Colossal Biosciences: Bringing Extinct Animals Back to Life

Colossal Biosciences, a biotechnology company founded in 2021 by serial entrepreneur Ben Lamm and world-renowned geneticist Dr. George Church, has captured global attention for its ambitious de-extinction goals. The company leverages cutting-edge genetic engineering techniques, such as CRISPR-Cas9, to bring back extinct species and restore ecosystems disrupted by their absence. Colossal’s work represents a fusion of synthetic biology with conservation science. Among the species it aims to revive are the woolly mammoth, the thylacine (Tasmanian tiger), and the dodo bird—three iconic animals that vanished from the Earth under markedly different circumstances.

A cornerstone of their work is the use of CRISPR-Cas9, a powerful gene-editing tool that allows for precise modifications to DNA. This enables the insertion of genes from extinct species, like the woolly mammoth, into the genomes of closely related living species, such as the Asian elephant, or the modification of existing genes to recreate traits like thick fur or cold resistance. In addition, Colossal utilizes genome sequencing to extract and analyze ancient DNA from preserved remains of extinct species. By comparing these ancient genomes to those of their modern relatives, they can identify key genetic differences responsible for extinct traits. When necessary, the company applies synthetic biology to synthesize DNA segments, recreating functional versions of genes that may be degraded or missing in ancient samples. All together these tools create a powerful toolkit of solutions to de-extinct species. 

The Woolly Mammoth

The woolly mammoth (Mammuthus primigenius), a close relative of modern elephants, roamed the northern hemisphere during the Pleistocene epoch. These colossal herbivores were adapted to cold environments, with thick fur, insulating fat layers, and curved tusks for foraging through snow. The species became extinct around 4,000 years ago, likely due to a combination of climate change and human hunting.

Colossal’s plan to de-extinct the woolly mammoth starts with engineering a “cold-resistant elephant” by splicing mammoth genes into the genome of its closest living relative, the Asian elephant. Traits such as subcutaneous fat, dense fur, and cold tolerance will be introduced to create a hybrid capable of surviving Arctic conditions. 

The team at Colossal recently announced that they have successfully developed induced pluripotent stem cells (iPSCs) from Asian elephant placental tissue. These are stem cells that can transform into any type of cell in the body. The iPSCs are a critical first step to being able to edit sperm and egg cells fertilized in vitro and injected into a surrogate to spawn a woolly mammoth. This milestone advancement was one of the primary early goals of the mammoth project, and supports the feasibility of future multiplex ex utero mammoth gestation.

The Thylacine (Tasmanian Tiger)

The thylacine (Thylacinus cynocephalus), a carnivorous marsupial native to Tasmania, mainland Australia, and New Guinea, went extinct in the 20th century. The species was hunted to extinction due to its perceived threat to livestock, compounded by habitat destruction and disease. The last known thylacine died in captivity in 1936.

Colossal aims to de-extinct the thylacine using DNA samples preserved in museum specimens. The company plans to edit the genome of the closest living relative of the thylacine, the numbat or dunnart, and utilize surrogate mothers to gestate the engineered embryos. Recently, the company announced progress on this mission with numerous advancements in multiplex editing and marsupial IVF treatments including achieving 300+ unique edits in a single cell and the first artificial reproductive technologies for marsupials to induce ovulation and grow embryos.

The Dodo Bird

The dodo (Raphus cucullatus), a flightless bird native to Mauritius, has become a symbol of human-driven extinction. The dodo disappeared in the late 1600s, within a century of human settlement on the island. Its extinction was driven by overhunting, habitat destruction, and the introduction of non-native predators like rats and pigs, which ate dodo eggs.

Colossal’s strategy to revive the dodo involves reconstructing its genome by comparing preserved DNA fragments with those of closely related pigeon species, such as the Nicobar pigeon. By editing pigeon embryos with dodo-specific genetic traits, scientists hope to recreate a modern version of this extinct bird. The dodo’s return could support the restoration of Mauritius’s damaged ecosystems by promoting seed dispersal and fostering biodiversity.

Challenges and Ethical Considerations

Colossal’s de-extinction efforts face numerous scientific and ethical challenges. The technical hurdles of reconstructing extinct genomes, engineering viable embryos, and raising hybrid animals in captivity are immense. But the company is clearly making strides to prove that science that seemed impossible is now possible. 

Ethical concerns also abound. Critics argue that focusing on de-extinction diverts resources from conserving endangered species and habitats. Others question whether it is humane to create animals for experimental purposes or release them into unfamiliar environments. However, proponents of de-extinction, including Colossal, contend that their work complements conservation efforts by generating tools and knowledge that can benefit living species. Already the company has made strides to help combat elephant EEHV, to improve tracking and monitoring of animals under threat from poachers, and to create resistance in the northern quoll against the invasive cane toad.