Scientists Turn to Human Ancestors’ DNA in Search for New Antibiotics

Microbe-fighting molecules that once existed in Neanderthals and Denisovans have been re-created in the lab and tested in mice

A model of a Neanderthal seen from the chest up
A model of a Neanderthal at the Natural History Museum in London. Researchers theorize that molecules that existed in our extinct ancestors could be used to treat pathogens today. Mike Kemp / In Pictures via Getty Images

To find a way to fight modern-day pathogens, some scientists are looking to our distant ancestors.

In a new paper published late last month in the journal Cell Host & Microbe, researchers say they’ve re-created molecules from Neanderthals and Denisovans that don’t exist in living organisms—a process they’re calling “molecular de-extinction.” These molecules had been identified by A.I. as potential candidates for medical use as antimicrobial treatments.

“This is completely new. We came up with the term ‘molecular de-extinction’ and this is the first peer-reviewed paper that describes it,” César de la Fuente, a co-author of the study and a bioengineer at the University of Pennsylvania, tells Vox’s Sigal Samuel. “So, it’s quite exciting for us.”

By using the word “de-extinction,” the research team calls to mind the efforts of genetics companies working on stunts like “bringing back” the woolly mammoth, the Tasmanian tiger or the dodo. Like these companies, though, the scientists aren’t taking long-dead molecules from the bodies of Neanderthals and Denisovans and reviving them—instead, they’re using the organisms’ molecules as a blueprint to create new ones in the lab.

“We’ve always dreamed of bringing back extinct organisms like the dinosaurs, as in Jurassic Park. But of course, that has a lot of ethical, ecological and technical problems,” de la Fuente told New Scientist’s Carissa Wong late last year, when the paper had been published as a preprint and had not been peer reviewed. “Instead of bringing back entire organisms, we thought, could we bring back molecules from the past that could help with problems like antibiotic resistance we see today?”

Researchers are trying to uncover new ways of developing drugs to safeguard against new pathogens and emerging antibiotic-resistant bacteria, the authors write in the paper. The overuse of existing antibiotics has led to the evolution of bacteria that aren’t stymied by the typical treatments, per Vox. And it’s a problem with a high death toll: Drug-resistant infections could kill ten million people annually by 2050, according to a 2019 study.

Instead, the researchers suggest creating new antibiotics from molecules that once protected now-extinct organisms could help defend against illness in people alive now.

“We’re motivated by the notion of bringing back molecules from the past to address problems that we have today,” de la Fuente tells Nature News’ Saima Sidik.

To do so, the researchers used a machine learning tool to look at the proteins in modern humans and our closest extinct relatives, Neanderthals and Denisovans. Many organisms make bits of proteins called peptides that can defend against microbes. The tool examined these molecules in our ancestors’ genomes and predicted which ones might be successful antibiotics for living humans. Then, the researchers created the most promising candidates in the lab.

The team used six peptides—four from modern humans, one from Neanderthals and one from Denisovans—to treat mice that had been infected with bacteria, writes Nature News. The treatments stopped one type of bacterium from growing in muscles, but they didn’t kill it, per the publication. With high doses, five of the peptides killed a different kind of bacterium that grew in skin infections.

Jonathan Stokes, a biochemist at McMaster University in Canada who wasn’t involved in the research, tells Vox that this approach to finding new drugs is creative. “I think this technique will augment other antibiotic discovery efforts to help us discover structurally and functionally novel antibacterial therapies that overcome existing resistance mechanisms,” he tells the publication.

“Given the current global mass extinction, this ability to ‘de-extinct’ potential antibiotics is hugely important. The antimicrobial peptides are non-toxic, comparably potent to other antimicrobial peptides and had good effectiveness in a mouse model,” Sam Williams, a biochemist at the University of Bristol in England who did not contribute to the study, said to New Scientist last year.

Nathanael Gray, a chemical biologist at Stanford University, tells Nature News that he does not think molecular de-extinction will have a big impact on drug discovery, unless the algorithm used to sift through the ancient molecules becomes more accurate.

As de la Fuente notes to Vox, the study did not test whether mice could develop a resistance to the peptides, which would render them less useful. “It’s something to do in the future,” he tells the publication.

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