Of Mammoths and Men: A Brief History of Genetic Resurrection

The Dire Wolves, which went extinct approximately 10,000 years ago, are back again. But are they really the Dire Wolves? Can we bring back other behemoths of the past? Can we save those endangered?

The recent announcement by Colossal Biosciences of the birth of three genetically engineered canids, Romulus, Remus, and Khaleesi, conceived to resemble the extinct dire wolf (Aenocyon dirus), marks a critical breakthrough in the field of de-extinction. This development not only indicates the advancements in genetic engineering but also prompts a reevaluation of conservation strategies in the face of accelerating biodiversity loss. It also raises the question – if we will be able to de-extinct than should we fear extinct?

Ever heard about the incredible science that might just save the northern white rhinoceros? Only two females are left, and neither can reproduce. Sounds like the end of the line, right? Well, not quite. The BioRescue consortium, working with Colossal Biosciences, has created 30 viable embryos using in vitro fertilisation and stem cell technology. They’re now stored in cryogenic facilities, with plans to implant them into southern white rhino surrogates to bring the species back. But can science really move fast enough to keep up with how quickly we’re losing species?

As exciting as de-extinction science is, the truth is – it’s not a silver bullet. In our world, species are disappearing faster than we can evaluate, let alone bring them back. According to the 2024 Living Planet Index, there has been an average decline of 73% in monitored wildlife populations between 1970 and 2020. This analysis encompasses data from approximately 35,000 populations across 5,495 species of mammals, birds, amphibians, reptiles, and fish. It’s important to note that this figure represents an average decline in population sizes and does not imply that 73% of species have gone extinct. Yet, current extinction rates are estimated to be 100 to 1,000 times higher than the natural background rate. This acceleration is primarily driven by human activities, including habitat destruction, overexploitation, pollution, invasive species introduction, and climate change.

De-extinction can help in specific cases, like with the northern white rhino, where we have preserved genetic material and a plan. But for the thousands of species we’re losing due to habitat destruction, climate change, and pollution, the pace of science just can’t keep up. So while the tech is promising and can indubitably bolster conservation efforts, it needs to go hand-in-hand with serious global action to protect ecosystems before species go extinct in the first place.

A Brief History of De-Extinction Efforts

De-extinction, or resurrection biology, refers to the process of reviving extinct species or creating organisms that closely resemble them. The roots of de-extinction lie in the development of cloning technology in the 20th century. The first landmark moment came in 1996 with the birth of Dolly the sheep, the first mammal cloned from an adult somatic cell using a technique called somatic cell nuclear transfer (SCNT). This technique involves transferring the nucleus of a donor cell into an egg cell that has had its nucleus removed. Dolly’s birth proved that cloning complex organisms was scientifically feasible and paved the way for future de-extinction efforts.

Another trailblazing moment for cloning was manifested by the 2003 attempt to clone the Pyrenean ibex (Bucardo, a wild goat native to France and Spain). Howbeit, the cloned animal died shortly after birth, highlighting the limitations of cloning as a standalone technique. This is not to suggest a permanent obstruction as the writing of this article emanates from the de-extinction of the dire wolve, which lived in the late Pleistocene epoch. While Romulus, Remus and Khaleesi are not exact replicas of the dire wolves, they possess similar traits, hence rendering the development as a breakthrough in gene-editing technology.

The emergence of genome sequencing and CRISPR-Cas9 gene editing in the early 2010s greatly expanded the possibilities of de-extinction. Rather than relying solely on cloning whole genomes from preserved tissue, scientists could now edit the genomes of living relatives to resemble extinct species. This approach is often termed “genetic back-breeding” or “genetic proxy creation.”

One of the most ambitious de-extinction projects involves the woolly mammoth (Mammuthus primigenius). Since 2013, geneticist George Church and his team at Harvard have been working to insert woolly mammoth genes into the genome of the Asian elephant—its closest living relative— using CRISPR. The goal is not to recreate an exact replica, but a mammoth-elephant hybrid capable of surviving in Arctic conditions and possibly aiding in climate change mitigation through grassland restoration.

Similarly, the group Revive & Restore, founded by Stewart Brand and Ryan Phelan, is attempting to edit the genome of the band-tailed pigeon to reintroduce traits of the extinct passenger pigeon. While progress has been slower than anticipated, this project represents a model for de-extinction focused on ecological restoration. In 2021, Colossal Biosciences, announced its goal to bring back the woolly mammoth by 2027. The company raised over $75 million in venture funding and began similar work on the Tasmanian tiger (Thylacine) and the dodo, in collaboration with the University of Melbourne and other institutions .

The Dire Wolf: A Glimpse into the Pleistocene

The dire wolf, which roamed North America until its extinction approximately 10,000 years ago, was a formidable predator, larger and more robust than the modern gray wolf. Despite morphological similarities, genetic studies have revealed that dire wolves diverged from gray wolves millions of years ago, representing a distinct evolutionary lineage .

The maverick behind the marvel is, Colossal Biosciences, a biotechnology company co-founded by entrepreneur Ben Lamm and Harvard geneticist George Church, has been at the forefront of de extinction research. The company’s recent achievement involves the creation of three canids, Romulus, Remus, and Khaleesi, engineered to express traits associated with the extinct dire wolf.

The de-extinction of dire wolf-like canids by Colossal Biosciences relied on a multi-stage scientific process combining ancient DNA analysis, advanced genome editing, and assisted reproduction techniques.

The first step involved the extraction and sequencing of ancient DNA from two fossilised remains of dire wolves: a 13,000-year-old tooth and a 72,000-year-old ear bone. These genetic samples were used to identify critical differences between the extinct dire wolf (Aenocyon dirus) and its closest living relative, the gray wolf. Through this comparative analysis, scientists isolated specific genetic markers associated with phenotypic traits unique to dire wolves.

