Scientists ‘Resurrect’ Extinct Antimicrobial Peptides of Neanderthals and Denisovans

Jul 08, 2023

Molecular de-extinction could offer avenues for drug discovery by reintroducing bioactive molecules that are no longer encoded by living organisms.

Archaic human peptides display in vitro and in vivo antimicrobial activities with low host toxicity. Image credit: Ella Marushchenko.

Human genomes and the genomes of our ancient ancestors express proteins with natural antimicrobial properties.

Molecular de-extinction hypothesizes that these molecules could be prime candidates for safe new drugs.

Naturally produced and selected through evolution, these molecules offer promising advantages over molecular discovery using AI alone.

“We need to think big in antibiotics research,” said Dr. Cesar de la Fuente, a researcher at the University of Pennsylvania.

“Over one million people die every year from drug-resistant infections, and this is predicted to reach 10 million by 2050.”

“There hasn’t been a truly new class of antibiotics in decades, and there are so few of us tackling this issue that we need to be thinking about more than just new drugs. We need new frameworks.”

In the study, the authors explored the proteomic expressions of two extinct hominins — Neanderthals and Denisovans — and found dozens of small protein sequences with antibiotic qualities.

Their lab then worked to synthesize these molecules, bringing these long-since-vanished chemistries back to life.

“The computer gives us a sequence of amino acids,” Dr. de la Fuente said.

“These are the building blocks of a peptide, a small protein. Then we can make these molecules using a method called ‘solid-phase chemical synthesis’.”

“We translate the recipe of amino acids into an actual molecule and then build it.”

The researchers next applied these molecules to pathogens in a dish and in mice to test the veracity and efficacy of their computational predictions.

“The ones that worked, worked quite well,” Dr. de la Fuente said.

“In two cases, the peptides were comparable — if not better — than the standard of care.”

“The ones that didn’t work helped us learn what needed to be improved in our AI tools.”

“We think this research opens the door to new ways of thinking about antibiotics and drug discovery, and this first step will allow scientists to explore it with increasing creativity and precision.”

With de-extinction established for these molecules, the scientists are now thoughtfully exploring the consequences of resurrecting the past.

“We are opening an entirely new avenue for learning about the ways our bodies prevent and fight diseases,” Dr. de la Fuente said.

“We’re in conversation with bioethicists about what it means to bring genetic material back to life,” he added.

“We’re doing it for medicine, but what if someone else resurrects something toxic or harmful?”

“We’re also collaborating with patent lawyers. Current peptide sequences are not patentable by law. But what about those we recreate from extinct organisms?”

The study is published in the journal Cell Host & Microbe.

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Jacqueline R.M.A. Maasch et al. 2023. Molecular de-extinction of ancient antimicrobial peptides enabled by machine learning. Cell Host & Microbe 31 (8): 1260-1274; doi: 10.1016/j.chom.2023.07.001