In the neverending battle against bacterial infections, scientists have found an unlikely ally: the long-extinct Neanderthals. Scientists from the University of Pennsylvania have tapped into the archaic genetic code of our ancient relatives, unearthing a potential pharmaceutical goldmine—a new kind of antibiotic built from Neanderthal DNA.

Evolving resistance

Since the advent of penicillin, antibiotics have been the cornerstone of our defense against bacterial diseases. However, bacteria are cunning adversaries, evolving resistance to our drugs and thus escalating a biological arms race. It’s a stark reality underscored by the CDC’s warning of a looming post-antibiotic era, propelled by antibiotic misuse.

According to a systematic analysis published in 2022, in 2019 alone, 1.3 million deaths were estimated to be directly attributable to antimicrobial resistance, the majority in sub-Saharan Africa and Asia.

A report from the World Health Organization (WHO) shows that more than half of the bacteria responsible for bloodstream infections in hospitals—specifically, Klebsiella pneumoniae and Acinetobacter species—are now resistant to multiple drugs. These infections are particularly severe and typically require treatment with the most powerful antibiotics available, known as carbapenems. Alarmingly, the study found that 8% of the bloodstream infections caused by Klebsiella pneumoniae are not responding even to these potent drugs.

Even common bacterial infections that traditionally have been routinely treated with antibiotics are showing concerning levels of resistance. Neisseria gonorrhoeae, the bacteria responsible for the widely known sexually transmitted infection gonorrhea, has developed resistance to ciprofloxacin, an antibiotic commonly prescribed in oral form, in over 60% of cases. Furthermore, E. coli, typically the culprit behind urinary tract infections, has also grown alarmingly defiant.

More than 20% of E. coli cases show resistance not just to the primary antibiotics (ampicillin and co-trimoxazole) but also to the secondary line of defense, fluoroquinolones, which are usually reserved for more difficult cases.

Jurassic Park, for antibiotics

With drug-resistant infections threatening to increase mortality rates, the pursuit of novel antibiotics is more critical than ever. With this urgency in mind, some scientists have turned to artificial intelligence (AI) for help. Essentiall, they employed machine learning algorithms to scour the human genome, sifting through thousands of proteins to identify those capable of fighting infections. These small molecules, or peptides, form the front line of our immune system’s defenses.

Using this approach, researchers at the University of Pennsylvania have identified more than 2,500 antimicrobial peptides within the human DNA. Some of these could be repurposed into new pharmaceutical drugs that could neutralize even the sturdiest bacteria that currently don’t respond to our antibiotics.

But the treasure hunt didn’t stop there. The findings got everyone thinking: What germ-killing peptides could lurk in the genomes of our extinct relatives? So the researchers applied the same AI model, known as panCleave, to the genomes of Neanderthals and Denisovans. This led to the discovery of the aptly named neanderthalin-1, a peptide synthesized using a meticulous technique that joins amino acids sequentially.

When the researchers synthesized neanderthalin-1 and used it against skin infection in mice, it worked. The Neanderthal-based drug rivaled the performance of the modern antibiotic Polymyxin B.

“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, who co-authored the study, told Vox. “So it’s quite exciting for us.”

The study serves as a profound reminder of life’s interconnectedness through time, with the neanderthalin-1 peptide emerging as a gift from our distant relatives. While not yet a clinical reality, the potential here is striking.

However, it’s crucial to note that this research is in its early stages. The effectiveness of neanderthalin-1 in humans is yet to be determined. There’s also the concern that pathogens could still quickly develop resistance to drugs derived from ancient DNA.

Nevertheless, the findings represent a significant step toward innovative antibiotics, illustrating the fusion of ancient genetic insights with modern AI technology. As the algorithms improve and peptide synthesis progresses, the hope for a new category of antibiotics becomes more concrete.

The findings appeared in the journal Cell Host & Microbe.