The procedure, known as cranial trephination, was performed thousands of years ago in different parts of the world, including Europe, Africa, China and South America. A 2020 paper listed trephination as one of “the first three procedures that marked the dawn of surgery,” along with circumcision and bladder stone removal.

Versions of the procedure, called either a craniotomy or craniectomy, are still practiced today “as emergency treatment for brain swelling, bleeding, as well as for surgeries to treat epilepsy and to remove some tumors,” said John Verano, a professor of anthropology at Tulane University, who described the new paper as an interesting case report.

Although the electric drills used today are a far cry from the handheld flints and metal tools used thousands of years ago, the objective — making a hole in the skull — is the same. However, Verano stressed that trephination was not brain surgery.

“They were careful not to cut through the membrane protecting the brain, which would lead to meningitis and death if not done under strictly sterile conditions,” he said.

Archaeologists and anthropologists cannot be certain what conditions ancient healers were treating by cutting into the skull, but most speculation centers on serious head injuries. Other possibilities include epilepsy, mental illness and swelling in the brain.

“It’s a piece of a larger story from which we’re still missing major chapters,” said Rachel Kalisher, an author of the paper and doctoral candidate in archaeology at Brown University’s Joukowsky Institute for Archaeology and the Ancient World.

The brothers’ bones were found in 2016 buried beneath the floor of a Bronze Age house in Megiddo, which, roughly 4,000 years ago, was a wealthy, cosmopolitan city on a major trade route connecting Egypt, Syria and Mesopotamia.

Kalisher and her colleagues found widespread lesions on the bones, tiny holes that can be a symptom of various diseases, including tuberculosis and leprosy. Their presence offered researchers “a puzzle that you work backward from,” Kalisher said.

Lesions caused by disease take time to form, meaning the brothers had probably been living with their illnesses for several months or longer before they died. Still, Kalisher, who has been working at the Megiddo site since 2014, cautioned that it is not clear whether the cranial surgery was performed to treat the brother’s disease.

Researchers were able to tell that the older brother, who was probably between 21 and 46, was alive when the surgery started, but he died during or soon after the procedure. There were no signs that the bone had time to heal.

The surgery left a 1½-inch square opening in the skull and was likely created using a stone or metal implement with a sharp, sloping edge, Kalisher said.

“They would make these crosshatches into the cranium and they would wedge out the pieces,” she said. “We actually have two of the wedged-out pieces.”

Verano said the method used for trephination in Megiddo “was relatively common in central highland Peru in late pre-Hispanic times, although it was not particularly successful compared to other methods.”

Kalisher said archaeologists have not found evidence to suggest that the patient received any kind of anesthesia before the surgery. But even if anesthesia had been used, it would have done little good.

“In a nutshell, anesthesia would only be useful for deadening the nerves in the scalp, as there are no sensory nerves in the skull bone,” Verano said. “So the pain would be brief when the scalp is cut. Also, if the patient had a head injury, they might be unconscious or delirious, and thus relatively insensitive to pain.”

The brothers appear to have been elite members of Megiddo’s society based on the location and contents of the burial site.

The house where the bones were found was next to the city’s late-Bronze Age palace. Burial contents included fine Cypriot pottery and prime cuts of meat, either from sheep or goats, Kalisher said.

Kalisher and her colleagues have sent samples of bone and teeth for pathogen DNA testing to Germany’s Max Planck Institute for Evolutionary Anthropology in an attempt to determine the specific disease or diseases that afflicted the brothers.

It won’t be easy. The Mediterranean climate, with its fluctuations between hot, dry summers and cold, wet winters, is not ideal for preserving organic material.

But if the tests can identify a disease afflicting the brothers, the information will help Kalisher and others “understand what clinical symptoms they may have been experiencing.”

Illness altered the appearance of the younger brother’s nasal surface, something that can happen in people afflicted with leprosy. Researchers found no other signs of leprosy in the younger man, but are intrigued by the possibility.

If confirmed by testing, it would be one of the earliest cases of leprosy ever discovered.