Following the identification of these markers, researchers employed CRISPR-Cas9 genome editing technology to modify the DNA of gray wolf cells. They targeted 14 genes, successfully incorporating 20 distinct traits that defined the dire wolf, including a larger body size, a more robust skeletal structure, and particular coat pigmentation patterns. This editing process marked a significant leap in synthetic biology, pushing the boundaries of what can be replicated from extinct genomes.

Once the edits were complete, the altered nuclei were transferred into enucleated ova—eggs from which the original genetic material had been removed. These ova were then cultivated into embryos and implanted into surrogate domestic dogs. The pregnancies were closely monitored, and the pups were delivered via cesarean section. Today, these three pups, Romulus, Remus, and Khaleesi, are being raised in a secure 2,000-acre preserve, where they are observed for health, behaviour, and ecological compatibility.

This meticulous process illustrates the remarkable fusion of paleogenetics, gene editing, and reproductive science, representing a significant milestone in the broader field of de-extinction and synthetic conservation biology.

While the de-extinction of dire wolf-like canids is an imperative scientific achievement, it has also sparked a series of ethical, ecological, and strategic debates within the scientific community and beyond. These discourses attempt to place the trajectory of de-extinction technologies relative to the pace of traceable biodiversity loss.

One of the primary concerns relates to authenticity. Despite the groundbreaking use of genome editing, the genetic modifications applied to gray wolf cells were relatively limited in scope. Moreover, genetic studies have shown that dire wolves diverged from gray wolves millions of years ago, suggesting a substantial evolutionary distance between the two species. As a result, many scientists contend that the animals produced by Colossal Biosciences are not genuine dire wolves but rather genetically engineered hybrids or proxies that merely mimic certain physical traits of the extinct species. This raises philosophical questions about what constitutes a “true” de-extinct species and whether partial genetic resemblance is sufficient for claiming revival. We may infer that de-extinction, given the limited number of species it can be applied to and revive, is only capable of regenerating certain traits, rather than fully replicating extinct species.

Another crucial concern arises from the ecological impact of reintroducing such engineered species into modern ecosystems. The environments dire wolves once inhabited have changed drastically over the past 10,000 years, and the ecological niches they once occupied may no longer exist. Introducing a novel predator, especially one designed to replicate a long-extinct apex species, could lead to unforeseen consequences, such as imbalances in prey populations, competition with existing wildlife, or the spread of new diseases. Without extensive ecological modelling and long-term observation, the risks of disruption could outweigh the intended benefits. Nevertheless, as of the moment, we are unsure when and how Colossus’s dire wolves would be brought out of the company’s facilities and into the wild.

Lastly, there is an escalating contention surrounding conservation priorities. De-extinction efforts require substantial financial and scientific resources, which some argue could be better allocated to protecting endangered species and preserving habitats that are under immediate threat. While the technologies developed through de-extinction research can certainly inform conservation biology, critics warn that such high-profile projects may draw over-proportionate attention, and divert funding away from more pressing and achievable conservation goals. There is a risk that the allure of resurrecting charismatic extinct species could overshadow the urgent need to save those that are still hanging on today.

Taken together, these concerns underscore the need for a balanced approach, one that embraces scientific innovation while remaining grounded in ecological responsibility and ethical foresight.

Despite these concerns, proponents argue that the technologies developed through de-extinction research could enhance conservation efforts by improving genetic diversity and resilience in endangered populations. We do not refute the argument, and believe the incorporation of de extinctions technologies will aid conservation efforts vitally. However, the solutions for biodiversity loss cannot be viewed exclusively from the prism of de-extinction technologies due to their explicit limitations. Therefore, de-extinction and its treading in prosperity must be embedded in the broader framework of preserving global biodiversity. Hence, de-extinction efforts complement conservation efforts to ensure greater preservation of earth’s biodiversity.

The methodologies refined during the dire wolf project extend far beyond the goal of de-extinction itself and hold broader applications within the field of conservation biology. One such application lies in the realm of genetic rescue. The same gene-editing techniques used to introduce specific traits in engineered canids can be applied to endangered species, helping to enhance genetic diversity within shrinking populations. This, in turn, could improve their adaptability to environmental pressures and increase their chances of survival.

Additionally, these technologies open new possibilities for habitat restoration. By reintroducing species that once played critical ecological roles, such as top predators or key pollinators, scientists can potentially rebalance ecosystems that have been disrupted by human activity or environmental degradation. Furthermore, the high-profile nature of de-extinction projects can serve as a powerful tool for public engagement. Stories of ancient species returning in modern form capture public imagination and can inspire renewed interest in biodiversity, prompting greater support for conservation efforts worldwide. In this way, the scientific advancements behind projects like the dire wolf revival may contribute not only to the future of synthetic biology, but also to the long-term protection of life on Earth.

The endeavour to revive the dire wolf exemplifies the intersection of cutting-edge science and conservation. While it offers exciting possibilities for biodiversity preservation, it also necessitates careful consideration of ethical, ecological, and practical implications. As we advance in our ability to manipulate genetic material, it is imperative to balance innovation with responsibility, ensuring that our actions contribute positively to the planet’s ecological integrity. De-extinction technology has evolved from speculative fiction to a frontier of biological innovation. From early cloning efforts to genome editing and synthetic biology, scientists have made impressive strides in their quest to reverse extinction. Whether driven by ecological restoration, scientific curiosity, or biotechnology entrepreneurship, de-extinction continues to challenge our understanding of life, death, and responsibility to the natural world. While its full potential and implications remain uncertain, it serves as a powerful symbol of both the possibilities and perils of human intervention in nature.

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