cloud computing division.

Read More »

John Deere unveils more autonomous farm machines to address skill labor shortage

Join our daily and weekly newsletters for the latest updates and exclusive content on industry-leading AI coverage. Learn More Self-driving tractors might be the path to self-driving cars. John Deere has revealed a new line of autonomous machines and tech across agriculture, construction and commercial landscaping. The Moline, Illinois-based John Deere has been in business for 187 years, yet it’s been a regular as a non-tech company showing off technology at the big tech trade show in Las Vegas and is back at CES 2025 with more autonomous tractors and other vehicles. This is not something we usually cover, but John Deere has a lot of data that is interesting in the big picture of tech. The message from the company is that there aren’t enough skilled farm laborers to do the work that its customers need. It’s been a challenge for most of the last two decades, said Jahmy Hindman, CTO at John Deere, in a briefing. Much of the tech will come this fall and after that. He noted that the average farmer in the U.S. is over 58 and works 12 to 18 hours a day to grow food for us. And he said the American Farm Bureau Federation estimates there are roughly 2.4 million farm jobs that need to be filled annually; and the agricultural work force continues to shrink. (This is my hint to the anti-immigration crowd). John Deere’s autonomous 9RX Tractor. Farmers can oversee it using an app. While each of these industries experiences their own set of challenges, a commonality across all is skilled labor availability. In construction, about 80% percent of contractors struggle to find skilled labor. And in commercial landscaping, 86% of landscaping business owners can’t find labor to fill open positions, he said. “They have to figure out how to do

Read More »

2025 playbook for enterprise AI success, from agents to evals

Join our daily and weekly newsletters for the latest updates and exclusive content on industry-leading AI coverage. Learn More 2025 is poised to be a pivotal year for enterprise AI. The past year has seen rapid innovation, and this year will see the same. This has made it more critical than ever to revisit your AI strategy to stay competitive and create value for your customers. From scaling AI agents to optimizing costs, here are the five critical areas enterprises should prioritize for their AI strategy this year. 1. Agents: the next generation of automation AI agents are no longer theoretical. In 2025, they’re indispensable tools for enterprises looking to streamline operations and enhance customer interactions. Unlike traditional software, agents powered by large language models (LLMs) can make nuanced decisions, navigate complex multi-step tasks, and integrate seamlessly with tools and APIs. At the start of 2024, agents were not ready for prime time, making frustrating mistakes like hallucinating URLs. They started getting better as frontier large language models themselves improved. “Let me put it this way,” said Sam Witteveen, cofounder of Red Dragon, a company that develops agents for companies, and that recently reviewed the 48 agents it built last year. “Interestingly, the ones that we built at the start of the year, a lot of those worked way better at the end of the year just because the models got better.” Witteveen shared this in the video podcast we filmed to discuss these five big trends in detail. Models are getting better and hallucinating less, and they’re also being trained to do agentic tasks. Another feature that the model providers are researching is a way to use the LLM as a judge, and as models get cheaper (something we’ll cover below), companies can use three or more models to

Read More »

OpenAI’s red teaming innovations define new essentials for security leaders in the AI era

Join our daily and weekly newsletters for the latest updates and exclusive content on industry-leading AI coverage. Learn More OpenAI has taken a more aggressive approach to red teaming than its AI competitors, demonstrating its security teams’ advanced capabilities in two areas: multi-step reinforcement and external red teaming. OpenAI recently released two papers that set a new competitive standard for improving the quality, reliability and safety of AI models in these two techniques and more. The first paper, “OpenAI’s Approach to External Red Teaming for AI Models and Systems,” reports that specialized teams outside the company have proven effective in uncovering vulnerabilities that might otherwise have made it into a released model because in-house testing techniques may have missed them. In the second paper, “Diverse and Effective Red Teaming with Auto-Generated Rewards and Multi-Step Reinforcement Learning,” OpenAI introduces an automated framework that relies on iterative reinforcement learning to generate a broad spectrum of novel, wide-ranging attacks. Going all-in on red teaming pays practical, competitive dividends It’s encouraging to see competitive intensity in red teaming growing among AI companies. When Anthropic released its AI red team guidelines in June of last year, it joined AI providers including Google, Microsoft, Nvidia, OpenAI, and even the U.S.’s National Institute of Standards and Technology (NIST), which all had released red teaming frameworks. Investing heavily in red teaming yields tangible benefits for security leaders in any organization. OpenAI’s paper on external red teaming provides a detailed analysis of how the company strives to create specialized external teams that include cybersecurity and subject matter experts. The goal is to see if knowledgeable external teams can defeat models’ security perimeters and find gaps in their security, biases and controls that prompt-based testing couldn’t find. What makes OpenAI’s recent papers noteworthy is how well they define using human-in-the-middle

Read More »