DNA sequencing has long been revolutionizing science and the field of genomics. Since the process was developed in the 1970s, nearly 30 million people have had their genomes sequenced to gain vital insights into their health, such as predispositions to allergies and diseases. Genomic sequencing is instrumental to the future of public health and can even track the proliferation of viruses like COVID-19 and malaria.
Thanks to advances in science and technology, genomic sequencing has never been more accessible than the present. Today, an entire genome can be sequenced for less than $1,000, leading scientists and ambitious entrepreneurs like Colossal Biosciences’ Ben Lamm to push the envelope of the process’s potential and applications.
Colossal Biosciences’ mission, according to its website, is “Through technological and engineering breakthroughs in biosciences and genetics, 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.”
Colossal Biosciences: Mitigating the Current Extinction Crisis
While genomic sequencing has always been known for its benefits to human health care, plants and animals can also have their genome sequenced. In addition to providing vital information such as a species’ evolutionary history and native environment, genomic sequencing may be the key to preventing extinction and even reversing it. This has prompted the creation of a scientific field known as conservation genomics, which uses whole-genome sequencing technology to combat urgent issues plaguing our fauna.
In an effort to mitigate the current extinction crisis (which currently results in up to an estimated 150 species of plants and animals lost each day), several companies around the globe have embraced conservation genomics and the importance of sequencing species and analyzing the data these sequences hold. Colossal Biosciences, the billion-dollar startup well known for its innovative de-extinction projects, is one enterprise heavily invested in conservation genomics and how it can benefit endangered and extinct species.
In addition to Colossal’s project’s reliance on genetic sequencing, Colossal’s co-founder George Church has an extensive history with the process. In 1984, Church pioneered the first direct genomic sequencing method. That same year, Church helped initiate the Human Genome Project, which officially launched in 1990 and generated the first sequence of a human genome. The Human Genome Project took 13 years to complete and remains the world’s largest collaborative biological project.
The Sequence to Predicting Extinction
Despite being a relatively new scientific field, conservation genomics is already being used to inform wildlife management decisions and aid endangered (and potentially even extinct) species.
In a study published in Science, researchers from the San Diego Zoo Wildlife Alliance and the University of California, Santa Cruz, found that a species’ vulnerability to extinction can be determined by evolutionary information found in the genomic sequence of just one individual.
According to the study, species with a small population throughout their evolutionary history are more likely to be at risk of extinction, as genomic sequences reveal that these species are more likely to face harmful genetic mutations and have lower diversity.
“These results show that genetic information, even if only from a single individual for a given species, offers immediate, actionable guidance for scientists designing conservation strategies as well as those with boots in the field,” said Aryn P. Wilder, Ph.D., one of the paper’s two lead authors.
This has incredible implications for conservation, as these precursors to endangerment can be spotted by an algorithm that automatically ranks a species’ risk of extinction from “least concern” to “critically endangered.” For species that are understudied and underdocumented, scientists just need to sequence one individual’s genome to determine an entire population’s conservation status and potential management practices.
Genetically Engineering a Species’ Future
Once a species’ conservation status has been determined, scientists can use a fully sequenced genome to make informed genetic modifications. Whether using highly precise gene-editing tools like CRISPR, or tried-and-true breeding processes like artificial selection, genetic modifications to a species help ensure they have the fitness or necessary traits to endure indefinitely.
In a process known as genetic rescue, scientists can use a genomic sequence to determine which genes are negatively impacting the survival of a species and work to replace those genes with ones beneficial to survival.
Colossal Biosciences: Sequencing the Mammoth’s Revival
Colossal Biosciences is using the genomic sequences of the African and Asian elephants to revive the long-extinct woolly mammoth.
With the help of the Vertebrate Genome Project — a scientific consortium dedicated to generating error-free sequences for all living vertebrate species — Colossal has successfully generated DNA sequences of the Asian and African elephant.
Not only do these sequences aid in the conservation of endangered species, but they also provide a reference genome for which woolly mammoth DNA can be transferred to create a hybrid species. The woolly mammoth was the first extinct species to have its genome partially sequenced in 2008 after scientists were able to extract hair from two ancient specimens found buried in Siberian permafrost.
Colossal plans to transfer cold-adapted genes found in the woolly mammoth’s genomic sequence into the cells of an Asian elephant, which shares 99.6% of its DNA with the mammoth. Doing so would create a hybrid species functionally equivalent to the mammoth that can be reintroduced as an Arctic keystone species to slow rising temperatures and permafrost melts.
While the team at Colossal Biosciences certainly has their work cut out for themselves, including sequencing as many mammoth specimens as possible for an accurate and gapless genome, developing a reference genome for both elephant species is a significant step toward their goal.
The Northern White Rhino: A Colossal Emergency
Colossal remains years away from its goal of reviving the mammoth by 2027, but the company continues to use its groundbreaking strategies to protect species in urgent need. One species in desperate need of conservation is the northern white rhino. Not only is the northern white rhino critically endangered, but its entire population consists of only two remaining females, Najin and Fatu, both of which live in a wildlife sanctuary in Kenya.
While some would consider the northern white rhino doomed for extinction, Colossal Biosciences’ recent partnership with BioRescue — a consortium dedicated to saving the species — has revitalized hope.
Using the principles of genetic rescue, Colossal has created a toolkit for rebounding the northern white rhino that involves sequencing preserved museum samples and specimens to uncover favorable genes no longer found in the living population. Colossal can then insert these genes into embryos created from the species’ two remaining females to establish a genetically diverse population.
BioRescue has already created 29 viable embryos which can be edited and inserted in a southern white rhino surrogate (the northern white rhino’s sister taxon, or closest relative) to produce northern white rhino calves, which can insulate future herds from disease and prevent potential inbreeding.
With Colossal and BioRescue working side by side, the pair have high hopes that a healthy new member of the species will be born as early as 2025. In a world on the cusp of its sixth mass extinction event, Colossal Biosciences’ conservation toolkit and innovative use of genomic sequencing are quickly becoming the answer to rebounding endangered species’ populations and reversing elimination.
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