Arctic Permafrost DNA Emerges as Biotech's Next Drug Discovery Frontier

By Sophie Lindqvist

Biosynthetic gene clusters of up to 100,000 base pairs sit buried in Canada's Arctic permafrost, and Canadian researchers are now sequencing that frozen DNA in a bid to feed the next generation of antibiotic and therapeutic discovery. The commercial stakes are explicit: antibiotics alone are "a billion-dollar industry globally," says Srijak Bhatnagar, PhD, who leads the Enviromics Group, a computational biology and environmental microbiology lab at Athabasca University.

Bhatnagar's team has spent years gathering environmental DNA from Canada's Arctic waters. The permafrost and ancient boreal soils hold rich DNA that has degraded over thousands of years, and the frozen organisms it preserves amount to a historical record with unusual scientific value.

What does the permafrost actually contain?

"Permafrost is revealing frozen organisms that are a historical record from tens of thousands of years ago. They could be cold-adapted, ancient, or new in the sense that humanity has not seen them in a while," Bhatnagar tells GEN.

His framing matters for R&D portfolio decisions: the motivation for biotech firms bioprospecting the Arctic for biosynthetic gene clusters is, in his words, not only academic but commercial. The play is to identify gene clusters encoding novel chemistry that conventional, extensively mined environments no longer yield.

Labs in the field also aim to biosynthesize complex bioproducts in scalable fermenters, which would spare researchers from having to grow the Arctic's sensitive native organisms at all — a workflow shortcut that sidesteps one of the field's oldest bottlenecks.

How do researchers access unculturable microbes?

Historically, nearly 99% of environmental microbes could not be cultivated under conventional laboratory conditions, leaving major biochemical pathways hidden, says Justin Nodwell, PhD, a biochemistry professor at the University of Toronto. His lab specializes in taking streptomycete biosynthetic gene clusters — genes found in unculturable environmental microbes that stay silent under standard conditions — and using synthetic biology to express them in Streptomyces to produce new antibiotics and natural products.

Canadian labs are attacking the cultivation hurdle through high-throughput metagenomics and single-cell DNA sequencing. "When we obtain total genomic material directly from permafrost cores, bioinformaticians can build complete genomes of unculturable organisms, and this shows cryptic BGCs," Nodwell says.

The approach responds to a well-documented frustration known as the dereplication problem: researchers keep rediscovering known compounds. Specialized metabolism from conventional environments has already been mined extensively, not only for antibiotics but for chemotherapeutics — doxorubicin and rapamycin are the standard examples.

"You tend to rediscover things that are known. And that certainly is something we've encountered in this lab. In terms of whether going to Arctic environments is going to lead to new metabolites, I think scientifically that's very interesting though the jury isn't entirely in," Nodwell says.

He points to the work of Hazel Barton, PhD, a microbiologist and ecologist at the University of Alabama who studies cave microbiomes, including New Mexico's Lechuguilla Cave, sealed off from the surface for roughly 4 million years. The question for microbiologists, Nodwell says, is whether "there is new stuff down there, stuff that hadn't been sampled before. At the very least, there should be stuff that hasn't been exposed to antibiotics used in medicine."

Why is refactoring the gene clusters so expensive?

The main technical obstacle, from Nodwell's synthetic biology perspective, arises when a BGC identified in a non-culturable cold-adapted environment must be refactored for expression in a standard warm-adapted host such as Streptomyces. Some clusters run to 100,000 base pairs — an enormous amount of synthetic DNA to manufacture.

"[If] you're going to do it synthetically, it's very expensive. If you're going to do it by PCR, that's a lot of reactions. It's a major undertaking to build something like that. But it is doable," he says.

Cluster boundaries compound the cost problem. Algorithms locate biosynthetic genes reliably, but the edges remain, in Nodwell's words, somewhat mysterious. A run of perhaps 15 genes clearly involved in making a molecule may be flanked by genes of uncertain function. Without knowing the biochemical pathway, defining the cutoff remains, he says, "a judgment call you have to make."

He also cautions against inflated expectations: "I guess we'll also find some things that we've seen before — but whether that can be turned into distributable medicinal products — it's impossible to say."

Who owns the Arctic's genetic data?

Bhatnagar warns of a "blind curve" in the Canadian effort. Researchers can sequence permafrost data and post it to public repositories such as GenBank or SRA — but because of financial mismatches, "a company elsewhere, most likely [in the] US, is going to mine it, create a product that could, for all we know, be a billion-dollar product," he says.

Canada has not signed the UN Nagoya Protocol on Access to Genetic Resources, so it does not protect biocultural property. For the Indigenous populations of the Canadian Arctic, questions of biopiracy and ownership of genetic material are critical.

"Canada is not a signatory of Nagoya Protocol, so we do not protect biocultural property. [For indigenous populations] that genetic knowledge is coming from what was their biocultural property, and they would ask: What's our benefit?" Bhatnagar says.

He draws on personal history: "I come from India (originally), and I distinctly remember in my childhood reading articles about how some of the traditional plants and medicines that we had been using; a western company basically isolated the chemical and patented it, and I'm like how can you patent it when we have been using it for like thousands of years?"

The pattern he describes — outsiders gathering traditional knowledge and patenting derived compounds without benefit-sharing — is precisely the risk researchers say Canada has yet to fence off. Bhatnagar and colleagues argue that Arctic bioprospecting must pair scientific rigor with ethical stewardship, meaning concrete frameworks protecting Indigenous biocultural rights before local sequencing efforts become someone else's commercial windfall.

With sequencing pipelines already producing public data and synthetic biology costs falling, the window for settling those ownership terms is narrowing as fast as the permafrost itself.